Home miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
Article Open Access

miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway

  • Jingyun Zhao , Leilei Liu , Wei Zhao , Cuiting Lv , Na Zhang , Xinzhuan Jia and Zhengmao Zhang EMAIL logo
Published/Copyright: June 9, 2023
Download Article (PDF)
Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

The miR-141-3p has been reported to participate in regulating autophagy and tumor-stroma interactions in ovarian cancer (OC). We aim to investigate whether miR-141-3p accelerates the progression of OC and its effect on macrophage 2 polarization by targeting the Kelch-like ECH-associated protein1-Nuclear factor E2-related factor2 (Keap1-Nrf2) pathway. SKOV3 and A2780 cells were transfected with miR-141-3p inhibitor and negative control to confirm the regulation of miR-141-3p on OC development. Moreover, the growth of tumors in xenograft nude mice treated by cells transfected with miR-141-3p inhibitor was established to further testify the role of miR-141-3p in OC. The expression of miR-141-3p was higher in OC tissue compared with non-cancerous tissue. Downregulation of miR-141-3p inhibited the proliferation, migration, and invasion of ovarian cells. Furthermore, miR-141-3p inhibition also suppressed M2-like macrophage polarization and in vivo OC progression. Inhibition of miR-141-3p significantly enhanced the expression of Keap1, the target gene of miR-141-3p, and thus downregulated Nrf2, while activation of Nrf2 reversed the reduction in M2 polarization by miR-141-3p inhibitor. Collectively, miR-141-3p contributes to tumor progression, migration, and M2 polarization of OC by activating the Keap1-Nrf2 pathway. Inhibition of miR-141-3p attenuates the malignant biological behavior of ovarian cells by inactivating the Keap1-Nrf2 pathway.

Keywords: ovarian cancer; macrophage; polarization; miR-141-3p; Keap1; Nrf2

1 Introduction

Ovarian cancer (OC) is a common cause of morbidity and mortality in women with early metastasis and high malignancy [1]. Currently, the incidence and progression of OC are related to a variety of factors, including gene mutation and signal pathway abnormalities [2]. With the progress of basic and clinical research, people have a deeper understanding of the development and progress of OC, but the survival and prognosis of OC patients have not improved significantly in recent decades. Therefore, the treatment of patients with OC remains a major clinical challenge, requiring further research on tumorigenesis and new therapies at the molecular level.

MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules consisting of approximately 21–25 nucleotides. These small miRNAs typically target one or more mRNAs, and they regulate gene expression by inhibiting or disrupting target mRNAs at the translational level. miRNAs are abnormally expressed in a variety of malignant tumors and closely related to the occurrence and development of cancers [3,4]. Studies have shown that miR-141-3p is involved in the occurrence and development of a variety of tumors including colorectal cancer [5], prostate cancer [6], breast cancer [7], and so on. At present, the research on the roles of miR-141-3p in OC is limited, and the conclusions are inconsistent. Therefore, our study will first detect the expression of miR-141-3p in ovarian carcinoma tissues and further investigate its molecular mechanisms.

The tumor microenvironment mainly consisted of the extracellular matrix, fibroblasts, vascular endothelial cells, and immunocytes [8]. These components play important roles in tumor structure and biology, contributing to tumor cells’ survival, proliferation, and migration [9]. Macrophages are attracted and activated by tumor microenvironment-derived cytokines, further differentiating into tumor-associated macrophages (TAMs) and contributing to complicated inflammation conditions [10]. It has indicated that TAMs were multifunctional and heterogeneous and will differentiate into M2-like macrophage, which exerts anti-inflammatory and expresses specific series of molecules, including Arginase 1 (Arg1), interleukin 10 (IL-10), and C-C Motif Chemokine Receptor 2 (CCR2) [11]. In contrary, M1-like macrophage is pro-inflammatory and secretes Il-1β and TNF-α, which prevent the cancerous phenotype. Therefore, M2 was highly associated with worse clinical prognosis [12] and higher density of M2 TAMs appears to correlate with tumor cell proliferation, metastasis, and intra-tumoral microvascular density, and M1 generally indicates better prognosis [13].

Nuclear factor E2-related factor2 (Nrf2), also known as carotenoid 2-like factor2 (NFE2L2), belong to the CNC-bZIP (cap “n” collar/basic Leucine zipper) family of transcription factors [12,14]. Nrf2 plays a key role in maintaining oxidation-reduction (redox) homeostasis by inducing the expression of multiple genes associated with antioxidant defense [15]. A highly conserved amino-terminal Neh2 domain of the Nrf2 [16] can bind to Kelch-like ECH-associated protein1 (Keap1). Under normal physiological conditions, Keap1 binds to Nrf2 and initiates its further degradation by ubiquitination or proteasome pathways [17]. Keap1/nrf2 was reported to involve in diverse aspects of cancer, such as angiogenesis [18] and drug resistance [19]. Studies show that in lung adenocarcinoma, miR-141-3p inhibits Keap1 mRNA translation and positively regulates Nrf2 activity [20]. Previous studies [12,21] demonstrated that cancer cells induced macrophages M2 phenotype transformation through Nrf2 activation. TAM secretes VEGF to promote cancer cell migration by Nrf2-induced epithelial–mesenchymal transition. These findings not only explain the cancer cell and macrophage interaction to contribute to tumor progression but also provides comprehensive insights into the role of Nrf2 in TAM formation and tumor metastasis [12]. Nrf2 overexpression was reported to be positively associated with OC progression [22], and also contributes to the chemoresistance and angiogenesis in OC [23]. This study will explore whether miR-141-3p can regulate NRF2 expression by targeting Keap1 to promote M2 transformation in OC in vivo and in vitro, thus providing a theoretical basis for the pathogenesis and treatment strategy of OC through reducing M2 macrophages.

2 Methods

2.1 Patients and tumor tissues

A total of 28 surgery resected OC samples from our hospital were selected. The patients were diagnosed with epithelial OC or malignant ovarian germ cell tumors by postoperative pathology and confirmed not receiving radiotherapy or chemotherapy before operation. Patients with other malignant tumors or autoimmune diseases were excluded. All the samples were stored in –80°C refrigerator after collection. Another 28 matching non-cancer specimens were selected as control. All subjects signed informed consent voluntarily for using their sample and clinical data, and this study was approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University.

2.2 GSE dataset collection

The microarray data from the GEO database (http://www.ncbi.nlm.nih.gov/gds/) were retrieved to verify our findings. The detailed screening criteria included homo sapiens, OC, and expression profiling. The selected dataset should include OC sample and non-carcinomatous sample, and each group contained more than ten samples. Finally, the GSE81873 dataset were obtained, including primary tumor tissue of 19 advanced epithelial OC patients and 13 samples from benign ovarian masses were assayed. No ethical approval or informed consent was required due to the public availability of data.

2.3 Cell culture

Human endometrial epithelial cells were purchased from Shanghai Cell Bank of the Chinese Academy of Sciences and cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS). OC cell lines, A2780 and SKOV3, as well as macrophage cell THP-1, (all purchased from Cell Center of Peking Union Medical College) were cultured in RPMI 1640 medium (Hyclone Corporation, USA) supplied with 10% FBS (PAN, Germany) and cyanin-streptomycin (100 U/ml and 0.1 mg/ml, Beyotime, Shanghai, China), and the cells were cultured at 37°C, 5% CO2 incubator. When the cells reached 70–80% fusion, 0.5% trypsin was used for cell digestion and passage.

2.4 Co-culture of SKOV3 and THP-1

Human monocytic cell line THP-1 (1 × 105/well) were incubated with 100 ng/ml PMA for 48 h to achieve their differentiation towards macrophage, termed as M0 macrophages. Then, transwell inserts were placed into a six-well plate for co-culture. M0 macrophages were seeded into the lower chamber and SKOV3 or A2780 cells with various treatment were seeded into the upper chamber. 24 h after incubation, cell proliferation was determined by CCK8 assay, and M2 polarization status of macrophages were determined by flow cytometry using M2 biomarker CD206 (BioLegend, CA, USA). The IL-10, Arg1, iNOS, and TGF-β mRNA levels in macrophages were also measured by Quantitative Real-time PCR (qRT-PCR) assay.

2.5 Flow cytometry

Polarization of macrophages were collected for flow cytometry. The cells were maintained with PE-labeled CD206 (BioLegend) for 30 min at room temperature. Next the stained cells were analyzed using a BD Accuri™ C6 cytometer (BD Biosciences).

2.6 Cell transfection

Cells (1 × 106/well) were inoculated on six-well plates. When 80% confluence was achieved, 100 nmol/L miR-141-3p inhibitor plasmid and negative control (NC) (designed and synthesized by GenePharma, Shanghai, China) were transfected into OC cells according to the instruction of Lipofectamine 2000 regent [24]. The transfection efficiency was determined by qRT-PCR.

2.7 qRT-PCR

Total RNA was extracted from the OC cells using Trizol reagent (Invitrogen, CA, USA). Reverse transcription and qRT-PCR were performed according to the instruction of the Prime script RT Reagent Kit (Takara, Tokyo, Japan) and SYBR PrimeScript miRNA RT-PCR Kit (Takara, Japan). U6 and β-actin were used as an internal reference, and all the involved primer sequences are shown in Table 1.

Table 1

qRT-PCR primer sequences

Gene Sequence
miR-141-3p F: 5′-GCGGAAAGAGGCCCCG-3′
R: 5′-AGTGCAGGGTCCGAGGTATT-3′
U6 F: 5′-GAGGGCCTATTTCCCATGATT-3′
R: 5′-TAATTAGAATTAATTTGACT-3′
IL-10 F: 5′-TCTCCGAGATGCCTTCAGCAGA-3′
R: 5′-TCAGACAAGGCTTGGCAACCCA-3′
Arg1 F: 5′-TCATCTGGGTGGATGCTCACAC-3′
R: 5′-GAGAATCCTGGCACATCGGGAA-3′
iNOS F: 5′-CAGCGGGATGACTTTCCAA-3′
R: 5′-AGGCAAGATTTGGACCTGCA-3′
TGF-α F: 5′-CAGATTCCCACACTCAGTT-3′
R: 5′-TACCCAGAATGGCAGACACA-3′
β-actin F: 5′-CACCATTGGCAATGAGCGGTTC-3′
R: 5′-AGGTCTTTGCGGATGTCCACGT-3′

2.8 CCK-8 assay

Cells at logarithmic growth with concentration of 5 × 104/well (100 μl) were inoculated in a 96-well culture plate. The proliferation of cells was measured at 24, 48, and 72 h according to the instructions of the CCK-8 Kit (Beyotime, Beijing, China). The absorbance value (OD value) at 450 nm wavelength was measured by using a Multiskan MK3 microplate reader (Thermo Fisher Scientific, CA, USA) and experiments were repeated three times.

2.9 Wound-healing assay

OC cells with a concentration of 5 × 104 cells/well were inoculated into a six-well plate. After the cells adhered to the culture medium, a sterilized two-milliliter pipette tip was used to generate wounding across the cell monolayer, and the debris was washed with PBS twice. The cells were observed with an inverted fluorescence microscope at 0, 24, and 48 h after treatment. The scratch width was calculated by ImageJ software (NIH, USA).

2.10 Transwell assay

SKOV3 and A2780 cells were diluted with a cell density of 2 × 105 cells/ml. 200 μl of cells were loaded into the upper chamber of a 24-well culture insert (Corning, USA), the chamber was preloaded with Matrigel (BD Biosciences, USA), and 1 ml RPMI-1640 culture medium was supplemented. The lower chamber was cultured for 24 h with 600 μl of RPMI-1640 medium containing 10% FBS. The cells which migrated into the bottom surface were fixed in 4% paraformaldehyde for 20 mins and dried at room temperature (25°C), then dyed with crystal violet for 20 mins. The invasion of cells was observed under a light microscope, and the average number of cells passing through the Matrigel matrix was calculated. The experiment was repeated three times.

2.11 Dual-luciferase reporter assay

The NC plasmid and miR-141-3p mimics were co-transfected with the 3′-untranslated regions (UTR) reporter vector with wild type Keap1 3′-UTR sequence (pGL3 Keap1 3′-UTR-WT) and mutant KEAP1 (pGL3Keap1-MT, Promega, USA) reporter vector. After being transfected for 48 h, the supernatant of cells was absorbed and washed with cold PBS. Lysis buffer was added to lysate cells. The lysed cells were collected. The luciferase activity of cell supernatant was detected by luciferase Kit (cat#: RG009, Beyotime). The relative luciferase activity of each group was calculated.

2.12 In vivo analysis of the M2 polarization of macrophage in xenograft mice

Six-week-old female C57BL/6J mice (purchased from the animal experiment center of Hebei Medical University) with weights of 20–23 g were used to establish a tumor model with six in each group. A total of 0.2 ml cell suspension with a concentration of 2 × l06 ml OC cells, stably transfected with plasmid containing miRNA-NC and miR-141-3p inhibitor, were subcutaneously inoculated into the back of the nude mice. Three weeks later, the mice were then euthanized for excision of the tumors, which were weighed, fixed, and paraffin embedded. During this period, the tumor volume was measured using a vernier caliper and calculated based on the formula: (length (mm) × width (mm))/2. The tumor inhibition rate (%) = (tumor weight of control group – tumor weight of treatment group)/tumor weight of control group × 100%. Next the expression patterns of macrophage marker Mac-2 and M2 surface molecule CD206 were determined using immunohistochemistry.

2.13 Western blot

The protocol was modified based on publications [25,26]. Proteins of cells were lysed and collected with RIPA lysis solution. Protein concentration was determined by the BCA method. The protein samples of each group were loaded in equal quantities and transferred to the polyvinylidene fluoride membrane (BD Biosciences, USA) after electrophoresis. The membrane was blocked with QuickBlock™ blocking buffer (Beyotime) at room temperature and incubated overnight with a specific primary antibody for Keap1, Nrf2, HO-1, and β-actin (#ab227828, #ab137550, # ab13243, and #ab115777, Abcam, UK) at 4°C. TBST was used for a full washing, and the corresponding secondary antibody was added and incubated at room temperature for 1 h. After washing, ECL luminescent solution (Millipore, USA) was dropped to visualize protein bands. β-actin served as the internal reference.

2.14 Rescue assay

Nrf2 activator-2 (compound O15, HY-145879) was purchased from Med chem express (MCE, CA, USA), and this compound (5.0 μM) was added into the cell culture medium of SKOV3 followed by miR-141-3p inhibitor treatment. After 48 h, the cells were harvested for subsequent assays.

2.15 Statistical analysis

SPSS 20.0 software was used for statistical processing. All data were expressed as mean value ± standard deviation. An independent sample T-test or nonparametric test was used for quantitative data of the two groups, and one-way analysis of variance was used for inter-group comparison. p < 0.05 was considered statistically significant.

  1. Ethical approval: This study was approved by the ethics committee of Fourth Hospital of Hebei Medical University for tissue analysis and data sharing. The animal study and protocols were approved by the animal ethics and welfare committee of Fourth Hospital of Hebei Medical University. All experiments are reported following the ARRIVE guideline.

3 Results

3.1 miR-141-3p is upregulated in ovarian tumor tissues and cells

In this study, 28 ovarian tissues and non-tumor ovary tissues with age matching were collected to analyze the expression of miR-141-3p. Results showed that miR-141-3p was upregulated in ovarian tissues when compared with non-tumor tissues (Figure 1a). The median Ct value of miR-141-3p was used as threshold to distinguish the higher or lower expression level in OC tissues, then the distribution of miR-141-3p expression among all the clinical parameters is shown in Table 2. The expression of miR-141-3p was significantly associated with high clinical stages and lymph node metastasis (p < 0.05, Table 2). Furthermore, the analyzed results of the GSE81873 dataset also support our conclusions (Figure 1b). The expression level of miR-141-3p in two OC cell lines, A2780 cells and SKOV3 cells, was significantly higher than that in human ovarian surface epithelial cell line (HOSEpiC) (Figure 1c), which suggested that miR-141-3p was over-expressed in OC, which possibly was associated with malignant behavior of OC.

Figure 1 Expression of miR-141-3p in OC tissues and ovarian cells. (a) miR-141-3p expression in 28 collected paired tissues; (b) miR-141-3p expression in GSE81873 dataset, including 13 benign tissues and 19 epithelial OC tissues. The differential expression was analyzed by GEO2R, an online analysis tool of GEO and demonstrated as Log of fold change (Log FC); and (c) miR-141-3p expression in ovarian cells and normal ovarian cells. ** p < 0.01.
Figure 1

Expression of miR-141-3p in OC tissues and ovarian cells. (a) miR-141-3p expression in 28 collected paired tissues; (b) miR-141-3p expression in GSE81873 dataset, including 13 benign tissues and 19 epithelial OC tissues. The differential expression was analyzed by GEO2R, an online analysis tool of GEO and demonstrated as Log of fold change (Log FC); and (c) miR-141-3p expression in ovarian cells and normal ovarian cells. ** p < 0.01.

Table 2

Expression of miR-141-3p and clinical pathology in ovarian tumor tissues

N High (N) Low (N) p
Age (year) ≤60 11 6 5 0.70
>60 17 8 9
Menopause Yes 18 10 8 0.82
No 10 6 4
Pathological type Epithelial OC 15 13 2 0.372
Malignant ovarian germ cell tumors 13 9 4
Clinical stage Ⅰ–Ⅱ 20 6 13 0.005
Ⅲ–Ⅳ 8 8 1
Histological grading Serous 21 10 11 0.378
Mucinous 7 4 3
Lymph node metastasis No 21 8 13 0.029
Yes 7 6 1

3.2 Downregulated miR-141-3p inhibits proliferation and invasion of ovarian cells

To further explore the role of miR-141-3p in OC, miR-141-3p NC or miR-141-3p inhibitor was transfected into SKOV3 and A2780 cells. The transfection efficiency for miR-141-3p downregulation was confirmed by qRT-PCR (Figure 2a). The proliferation of two ovarian cells was inhibited after transfected with miR-141-3p inhibitor (Figure 2b). Furthermore, the migration ability of ovarian cells decreased due to inhibition of miR-141-3p (Figure 2c and d). Subsequent transwell assays with Matrigel additionally confirmed that miR-141-3p inhibition impaired invasion capacity of OC cells (Figure 2e and f). Thus, these data supported that miR-141-3p promoted proliferation, migration, and invasion of OC cells.

Figure 2 Downregulation of miR-141-3p inhibits proliferation and invasion of SKOV3 and A2780 cells. (a) The transfection efficiency in A2780 and SKOV3 cells measured by qRT-PCR; (b) cell proliferation in A2780 and SKOV3 cells tested by CCT-8 assay; (c) a representative image of ovarian cells migration characterized by wound-healing assay; scale bar, 50 μM; (d) comparisons of wound-healing width between two groups performed by paired t-test. (e and f) transwell assay was carried out to test the invasion of SKOV3 cells. The cells number per field was analyzed by Image J. scale bar, 20 μM; ** p < 0.01.
Figure 2

Downregulation of miR-141-3p inhibits proliferation and invasion of SKOV3 and A2780 cells. (a) The transfection efficiency in A2780 and SKOV3 cells measured by qRT-PCR; (b) cell proliferation in A2780 and SKOV3 cells tested by CCT-8 assay; (c) a representative image of ovarian cells migration characterized by wound-healing assay; scale bar, 50 μM; (d) comparisons of wound-healing width between two groups performed by paired t-test. (e and f) transwell assay was carried out to test the invasion of SKOV3 cells. The cells number per field was analyzed by Image J. scale bar, 20 μM; ** p < 0.01.

3.3 MiR-141-3p promotes M2 polarization in vitro

SKOV3 cells were selected to investigate the influence of miR-141-3p on THP-1 macrophage polarization due to relatively higher expression of miR-141-3p. The plasmids containing miR-141-3p NC or miR-141-3p inhibitor were transfected into SKOV3 cells, respectively. Then, different groups of SKOV3 cells were co-cultured with differentiated M0 type macrophages. The surface markers of M2 were detected by flow cytometry. The results showed that M0 type macrophages co-cultured with SKOV3 (NC) remarkedly upregulated the expression of CD206 in M0 compared with the normal cultured control cells, while this phenomenon was reversed by miR-141-3p inhibitor transfection in ovarian cells (Figure 3a). Consistently, M2 specific molecules including Arg1 and IL-10 were declined by miR-141-3p inhibition. On the other hand, M1 specific molecules including iNOS and TNF-α were elevated when M0 macrophages were co-cultured with SKOV3-miR-141-3p inhibitor compared with SKOV3-NC (Figure 3b–e). These results demonstrated that miR-141-3p contributed to the M2 polarization of macrophages in vitro, and miR-141-3p inhibition could attenuate M0 polarization towards M2 like phenotype.

Figure 3 MiR-141-3p promotes M2 polarization in vitro. M0 THP-1 macrophage was co-cultured with SKOV3 cells transfected with miR-141-3p inhibitor for 48 h. (a) M2 biomarker CD206 were detected by flow cytometry. (b–e) qRT-PCR was performed to measure the mRNA level of specific molecules (Arg1, IL-10, iNOS, and TNF-α), respectively corresponding to M1 and M2. ** p < 0.01.
Figure 3

MiR-141-3p promotes M2 polarization in vitro. M0 THP-1 macrophage was co-cultured with SKOV3 cells transfected with miR-141-3p inhibitor for 48 h. (a) M2 biomarker CD206 were detected by flow cytometry. (b–e) qRT-PCR was performed to measure the mRNA level of specific molecules (Arg1, IL-10, iNOS, and TNF-α), respectively corresponding to M1 and M2. ** p < 0.01.

3.4 MiR-141-3p downregulation prevented growth of OC cells and reduced M2-like macrophage polarization in vivo

SKOV3 cells stably transfected with miR-141-3p inhibitor or NC were subcutaneously injected into the back of female nude mice, to investigate whether miR-141-3p affected OC xenograft in vivo. Mice xenografted with SKOV3 with miR-141-3p inhibitor exhibited reduced tumor volume and weight compared with NC group (Figure 4a and b). qRT-PCR also confirmed that miR-141-3p expression was significantly lower in tumor tissues from mice of miR-141-3p inhibitor group compared with NC group (Figure 4c). Moreover, miR-141-3p inhibition remarkably reduced the M2 marker CD206 positive cells infiltration into the tumor tissues (Figure 4d), while iNOS as M1 biomarker increased instead.

Figure 4 The effect of miR-141-3p on OC cell development and M2 polarization were analyzed in vivo. (a and b) tumor volume and weight were recorded. (c) miR-141-3p expression within tumor tissue of mice was measured by qRT-PCR. (d) M1 marker iNOS and M2 marker CD206 determined by immunohistochemistry. ** p < 0.01; Bars, 50 μm.
Figure 4

The effect of miR-141-3p on OC cell development and M2 polarization were analyzed in vivo. (a and b) tumor volume and weight were recorded. (c) miR-141-3p expression within tumor tissue of mice was measured by qRT-PCR. (d) M1 marker iNOS and M2 marker CD206 determined by immunohistochemistry. ** p < 0.01; Bars, 50 μm.

3.5 miR-141-3p directly targeted keap1 and downregulated its expression

Bioinformatics method was utilized to find the possible downstream molecules of miR-141-3p in OC. The binding sites of miR-141-3p and Keap1 were predicted using TargetScan (http://www.Targetscan.Org/) gene prediction software. The dual luciferase reporter gene assay showed that the luciferase activity was significantly decreased after co-transfection of miR-141-3p mimics with pGL3 3′-UTR of Keap1-WT reporter vector (p < 0.05 vs Keap1-Mut reporter vector) (Figure 5a and b). To further evaluate the direct regulation of miR-141-3P on keap1, we designed the following treatment for SKOV3 and A2780: mimics NC, miR-141-3p mimics, inhibitor NC, and miR-141-3p inhibitor. After treatment for 24 h, the cellular protein levels of keap1 and Nrf2 were detected by western blot. As displayed in Figure 5c, keap1 was up-regulated when miR-141-3p was inhibited, however, this was reversed by miR-141-3p mimics; meanwhile, Nrf2 showed opposite trend. Collectively, the above data indicated that miR-141-3p could suppress keap1 to boost M2 polarization and promote tumor development.

Figure 5 miR-141-3p directly binding to Keap1 and affects its expression. (a) the binding site of miR-141-3p to mRNA of Keap1 predicted by TargetScan; (b) dual-luciferase reporter assay result predicted the targeted binding relationship between miR-141-3p and Keap1; (c) representative western blot image and column comparison of protein expression in SKOV-3 cells with various treatment. ** p < 0.01.
Figure 5

miR-141-3p directly binding to Keap1 and affects its expression. (a) the binding site of miR-141-3p to mRNA of Keap1 predicted by TargetScan; (b) dual-luciferase reporter assay result predicted the targeted binding relationship between miR-141-3p and Keap1; (c) representative western blot image and column comparison of protein expression in SKOV-3 cells with various treatment. ** p < 0.01.

3.6 miR-141-3p mimic upregulated OC proliferation and M2 polarization via Keap1/Nrf2 pathway

To determine whether the proliferation and M2 polarization induced by miR-141-3p is dependent with direct degrading of keap1, miR-141-3p mimics and NC mimics were transiently transfected into the SKOV3. Results demonstrated that SKOV3 cells transfected with miR-141-3p mimics significantly increased proliferation of cells, but its effect was abolished by Nrf2 inhibitor ML3508 (Figure 6a). Consequently, cancer cells were employed to co-culture with M0 macrophages. As anticipated, Nrf2 inhibitor reversed the effect of miR-141-3p mimic on M2 polarization. Changes in specific biomarkers for M1 and M2-like macrophage by miR-141-3p were partly restored by Nrf2 inhibitor, which included CD206 determined by flow cytometry (Figure 6b), and iNOS, TNF-α, Arg1, and IL-10 were confirmed by qRT-PCR (Figure 6c–f). In the protein level, Nrf2 activation by miR-141-3p mimics was abolished by ML3508, which further suggested that miR-141-3p effect on OC cells was dependent on keap1/Nrf2 signaling pathway (Figure 6g).

Figure 6 miR-141-3p promotes OC proliferation and M2 polarization via Keap1/Nrf2 pathway. (a) The miR-141-3p mimic promotes the proliferation of SKOV3 cells, while the promotional effect of miR-141-3p was abolished by Nrf2 inhibitor ML3508; (b) miR-141-3p mimic increases expression of M2-like macrophage biomarker CD206 and this effect is abolished by Nrf2 inhibitor; (c–f) The increasing mRNA levels of Arg1 and IL-10, and decreasing mRNA levels of iNOS and TNF-α caused by miR-141-3p mimic are reversed by Nrf2 inhibitor ML3508; (g) The protein levels of Keap1 and Nrf2 in SKOV3 cells after being treated by miR-141-3p NC, miR-141-3p mimic, and miR-141-3p mimic + ML3508.
Figure 6

miR-141-3p promotes OC proliferation and M2 polarization via Keap1/Nrf2 pathway. (a) The miR-141-3p mimic promotes the proliferation of SKOV3 cells, while the promotional effect of miR-141-3p was abolished by Nrf2 inhibitor ML3508; (b) miR-141-3p mimic increases expression of M2-like macrophage biomarker CD206 and this effect is abolished by Nrf2 inhibitor; (c–f) The increasing mRNA levels of Arg1 and IL-10, and decreasing mRNA levels of iNOS and TNF-α caused by miR-141-3p mimic are reversed by Nrf2 inhibitor ML3508; (g) The protein levels of Keap1 and Nrf2 in SKOV3 cells after being treated by miR-141-3p NC, miR-141-3p mimic, and miR-141-3p mimic + ML3508.

4 Discussion

OC is one of the most common malignant tumors in women in the clinic. Patients with OC have a high risk of long-term recurrence and the overall survival rate is relatively low [27]. The pathogenesis of OC involves multiple genes and steps [9]. Currently, there are neither effective targeted therapeutic drugs nor markers that can predict the long-term prognosis.

miRNAs are small non-coding molecules that recognize 3′-UTR of specific mRNAs and negatively regulate mRNA abundance through translation blocking or forced degradation [20]. Our study manifested that miR-141-3p was aberrantly upregulated in OC both in vitro and in vivo, and inhibiting miR-141-3p could significantly impede ovarian cells proliferation and migration as well as tumor progression in nude mice. Clinical and experimental data fully demonstrated that M2-like TAM promotes the malignant evolution of tumors. At the initial stage of tumorigenesis, TAM created an inflammatory microenvironment and promoted cell mutation and growth. In the process of tumor deterioration and development, M2-1ike TAM secretes corresponding cytokines, promotes aberrant angiogenesis in tumors, and enhances the ability of tumor cells to migrate and invade [28]. At the tumor metastasis site, M2 like TAM modifies the microenvironment of the target tissue to better accept tumor cells. In addition, M2 like TAM promotes the implantation of tumor in target organs and subsequent continuous proliferation, and finally promotes the distal metastasis of tumor cells [29]. Hence, deep understanding of the M2 polarization and its regulation will add inspiration and value to cancer therapy. In this study, we further explored the influence of miR-141-3p on M2 polarization and found that ovarian cells treated with miR-141 inhibitor could suppress M2 related cytokines, while reinforce M1 macrophage polarization.

Long-term oxidative stress is highly correlated with the occurrence of many diseases, including OC [30]. Recently, keap1/Nrf2 has been believed to promote the occurrence and development of diseases, including OC [31]. In normal cells, appropriately upregulating the expression of Nrf2 can increase the antioxidant activity and reduce the risk of carcinogenesis. On the other hand, inhibiting the expression level of Nrf2 can inhibit the growth of tumor cells [32]. In normal physiological conditions, Keap1 exists in the cytoplasm and binds with Nrf2, which mediates Nrf2 inhibition. The Keap1-Nrf2 system is involved in the pathological process of different diseases. The disrupted binding of Keap1 to Nrf2 is an important step to shift cells into a state of oxidative, and their expression or regulation become abnormal in tumors [33,34]. Mitsuishi et al. [35] indicated that downregulation or deletion of the Keap1 gene significantly activated Nrf2. When continuously activated, Nrf2 is conducive to the growth of cancer cells. Dogan et al. [36] reported that serum levels of Nrf2 and Keap1 in bladder cancer patients were found to be higher than the control group. Nrf2, acting as “switch” for oxidative stress, might participate in the process of TAMs, which is stimulated by oxidative stress [37]. We speculate that miR-141-3p might regulate oxidative stress in tumor cells through indirect regulation of Nrf2, and this conclusion needs to be confirmed in subsequent research.

However, the role of Keap1/nrf2 in OC is unclear at present. The results of the current study showed that compared with the normal group, miR-141-3p was downregulated, the expression of Keap1 was increased, and Nrf2 was decreased, which was correlated with the enhanced invasion and migration ability of ovarian cells. Using TargetScan (http://www.targetscan.Org/), online prediction software, we predicted that miR-141-3p binds with Keap1, and dual luciferase experimental results further validate that miR-141-3p downregulates expression of Keap1. Additionally, using miR-141-3p mimic and inhibitor, keap1/nrf2 was found to be negatively regulated by miR-141-3p.

Immune microenvironments play important roles in tumor progression. Recent research demonstrated promoting Nrf2 stabilization and activation induces polarization from M1 to M2 in cancer cells HCT-116 and MCF-7 [21]. Keap1 contains stress sensors in response oxidative stress pathway [38], downregulation of Keap1 leads to Nrf2 to activate a series of downstream genes and the activation of oxidative stress, this creates an advantageous condition for TAM [39,40].

Currently, the therapeutic application of miRNA in human diseases have entered the stage of clinical trials. Once overcoming the degradation of miRNA nuclease and the adverse reaction of non-specific inflammatory immune response, miRNA can play its potential in clinical treatment [41,42]. Our study shows that miR-141-3p indirectly activates Nrf2 through binding Keap1, which enhances M2 polarization. Results of both in vitro and in vivo demonstrated that miR-141-3p inhibition could notably prevent M2 while boost M1 macrophage polarization, at least partly via regulating keap1/Nrf2. These results suggest that designing antisense oligonucleotides of miR-141-3p could regulate M2 polarization in vivo. Of course, our research conclusion is preliminary. The dysregulated expression of miR-141-3p in OC patients need to be analyzed in a larger clinical sample, and the specific regulatory effect of inhibiting miR-141-3p in OC needs further exploration and verification. The packing vector, administration site, and dosage of miR-141-3p inhibitor require further research and exploration.

At present, there is little clinical consensus on how to choose treatment for OC after frontline progression. Immunotherapy, chemotherapy, radiotherapy, targeted therapy, and other therapies have great potential for synergistic effects, bringing hope for improving the treatment and survival of OC. Our study provides a working basis for the study of miR-141-3p as an immune therapeutic target in OC. Further research is needed to explore the effect of regulating miR-141-3p in OC patients.

In a conclusion, our study demonstrates that miR-141-3p is upregulated in OC patients and targets Keap1 to increase the expression of Nrf2, which promotes M2 transformation and boosts the tumor progression. Inhibition of miR-141-3p prevented the activation of Keap1/Nrf2 pathway to some degree and attenuates M2 polarization, thus, suppressing OC development. miR-141-3p has a potential to be used as a clinical drug target for the treatment of solid tumors, and it can also be an effective targeted therapeutic marker that can predict the long-term prognosis for OC.

tel: +86-13933129926

  1. Funding information: The study was supported by the project of “miRNA-29 expression on tumor-related macrophage polarization in ovarian cancer” from Hebei Provincial Department of Health (20221320).

  2. Author contributions: Z.M.Z. and J.Y.Z. conceived and designed the study. J.Y.Z, L.L.L., and W.Z. performed the experiment and acquired the analyzed data. C.T.L., N.Z., and X.Z.J. performed bioinformatic analysis and conducted the statistical analysis. J.Y.Z. drafted the manuscript.

  3. Conflict of interest: The authors declare that there is no conflict of interest.

  4. Data availability statement: The data used can be obtained from the corresponding author on reasonable request.

References

[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30. 10.3322/caac.21387.Search in Google Scholar PubMed

[2] Worzfeld T, Pogge von Strandmann E, Huber M, Adhikary T, Wagner U, Reinartz S, et al. The unique molecular and cellular microenvironment of ovarian cancer. Front Oncol. 2017;7:24. 10.3389/fonc.2017.00024.Search in Google Scholar PubMed PubMed Central

[3] Forterre A, Komuro H, Aminova S, Harada M. A comprehensive review of cancer MicroRNA therapeutic delivery strategies. Cancers (Basel). 2020;12(7):1852. 10.3390/cancers12071852.Search in Google Scholar PubMed PubMed Central

[4] Iorio MV, Croce CM. MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 2017;9(6):852. 10.15252/emmm.201707779.Search in Google Scholar PubMed PubMed Central

[5] Liu X, Wang C. Long non-coding RNA ATB is associated with metastases and promotes cell invasion in colorectal cancer via sponging miR-141-3p. Exp Ther Med. 2020;20(6):261. 10.3892/etm.2020.9391.Search in Google Scholar PubMed PubMed Central

[6] Huang S, Wa Q, Pan J, Peng X, Ren D, Huang Y, et al. Downregulation of miR-141-3p promotes bone metastasis via activating NF-kappaB signaling in prostate cancer. J Exp Clin Cancer Res. 2017;36(1):173. 10.1186/s13046-017-0645-7.Search in Google Scholar PubMed PubMed Central

[7] Dong S, Ma M, Li M, Guo Y, Zuo X, Gu X, et al. LncRNA MEG3 regulates breast cancer proliferation and apoptosis through miR-141-3p/RBMS3 axis. Genomics. 2021;113(4):1689–704. 10.1016/j.ygeno.2021.04.015.Search in Google Scholar PubMed

[8] Zhang Y, Huang X, Liu J, Chen G, Liu C, Zhang S, et al. New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis. Cancer Cell Int. 2021;21(1):372. 10.1186/s12935-021-02068-7.Search in Google Scholar PubMed PubMed Central

[9] Aviles D, Warshal D, Buchbinder M, Ostrovsky O. Influence of aberrant epigenetic changes and the tumor microenvironment in ovarian cancer metastasis. In: Sergi CM, editor. Metastasis. Brisbane (AU); 2022. 10.36255/exon-publications.metastasis.ovarian-cancer-epigenetics.Search in Google Scholar PubMed

[10] Nowak M, Klink M. The role of tumor-associated macrophages in the progression and chemoresistance of ovarian cancer. Cells. 2020;9(5):1299. 10.3390/cells9051299.Search in Google Scholar PubMed PubMed Central

[11] Wang W, Sheng L, Chen Y, Li Z, Wu H, Ma J, et al. Total coumarin derivates from Hydrangea paniculata attenuate renal injuries in cationized-BSA induced membranous nephropathy by inhibiting complement activation and interleukin 10-mediated interstitial fibrosis. Phytomedicine. 2022;96:153886. 10.1016/j.phymed.2021.153886.Search in Google Scholar PubMed

[12] Feng R, Morine Y, Ikemoto T, Imura S, Iwahashi S, Saito Y, et al. Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction. Cell Commun Signal. 2018;16(1):54. 10.1186/s12964-018-0262-x.Search in Google Scholar PubMed PubMed Central

[13] Carreras J, Hiraiwa S, Kikuti YY, Miyaoka M, Tomita S, Ikoma H, et al. Artificial neural networks predicted the overall survival and molecular subtypes of diffuse large B-cell lymphoma using a pancancer immune-oncology panel. Cancers (Basel). 2021;13(24):6384. 10.3390/cancers13246384.Search in Google Scholar PubMed PubMed Central

[14] Sen Z, Weida W, Jie M, Li S, Dongming Z, Xiaoguang C. Coumarin glycosides from Hydrangea paniculata slow down the progression of diabetic nephropathy by targeting Nrf2 anti-oxidation and smad2/3-mediated profibrosis. Phytomedicine. 2019;57:385–95. 10.1016/j.phymed.2018.12.045.Search in Google Scholar PubMed

[15] Dodson M, de la Vega MR, Cholanians AB, Schmidlin CJ, Chapman E, Zhang DD. Modulating NRF2 in disease: Timing is everything. Annu Rev Pharmacol Toxicol. 2019;59:555–75. 10.1146/annurev-pharmtox-010818-021856.Search in Google Scholar PubMed PubMed Central

[16] Zhuang C, Miao Z, Sheng C, Zhang W. Updated research and applications of small molecule inhibitors of Keap1-Nrf2 protein-protein interaction: A review. Curr Med Chem. 2014;21(16):1861–70. 10.2174/0929867321666140217104648.Search in Google Scholar PubMed

[17] Taguchi K, Yamamoto M. The KEAP1-NRF2 system in cancer. Front Oncol. 2017;7:85. 10.3389/fonc.2017.00085.Search in Google Scholar PubMed PubMed Central

[18] Zhang C, Kong X, Ma D. miR-141-3p inhibits vascular smooth muscle cell proliferation and migration via regulating Keap1/Nrf2/HO-1 pathway. IUBMB Life. 2020;72(10):2167–79. 10.1002/iub.2374.Search in Google Scholar PubMed

[19] van Jaarsveld MT, Helleman J, Boersma AW, van Kuijk PF, van Ijcken WF, Despierre E, et al. miR-141 regulates KEAP1 and modulates cisplatin sensitivity in ovarian cancer cells. Oncogene. 2013;32(36):4284–93. 10.1038/onc.2012.433.Search in Google Scholar PubMed

[20] Akdemir B, Nakajima Y, Inazawa J, Inoue J. miR-432 induces NRF2 stabilization by directly targeting KEAP1. Mol Cancer Res. 2017;15(11):1570–8. 10.1158/1541-7786.MCR-17-0232.Search in Google Scholar PubMed

[21] Liu H, Zhao D, Li H, Zhang W, Lin Q, Wang X, et al. Blocking iASPP/Nrf2/M-CSF axis improves anti-cancer effect of chemotherapy-induced senescence by attenuating M2 polarization. Cell Death Dis. 2022;13(2):166. 10.1038/s41419-022-04611-4.Search in Google Scholar PubMed PubMed Central

[22] Liew PL, Hsu CS, Liu WM, Lee YC, Lee YC, Chen CL. Prognostic and predictive values of Nrf2, Keap1, p16 and E-cadherin expression in ovarian epithelial carcinoma. Int J Clin Exp Pathol. 2015;8(5):5642–9.Search in Google Scholar

[23] Wu J, Zhang L, Li H, Wu S, Liu Z. Nrf2 induced cisplatin resistance in ovarian cancer by promoting CD99 expression. Biochem Biophys Res Commun. 2019;518(4):698–705. 10.1016/j.bbrc.2019.08.113.Search in Google Scholar PubMed

[24] http://tools.thermofisher.com/content/sfs/manuals/Lipofectamine_2000_Reag_protocol.pdf.Search in Google Scholar

[25] Zhang S, Xin H, Li Y, Zhang D, Shi J, Yang J, et al. Skimmin, a Coumarin from Hydrangea paniculata, slows down the progression of membranous glomerulonephritis by anti-inflammatory effects and inhibiting immune complex deposition. Evid Based Complement Altern Med. 2013;2013:819296. 10.1155/2013/819296.Search in Google Scholar PubMed PubMed Central

[26] Zhang S, Yang J, Li H, Li Y, Liu Y, Zhang D, et al. Skimmin, a coumarin, suppresses the streptozotocin-induced diabetic nephropathy in Wistar rats. Eur J Pharmacol. 2012;692(1–3):78–83. 10.1016/j.ejphar.2012.05.017.Search in Google Scholar PubMed

[27] Liu S, Wu M, Wang F. Research progress in prognostic factors and biomarkers of ovarian cancer. J Cancer. 2021;12(13):3976–96. 10.7150/jca.47695.Search in Google Scholar PubMed PubMed Central

[28] Jayasingam SD, Citartan M, Thang TH, Mat Zin AA, Ang KC, Ch’ng ES. Evaluating the polarization of tumor-associated macrophages into M1 and M2 phenotypes in human cancer tissue: Technicalities and challenges in routine clinical practice. Front Oncol. 2019;9:1512. 10.3389/fonc.2019.01512.Search in Google Scholar PubMed PubMed Central

[29] Guo Q, Jin Z, Yuan Y, Liu R, Xu T, Wei H, et al. New mechanisms of tumor-associated macrophages on promoting tumor progression: Recent research advances and potential targets for tumor immunotherapy. J Immunol Res. 2016;2016:9720912. 10.1155/2016/9720912.Search in Google Scholar PubMed PubMed Central

[30] Trifanescu O, Gruia MI, Gales L, Trifanescu R, Anghel R. Tumor is an oxidative stress factor in ovarian cancer patients. Chirurgia (Bucur). 2018;113(5):687–94. 10.21614/chirurgia.113.5.687.Search in Google Scholar PubMed

[31] Tossetta G, Marzioni D. Natural and synthetic compounds in ovarian Cancer: A focus on NRF2/KEAP1 pathway. Pharmacol Res. 2022;183:106365. 10.1016/j.phrs.2022.106365.Search in Google Scholar PubMed

[32] Singh A, Misra V, Thimmulappa RK, Lee H, Ames S, Hoque MO, et al. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med. 2006;3(10):e420. 10.1371/journal.pmed.0030420.Search in Google Scholar PubMed PubMed Central

[33] Taguchi K, Yamamoto M. The KEAP1-NRF2 system as a molecular target of cancer treatment. Cancers (Basel). 2020;13(1):46. 10.3390/cancers13010046.Search in Google Scholar PubMed PubMed Central

[34] Leinonen HM, Kansanen E, Polonen P, Heinaniemi M, Levonen AL. Dysregulation of the Keap1-Nrf2 pathway in cancer. Biochem Soc Trans. 2015;43(4):645–9. 10.1042/BST20150048.Search in Google Scholar PubMed

[35] Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, et al. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell. 2012;22(1):66–79. 10.1016/j.ccr.2012.05.016.Search in Google Scholar PubMed

[36] Dogan C, Yazici CM, Akgul M, Turker P. The evaluation of the relation between bladder cancer and oxidative stress using NRF-2/KEAP-1 pathway, zinc and copper levels. Urol J. 2021;18(4):422–8. 10.22037/uj.v18i.6439.Search in Google Scholar PubMed

[37] Orsolic N, Kunstic M, Kukolj M, Gracan R, Nemrava J. Oxidative stress, polarization of macrophages and tumour angiogenesis: Efficacy of caffeic acid. Chem Biol Interact. 2016;256:111–24. 10.1016/j.cbi.2016.06.027.Search in Google Scholar PubMed

[38] Baird L, Yamamoto M. The molecular mechanisms regulating the KEAP1-NRF2 pathway. Mol Cell Biol. 2020;40(13):e00099–20. 10.1128/MCB.00099-20.Search in Google Scholar PubMed PubMed Central

[39] Luput L, Licarete E, Sesarman A, Patras L, Alupei MC, Banciu M. Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner. Oncol Rep. 2017;37(4):2472–80. 10.3892/or.2017.5466.Search in Google Scholar PubMed

[40] Alupei MC, Licarete E, Patras L, Banciu M. Liposomal simvastatin inhibits tumor growth via targeting tumor-associated macrophages-mediated oxidative stress. Cancer Lett. 2015;356(2 Pt B):946–52. 10.1016/j.canlet.2014.11.010.Search in Google Scholar PubMed

[41] Rupaimoole R, Slack FJ. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16(3):203–22. 10.1038/nrd.2016.246.Search in Google Scholar PubMed

[42] Inoue J, Inazawa J. Cancer-associated miRNAs and their therapeutic potential. J Hum Genet. 2021;66(9):937–45. 10.1038/s10038-021-00938-6.Search in Google Scholar PubMed

Received: 2023-02-13
Revised: 2023-05-03
Accepted: 2023-05-08
Published Online: 2023-06-09

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0729
Keywords for this article
ovarian cancer; macrophage; polarization; miR-141-3p; Keap1; Nrf2
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 9.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/med-2023-0729/html
Scroll to top button