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HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis

  • Jing Xu EMAIL logo and Nana Lin
Published/Copyright: May 13, 2024
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Open Medicine
From the journal Open Medicine Volume 19 Issue 1

Abstract

Ulcerative colitis (UC) has been identified as a severe inflammatory disease with significantly increased incidence across the world. The detailed role and mechanism of HOXD10 in UC remain unclear. In present study, we found that HOXD10 was lowly expressed in UC samples and was notably decreased by dextran sulfate sodium (DSS) administration. Overexpression of HOXD10 dramatically ameliorated DSS-induced UC symptoms, including the loss of weight, increased disease activity index values, and the shortened colon length. Additionally, terminal-deoxynucleoitidyl transferase mediated nick end labeling and immunohistochemistry staining assays showed that HOXD10 overexpression suppressed cell apoptosis and facilitated proliferation of colon tissues after DSS treatment. Moreover, HOXD10 overexpression obviously suppressed DSS-triggered inflammatory response by decreasing the expression level of TNF-α, IL-6, and IL-1β. Furthermore, overexpression of HOXD10 effectively restored the intestinal permeability, thereby alleviating DSS-induced intestinal barrier dysfunction. Mechanistic study demonstrated that HOXD10 significantly reduced the activities of Rho/ROCK/MMPs axis in colon tissues of mice with UC. In conclusion, this study revealed that HOXD10 might effectively improve DSS-induced UC symptoms by suppressing the activation of Rho/ROCK/MMPs pathway.

Keywords: ulcerative colitis; HOXD10; inflammatory response; intestinal barrier function; Rho/ROCK/MMPs axis

1 Introduction

Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease, that can harm rectum and colon and frequently relapses [1,2]. Abdominal pain and bloody diarrhea are the typical symptoms of UC, which can be diagnosed via colonoscopy and colon biopsy [3,4]. In recent years, the incidence of UC has increased worldwide. In addition, the leakage of the intestinal epithelial barrier and the decreased intestinal permeability are important pathological features of UC [5,6]. Extracellular mucus and tight junctions are considered as vital components of mucosal barrier, protecting against harmful substances in the intestinal cavity. It has been reported that the release of UC submucosal inflammatory factors destroys the structural integrity of intestinal mucosal barrier, contributing to changes in intestinal mucosal permeability, thereby exacerbating abnormal submucosal immune responses [7,8]. Therefore, it is essential to explore the potential targeted genes that modulate intestinal permeability and inflammation in UC.

HOXD10, a member of the human homeobox (HOX) gene family, is closely associated with cell differentiation and morphogenetic embryo development [9]. Previous study illustrated that HOXD10 depletion down-regulates the activity and migration of RAFLS in rheumatoid arthritis and ameliorates arthritis by inhibiting p38/c-Jun signaling pathway [9]. Ruan et al. discovered that HOXD10 exerts anti-inflammatory and neuroprotective effects. HOXD10 overexpression suppresses neuronal apoptosis, inflammatory response, and oxidative stress, thereby restoring cognitive deficits in Alzheimer’s disease mice [10]. Besides, HOXD10 also plays crucial roles in tumorigenesis. For example, HOXD10 is identified as a tumor suppressor gene to inhibit cancer development and enhance apoptosis in human cholangiocarcinoma [11]. Down-regulation of HOXD10 facilitates endometrial carcinoma progression and aggravates its malignant phenotype [12]. However, the role and mechanism of HOXD10 in UC are still unclear. Data analysis of GEO chip (GSE48634) indicated that HOXD10 was significantly low expressed in the colon tissues of UC patients. Therefore, we speculated that HOXD10 plays an important role in UC.

Emerging evidence reported that Rho/ROCK signaling pathway plays a vital role in various inflammatory response, such as in rheumatoid arthritis [13] and non-specific neuroinflammation [14]. In addition, it is reported that the Rho/ROCK inactivation protects the integrity of the epithelial barrier induced by dextran sulfate sodium (DSS), relieves oxidative stress, and inhibits the expression of inflammatory mediators and pro-inflammatory cytokines [15]. Zhang et al. discovered that sishen improves UC by modulating the Rho/ROCK axis [16]. Moreover, matrix metalloproteinases (MMPs) are also associated with the decreased intestinal tissue tight junction protein Claudin-5. The increased expression of MMP-2 and MMP-9 has been shown to enhance intestinal mucosal permeability, suggesting that the expression of MMPs promotes the destruction of epithelial barrier and aggravates the symptoms of UC [17,18]. Interestingly, it is reported that Rho/ROCK signaling regulates the expression of MMPs in diverse human diseases [19]. For example, Rho/ROCK inactivation reduces the expression of MMPs in hepatocellular carcinoma [20]. Based on these findings, the inactivation of Rho/ROCK/MMPs cascade signals may be critical to mitigate UC development. However, few studies have revealed the upstream genes that regulate Rho/ROCK/MMPs axis during UC progression. Notably, previous study proved that HOXD10 is capable of inhibiting the activity of Rho/ROCK axis [10,11]. Nevertheless, whether HOXD10 regulates the Rho/ROCK/MMP pathway in UC remains unclear.

This study for the first time revealed that HOXD10 reduced inflammatory response and apoptosis of intestinal tissue cells, and ameliorated intestinal barrier function by modulating Rho/ROCK/MMPs axis, thereby increasing intestinal permeability in DDS-induced UC mice model.

2 Materials and methods

2.1 Animals treatment

The 24 C57BL/6 male mice were obtained from Chengdu Dasuo Experimental Animal Co., Ltd (China) and were kept in animal facilities at controlled environment (23 ± 3°C, 60 ± 15% humidity). Additionally, all mice had free access to the same food and water. All experiments were supported by the Animal Ethical Committee of Affiliated Hangzhou First People’s Hospital.

2.2 Induction of UC

The 24 C57BL/6 male mice aged 8–10 weeks were divided into four groups with six mice in each group: sham + AAV-NC group, sham + AAV-HOXD10 group, DSS + AAV-NC group, and DSS + AAV-HOXD10 group. The mice in DSS + AAV-NC and DSS + AAV-HOXD10 group were treated with 4% DSS (9011-18-1, Guangxi Qili Pharmaceutical Co. Ltd, China), while the mice in sham + AAV-NC and sham + AAV-HOXD10 group were treated with water without DSS. To investigate the effects of HOXD10 on UC, 1 × 1011 vg adeno-associated virus 9 (AAV-9) particles carrying HOXD10 or its scramble control obtained from Han Hang Seng Technology (Shanghai) Co., Ltd (China) were injected into each mouse in the indicated group (sham + AAV-HOXD10 and DSS + AAV-HOXD10 group or sham + AAV-NC and DSS + AAV-NC group, respectively) through tail vein and the UC model was established 2 weeks later. The body weight, diarrhea, and bleeding were observed and recorded daily after the modeling began. Then the disease activity index (DAI) was estimated based on the data of body weight loss, stool occult blood positivity, or hemorrhoea as well as stool consistency as described in previous reports [8,21]. After 7 days, mice blood from caudal vein was harvested and centrifuged at 12,000 rpm for 5 min for subsequent analyses. Then the mice were sacrificed for isolating colon tissues. The length from the cecum to the anus was measured and the colon tissues were preserved in liquid nitrogen for next experiments.

2.3 Bioinformatics analysis

The data were collected from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). The expression profiling data of GSE48634 chip was analyzed using GEO2R platform to reveal the potential genes in UC. The screening criteria were p < 0.05, log2 FC (fold change) >1.5, or log2 FC < − 1.5 [22]. The filtering information of GSE48634 chip was as described in previous report [23]. Briefly, the GSE48634 chip contains 68 patients diagnosed with UC and 69 healthy controls (collected from the UC microarrays without disease).

2.4 Quantitative real time polymerase chain reaction (qPCR)

Total RNA of colon tissues was extracted employing Beyozol reagent (R0011, Beyotime, China) following the manufacturer’s instruction. A BeyoRT™ First Strand cDNA Synthesis Kit (D7166, Beyotime, China) was utilized to produce the complementary DNA according to the protocol of the kit. Then the qRT-PCR was conducted with MonAmp™ Taqman qPCR Mix (MQ30101S, MQ30101S, Monad, China) on a fluorescence quantitative PCR instrument (CFX96, Bio-rad, USA). The relative expression level of targeted genes was analyzed using 2–ΔΔCt method and β-actin was regarded as the control gene. All sequences of primers are provided in Table 1.

Table 1

Sequences of qRT-PCR primers

Gene Forward Reverse
HOXD10 5′-GACATGGGGACCTATGGAATGC-3′ 5′-CGGATCTGTCCAACTGTCTACT-3′
IL-6 5′-CTGCAAGAGACTTCCATCCAG-3′ 5′-AGTGGTATAGACAGGTCTGTTGG-3′
IL-1β 5′-GCAACTGTTCCTGAACTCAACT-3′ 5′-ATCTTTTGGGGTCCGTCAACT-3′
TNF-α 5′-AGAACTCCAGGCGGTGTCT-3′ 5′-TCCCTCAGGGGTGTCCTTAG-3′
β-actin 5′-AACCCTAAGGCCAACCGTGAAAAG-3′ 5′-GCTCGAAGTCTAGGGCAACATA-3′

2.5 Western blotting

Colon tissues were lysed using pre-chilled RIPA lysis buffer (P0013D, Beyotime, China) and then were centrifuged (12,000 rpm, 15 min) at 4°C for harvesting total protein. Then the concentration of protein was determined utilizing BCA Protein Quantification Kit BCA (20201ES76; YESEN, China) according to the protocol of kit. Next, total protein from tissues were separated with SDS-PAGE and transferred onto polyvinylidene fluoride membranes (PW60101S; Monad, China). The membranes were blocked using 5% bovine serum albumin (Standard Grade, 36101ES25; YESEN, China) dissolving in tris borate saline with 0.1% tween 20. After blocking, the membranes were incubated with specific primary antibodies, anti-HOXD10 antibody (1:1,000, ab138508; Abcam, UK), anti-BAX-antibody (1:1,000, ab32503; Abcam, UK), Bcl-2 rabbit mAb (1:1,000, A19693; Abclonal, China), anti-cleaved caspase-3 antibody (1:1,000, ab2302; Abclonal, China), caspase-3 rabbit pAb (1:1,000, A2156; Abclonal, China), phospho-NF-κB p65 (Ser536) (93H1) rabbit mAb (1:1,000, 3033; Cell Signaling Technology, USA), MUC2 rabbit mAb (1:1,000, A4767; Abclonal, China), anti-Claudin 3 antibody (1:1,000, ab15102; Abcam, UK), Occludin polyclonal antibody (1:1,000, 71-1500; Invitrogen Antibodies, USA), ZO-1 rabbit pAb (1:1,000, A0659; Abclonal, China), RhoA rabbit mAb (1:1,000, A19106; Abclonal, China), Rac1/Cdc42 antibody (1:1,000, 4651; Cell Signaling Technology, USA), ROCK1 rabbit mAb (1:1,000, A11158; Abclonal, China), ROCK2 rabbit mAb (1:1,000, A2395; Abclonal, China), MMP2 rabbit mAb (1:1,000, A19080; Abclonal, China), MMP2 rabbit mAb (1:1,000, A19080; Abclonal, China), or β-actin rabbit mAb (1:1,000, AC038; Abclonal, China) overnight at 4°C. Finally, the membranes were incubated with goat anti-rabbit IgG H&L (HRP) (1:5,000, ab6721; Abcam, UK) and the protein bands were detected utilizing Super ECL Detection Reagent ECL kit (36208ES60; YESEN, China) on a Hesper chemiluminescence imaging system (GD50401; Monad, China). The relative expression of targeted protein was analyzed with Image Lab software [24].

2.6 Immunofluorescence staining

The immunofluorescence staining was performed as described in previous study [25]. Briefly, the colon tissue sections (4 μm thick) embedded in paraffin are dewaxed and rehydrated. Then the sections were incubated with primary antibody anti-HOXD10 antibody (1:50, ab138508; Abcam, UK), MUC2 rabbit mAb (1:1,000, A4767; Abclonal, China), Occludin polyclonal antibody (1:1,000, 71-1500; Invitrogen Antibodies, USA), or ZO-1 rabbit pAb (1:1,000, A0659; Abclonal, China) overnight. After washing three times using phosphate buffer saline (PBS; C0221A, Beyotime, China), the sections were treated with biotin-labeled goat anti-rabbit IgG (H+L) with high mole ratio (1:200, A0279; Beyotime, China) for 1 h, followed by incubating with fluorescein diacetate (1:50, 40720ES03; YESEN, China) for another 1 h. Next, the sections were stained with 2-(4-amidinophenyl)-6-indolecarbamidine dihydrochloride (C1002; Beyotime, China) for 30 min. Finally, the images of random six fields were obtained employing a fluorescence microscope (BX53FL, Olympus, Japan).

2.7 Hematoxylin & eosin (H&E) staining

The colon tissues were fixed using 4% paraformaldehyde fix solution (P0099; Beyotime, China) and embedded in paraffin, followed by cutting into 4 μm sections with a freezing microtome (FS800; Shenzhen Rayward Life Technology Co., Ltd, China). Next, a hematoxylin and eosin staining kit (C0105M, Beyotime, China) was employed to stain the sections following the kit’s protocol. Finally, the histological analysis of the tissue slices was performed utilizing an optical microscope (THUNDER Imager Tissue, Leica, Germany).

2.8 Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay

Cell apoptosis in colon tissues were examined by employing a TUNEL Apoptosis Detection Kit (40308ES20; YESEN, China) as described in previous report [26]. Briefly, colon tissue sections (4 μm thick) were treated with PBS containing 1% endopeptidase K (ST535; Beyotime, China) for 15 min. Then the enzyme and label reagent were added to the tissue sections in a ratio of 1:9, followed by treating the sections with 50 μL of converter-POD for 30 min. Finally, the images of random six fields were observed with an optical microscope (THUNDER Imager Tissue, Leica, Germany).

2.9 Immunohistochemistry (IHC) staining

IHC staining was introduced to determine the ki-67 expression in colon tissues. The tissues (4 μm thick) were fixed using 4% paraformaldehyde fix solution (P0099; Beyotime, China) and embedded in paraffin, followed by cutting into 4 μm sections with a freezing microtome (FS800, Shenzhen Rayward Life Technology Co., Ltd, China). Ki-67 rabbit mAb (A11005) and biotin-labeled goat anti-rabbit IgG (H+L) were incubated with sections successively according to the procedure described in previous report [27]. Finally, the images of sections were observed with an optical microscope (THUNDER Imager Tissue, Leica, Germany).

2.10 Enzyme-linked immunosorbent assay (ELISA)

The expression level of TNF-α, IL-6, and IL-1β in serum was detected using mouse TNF-α (tumor necrosis factor alpha) ELISA Kit (E-EL-M3063, Elabscience, China), mouse IL-6 (interleukin 6) ELISA Kit (E-EL-M0044c, Elabscience, China), or mouse IL-1β (interleukin 1 beta) ELISA Kit (E-EL-M0037c, Elabscience, China) according to the manufacturer’s instructions, respectively.

2.11 Intestinal barrier function analysis

For measurement of FITC-dextran, mice were given FITC-dextran (MW: 4 kD, HY-128868A, MCE, USA) by gavage administration after fasting for 4 h. After another 4 h, blood was collected from caudal vein and plasma by centrifugation at 4°C (12,000 rpm, 10 min). Then the plasma was diluted with PBS, and the content of FITC-dextran in serum was detected by a fluorescence spectrophotometer (933N, Ditu (Shanghai) Biotechnology Co., Ltd, China) at excitation wavelength of 485 nm and emission wavelength of 525 nm. The concentration of FITC-dextran in untreated serum diluted with PBS was used to draw the standard curve.

2.12 Period-Schiff (PAS) staining

The goblet cells loss was determined by performing PAS staining analysis on colon tissues. The experiments were performed using a Periodic Acid-Schiff Staining Kit (C0142S, Beyotime, China) according to the manufacturer’s protocol. Finally, the images of sections (4 μm thick) were observed with an optical microscope (THUNDER Imager Tissue, Leica, Germany).

2.13 Statistical analysis

All the data were presented as the mean ± SD and the statistical analyses were conducted by Graphpad Prism 8.0. Student’s t-test was employed for two group comparisons, while one-way ANOVA with Bonferroni post-test was introduced for multiple group comparisons. The p ＜ 0.05 was regarded as statistically significant. All the experiments were repeated three times.

3 Results

3.1 HOXD10 is down-regulated in UC

A microarray was performed to compare the expression profile of genes in healthy control samples and UC samples from GSE48634 chip. The data illustrated that HOXD10 was notably low expressed in UC samples (Figure 1a and b). To confirm the expression level of HOXD10 in UC, the C57BL/6 mice were employed to induce UC by administrating DSS. As shown in Figure 1c and d, the expression of HOXD10 in colon tissues was markedly decreased in DSS group compared with sham group (Figure 1c and d). Moreover, immunofluorescence staining of HOXD10 proved that HOXD10-positive cells in colon tissues of mice were dramatically reduced in DSS group (Figure 1e). Taken together, these findings demonstrated that HOXD10 expression was decreased in UC, suggesting that HOXD10 might be associated with the progression of UC.

Figure 1 HOXD10 is down-regulated in UC. (a) The genes expression profiles exhibited as the manner of heatmap. X-axis: samples; Y-axis: genes. Red: high expression; blue: low expression. (b) The expression level of HOXD10 obtained by analyzing the data from GSE48634 chip (*** p < 0.001). (c) The mRNA level of HOXD10 detected via qRT-PCR analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). (d) The protein level of HOXD10 detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). (e) The expression level of HOXD10 detected by immunofluorescence analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). Student’s t-test was employed for the statistical analysis in two groups.
Figure 1

HOXD10 is down-regulated in UC. (a) The genes expression profiles exhibited as the manner of heatmap. X-axis: samples; Y-axis: genes. Red: high expression; blue: low expression. (b) The expression level of HOXD10 obtained by analyzing the data from GSE48634 chip (*** p < 0.001). (c) The mRNA level of HOXD10 detected via qRT-PCR analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). (d) The protein level of HOXD10 detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). (e) The expression level of HOXD10 detected by immunofluorescence analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). Student’s t-test was employed for the statistical analysis in two groups.

3.2 HOXD10 overexpression relieves DSS-induced UC

To investigate the roles of HOXD10 in DSS-induced UC, AAV particles carrying scramble sequences (NC) or HOXD10 were used to ectopically express HOXD10. Western blotting analysis indicated that AAV-HOXD10 increased HOXD10 expression in colon tissues and remarkably recovered the level of HOXD10 in DSS mouse model (Figure 2a). Compared with the sham group, DSS induction notably reduced the food intake of mice over a 7-day period. However, HOXD10 overexpression effectively restored the food intake of mice after DSS treatment (Figure 2b). In addition, the DSS treatment caused significant colitis-associated symptoms in mice, including the loss of weight, increase in DAI values, and shortened colon [28]. Compared with mice in AAV-NC group, AAV-HOXD10 dramatically ameliorated the DSS-induced symptoms, with less weight loss, lower DAI scores, and longer colon length (Figure 2c–e). Furthermore, H&E staining assay demonstrated that DSS treatment resulted in severe diffuse destruction of the colon epithelium and extensive infiltration of inflammatory cells in the epithelium and lamina propria, while HOXD10 overexpression efficiently restored these damages (Figure 2f). Collectively, these results proved that HOXD10 reduced the sensitivity of mice to DSS exposure.

Figure 2 HOXD10 overexpression relieves DSS-induced UC. (a) The protein level of HOXD10 detected via western blotting analysis (*** p < 0.001, ** p < 0.01, C57BL/6 male mice, n = 6/group). (b) The food intake of mice over a 7-day period (*** p < 0.001). (c) The body weight of mice in indicated groups (*** p < 0.001, C57BL/6 male mice, n = 6/group). (d) The DAI score of mice in indicated groups (*** p < 0.001, C57BL/6 male mice, n = 6/group). (e) The colon length of mice in indicated groups (*** p < 0.001, * p < 0.05, C57BL/6 male mice, n = 6/group). (f) The H&E staining assay (C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.
Figure 2

HOXD10 overexpression relieves DSS-induced UC. (a) The protein level of HOXD10 detected via western blotting analysis (*** p < 0.001, ** p < 0.01, C57BL/6 male mice, n = 6/group). (b) The food intake of mice over a 7-day period (*** p < 0.001). (c) The body weight of mice in indicated groups (*** p < 0.001, C57BL/6 male mice, n = 6/group). (d) The DAI score of mice in indicated groups (*** p < 0.001, C57BL/6 male mice, n = 6/group). (e) The colon length of mice in indicated groups (*** p < 0.001, * p < 0.05, C57BL/6 male mice, n = 6/group). (f) The H&E staining assay (C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.

3.3 HOXD10 overexpression inhibits DSS-induced apoptosis and promotes proliferation of colon tissues

Subsequently, the effects of HOXD10 on cell proliferation and apoptosis of colon tissues were estimated via immunology technique. The ki-67 immunoreactivity and TUNEL assay were introduced to detect cell proliferation and apoptosis in colon tissues, respectively. Ki-67 positive cells were decreased in DSS-treated mice compared with sham mice, which were significantly increased by overexpression of HOXD10 (Figure 3a). Additionally, DSS treatment notably induced cell apoptosis in colon tissues, whereas overexpression of HOXD10 effectively attenuated DSS-induced cell apoptosis (Figure 3b). Moreover, the detection of markers of apoptosis illustrated that DSS administration increased the expression of BAX and the ratio of cleaved-caspase-3/caspase-3 but decreased BCL-2 expression in colon tissues. However, overexpression of HOXD10 obviously counteracted these effects (Figure 3c). Overall, these data indicated that HOXD10 alleviated DSS-induced UC in mice by suppressing apoptosis and facilitating proliferation.

Figure 3 HOXD10 overexpression inhibits DSS-induced apoptosis and promotes proliferation of colon tissues. (a) Cell proliferation in colon tissues detected via ki-67 staining assay (*** p < 0.001, C57BL/6 male mice, n = 6/group). (b) Cell apoptosis in colon tissues detected via TUNEL analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). (c) The expression of apoptosis-related proteins detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.
Figure 3

HOXD10 overexpression inhibits DSS-induced apoptosis and promotes proliferation of colon tissues. (a) Cell proliferation in colon tissues detected via ki-67 staining assay (*** p < 0.001, C57BL/6 male mice, n = 6/group). (b) Cell apoptosis in colon tissues detected via TUNEL analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). (c) The expression of apoptosis-related proteins detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.

3.4 HOXD10 inhibits DSS-induced inflammatory response and inflammatory pathway

Previous studies revealed that DSS-induced UC enhanced the production of proinflammatory factors and activated inflammation-related signaling pathway [29]. Thus, the expression levels of TNF-α, IL-6, and IL-1β in serum were determined by qRT-PCR and ELISA assays, and the results indicated that they were dramatically up-regulated in DSS-challenged mice. As expected, pre-treatment of HOXD10 effectively decreased the expression of inflammatory cytokines (Figure 4a and b). In addition, the p-NF-κB expression and the ratio of p-NF-κB/NF-κB increased by DSS administration in colon tissues were markedly reduced by HOXD10 overexpression (Figure 4c). These results suggested that HOXD10 significantly suppressed inflammatory response in DSS-induced UC.

Figure 4 HOXD10 inhibits DSS-induced inflammatory response and inflammatory pathway. (a) The expression levels of TNF-α, IL-6, and IL-1β detected via qRT-PCR analysis (*** p < 0.001, ** p < 0.01, * p < 0.05, C57BL/6 male mice, n = 6/group). (b) The expression levels of TNF-α, IL-6, and IL-1β detected via ELISA (*** p < 0.001, * p < 0.05, C57BL/6 male mice, n = 6/group). (c) The expression levels of NF-κB and p-NF-κB detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.
Figure 4

HOXD10 inhibits DSS-induced inflammatory response and inflammatory pathway. (a) The expression levels of TNF-α, IL-6, and IL-1β detected via qRT-PCR analysis (*** p < 0.001, ** p < 0.01, * p < 0.05, C57BL/6 male mice, n = 6/group). (b) The expression levels of TNF-α, IL-6, and IL-1β detected via ELISA (*** p < 0.001, * p < 0.05, C57BL/6 male mice, n = 6/group). (c) The expression levels of NF-κB and p-NF-κB detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.

3.5 HOXD10 reverses the intestinal permeability and improves intestinal barrier function

Intestinal barrier dysfunction contributes to the up-regulation of FITC-dextran [8]. As shown in Figure 5a, DSS treatment dramatically elevated the content of FITC-dextran in serum compared with sham mice. Nevertheless, overexpression of HOXD10 effectively reduced the production of FITC-dextran (Figure 5a). Then PAS staining was performed to investigate the number of mucin-filled goblet cells and the morphology of intestinal crypts. The results showed that DSS administration obviously reduced the number of goblet cells and crypt depth in colon tissues, while pre-treatment with HOXD10 effectively attenuated these effects (Figure 5b and c). Since the vital components of the intestinal mucus were secreted via goblet cells, MUC-2 (in colon tissues) was significantly decreased in DSS-treated group and was recovered after AAV-HOXD10 pre-treatment (Figure 5d). Epithelial tight junction has been discovered to be crucial for maintaining the integrity of epithelium and inhibiting inflammatory response [8]. Hence, the effects of HOXD10 on proteins (Claudin 3, Occludin, and ZO-1) associated with tight junction in colon tissues were determined. Immunofluorescence assay demonstrated that the expression levels of Occludin and ZO-1 in colon tissues were obviously reduced in DSS-induced mouse model group but were effectively recovered by overexpression of HOXD10 (Figure 5e). Consistently, western blotting analysis confirmed that DSS administration decreased the tight junction proteins’ expression in colon tissues, which was notably restored by HOXD10 overexpression (Figure 5f). Taken together, these findings implied that HOXD10 ameliorated DSS-injured intestinal barrier function by restoring intestinal permeability and tight epithelial junctions.

Figure 5 HOXD10 reverses the intestinal permeability and improves intestinal barrier function. (a) The content of FITC–dextran in serum (*** p < 0.001, C57BL/6 male mice, n = 6/group). (b) The goblet cells loss detected via PAS staining (*** p < 0.001, ** p < 0.01, C57BL/6 male mice, n = 6/group). (c) The quantitative data of crypt depth (*** p < 0.001, ** p < 0.01, C57BL/6 male mice, n = 6/group). (d and e) The expression levels of MUC-2, occluding, and ZO-1 detected via immunofluorescence analysis (*** p < 0.001, * p < 0.05, C57BL/6 male mice, n = 6/group). (f) The expression levels of Claudin3, occluding, and ZO-1 detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.
Figure 5

HOXD10 reverses the intestinal permeability and improves intestinal barrier function. (a) The content of FITC–dextran in serum (*** p < 0.001, C57BL/6 male mice, n = 6/group). (b) The goblet cells loss detected via PAS staining (*** p < 0.001, ** p < 0.01, C57BL/6 male mice, n = 6/group). (c) The quantitative data of crypt depth (*** p < 0.001, ** p < 0.01, C57BL/6 male mice, n = 6/group). (d and e) The expression levels of MUC-2, occluding, and ZO-1 detected via immunofluorescence analysis (*** p < 0.001, * p < 0.05, C57BL/6 male mice, n = 6/group). (f) The expression levels of Claudin3, occluding, and ZO-1 detected via western blotting analysis (*** p < 0.001, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.

3.6 HOXD10 inhibits the activity of Rho/ROCK/MMPs axis

It has been reported that HOXD10 is able to regulate Rho/ROCK axis [10,11] and the inactivation Rho/ROCK pathway is involved in the DSS-induced epithelial barrier dysfunction, oxidative stress, and inflammatory reaction [13]. Additionally, emerging evidence verified that the members of MMP family exert essential roles in the UC progression and the Rho/ROCK inactivation down-regulates MMPs expression in hepatocellular carcinoma [14–16]. Therefore, we further explored whether HOXD10 modulates Rho/ROCK/MMPs axis in the development of DSS-induced UC by determining the expression level of proteins related to Rho/ROCK/MMPs axis (RhoA, Rac1, ROCK1, ROCK2, MMP2, and MMP9). As shown in Figure 6, DSS treatment notably increased the protein level of RhoA, Rac1, ROCK1, ROCK2, MMP2, and MMP9 in colon tissues, whereas HOXD10 overexpression effectively attenuated these effects. Collectively, these results revealed that HOXD10 suppressed the activity of Rho/ROCK/MMPs axis activated by DSS.

Figure 6 HOXD10 inhibits the activity of Rho/ROCK/MMPs axis. The expression levels of RhoA, Rac1, ROCK1, ROCK2, MMP2, and MMP9 detected via western blotting analysis (*** p < 0.001, ** p < 0.01, * p < 0.05, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.
Figure 6

HOXD10 inhibits the activity of Rho/ROCK/MMPs axis. The expression levels of RhoA, Rac1, ROCK1, ROCK2, MMP2, and MMP9 detected via western blotting analysis (*** p < 0.001, ** p < 0.01, * p < 0.05, C57BL/6 male mice, n = 6/group). The one-way ANOVA with Bonferroni post-test was introduced for the statistical analysis in multiple groups.

4 Discussion

This study revealed that HOXD10 was low-expressed in UC sample and was dramatically down-regulated by DSS treatment. In addition, overexpression of HOXD10 effectively alleviated DSS-induced UC symptoms, including the loss of weight, increase in DAI values, and shortened colon. Moreover, AAV-HOXD10 pre-treatment dramatically inhibited apoptosis and inflammatory response in colon tissues triggered by DSS. Moreover, HOXD10 overexpression recovered intestinal permeability, thereby improving DSS-challenged intestinal barrier function. Furthermore, HOXD10 suppressed the activation of Rho/ROCK/MMPs pathway in DSS-induced UC mouse model. Overall, these findings uncovered that HOXD10 might ameliorate DSS-induced colitis by mediating Rho/ROCK/MMPs axis.

As the main type of inflammatory bowel disease, UC has plagued many patients due to its high incidence and recurrence rate [30]. Previous studies have verified that a variety of factors including genes, environment, persistent neutrophil infiltration, and excessive production of pro-inflammatory factors initiate the progression of UC [31]. However, many therapies present irreversible side effects, including emesis, intoxication, systemic edema, and anemia [32]. Therefore, it is essential to explore new therapeutic targets and molecular mechanisms related to UC [33]. It has been reported that HOXD10 is a vital tumor suppressor that inhibits cells migration in various cancers [34–36]. In addition, increasing evidence has proved that HOXD10 is involved in inflammatory effects in diverse diseases such as rheumatoid arthritis [9] and Alzheimer’s disease [10]. Nevertheless, the detailed roles of HOXD10 in UC remain unclear. In this study, we analyzed the data of GSE48634 chip utilizing GEO2R analysis platform and discovered that HOXD10 expression was reduced in UC samples compared with healthy control samples. In previous studies, DSS-induced colitis in mouse is regarded as the well-known animal model for exploring the pathogenesis of UC. Therefore, DSS-induced mouse colitis model was introduced to mimic the clinical features of UC [32]. In line with the data from GEO database, the expression level of HOXD10 was notably down-regulated in DSS-treated mice as detected by qRT-PCR, western blotting, and immunofluorescence staining assays. These findings implied that HOXD10 may serve as a protective gene in UC patients.

Consistent with previous reporters, the clinical symptoms including weight loss, increased DAI value, and shortened colon were observed in model mice [37]. The obvious improvements of mice weight, DAI score, and colon length were observed by pre-treating mice with AAV-HOXD10. Moreover, overexpression of HOXD10 effectively restored the destruction of the colon epithelium and reduced the infiltration of inflammatory cells in the epithelium and lamina.

Recent studies verified that the imbalance of apoptosis and proliferation in colon is closely related to the pathogenesis of UC [38,39]. Consistently, we revealed that DSS administration notably inhibited proliferation and facilitated apoptosis in colon tissues, while HOXD10 overexpression effectively enhanced cell viability and suppressed apoptosis. Moreover, the excessive secretion of inflammation cytokines such as TNF-α, IL-6, and IL-1β and the phosphorylation of NF-κB have been found to affect the clinical symptoms of UC [40–46]. This study illustrated that the expressions of TNF-α, IL-6, and IL-1β at mRNA and protein level were remarkably reduced in AAV-HOXD10 group compared with DSS-treated group. In addition, HOXD10 overexpression suppressed NF-κB phosphorylation induced by DSS in colon tissues. These results demonstrated that HOXD10 was able to suppress inflammatory response in mice with UC.

The increased intestinal permeability is one of the leading characteristic of UC [47]. The mice in DSS-challenged group presented more serum FITC-dextran, suggesting the severe damages in intestinal mucosa. However, HOXD10 overexpression dramatically reduced the level of FITC-dextran, indicating that HOXD10 effectively ameliorated intestinal barrier.

The reduction of goblet cells is considered as an important feature of UC [8]. Our results revealed that DSS contributed to goblet cells loss and intestinal crypt distortion by employing PAS staining assay, while overexpression of HOXD10 effectively offset these effects. In addition, HOXD10 overexpression reversed the decrease in MUC-2 expression induced by DSS treatment. Moreover, previous study has proved that the intercellular tight junction is the vital guarantee for the integrity of intestinal mucus [8]. Tight junction proteins are considered to be the crucial component of the intestinal mucosal barrier, which reduce the space between intestinal epithelial cells and retain lumen material. These proteins such as Claudin 3, occluding, and ZO-1 are closely related to maintaining intestinal permeability [48]. It is reported that multiple drugs affect DSS-induced inflammation by regulating tight junction related proteins [49,50]. In line with previous reporters, in this study, DSS treatment decreased the expression level of Claudin 3, occluding, and ZO-1, whereas HOXD10 overexpression notably reversed these changes. These results proved that HOXD10 improved epithelial barrier dysfunction by eliminating DSS induced the decrease in goblet cells and MUC-2 and recovering the tight junction of adjacent epithelial cells.

Rho/ROCK axis has been reported to be closely associated with inflammatory response and epithelial barrier dysfunction [15] and HOXD10 is related to the inactivation of Rho/ROCK pathway [10,11]. Moreover, previous studies have demonstrated that the inactivation of Rho/ROCK suppresses the expression of MMPs and the members of MMPs are closely related to the pathogenesis of UC [17,18,20]. Therefore, we explored the effects of HOXD10 on Rho/ROCK/MMPs signals in experimental UC mouse model. Interestingly, DSS treatment significantly increased the expression levels of proteins related to Rho/ROCK/MMPs axis, which were obviously reduced by HOXD10 overexpression. These data confirmed that HOXD10 suppressed the activity of Rho/ROCK/MMPs axis in mice with UC.

However, this study is limited by the lack of direct evidence that the regulation of HOXD10 on UC processes is associated with the Rho/ROCK/MMPs axis. Further experiments are required to verify whether HOXD10 influences UC progression by mediating Rho/ROCK/MMPs axis and how HOXD10 inhibits the activation of Rho/ROCK/MMPs signaling.

5 Conclusion

In conclusion, this study for the first time elucidated that HOXD10 may effectively alleviate DDS-induced UC progression and suppress apoptosis and inflammatory response in mice by regulating Rho/ROCK/MMPs axis.

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Acknowledgements

Not applicable.

  1. Funding information: Not applicable.

  2. Author contributions: All authors contributed to the study conception and design. Material preparation and the experiments were performed by Jing Xu. Data collection and analysis were performed by Jing Xu and Nana Lin. The first draft of the manuscript was written by Nana Lin and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: The authors state that there are no conflicts of interest to disclose.

  4. Data availability statement: All data generated or analyzed during this study are included in this published article. The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Received: 2023-01-31
Revised: 2023-09-26
Accepted: 2023-10-17
Published Online: 2024-05-13

© 2024 the author(s), published by De Gruyter

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

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  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
https://doi.org/10.1515/med-2023-0844
Keywords for this article
ulcerative colitis; HOXD10; inflammatory response; intestinal barrier function; Rho/ROCK/MMPs axis
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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