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Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis

  • Li Su , Yi Huang , Lei Zheng , Zhifa Zhu , Yue Wu and Ping Li EMAIL logo
Published/Copyright: May 6, 2022
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Open Medicine
From the journal Open Medicine Volume 17 Issue 1

Abstract

The present study intends to clarify the hypothesis that isocitrate dehydrogenase 1 (IDH1) mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis through the in vitro and in vivo experiments. Cholangiocarcinoma RBE cell line was transfected with IDH1 R132C mutation plasmids and treated with erastin to induce ferroptosis, which were then microscopically photographed. Cell viability rate was calculated by trypan blue staining. The lipid ROS level was determined by using flow cytometer. The BALB/c nude mice were injected subcutaneously with IDH1 knockout (KO), WT, or R132C mutation cell line, followed by injecting erastin intraperitoneally. The tumor tissue was surgically separated for the measurement of tumor volume and weight. The results showed that IDH1 mutant RBE cell line are sensitive to erastin-induced ferroptosis, evidenced by the increased number of propidium iodide-positive cells, the decreased cell viability, and increased lipid ROS level. However, current targeted inhibitors of IDH1 mutation (AG120 and IDH305) reversed these effects caused by IDH1 mutation. The in vivo experiment showed that IDH1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to erastin-induced ferroptosis. This study indicated that IDH1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to erastin-induced ferroptosis.

Keywords: cholangiocarcinoma; IDH1; mutation; ferroptosis

1 Introduction

Cholangiocarcinoma is an adenocarcinoma of the epithelial cells that occurs anywhere in the bile duct, which can be classified into intrahepatic, periportal, and distal types based on its clinical features. Surgery and liver transplantation are the recommended treatment options for all types of bile duct cancer in a small number of patients. The 5-year survival rate for patients with early-stage intrahepatic cholangiocarcinoma is 15%. However, if intrahepatic cholangiocarcinoma has spread to more distant parts of the body, the 5-year survival rate decreases to 2% [1]. Since surgery cannot completely remove metastatic tumors, other non-surgical treatments are recommended.

Iron-dependent lipid peroxide accumulation leads to cell death in the form of “ferroptosis” [2]. Recent studies have shown that ferroptosis is closely related to various human diseases and closely related to the mechanisms and treatments of tumorigenesis [3]. Studies have shown that herbal monomers (quercetin [4], artemisinin [5], salvia [6], etc.) can exert antitumor effects by inducing ferroptosis. In addition, Han et al. [7] found significantly lower levels of glutathione (GSH), peroxides, glutathione peroxidase (GPX) and ferrous iron [Fe2+] in extrahepatic cholangiocarcinoma compared to controls, suggesting the dysregulated iron metabolism and GPX-regulated ferroptosis.

Gene mutations are thought to play a key role in the development and progression of cholangiocarcinoma. Mutations in several genes (e.g., KRAS, Tp53, etc. [8]) have been found to be associated with the development of bile duct cancer. Mutations in isocitrate dehydrogenase 1 (IDH1) are presented in several human cancers including cholangiocarcinoma [9]. Wang et al. [10] found that mutated IDH1 was associated with a beneficial prognosis in cholangiocarcinoma and inhibited tumor growth by suppressing Akt signaling. Our previous study [11] demonstrated that IDH1 mutations in cholangiocarcinoma impair tumor progression by inhibiting isocitric acid metabolism. It raises the possibility that IDH1 mutation in cholangiocarcinoma impairs tumor progression by inducing ferroptosis. It was shown that the mutant form of IDH1/2 catalyzes the irreversible accumulation of 2-hydroxyglutaric acid (2HG), which is an alternative marker for IDH1 mutated intrahepatic cholangiocarcinoma [12], while 2HG produced by IDH1 mutations has been reported to promote erastin-induced ferroptosis in human fibroma cells and esophageal squamous carcinoma cells [13].

Erastin is a recognized inducer of ferroptosis that has been validated in a variety of tumor cells, such as breast cancer [14], hepatocellular carcinoma [15], and acute myeloid leukemia [16]. However, the effects of erastin on cholangiocarcinoma are little reported. Combined with the findings from previous studies, this study aimed to explore whether IDH1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to erastin-induced ferroptosis.

2 Materials and methods

2.1 Plasmid, chemicals, reagents, and materials

Cholangiocarcinoma RBE cell line was purchased from the American Type Culture Collection (ATCC). AG-120 (CSNpharm), IDH305 (DC Chemicals), erastin (MedChemExpress, ME) were purchased commercially. Male BALB/c nude mice were purchased from Guangzhou Laboratory Animal Center (Guangzhou, China).

2.2 Cell culture

Cells were cultured in complete Dulbecco’s modified Eagle medium (DMEM) containing fetal bovine serum (FBS, 10%) and antibiotics (penicillin and streptomycin, 1%) under 37°C in the presence of CO2 (5%) at constant humidity.

2.3 Cell viability

The cells (30 × 104) were inoculated into 12 well plates and cultured under the specified treatment conditions (DMSO or erastin) for 12 h. Subsequently, the cells were digested with trypsin and collected for trypan blue staining. The cell viability was counted and calculated by using an automated cell counter (Count Star, IC 1000). Cell viability under test conditions is reported as a percentage relative to those before treatment.

2.4 Construction of IDH1 mutation cell line

The IDH1 knockout (IDH1 KO) cell line was constructed using CRISPR-Cas9 (Shanghai Liangtai Biotech Company, Shanghai, China). In brief, when the RBE cells reached 70% confluency, cells were transfected with CRISPR-Cas9 knockout plasmids containing guide RNA sequence of IDH1 and sequence of Cas9 protein.

The IDH1 R132C mutation cell line was constructed by transfecting the IDH1 KO cell line with IDH1 R132C mutation plasmids. IDH1 KO REB cells transfected with vector (empty plasmid) and plasmids containing WT IDH1 were respectively named as Vector group and IDH1 WT group.

2.5 Groups

After construction of IDH1 Mutation, IDH1 WT, and Vector cell line, cells were treated with 5 µM erastin (DMSO as control) for 12 h. In another experiment, after construction of IDH1 Mutation cell line, cells were treated with AG120 (0.5 µM) or IDH305 (5 nM) for 12 h, followed by administration of 5 µM erastin (DMSO as control) for 12 h.

2.6 Cell state and propidium iodide (PI) staining

According to the grouping, PI dye was added to the cells treated with erastin and incubated at 37°C for 15 min. The cell state was captured by microscope, and the PI-stained cells were observed and photographed by fluorescence microscope.

2.7 Cellular lipid ROS assay

Cells were seeded (6-well dishes, 400,000 cells/well) for 24 h, and then stained with C11-BODIPY 581/591 (Thermo Fisher Scientific, San Jose, CA, USA; D3861) for 30 min at 37°C and then harvested by trypsinization. Cells were re-suspended in PBS and strained through a 40 µm cell strainer (BD Falcon), and then analyzed cells using flow cytometer (Accuri C6, BD Biosciences) equipped with 488 nm laser for excitation. Data were collected from the FL1. A minimum of 10,000 cells were analyzed per condition.

2.8 Xenograft mouse model

Male BALB/c nude mice (6 weeks old) were housed in a room (a 12-h light–dark cycle) and fed under experimental conditions (22–24°C, humidity of 50 ± 5%). Animal procedures were approved by the Animal Care and Use Committee in First Affiliated Hospital of Anhui Medical University. After acclimatization for 1 week, the mice were grouped into three groups, which were, respectively, subcutaneously injected with 2 × 106 REB IDH1 KO, REB IDH1 WT, or Vector cell line. After 1 week, mice in each group were sub-grouped into 2 groups: erastin was injected intraperitoneally at a dose of 15 mg/kg in one group, and an equal volume of DMSO was injected intraperitoneally in the other group, every 2 days for 20 days. Mice were administered once every 2 days, a total of 10 times. After the first administration, the diameter and volume of tumor tissue of mice in each group were measured every 3 days until the end of the administration. Animals were executed and tumor tissue was surgically isolated and removed, photographed, and focused. The tumor volume was measured every 3 days, according to the formula: length × width2 × 0.52.

2.9 Statistics

GraphPad 6.0 software was used for statistical analysis. Data were represented as mean value ± SD. Student’s t-test was used for the comparisons between the two groups and one-way analysis of variance (ANOVA) was used for the comparisons among three or more than three groups. p < 0.05 was considered as significant.

3 Results

3.1 IDH1 mutation promoted erastin-induced ferroptosis in cholangiocarcinoma RBE cell line

To gain a clear understanding on the functional role of IDH1 in the ferroptosis, cholangiocarcinoma RBE cell line was, respectively, transfected with WT or Mutant IDHI expressing plasmid to construct and IDH1 WT or knockdown cell lines, followed by erastin treatment. The microscopical photograph showed that the number of PI-positive cells was enhanced in erastin-treated IDH1 WT cell line (Figure 1a and b). As shown in Figure 1c, the cell viability assay showed that the viability of erastin-treated IDH1 mutation cell line was significantly decreased as compared to that of erastin-treated IDH1 knockdown or IDH1 WT cell line. Besides, since excessive accumulation of lipid ROS is a critical cause of ferroptosis, the subsequent assay was performed to determine whether mutant IDH1 could promote the sensitivity of cholangiocarcinoma to erastin by increasing lipid ROS. As shown in Figure 1d–e, the lipid ROS levels in erastin-treated IDH1 mutation cell lines were increased compared to that in erastin-treated IDH1 knockdown or WT cell line. Taken together, IDH1 mutation could aggravate erastin-induced ferroptosis in cholangiocarcinoma by increasing lipid ROS.

Figure 1 IDH1 mutation promotes erastin-induced ferroptosis in cholangiocarcinoma RBE cell line. The IDH1 KO RBE cell line was constructed using CRISPR-Cas9, and then the IDH1 KO cell line was, respectively, transfected with Vector, IDHI WT, or IDHI R132C mutation plasmid to construct the IDH1 WT or mutation cell lines, followed by erastin (5 μM) treatment for 12 h, and (a) cells were microscopically photographed. (b) The number of PI-positive cells was statistically quantified. (c) The trypan blue staining assay was used to determine the cell viability. (d and e) The lipid ROS levels were determined by using flow cytometer. *p < 0.05 vs DMSO treatment group, # p < 0.05, ### p < 0.001 vs IDH1 WT or IDH1 R132C group.
Figure 1

IDH1 mutation promotes erastin-induced ferroptosis in cholangiocarcinoma RBE cell line. The IDH1 KO RBE cell line was constructed using CRISPR-Cas9, and then the IDH1 KO cell line was, respectively, transfected with Vector, IDHI WT, or IDHI R132C mutation plasmid to construct the IDH1 WT or mutation cell lines, followed by erastin (5 μM) treatment for 12 h, and (a) cells were microscopically photographed. (b) The number of PI-positive cells was statistically quantified. (c) The trypan blue staining assay was used to determine the cell viability. (d and e) The lipid ROS levels were determined by using flow cytometer. *p < 0.05 vs DMSO treatment group, # p < 0.05, ### p < 0.001 vs IDH1 WT or IDH1 R132C group.

3.2 Inhibitors of IDH1 mutation reversed its effects on erastin-induced ferroptosis in cholangiocarcinoma RBE cell line

Current targeted inhibitors (AG120 and IDH305) of IDH1 mutation can selectively inhibit mutant IDH protein, which were used to further verify the effects of IDH1 mutation on erastin-induced ferroptosis in cholangiocarcinoma. The microscopical photograph showed that, as compared to the DMSO treatment, the number of PI-positive cells was significantly decreased after AG120 or IDH305 treatment (Figure 2a and b). The Trypan blue staining assay showed that, compared to the DMSO treatment, the viability of IDH1 mutation cell line was significantly increased, but there was no significant change in the IDH1 mutation inhibitors groups (Figure 2c). Besides, as shown in Figure 2d and e, AG120 or IDH305 treatment decreased the lipid ROS levels in IDH1 mutation cell line as compared to that with DMSO treatment. Taken together, AG120 and IDH305 could reverse IDH1 mutation effects on erastin-induced ferroptosis in cholangiocarcinoma.

Figure 2 Inhibitors of IDH1 mutation reversed its effects on erastin-induced ferroptosis in cholangiocarcinoma RBE cell line. Current targeted inhibitors of IDH1 (AG120 and IDH305) were administrated into IDH1 R132C mutation cell line with erastin and DMSO treatment, and (a) cells were microscopically photographed. (b) The number of PI-positive cells was statistically quantified. (c) The trypan blue staining assay was used to determine the effects of AG120 or IDH305 on the cell viability. (d) The effects of AG120 or IDH305 on the lipid ROS levels were determined by using flow cytometer, and (d and e) statistically quantified. ***p < 0.001 vs DMSO treatment group.
Figure 2

Inhibitors of IDH1 mutation reversed its effects on erastin-induced ferroptosis in cholangiocarcinoma RBE cell line. Current targeted inhibitors of IDH1 (AG120 and IDH305) were administrated into IDH1 R132C mutation cell line with erastin and DMSO treatment, and (a) cells were microscopically photographed. (b) The number of PI-positive cells was statistically quantified. (c) The trypan blue staining assay was used to determine the effects of AG120 or IDH305 on the cell viability. (d) The effects of AG120 or IDH305 on the lipid ROS levels were determined by using flow cytometer, and (d and e) statistically quantified. ***p < 0.001 vs DMSO treatment group.

3.3 IDH1 mutation promotes erastin-induced tumor growth inhibition in cholangiocarcinoma

Male BALB/c nude mice were injected subcutaneously with IDH1 Knockdown cell line. One week later, the mice were injected intraperitoneally with erastin at a dose of 15 mg/kg. After the first administration, the diameter and volume of tumor tissue of mice in each group were measured every 3 days until the end of the administration. The animals were executed and the tumor tissue was surgically separated and removed for photography (Figure 3b). In total, the tumor volume and weight were, respectively, decreased by erastin treatment as compared to that by DMSO treatment in IDH1 mutation group, indicating the simulative effects of erastin on inhibiting tumor growth. Besides, erastin had no significant effect on IDH1 WT cell line and IDH1 knockout cell line. Taken together, IDH1 mutation promotes erastin-induced tumor growth inhibition in cholangiocarcinoma.

Figure 3 IDH1 mutation promotes erastin-induced tumor growth inhibition in cholangiocarcinoma. Male BALB/c nude mice were injected subcutaneously with IDH1 KO, WT, or mutation cell line. One week later, mice were injected intraperitoneally with erastin or DMSO at a dose of 15 mg/kg. (a) After administration, the diameter and volume of the tumor tissue were measured every 3 days until the end of the administration. The animals were executed and the tumor tissue was surgically removed for photography (b), and for the measurement of (c) tumor weight. *p < 0.05 vs DMSO treatment group, #p < 0.05 vs IDH1 WT group.
Figure 3

IDH1 mutation promotes erastin-induced tumor growth inhibition in cholangiocarcinoma. Male BALB/c nude mice were injected subcutaneously with IDH1 KO, WT, or mutation cell line. One week later, mice were injected intraperitoneally with erastin or DMSO at a dose of 15 mg/kg. (a) After administration, the diameter and volume of the tumor tissue were measured every 3 days until the end of the administration. The animals were executed and the tumor tissue was surgically removed for photography (b), and for the measurement of (c) tumor weight. *p < 0.05 vs DMSO treatment group, #p < 0.05 vs IDH1 WT group.

4 Discussion

In our previous study, IDH1 was identified as a high frequency mutated gene in patients with cholangiocarcinoma. The in vitro study showed that IDH1 promoted cell proliferation, invasion and migration, whereas conversed results were found in IDH1 R132C mutation cells. The in vivo study indicated that tumor volume in mice transplanted with the IDH WT cells was significantly increased when compared with that in mice transplanted with the IDH R132C mutation cells. These results supported that IDH1 R132C mutation impaired the development of cholangiocarcinoma [11]. Partly similar and more in-depth is this article reveals that IDH1 R132C mutation damages cholangiocarcinoma by inducing ferroptosis, and the evidence is the increase of lipid ROS level. However, current targeted inhibitors of IDH1 mutation (AG120 and IDH305) reversed these effects caused by IDH1 mutation. The in vivo experiment showed that IDH1 mutation promotes erastin-induced tumor growth inhibition in cholangiocarcinoma. Taken together, IDH1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing the cells to erastin-induced ferroptosis.

IDH1 mutations have been identified in many types of cancer, including glioma [17], colon cancer [18], leukemia [19], and prostate cancer [20]. In recent years, ferroptosis has become an important subject of tumor research, whose predictive and prognostic value in patients with cholangiocarcinoma has been reported recently. By constructing ferroptosis scores, a previous study effectively predicted the prognoses of patients with cholangiocarcinoma, and discovered the potential gene targets to further enhance the efficacy of photodynamic therapy [21]. Besides, Han et al. [7] found significantly lower levels of GSH, peroxides, GPX, and ferrous iron [Fe2+] in extrahepatic cholangiocarcinoma compared to controls, suggesting dysregulated iron metabolism and GPX-regulated ferroptosis. This study indicated the important role of IDH1 mutation in the progression of ferroptosis in cholangiocarcinoma.

A previous study [7] indicated that mutant IDH1 reduces the protein level of GPX4, a key enzyme in removing lipid ROS and ferroptosis, and promotes depletion of glutathione. Consistently, the lipid ROS levels in erastin-treated IDH1 mutation cell line was increased compared to that in erastin-treated IDH1 knockout or WT cell line, indicating that IDH1 mutation could aggravate erastin-induced ferroptosis in cholangiocarcinoma by increasing lipid ROS. It is believed that excessive accumulation of lipid peroxide (lipid ROS) is a critical cause leading to ferroptosis [22]. Deeper investigations should be performed to further validate the links between lipid ROS and tumor progression in cholangiocarcinoma. Yuan et al. [23] indicated that targeting the ROS/Tnf/JNK axis may provide opportunities for intrahepatic cholangiocarcinoma therapy. Thongsom et al. [24] suggested that piperlongumine induces G2/M phase arrest and apoptosis in cholangiocarcinoma cells through the ROS-JNK-ERK signaling pathway.

Wandee et al. [25] indicated that derrischalcone suppresses cholangiocarcinoma cells through targeting ROS-mediated mitochondrial cell death, Akt/mTOR, and FAK pathways. The involvement of these pathways in the regulatory network between IDH1 mutation-mediated tumor progression and ROS-induced ferroptosis, need validations of more molecular mechanism experiments.

In conclusion, this study indicated that IDH1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to erastin-induced ferroptosis. This study may provide a potential mechanism for better understanding the role of IDH1 mutation in cholangiocarcinoma.

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Acknowledgements

Not applicable.

  1. Funding information: No funding was received.

  2. Author contributions: L. Su designed the study and drafted the article, L. Su, Y. Huang, L. Zheng, Z. Zhu, and Y. Wu performed the study and analyzed the data, P. Li contributed to the analysis tool and revised the article. All authors read and approved the article.

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

  4. Data availability statement: The data that support the findings of this study are available on request from the corresponding author.

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Received: 2022-01-04
Revised: 2022-03-17
Accepted: 2022-03-23
Published Online: 2022-05-06

© 2022 Li Su et al., published by De Gruyter

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

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  46. miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2
  47. hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling
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  51. Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway
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  54. lncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox
  55. NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
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  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
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  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
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  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
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  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
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  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
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  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
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  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
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  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
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  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
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  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
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  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
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  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
https://doi.org/10.1515/med-2022-0477
Keywords for this article
cholangiocarcinoma; IDH1; mutation; ferroptosis
Creative Commons
BY 4.0

Articles in the same Issue

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  3. A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma
  4. Differences in complications between hepatitis B-related cirrhosis and alcohol-related cirrhosis
  5. Effect of gestational diabetes mellitus on lipid profile: A systematic review and meta-analysis
  6. Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4
  7. Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data
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  18. Expression of DNM3 is associated with good outcome in colorectal cancer
  19. Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation
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  21. SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis
  22. lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells
  23. circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer
  24. Prognostic value of nicotinamide N-methyltransferase in human cancers: Evidence from a meta-analysis and database validation
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  26. A pan-cancer analysis of the oncogenic role of Holliday junction recognition protein in human tumors
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  30. Cardiac contractility modulation ameliorates myocardial metabolic remodeling in a rabbit model of chronic heart failure through activation of AMPK and PPAR-α pathway
  31. Quercitrin protects human bronchial epithelial cells from oxidative damage
  32. Smurf2 suppresses the metastasis of hepatocellular carcinoma via ubiquitin degradation of Smad2
  33. circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury
  34. Sonoclot’s usefulness in prediction of cardiopulmonary arrest prognosis: A proof of concept study
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  37. LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the β-catenin pathway
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  40. Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?
  41. Analysis of the expression and prognostic value of MT1-MMP, β1-integrin and YAP1 in glioma
  42. Optimal diagnosis of the skin cancer using a hybrid deep neural network and grasshopper optimization algorithm
  43. miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells
  44. Clinical value of SIRT1 as a prognostic biomarker in esophageal squamous cell carcinoma, a systematic meta-analysis
  45. circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8
  46. miR-22-5p regulates the self-renewal of spermatogonial stem cells by targeting EZH2
  47. hsa-miR-340-5p inhibits epithelial–mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling
  48. circ_0085296 inhibits the biological functions of trophoblast cells to promote the progression of preeclampsia via the miR-942-5p/THBS2 network
  49. TCD hemodynamics findings in the subacute phase of anterior circulation stroke patients treated with mechanical thrombectomy
  50. Development of a risk-stratification scoring system for predicting risk of breast cancer based on non-alcoholic fatty liver disease, non-alcoholic fatty pancreas disease, and uric acid
  51. Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway
  52. circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis
  53. Human amniotic fluid as a source of stem cells
  54. lncRNA NONRATT013819.2 promotes transforming growth factor-β1-induced myofibroblastic transition of hepatic stellate cells by miR24-3p/lox
  55. NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
  56. Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak
  57. Risk factors for adverse drug reactions associated with clopidogrel therapy
  58. Serum zinc associated with immunity and inflammatory markers in Covid-19
  59. The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies
  60. LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis
  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
  68. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis
  69. miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1
  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
  78. circRNF20 aggravates the malignancy of retinoblastoma depending on the regulation of miR-132-3p/PAX6 axis
  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
  80. Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy
  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
  88. A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia
  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
  92. Value of ultrasonography parameters in diagnosing polycystic ovary syndrome
  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
  99. Identification of osteoporosis based on gene biomarkers using support vector machine
  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
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  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
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