Regio- and Stereoselective Transfer Hydrogenation of Aryloxy Group-Substituted Unsymmetrical 1,2-Diketones: Synthetic Applications and Mechanistic Studies.

Developing a general method that leads to the formation of different classes of chiral bioactive compounds and their stereoisomers is an attractive but challenging research topic in organic synthesis. Furthermore, despite the great value of asymmetric transfer hydrogenation (ATH) in both organic synthesis and the pharmaceutical industry, the monohydrogenation of unsymmetrical 1,2-diketones remains underdeveloped. Here, we report the aryloxy group-assisted highly regio-, diastereo-, and enantioselective ATH of racemic 1,2-diketones. The work produces a myriad of enantioenriched dihydroxy ketones, and further transformations furnish all eight stereoisomers of diaryl triols, polyphenol, emblirol, and glycerol-type natural products. Mechanistic studies and calculations reveal two working modes of the aryloxy group in switching the regioselectivity from a more reactive carbonyl to a less reactive one, and the potential of ATH on 1,2-diketones in solving challenging synthetic issues has been clearly demonstrated.

Mechanism of PTPN18 for regulating the migration and invasion of endometrial cancer cells via the MYC/PI3K/AKT pathway.

OBJECTIVE: Endometrial cancer (EC) is a prevalent gynecologic malignancy. The critical role of PTPN18 in EC has been reported, while its role in the aerobic glycolysis of EC cells remains unclear. Our current study focused on the mechanism of PTPN18 in the regulation of aerobic glycolysis in EC. METHODS: PTPN18 expression levels in endometrial stromal cells (KC02-44D) and EC cells (KLE, HEC-1-A, HEC-1B, and HEC-50) were determined. Following transfection of sh-PTPN18 in HEC-1-A cells, the changes in cell migratory and invasive abilities were assessed by the Transwell assay, and the changes in glucose consumption, lactic acid secretion, and ATP levels were detected using kits. The expression levels of glycolysis-related proteins HIF-1α, PKM2, and LDHA and the activation of the MYC/PI3K/AKT pathway were detected by Western blot. Additionally, sh-PTPN18 and pcDNA3.1-MYC were transfected into HEC-1-A cells to further explore their roles in the changes in aerobic glycolysis, migration, and invasion ability of EC cells. RESULTS: Expression of PTPN18 in EC cells was up-regulated (HEC-1-A>HEC-1B>HEC-50>KLE). PTPN18 knockdown suppressed EC cell migration and invasion. Additionally, PTPN18 knockdown reduced glucose consumption, lactate production, ATP levels, and glycolysis-related protein levels (HIF-1α, PKM2, LDHA). PTPN18 knockdown inhibited the activation of the MYC/PI3K/AKT pathway in EC cells. MYC overexpression partially annulled the inhibitory effects of PTPN18 knockdown on aerobic glycolysis, migration, and invasion of EC cells. CONCLUSION: Our present study provided evidence that the knockdown of PTPN18 inhibited the aerobic glycolysis, migration, and invasion of EC cells by suppressing the MYC/PI3K/AKT pathway.

Current knowledge of ferroptosis in the pathogenesis and prognosis of oral squamous cell carcinoma.

Therapeutic strategies are the hot-spot issues in treating patients with advanced oral squamous cell carcinoma (OSCC). Mounting studies have proved that triggering ferroptosis is one of the promising targets for OSCC management. In this study, we performed a first attempt to collect the current evidence on the proposed roles of ferroptosis in OSCC through a comprehensive review. Based on clinical data from the relevant studies within this topic, we found that ferroptosis-associated tumor microenvironment, ferroptosis-related genes (FRGs), and ferroptosis-related lncRNAs exhibited a potent prognostic value for OSCC patients. Mechanistically, experimental data revealed that the proliferation and tumorigenesis of OSCC might be associated with the inhibition of cellular ferroptosis through the activation of glutathione peroxidase 4 (GPX4) and adipocyte enhancer-binding protein 1 (AEBP1), suppression of glutathione (GSH) and Period 1 (PER1) expression, and modulation of specific non-coding RNAs (i.e., miR-520d-5p, miR-34c-3p, and miR-125b-5p) and their targeted proteins. Several specific interventions (i.e., Quisinostat, Carnosic acid, hyperbaric oxygen, melatonin, aqueous-soluble sporoderm-removed G. lucidum spore powder, and disulfiram/copper complex) were found to dramatically induce ferroptosis cell death of OSCC via multiple mechanisms. This review highlighted the pivotal role of ferroptosis in the pathogenesis and prognosis of OSCC. Future anticancer therapeutic strategies targeting ferroptosis and its associated molecules might provide a new insight for OSCC treatment.

The Combination of circEPSTI1 and MIF Offers Diagnostic Value for Endometrial Cancer.

Background: Circular RNAs (circRNAs) exhibit unique patterns of expression and high levels of stability in patient plasma samples such that they represent ideal non-invasive biomarkers that can be leveraged to detect a wide array of diseases including endometrial cancer (EC). This study was designed to identify circRNAs with potential diagnostic utility in serum samples from EC patients while also evaluating the utility of macrophage migration inhibitory factor (MIF) as a biomarker when screening for this form of cancer in the clinic. Methods: Levels of circEPSTI1 and MIF were assessed in the plasma of EC patients and healthy subjects (n=186 each) through qPCR and ELISAs. The diagnostic utility of these biomarkers was assessed with receiver operating characteristic curve (ROC) analyses. Results: Relative to healthy subjects, EC patient serum contained significantly elevated circEPSTI1 and MIF. An association was noted between circEPSTI1 expression in stages, histologic grade, and residual tumor. ROC curves confirmed that serum circEPSTI1 levels distinguished between controls and patients with EC with an Area of 0.835 and serum MIF levels distinguished between controls and patients with EC with an Area of 0.6646. When instead diagnosing patients based on the combination of MIF and circEPSTI1, the Area further rose to 0.8604. Conclusion: Assessing the combination of circEPSTI1 and MIF may be a viable approach to reliably diagnosing EC.

Wemics: A Single-Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation.

DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X-chromosome inactivation. Despite tremendous efforts in DNA methylation research, accurate quantification of cytosine methylation remains a challenge. Here, a single-base methylation quantification approach is introduced by weighting methylation of consecutive CpG sites (Wemics) in genomic regions. Wemics quantification of DNA methylation better predicts its regulatory impact on gene transcription and identifies differentially methylated regions (DMRs) with more biological relevance. Most Wemics-quantified DMRs in lung cancer are epigenetically conserved and recurrently occurred in other primary cancers from The Cancer Genome Atlas (TCGA), and their aberrant alterations can serve as promising pan-cancer diagnostic markers. It is further revealed that these detected DMRs are enriched in transcription factor (TF) binding motifs, and methylation of these TF binding motifs and TF expression synergistically regulate target gene expression. Using Wemics on epigenomic-transcriptomic data from the large lung cancer cohort, a dozen novel genes with oncogenic potential are discovered that are upregulated by hypomethylation but overlooked by other quantification methods. These findings increase the understanding of the epigenetic mechanism by which DNA methylation regulates gene expression.

Therapeutic effects and molecular mechanisms of quercetin in gynecological disorders.

Quercetin is a representative flavonoid that is widely present in fruits, herbs, and vegetables. It is also an important active core component in traditional Chinese medicines. As an important flavonoid, quercetin has various properties and exerts antioxidant, anti-inflammatory, and cardioprotective effects. The public interest in quercetin is increasing, and quercetin has been used to prevent or treat numerous of diseases, such as polycystic ovary syndrome (PCOS), cancer, autoimmune diseases and chronic cardiovascular diseases, in clinical experiments and animal studies due to its powerful antioxidant properties and minimal side effects. Quercetin exerts marked pharmacological effects on gynecological disorders; however, there have been no reviews about the potential health benefits of quercetin in the context of gynecological disorders, including PCOS, premature ovary failure (POF), endometriosis (EM), ovarian cancer (OC), cervical cancer (CC) and endometrial carcinoma (EC). Thus, this review aimed to summarize the biological effects of quercetin on gynecological disorders and its mechanisms.

Retraction: Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway.

[Retraction to: BMB Rep. 2022 June 30; 55(6): 299-304.] Retraction: "Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway," by Zhe Shi, Liyuan Zhou, Yan Zhou, Xiaoyan Jia, Xiangjun Yu, Xiaohong An and Yanzhen Han, BMB Rep. 2022; 55(6) 299-304: The above article, published online on 30 June 2022 in BMB Reports https://doi.org/10.5483/ BMBRep.2022.55.6.044), has been retracted by agreement between the authors and the journal's Editor in Chief. The authors unable to replicate certain results presented in the article and have therefore made the difficult decision to withdraw it. Editorial Board, BMB Reports.

PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma.

Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyltransferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8+ T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8+ T cells in vivo. Moreover, PRMT1 deletion in melanoma cells facilitated formation of double-stranded RNA derived from endogenous retroviral elements (ERV) and stimulated an intracellular interferon response. Mechanistically, PRMT1 deficiency repressed the expression of DNA methyltransferase 1 (DNMT1) by attenuating modification of H4R3me2a and H3K27ac at enhancer regions of Dnmt1, and DNMT1 downregulation consequently activated ERV transcription and the interferon signaling. Importantly, PRMT1 inhibition with DCPT1061 synergized with PD-1 blockade to suppress tumor progression and increase the proportion of CD8+ T cells as well as IFNγ+CD8+ T cells in vivo. Together, these results reveal an unrecognized role and mechanism of PRMT1 in regulating antitumor T-cell immunity, suggesting PRMT1 inhibition as a potent strategy to increase the efficacy of ICB. SIGNIFICANCE: Targeting PRMT1 stimulates interferon signaling by increasing expression of endogenous retroviral elements and double-stranded RNA through repression of DNMT1, which induces antitumor immunity and synergizes with immunotherapy to suppress tumor progression.

Pan-cancer tRNA-derived fragment CAT1 coordinates RBPMS to stabilize NOTCH2 mRNA to promote tumorigenesis.

Transfer RNA-derived fragments (tRFs) are a class of small non-coding regulatory RNAs that are involved in the pathophysiology of many diseases. However, the role of tRFs in cancer progression remains largely elusive. Here, we demonstrate that a pan-cancer 3'-tRF, CAT1 (cancer associated tRF 1), is ubiquitously upregulated in tumors and associated with poor prognosis of a variety of cancers, including lung cancer. The upregulated CAT1 in cancer cells binds to RNA-binding protein with multiple splicing (RBPMS) and displaces NOTCH2 association from RBPMS, thereby inhibiting the subsequent CCR4-NOT deadenylation-complex-mediated NOTCH2 mRNA decay. The CAT1-enhanced NOTCH2 expression promotes lung cancer cell proliferation and metastasis in vitro and in vivo. In addition, plasma CAT1 levels are substantially increased in patients with lung cancer compared to non-cancer control subjects. Our findings reveal an intrinsic connection between cancer-specific upregulation of CAT1 and cancer progression, show the regulation of NOTCH signaling in cancer by a 3'-tRF, and highlight its great clinical potential.

[Research progress on the questionnaire related to persistent postural-perceptual dizziness].

Persistent postural-perceptual dizziness（PPPD） is the most common chronic vestibular disease, the clinical manifestation is dizziness, unstable and non-rotational dizziness for three months or more. And the symptom is exacerbated by upright posture, active or passive movement, and complex visual stimuli. In addition, PPPD is a functional disease, so routine vestibular function tests and imaging tests are often negative. According to the diagnostic criteria established by the Barany Association, the diagnosis of PPPD often relies on history. This article provides a review of PPPD-related questionnaires.

Effects of different radical distal gastrectomy on postoperative inflammatory response and nutritional status in patients with gastric cancer.

Objectives: The inflammatory response caused by gastric cancer surgery and the low nutritional status of patients with gastric cancer can cause growth of tumour cells, reduce immunity, and increase tumour burden. We investigated the effects of different surgical methods on postoperative inflammatory response and nutritional status in patients with distal gastric cancer. Methods: Clinical data of 249 patients who underwent radical distal gastrectomy for distal gastric cancer from February 2014 to April 2017 were retrospectively analysed. Patients were divided according to the surgical method (open distal gastrectomy [ODG], laparoscopic-assisted distal gastrectomy [LADG] and total laparoscopic distal gastrectomy [TLDG]). Characteristics of different surgical procedures, including inflammation parameters and nutritional indicators, and different time points (preoperatively, 1 day postoperatively, and 1 week postoperatively) were compared using non-parametric test analysis. Results: At postoperative day 1, white blood cell count [WBC], neutrophil count [N], neutrophil/lymphocyte ratio [NLR], and platelet/lymphocyte ratio [PLR] increased in the three groups, and ΔN and ΔNLR were significant; the smallest change was observed in TLDG (P < 0.05). Albumin [A]and prognostic nutrition index [PNI] significantly decreased; the smallest ΔA and ΔPNI, which were statistically significant, were noted in TLDG. One week postoperatively, WBC, N, NLR, and PLR decreased, and WBC, N, and NLR showed significant difference. A and PNI of the three groups increased after 1 week, and A and PNI showed significant differences. Conclusion: Postoperative inflammatory response and nutritional status of patients with distal gastric cancer are associated with the surgical technique. TLDG has little influence on the inflammatory response and nutritional level compared with LADG and ODG.

Discovery of LL-K8-22: A Selective, Durable, and Small-Molecule Degrader of the CDK8-Cyclin C Complex.

The CDK8-cyclin C complex is an important anti-tumor target, but unlike CDK8, cyclin C remains undruggable. Modulators regulating cyclin C activity directly are still under development. Here, a series of hydrophobic tagging-based degraders of the CDK8-cyclin C complex were designed, synthesized, and evaluated to identify the first dual degrader, LL-K8-22, which induced selective and synchronous degradation of CDK8 and cyclin C. Proteomic and immunoblot studies exhibited that LL-K8-22 significantly degraded CDK8 without reducing CDK19 and did not degrade other cyclin proteins except cyclin C. Moreover, LL-K8-22 showed enhanced anti-proliferative effects over its parental molecule, BI-1347, with potency increased by 5-fold in MDA-MB-468 cells. LL-K8-22 exhibited more pronounced effects on CDK8-cyclin C downstream signaling than BI-1347, suppressing STAT1 phosphorylation more persistently. RNA-sequencing analysis revealed that LL-K8-22 inhibited E2F- and MYC-driven carcinogenic transcriptional programs. Overall, LL-K8-22 is the first-in-class degrader of cyclin C and would be useful for studying the unknown functions of cyclin C.

The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials.

Aims: Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs). Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4. Results: Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups versus placebo or standard diabetes therapies (SMD: -1.21; 95% CI: -1.91, -0.52, p < 0.001). The effects of CRP (SMD: 0.25; 95% CI: -0.47, -0.03, p = 0.02) and leptin (SMD: -0.22; 95% CI: -0.43, -0.01, p = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, p < 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: -0.38; 95% CI: -0.61, -0.15, p = 0.001). Conclusion: This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.

[Clinical application progress of subjective visual vertical test].

Subjective visual vertical test is considered as an effective technique to evaluate otolith organ function and central pathway of gravity perception. This test is non-invasive, easy to operate and has little stimulation. At present, there are few such studies in China. This paper reviews the concept, measurement principle and method, influencing factors, application, advantages and disadvantages of subjective visual vertical test.

[Application of computerized cognitive behavioral therapy in patients with persistent postural-perceptual dizziness].

Objective:A computerized cognitive behavioral therapy intervention program was constructed for patients with persistent postural-perception dizziness（PPPD） and its effects on dizziness symptoms, negative emotions and balance function were investigated. Methods:A randomized controlled trial design was used to select 86 patients with PPPD who were seen in the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University from July 2020 to July 2021. Randomly assigned to the control group（43 patients） and the experimental group（43 patients）. The control group was routinely treated with medication and vestibular rehabilitation, while the experimental group underwent computerized cognitive behavioral therapy for a total of 9 sessions over 8 weeks; their dizziness symptoms（DHI）, negative affect（GAD-7, PHQ-9） and balance function（BBS） were compared at baseline, 4 and 8 weeks later. Results:After 4 and 8 weeks of intervention, the improvement of dizziness symptoms and negative mood in both groups had a between-group effect, time effect, and interaction effect（P<0.05）. The improvement of balance function had only a time effect and interaction effect（P<0.05）, and no difference in between-group effect was seen（P>0.05）. Conclusion:Computerized cognitive behavioral therapy can be used as an adjunctive treatment to alleviate patients' dizziness, negative affect, and balance function, but no additional benefit has been seen in terms of balance function improvement.

Sex difference in response to non-small cell lung cancer immunotherapy: an updated meta-analysis.

BACKGROUND: Studying sex differences in the efficacy of immunotherapy may contribute to the practice of the precision medicine, especially in non-small cell lung cancer (NSCLC), a kind of cancer with sexual bimorphism. METHODS: Published randomized controlled trials (RCTs), published by PubMed, Medline, Embase, and Scopus, before 15 June 2022, testing immunotherapy (CTLA-4 or PD-1/L1 inhibitor alone, combination or with chemotherapy) versus non-immunotherapy (receiving chemotherapy or placebo only) were included to assess different efficacy between males and females. The primary endpoint was overall survival (OS). This meta-analysis was registered with PROSPERO (CRD42022298439). RESULTS: Sixteen RCTs, involving 10,155 patients with advanced NSCLC, was collected in this meta-analysis. The pooled HR comparing immunotherapy vs non-immunotherapy were 0.76 (95%CI 0.71-0.81) for males and 0.74 (95%CI 0.63-0.87) for females. The pooled HRs comparing immune-checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy were 0.79 (95%CI 0.70-0.89) for males and 0.63 (95%CI 0.42-0.92) for females. The pooled HRs comparing ICIs versus chemotherapy were 0.74 (95%CI 0.67-0.81) for males and 0.83 (95%CI 0.73-0.95) for females. In squamous NSCLC, the pooled HRs comparing immunotherapy vs non-immunotherapy were 0.73 (95%CI 0.58-0.91) for males and 0.74 (95%CI 0.37-1.48) for females. In non-squamous NSCLC, the pooled HRs comparing immunotherapy versus non-immunotherapy were 0.62 (95%CI 0.71-0.94) for males and 0.59 (95%CI 0.39-0.89) for females. CONCLUSION: Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. Meanwhile, there are sex differences in the efficacy of immunotherapy.KEY MESSAGECompared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC.The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC.

[Serum 25-hydroxyvitamin D expression and its correlation in patients with vestibular neuritis].

Objective:To investigate the expression level of serum 25-（OH） D and its correlation in patients with vestibular neuritis（VN）. Methods:30 acute VN patients and 50 age-and sex-matched healthy controls who attended the Otolaryngology, Head and Neck Surgery Department of the First Hospital of Shanxi Medical University from October 2020 to October 2021 were selected. The demographic and clinical data of all subjects were recorded, the levels of serum 25-（OH） D and inflammatory markers were measured and compared, and the changes of serum 25-（OH） D levels in convalescent patients with VN were followed up. Results:The serum level of 25-（OH） D in the acute phase VN group was significantly lower than that in healthy controls[（10.14±2.92） ng/mL vs （20.61±4.70） ng/mL, P<0.01], and the deficiency rate of 100.0%（30/30） was significantly higher than 54.0%（27/50）. Moreover, the serum level of 25-（OH） D in the recovery period（3 months later） was significantly higher[（10.14±2.92） ng/mL vs （15.94±4.88） ng/mL, P<0.01], and the deficiency rate was significantly decreased by 76.7%（23/30）. However, the serum 25-（OH） D level was significantly lower in both the VN group than that in both the acute period and the recovery group, and the deficiency rate was significantly higher than that in the control group. Multivariate binary Logistic regression model analysis showed that low-level serum 25-（OH） D was associated with the onset of VN, with an OR value of 0.193（95%CI=0.043-0.861, P=0.031）. In addition, the results of this study showed that peripheral blood leukocyte（WBC） and neutrophil / lymphocyte ratio（NLR） levels in the acute VN group were significantly higher than in healthy controls[（7.65±3.02） ×108/L vs （5.50±2.50） ×108/L, P<0.01; （2.46±2.95） ×100% vs（1.67±0.92） ×100%, P<0.01 ], and there was no significant difference in Platelet / lymphocyte ratio（PLR） and and average platelet volume（MPV） levels in the two groups（P>0.05）. There were no significant differences in age distribution, sex ratio, body mass index, persistent health problems, or lifestyle groups（P>0.05）. Conclusion:This study is the first to detect serum 25-（OH） D level and inflammation index level, and dynamically assess the serum 25-（OH） D level in different stages, found that low serum 25-（OH） D is associated with the onset of VN, physiological concentration of serum 25-（OH） D is a protective factor of VN, vitamin D supplementation therapy may be a new target of VN treatment.

Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway.

Chloride channel-5 (ClC-5), an important branch of the ClC family, is involved in the regulation of the proliferation and cell-fate of a variety of cells, including tumor cells. However, its function in cholangiocarcinoma (CCA) cells remains enigmatic. Here, we discovered that ClC-5 was up-regulated in CCA tissues and CCA cell lines, while ClC-5 silencing inhibited CCA cell proliferation and induced apoptosis. Further mechanism studies revealed that ClC-5 inhibition could inhibit Wnt/ß-catenin signaling activity and further activate the mitochondria apoptotic pathway in CCA cells. Furthermore, rescuing Wnt/ß-catenin signaling activation eliminated the anti-tumor function of ClC-5 knockdown. Together, our research findings illustrated that ClC-5 inhibition plays an anti-tumor role in CCA cells via inhibiting the activity of the Wnt/ß-catenin pathway, which in turn activates the mitochondrial apoptotic pathway. [BMB Reports 2022; 55(6): 299-304].