High expression of HM13 correlates with poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate, and the identification of early prognostic markers is crucial for improving patient outcomes. This study aimed to investigate the correlation between the expression of Histocompatibility Minor 13 (HM13) and the prognosis of HCC patients. HM13 protein expression was assessed in HCC tissues and cells through immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and western blot. The relationship between HM13 expression and clinicopathological data of HCC was evaluated. Bioinformatics analyses, including Gene Expression Omnibus (GEO) database, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter (K-M plotter), were employed to analyze HM13 expression and its association with patient survival. HM13 was significantly overexpressed in HCC tissues and cells compared to normal controls. IHC revealed that HM13 protein was primarily localized in the cytoplasm and highly expressed in HCC tissues. Interestingly, patients with high HM13 expression had significantly poorer overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS) than those with low expression. HM13 expression was associated with Edmondson grade, metastasis, microvascular invasion, and alpha-fetoprotein (AFP) levels. Multivariate analysis identified HM13 as an independent prognostic factor for poor OS in HCC. HM13 was markedly overexpressed in HCC and correlated with poor prognosis, suggesting its potential as a promising biomarker for early prognostic detection in HCC patients.

USP53 Affects the Proliferation and Apoptosis of Breast Cancer Cells by Regulating the Ubiquitination Level of ZMYND11.

Breast cancer is the most common female malignancy worldwide. Ubiquitin-specific peptidase 53 (USP53) has been shown to exert cancer-suppressing functions in several solid tumors, but its role and the underlying mechanism in breast cancer has not been clearly elucidated. Therefore, we have carried out a series of detailed studies on this matter at the levels of bioinformatics, clinical tissue, cell function and animal model. We found that USP53 expression was downregulated in breast cancer specimens and was negatively correlated with the clinical stages. Gain- and loss-of-function experiments demonstrated USP53 inhibited proliferation, clonogenesis, cell cycle and xenograft growth, as well as induced apoptosis and mitochondrial damage of breast cancer cells. Co-immunoprecipitation data suggested that USP53 interacted with zinc finger MYND-type containing 11 (ZMYND11), and catalyzed its deubiquitination and stabilization. The 33-50 amino acid Cys-box domain was key for USP53 enzyme activity, but not essential for its binding with ZMYND11. The rescue experiments revealed that the anti-tumor role of USP53 in breast cancer cells was at least partially mediated by ZMYND11. Both USP53 and ZMYND11 were prognostic protective factors for breast cancer. USP53-ZMYND11 axis may be a good potential biomarker or therapeutic target for breast cancer, which can provide novel insights into the diagnosis, treatment and prognosis.

Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.

Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that exhibits divergent roles in various cancer types (oncogenic and anti-oncogenic). This study investigates the interaction of TRIM26 with the tumor suppressor protein p53 in colorectal cancer (CRC) cells by performing a comprehensive set of biochemical, cell-based assays, and xenograft experiments. As a result, we found that overexpression of TRIM26 significantly enhances CRC cell proliferation and colony formation, while knockdown of TRIM26 suppresses these processes. Xenograft experiments further validated the tumor-promoting role of TRIM26 in CRC. Supporting this is that TRIM26 is highly expressed in human CRC tissues as revealed by our analysis of the TCGA database. Biochemically, TRIM26 directly bound to the C-terminus of p53 and facilitated its ubiquitination, resulting in proteolytic degradation and attenuated p53 activity independently of MDM2. Also, TRIM26 increased the MDM2-mediated ubiquitination of p53 by binding to MDM2's C-terminus. This study uncovers the oncogenic potential of TRIM26 in CRC by inhibiting p53 function. Through its ubiquitin ligase activity, TRIM26 destabilizes p53, consequently promoting CRC cell proliferation and tumor growth. These findings shed light on the complex involvement of TRIM26 in cancer and identify this ubiquitin ligase as a potential therapeutic target for future development of CRC treatment.

Long-Term Effect of ß-Blocker Use on Clinical Outcomes in Postmyocardial Infarction Patients: A Systematic Review and Meta-Analysis.

Background: Prior studies provided inconsistent results regarding long-term effect of ß-blocker use on clinical outcomes in postmyocardial infarction (MI) patients. Methods: We searched for articles regarding long-term effect of ß-blocker use on clinical outcomes in patients after MI and published them before July 2021 in the databases as follows: PubMed, Web of Science, MEDLINE, EMBASE, and Google Scholar. STATA 12.0 software was used to compute hazard ratios (HRs) and their 95% confidence intervals (CIs). Results: The study indicated that ß-blocker group had significantly lower long-term all-cause mortality, cardiovascular mortality, major adverse cardiac events (MACEs) in post-MI patients, compared to no ß-blocker group (all-cause mortality: HR, 0.67; 95% CI: 0.56-0.80; cardiovascular mortality: HR, 0.62; 95% CI: 0.49-0.78; MACE: HR, 0.87; 95% CI: 0.75-1.00). The study indicated no significant long-term effect of ß-blocker use on risk of hospitalization for heart failure (HF), risk of recurrent MI, risk of stroke, and risk of repeat revascularization in post-MI patients (risk of hospitalization for HF: HR, 0.82; 95% CI: 0.58-1.16; risk of recurrent MI: HR, 0.93; 95% CI: 0.78-1.11; risk of stroke: HR, 0.94; 95% CI: 0.79-1.12; risk of repeat revascularization: HR, 0.91; 95% CI: 0.80-1.04). Conclusions: The meta-analysis demonstrated significant long-term effects of ß-blocker use on all-cause mortality, cardiovascular mortality, and risk of MACE in post-MI patients, whereas no significant long-term effect was shown on risk of hospitalization for HF, risk of recurrent MI, risk of stroke, and risk of repeat revascularization in post-MI patients.

Integrated Bioinformatic Analysis of Competing Endogenous RNA Network of Choriocarcinoma.

BACKGROUND Numerous studies have demonstrated that noncoding RNAs are involved in choriocarcinoma (CC). The competing endogenous RNA (ceRNA) network plays an important role in the occurrence and development of carcinoma. However, the involvement of the ceRNA network in CC remains unclear. The current study aimed to investigate the regulatory mechanism of ceRNA in CC. MATERIAL AND METHODS We downloaded the messenger RNAs (mRNAs) expression profiles (GSE20510 and GSE65654) and microRNAs (miRNAs) expression profiles (GSE32346 and GSE130489) from GEO datasets. The limma package of R software was used to identify differentially expressed RNAs (DERNAs). Then, we performed functional annotation of the differentially expressed mRNAs (DEmRNAs). TargetScan, miRDB, miRWalk, and Starbase were used to construct a CC-specific ceRNA network and select key molecules. RESULTS The results identified a total of 177 DEmRNAs and 189 differentially expressed miRNAs (DEmiRNAs) between the trophoblast and CC cell line samples. Ten differentially expressed lncRNAs (DElncRNAs) were obtained based on experimental studies. The DEmRNAs were mainly enriched in cell proliferation, positive regulation of the apoptotic process, and cell death. A total of 10 genes were ascertained as hub genes. Based on DEmRNAs, DEmiRNAs, and DElncRNAs, a CC-specific ceRNA network was established. Five DElncRNAs, 15 DEmiRNAs, and 45 DEmRNAs were identified. In addition, LINC00261, MEG3, MALAT1, H19, and OGFRP1 were identified as 5 key lncRNAs in choriocarcinoma. CONCLUSIONS This study provides novel insights into CC mechanisms and identified potential therapeutic targets for CC.

ADAM12 silencing promotes cellular apoptosis by activating autophagy in choriocarcinoma cells.

ADAM metallopeptidase domain 12 (ADAM12) has been demonstrated to mediate cell proliferation and apoptosis resistance in several types of cancer cells. However, the effect of ADAM12 silencing on the proliferation and apoptosis of choriocarcinoma cells remains unknown. The present study revealed that ADAM12 silencing significantly inhibited cellular activity and proliferation in the human choriocarcinoma JEG3 cell line and increased the rate of apoptosis. In addition, ADAM12 silencing significantly increased the expression levels of the autophagy proteins microtubule­associated protein­light­chain 3 (LC3B) and autophagy related 5 (ATG5) and the fluorescence density of LC3B in JEG­3 cells. However, the suppression of autophagy by 3­methyladenine could block ADAM12 silencing­induced cellular apoptosis. ADAM12 silencing reduced the levels of the inflammatory factors interleukin­1ß, interferon­Î³ and TNF­α, and inactivated nuclear p65­NF­κB and p­mTOR in JEG­3 cells. The downregulation of p­mTOR expression by ADAM12 silencing was rescued in 3­methyladenine­treated JEG­3 cells, indicating that mTOR might participate in the autophagy­mediated pro­apoptotic effect of ADAM12 silencing. In conclusion, ADAM12 silencing promoted cellular apoptosis in human choriocarcinoma JEG3 cells, which might be associated with autophagy and the mTOR response. These findings indicate that ADAM12 silencing might be a potential novel therapeutic target for choriocarcinoma.

Gender differences in caregiving among a schizophrenia population.

BACKGROUND: The present study aimed to investigate differences in family burden and caregiver distress in a population of caregivers for schizophrenia, by separating patient gender and caregiver gender. METHODS: A sample of 327 primary family caregivers was recruited from a Chinese rural community through a one-stage cluster-sampling method. A cross-sectional design was employed, using validated measures to assess both family burden and primary caregivers' depression and anxiety. RESULTS: Significant differences by gender were detected in family burden and caregiver distress. Family burden was significantly higher for male patients on the domains of effect on physical and mental health of others, and significantly higher for female caregivers on the domains of financial burden and effect on physical and mental health of others. Caregivers of male patients were more likely to suffer from anxiety than caregivers of female patients (52.7% vs 38.1%, P=0.012); female caregivers were more likely to suffer from depression (51.2% vs 38.6%, P = 0.031) and anxiety (51.6% vs 38.1%, P=0.020) than male caregivers. CONCLUSION: The results reinforced the expected differences in caregiving experiences of a schizophrenia population by gender, which has implications for the future design of gender-specific interventions to alleviate family burden and caregiver distress.

IκB kinase b Mediating the Downregulation of p53 and p21 by Lipopolysaccharide in Human Papillomavirus 16+ Cervical Cancer Cells.

BACKGROUND: Cervical cancer is the second most common cancer of woman in the world, and human papillomavirus (HPV) infection plays an important role in the development of most of the cases. IκB kinase ß (IKKß) is a kinase-mediating nuclear factor kappa B (NF-κB) activation by phosphorylating the inhibitor of NF-κB (IκB) and is related by some diseases caused by virus infection. However, there is little known about the correlation between IKKß and HPV infection in cervical cancer. This study aimed to investigate the expression of IKKß protein in cervical cancer tissues and effects of inflammation on HPV positive or negative cervical cancer cells through detecting the expression of IKKß, IκBα, p53, and p21 proteins after treated with lipopolysaccharide (LPS) to mimic bacterial infection. We also examined the effects of LPS on cervical cancer cells after blocking IKKß with pharmacological inhibitor. METHODS: Thirty-six matched specimens of cervical cancer and adjacent normal tissues were collected and analyzed in the study. The expression of IKKß in the tissue specimens was determined by immunohistochemical staining. In addition, Western blot was used to detect the expression level changes of IKKß, IκBα, p53, and p21 after LPS stimulated in the HPV16+ (SiHa) and HPV16- (C33A) cervical cancer cell lines. Furthermore, the effects of IKKß inhibitor SC-514 on LPS-induced expression change of these proteins were investigated. RESULTS: The expression of IKKß was higher in cervical cancer than adjacent normal tissues, and there was no significant difference between tumor differentiation, size, and invasive depth with IKKß expression. The LPS, which increased the expression level of IKKß protein but decreased in the IκBα, p53 and p21 proteins, was illustrated in HPV16+ (SiHa) but not in HPV16- (C33A) cells. Moreover, IKKß inhibitor SC-514 totally reversed the upregulation of IKKß and downregulation of p53 and p21 by LPS in SiHa cells. CONCLUSIONS: IKKß may mediate the downregulation of p53 and p21 by LPS in HPV16+ cervical cancer cells.

[A clinical analysis of gynecological diseases in 147 children].

OBJECTIVE: To study the clinical features of gynecological diseases in hospitalized children. METHODS: A retrospective analysis was performed for the clinical data of 147 children with gynecological diseases who were hospitalized and treated in the department of gynecology. RESULTS: Among the 147 children, ovarian tumors were most common (53 cases, 36.1%), followed by reproductive tract dysplasia or malformation (29 cases, 19.7%), adolescent dysfunctional uterine bleeding (18 cases, 12.2%), traumatic injury in the vulva/vagina (15 cases, 10.2%), and vaginal foreign body (8 cases, 5.4%). The main symptoms of ovarian tumors included abdominal pain and abdominal or pelvic mass. Progressive abdominal pain was a main symptom in children with reproductive tract dysplasia or malformation. The children with adolescent dysfunctional uterine bleeding manifested as irregular or a lot of vaginal bleeding. The children with ovarian tumors and reproductive tract malformation or dysplasia were given surgical treatment, and those with adolescent dysfunctional uterine bleeding were given different sex hormones based on their clinical manifestations and endometrial thickness. Eight children with vaginal foreign body underwent hysteroscopy for vaginal examination, and the foreign body was successfully removed without the damage of the hymen. One patient with tubal pregnancy underwent laparoscopic tubal pregnancy debridement. One patient with hydatid mole was diagnosed with invasive hydatid mole after complete curettage of uterine cavity and then received chemotherapy. CONCLUSIONS: The top three gynecological diseases in children are ovarian tumors, reproductive tract dysplasia or malformation, and adolescent dysfunctional uterine bleeding. Common chief complaints of the patients include abdominal pain, abdominal masses, and irregular vaginal bleeding. Diagnosis and treatment should fully consider the physiological and reproductive features of children and give full play to the advantages of laparoscopy, hysteroscopy, and ultrasound.

MiR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis.

AIM: To profile expression of microRNAs (miRNAs) in gastric cancer cells and investigate the effect of miR-374b-5p on gastric cancer cell invasion and metastasis. METHODS: An miRNA microarray assay was performed to identify miRNAs differentially expressed in gastric cancer cell lines (MGC-803 and SGC-7901) compared with a normal gastric epithelial cell line. Upregulation of miR-374b-5p was newly identified and confirmed via quantitative real-time reverse transcription-PCR (qRT-PCR). MGC-803 cells were transfected with a synthesized anti-miR-374b-5p sequence or a control vector using Lipofectamine reagent, or treated with transfection reagent alone or phosphate-buffered saline as controls. Rate of transfection was verified after 48 h by qRT-PCR. Cells were then subjected to transwell migration, wound scratch and cell counting kit-8 assays. A bioinformatic analysis to identify miR-374b-5p target genes was performed using miRanda, PicTar and TargetScan software. A dual luciferase reporter assay was performed to evaluate the influence of miR-374b-5p on target gene activation, and qRT-PCR and Western blot were used to evaluate the levels of target mRNA and protein following transfection with miR-374b-5p antisense oligonucleotides. RESULTS: The microarray profiling revealed downregulation of 14 (fold change < 0.667; P < 0.05) and upregulation of 12 (fold change > 1.50; P < 0.05) miRNAs in MGC-803 and SGC-7901 cells compared with GES-1 controls. The upregulation of miR-374b-5p (fold change = 1.75 and 1.64 in MGC-803 and SGC-7901, respectively; P < 0.05) was confirmed by qRT-PCR. Compared with the control groups, the restoration of miR-374b-5p expression with anti-miR-374b-5p significantly suppressed the metastasis, invasion and proliferation of MGC-803 cells. The bioinformatic analysis predicted that the 3' untranslated region (UTR) of reversion-inducing cysteine-rich protein with Kazal motif (RECK) contains three miR-374b-5p target sequences. RECK was verified as a target gene in a dual luciferase reporter assay showing that activation of RECK 3'UTR-pmirGLO was increased by co-transfection with miR-374b-5p. Finally, transfection of miR-374b-5p antisense oligonucleotides increased mRNA and protein levels of RECK in MGC-803 cells (P < 0.05). CONCLUSION: These findings indicate that upregulation of miR-374b-5p contributes to gastric cancer cell metastasis and invasion through inhibition of RECK expression.

MicroRNA-218 inhibits the proliferation of human choriocarcinoma JEG-3 cell line by targeting Fbxw8.

MicroRNAs (miRNAs) are endogenous 19-25 nucleotide noncoding single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, we showed that miR-218 expression levels were decreased while Fbxw8 expression levels were increased in human choriocarcinoma cell lines, and identified Fbxw8 as a novel direct target of miR-218. Overexpression of miR-218 inhibited cell growth arrest at G2/M phase, suppressed the protein levels of cyclin A and up-regulated the expression levels of p27 through decreasing the levels of Fbxw8. On the other hand, forced expression of Fbxw8 partly rescued the effect of miR-218 in the cells, attenuated cell proliferation decrease the percentage of cells at G2/M phase, induced cyclin A protein expression and suppressed the protein level of p27 through up-regulating the levels of Fbxw8. Taken together, these findings will shed light the role to mechanism of miR-218 in regulating JEG-3 cells proliferation via miR-218/Fbxw8 axis, and miR-218 may serve as a novel potential therapeutic target in human choriocarcinoma in the future.

[Proliferation and apoptosis of choriocarcinoma cell JEG-3 induced by VB2 and its in vitro mechanism].

OBJECTIVE: To investigate the effect of purified vitexin compound 2 (VB2), a noval lignanoid from the acetoacetate extract of Vitex negundo seed on the proliferation and apoptosis as well as the expression of mTOR and 4E-BP1 mRNA signal pathway in human choriocarcinoma JEG-3 cell lines in vitro. METHODS: The inhibitory effect of different concentrations of VB2 on JEG-3 cells was examined by methyl thiazolyl tetrazolium (MTT) assay. Flow cytormetry was used to analyze the apoptosis after using different concentrations of VB2, and the expression of mTOR and 4E-BP1 mRNA was determined by RT-PCR. RESULTS: The inhibitory rate of JEG-3 cell growth which was cultured with different concentrations of VB2 (2.5, 5.0, 10.0, 20.0, 40.0, 80.0, and 160.0 µmol/L) for 24, 48, or 72 hours increased from (6.34±0.41)% to (85.89±0.81)%, and it was positively correlated with the dose and time of culture (P<0.05). VB2 at 5.0, 10.0, or 20.0 µmol/L increased the rate of JEG-3 cell apoptosis in vitro from (9.26±1.02)% to (35.55±1.24)% after 48 hour culture, which was in a dose dependent manner (P<0.05), while 5.0, 10.0, or 20.0 µmol/L of VB2 down-regulated the mRNA levels of mTOR and 4E-BP1 after 48 hour culture, which presented a significant negative correlation between VB2 and the mRNA levels of mTOR and 4E-BP1(P<0.05). CONCLUSION: VB2 can restrain the proliferation of choriocarcinoma cell JEG-3 and induce its apoptosis. This effect may be related to the inhibition of VB2 on the mRNA expression of JEG-3 cell mTOR and 4E-BP1.

Purified vitexin compound 1 suppresses tumor growth and induces cell apoptosis in a mouse model of human choriocarcinoma.

OBJECTIVE: In our previous study, we had isolated a series of lignan compounds, termed vitexins, from the seed of Chinese herb Vitex negundo and found broad antitumor activities of these compounds in many cancer xenograft models and cell lines. This study was aimed to determine the antitumor effect of purified vitexin compound 1 (VB1) on choriocarcinoma in vitro and in vivo. MATERIALS AND METHODS: The severe combined immunodeficiency mouse model of choriocarcinoma was established to investigate the in vivo effect of VB1. Its effect on proliferation and apoptosis in JEG-3 cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay and flow cytometry, respectively. The expression of caspase-3, Bcl-2, and some molecules involved in the mammalian target of rapamycin (mTOR) signaling was detected by Western blot. RESULTS: Vitexin compound 1 significantly inhibited the growth of choriocarcinoma in severe combined immunodeficient mice and reduced the serum ß-human chorionic gonadotropin level. Vitexin compound 1 inhibited cell proliferation, induced apoptosis, and inhibited the mTOR signaling in JEG-3 cell line. CONCLUSION: Vitexin compound 1 could inhibit choriocarcinoma via inducing cell apoptosis and suppressing the mTOR pathway.