RNA m6A methylation regulators in liver cancer.

Liver cancer is one of the most common cancers in the world and a primary cause of cancer-related death. In recent years, despite the great development of diagnostic methods and targeted therapies for liver cancer, the incidence and mortality of liver cancer are still on the rise. As a universal post-transcriptional modification, N6-methyladenosine (m6A) modification accomplishes a dynamic and reversible m6A modification process, which is executed by three types of regulators, methyltransferases (called writers), demethylases (called erasers) and m6A-binding proteins (called readers). Many studies have shown that m6A RNA methylation has an important impact on RNA metabolism, whereas its regulation exception is bound up with the occurrence of human malignant tumors. Aberrant methylation of m6A RNA and the expression of related regulatory factors may be of the essence in the pathogenesis and progression of liver cancer, yet the precise molecular mechanism remains unclear. In this paper, we review the current research situations of m6A methylation in liver cancer. Among the rest, we detail the mechanism by which methyltransferases, demethylases and m6A binding proteins regulate the occurrence and development of liver cancer by modifying mRNA. As well as the potential effect of m6A regulators in hepatocarcinogenesis and progression. New ideas and approaches will be given to the prevention and treatment of liver cancer through the following relevant research results.

Recurrent steroid cell tumor not otherwise specified with elevated testosterone and prolactin concentrations and impaired glucose metabolism: a case report.

Steroid cell tumor not otherwise specified (SCT-NOS) is a rare type of sex cord-stromal tumor with malignant potential. A 19-year-old woman underwent laparoscopic bilateral cystectomy, and postoperative pathology showed bilateral ovarian SCT-NOS. She had recurrence of the right tumor 8 years after the surgery, with shortened menstrual cycles, elevated testosterone and prolactin concentrations, and impaired glucose metabolism. We performed a laparoscopic right salpingo-oophorectomy. Testosterone and prolactin concentrations rapidly decreased and returned to the normal range after surgery. Subsequently, she had regular menstrual cycles and good glycemic control. The findings in our case suggest that there is a possibility of late recurrence in SCT-NOS. Therefore, we suggest that the postoperative follow-up period should be 10 years for this condition.

SLFN5 promotes reversible epithelial and mesenchymal transformation in ovarian cancer.

Ovarian cancer is a disease with increasing incidence worldwide, and there is an urgent need for chemotherapy and biological targeted therapy. Epithelial-mesenchymal transformation (EMT) is an important initiation stage for tumor cells to acquire the ability to invade and metastasize. A growing number of findings suggest that human Schlafen family member 5(SLFN5) plays a key role in malignancy. However, the role of SLFN5 in ovarian cancer cells has not been fully elucidated. Samples were collected from patients with ovarian cancer diagnosed in Hangzhou First People's Hospital, and the expression of SLFN5 was detected by fluorescence quantitative PCR. The relationship between SLFN5 expression and the progression and malignancy of ovarian cancer was analyzed by using the expression profile data from the Cancer Genome Atlas (TCGA) database. The mRNA expression levels of SLFN5 related upstream and downstream signaling pathways were studied by fluorescence quantitative PCR. Silencing SLFN5 was performed by siRNA transfection. The expression of SLFN5 and transfer-related proteins was examined by Western blot. Transwell and wound healing experiments investigated the migration and invasion ability of ovarian cancer cells. TCGA database analysis results showed that in the population with high SLFN5 expression, compared with the group with low SLFN5 expression, OS was worse (P = 0.011). SLFN5 silencing had a significant inhibitory effect on EMT and invasion movement of ovarian cancer cells. RT-PCR method was used to detect the mRNA changes of SLFN5 in ovarian cancer tissue and adjacent tissue. It was found that the expression of SLFN5 in ovarian cancer tissue was increased, with a significant difference (P < 0.05). Together, these results suggest that SLFN5 may play a synergistic role in tumorigenesis and development of ovarian cancer cells, providing a potential target for future drug development for the treatment of ovarian cancer.

Ferroptosis: A New Promising Target for Ovarian Cancer Therapy.

Ferroptosis is a novel kind of regulated cell death distinct from autophagy, apoptosis, and necrosis; it is predominantly caused by the iron-dependent lipid peroxidation. According to studies, numerous conventional signaling pathways and biological processes are implicated in the process of ferroptosis. In recent years, researchers have shown that ferroptosis plays an important role in the genesis, development, and metastasis of malignancies, including ovarian cancer. Several studies have revealed that ferroptosis has synergistic effects with chemotherapy, radiotherapy, and immunotherapy in inhibiting the growth of ovarian cancer cells. This suggests that ferroptosis is important in ovarian cancer treatment and may be a new target. In this review, we summarize the features of ferroptosis, including its underlying basis and function in ovarian cancer, as well as its potential applications in the treatment of ovarian cancer.

Midgut malrotation presenting with hyperemesis gravidarum: A case report.

RATIONALE: Midgut malrotation is a rare congenital abnormality resulting from failure of complete intestinal rotation and subsequent fixation during early fetal development. There appeared to be no obvious symptoms in most patients, and a few patients may exhibit symptoms similar to hyperemesis gravidarum, such as nausea and vomiting. Here, we present a case of midgut malrotation presenting as hyperemesis gravidarum. PATIENT CONCERNS: A 27-year-old woman with an intrauterine pregnancy of 27 + 6 weeks complained of severe nausea and vomiting for 2 weeks. DIAGNOSIS: Magnetic resonance imaging showed obvious dilatation in the proximal part of the duodenum and gastric cavity and the absence of a duodenal path dorsal to the superior mesenteric artery, which was diagnosed as midgut malrotation. INTERVENTIONS: Considering that the patient's vital signs were stable, without manifestation of peritonitis or the risks of surgery to the fetus, conservative treatment was adopted. Unfortunately, the fetus developed severe hydrocephalus at 32 weeks. The patient and her family decided to abandon the fetus, and a mid-trimester-induced abortion was performed. OUTCOMES: The related symptoms completely disappeared after delivery, and the relevant examination after discharge also confirmed the presence of midgut malrotation without gastrointestinal discomfort within 1 year after delivery. LESSONS: Midgut malrotation can be considered as a differential diagnosis of hyperemesis gravidarum. Conservative treatment under close monitoring is desirable in pregnant women diagnosed with midgut malrotation.

Characterization of the Potential Role of NTPCR in Epithelial Ovarian Cancer by Integrating Transcriptomic and Metabolomic Analysis.

BACKGROUND: Epithelial ovarian carcinoma (EOC) is a malignant tumor with high motility in women. Our previous study found that dysregulated nucleoside-triphosphatase cancer-related (NTPCR) was associated with the prognosis of EOC patients, and thus, this present study attempted to explore the potential roles of NTPCR in disease progression. METHODS: Expressed level of NTPCR was investigated in EOC tissues by RT-qPCR and Western blot analysis. NTPCR shRNA and overexpression vector were generated and transfected into OVCAR-3 or SKOV3 cells to detect the effect of NTPCR on cell proliferation, cell cycle, cell migration, and invasion. Transcriptomic sequencing and metabolite profiling analysis were performed in shNTPCR groups to identify transcriptome or metabolite alteration that might contribute to EOC. Finally, we searched the overlapped signaling pathways correlated with differential metabolites and differentially expressed genes (DEGs) by integrating analysis. RESULTS: Comparing para-cancerous tissues, we found that NTPCR is highly expressed in cancer tissues (p < 0.05). Overexpression of NTPCR inhibited cell proliferation, migration, and invasion and reduced the proportion of S- and G2/M-phase cells, while downregulation of NTPCR showed the opposite results. RNA sequencing analysis demonstrated cohorts of DEGs were identified in shNTPCR samples. Protein-protein interaction networks were constructed for DEGs. STAT1 (degree = 43) and OAS2 (degree = 36) were identified as hub genes in the network. Several miRNAs together with target genes were predicted to be crucial genes related to disease progression, including hsa-miR-124-3p, hsa-miR-30a-5p, hsa-miR-146a-5, EP300, GATA2, and STAT3. We also screened the differential metabolites from shNTPCR samples, including 22 upregulated and 22 downregulated metabolites. By integrating transcriptomics and metabolomics analysis, eight overlapped pathways were correlated with these DEGs and differential metabolites, such as primary bile acid biosynthesis, protein digestion, and absorption, pentose, and glucuronate interconversions. CONCLUSION: NTPCR might serve as a tumor suppressor in EOC progression. Our results demonstrated that DEGs and differential metabolites were mainly related to several signaling pathways, which might be a crucial role in the progression of NTPCR regulation of EOC.

Dexamethasone may inhibit placental growth by blocking glucocorticoid receptors via phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin and reactive oxygen species/AMP-activated protein kinase signalling pathways in human placental JEG-3 cells.

This study explored the molecular mechanism underlying the effects of dexamethasone (DEX, 1 µM) on glucose transporters (GLUT) in JEG-3 human placental choriocarcinoma cells. JEG-3 cells were treated with DEX, an expression plasmid encoding human glucocorticoid receptor α (GRα), pcDNA3.1-GRα, GRα short interference (si) RNA, LY294002, xanthine oxidase (XO)/hypoxanthine (HX), rapamycin, insulin-like growth factor (IGF) 1, N-acetylcysteine (NAC) or phosphatidic acid (PA), and cell proliferation, apoptosis, mitochondrial membrane potential (MMP), human chorionic gonadotrophin (hCG) content, human placental lactogen (hPL) content, glucose uptake, reactive oxygen species levels and signalling pathway modulation were evaluated. Treatment of JEG-3 cells with DEX (1 µM), GRα siRNA, LY294002 (50 µM), XO/HX (7.2 µM/36 nM) or rapamycin (80 nM) inhibited cell proliferation, induced apoptosis, significantly decreased MMP and hCG and hPL content and increased ROS levels. In addition, glucose uptake was decreased through downregulation of the mRNA and protein expression of GRα, GLUT1 and GLUT3. Treatment of JEG-3 cells with GRα siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. The effects of GRα overexpression and IGF1 (100 nM), NAC (5 nM) or PA (100 µM) treatment on JEG-3 cells contrasted with those of DEX treatment. DEX blocked glucose uptake by downregulating GRα expression, which reduced GLUT1 and GLUT3 mRNA and protein expression, which, in turn, may have inhibited the PI3K/AKT/mTOR pathway and activated the ROS/AMPK pathway.

Integrated analysis of transcriptomic and metabolomic data demonstrates the significant role of pyruvate carboxylase in the progression of ovarian cancer.

The aim of this study was to explore prognosis-related biomarkers and underlying mechanisms during ovarian carcinoma progression and development. mRNA expression profiles and GSE49997 dataset were downloaded. Survival analyses were performed for genes with high expression levels. Expression level of candidate genes was explored in four ovarian cancer cells lines. Pyruvate carboxylase (PC) was found to be one of significantly differentially expressed gene (DEG). The role of PC knockdown was analyzed in SKOV cells using cell proliferation, flow cytometric, and Transwell migration and invasion assays. DEGs and metabolites in PC-shRNA (shPC)-treated samples vs. control groups were identified. PC was a prognosis-related gene and related to metabolic pathway. Knockdown of PC regulated cell proliferation, cell cycle progression, and migration and invasion of SKOV-3 cells. Transcriptome sequencing analyses showed STAT1 and TP53 gained higher degrees in PPI network. A total of 44 metabolites were identified. These DEGs and metabolites in PC samples were related with neuroactive ligands receptor interaction, glycine, serine and threonine metabolism, and ABC transporter pathways. PC may affect the tumor biology of ovarian cancer through the dysregulation of glycine, serine, and threonine metabolism, and ABC transporter pathways, as well as STAT1 and TP53 expression.

Revealing the action mechanisms of dexamethasone on the birth weight of infant using RNA-sequencing data of trophoblast cells.

Dexamethasone (DEX) could induce low birth weight of infant, and low birth weight has close associations with glucocorticoid levels, insulin resistance, hypertension, and metabolic syndrome in adulthood. This study was designed to reveal the action mechanisms of DEX on the birth weight of infant.Using quantitative real-time polymerase chain reaction (qRT-PCR), trophoblast cells of human placenta were identified and the optimum treatment time of DEX were determined. Trophoblast cells were treated by DEX (DEX group) or ethanol (control group) (each group had 3 samples), and then were performed with RNA-sequencing. Afterward, the differentially expressed genes (DEGs) were identified by R package, and their potential functions were successively enriched using DAVID database and Enrichr method. Followed by protein-protein interaction (PPI) network was constructed using Cytoscape software. Using Enrichr method and TargetScan software, the transcription factors (TFs) and micorRNAs (miRNAs) targeted the DEGs separately were predicted. Based on MsigDB database, gene set enrichment analysis (GSEA) was performed.There were 391 DEGs screened from the DEX group. Upregulated SRR and potassium voltage-gated channel subfamily J member 4 (KCNJ4) and downregulated GALNT1 separately were enriched in PDZ (an acronym of PSD-95, Dlg, and ZO-1) domain binding and Mucin type O-glycan biosynthesis. In the PPI network, CDK2 and CDK4 had higher degrees. TFs ATF2 and E2F4 and miRNA miR-16 were predicted for the DEGs. Moreover, qRT-PCR analysis confirmed that SRR and KCNJ4 were significantly upregulated.These genes might affect the roles of DEX in the birth weight of infant, and might be promising therapeutic targets for reducing the side effects of DEX.

Early dexamethasone treatment induces placental apoptosis in sheep.

Glucocorticoid treatment given in late pregnancy in sheep resulted in altered placental development and function. An imbalance of placental survival and apoptotic factors resulting in an increased rate of apoptosis may be involved. We have now investigated the effects of dexamethasone (DEX) in early pregnancy on binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 49, intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at 40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and 140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax, p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC numbers and apoptotic markers were restored to normal. In males, ovine placental lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG significantly decreased compared to controls. In contrast to females, these changes were independent of altered BNC numbers or apoptotic markers. Early DEX was associated with sex-specific, transient alterations in BNC numbers, which may contribute to changes in placental and fetal development. Furthermore, in females, altered placental apoptosis markers may be involved.

Gum chewing slightly enhances early recovery from postoperative ileus after cesarean section: results of a prospective, randomized, controlled trial.

Postoperative ileus is one of the common problems after abdominal surgeries. It contributes to delayed recovery and prolongs hospital stay. Sham feeding, such as gum chewing, may accelerate return of bowel function and reduce morbidity and length of hospital stay. This study aimed to determine whether gum chewing in the immediate postoperative period facilitates a return to bowel function in cesarean-delivery patients. Three hundred eighty-eight patients who underwent cesarean delivery were randomly assigned to a gum-chewing group (group G, N = 193) or a control group (group C, N = 195). Demographic data, duration of surgery, type of anesthesia, and time of discharge from hospital were recorded. Patients in the gum-chewing group chewed gum three times per day as soon as returning from the operating theater to the ward until the time they defecated or were discharged. Patients were asked to chew gum at least half an hour each time. The T test and Pearson chi-square test was used for statistical analysis. Groups were comparable in age, weight, height, weeks of gestation, duration of surgery, and type of anesthesia. Bowel sounds were 5 hours earlier in the gum-chewing group (mean 18.2 hours) than in the control group (mean 23.2 hours). Passing flatus was 5.3 hours earlier in group G (mean 34.6 hours) than in group C (mean 39.9 hours). Patients having mild ileus symptoms were 9% less in group G (mean 12%) than in group C (mean 21%). The difference between the two groups were all highly significant (p < 0.001). Gum chewing was easily tolerated without any complications. Gum chewing is an inexpensive, convenient, and physiological method in enhancing the recovery of bowel function. But this may not facilitate early hospital discharge, lactation, or defecation.

[Study of luminescence properties of nano-size ZnO embedded in SiO2 layer grown by radio-frequency magnetron sputtering].

Nano-size ZnO embedded in SiO2 layers were grown by radio-frequency magnetron sputtering. Absorption spectra and PL spectra were employed to study the optical character of the samples at room temperature. Absorption spectra blue-shifted when the size of nano-meter ZnO decreased, which indicated that quantum size effect became stronger with decreasing the size of ZnO. PL spectra show two peaks at about 387 and 441 nm, respectively. It was concluded that the UV emission originates from the radiative recombination of free-exciton, and the blue emission is due to the electron transition from donor levels of oxygen vacancies to the top of valence band. The origin of the two peaks is demonstrated by time-resolved spectra and luminescence decay curve.