Troponin T1 in tumorigenesis and immune modulation: Insights into multiple cancers and kidney renal clear cell carcinoma.

Troponin T1 (TNNT1) plays a crucial role in muscle contraction but its role in cancer, particularly in kidney renal clear cell carcinoma (KIRC), is not well-understood. This study explores the expression, clinical significance and biological functions of TNNT1 in various cancers, with an emphasis on its involvement in KIRC. We analysed TNNT1 expression in cancers using databases like TCGA and GTEx, assessing its prognostic value, mutation patterns, methylation status and functional implications. The study also examined TNNT1's effect on the tumour microenvironment and drug sensitivity in KIRC, complemented by in vitro TNNT1 knockdown experiments in KIRC cells. TNNT1 is overexpressed in several cancers and linked to adverse outcomes, showing frequent upregulation mutations and abnormal methylation. Functionally, TNNT1 connects to muscle and cancer pathways, affects immune infiltration and drug responses, and its overexpression in KIRC is associated with advanced disease and reduced survival. Knocking down TNNT1 curbed KIRC cell growth. TNNT1's aberrant expression plays a significant role in tumorigenesis and immune modulation, highlighting its value as a prognostic biomarker and a potential therapeutic target in KIRC and other cancers. Further studies are essential to understand TNNT1's oncogenic mechanisms in KIRC.

Tectoridin inhibits the growth of bladder cancer by regulating PI3K/MAPK pathway through RAB27B.

Bladder cancer (BC) is a common and malignant tumor of the urinary tract, and its treatment options are limited. Tectoridin (TEC) has antitumor activity against prostate and colon cancer, but its effects on BC are poorly understood. BC cells were treated with increasing concentrations of TEC, and its effects on cell proliferation, migration, invasiveness, and apoptosis were assessed. Xenograft mouse model was used to evaluate the influences of TEC on BC tumor growth. Western blot analysis was conducted to explore the downstream pathways affected by TEC. TEC treatment decreased BC cell viability in a dose-dependent manner (IC50 ≈ 25 µM), and inhibited cell proliferation, migration, and invasiveness while promoting apoptosis. Clinical analysis revealed high expression of RAB27B in BC tumor tissues, particularly in advanced stages, correlating with an unfavorable prognosis. In vitro experiments demonstrated that TEC suppressed the PI3K/MAPK pathway by targeting RAB27B, and overexpression of RAB27B counteracted the antitumor effects of TEC. In xenograft models, TEC administration suppressed tumor growth, reduced tumor volume, inhibited cell proliferation, and suppressed the PI3K/MAPK pathway, highlighting its potential as an inhibitor of tumor growth. TEC suppresses BC tumor growth by targeting RAB27B and inactivating the PI3K/MAPK signaling and may provide a promising therapeutic target for BC treatment.

Long non-coding RNA LINC00491 accelerates head and neck squamous cell carcinoma progression through regulating miR-508-3p/SATB1 axis and activating Wnt signaling pathway.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck epidermis. Accumulating long non-coding RNAs (lncRNAs) have been proven to be involved in the occurrence and development of HNSCC. LncRNA long intergenic non-protein coding RNA 491 (LINC00491) has been confirmed to regulate the progression of some cancers. In our study, we aimed to explore the potential biological function of LINC00491 and expound the regulatory mechanism by which LINC00491 affects the progression of HNSCC. RT-qPCR was utilized to analyze the expression of LINC00491 in HNSCC cell lines and the normal cell line. Functionally, we carried out a series of assays to measure cell proliferation, apoptosis, migration and invasion, such as EdU assay, colony formation, wound healing and western blot assays. Also, mechanism assays including RNA pull down and RIP were also implemented to investigate the interaction of LINC00491 and RNAs. As a result, we discovered that LINC00491 was highly expressed in HNSCC cells. In addition, LINC00491 depletion suppressed cell proliferation, migration and EMT process. Furthermore, we discovered that LINC00491 could bind to miR-508-3p. MiR-508-3p overexpression can restrain HNSCC cell growth. Importantly, miR-508-3p can target SATB homeobox 1 (SATB1) in HNSCC cells. Further, Wnt signaling pathway was proved to be activated by LINC00491 through SATB1 in HNSCC cells. In a word, LINC00491 accelerated HNSCC progression through regulating miR-508-3p/SATB1 axis and activating Wnt signaling pathway.

Transcription factor ZmDof22 enhances drought tolerance by regulating stomatal movement and antioxidant enzymes activities in maize (Zea mays L.).

KEY MESSAGE: The Dof22 gene encoding a deoxyribonucleic acid binding with one finger in maize, which is associated with its drought tolerance. The identification of drought stress regulatory genes is essential for the genetic improvement of maize yield. Deoxyribonucleic acid binding with one finger (Dof), a plant-specific transcription factor family, is involved in signal transduction, morphogenesis, and environmental stress responses. In present study, by weighted correlation network analysis (WGCNA) and gene co-expression network analysis, 15 putative Dof genes were identified from maize that respond to drought and rewatering. A real-time fluorescence quantitative PCR showed that these 15 genes were strongly induced by drought and ABA treatment, and among them ZmDof22 was highly induced by drought and ABA treatment. Its expression level increased by nearly 200 times after drought stress and more than 50 times after ABA treatment. After the normal conditions were restored, the expression levels were nearly 100 times and 40 times of those before treatment, respectively. The Gal4-LexA/UAS system and transcriptional activation analysis indicate that ZmDof22 is a transcriptional activator regulating drought tolerance and recovery ability in maize. Further, overexpressed transgenic and mutant plants of ZmDof22 by CRISPR/Cas9, indicates that the ZmDof22, improves maize drought tolerance by promoting stomatal closure, reduces water loss, and enhances antioxidant enzyme activity by participating in the ABA pathways. Taken together, our findings laid a foundation for further functional studies of the ZmDof gene family and provided insights into the role of the ZmDof22 regulatory network in controlling drought tolerance and recovery ability of maize.

[Experience in diagnosis and treatment of 6 cases of renal Ewing's sarcoma with venous thrombus].

OBJECTIVE: To review and analyze the clinical diagnosis and treatment of renal Ewing's sarcoma with venous tumor embolus, to follow up the survival and prognosis of the patients, and to provide help for the diagnosis and treatment of the disease. METHODS: Clinical data (including general data, surgical data and postoperative pathological data) of patients diagnosed with renal Ewing's sarcoma with venous tumor embolus in Peking University Third Hospital from June 2016 to June 2022 were collected, and the prognosis of the patients was followed up to analyze the influence of diagnosis and treatment process on the prognosis of the disease. RESULTS: There were 6 patients, including 1 male and 5 females. There were 4 cases of left renal tumor and 2 cases of right renal tumor. The median age at diagnosis was 28 years (16-52 years). The imaging findings were all exogenous tumors with internal necrotic tissue and hemorrhage. The mean maximum tumor diameter was 12.6 cm, and the mean tumor thrombus length was 7.8 cm. Four patients underwent open surgery and 2 patients underwent laparoscopic surgery. The postoperative pathological results were renal Ewing sarcoma. Immunohistochemical results showed 3 cases of CD99 (+), 2 cases of FLI-1 (+), and 1 case of CD99, FLI-1 (-). 3 patients received chemotherapy (cyclophosphamide, doxorubicin, vincristine/ifosfamide, etoposide), 1 case received chemotherapy combined with radiotherapy, and 2 cases received no adjuvant therapy. The mean overall survival (OS) of the 6 patients was 37 months, and the mean OS of the 4 patients (47 months) who received chemotherapy was significantly higher than that of the 2 patients (16 months) who did not receive chemotherapy (P=0.031). CONCLUSION: Renal Ewing's sarcoma with venous tumor embolus is rare in clinic, and it is common in young female patients. The operation is difficult and the prognosis is poor. Surgical resection, adjuvant radiotherapy and chemotherapy can improve the overall survival rate of the patients.

p53 missense mutant G242A subverts natural killer cells in sheltering mouse breast cancer cells against immune rejection.

Cancer cells acquire immunoediting ability to evade immune surveillance and thus escape eradication. It is widely known that mutant proteins encoded from tumor suppressor TP53 exhibit gain-of-function in cancer cells, thereby promoting progression; however, how mutant p53 contributes to the sheltering of cancer cells from host anticancer immunity remains unclear. Herein, we report that murine p53 missense mutation G242A (corresponding to human G245A) suppresses the activation of host natural killer (NK) cells, thereby enabling breast cancer cells to avoid immune assault. We found that serial injection of EMT6 breast cancer cells that carry wild-type (wt) Trp53, like normal fibroblasts, promoted NK activity in mice, while SVTneg2 cells carrying Trp53 G242A+/+ mutation decreased NK cell numbers and increased CD8+ T lymphocyte numbers in spleen. Innate immunity based on NK cells and CD8 T cells was reduced in p53 mutant-carrying transgenic mice (Trp53 R172H/+, corresponding to human R175H/+). Further, upon co-culture with isolated NK cells, EMT6 cells substantively activated NK cells and proliferation thereof, increasing interferon-gamma (IFN-γ) production; however, SVTneg2 cells suppressed NK cell activation. Further mechanistic study elucidated that p53 can modulate expression by cancer cells of Mult-1 and H60a, which are activating and inhibitory ligands for NKG2D receptors of NK cells, respectively, to enhance immune surveillance against cancer. Our findings demonstrate that wt p53 is requisite for NK cell-based immune recognition and elimination of cancerous cells, and perhaps more importantly, that p53 missense mutant presence in cancer cells impairs NK cell-attributable responses, thus veiling cancerous cells from host immunity and enabling cancer progression.

Passive In-Line Chlorination for Drinking Water Disinfection: A Critical Review.

The world is not on track to meet Sustainable Development Goal 6.1 to provide universal access to safely managed drinking water by 2030. Removal of priority microbial contaminants by disinfection is one aspect of ensuring water is safely managed. Passive chlorination (also called in-line chlorination) represents one approach to disinfecting drinking water before or at the point of collection (POC), without requiring daily user input or electricity. In contrast to manual household chlorination methods typically implemented at the point of use (POU), passive chlorinators can reduce the user burden for chlorine dosing and enable treatment at scales ranging from communities to small municipalities. In this review, we synthesized evidence from 27 evaluations of passive chlorinators (in 19 articles, 3 NGO reports, and 5 theses) conducted across 16 countries in communities, schools, health care facilities, and refugee camps. Of the 27 passive chlorinators we identified, the majority (22/27) were solid tablet or granular chlorine dosers, and the remaining devices were liquid chlorine dosers. We identified the following research priorities to address existing barriers to scaled deployment of passive chlorinators: (i) strengthening local chlorine supply chains through decentralized liquid chlorine production, (ii) validating context-specific business models and financial sustainability, (iii) leveraging remote monitoring and sensing tools to monitor real-time chlorine levels and potential system failures, and (iv) designing handpump-compatible passive chlorinators to serve the many communities reliant on handpumps as a primary drinking water source. We also propose a set of reporting indicators for future studies to facilitate standardized evaluations of the technical performance and financial sustainability of passive chlorinators. In addition, we discuss the limitations of chlorine-based disinfection and recognize the importance of addressing chemical contamination in drinking water supplies. Passive chlorinators deployed and managed at-scale have the potential to elevate the quality of existing accessible and available water services to meet "safely managed" requirements.

Metformin exerts an antitumor effect by inhibiting bladder cancer cell migration and growth, and promoting apoptosis through the PI3K/AKT/mTOR pathway.

BACKGROUND: To observe and explore the effect of metformin on the migration and proliferation of bladder cancer T24 and 5637 cells in vitro. METHODS: Bladder cancer T24 and 5637 cell lines were cultured in vitro, and were divided into group A (blank control group) and group B (metformin group: 5, 10, 15, and 20 mmol/L); both groups were plated on 6-well plates at the same time. Culture in 24-well plates was used for wound healing assays and in 96-well plates for Transwell migration and invasion, and Cell Counting Kit-8 proliferation experiments. We observed and detected the cell migration and proliferation ability of each group at 48 h, and calculated the cell migration area and survival rate. Flow cytometry was used to detect cell apoptosis in the groups. The apoptosis-related proteins, cleaved-caspase 3, cleaved-PARP, and the PI3K/AKT/mTOR signaling pathway member proteins PI3K, phosphorylated (p)-PI3K, AKT, p-AKT, mTOR, and p-mTOR were detected using western blotting. RESULTS: After 48 h of treatment with different concentrations of metformin, the cell migration and proliferation capabilities were significantly lower than those in the blank control group. The proliferation and migration abilities of T24 and 5637 cells decreased in a metformin concentration-dependent manner (P < 0.05). The apoptosis rate under different concentrations of metformin, as detected by flow cytometry, showed a significantly higher rate in the metformin group than in the control group (P < 0.05). Compared with that in the control group, the level of cleaved-caspase 3 and cleaved-PARP protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05). CONCLUSION: Metformin inhibited bladder cancer T24 and 5637 cell migration and proliferation, and induced their apoptosis. The mechanism might involve inhibition of the activation of the PI3K/AKT/mTOR signaling pathway.

Solasonine alleviates high glucose-induced podocyte injury through increasing Nrf2-medicated inhibition of NLRP3 activation.

The worldwide high prevalence of diabetic nephropathy is one of the common causes of renal failure in diabetic patients. Hyperglycemia-caused podocyte injury is considered as a major contributor to diabetic kidney disease, accompanied by a chronic inflammatory condition. Pyroptosis, a characterized inflammatory form of programmed cell death, is believed to be involved in the pathogenesis of diabetic nephropathy. Solasonine (SS) is a natural alkaloid and received attention as a potential anticancer agent. However, its protective effect against hyperglycemia-caused podocyte injury remains to be determined. Our study found that SS alleviates cell apoptosis, and reduces pyroptosis and oxidative damage in high glucose (HG)-treated MPC5 podocytes. Pro-inflammatory cytokines, including interleukin (IL)-1ß and IL-18, and caspase-1 activity were markedly suppressed by SS in HG-treated MPC5 podocytes. SS also reduced HG-induced oxidative damage in MPC5 podocytes. Nrf2 expression was activated by SS in vitro under a HG condition. In addition, Nrf2 silencing attenuated the protective effect of SS against apoptosis, pro-inflammatory cytokines release, caspase-1 activity, and oxidative damage in MPC5 podocytes under a HG condition. Taken together, our findings revealed for the first time that SS alleviated high glucose-induced podocyte apoptosis, pyroptosis, and oxidative damage via regulating the Nrf2/NLRP3 signaling pathway. Our results indicate that SS has the potential as a therapeutic agent for podocyte injury in diabetic nephropathy.

Identification of C3 and FN1 as potential biomarkers associated with progression and prognosis for clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies, but the pathogenesis and prognosis of ccRCC remain obscure, which need to be better understand. METHODS: Differentially expressed genes were identified and function enrichment analyses were performed using three publicly available ccRCC gene expression profiles downloaded from the Gene Expression Omnibus database. The protein-protein interaction and the competing endogenous RNA (ceRNA) networks were visualized by Cytoscape. Multivariate Cox analysis was used to predict an optimal risk mode, and the survival analysis was performed with the Kaplan-Meier curve and log-rank test. Protein expression data were downloaded from Clinical Proteomic Tumor Analysis Consortium database and Human Protein Atlas database, and the clinical information as well as the corresponding lncRNA and miRNA expression data were obtained via The Cancer Genome Atlas database. The co-expressed genes and potential function of candidate genes were explored using data exacted from the Cancer Cell Line Encyclopedia database. RESULTS: Of the 1044 differentially expressed genes shared across the three datasets, 461 were upregulated, and 583 were downregulated, which significantly enriched in multiple immunoregulatory-related biological process and tumor-associated pathways, such as HIF-1, PI3K-AKT, P53 and Rap1 signaling pathways. In the most significant module, 36 hub genes were identified and were predominantly enriched in inflammatory response and immune and biotic stimulus pathways. Survival analysis and validation of the hub genes at the mRNA and protein expression levels suggested that these genes, particularly complement component 3 (C3) and fibronectin 1 (FN1), were primarily responsible for ccRCC tumorigenesis and progression. Increased expression of C3 or FN1 was also associated with advanced clinical stage, high pathological grade, and poor survival in patients with ccRCC. Univariate and multivariate Cox regression analysis qualified the expression levels of the two genes as candidate biomarkers for predicting poor survival. FN1 was potentially regulated by miR-429, miR-216b and miR-217, and constructed a bridge to C3 and C3AR1 in the ceRNA network, indicating a critical position of FN1. CONCLUSIONS: The biomarkers C3 and FN1 could provide theoretical support for the development of a novel prognostic tool to advance ccRCC diagnosis and targeted therapy.

MiR-186-5p suppresses cell migration, invasion, and epithelial mesenchymal transition in bladder cancer by targeting RAB27A/B.

Bladder cancer (BCa) is a common malignancy in the urinary system. Ras-related protein Rab-27A (RAB27A) and Ras-related protein Rab-27B (RAB27B) have been verified to be closely related to the development of many tumors. Since the role of both RAB27A and RAB27B in BCa have not been reported, we intended to explore the function and mechanism of RAB27A and RAB27B in BCa development. Reverse transcription quantitative polymerase chain reaction revealed that RAB27A/B showed high expression in BCa tissues and cells. Cell counting kit-8, wound healing and Transwell assays as well as western blot analyses revealed that silencing RAB27A/B suppressed BCa cell proliferation, migration and invasion as well as the epithelial-mesenchymal transition (EMT) process. Based on bioinformatics analysis and our experiments, microRNA-186-5p (miR-186-5p) was found to be the upstream miRNA of RAB27A/B in BCa. MiR-186-5p expression was significantly downregulated in BCa cells and tissues. MiR-186-5p directly targeted the 3'-untranslated region (3'-UTR) of RAB27A/B and downregulated both mRNA and protein levels of RAB27A/B in BCa cells. MiR-186-5p overexpression suppressed BCa cell proliferation, migration and invasion as well as the EMT process in vitro and inhibited tumor growth in vivo. Overexpressing RAB27A/B rescued the inhibitory effect of miR-186-5p on malignant phenotypes of BCa cells. Furthermore, miR-186-5p inactivated the phosphatidylinositol 3-Kinase (PI3K)/mitogen-activated protein kinase (MAPK) signaling pathway by downregulating the expression of RAB27A/B, as shown in western blot analysis. Overall, miR-186-5p suppressed BCa cell proliferation, migration, invasion and EMT process and inhibited xenograft tumor growth by targeting RAB27A/B to inactivate the PI3K/MAPK signaling.

Systematic Analysis of the Maize OSCA Genes Revealing ZmOSCA Family Members Involved in Osmotic Stress and ZmOSCA2.4 Confers Enhanced Drought Tolerance in Transgenic Arabidopsis.

OSCAs are hyperosmolality-gated calcium-permeable channel proteins. In this study, two co-expression modules, which are strongly associated with maize proline content, were screened by weighted correlation network analysis, including three ZmOSCA family members. Phylogenetic and protein domain analyses revealed that 12 ZmOSCA members were classified into four classes, which all contained DUF221 domain. The promoter region contained multiple core elements responsive to abiotic stresses and hormones. Colinear analysis revealed that ZmOSCAs had diversified prior to maize divergence. Most ZmOSCAs responded positively to ABA, PEG, and NaCl treatments. ZmOSCA2.3 and ZmOSCA2.4 were up-regulated by more than 200-fold under the three stresses, and showed significant positive correlations with proline content. Yeast two-hybrid and bimolecular fluorescence complementation indicated that ZmOSCA2.3 and ZmOSCA2.4 proteins interacted with ZmEREB198. Over-expression of ZmOSCA2.4 in Arabidopsis remarkably improved drought resistance. Moreover, over-expression of ZmOSCA2.4 enhanced the expression of drought tolerance-associated genes and reduced the expression of senescence-associated genes. We also found that perhaps ZmOSCA2.4 was regulated by miR5054.The results provide a high-quality molecular resource for selecting resistant breeding, and lay a foundation for elucidating regulatory mechanism of ZmOSCA under abiotic stresses.

Targeted Delivery of Doxorubicin Liposomes for Her-2+ Breast Cancer Treatment.

The adverse side effects and toxicity caused by the non-targeted delivery of doxorubicin has emphasized the demand of emerging a targeted delivery system. The goal of this study is to enhance the delivery of doxorubicin by formulating an aptamer-labeled liposomal nanoparticle delivery system that will carry and deliver doxorubicin specifically into Her-2+ breast cancer cells. Twelve liposomal batches were prepared using different saturated (HSPC and DPPC) and unsaturated (POPC and DOPC) lipids by thin film hydration. The liposomes were characterized for their particle size, zeta potential, and drug encapsulation efficiency. The particles were also assessed for in vitro toxicity and DOX delivery into the breast cancer cells. The formulations, F1 through F12, had a small particle size of less than 200 nm and a high entrapment efficiency of about 88 ± 5%. The best formulation, F5, had a particle size of 101 ± 14nm, zeta potential of + 5.63 ± 0.46 mV, and entrapment efficiency of ≈ 93%. The cytotoxicity studies show that the DOX-loaded liposomal formulations are more effective in killing cancer cells than the free DOX in both MCF-7 and SKBR-3 cells. The uptake studies show a significant increase in the uptake of the aptamer-labeled liposomes (i.e., F5) by more than 60% into Her-2+ MCF-7 and SKBR-3 breast cancer cells compare to non-aptamer-labeled nanoparticles. F5 also shows ≈ 1.79-fold increase in uptake of DOX in the Her-2+ cells compared to the Her-2- cells. This preliminary study indicates that aptamer-labeled F5 nanoparticles among several batches showed the highest uptake as well as the targeted delivery of doxorubicin into Her-2+ breast cancer cells. Thus, aptamer targeted approach results in substantial reduction in the dose of DOX and improves the therapeutic benefits by promoting the target specificity.

Recent perspectives of management of breast cancer metastasis - an update.

Breast cancer is the leading cause of cancer related deaths in women and one of the most common cancers globally. The major obstacle in the management of breast cancer, especially at advanced stages, is metastasis. Metastasis in the advanced stages of breast cancer could decrease survival to approximately 5 years. The reasons could include lack of targeted receptors or chemotherapeutic agents for the management of advanced-stage breast cancer metastasis. The new emerging avenues for the management of this deadly pathological state include local manipulations like radiofrequency ablation (RFA), microwave thermotherapy, cryosurgery (cryotherapy), chemoembolization, radioembolization, breast surgery, or metastasectomy. Few single-institution reports showed improved survival in selected patients like those with oligometastatic stage IV breast cancer. The present review article focused on these emerging new multimodality treatment approaches for a possible efficient management.

Highly and moderately aggressive mouse ovarian cancer cell lines exhibit differential gene expression.

Patients with advanced epithelial ovarian cancer often experience disease recurrence after standard therapies, a critical factor in determining their five-year survival rate. Recent reports indicated that long-term or short-term survival is associated with varied gene expression of cancer cells. Thus, identification of novel prognostic biomarkers should be considered. Since the mouse genome is similar to the human genome, we explored potential prognostic biomarkers using two groups of mouse ovarian cancer cell lines (group 1: IG-10, IG-10pw, and IG-10pw/agar; group 2: IG-10 clones 2, 3, and 11) which display highly and moderately aggressive phenotypes in vivo. Mice injected with these cell lines have different survival time and rates, capacities of tumor, and ascites formations, reflecting different prognostic potentials. Using an Affymetrix Mouse Genome 430 2.0 Array, a total of 181 genes were differentially expressed (P < 0.01) by at least twofold between two groups of the cell lines. Of the 181 genes, 109 and 72 genes were overexpressed in highly and moderately aggressive cell lines, respectively. Analysis of the 109 and 72 genes using Ingenuity Pathway Analysis (IPA) tool revealed two cancer-related gene networks. One was associated with the highly aggressive cell lines and affiliated with MYC gene, and another was associated with the moderately aggressive cell lines and affiliated with the androgen receptor (AR). Finally, the gene enrichment analysis indicated that the overexpressed 89 genes (out of 109 genes) in highly aggressive cell lines had a function annotation in the David database. The cancer-relevant significant gene ontology (GO) terms included Cell cycle, DNA metabolic process, and Programmed cell death. None of the genes from a set of the 72 genes overexpressed in the moderately aggressive cell lines had a function annotation in the David database. Our results suggested that the overexpressed MYC and 109 gene set represented highly aggressive ovarian cancer potential biomarkers while overexpressed AR and 72 gene set represented moderately aggressive ovarian cancer potential biomarkers. Based on our knowledge, the current study is first time to report the potential biomarkers relevant to different aggressive ovarian cancer. These potential biomarkers provide important information for investigating human ovarian cancer prognosis.

Effects of Prevotella copri on insulin, gut microbiota and bile acids.

Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1ß (IL-1ß) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.

METTL3 regulates the proliferation, metastasis and EMT progression of bladder cancer through P3H4.

Bladder cancer, the most common malignant tumor in the urinary system, exhibits significantly up-regulated expression of P3H4, which is associated with pathological factors. The objective of this study was to elucidate the underlying mechanism of P3H4 in bladder cancer. Initially, we analyzed P3H4 gene expression using the TCGA database and evaluated P3H4 levels in clinical samples and various bladder cell lines. P3H4 was found to be markedly overexpressed in bladder cancer samples. Subsequently, bladder cancer cells were transfected with shRNA targeting P3H4 (sh-P3H4), sh-METTL3, and P3H4 overexpression vectors (P3H4 OE). Viability, migration, and invasion of bladder cancer cells were assessed using CCK-8, wound healing, and transwell assays. Western blot analysis was performed to determine the levels of EMT-associated proteins, while RNA stability assays determined the half-life of P3H4. Knockdown of P3H4 resulted in inhibition of bladder cancer cell proliferation, migration, invasion, and EMT progression. Mechanistically, METTL3 was found to regulate the mRNA stability of P3H4 in bladder cancer. Moreover, overexpression of P3H4 reversed the inhibitory effects of METTL3 knockdown on bladder cancer cell behaviors. Stable cell lines were established by infecting EJ cells with lentiviral vectors containing sh-METTL3 or P3H4 OE. These cells were then implanted into the skin of BALB/c nude mice, and IHC analysis was used to analyze the expression levels of EMT-associated proteins. In vivo studies demonstrated that inhibition of METTL3 suppressed bladder cancer growth and EMT through P3H4. In conclusion, our findings suggest that METTL3 regulates the proliferation, metastasis, and EMT progression of bladder cancer through P3H4, highlighting its potential as a therapeutic target.

The role of uterus mitochondrial function in high-fat diet-related adverse pregnancy outcomes and protection by resveratrol.

This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.

A Single Measurement System May Not Be Enough for Questionable High Free T4 Levels.

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Placental Malfunction, Fetal Survival and Development Caused by Sow Metabolic Disorder: The Impact of Maternal Oxidative Stress.

The energy and metabolic state of sows will alter considerably over different phases of gestation. Maternal metabolism increases dramatically, particularly in late pregnancy. This is accompanied by the development of an increase in oxidative stress, which has a considerable negative effect on the maternal and the placenta. As the only link between the maternal and the fetus, the placenta is critical for the maternal to deliver nutrients to the fetus and for the fetus' survival and development. This review aimed to clarify the changes in energy and metabolism in sows during different pregnancy periods, as well as the impact of maternal oxidative stress on the placenta, which affects the fetus' survival and development.