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BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers. [ABSTRACT FROM AUTHOR]

BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers. [ABSTRACT FROM AUTHOR]

Abstract: Overexpression of zinc-dependent metalloproteinase, aminopeptidase N (APN/CD13), is considered to be involved in the process of tumor invasion and metastasis. Herein we describe the synthesis and in vitro enzymatic inhibition assay of antineoplaston AS2–5 scaffold peptidomimetic compounds. The results demonstrated that most of these l-iso-glutamine derivatives displayed selective inhibitory activity against APN as compared with MMP-2, with IC50 values in the micromole range. The structure–activity relationships were also briefly discussed. [Copyright &y& Elsevier]

It is widely acknowledged that glucose serves as the primary energy source for organisms. However, fish exhibit persistent postprandial hyperglycemia and are thought to have low glucose tolerance. Glycolysis serves as the ubiquitous pathway for glucose catabolism, with phosphofructokinase (PFK) acting as a crucial rate-limiting enzyme in this process and playing an indispensable role. PFK is classified into three isoforms based on their major expression sites, i.e., PFKM (skeletal muscle type), PFKL (liver type) and PFKP (platelet type). In this study, grass carp (Ctenopharyngodon idella) was used as animal model and the open reading frame (ORF) sequences of six PFK genetic isoforms of grass carp were cloned. Real-time PCR was used to detect its tissue distribution, and expression changes in oral glucose tolerance test (OGTT), insulin and glucagon injection experiments. The results showed that the ORF of pfkla , pfklb , pfkma , pfkmb , pfkpa and pfkpb genes was 2343, 2340, 2355, 2331, 2364 and 2349 bp in length, respectively. The results of tissue distribution showed that pfkla and pfklb , homologous to mammalian pfkl , exhibited low expression levels in the liver of grass carp, but were expressed at the highest level in the brain. Muscle-type pfkma and pfkmb mRNA were found to be highly expressed in both red and white muscle, with pfkmb also exhibiting high expression levels in the heart, while platelet type pfkpa and pfkpb showed high mRNA abundances in the brain and heart. Oral glucose administration stimulated pfkma and pfkmb mRNA expression in the red muscle, and up-regulated pfklb mRNA levels in the liver at 3 h post treatment, but it suppressed liver-type and platelet-type PFK genes expression in the brain. The expression of pfkmb in white muscle and pfkmb and pfkpb in heart were promoted by insulin, whereas the expression of pfkla and pfkpb in the brain, pfkma and pfkmb in the red muscle, pfkma in the white muscle, and pfklb in the liver was suppressed by insulin. As for glucagon, it inhibited pfkma and pfkmb mRNA expression in the red muscle, as well as pfklb in the liver, but it up-regulated PFK genes expression in most tissues detected, such as brain (pfklb , pfkpa and pfkpb), white muscle (pfkma and pfkmb), liver (pfkla) and heart (pfkmb and pfkpb). Our results suggest that PFK family genes have different or even opposite expression patterns in response to glucose, insulin and glucagon stimulation in various tissues of grass carp, which may contribute to glucose intolerance in fish. [Display omitted] • Brain, heart, red and white muscle are the main tissues for PFK expression. • Glucose promoted PFK expression in muscle (M-type), liver (pfklb), heart (pfkpb). • Insulin up-regulated expression of pfkmb in white muscle, pfkmb and pfkpb in heart. • Glucagon up-regulated PFK expression in most tissues, except for red muscle. • PFK family genes have different or even opposite expression patterns. [ABSTRACT FROM AUTHOR]

Endometriosis (EMT) is an aggressive disease of the reproductive system, also called "benign cancer". However, effective treatments for EMT are still lacking in clinical practice. Interestingly, immune infiltration is significantly involved in EMT pathogenesis. Currently, no studies have shown the involvement of cuproptosis-related genes (CRGs) in regulating immune infiltration in EMT. This study identified three CRGs such as GLS, NFE2L2, and PDHA1, associated with EMT using machine learning algorithms. These three CRGs were upregulated in the endometrium of patients with moderate/severe EMT and downregulated in patients with infertility. Single sample genomic enrichment analysis (ssGSEA) revealed that these CRGs were closely correlated with autoimmune diseases such as systemic lupus erythematosus. Furthermore, these CRGs were correlated with immune cells such as eosinophils, natural killer cells, and macrophages. Therefore, profiling patients based on these genes aid in a more accurate diagnosis of EMT progression. The mRNA and protein expression levels of GLS, NFE2L2 and PDHA1 were validated by qRT-PCR and WB studies in EMT samples. These findings provide a new idea for the pathology and treatment of endometriosis, suggesting that CRGs such as GLS, NFE2L2 and PDHA1 may play a key role in the occurrence and development of endometriosis. [ABSTRACT FROM AUTHOR]

Early life stress such as maternal separation (MS), is a major risk factor for developing psychiatric disorders in adulthood. Connexin 43 (CX43), the main type of connexins expressed in astrocytes, has been indicated to participate in depression disorders. Nevertheless, the role of CX43 in MS-induced cognitive impairment and astrocyte dysfunction is unclear. Neonatal C57BL/6 mice were exposed to MS to mimic early life stress. Adeno-associated virus carrying CX43 was inoculated into mice for CX43 overexpression. Sucrose preference test, forced swim test and Morris water maze were performed for evaluating depression-like behaviors and spatial learning and memory of mice in adulthood. Real time quantitative polymerase chain reaction was conducted to detect CX43 mRNA expression in mouse brain. Immunofluorescence staining and western blotting were used for measuring expression levels of astrocytic markers in murine hippocampal dentate gyrus. The results showed that overexpressing CX43 attenuated MS exposure-induced depression-like behaviors and decrease in spatial learning and memory in mice. Upregulating CX43 alleviated MS exposure-induced downregulation of astrocytic markers. Collectively, CX43 overexpression attenuates cognitive deficits and astrocyte dysfunction in mice exposed to MS. [ABSTRACT FROM AUTHOR]

Background. MutS homolog 2 (MSH2), with the function of identifying mismatches and participating in DNA repair, is the "housekeeping gene" in the mismatch repair (MMR) system. MSH2 deficiency has been reported to enhance cancer susceptibility for the association of hereditary nonpolyposis colorectal cancer. However, the expression and prognostic significance of MSH2 have not been studied from the perspective of pan-cancer. Methods. The GTEx database was used to analyze the expression of MSH2 in normal tissues. The TCGA database was used to analyze the differential expression of MSH2 in pan-cancers. The prognostic value of MSH2 in pan-cancer was assessed using Cox regression and Kaplan-Meier analysis. Spearman correlations were used to measure the relationship between the expression level of MSH2 in pan-cancer and the level of immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). Results. MSH2 is highly expressed in most type of cancers and significantly correlated with prognosis. In COAD, KIRC, LIHC, and SKCM, the expression of MSH2 was significantly positively correlated with the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, and neutrophils. In THCA, MSH2 expression correlated with CD8+T Cell showed a significant negative correlation. MSH2 had significantly negative correlations with stromal score and immune score in a variety of cancers and significantly correlated with TMB and MSI of a variety of tumors. Conclusions. MSH2 may play an important role in the occurrence, development, and immune infiltration of cancer. MSH2 can emerge as a potential biomarker for cancer diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM), a chronic metabolic disease, severely impairs male reproductive function. However, the underpinning mechanisms are still incompletely defined, and there are no effective strategies or medicines for these reproductive lesions. Icariin (ICA), the main active component extracted from Herba epimedii, is a flavonoid traditionally used to treat testicular dysfunction. Whether ICA can improve male reproductive dysfunction caused by DM and its underlying mechanisms are still unclear. In this study, by employing metformin as a comparative group, we evaluated the protective effects of ICA on male reproductive damages caused by DM and explored the possible mechanisms. Methods: Rats were fed with a high fat diet (HFD) and then intraperitoneally injected with streptozotocin (STZ) to induce diabetes. Diabetic rats were randomly divided into T2DM + saline group, T2DM + metformin group and T2DM + ICA group. Rats without the treatment of HFD and STZ were used as control group. The morphology of testicular tissues was examined by histological staining. The mRNA expression levels were determined by quantitative real-time PCR. Immunostaining detected the protein levels of proliferating cell nuclear antigen (PCNA), hypoxia-inducible factor 1-alpha (HIF-1α) and sirtuin 1 (SIRT1) in testicular tissues. TUNEL assay was performed to determine cell apoptosis in the testicular tissues. The protein expression levels of HIF-1α and SIRT1 in the testicular tissues were determined by western blot assay. Results: ICA effectively improved male reproductive dysfunction of diabetic rats. ICA administration significantly decreased fasting blood glucose (FBG) and insulin resistance index (IRI). In addition, ICA increased testis weight, epididymis weight, sperm number, sperm motility and the cross-sectional area of seminiferous tubule. ICA recovered the number of spermatogonia, primary spermatocytes and Sertoli cells. Furthermore, ICA upregulated the expression of PCNA, activated SRIT1-HIF-1α signaling pathway, and inhibited intrinsic mitochondria dependent apoptosis pathway by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase 3. Conclusion: These results suggest that ICA could attenuate male reproductive dysfunction of diabetic rats possibly via increasing cell proliferation and decreasing cell apoptosis of testis. ICA potentially represents a novel therapeutic strategy against DM-induced testicular damages. [ABSTRACT FROM AUTHOR]