DNA and cell biology最新文献

We recently demonstrated that prostaglandin production in brain endothelial cells is both necessary and sufficient for the generation of fever during systemic immune challenge. I here discuss this finding in light of the previous literature and point to some unresolved issues.

Lin28B plays an important role in puberty initiation in sheep. This study aimed to discuss the correlation between different growth periods and the methylation status of cytosine-guanine dinucleotide (CpG) islands in the promoter region of the Lin28B gene in the Dolang sheep's hypothalamus. In this study, the sequence of the Lin28B gene promoter region in Dolang sheep was obtained by cloning and sequencing, and methyl groups of the CpG island of the Lin28B gene promoter in the hypothalamus were detected by bisulfite sequencing PCR during the three periods of prepuberty, adolescence, and postpuberty in Dolang sheep. Lin28B expression in the Dolang sheep's hypothalamus was detected by fluorescence quantitative PCR at three stages: prepuberty, puberty, and postpuberty. In this experiment, the 2993-bp Lin28B promoter region was obtained, and it was predicted that there was a CpG island containing 15 transcription factor binding sites and 12 CpG sites, which may play a role in gene expression regulation. Overall, methylation levels increased from prepuberty to postpuberty, while Lin28B expression levels decreased, indicating that Lin28B expression was negatively correlated with promoter methylation levels. Variance analysis showed significant differences in the methylation status of CpG5, CpG7, and CpG9 between pre- and postpuberty (p < 0.05). Our data show that Lin28B expression is increased by demethylation of promoter CpG islands, with CpG5, CpG7, and CpG9 implicated as critical regulatory sites.

Improving livestock and poultry growth rates and increasing meat production are urgently needed worldwide. Previously, we produced a myostatin (MSTN) and fibroblast growth factor 5 (FGF5) double-knockout (MF^-/-) sheep by CRISPR Cas9 system to improve meat production, and also wool production. Both MF^-/- sheep and the F1 generation (MF^+/-) sheep showed an obvious "double-muscle" phenotype. In this study, we identified the expression profiles of long noncoding RNAs (lncRNAs) in wild-type and MF^+/- sheep, then screened out the key candidate lncRNAs that can regulate myogenic differentiation and skeletal muscle development. These key candidate lncRNAs can serve as critical gatekeepers for muscle contraction, calcium ion transport and skeletal muscle cell differentiation, apoptosis, autophagy, and skeletal muscle inflammation, further revealing that lncRNAs play crucial roles in regulating muscle phenotype in MF^+/- sheep. In conclusion, our newly identified lncRNAs may emerge as novel molecules for muscle development or muscle disease and provide a new reference for MSTN-mediated regulation of skeletal muscle development.

Epithelial ovarian cancer (EOC) treatment strategies mainly focused on surgery combined with chemotherapy. Recent targeted therapy techniques emerge as milestone and could be used for management of ovarian cancer (OC) progression with more efficacy. The aim is to evaluate the therapeutic and diagnostic potential of microRNA (miRNA) in management of EOC using in silico and quantitative real-time PCR (qRT-PCR) expression analysis. We performed functional enrichment and miRNA-Target genes expression analysis in 48 EOC and 22 normal tissue samples using qRT-PCR and correlated with miRNA expression data in matched samples to evaluate the diagnostic and therapeutic potential of miRNA in OC management. In silico functional enrichment analysis revealed miRNA association with disease. Target genes of miRNAs participate in several biologically important pathways leading to cancer progression. Targets of miRNA-205 and miRNA-34a were significantly downregulated, and upregulated, respectively, in EOC. Moreover, significant negative correlation between relative expression of miRNA-205 and target genes (BCL2, ZEB1, E2F1, and TP53) was observed with r = -0.813; r = -0.755; r = -0.559; and r = -0.767, respectively. Similarly, miRNA-34a also showed higher negative correlation with target genes (MDM4, MAPK3, BRCA1, AREG) with r = -0.840; r = -0.870; r = -0.622; and r = -0.623, respectively. In addition, receiver operating characteristics analysis of combined miRNA panel, miRNA-205-Target gene panel, and miRNA-34a-Target gene panel exhibited higher diagnostics value with area under the curve (AUC) of 92.7 (p < 0.0001), 94.8 (p < 0.0001), and 98.3 (p < 0.0001), respectively. Negative Correlation between miRNA and target genes expression data in matched samples highlights therapeutic potential of miRNA in EOC management. Moreover, combined diagnostic potential of miRNA-target gene panel could predict risk of EOC with higher AUC, sensitivity, and specificity.

miRNAs are a type of small endogenous noncoding RNA composed of 20-22 nucleotides that can regulate gene expression by targeting the 3' untranslated region of mRNA. Many investigations have discovered that miRNAs have a role in the development and progression of human cancer. Several aspects of tumor development are affected by miR-425, including growth, apoptosis, invasion, migration, epithelial-mesenchymal transition, and drug resistance. In this article, we discuss the properties and research development of miR-425, focusing on the regulation and function of miR-425 in various cancers. Furthermore, we discuss the clinical implications of miR-425. This review may broaden our horizon for better understanding the role of miR-425 as biomarkers and therapeutic targets in human cancer.

To investigate the effect of paired box protein 5 (PAX5)/integrin subunit alpha X (ITGAX) in atherosclerosis (AS). AS model was established using ApoE^-/- mice (C57BL/6). Human vascular smooth muscle cells (HVSMCs) were stimulated with ox-LDL. Quantitative reverse transcription polymerase chain reaction and Western blotting were used to detect the expression levels of genes and proteins. Reporter constructs and luciferase assays were used to investigate the role of ITGAX and PAX5. Cells proliferation and inflammation factors were detected. The results presented that aortic plaque area, lipid content, serum triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels were significantly increased in the high-fat diet group (p < 0.05). ITGAX was upregulated in atherosclerotic tissues. In addition, ox-LDL treatment induced HVSMCs proliferation, migration, and invasion. Reporter constructs and luciferase assays indicated ITGAX interaction with PAX5. Furthermore, siITGAX and siPAX5 cotransfection restored the rate of HVSMCs in G1 and S and G2/M phases, decreased the content of tumor necrosis factor-alpha (TNF-ɑ), interleukin (IL)-6, and IL-8 (p < 0.05). Interestingly, siITGAX and siPAX5 cotransfection also decreased the expression levels of TNF-α, TNF-R1, TNF-R2, CD19, and CD86 (p < 0.05). Our results suggest that ITGAX may be a potential therapeutic target for AS.

Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) is an aggressive malignancy with a high recurrence rate and reduced overall survival. Immune checkpoint inhibition (ICI) has shown modest results in this subgroup, highlighting the need for improved targeted therapeutic options. Notch is a defining feature of TNBC and drives the expression of interleukin-1 beta (IL1β) and C-C motif chemokine ligand 2 (CCL2). These cytokines are involved in the recruitment of tumor-associated macrophages (TAMs) to the tumor, resulting in immune evasion and tumor progression. Targeting Notch, IL1β or CCL2 may reduce TAM recruitment and resistance to ICI, illuminating the potential of combination immunotherapy in TNBC.

The present study was designed to evaluate the effects of resveratrol, atorvastatin, and a combination of resveratrol and atorvastatin on expression levels of genes involved in the cholesterol metabolic pathway in the fatty liver of C57/BL6 mice. A high-fat diet was used to induce fatty liver in C57/BL6 mice treated with resveratrol, atorvastatin, or a combination of resveratrol and atorvastatin. Pathological and biochemical studies were performed. In addition, hepatic gene expressions of ATP-binding cassette transporter A1 (ABCA1), ABCG1, liver X receptor (LXR)α, scavenger receptor B1 (SR-B1), low-density lipoprotein receptor (LDLR), and miR33 were evaluated by the real-time PCR method, and the Western blot method was used to measure the ABCA1, ABCG1, and LXRα protein levels. Resveratrol and atorvastatin reduced fat accumulation in the liver of mice with fatty liver, and this effect was correlated with decreased blood glucose levels, triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol blood levels compared with the positive control (PC) group. In contrast to the animals of the PC group, fatty liver groups that received resveratrol and atorvastatin had a significant effect on the mRNA levels of the ABCA1, ABCG1, LXRα, SR-B1, LDLR, and miR33 genes. Moreover, resveratrol and atorvastatin administration elevated ABCA1 and ABCG1 and reduced LXRα protein expression. Obtained results showed that resveratrol and atorvastatin combination therapy can improve nonalcoholic fatty liver disease by targeting genes involved in cholesterol metabolism and miR33.

Cornus officinalis is a perennial deciduous tree or shrub. Its mature fruits are extracted and used in Traditional Chinese Medicine, called Shanzhuyu. The characteristic active components of C. officinalis include loganin and morroniside, which belong to iridoid glycosides. 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is a key enzyme in the cytoplasmic mevalonate pathway providing the precursor molecules isopentenyl pyrophosphate and dimethylallyl pyrophosphate for isoprenoid biosynthesis such as sterols, triterpenes, and their derivatives such as iridoid glycosides. Different concentrations of methyl jasmonate (MeJA) and ethephon (ETH) solutions were sprayed on C. officinalis seedlings, and the effect of hormones on CoHMGS gene expression was detected by real-time fluorescence quantitative PCR. The quantitative real-time PCR results showed that 750 mg/L ETH treatment had the most significant induction effect on CoHMGS gene expression. The HPLC analysis of extracts revealed that the treatment could also significantly increase the content of morroniside and loganin in the leaves of C. officinalis. By use of a CoHMGS-green fluorescent protein (GFP) fusion construct for heterologous expression in tobacco, laser scanning confocal microscopy revealed a cytoplasmic localization. This preliminary study of the CoHMGS gene could prepare the ground for more precisely elucidating the synthesis of secondary metabolite in C. officinalis.