DNA and cell biology最新文献

Tail fat weight is a key economic trait in fat-tailed sheep; reducing tail fat deposition is of significant importance for improving the economic efficiency of sheep farming. In this article, we measured the live weight before slaughter, tail fat weight, and carcass weight of Hu male sheep at 6 months of age and performed the descriptive statistical analysis. The results indicated the coefficient of variation of tail fat-related-traits ranged from 25% to 50%. Simultaneously, we selected IGFBP3 and TUSC5 as candidate genes based on their close association with fat deposition. Target regions were amplified using gene-specific primers in PCR, followed by Sanger sequencing of PCR products to identify genetic variants. Polymorphisms were subsequently validated using the KASPar genotyping assay. Finally, quantitative reverse transcription PCR (qRT-PCR) was performed to determine the expression levels of IGFBP3 and TUSC5. Our findings revealed a missense mutation (g.83695349 C>T) in exon 1 of the IGFBP3 gene and a synonymous mutation (g.41771645 C>T) in exon 2 of the TUSC5 gene. Association analysis showed that these mutations were significantly correlated (p < 0.05) with tail fat weight traits. Moreover, the tail fat weight of the mutant genotypes (CT and TT) was significantly reduced compared with that of the CC genotype, suggesting that the gene may exert a negative regulatory effect on this trait, thereby leading to the reduction of tail fat weight. Furthermore, the genotype combinations showed a significant relationship with tail fat traits. Moreover, qRT-PCR results showed that TUSC5 and IGFBP3 genes were expressed in all experimental tissues of Hu sheep, and the highest expression was observed in tail fat compared with other tissues (heart, liver, spleen, lung, kidney, rumen, duodenum, muscle, and lymph). Notably, their expression levels were significantly lower in the large-tail fat group than in the small-tail fat group. Overall, these results will provide novel candidate variation for reducing tail fat deposition in sheep breeding practice.

Why plants need fertilization to produce seeds has long been discussed. We recently identified a new specialized tissue required for seed formation at the ovule's chalazal end, showing the final form of the phloem end and supporting its transport function; however, it is blocked by callose deposition. Callose is removed after central cell fertilization (open state), allowing nutrients to be transported to the seed. However, if fertilization fails, callose deposition persists (closed state), preventing the tissue from transporting nutrients. A β-1,3-glucanase gene, AtBG_ppap, was identified, and the AtBG_ppap mutant showed the closed state, producing smaller seeds due to incomplete callose degradation. Contrarily, the AtBG_ppap overexpression line produced larger seeds due to continuous callose degradation, showing that the tissue is the "gateway" for the seed nutrients.

Autoimmune and inflammatory diseases are rising globally yet widely effective therapies remain elusive. Most treatments have limited efficacy, significant potential side effects, or eventually lose response, underscoring the urgent need for new therapeutic approaches. We recently discovered that ETS2, a transcription factor, functions as a master regulator of macrophage-driven inflammation-and is causally linked to the pathogenesis of multiple inflammatory diseases via human genetics. The pleotropic inflammatory effects of ETS2 included upregulation of many cytokines that are individually targeted by current disease therapies, including TNFα, IL-23, IL1β, and TNF-like ligand 1A signaling. With the move toward combination treatment-to maximize efficacy-targeting ETS2 presents a unique opportunity to potentially induce a broad therapeutic effect. However, there will be multiple challenges to overcome since direct ETS2 inhibition is unlikely to be feasible. Here, we discuss these challenges and other unanswered questions about the central role that ETS2 plays in macrophage inflammation.

STING, an endoplasmic reticulum-localized protein with multiple transmembrane domains, has been implicated in colorectal cancer (CRC) development. This study investigated the association between STING rs7380824 polymorphism and CRC susceptibility using both bioinformatics analysis and a case-control study. Bioinformatics predictions from SIFT and PolyPhen indicated that the rs7380824 variant, which results in an amino acid substitution from arginine (R) to glutamine (Q) at position 293, is likely to be deleterious, with a SIFT score of 0.000 and a PolyPhen score of 0.999. A total of 870 CRC patients and 870 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression analysis demonstrated that individuals carrying the CT and TT genotypes had an increased risk of CRC with OR (95% CI) of 1.564 (1.115-2.192) and 1.551 (1.271-1.893), respectively. Stratified analysis showed that the rs7380824 C > T variant increased CRC risk in all age and gender groups. Furthermore, non-smokers with the CT or TT genotype had a higher CRC risk (OR = 1.661, 95% CI: 1.333-2.071, p < 0.001), while no significant association was observed among smokers (p = 0.238). Similarly, non-drinkers carrying the CT or TT genotype showed an increased CRC risk (OR = 1.746, 95% CI: 1.395-2.185, p < 0.001), whereas no significant difference was detected among drinkers (p = 0.265). This study identifies STING rs7380824 polymorphism as a significant contributor to CRC susceptibility, with bioinformatics predictions and case-control analysis confirming its deleterious impact and the association with increased CRC risk. In addition, these findings underscore the interplay between genetic and environmental factors in CRC development, highlighting STING's potential as a genetic biomarker for CRC risk assessment in the Chinese population.

We review current studies on the anti-inflammatory and antifibrotic effects of herbal medicines and their active ingredients. To explore how these active ingredients target long noncoding RNA to exert their effects, we searched PubMed and Chinese National Knowledge Infrastructure databases for preclinical and clinical studies of long noncoding RNAs (lncRNA), herbal medicine, inflammation, and fibrosis. The active ingredients of herbal medicines were able to target lncRNAs. These interactions can have anti-inflammatory and antifibrotic effects on various diseases. The current studies provide preliminary insights but are not comprehensive. Targeting lncRNAs with herbal medicine ingredients is a promising direction for further research. This approach could lead to new alternative treatments for inflammation and fibrosis-related diseases.

Gastric cancer (GC) remains the leading cause of cancer deaths worldwide. GC development is a multistep and multifactorial process, and the molecular characterization of the multistage progression of gastric lesions to GC is poorly understood. Induction of ferroptosis driven by iron-dependent phospholipid peroxidation ameliorates the malignant progression of GC. Here, we found that solute carrier family 47 member 1 (SLC47A1) promoted GC progression by regulating ferroptosis. Clinically, SLC47A1 was elevated during the progression of gastritis to GC, and its high expression was associated with poor prognosis in patients with GC. Knockdown of SLC47A1 significantly inhibited cell proliferation, colony formation, and tumor growth. Further studies revealed that SLC47A1 was a regulator of ferroptosis rather than apoptosis or necrosis. Knockdown of SLC47A1 promoted ferroptosis in GC cells, as evidenced by increased erastin-induced cytoplasmic membrane rupture, cell death, lipid peroxidation, and malondialdehyde levels. Mechanistically, GATA6 promoted SLC47A1 transcription, leading to elevated SLC47A1 expression and promoting ferroptosis in GC cells. In summary, our study revealed the significant role of SLC47A1 in the development and progression of GC through regulating ferroptosis. Targeting the GATA6/SLC47A1 axis may be a promising therapeutic strategy for GC.

Cuproptosis is a new mode of cell death that is closely related to mitochondrial stress. The purpose of this study is to investigate the amount of copper, copper-associated genes DLAT and FDX1 oxidative stress (OS) status in obesity. Since there is a close relationship between OS and cuproptosis, evaluating the effect of various strategies to reduce OS, including quercetin (QUER) and caloric restriction (CR), is another goal of this study. In this study, 30 male BALB-C mice aged 8 weeks and weighing 25 g, including the groups receiving normal diet (ND), ND with QUER (15 mg/kg, IP) and CR, a high-fat diet (HFD) with the QUER, CR or a combination of both were used. The activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase (GR), amount of copper in the liver and kidney tissues, and expression of DLAT and FDX1 genes were measured in all studied groups. The amount of copper in the liver and kidney tissue as well as the expression of FDX1 and DLAT in the HFD group increased significantly compared with the ND group. QUER, CR or their combination could significantly reduce the amount of copper as well as the expression of FDX1 and DLAT in liver and kidney tissues. QUER and CR, also significantly increased the activity of GR, SOD and GPX in serum, liver, and kidney tissues. Based on the results, QUER, CR and especially the simultaneous use of both, was able to reduce the amount of copper and its related cuproptosis. These effects may reduce cuproptosis-associated cell death. Therefore, the use of antioxidants and CR may be a promising solution to protect the human body against the effects of cuproptosis in conditions like obesity.

Chromatin immunoprecipitation (ChIP) assesses DNA-proteins interactions and hence helps to generate intricate relationships and vital information. ChIP determines the genomic location of specific proteins or post-translational modifications at an individual locus or genome-wide. The protocol endures complexity; hence it is of utmost importance to identify the variable responsible for experimental erraticism. The most sensitive and critical step involves the chromatin fragmentation step. In the current study, the parameters required for chromatin shearing in the Kasumi-1 cell line have been optimized. To address this, the protocol includes the fixation of cells with formaldehyde followed by cell lysis and nuclei isolation. Further chromatin shearing using various sonication buffers and sonicator parameters was performed. Successful sonication was observed at the following settings: peak incident power of 150 W, duty factor 7.0%, cycles per burst 200, and water fill level 8 generating fragments of ∼250-600 bp in 7 min. To analyze enriched DNA sequences that are associated with the target protein ChIP coupled with quantitative PCR was performed. With this study, the optimal procedure has been standardized for a percentage of detergents, SDS (0.15%), DOC (0.05%) in the sonication buffer, and duration of sonication to achieve the desired fragmentation pattern. The quality of shearing determines the success of the experiment.

Sepsis is a serious systemic inflammatory condition triggered by a variety of pathogens, including bacteria and viruses, that can result in multiple organ failure and a life-threatening situation. Despite advances in medical care, the mortality rate for sepsis remains high even with aggressive treatment strategies such as antibiotic therapy, fluid resuscitation, and respiratory and circulatory support. Extracellular vesicles (EVs), as a novel nanoscale biocarrier, exhibit diverse biological functions including immune modulation and tissue regeneration, suggesting promising applications in the field. This article provides an overview of the diverse therapeutic effects of EVs derived from various sources in the management of sepsis. Furthermore, EVs not only possess intrinsic therapeutic properties, such as immune modulation, but also function as targeted delivery vehicles for a variety of drug molecules, leading to synergistic therapeutic outcomes. In conclusion, extracellular vesicle therapy is poised to emerge as a dynamic and innovative force driving advancements in sepsis treatment.