DNA and cell biology最新文献

The occurrence of diabetic kidney disease (DKD), a critical microvascular issue in diabetes, is progressively on the rise. In recent years, long noncoding RNAs (lncRNAs) have garnered considerable attention as a novel and critical layer of biological regulation. Our knowledge regarding the roles and underlying mechanisms of lncRNAs in various diseases, including DKD, continues to evolve. Similarly, microRNAs (miRNAs), which are small noncoding RNAs, have been recognized as crucial contributors to cellular processes and disease pathogenesis. Emerging studies have highlighted the complex interactions between lncRNAs and miRNAs, particularly in the context of DKD, underscoring their importance in complex human diseases. Renal intrinsic cell damage is an important cause of inducing DKD. Persistent high glucose stimulation leads to remodeling of renal intrinsic cells and a cascade of pathological changes. This article aims to review recent literature on the lncRNAs-mediated regulation of miRNAs affecting renal intrinsic cells in DKD and to propose novel molecular-level therapeutic strategies for DKD. Through in-depth investigation of this dynamic molecular interaction, we can gain a profound understanding of the potential mechanisms underlying diabetic nephropathy, potentially identifying new targets for therapeutic intervention and paving the way for personalized and effective treatments.

The lung as an organ that is fully exposed to the external environment for extended periods, comes into contact with numerous inhaled microorganisms. Lung macrophages are crucial for maintaining lung immunity and operate primarily through signaling pathways such as toll-like receptor 4 and nuclear factor-κB pathways. These macrophages constitute a diverse population with significant plasticity, exhibiting different phenotypes and functions on the basis of their origin, tissue residence, and environmental factors. During lung homeostasis, they are involved in the clearance of inhaled particles, cellular remnants, and even participate in metabolic processes. In disease states, lung macrophages transition from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. These distinct phenotypes have varying transcriptional profiles and serve different functions, from combating pathogens to repairing inflammation-induced damage. However, macrophages can also exacerbate lung injury during prolonged inflammation or exposure to antigens. In this review, we delve into the diverse roles of pulmonary macrophages the realms in homeostasis, pneumonia, tuberculosis, and lung tumors.

The mitotic phase involves the distribution and regulation of genetic material. Defects in gene regulation can lead to serious errors in genetic transmission, such as increased instability of chromosomes, thereby increasing susceptibility to cancer and promoting its development. The maintenance of chromosome stability depends on several mechanisms, such as efficient DNA repair, proper sister chromatid separation, and timely cytokinesis. The serine/threonine kinase Plk1 is a key molecule in maintaining chromosome stability, participating in multiple stages of precise regulation during mitosis, including promoting entry into mitosis, facilitating centrosome maturation and bipolar spindle formation, promoting sister chromatid separation, and facilitating cytokinesis. Several proteins can regulate the kinase activity of Plk1 through protein-protein interactions, coordinating the genetic stability of the cell, including the kinases Aurora A, c-Abl, and Chk1 as well as the phosphatase phosphatase and tension homolog (PTEN). PTEN has been described as an essential regulator of Plk1 for dephosphorylation and chromosomal stability during cell division, and Plk1 may directly interact with and phosphorylate PTEN at centromeres. Here, we review the bidirectional interplay between Plk1 and PTEN and how it contributes to genomic stability during mitosis.

The taxonomic classification of Babu tea (Family Theaceae) was preliminarily investigated by analyzing its epigenetic morphology and chromosomal features. Morphological observations of three Babu Tea phenotypes (red flower/purple bud, pink flower/purple bud, and white flower/green bud) revealed that the stomata were located exclusively on the lower epidermis, and the anticlinal walls of epidermal cells were deeply undulated. The stomatal apparatus also consisted of two crescent-shaped guard cells, forming a spindle shape with thickened "T-shaped" ends. Furthermore, the outer stomatal arches had smooth surfaces, while the inner ones were shallowly undulated. Finally, subsidiary cells were covered by a shallowly undulated epidermal stratum corneum that was composed of three layers. Their pollen grains exhibited a prolate spherical shape. Based on pollen morphology, the Babu Tea was therefore classified within Sect. Theopsis Coh. St., Camellia. Chromosome counting and karyotype analysis further confirmed that the three phenotypes share a chromosome count of 2n = 2x = 30, with their karyotypes classified as Type 2A. These findings suggest that the three phenotypes share a common evolutionary origin.

Acute exacerbation of asthma is often characterized by increased mucus production and hypersecretion. While mucins are believed to play a role in the pathogenesis and pathophysiology of airway diseases, no genetic studies on mucin genes have been conducted to date. We initially analyzed a genome-wide association dataset of 608 asthmatics, focusing on mucin gene polymorphisms. Subsequently, we conducted fine genotyping of the MUC13 gene in a separate cohort of 704 bronchial asthma patients monitored for over a year. Using generalized linear models and multiple logistic regression analyses, we evaluated the genetic associations of single nucleotide polymorphisms (SNPs) with the frequency of annual exacerbations and the likelihood of frequent exacerbations. Among 105 SNPs in 14 mucin genes analyzed, rs6765247 in MUC13 showed the most significant association with annual asthma exacerbation frequency. Fine genotyping revealed that individuals homozygous for the minor allele of rs6765247T>G had significantly more annual exacerbations compared to those with the common allele (mean ± SD; 0.94 ± 1.73 vs. 0.43 ± 1.02 and 0.35 ± 0.79, p = 0.001). The frequency of minor allele homozygotes was 3.2 times higher in frequent exacerbators than in nonfrequent exacerbators. The associations were particularly significant in smokers (interaction p = 0.009). These findings indicate that MUC13 is important in exacerbating asthma due to smoking and could be used as a marker to predict frequent exacerbations in smokers.

The side effects associated with flutamide as a first-line drug treating prostate cancer, including hepatotoxicity, the aim of this research was to use melatonin as an anticancer candidate to reduce the dose of flutamide and reduce its side effects. We evaluated the effect of melatonin, flutamide, and melatonin-flutamide combination therapy in LNCaP, DU145, and PC3 cell lines. The assessment includes Hoechst dye staining, scratch-wound assay, colony formation assay, flow cytometric analysis of apoptosis and DNA cell cycle, real-time PCR (BAX [BCL2 Associated X]/B-cell lymphoma-2 [BCL2], E-cadherin, Zinc finger protein SNAI2 [SNAIL], Hypoxia Inducible Factor 1 Subunit Alpha [HIF1α], Vascular Endothelial Growth Factor C [VEGFC], and kallikrein-related peptidase 3 [KLK3] genes). To determine Half maximal inhibitory concentration (IC50) levels, cell lines were exposed to different concentrations of the drugs. Our data indicated that IC50 values for melatonin (75 µM) and three cell lines and flutamide (12 and 10 µM) for PC3 and LNCaP/DU145, respectively, with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide were approved by flow cytometry in a dose and time-dependent manner which was as a consequence of cell cycle arrest at G0/G1 phase. Due to the efficacy of melatonin in combination with flutamide, we used 75 µM melatonin, and 5 µM flutamide instead of 12 µM in DU145, and 6 µM in PC3 and LNCaP, respectively. The combination of melatonin and flutamide significantly upregulated the expression of BAX/BCL2 ratio in all three cell lines (p < 0.0001) and downregulated the expression of KLK3 (p < 0.01), HIF1α (p < 0.01), VEGFC (p < 0.001), and epithelial-mesenchymal transition pathway genes in PC3 and LNCaP (p < 0.01). Melatonin in combination with flutamide reduced its dose and increased the sensitivity of prostate cancer cells to treatment.

This study presents a case of autosomal dominant polycystic kidney disease (ADPKD) involving a mosaic microdeletion in the PKD1 gene and explores the application of long-read sequencing technologies for haplotype construction and preimplantation genetic testing (PGT). We report on a family where the proband was clinically diagnosed with PKD and found to have a partial deletion of the PKD1 gene because of the mosaic deletion mutation of PKD1 in the mother of the proband. Utilizing Oxford Nanopore long-read sequencing, we successfully constructed the haplotype of the deleted fragment region and identified an unaffected embryo for transplantation, resulting in a successful pregnancy. The prenatal genetic diagnosis confirmed the absence of deletion abnormalities in the fetus. Our findings underscore the significance of integrating advanced genomic technologies into clinical practice for PGT in ADPKD, particularly in cases involving partial deletion of X chromosome mosaic embryo transferred or complex structural variants. This approach not only prevents the transmission of ADPKD but also demonstrates the utility of long-read sequencing in overcoming the limitations of traditional PGT methods. Further research is warranted to evaluate the broader application of long-read sequencing for other monogenic disorders and to refine these techniques for enhanced diagnostic precision and clinical outcomes.

Cellular plasticity, which refers to the capacity of cells to alter their identity or potency in response to a variety of stimuli, is emerging as an essential component in tissue repair. Despite the fact that stem cells have historically been considered to be the major agents of plasticity, new research has demonstrated that even differentiated cells in organs including the stomach, pancreas, and lungs are capable of displaying plasticity under specific physiological conditions, such as during injury and repair. One element essential for many physiological processes is vitamin B12 (VB12). Beyond its well-known roles in red blood cell production and nervous system maintenance, VB12 is critical for one-carbon metabolism and DNA synthesis and repair, processes indispensable for cellular health and tissue integrity. With its wide spectrum of actions, VB12 may have the potential to significantly influence tissue plasticity and repair, paving the way for new therapeutic interventions. Investigating fundamental processes and considering consequences for illness and aging, this perspective contemplates the junction of VB12, cell plasticity, and tissue repair.

Wilms' tumor (WT) is the most prevalent renal cancer in children. Numerous studies have shown that vir-like n6-methyladenosine (m6A) methyltransferase-associated protein (VIRMA), a necessary component and the largest methyltransferase, contributes to the advancement of multiple cancers. However, its function has not been characterized in WT. Hence, we examined the potential role of VIRMA in WT by analyzing its effect on the m6A modification of stearoyl-CoA desaturase (SCD). We utilized bioinformatics to narrow 12 differentially expressed (DE) genes in WT to a single gene. The expressions of SCD and VIRMA were analyzed via quantitative real-time PCR and western blotting. The influence of SCD on the malignancy attributes of WT cells and adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling was assessed through Cell counting Kit-8, Ethynyl-2'-deoxyuridine, transwell, and western blotting assays. The specific interactions between SCD and VIRMA were confirmed through methylated RNA immunoprecipitation, western blotting, and RNA stability assays, followed by rescue experiments to show underlying mechanisms. The SCD expression was found to be elevated in WT samples. Furthermore, its silencing mitigated the malignant characteristics of WT cells while increasing the protein levels of key AMPK signaling molecules. Moreover, VIRMA was also upregulated in WT samples and demonstrated a positive association with SCD expression. The relative enrichment of SCD m6A, its protein, and its mRNA stability were enhanced in VIRMA-overexpressed WT cells. Mechanically, VIRMA overexpression accelerated the malignant phenotypes of WT cells by interacting with SCD. Overall, the results demonstrate that VIRMA-mediated m6A methylation of SCD promotes WT progression by modulating the AMPK pathway.

Abiotic stress causes major crop losses worldwide. Plants have evolved complex intricate signaling network involving transcriptional regulators and posttranslational modifications (PTMs). Ubiquitination-a key PTM-regulates protein degradation through the ubiquitin-proteasome system (UPS). The UPS plays a pivotal role in detecting and modulating plant responses to environmental fluctuations. The E3 ligase family in plants is extensive, offering high substrate specificity and playing a vital role in signaling and protein turnover. Really Interesting New Gene (RING) proteins primarily function as E3 ubiquitin ligases, their functional diversity facilitates the transfer of ubiquitin molecules to specific target proteins. Plants possess abscisic acid (ABA)-dependent and ABA-independent stress-signaling pathways. RING-type E3 ligases regulate ABA signaling either negatively or positively in response to stress by regulating protein degradation, modulating transcription factors, ABA biosynthesis, and degradation. This dynamic interaction between ABA and E3 ligase proteins helps plants to adapt to environmental stress. Negative regulators, such as AIP2 and OsDSG1, target ABI3 for degradation. Keep on going (KEG) ubiquitinates ABI5, ABF1, and ABF3, though KEG itself is subject to feedback regulation by ABA levels, leading to its degradation. Positive regulators include SDIR1, OsSDIR1, AIRP1, RHA2b/RHA2a, and XERICO, along with its maize orthologs ZmXerico1 and ZmXerico2. Additionally, SINAT5 and BOI regulate auxin and gibberellin signaling, integrating hormonal responses to stress. The functional diversity of RING-type E3 ligases offers promising targets for genetic engineering to enhance crop resilience under adverse environmental conditions. Understanding these molecular mechanisms could lead to the development of climate-resilient crops, crucial for sustaining global food security.