DNA and cell biology最新文献

Primary cilia are microtubule-based organelles that mediate various biological processes. Pancreatic cells are typically ciliated; however, the role of primary cilia in acute pancreatitis (AP) is largely unknown. Here, we report that the loss of primary cilia, mediated by SHCBP1 (SHC1 binding protein), exerted a provocative effect on AP. Primary cilia are extensively lost in inflamed pancreatic cells in vitro and in mouse tissues with AP in vivo. Abrogation of primary cilia aggravated lipopolysaccharide (LPS)-induced inflammation in pancreatic cells. Mechanistically, AP induced the overexpression of SHCBP1 mitotic factor, which is localized to the base of primary cilia. SHCBP1 deficiency relieved LPS- and cerulein-induced pancreatitis by preventing the loss of primary cilia in vitro and in vivo. Collectively, we reveal that inflammation-induced loss of primary cilia aggravates AP. Furthermore, abrogating SHCBP1 to prevent primary cilia loss is an efficient strategy to combat AP.

Around 50% of all occurrences of infertility are attributable to the male factor, which is a significant global public health concern. There are numerous circumstances that might interfere with spermatogenesis and cause the body to produce abnormal sperm. While evaluating sperm, the count, the speed at which they migrate, and their appearance are the three primary characteristics that are analyzed. MicroRNAs, also known as miRNAs, are present in all physiological fluids and tissues. They participate in both physiological and pathological processes. Researches have demonstrated that the expression of microRNA genes differs in infertile men. These genes regulate spermatogenesis at various stages and in several male reproductive cells. Hence, microRNAs have the potential to act as useful indicators in the diagnosis and treatment of male infertility and other diseases affecting male reproduction. Despite this, additional research is necessary to determine the precise miRNA regulation mechanisms.

Genetic variation and epigenetic factors are thought to contribute to the development of hypersensitivity to aspirin. DNA methylation fluctuates dynamically throughout the day. To discover new CpG methylation in lymphocytes associated with aspirin-exacerbated respiratory disease (AERD), we evaluated changes in global CpG methylation profiles from before to after an oral aspirin challenge in patients with AERD and aspirin-tolerant asthma (ATA). Whole-genome CpG methylation levels of peripheral blood mononuclear cells were quantified with an Illumina 860K Infinium Methylation EPIC BeadChip array and then adjusted for inferred lymphocyte fraction (ILF) with GLINT and Tensor Composition Analysis. Among the 866,091 CpGs in the array, differentially methylated CpGs (DMCs) were found in 6 CpGs in samples from all 12 patients with asthma included in the study (AERD, n = 6; ATA, n = 6). DMCs were found in 3 CpGs in the 6 ATA samples and in 615 CpGs in the 6 AERD samples. A total of 663 DMCs in 415 genes and 214 intergenic regions differed significantly in the AERD compared with the ATA. In promoters, 126 CpG loci were predicted to bind to 38 transcription factors (TFs), many of which were factors already known to be involved in the pathogenesis of asthma and immune responses. In conclusion, we identified 615 new CpGs methylated in peripheral blood lymphocytes by oral aspirin challenge in AERD but not in ATA. These findings indicate that oral aspirin challenge induces epigenetic changes in ILFs, specifically in AERD patients, possibly via changes in TF binding, which may have epigenetic effects on the development of AERD.

Cornus iridoid glycosides (CIGs), including loganin and morroniside, are the main active components of Cornus officinalis. As one of the key enzymes in the biosynthesis of CIGs, geranyl pyrophosphate synthase (GPPS) catalyzes the formation of geranyl pyrophosphate, which is the direct precursor of CIGs. In this study, the C. officinalis geranyl pyrophosphate synthase (CoGPPS) sequence was cloned from C. officinalis and analyzed. The cDNA sequence of the CoGPPS gene was 915 bp (GenBank No. OR725699). Phylogenetic analysis showed that CoGPPS was closely related to the GPPS sequence of Actinidia chinensis and Camellia sinensis, but relatively distantly related to Paeonia lactiflora and Tripterygium wilfordii. Results from the quantitative real-time PCR showed the spatiotemporal expression pattern of CoGPPS; that is, CoGPPS was specifically expressed in the fruits. Subcellular localization assay proved that CoGPPS was specifically found in chloroplasts. Loganin and morroniside contents in the tissues were detected by high-performance liquid chromatography, and both compounds were found to be at higher levels in the fruits than in leaves. Thus, this study laid the foundation for further studies on the synthetic pathway of CIGs.

HeberNasvac, a therapeutic vaccine for chronic hepatitis B, is able to safely stimulate multiple Toll-like receptors, increasing antigen presentation in vitro and in a phase II clinical trial (Profira) in elderly volunteers who were household contacts of respiratory infection patients. Thus, a new indication as a postexposure prophylaxis or early therapy for respiratory infections has been proposed. In this study, we evaluated the expression of several interferon-stimulated genes (ISGs) after mucosal administration of HeberNasvac and compared this effect with the nasal delivery of interferon alpha 2b (Nasalferon). Molecular studies of blood samples of 50 subjects from the Profira clinical trial who were locally treated with HeberNasvac or Nasalferon and concurrent untreated individuals were compared based on their relative mRNA expression of OAS1, ISG15, ISG20, STAT1, STAT3, and DRB1-HLA II genes. In most cases, the gene expression induced by HeberNasvac was similar in profile and intensity to the expression induced by Nasalferon and significantly superior to that observed in untreated controls. The immune stimulatory effect of HeberNasvac on ISGs paved the way for its future use as an innate immunity stimulator in elderly persons and immunocompromised subjects or as part of Mambisa, a nasal vaccine to prevent severe acute respiratory syndrome coronavirus 2 infection.

The effector proteins of several pathogenic bacteria contain the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif or other similar motifs. The EPIYA motif is delivered into the host cells by type III and IV secretion systems, through which its tyrosine residue undergoes phosphorylation by host kinases. These motifs atypically interact with a wide range of Src homology 2 (SH2) domain-containing mammalian proteins through tyrosine phosphorylation, which leads to the perturbation of multiple signaling cascades, the spread of infection, and improved bacterial colonization. Interestingly, it has been reported that EPIYA (or EPIYA-like) motifs exist in mammalian proteomes and regulate mammalian cellular-signaling pathways, leading to homeostasis and disease pathophysiology. It is possible that pathogenic bacteria have exploited EPIYA (or EPIYA-like) motifs from mammalian proteins and that the mammalian EPIYA (or EPIYA-like) motifs have evolved to have highly specific interactions with SH2 domain-containing proteins. In this review, we focus on the regulation of mammalian cellular-signaling pathways by mammalian proteins containing these motifs.

Vitiligo is one of the common chronic autoimmune skin diseases in clinic, which is characterized by localized or generalized depigmentation and seriously affects the physical and mental health of patients. At present, the pathogenesis of vitiligo is not clear; mainly, heredity, autoimmunity, oxidative stress, melanocyte (MC) self-destruction, and the destruction, death, or dysfunction of MCs caused by various reasons are always the core of vitiligo. Regulatory cell death (RCD) is an active and orderly death mode of cells regulated by genes, which widely exists in various life activities, plays a pivotal role in maintaining the homeostasis of the organism, and is closely related to the occurrence and development of many diseases. With the deepening of the research and understanding of RCD, people gradually found that there are many different forms of RCD in the lesions and perilesional skin of vitiligo patients, such as apoptosis, autophagy, pyroptosis, ferroptosis, and so on. Different cell death modes have different mechanisms in vitiligo, and different RCDs can interact and regulate each other. In this article, the mechanism related to RCD in the pathogenesis of vitiligo is reviewed, which provides new ideas for exploring the pathogenesis and targeted treatment of vitiligo.

Vesicular stomatitis virus (VSV) is a promising oncolytic virus for treating solid tumors. We recently engineered a replicating VSV that specifically targets and destroys Her2/neu-expressing cancer cells. This virus was created by eliminating its natural binding site and adding a coding sequence for a single chain antibody to the Her2/neu receptor into its genome. Such an approach can be tailored to target various cellular surface molecules. This mini review will discuss genomic modifications of VSVs and their role in oncolytic therapy and discuss some challenges for moving VSVs to clinical applications.