Inflammation and Regeneration最新文献

Skeletal muscles have an extraordinary capacity to regenerate themselves when injured. Skeletal muscle stem cells, called satellite cells, play a central role in muscle regeneration via three major steps: activation, proliferation, and differentiation. These steps are affected by multiple types of cells, such as immune cells, fibro-adipogenic progenitor cells, and vascular endothelial cells. The widespread use of single-cell sequencing technologies has enabled the identification of novel cell subpopulations associated with muscle regeneration and their regulatory mechanisms. This review summarizes the dynamism of the cellular community that controls and promotes muscle regeneration, with a particular focus on skeletal muscle stem cells.

Background: Rheumatoid arthritis (RA) is associated with immune dysfunction. UBASH3A as a negative regulator of T cell receptors (TCRs) signaling is a susceptible factor in RA. The aim of this study was to determine the role of UBASH3A in RA pathogenesis, by assessing the role of super-enhancer (SE) in the control of UBASH3A expression in CD4⁺ T cells and the contribution of the latter in proinflammatory cytokine production in patients with RA.

Methods: UBASH3A mRNA and protein levels were quantified by PCR and western blotting, respectively. The cells were treated with a locked nucleic acid to inhibit enhancer RNA (eRNA) expression. Chromatin immunoprecipitation was used to identify the factors recruited to UBASH3A loci displaying SE architecture. CD4⁺ T cells were transfected with UBASH3A plasmids, and cytokine levels were measured by a cytometric bead array.

Results: UBASH3A was extracted as a RA susceptibility gene associated with SNPs in the SEs that are highly expressed in CD4⁺ T cells by in silico screening. UBASH3A mRNA and protein expression levels were lower in CD4⁺ T cells of RA patients than in the control. eRNA_1 and eRNA_3 knockdown reduced UBASH3A mRNA levels. RA patients exhibited accumulation of BTB and CNC homology 2 (BACH2), the silencing transcription factor, at the UBASH3A loci in CD4⁺ T cells, but not the SE-defining factor, mediator complex subunit 1 (MED1)/bromodomain 4 (BRD4). However, opposite changes were observed in the control. Stimulation of TCRs expressed on CD4⁺ T cells of RA patients resulted in interleukin (IL)-6 production, while UBASH3A over-expression significantly inhibited the production.

Conclusions: In RA, transcription of UBASH3A is suppressed via epigenetic regulation of SE in CD4⁺ T cells. Low UBASH3A levels result in excessive TCR signal activation with subsequent enhancement of IL-6 production.

Background: The intestine is rich in food-derived and microbe-derived antigens. Regulatory T cells (Tregs) are an essential T-cell population that prevents systemic autoimmune diseases and inhibits inflammation by encountering antigens. Previously, it was reported that the functional loss of Tregs induces systemic inflammation, including inflammatory bowel disease and graft-versus-host disease in human and murine models. However, there is a dearth of information about how Tregs localize in different tissues and suppress effector cells.

Main body: The development of Tregs and their molecular mechanism in the digestive tract have been elucidated earlier using murine genetic models, infectious models, and human samples. Tregs suppress immune and other nonimmune cells through direct effect and cytokine production. The recent development of in vivo imaging technology allows us to visualize how Tregs localize and move in the settings of inflammation and homeostasis. This is important because, according to a recent report, Treg characterization and function are regulated by their location. Tregs located in the proximal intestine and its draining lymph nodes induce tolerance against food antigens, and those located in the distal intestine suppress the inflammation induced by microbial antigens. Taken together, various Tregs are induced in a location-specific manner in the gastrointestinal tract and influence the homeostasis of the gut.

Conclusion: In this review, we summarize how Tregs are induced in the digestive tract and the application of in vivo Treg imaging to elucidate immune homeostasis in the digestive tract.

Due to increased resistance to standard chemo/radiotherapies and relapse, highly tumorigenic cancer stem cells (CSCs) have been proposed as a promising target for the development of effective cancer treatments. In order to develop innovative cancer therapies that target CSCs, much attention has focused on the iron metabolism of CSCs, which has been considered to contribute to self-renewal of CSCs. Here, we review recent advances in iron metabolism and conventional iron metabolism-targeted cancer therapies, as well as therapy resistance of CSCs and potential treatment options to overcome them, which provide important insights into therapeutic strategies against intractable cancers. Potential treatment options targeting iron homeostasis, including small-molecule inhibitors, nanotechnology platforms, ferroptosis, and 5-ALA-PDT, might be a focus of future research for the development of innovative cancer therapies that tackle CSCs.

The microenvironment of the thymus is composed of a group of stromal cells that include endoderm-derived thymic epithelial cells (TECs) and mesenchymal stromal cells such as fibroblasts and serves as a site for the development of T cells. TECs are known to play an essential role in T cell differentiation and selection. Mesenchymal stromal cells have been less studied in terms of their immunological significance compared to TECs. Recently, new technologies have made it possible to identify and characterize mesenchymal stromal cells in the thymus, revealing their unique functions in thymic organogenesis and T cell development. This review outlines the current views on mesenchymal stromal cells in the thymus, particularly highlighting the newly discovered function of thymic fibroblasts in T cell repertoire selection.

The intestinal microbiome is dominated by bacteria and plays a pivotal role in the occurrence and development of disease, including several metabolic and autoimmune disorders. While intestinal viral communities, primarily made up of bacteriophages, are also thought to play a role in disease pathogenesis in the gastrointestinal tract, they have received much less attention than intestinal bacteria. Thus, there is limited information about the relationship between bacteriophages and disease. This review explores a potential role for the intestinal viral microbiome in various metabolic and autoimmune diseases.

Background: Multiple sclerosis (MS) is a progressive autoimmune demyelinating disease of the central nervous system. To date, there is no effective therapy for it. Our study aimed to determine the potential role of platelet-rich plasma (PRP) in the treatment of MS in cats.

Methods: The current study was conducted on 15 adult Persian cats that were divided into three groups: control negative, control positive (ethidium bromide (EB)-treated group), and PRP co-treated group (EB-treated group intrathecally injected with PRP on day 14 post-spinal cord injury). PRP was obtained by centrifuging blood on anticoagulant citrate dextrose and activating it with red and green laser diodes. The Basso-Beattie-Bresnahan (BBB) scores were used to assess the motor function recovery on days 1, 3, 7, 14, 20, and 28 following 14 days from EB injection. Moreover, magnetic resonance imaging (MRI) analysis, histopathological investigations, transmission electron microscopy (TEM) studies, and immunohistochemical analysis were conducted, and the gene expressions of nerve growth factors (NGFs), brain-derived neurotrophic factors (BDNF), and stromal cell-derived factors (SDF) were evaluated.

Results: Our results indicated that PRP had a significant ameliorative effect on the motor function of the hindlimbs as early as day 20 and so on. MRI revealed that the size and intensity of the lesion were significantly reduced in the PRP co-treated group. The histopathological and TEM investigations demonstrated that the PRP co-treated group had a significant improvement in the structure and organization of the white matter, as well as a high remyelination capacity. Furthermore, a significant increase in myelin basic protein and Olig2 immunoreactivity as well as a reduction in Bax and glial fibrillar acidic protein immune markers was observed. NGFs were found to be upregulated by gene expression.

Conclusion: As a result, we concluded that the intrathecal injection of PRP was an effective, safe, and promising method for the treatment of MS.

Cellular metabolisms produce reactive oxygen species (ROS) which are essential for cellular signaling pathways and physiological functions. Nevertheless, ROS act as "double-edged swords" that have an unstable redox balance between ROS production and removal. A little raise of ROS results in cell proliferation enhancement, survival, and soft immune responses, while a high level of ROS could lead to cellular damage consequently protein, nucleic acid, and lipid damages and finally cell death. ROS play an important role in various pathological circumstances. On the contrary, ROS can show selective toxicity which is used against cancer cells and pathogens. Photodynamic therapy (PDT) is based on three important components including a photosensitizer (PS), oxygen, and light. Upon excitation of the PS at a specific wavelength, the PDT process begins which leads to ROS generation. ROS produced during PDT could induce two different pathways. If PDT produces control and low ROS, it can lead to cell proliferation and differentiation. However, excess production of ROS by PDT causes cellular photo damage which is the main mechanism used in cancer treatment. This review summarizes the functions of ROS in living systems and describes role of PDT in production of controllable ROS and finally a special focus on current ROS-generating therapeutic protocols for regeneration and wound healing.

Alzheimer's disease (AD) is one of the major neurodegenerative diseases and the most common form of dementia. Characterized by the loss of learning, memory, problem-solving, language, and other thinking abilities, AD exerts a detrimental effect on both patients' and families' quality of life. Although there have been significant advances in understanding the mechanism underlying the pathogenesis and progression of AD, there is no cure for AD. The failure of numerous molecular targeted pharmacologic clinical trials leads to an emerging research shift toward non-invasive therapies, especially multiple targeted non-invasive treatments. In this paper, we reviewed the advances of the most widely studied non-invasive therapies, including photobiomodulation (PBM), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and exercise therapy. Firstly, we reviewed the pathological changes of AD and the challenges for AD studies. We then introduced these non-invasive therapies and discussed the factors that may affect the effects of these therapies. Additionally, we review the effects of these therapies and the possible mechanisms underlying these effects. Finally, we summarized the challenges of the non-invasive treatments in future AD studies and clinical applications. We concluded that it would be critical to understand the exact underlying mechanisms and find the optimal treatment parameters to improve the translational value of these non-invasive therapies. Moreover, the combined use of non-invasive treatments is also a promising research direction for future studies and sheds light on the future treatment or prevention of AD.