简介：AbstractPreeclampsia (PE) is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year. Unfortunately, there is no effective management to arrest the progression of this disease unless delivery. Therefore, standardized management or preventive treatments are needed urgently. PE is closely associated with placental hypoxia, which increases the secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) as well as soluble endoglin (sEng) into the maternal circulation. Metformin has been found to inhibit those anti-angiogenic factors so it might be a candidate to prevent or treat PE. Women who are diagnosed with gestational diabetes mellitus (GDM) are more likely to have complications of hypertension or PE, so this review aims to demonstrate that the application of metformin in GDM might prevent the onset or progression of PE complicated with GDM.

简介：AbstractPancreatic cancer is an aggressive malignancy with a high recurrence rate even after curative-intent resection. Improvements in survival have not been achieved in the last 25 years thus highlighting the need for effective multimodal treatment strategies. The role of radiation therapy for pancreatic cancer remains ill-defined due to historical lack of a standard definition of resectability, and the use of antiquated radiation delivery techniques and chemotherapy regimens. Current level I data regarding neoadjuvant chemoradiotherapy for resectable and borderline resectable pancreatic adenocarcinoma (PDAC) are limited to 2 randomized controlled trials and several retrospective studies and suggest that it may lead to an increased likelihood of a margin-negative resection and certainly allows for improved patient selection for pancreaticoduodenectomy when compared to upfront surgery. In the adjuvant setting, data are similarly lacking but suggest that chemoradiotherapy may be beneficial for patients at high risk of locoregional recurrence. Here we review existing data regarding the role of radiation in PDAC.

简介：AbstractSystemic sclerosis (SSc) is characterized by immune dysfunction, vasculopathy, chronic fibrosis of skin and internal organs with complex etiology. With the rapid development and the application in biomedicine of epigenetics, accumulating evidence has shown that epigenetics plays an important role in the pathogenesis of SSc. Environmental factors via epigenetics are needed to trigger and maintain for the disease in the subjects with genetic predisposition to SSc. The role of epigenetics in the pathogenesis of SSc includes hypermethylation of the promoter region of nitric oxide synthase and bone morphogenetic protein receptors II, up-regulation of histone deacetylases 4 and 5 expression, and down-regulation of miR-193b and miR-152 in endothelial cells inducing vascular dysfunction; DNA hypermethylation and hypoacetylation of histone H3 and H4 in Friend leukemia virus integration 1 and Kruppel-like factor 5 genes, and the abnormal expression of miR-29, miR-129-5p and miR-135b in fibroblasts causing excessive fibrosis; DNA hypomethylation in the promoter regions of CD11a and CD70 genes in CD4+T cells resulting in immune dysfunction. Studies on the role of epigenetics in SSc are of great significance for better understanding the pathogenic machanism of SSc, which is helpful to find new molecular targets for treating SSc, and consequently, improve the prognosis of SSc.

简介：AbstractThe early intestinal microbiota plays an important role in immune regulation, and the unbalanced composition may increase the occurrence of allergic diseases, including atopic dermatitis. This review summarizes the latest studies in the occurrence and development of intestinal microflora and its relationship with atopic dermatitis. These results are conducive to understand the differences in the composition of intestinal microbiota between patients with atopic dermatitis and healthy people, and provide a potential intervention for prevention or treatment of atopic dermatitis.

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简介：AbstractExtracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.

简介：AbstractBoth fatty acids (FAs) and calcium ions play important roles in contraceptive cycles via several systems. Polyunsaturated FAs (PUFAs) act as precursors for prostaglandin production and can alter the expression of numerous crucial catalysts that are involved in prostaglandin and steroid digestion. Lipids are essential components of cell membranes. A diet rich in PUFAs enhances sperm motility and viability. It also improves testis development and spermatogenesis in several domesticated animal species. Increased PUFA content in spermatozoa increases plasma membrane fluidity, which is important for fertilization. However, the major drawback of high dietary PUFA intake is that it increases the levels of reactive oxygen species in the body. An increase in reactive oxygen species levels markedly affects fertility. Calcium is an important component that acts as an intra-cellular secondary messenger and plays an important role in some of the physiological processes that occur in male gametes. Some of these processes include spermatogenesis, sperm motility, capacitation, acrosome response, and fusion of gametes. These processes are associated with calcium influx through ion protein channels. Dietary fat intake is associated with increased intestinal calcium absorption. In this review, we discuss the impact of lipids, particularly PUFAs and monounsaturated FAs, and calcium ions on male reproduction, along with their effects on each other.

简介：AbstractCilia are microtubule-based filamentous organelles that play a vital role in embryogenesis. Multiple signal transduction pathways are orchestrated by cilia, such as Hedgehog and planar cell polarity signals. Various studies, spanning over last 2 decades, have emphasized the role of cilia-mediated signaling cascades in regulating neural tube patterning and development. Moreover, the deficiency of certain ciliary genes have been reported to cause neural tube defects (NTDs), which are a set of disorders that occur due to perturbation of normal neural tube closure. However, the mechanisms underlying cilia dysfunction resulting NTDs remain unclear. Recent studies have highlighted the association of phosphoinositide signaling with cilia, thereby conferring novel insights into the function of cilia during neural tube development. Here, we have reviewed recent studies on cilia, focusing on the molecular mechanism underlying the involvement of cilia in neural tube development and the role of ciliary disruption in the development of NTDs.

简介：AbstractAlthough whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders, about half of the patients still do not receive a molecular diagnosis. The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing (RNA-seq) in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence. RNA-seq data can be used to identify aberrantly spliced genes, detect allele-specific expression, and identify gene expression outliers. Amongst eight studies utilizing RNA-seq, a mean diagnostic uplift of 15% has been reported. Here, we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.

简介：AbstractPancreatic ductal adenocarcinoma is the main cause of cancer-related mortality, with a lack of effective treatments and overall survival rates far lower than other solid cancers. This clinical challenge is related to late diagnosis as well as primary or acquired resistance to therapy-induced apoptosis. Targeting nonapoptotic cell death pathways may provide alternative therapeutic strategies to overcome drug resistance. In particular, recent studies have suggested that ferroptosis, a type of iron-dependent nonapoptotic cell death, is a promising target for pancreatic ductal adenocarcinoma. Ferroptosis can be triggered by inhibiting or activating the redox or iron metabolism-related pathways, mediated by extrinsic/membrane transports (e.g., solute carrier family 7 member 11) or intrinsic/enzymes (e.g., glutathione peroxidase 4). Although the exact effector molecule remains obscure, reactive oxygen species-induced lipid peroxidation and subsequent plasma membrane damage appears to play a central role in mediating ferroptotic death. While treatment-induced ferroptosis is beneficial to suppress tumor growth, inflammation-related immunosuppression caused by ferroptotic damage may promote the occurrence of pancreatic ductal adenocarcinoma. In this review, we outline the latest knowledge about the regulation and function of ferroptosis in pancreatic tumorigenesis and therapy.

简介：AbstractPancreatic neuroendocrine tumors (pNET) are heterogenous tumors originated from the diffuse neuroendocrine cells of pancreas, which show the function of synthesis, storage and secretion of peptide hormones and biomimetic amines. Biomarkers play a crucial role in the diagnosing, evaluating prognosis and predicting treatment response for pNET patients. Traditional NET markers such as chromogranin A and Neuron Specific Enolase, as a diagnostic biomarker, have relatively low sensitivity and specificity in pNET patients. The emergence of new types of biomarkers provides more reliable indicators for diagnosis and prognosis evaluation. Among them, NETest score is a promising biomarker with the highest diagnostic sensitivity (80%) and specificity (94%). In addition, this molecule can be also used as a prognostic biomarker, which can predict disease progression and shorter overall survival. Biomarkers related to therapeutic targets, such as vascular endothelial growth factor, vascular endothelial growth factor receptor, and key molecules of mTOR signaling pathway, have capability to predict response of treatment. With the development of next-generation sequencing, chip array, and digital droplet PCR, novel biomarkers such as circulating tumor cells, tumor-derived exosomes, and circulating tumor DNA and mRNA are expected to provide more accurate diagnosis, prognostic information, and prospective therapeutic targets. In this paper, biomarkers of pancreatic neuroendocrine tumor and their role in diagnosis, prognosis, diagnosis, treatment and monitoring are systematically introduced. Our conclusions can provide new basis for clinicians in the diagnosis and treatment process.

简介：AbstractAutoimmune diseases with hematological manifestations are often characterized by chronicity and relapses despite treatment, and the underlying pathogenetic mechanisms remain unknown. Epigenetic alterations play a vital role in the deregulation of immune tolerance and the development of autoimmune diseases. In recent years, study of epigenetic mechanisms in both adult and childhood autoimmune disorders has been seeking to explain the pathophysiology of these heterogeneous diseases and to elucidate the interaction between genetic and environmental factors. Various mechanisms, including DNA methylation, histone modifications (chromatin remodeling), and noncoding RNAs (ncRNAs), have been studied extensively in the context of autoimmune diseases. This paper summarizes the epigenetic patterns in some of the most common childhood autoimmune disorders with hematological manifestations, based on epigenetic studies in children with primary immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), and juvenile idiopathic arthritis (JIA). Research findings indicate that methylation changes in genes expressed on T cells, modifications at a variety of histone sites, and alterations in the expression of several ncRNAs are involved in the pathogenesis of these diseases. These mechanisms not only determine the development of these diseases but also affect the severity of the clinical presentation and biochemical markers. Further studies will provide new tools for the prevention and diagnosis of childhood autoimmune disorders, and possible novel treatment options.

简介：AbstractGlucagon is a potent glucose-elevating hormone that is secreted by pancreatic α- cells. While well-controlled glucagon secretion plays an important role in maintaining systemic glucose homeostasis and preventing hypoglycaemia, it is increasingly apparent that defects in the regulation of glucagon secretion contribute to impaired counter-regulation and hyperglycaemia in diabetes. It has therefore been proposed that pharmacological interventions targeting glucagon secretion/signalling can have great potential in improving glycaemic control of patients with diabetes. However, despite decades of research, a consensus on the precise mechanisms of glucose regulation of glucagon secretion is yet to be reached. Second messengers are a group of small intracellular molecules that relay extracellular signals to the intracellular signalling cascade, modulating cellular functions. There is a growing body of evidence that second messengers, such as cAMP and Ca2+, play critical roles in α-cell glucose-sensing and glucagon secretion. In this review, we discuss the impact of second messengers on α-cell electrical activity, intracellular Ca2+ dynamics and cell exocytosis. We highlight the possibility that the interaction between different second messengers may play a key role in the glucose-regulation of glucagon secretion.

简介：AbstractAutoimmune diseases are primary immune diseases in which autoreactive antibodies or sensitized lymphocytes destroy and damage tissue and cellular components, resulting in tissue damage and organ dysfunction. Helper T cells may be involved in the pathogenesis of autoimmune diseases under certain conditions. This review summarizes recent research on the role of helper T cells in autoimmune diseases from two aspects, helper T cell-mediated production of autoantibodies by B cells and helper T cell-induced activation of abnormal lymphocytes, and provides ideas for the treatment of autoimmune diseases. The abnormal expression of helper T cells promotes the differentiation of B cells that produce autoantibodies, which leads to the development of different diseases. Among them, abnormal expression of Th2 cells and T follicular helper cells is more likely to cause antibody-mediated autoimmune diseases. In addition, abnormal activation of helper T cells also mediates autoimmune diseases through the production of abnormal cytokines and chemokines. Helper T cells play an essential role in the pathogenesis of autoimmune diseases, and a full understanding of their role in autoimmune diseases is helpful for providing ideas for the treatment of autoimmune diseases.

简介：AbstractNew discoveries based on genetic and epigenetic evidence have significantly expanded the understanding of diffuse gliomas. Molecular biomarkers detected in diffuse gliomas are not only potential targets for radiotherapy, chemotherapy, and immunotherapy, but are also able to guide surgical treatment. Previous studies have suggested that the optimal extent of resection of diffuse gliomas varies according to the expression of specific molecular biomarkers. However, the specific guiding role of these biomarkers in the resection of diffuse gliomas has not been systemically analyzed. This review summarizes several critical molecular biomarkers of tumorigenesis and progression in diffuse gliomas and discusses different strategies of tumor resection in the context of varying genetic expression. With ongoing study and advances in technology, molecular biomarkers will play a more important role in glioma resection and maximize the survival benefit from surgery for diffuse gliomas.

简介：AbstractAtopic dermatitis (AD) is a chronic inflammatory skin disease with xerosis, itchiness, as well as interconnection with immunoglobulin E (Ig E), mediated foods including airborne allergies. AD is not only related to the diminished stratum corneum barrier but also presents with an unusual expression of tight junctions (TJs) proteins. TJ barrier dysfunction leads to impairment in the stratum corneum (SC) barrier. The significant role of TJs in the epidermal barrier as indicated by Claudin-1 (Cldn-1) deficient mice that undergo high transepidermal water loss (TEWL) and skin dehydration. In atopic dermatitis, downregulation of Cldn-1 was observed due to inflammation. Still, a lack of distinct understanding exists in considering tight junction barrier impairment as a cause or outcome in atopic dermatitis. This review summarizes TJs main role in skin barrier function and TJ proteins (TJPs) expression observed in AD patients.

简介：AbstractThe main treatments for Parkinson’s disease (PD) currently include surgery, rehabilitation, and most commonly, drug therapy. However, the drugs that are currently used to treat PD provide only symptomatic relief and delayed disease progression but have no curative effect and cause many adverse reactions. When considering pathogenic factors and metabolic regulation, PD and type 2 diabetes have a high rate of comorbidity; this provides a theoretical basis for the treatment of PD with first-line antidiabetic drugs. Among these agents, metformin reduces neuronal damage in the brains of PD patients via neuroprotection and the inhibition of oxidative stress and inflammatory responses, thus providing a novel strategy for the clinical treatment of PD. Here, we present the current state of knowledge about the use of metformin to treat PD and discuss its clinical prospects.

简介：AbstractBackground:Acinetobacter baumannii (A. baumannii) has become one of the most important opportunistic pathogens inducing nosocomial pneumonia and increasing mortality in critically ill patients recently. The interaction between A. baumannii infection and immune response can influence the prognosis of A. baumannii related pneumonia. The target of the present study was to investigate the role of immunodeficiency in A. baumannii induced pneumonia.Methods:Male BALB/c mice were randomly divided into the normal immunity control (NIC) group, normal immunity infection (NIA) group, immune compromised control (CIC) group, and immune compromised infection (CIA) group (n = 15 for each group). Intraperitoneal injection of cyclophosphamide and intranasal instillation of A. baumannii solution were used to induce compromised immunity and murine pneumonia, respectively. The mice were sacrificed at 6 and 24 h later and the specimens were collected for further tests. Seven-day mortality of mice was also assessed.Results:After A. baumannii stimulation, the recruitment of neutrophils in mice with normal immunity increased sharply (P = 0.030 at 6 h), while there was no significant raise of neutrophil counts in mice with compromised immune condition (P = 0.092 at 6 h, P = 0.772 at 24 h). The Th cell polarization presented with pulmonary interleukin (IL)-4 and interferon (IFN)-γ level in response to the A. baumannii in CIA group were significantly depressed in comparison with in NIA group (IFN-γ: P = 0.003 at 6 h; P = 0.001 at 24 h; IL-4: P < 0.001 at 6 h; P < 0.001 at 24 h). The pulmonary conventional dendritic cell accumulation was even found to be inhibited after A. baumannii infection in immunocompromised mice (P= 0.033). Correspondingly, A. baumannii associated pneumonia in mice with compromised immunity caused more early stage death, more severe histopathological impairment in lung.Conclusion:A. baumannii could frustrate the immune response in immunocompromised conditions, and this reduced immune response is related to more severe lung injury and worse outcome in A. baumannii induced pneumonia.

简介：AbstractPurpose:The proposed pathological mechanism for scar formation is controversial, and increased attention has been paid to the fatty acids (FAs) in the formation of pathological scars. Notably, FAs are known to be important in inflammation and mechanotransduction, which is closely related to scar formation. Therefore, it is necessary to clarify the roles of FA in scar formation.Methods:Hypertrophic scar and keloid formed for more than a year and without other treatment, as well as normal skin samples were obtained from patients who underwent plastic surgery. Finally, keloids (n = 10), hypertrophic scars (n = 10), and normal skin samples (n = 10) were collected under informed consent. Primary dermal fibroblasts were isolated and cultured. The amount and variety of FAs were detected by lipid chromatography-mass spectrometry. Immunohistochemistry, real-time PCR, and western blotting were used to verify the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FASN) in the samples and their fibroblasts. Student's t-test, ANOVA, and orthogonal partial least square discriminant analysis were performed for statistical analysis (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).Results:Compared with full-thickness normal skin, there were 27 differential FAs in keloids and 15 differential FAs in hypertrophic scars (*p < 0.05 and variable influence on projection >1.0). The expression of SREBP1 and FASN was lower in pathological scars both at mRNA and protein levels (all*p < 0.05). However, the mRNA levels of SREBP1 (***p = 0.0002) and FASN (***p = 0.0021) in keloid-derived fibroblasts were higher than that in normal skin fibroblasts (NFBs), while the expression in hypertrophic scar-derived fibroblasts was lower than that in NFBs (both *p < 0.05). Whereas there was no significant difference in FASN protein expression between keloid-derived fibroblasts and NFBs (p > 0.05).Conclusion:FAs involved in pathological scars are abnormally changed in scar formation. Thus, fatty acid-derived inflammation and de novo synthesis pathway of FA may play a key role in the formation of pathological scars.

简介：AbstractAlthough considerable advances have been made in the field of assisted reproductive technology (ART), millions of couples still suffer from infertility and miscarriage. In a large number of cases, the etiology of these common reproductive failures remains unknown. However, the significance of autoantibodies in infertility and miscarriage has sparked extensive interest because of their pleiotropic roles in disrupting normal pregnancy. This review discusses the pleiotropic roles of a series of autoantibodies in infertility and miscarriage. A brief recapitulation of how the autoantibodies interfere with ART outcomes and treatments for this type of idiopathic infertility or miscarriage is also provided. While several disputes remain to be resolved, further studies employing better designs and larger sample sizes are required in view of the therapeutic potential of autoantibody inhibitors and the future of contraceptive vaccines.