Various diseases and toxic factors easily impair cellular and organic functions in mammals. Organ transplantation is used to rescue organ function, but is limited by scarce resources. Mesenchymal ...stem cell (MSC)‐based therapy carries promising potential in regenerative medicine because of the self‐renewal and multilineage potency of MSCs; however, MSCs may lose biological functions after isolation and cultivation for a long time in vitro. Moreover, after they are injected in vivo and migrate into the damaged tissues or organs, they encounter a harsh environment coupled with death signals due to the inadequate tensegrity structure between the cells and matrix. Preconditioning, genetic modification and optimization of MSC culture conditions are key strategies to improve MSC functions in vitro and in vivo, and all of these procedures will contribute to improving MSC transplantation efficacy in tissue engineering and regenerative medicine. Preconditioning with various physical, chemical and biological factors is possible to preserve the stemness of MSCs for further application in studies and clinical tests. In this review, we mainly focus on preconditioning and the corresponding mechanisms for improving MSC activities in vitro and in vivo; we provide a glimpse into the promotion of MSC‐based cell therapy development for regenerative medicine. As a promising consequence, MSC transplantation can be applied for the treatment of some terminal diseases and can prolong the survival time of patients in the near future.
The intestinal microbiota, composed of a large population of microorganisms, is often considered a "forgotten organ" in human health and diseases. Increasing evidence indicates that dysbiosis of the ...intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initiated and facilitated the CRC process are becoming increasingly clear. Hypothesis models have been proposed to illustrate the complex relationship between the intestinal microbiota and CRC. Recent studies have identified
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as CRC candidate pathogens. In this review, we summarized the mechanisms involved in microbiota-related colorectal carcinogenesis, including inflammation, pathogenic bacteria, and their virulence factors, genotoxins, oxidative stress, bacterial metabolites, and biofilm. We also described the clinical values of intestinal microbiota and novel strategies for preventing and treating CRC.
Current research has demonstrated that mitochondrial morphology, distribution, and function are maintained by the balanced regulation of mitochondrial fission and fusion, and perturbation of the ...homeostasis between these processes has been related to cell or organ dysfunction and abnormal mitochondrial redistribution. Abnormal mitochondrial fusion induces the fragmentation of mitochondria from a tubular morphology into pieces; in contrast, perturbed mitochondrial fission results in the fusion of adjacent mitochondria. A member of the dynamin family of large GTPases, dynamin-related protein 1 (Drp1), effectively influences cell survival and apoptosis by mediating the mitochondrial fission process in mammals. Drp1-dependent mitochondrial fission is an intricate process regulating both cellular and organ dynamics, including development, apoptosis, acute organ injury, and various diseases. Only after clarification of the regulative mechanisms of this critical protein in vivo and in vitro will it set a milestone for preventing mitochondrial fission related pathological processes and refractory diseases.
Pediococcus pentosaceus, a promising strain of lactic acid bacteria (LAB), is gradually attracting attention, leading to a rapid increase in experimental research. Due to increased demand for ...practical applications of microbes, the functional and harmless P. pentosaceus might be a worthwhile LAB strain for both the food industry and biological applications.
As an additive, P. pentosaceus improves the taste and nutrition of food, as well as the storage of animal products. Moreover, the antimicrobial abilities of Pediococcus strains are being highlighted. Evidence suggests that bacteriocins or bacteriocin-like substances (BLISs) produced by P. pentosaceus play effective antibacterial roles in the microbial ecosystem. In addition, various strains of P. pentosaceus have been highlighted for probiotic use due to their anti-inflammation, anticancer, antioxidant, detoxification, and lipid-lowering abilities.
Therefore, it is necessary to continue studying P. pentosaceus for further use. Thorough study of several P. pentosaceus strains should clarify the benefits and drawbacks in the future.
Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship ...with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the develop- ment and progression of major human diseases such as infectious diseases, liver diseases, gastrointesti- nal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics. Current research on the human microbiota has become much more sophisticated and more comprehensive. Therefore, we propose that research should focus on the host-microbe interaction and on causeeffect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.
Abstract
Background
We aimed to report the clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu Province.
Methods
We retrospectively investigated the clinical, ...imaging, and laboratory characteristics of confirmed cases of COVID-19 with World Health Organization interim guidance in 3 grade IIIA hospitals of Jiangsu from 22 January to 14 February 2020. Real-time RT-PCR was used to detect the new coronavirus in respiratory samples.
Results
Of the 80 patients infected with COVID-19, 41 were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. Nine patients were unconfirmed until a third nucleic acid test; 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 (78.75%) and 51 (63.75%) cases, respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (68.75%) showed abnormal density shadow and 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Currently, 21 cases have been discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days.
Conclusions
Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptibility. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that in Wuhan. Notably, infected patients may be falsely excluded based on 2 consecutively negative respiratory pathogenic nucleic acid test results.
Compared with the cases in Wuhan, 80 imported cases of COVID-19 in Jiangsu Province exhibited mild or moderate symptoms and no obvious gender susceptibility, lower proportion of liver dysfunction, and abnormal CT imaging and higher frequency of nucleic acid detection.
The liver is supplied by a dual blood supply, including the portal venous system and the hepatic arterial system; thus, the liver organ is exposed to multiple gut microbial products, metabolic ...products, and toxins; is sensitive to extraneous pathogens; and can develop liver failure, liver cirrhosis and hepatocellular carcinoma (HCC) after short-term or long-term injury. Although liver transplantation (LT) serves as the only effective treatment for patients with end-stage liver diseases, it is not very popular because of the complications and low survival rates. Although the liver is generally termed an immune and tolerogenic organ with adaptive systems consisting of humoral immunity and cell-mediated immunity, a high rejection rate is still the main complication in patients with LT. Growing evidence has shown that mesenchymal stromal cell (MSC) transplantation could serve as an effective immunomodulatory strategy to induce tolerance in various immune-related disorders. MSCs are reported to inhibit the immune response from innate immune cells, including macrophages, dendritic cells (DCs), natural killer cells (NK cells), and natural killer T (NKT) cells, and that from adaptive immune cells, including T cells, B cells and other liver-specific immune cells, for the generation of a tolerogenic microenvironment. In this review, we summarized the relationship between LT and immunoregulation, and we focused on how to improve the effects of MSC transplantation to improve the prognosis of LT. Only after exhaustive clarification of the potential immunoregulatory mechanisms of MSCs in vitro and in vivo can we implement MSC protocols in routine clinical practice to improve LT outcome.
Although stem cells have emerged as promising sources for regenerative medicine, there are many potential safety hazards for their clinical application, including tumorigenicity, an availability ...shortage, senescence, and sensitivity to toxic environments. Mesenchymal stem cells (MSCs) have various advantages compared to other stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs); thus, MSCs have been intensely investigated in recent studies. However, they are placed in a harsh environment after isolation and transplantation, and the adverse microenvironment substantially reduces the viability and therapeutic effects of MSCs. Intriguingly, melatonin (MT), which is primarily secreted by the pineal organ, has been found to influence the fate of MSCs during various physiological and pathological processes. In this review, we will focus on the recent progress made regarding the influence of MT on stem cell biology and its implications for regenerative medicine. In addition, several biomaterials have been proven to significantly improve the protective effects of MT on MSCs by controlling the release of MT. Collectively, MT will be a promising agent for enhancing MSC activities and the regenerative capacity via the regulation of reactive oxygen species (ROS) generation and the release of immune factors in regenerative medicine.
Liver diseases caused by viral infection, alcohol abuse and metabolic disorders can progress to end‐stage liver failure, liver cirrhosis and liver cancer, which are a growing cause of death ...worldwide. Although liver transplantation and hepatocyte transplantation are useful strategies to promote liver regeneration, they are limited by scarce sources of organs and hepatocytes. Mesenchymal stem cells (MSCs) restore liver injury after hepatogenic differentiation and exert immunomodulatory, anti‐inflammatory, antifibrotic, antioxidative stress and antiapoptotic effects on liver cells in vivo. After isolation and culture in vitro, MSCs are faced with nutrient and oxygen deprivation, and external growth factors maintain MSC capacities for further applications. In addition, MSCs are placed in a harsh microenvironment, and anoikis and inflammation after transplantation in vivo significantly decrease their regenerative capacity. Pre‐treatment with chemical agents, hypoxia, an inflammatory microenvironment and gene modification can protect MSCs against injury, and pre‐treated MSCs show improved hepatogenic differentiation, homing capacity, survival and paracrine effects in vitro and in vivo in regard to attenuating liver injury. In this review, we mainly focus on pre‐treatments and the underlying mechanisms for improving the therapeutic effects of MSCs in various liver diseases. Thus, we provide evidence for the development of MSC‐based cell therapy to prevent acute or chronic liver injury. Mesenchymal stem cells have potential as a therapeutic to prolong the survival of patients with end‐stage liver diseases in the near future.
•An altered fecal microbiome was associated with the Alzheimer’s disease (AD).•The depleted Firmicutes and enriched Proteobacteria linked with severity of AD.•Enterobacteriaceae was associated with ...the presence and progression of AD.•Models based on fecal microbiota discriminate AD from aMCI and health subjects.
(Background): Alzheimer’s disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the ‘gut-brain’ axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated.
A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC. And the microbial composition was distinct among aMCI, AD and healthy control groups. Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC. In addition, similar alterations were observed at the order, class and family levels of these two phyla. And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients. Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes. Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients. Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925). Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698).
Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects. These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.
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