Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

Sepsis,a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection,is a leading contributor to mortality in intensive care units.Sepsis-related deaths have been reported to account for 19.7%of all global deaths.However,no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis.Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis.Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry,targeting infection and/or imbalanced immune responses,have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment.Nanoplatforms can overcome the barriers faced by clinical strategies,including delayed diagnosis,drug resistance and incapacity to manage immune disorders.Here,we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts,summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies.Based on these state-of-the-art studies,this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models

Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.

A critical role of foxp3a-positive regulatory T cells in maintaining immune homeostasis in zebrafish testis development

Suppressive regulatory T cells(Treg cells)play a vital role in preventing autoimmunity and restraining excessive immune response to both self-and non-self-antigens.Studies on humans and mice show that the Forkhead box p3(Foxp3)is a key regulatory gene for the development and function of Treg cells.In zebrafish,Treg cells have been identified by using foxp3a as a reliable marker.However,little is known about the function of foxp3a and Treg cells in gonadal development and sex differentiation.Here,we show that foxp3a is essential for maintaining immune homeostasis in zebrafish testis development.We found that foxp3a was specifically expressed in a subset of T cells in zebrafish testis,while knockout of foxp3a led to deficiency of foxp3a-positive Treg cells in the testis.More than 80%of foxp3a^(-/-)mutants developed as subfertile males,and the rest of the mutants developed as fertile females with decreased ovulation.Further study revealed that foxp3a^(-/-)mutants had a delayed juvenile ovary-to-testis transition in definite males and sex reversal in about half of the definite females,which led to a dominance of later male development.Owing to the absence of foxp3a-positive Treg cells in the differentiating testis of foxp3a^(-/-)mutants,abundant T cells and macrophages expand to disrupt an immunosuppressive milieu,resulting in defective development of germ cells and gonadal somatic cells and leading to development of infertile males.Therefore,our study reveals that foxp3a-positive Treg cells play an essential role in the orchestration of gonadal development and sex differentiation in zebrafish.

Advances in microRNA and inflammatory bowel disease and their related mechanisms

Inflammatory bowel disease(IBD)is a complex and multifactorial disease characterized by chronic inflammation of the gastrointestinal tract,mainly manifested by the accumulation of immune cells and pro-inflammatory cytokines in the intestinal mucosa.It is a kind of immune digestive system disease with high incidence in humans and can be divided into ulcerative colitis(UC)and Crohn's disease(CD).The pathogenesis of IBD is complex,and numerous studies have shown that genetic,environmental,microbial,immune,autophagy and other factors may be involved in the pathogenesis of IBD.MicroRNAs(miRNAs)play an important role in the pathophysiology of IBD.Studies have confirmed that miRNA play an important role in the targeted regulation of intestinal barrier homeostasis,immune response,and intestinal epithelial autophagy.MiRNA have not only been confirmed as important diagnostic biomarkers for IBD.It also shows new prospects for treatment strategies for IBD.This article mainly describes the differences in miRNA expression between UC and CD,summarizes the relationship between miRNA and intestinal barrier,immune homeostasis and autophagy mechanism in the pathogenesis of IBD,and the research progress of miRNA involved in the diagnosis and treatment of IBD,so as to provide new insights for the development of IBD.

3efining the nature of human yo T cells： a biographical ketch of the highly empathetic

The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, 76 T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ap T cells are particularly well equipped to respond to the ＇missing self＇ and the ＇dangerous non-self＇, respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the ＇safe non-self＇ and dealing with the inevitable ＇distressed self＇, and it is within this more complex realm 76 T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human 76 T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life＇s many stresses.