Mesenchymal stem cell-derived exosomes regulate microglia phenotypes:a promising treatment for acute central nervous system injury

There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.

Single-cell transcriptome profiling of sepsis identifies HLA-DR^(low)S100A^(high)monocytes with immunosuppressive function

Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.

A bibliometric analysis of exertional heat stroke research in Web of Science

Background:Exertional heat stroke is a fatal condition and remains a health problem.This paper evaluates the publication trend regarding exertional heat stroke research between 1996 and 2015 using a bibliometric method.Methods:Articles regarding exertional heat stroke research published between 1996 and December 2015 were searched for in the SCI-EXPANDED database of Web of Science.The search results were analyzed with regard to publication year;publication quantity regarding countries/regions;authors;citation frequency;and journal distribution.Cite Space(v3.6) was used for a document co-citation visualization analysis.Results:In total,289 publications on heat stroke were located.After selection,209 original articles conducted across 28 countries/regions and published in 83 journals were included in the analysis.The USA,Isreal,and France were the most common locations for exertional heat stroke studies.The Cite Space visualization cluster analysis showed that exertional heat stroke-related mortality and protective measures were constant concerns of research.Conclusion:Research related to exertional heat stroke has been continuous concerned.USA is still the leading country in this field.

Establishment and effectiveness evaluation of a scoring system for exertional heat stroke by retrospective analysis

Background: Heat stroke(HS) is a serious, life-threatening disease. However, there is no scoring system for HS so far. This research is to establish a scoring system that can quantitatively assess the severity of exertional heat stroke(EHS).Methods: Data were collected from a total of 170 exertional heat stroke(EHS) patients between 2005 and 2016 from 52 hospitals in China. Univariate statistical methods and comparison of the area under the receiver operating characteristic(ROC) curve(AUC) were used to screen exertional heat stroke score(EHSS) parameters, including but not limited body temperature(T), Glasgow Coma Scale(GCS) and others. By comparing the sizes of the AUCs of the APACHE II, SOFA and EHSS assessments, the effectiveness of EHSS in evaluating the prognosis of EHS patients was verified.Results: Through screening with a series of methods, as described above, the present study determined 12 parameters – body temperature(T), GCS, p H, lactate(Lac), platelet count(PLT), prothrombin time(PT), fibrinogen(Fib), troponin I(Tn I), aspartate aminotransferase(AST), total bilirubin(TBIL), creatinine(Cr) and acute gastrointestinal injury(AGI) classification – as EHSS parameters. It is a 0–47 point system designed to reflect increasing severity of heat stroke. Low(EHSS<20) and high scores(EHSS>35) showed 100% survival and 100% mortality, respectively. We found that AUCEHSS>AUCSOFA>AUCAPACHE II.Conclusions: A total of 12 parameters – T, GCS, p H, Lac, PLT, PT, Fib, Tn I, AST, TBIL, Cr and gastrointestinal AGI classification – are the EHSS parameters with the best effectiveness in evaluating the prognosis of EHS patients. As EHSS score increases, the mortality rate of EHS patients gradually increases.

The procalcitonin-to-cortisol ratio is a potential prognostic predictor in sepsis with abdominal source:a retrospective observational study

BACKGROUND:The aim of the study was to investigate the procalcitonin-to-cortisol ratio(P/C ratio)as a prognostic predictor among septic patients with abdominal source.METHODS:We retrospectively enrolled 132 post-surgery patients between 18 and 90 years old with sepsis of the abdominal source.On the second day of sepsis onset,cortisol,procalcitonin(PCT),Acute Physiology and Chronic Health Evaluation(APACHE)II score,Sequential Organ Failure Assessment(SOFA)score,C-response protein(CRP),and other baseline characteristics were collected.In addition,the length of ICU stay,length of mechanical ventilation(MV)days,length of shock days,and 28-day mortality were also recorded.Univariate analysis was performed to screen potential risk factors.Stratified analysis was used to identify the interaction among the risk factors.Multivariate analysis was also utilized to demonstrate the relationship between the risk factors and mortality.The receiver operator characteristic(ROC)curve analysis was conducted to evaluate the risk factors.A restricted cubic spline(RCS)demonstrated the association between survival outcome and the P/C ratio variation.RESULTS:A total of twenty-nine patients died,and 103 patients survived within 28 d.There were significant differences in cortisol,PCT,P/C ratio,interleukin(IL)-6,SOFA,and APACHE II scores between the survival and non-survival groups.No significant interaction was observed in the stratified analysis.Logistic regression analysis revealed that P/C ratio(P=0.033)was significantly related to 28-day mortality.Based on ROC curves,P/C ratio(AUC=0.919)had a higher AUC value than cortisol or PCT.RCS analysis depicted a positive relationship between survival possibility and P/C ratio decrement.CONCLUSION:P/C ratio might be a potential prognostic predictor in septic patients with abdominal sources.