Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19

Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

Histone methylation in pancreatic cancer and its clinical implications

Pancreatic cancer(PC)is an aggressive human cancer.Appropriate methods for the diagnosis and treatment of PC have not been found at the genetic level,thus making epigenetics a promising research path in studies of PC.Histone methylation is one of the most complicated types of epigenetic modifications and has proved crucial in the development of PC.Histone methylation is a reversible process regulated by readers,writers,and erasers.Some writers and erasers can be recognized as potential biomarkers and candidate therapeutic targets in PC because of their unusual expression in PC cells compared with normal pancreatic cells.Based on the impact that writers have on the development of PC,some inhibitors of writers have been developed.However,few inhibitors of erasers have been developed and put to clinical use.Meanwhile,there is not enough research on the reader domains.Therefore,the study of erasers and readers is still a promising area.This review focuses on the regulatory mechanism of histone methylation,and the diagnosis and chemotherapy of PC based on it.The future of epigenetic modification in PC research is also discussed.

Multi-Omics Analysis Provides Insight into the Possible Molecular Mechanism of Hay Fever Based on Gut Microbiota

Due to the worldwide epidemic of allergic disease and a cure nowhere in sight,there is a crucial need to explore its pathophysiological mechanisms.As allergic disease has been associated with gut dysbiosis,we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis.Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen.This hyper reaction decreased the circulation of valine,isoleucine,aspartate,glutamate,glutamine,indole-propionate(IPA),and myo-inositol,and reduced short-chain fatty acids(SCFAs)in feces.Several beneficial genera belonging to Ruminococcaceae,Lachnospiraceae,and Clostridiales declined in the model group,whereas Helicobacter and Akkermansia were only expressed in the model group.Furthermore,the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria.Our results suggest that alterations in amino acids as well as their derivatives(especially valine,and IPA which is the reductive product of tryptophan),SCFAs,and the gut microbiome(specifically Akkermansia and Helicobacter)may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer,which further results in hay fever.

Overview of effect of traditional Chinese medicine on diabetic kidney disease by regulating podocyte

Diabetic kidney disease has now become the leading cause of end-stage renal disease.Podocytes are an important filtration barrier of the glomerulus,and their damage plays an important role in the occurrence and progression of glomerular sclerosis and DKD.This article discusses the molecular mechanism of traditional Chinese medicine on the protection of podocyte damage in diabetic kidney disease from the aspects of anti-oxidative stress,activating autophagy,and regulating signal pathways,in order to further deepen the modern material basis theory of traditional Chinese medicine treatment and provide reference for the treatment of DKD.

Genome-wide analysis of OCT4 binding sites in glioblastoma cancer cells

OCT4, a member of the POU family of gene products, is an octamer motif-binding transcription factor. As it is known to play a crucial role in cancer processes including proliferation, invasion, and chemoradioresistance, it is important to identify the direct targets of OCT4 in living cancer cells. Here, chromatin immunoprecipitation-sequencing （ChlP-seq） was used to identify OCT4 binding sites in glioblastoma cancer cells. The results showed that 5438 OCT4 binding sites were localized in the glioblastoma cancer genome and that these sites contained a consensus sequence TTTkswTw （k=T or G, s=C or G, w=A or T）, which occurred 3931 times in 2312 OCT4 binding regions. Furthermore, binding motifs of some other transcription factors were identified in OCT4 binding regions. Our results provide a valuable dataset for understanding gene regulation mechanisms underlying the function of OCT4 in glioblastoma cancer.

Early transcriptomic profiling variation caused by cluster allergen immunotherapy

Allergen immunotherapy is executed by the repeated administration of specific allergens to patients with allergic disorders to protect against allergic reactions.It is the only disease-modifying therapy for allergic rhinitis and asthma,and many clinical trials and meta-analyses have demonstrated its beneficial effects.[1]Immunologic changes associated with immunotherapy are complicated,and the underlying mechanism needs further elucidation.Cluster immunotherapy is an improved immunotherapy with an accelerated build-up schedule that achieves symprom improvement earlier than the conventional way.

Occupational Asthma Caused by Inhalable Royal Jelly ancl Its Cross-reactivity with Honeybee Venom

Royal jelly is a honeybee nutriment secreted from the glands in the hypopharynx of worker bees essential in the development of queen bees. Ingestion of royal jelly has been reporied to trigger rhinitis, asthma, and anaphylaxis, but occupational asthrna occurring after inhalation of volatile royal jelly is rare.

Gene Expression Pattern of Histone Acetylation Enzymes Changed in the Hypothalamus of Middle-Aged Female Rats:A Putative Mechanism for Female Reproductive Aging

Objective:Female reproductive aging is characterized by reduced responsiveness of the hypothalamus to E2-positive feedback,which can result in alterations of gene expression and luteinizing hormone(LH)surge dysfunction.We hypothesize that age-related changes in E2-responsive gene expression are due to altered histone acetylation by histone deacetylases(HDACs)or estrogen receptor-alpha(ERα)coactivators with histone acetyltransferase(HAT)activity.Methods:In the present study,young and middle-aged female rats were ovariectomized(OVX)and treated with E2 or oil once per day for 2 days.At the time of the expected LH surge,the anterior and posterior hypothalami were dissected,and gene expression of 11 HDACs and 4 ERαcoactivators with HAT activity was measured using real-time polymerase chain reaction.Results:In the anterior hypothalamus,age affected the gene expression of 3 HDACs(Hdac3,Hdac5,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp).E2 treatment significantly decreased mRNA levels of 4 HDACs(Hdac4,Hdac5,Hdac10,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp)in young females(3-4 months).However,none of the genes responded to E2 in the middle-aged females(9-11 months),except Hdac10.In the posterior hypothalamus,age influenced Hdac5 and Src1 mRNA expression.E2 treatment increased Hdac4 and Crebbp mRNA levels in the young but not middle-aged females.Conclusions:These data suggest that E2 regulates HDACs and ERαcoactivators with HAT activity in an age-and E2-dependent manner,which may contribute to the age-related gene expression changes on the day of LH surge in female reproductive aging.