The article is devoted to the study of the immunomodulating activity of rectal suppositories with an extract of licorice root and essential oils of chamomile and tea tree. Taking into account that medicine is intended...The article is devoted to the study of the immunomodulating activity of rectal suppositories with an extract of licorice root and essential oils of chamomile and tea tree. Taking into account that medicine is intended and prescribed for children, all the experiments were performed on immature nonlinear one-month rats with weight of 60.0-80.0 g. As a result, it was found out that rectal insertion of suppositories with an extract of licorice root causes an increase in the phagocytic function of neutrophils and increases the quantity of antibodies in the spleen and titers of hemagglutinins and hemolysins in serum, that indicating on the activation of nonspecific and humoral immunity of immature animals. Moreover, the prospects of possible application of suppositories with an extract of licorice root are showed for prevention and treatment of various immunodependent diseases, viral in particular.展开更多
Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepati...Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepatitis B （HB）, together with 33 healthy adults as controls. At same time the NK activity was detected when PBMCs were pretreated with recombinant IL-2 （rIL-2） in 19 patients with various types of HB and 14 normal controls. We also determined the IL-2 activity produced by PBMCs in 26 HB patients and 14 normal controls. The following results were obtained: （1） The NK activity was markedly elevated in early acute hepatitis B （AH） （P【0.01）; significantly decreased in chronic active hepatitis （CAH）, chronic persistent hepatitis （CPH） and fulminant hepatitis （FH） （P【0.01）, while that of convalescents with AH was within normal range 35.85±12.52%. （2） The early rise of NK activity in acute infection and the decline in convalescence and also the parallel change in SGPT level in 3 AH cases were observed. （3） The amount of IL-2 produced by PBMCs in HB patients was lower than that of normal controls （P【0.01 ）. （4）There was no correlation between the change of IL-2 activity and NK activity in HB patients （r=0.15; P】O.05）. （5） The NK activity of most normal subjects were enhanced when the PBMCs were pretreated with rIL-2 but the latter was still within the normal ranges. These results suggest that the mechanism of the effect of IL-2 in modulating the NK activity of HB patients is very complicated. IL-2 not only directly enhances the low NK activity of HB patients, but also depresses the high NK activity. This immunomodulating effect may be influenced by serum inhibitory facts as well as the amount and the combining ability of IL-2 receptor or on NK cell surface.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have bee...Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.展开更多
Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroot...Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.展开更多
Chinese yam(Dioscorea opposita Thunb.),as one of the medicinal and edible homologous plants,is rich in various nutrients and functional factors.In this study,Chinese yam fermented by Saccharomyces boulardii was perfor...Chinese yam(Dioscorea opposita Thunb.),as one of the medicinal and edible homologous plants,is rich in various nutrients and functional factors.In this study,Chinese yam fermented by Saccharomyces boulardii was performed to investigate its bioactive components and metabolic profile.And then,the main bioactive components and biological activities of fermented Chinese yam ethanol extract(FCYE)were evaluated.Results showed that there were 49 up-regulated metabolites and 52 down-regulated metabolites in fermented Chinese yam compared to unfermented Chinese yam.Besides,corresponding metabolic pathways analysis initially revealed that the distribution of bioactive substances was concentrated on alcoholsoluble small molecular substances.Ulteriorly,the total polyphenol content and the total flavonoid content in FCYE were significantly increased,and the corresponding antioxidant and immunomodulatory activities in vitro were also significantly enhanced.Our study provided a new reference for the comprehensive utilization of Chinese yam and laid a theoretical foundation for the development and application of natural probiotic-fermented products.展开更多
Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate...Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.展开更多
This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature An...This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.展开更多
Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammator...Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and asthma.Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH.This detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune cells.In this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.展开更多
Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D ma...Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.展开更多
The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic st...The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.展开更多
BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is ...BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.展开更多
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,whi...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.展开更多
Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and aging.However,be...Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and aging.However,because of the complex immune activities of its various components,a comprehensive understanding of Codonopsis Radix immune-regulating properties is still lacking.This knowledge gap hinders its widespread utilization in clinical practice.Therefore,this review aimed to assess the impact of Codonopsis Radix on the immune system and elucidate its underlying mechanisms.Additionally,we compared the immunomodulatory effects of different active ingredients derived from Codonopsis Radix to provide a theoretical basis for future investigations on immunomodulation.展开更多
Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essent...Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.展开更多
Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,live...Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver cancer.Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver complications.However,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver events.Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV DNA.Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.展开更多
This study was prepared due to a lack of studies on the immune modulatory effects of prodigiosin in mice against bacterial infection and the increased demand for natural resources. This study aimed to extract prodigio...This study was prepared due to a lack of studies on the immune modulatory effects of prodigiosin in mice against bacterial infection and the increased demand for natural resources. This study aimed to extract prodigiosin from Serratia rubidaea against Citrobacter freundii in mice by evaluating its immunomodulatory activity and histological alterations. A total of twenty-four Swiss mice were divided up into four groups of six mice each. C. freundii (1 × 106 cfu/ml) was administered orally to groups (2, 3 and 4) as an infectious dosage, and one milliliter was administered to the first group as a negative control. Following 24 hours from C. freundii infection, the Group 3 and Group 4 groups were given crude prodigiosin extract in the following dosage amounts: the third and fourth groups received (500 and 1000 µg/ml Intraperitoneal) respectively. ELISA test was performed to assess IgM, IL-6, and IL-10 on days 3, 7 and 14. IgM and IL-6 findings demonstrated a significant increase in Group2 and Group4 with differences (P < 0.05), however, G3 showed a significant decrease when compared to the negative control. The results of IL-10 concentration revealed that Group 2 and Group 4 had significant decreases with differences (P < 0.05), with Group 3 having the highest titer. In conclusion, the study’s findings showed that while prodigiosin’s high concentration can boost the immune system and help laboratory animals resist bacterial infection, its low concentration acts as an immune suppressant.展开更多
Various important medicines make use of secondary metabolites that are produced by plants.Medicinal plants,such as Withania somnifera and Tinospora cordifolia,are rich sources of chemically active compounds and are re...Various important medicines make use of secondary metabolites that are produced by plants.Medicinal plants,such as Withania somnifera and Tinospora cordifolia,are rich sources of chemically active compounds and are reported to have numerous therapeutic applications.The therapeutic use of medicinal plants is widely mentioned in Ayurveda and has folkloric importance in different parts of the world.The aim of this review is to summarize the phytochemical profiles,folkloric importance,and primary pharmacological activity of W.somnifera and T.cordifolia with emphasis on their action against the novel coronavirus.展开更多
This editorial aims to elucidate the intricate relationship between vitamin D and viral pathogenesis.It explores the anticipated role of vitamin D as a modulator in the immune response against severe acute respiratory...This editorial aims to elucidate the intricate relationship between vitamin D and viral pathogenesis.It explores the anticipated role of vitamin D as a modulator in the immune response against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and other viral pathogens.The editorial comments are based on the review article by Engin et al.The potential role of vitamin D in modulating immune responses has been highlighted by several studies,suggesting that it may influence both the risk and severity of infections.Vitamin D receptors are present in immunocompetent cells,which indicates that vitamin D can potentially modulate innate and adaptive immune responses.This context is relevant in the pathophysiology of coronavirus disease 2019(COVID-19),where the immune response to the virus can significantly impact the disease progression and outcome.The immunomodulatory effects of vitamin D can protect against SARSCoV-2 infection by enhancing innate and adaptive immune responses.It also maintains the integrity of the body's physical barriers and modulates inflammatory responses,thereby preventing entry and replication of the virus.Many studies have suggested that adequate vitamin D levels help alleviate morbidity and mortality associated with COVID-19.Furthermore,vitamin D supplementation has been linked with a lower risk of severe disease and mortality in COVID-19 patients,particularly in those with a deficiency during seasons with less sunlight exposure.展开更多
An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,decipherin...An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.展开更多
文摘The article is devoted to the study of the immunomodulating activity of rectal suppositories with an extract of licorice root and essential oils of chamomile and tea tree. Taking into account that medicine is intended and prescribed for children, all the experiments were performed on immature nonlinear one-month rats with weight of 60.0-80.0 g. As a result, it was found out that rectal insertion of suppositories with an extract of licorice root causes an increase in the phagocytic function of neutrophils and increases the quantity of antibodies in the spleen and titers of hemagglutinins and hemolysins in serum, that indicating on the activation of nonspecific and humoral immunity of immature animals. Moreover, the prospects of possible application of suppositories with an extract of licorice root are showed for prevention and treatment of various immunodependent diseases, viral in particular.
文摘Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepatitis B （HB）, together with 33 healthy adults as controls. At same time the NK activity was detected when PBMCs were pretreated with recombinant IL-2 （rIL-2） in 19 patients with various types of HB and 14 normal controls. We also determined the IL-2 activity produced by PBMCs in 26 HB patients and 14 normal controls. The following results were obtained: （1） The NK activity was markedly elevated in early acute hepatitis B （AH） （P【0.01）; significantly decreased in chronic active hepatitis （CAH）, chronic persistent hepatitis （CPH） and fulminant hepatitis （FH） （P【0.01）, while that of convalescents with AH was within normal range 35.85±12.52%. （2） The early rise of NK activity in acute infection and the decline in convalescence and also the parallel change in SGPT level in 3 AH cases were observed. （3） The amount of IL-2 produced by PBMCs in HB patients was lower than that of normal controls （P【0.01 ）. （4）There was no correlation between the change of IL-2 activity and NK activity in HB patients （r=0.15; P】O.05）. （5） The NK activity of most normal subjects were enhanced when the PBMCs were pretreated with rIL-2 but the latter was still within the normal ranges. These results suggest that the mechanism of the effect of IL-2 in modulating the NK activity of HB patients is very complicated. IL-2 not only directly enhances the low NK activity of HB patients, but also depresses the high NK activity. This immunomodulating effect may be influenced by serum inhibitory facts as well as the amount and the combining ability of IL-2 receptor or on NK cell surface.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
文摘Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.
基金supported by the National Natural Science Foundation of China(82202352,82271629)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNLH202202)+1 种基金the China Postdoctoral Science Foundation Funded Project(2023M732711)the Wenzhou Medical University grant(QTJ23004)。
文摘Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.
基金supported by National Natural Science Foundation of China(32172211)the Natural Science Foundation of Henan Province for Outstanding Youth,China(202300410365)+2 种基金the National Key Research and Development Program of China(2022YFF1103300)the Program for Science and Technology Innovation Talents in Universities of Henan Province(22HASTIT037)the Technology Development(Cooperation)project of Zhengzhou University(20210442A,20210327A).
文摘Chinese yam(Dioscorea opposita Thunb.),as one of the medicinal and edible homologous plants,is rich in various nutrients and functional factors.In this study,Chinese yam fermented by Saccharomyces boulardii was performed to investigate its bioactive components and metabolic profile.And then,the main bioactive components and biological activities of fermented Chinese yam ethanol extract(FCYE)were evaluated.Results showed that there were 49 up-regulated metabolites and 52 down-regulated metabolites in fermented Chinese yam compared to unfermented Chinese yam.Besides,corresponding metabolic pathways analysis initially revealed that the distribution of bioactive substances was concentrated on alcoholsoluble small molecular substances.Ulteriorly,the total polyphenol content and the total flavonoid content in FCYE were significantly increased,and the corresponding antioxidant and immunomodulatory activities in vitro were also significantly enhanced.Our study provided a new reference for the comprehensive utilization of Chinese yam and laid a theoretical foundation for the development and application of natural probiotic-fermented products.
基金This work was supported by grants from the National Natural Science Foundation of China(52072005 and 51872279).
文摘Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.
文摘This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.
基金supported by the National Nature Science Foundation of China(No.81873694)the Key Research and Development Program of Hubei Province(No.2022BCA005)Knowledge Innovation Program of Wuhan Basic Research(No.2022020801010446).
文摘Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and asthma.Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH.This detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune cells.In this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.
文摘Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.
文摘The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.
基金Supported by National Natural Science Foundation of China,No.81470982.
文摘BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.
基金Supported by Science and Technology Department Project of Jilin Province,China,No.20230101163JCthe Outstanding Youth Fund Project of Jilin Provincial Department of Education,China,No.JJKH20241324KJ.
文摘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.
基金funded by Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine(24HHZYSS00002)the National Key Research and Development Program of China(2022YFC3501800)the National Natural Science Foundation of China(82204878).
文摘Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and aging.However,because of the complex immune activities of its various components,a comprehensive understanding of Codonopsis Radix immune-regulating properties is still lacking.This knowledge gap hinders its widespread utilization in clinical practice.Therefore,this review aimed to assess the impact of Codonopsis Radix on the immune system and elucidate its underlying mechanisms.Additionally,we compared the immunomodulatory effects of different active ingredients derived from Codonopsis Radix to provide a theoretical basis for future investigations on immunomodulation.
文摘Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.
文摘Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United States.It is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver cancer.Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver complications.However,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver events.Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV DNA.Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.
文摘This study was prepared due to a lack of studies on the immune modulatory effects of prodigiosin in mice against bacterial infection and the increased demand for natural resources. This study aimed to extract prodigiosin from Serratia rubidaea against Citrobacter freundii in mice by evaluating its immunomodulatory activity and histological alterations. A total of twenty-four Swiss mice were divided up into four groups of six mice each. C. freundii (1 × 106 cfu/ml) was administered orally to groups (2, 3 and 4) as an infectious dosage, and one milliliter was administered to the first group as a negative control. Following 24 hours from C. freundii infection, the Group 3 and Group 4 groups were given crude prodigiosin extract in the following dosage amounts: the third and fourth groups received (500 and 1000 µg/ml Intraperitoneal) respectively. ELISA test was performed to assess IgM, IL-6, and IL-10 on days 3, 7 and 14. IgM and IL-6 findings demonstrated a significant increase in Group2 and Group4 with differences (P < 0.05), however, G3 showed a significant decrease when compared to the negative control. The results of IL-10 concentration revealed that Group 2 and Group 4 had significant decreases with differences (P < 0.05), with Group 3 having the highest titer. In conclusion, the study’s findings showed that while prodigiosin’s high concentration can boost the immune system and help laboratory animals resist bacterial infection, its low concentration acts as an immune suppressant.
文摘Various important medicines make use of secondary metabolites that are produced by plants.Medicinal plants,such as Withania somnifera and Tinospora cordifolia,are rich sources of chemically active compounds and are reported to have numerous therapeutic applications.The therapeutic use of medicinal plants is widely mentioned in Ayurveda and has folkloric importance in different parts of the world.The aim of this review is to summarize the phytochemical profiles,folkloric importance,and primary pharmacological activity of W.somnifera and T.cordifolia with emphasis on their action against the novel coronavirus.
文摘This editorial aims to elucidate the intricate relationship between vitamin D and viral pathogenesis.It explores the anticipated role of vitamin D as a modulator in the immune response against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and other viral pathogens.The editorial comments are based on the review article by Engin et al.The potential role of vitamin D in modulating immune responses has been highlighted by several studies,suggesting that it may influence both the risk and severity of infections.Vitamin D receptors are present in immunocompetent cells,which indicates that vitamin D can potentially modulate innate and adaptive immune responses.This context is relevant in the pathophysiology of coronavirus disease 2019(COVID-19),where the immune response to the virus can significantly impact the disease progression and outcome.The immunomodulatory effects of vitamin D can protect against SARSCoV-2 infection by enhancing innate and adaptive immune responses.It also maintains the integrity of the body's physical barriers and modulates inflammatory responses,thereby preventing entry and replication of the virus.Many studies have suggested that adequate vitamin D levels help alleviate morbidity and mortality associated with COVID-19.Furthermore,vitamin D supplementation has been linked with a lower risk of severe disease and mortality in COVID-19 patients,particularly in those with a deficiency during seasons with less sunlight exposure.
基金Supported by the European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.
