The role of innate immunity in diabetic nephropathy and their therapeutic consequences

Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.

m^(1)A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling

N^(1)-methyladenosine(m^(1)A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m^(1)A modification levels.Analysis of m^(1)A-associated genes identified TRMT61A as a key m^(1)A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m^(1)A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m^(1)A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m^(1)A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m^(1)A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.

Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1

Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Impact of exercise on markers of B cell-related immunity:A systematic review

Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

Hydroxytyrosol and Parkinson's disease:protective actions against alpha-synuclein toxicity

Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of 65years.According to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 years.In 2019,global estimates indicated over 8.5 million individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).

Ambroxol,the cough expectorant with neuroprotective effects

Ambroxol hydrochloride(2-amino-3,5-dibromo-N-methylbenzylamine hydrochloride)has been used as a mucolytic agent in the treatment of respiratory diseases since the late 1970s.Its effects on mucus membranes such as mucus disruption,increased mucus production,and low toxicity profile were addressed in its original German patent in 1966.These first described properties have kept Ambroxol available worldwide and over the counter in the pharmaceutical market to this day.

Corrigendum to“Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong”[J.Pharm.Anal.14(2024)225e243]

Original statement in the caption of Fig.5:Fig.5.JinMaiTong(JMT)treatment restored the perturbed central carbohydrate metabolism in the circulation and sciatic nerve of diabetic peripheral neuropathy(DPN)rats.Dash line arrows indicate the direct metabolic reactions,and solid line arrows indicate the indirect reactions.*P<0.05 and**P<0.01.ns:no significant difference.CON:control;TCA:tricarboxylic acid cycle;ADP:adenosine diphosphate:ATP:adenosine triphosphate;GDP:guanosine diphosphate;GTP:guanosine triphosphate.

Experimental and numerical study on protective effect of RC blast wall against air shock wave

Prototype experiments were carried out on the explosion-proof performance of the RC blast wall.The mass of TNT detonated in the experiments is 5 kg and 20 kg respectively.The shock wave overpressure was tested in different regions.The above experiments were numerically simulated,and the simulated shock wave overpressure waveforms were compared with that tested and given by CONWEP program.The results show that the numerically simulated waveform is slightly different from the test waveform,but similar to CONWEP waveform.Through dimensional analysis and numerical simulation under different working conditions,the equation for the attenuation rate of the diffraction overpressure behind the blast wall was obtained.According to the corresponding standards,the degree of casualties and the damage degree of the brick concrete building at a certain distance behind the wall can be determined when parameters are set.The above results can provide a reference for the design and construction of the reinforced concrete blast wall.

The life-history trait trade-offs mediated by reproduction and immunity in the brown planthopper,Nilaparvata lugens Stål

Reproduction and immune defense are costly functions,and they are expected to tradeoff with each other to drive evolution.The brown planthopper(BPH),Nilaparvata lugens Stål(Hemiptera,Delphacidae),is a global superpest that mostly damages rice crops.Yeast-like symbionts(YLS)exist in the abdominal fat body tissue and are tightly associated with the development,growth,and reproduction of BPH.Our previous research demonstrated that mating behavior promotes the release of YLS from the fat body into the hemolymph in the BPH,thereby triggering an immune response.Additionally,the fitness costs related to life-history traits of BPH(such as survival rate)have a strong dependence on the relative abundance of YLS.However,the possible relationship between reproduction and the immune response in BPH has not been identified.In this study,an omics-based approach was used to analyze the transcriptome of fat body tissues in mated and unmated BPH at 72 h post-eclosion,from which two antimicrobial peptide genes,NlDefensin A(NlDfA)and NlDefensin B(NlDfB),were selected since they were highly expressed in mated BPH.Subsequently,the full-length cDNA sequences of the NlDfA and NlDfB genes were cloned and analyzed.qPCR results showed up-regulation of the NlDfA and NlDfB genes in mated BPH when compared to unmated BPH.Spatial-temporal expression analysis indicated that the NlDfA and NlDfB genes were expressed in all tissues and developmental stages,and they were most highly expressed in the fat body at 24 h post-eclosion.Moreover,the symbionts in BPH were significantly inhibited by the in vitro expression of the NlDfA and NlDfB proteins.Furthermore,RNA interference(RNAi)-mediated suppression of NlDfA and NlDfB dramatically increased the relative abundance of YLS in the fat body,while YLS in the hemolymph decreased significantly.These BPHs also displayed some fitness disadvantages in survival,fecundity,hatchability,and possibly the vertical transmission of YLS from hemolymph to egg.Our results indicated that mating could heighten the immunity of BPH by upregulating the expression of the NlDfA and NlDfB genes,which protect the host from pathogen challenges during reproduction.However,the reduced content of YLS may act as a fitness disadvantage in dictating the life-history traits of BPH.This work has significant theoretical and practical implications for the precise green control technology that involves crucial gene targeting,as well as for the“endosymbionts for pest control”strategy in insects.

Anode surface engineering of zinc-ion batteries using tellurium nanobelt as a protective layer for enhancing energy storage performance

Over the years,zinc-ion batteries(ZIBs)have attracted attention as a promising next-generation energy storage technology because of their excellent safety,long cycling performance,eco-friendliness,and high-power density.However,issues,such as the corrosion and dissolution of the Zn anode,limited wet-tability,and lack of sufficient nucleation sites for Zn plating,have limited their practical application.The introduction of a protective layer comprising of tellurium(Te)nanobelts onto the surface of Zn anode has emerged as a promising approach to overcome these limitations and improve the electrochemical behav-ior by enhancing the safety and wettability of ZIBs,as well as providing numerous nucleation sites for Zn plating.In the presence of a Te-based protective layer,the energy power density of the surface-engineered Zn anode improved significantly(ranging from 310 to 144 W h kg^(-1),over a power density range of 270 to 1,800 W kg^(-1)),and the lifespan capability was extended.These results demonstrate that the proposed strategy of employing Te nanobelts as a protective layer holds great promise for enhancing the energy storage performance of zIBs,making them even more attractive as a viable energy storage solution forthefuture.

Protective effects of baffles with different positions,row spacings,heights on debris flow impact

The baffle effectively slowed down debris flow velocity,reduced its kinetic energy,and significantly shortened the distance of debris flow movement.Consequently,they are widely used for protection against natural hazards such as landslides and mudslides.This study,based on the threedimensional DEM(Discrete Element Method),investigated the impact of different baffle positions on debris flow protection.Debris flow velocity and kinetic energy variations were studied through single-factor experiments.Suitable baffle positions were preliminarily selected by analyzing the influence of the first-row baffle position on the impact force and accumulation mass of debris flow.Subsequently,based on the selected baffle positions and four factors influencing the effectiveness of baffle protection(baffle position(P),baffle height(h),row spacing(S_(r)),and angle of transit area(α)),an orthogonal design was employed to further explore the optimal arrangement of baffles.The research results indicate that the use of a baffle structure could effectively slow down the motion velocity of debris flows and dissipate their energy.When the baffle is placed in the transit area,the impact force on the first-row baffle is greater than that when the baffle is placed in the deposition area.Similarly,when the baffle is placed in the transit area,the obstruction effect on debris flow mass is also greater than that when the baffle is placed in the deposition area.Through orthogonal experimental range analysis,when the impact on the first row of baffles is used as the evaluation criterion,the importance of each influencing factor is ranked asα>P>S_(r)>h.When the mass of debris flow behind the baffle is regarded as the evaluation criterion,the rank is changed to P>α>S_(r)>h.The experimental simulation results show that the optimal baffle arrangement is:P_(5),S_(r)=16,α=35°,h=9.

Topological optimization of ballistic protective structures through genetic algorithms in a vulnerability-driven environment

Reducing the vulnerability of a platform,i.e.,the risk of being affected by hostile objects,is of paramount importance in the design process of vehicles,especially aircraft.A simple and effective way to decrease vulnerability is to introduce protective structures to intercept and possibly stop threats.However,this type of solution can lead to a significant increase in weight,affecting the performance of the aircraft.For this reason,it is crucial to study possible solutions that allow reducing the vulnerability of the aircraft while containing the increase in structural weight.One possible strategy is to optimize the topology of protective solutions to find the optimal balance between vulnerability and the weight of the added structures.Among the many optimization techniques available in the literature for this purpose,multiobjective genetic algorithms stand out as promising tools.In this context,this work proposes the use of a in-house software for vulnerability calculation to guide the process of topology optimization through multi-objective genetic algorithms,aiming to simultaneously minimize the weight of protective structures and vulnerability.In addition to the use of the in-house software,which itself represents a novelty in the field of topology optimization of structures,the method incorporates a custom mutation function within the genetic algorithm,specifically developed using a graph-based approach to ensure the continuity of the generated structures.The tool developed for this work is capable of generating protections with optimized layouts considering two different types of impacting objects,namely bullets and fragments from detonating objects.The software outputs a set of non-dominated solutions describing different topologies that the user can choose from.

Pharmacological Investigation on the Qi-Invigorating Action of Schisandrin B: Effects on Mitochondrial ATP Generation in Multiple Tissues and Innate/Adaptive Immunity in Mice

Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi.

Study of the Ballistic Impact Behavior of Protective Multi-Layer Composite Armor

The abalone shell,a composite material whose cross-section is composed of inorganic and organic layers,has high strength and toughness.Inspired by the abalone shell,several multi-layer composite plates with different layer sequences and thicknesses are studied as bullet-proof material in this paper.To investigate the ballistic performance of this multi-layer structure,the complete characterization model and related material parameters of large deformation,failure and fracture ofAl_(2)O_(3)ceramics andCarbon Fiber Reinforced Polymer(CFRP)are studied.Then,3D finite element models of the proposed composite plates with different layer sequences and thicknesses impacted by a 12.7 mm armor-piercing incendiary(API)are built using Abaqus to predict failure.The simulation results show that the CFRP/Al2O3 ceramic/Ultrahigh Molecular Weight Polyethylene(UHMWPE)/CFRP(1 mm/4 mm/4 mm/1 mm)composite is the optimized stack of layers.The simulation results under specified layer sequence and thickness have a reasonable correlation with the experimental results and reflect the failure and fracture of the multi-layer composite protective armor.

Effects of antioxidant‑rich Lactiplantibacillus plantarum inoculated alfalfa silage on rumen fermentation, antioxidant and immunity status, and mammary gland gene expression in dairy goats

Background Milk synthesis in lactating animals demands high energy metabolism,which results in an increased production of reactive oxygen metabolites(ROM)causing an imbalance between oxidants and antioxidants thereby inducing oxidative stress(OS)on the animals.To mitigate OS and postpartum disorders in dairy goats and gain insight into the impact of dietary choices on redox status during lactation,a feeding trial was conducted using alfalfa silage inoculated with a high-antioxidant strain of Lactiplantibacillus plantarum.Methods Twenty-four Guanzhong dairy goats(38.1±1.20 kg)were randomly assigned to two dietary treatments:one containing silage inoculated with L.plantarum MTD/1(RSMTD-1),and the other containing silage inoculated with high antioxidant activity L.plantarum 24-7(ES24-7).Results ES24-7-inoculated silage exhibited better fermentation quality and antioxidant activity compared to RSMTD-1.The ES24-7 diet elevated the total antioxidant capacity(T-AOC),superoxide dismutase(SOD),glutathione peroxi-dase(GSH-Px),and catalase(CAT)activities in milk,serum,and feces of lactating goats(with the exception of T-AOC in milk).Additionally,the diet containing ES24-7 inoculated silage enhanced casein yield,milk free fatty acid(FFA)content,and vitamin A level in the goats’milk.Furthermore,an increase of immunoglobulin(Ig)A,IgG,IgM,inter-leukin(IL)-4,and IL-10 concentrations were observed,coupled with a reduction in IL-1β,IL-2,IL-6,interferon(IFN)-γ,and tumor necrosis factor(TNF)-αconcentrations in the serum of lactating goats fed ES24-7.Higher concentrations of total volatile fatty acid(VFA),acetate,and propionate were observed in the rumen fluid of dairy goats fed ES24-7 inoculated silage.Moreover,the diet containing ES24-7 inoculated silage significantly upregulated the expression of nuclear factor erythroid 2 like 2(NFE2L2),beta-carotene oxygenase 1(BCO1),SOD1,SOD2,SOD3,GPX2,CAT,glu-tathione-disulfide reductase(GSR),and heme oxygenase 1(HMOX1)genes in the mammary gland,while decreased the levels of NADPH oxidase 4(NOX4),TNF,and interferon gamma(IFNG).Conclusions These findings indicated that feeding L.plantarum 24-7 inoculated alfalfa silage not only improved rumen fermentation and milk quality in lactating dairy goats but also boosted their immunity and antioxidant status by modulating the expression of several genes related to antioxidant and inflammation in the mammary gland.

Does Herd Immunity Reduce the Risk of Contracting COVID-19?

Herd immunity is often considered a measure to protect a whole community or population from disease if the vaccination threshold is met. Using the demographic and COVID-19 infection data from the state of Pennsylvania, United States, the study aimed to determine if herd immunity by vaccination is an effective way to reduce the spread of the COVID-19 virus. The Pennsylvania counties were split into two groups based on qualification of herd immunity: counties that met the COVID-19 herd immunization rate of 70% and counties that did not. The ANOVA test was used to analyze the difference between the groups with and without herd immunity by the COVID-19 vaccine. The results demonstrated that there was no significant statistical difference between counties that did achieve and those that did not achieve the herd immunity threshold for the COVID-19 vaccine. On the other hand, it was observed that there had been a significant decrease in positive cases between 2020 and 2023. This decline can be attributed to the overall protection by the vaccination and adaptability to the disease, not specifically due to herd immunity alone. Ultimately, these outcomes suggest that herd immunity cannot reduce the risk of contracting COVID-19. Increased efforts to get vaccinated should be implemented to protect the general community and a wider scope of age.

A novel chorismate mutase effector secreted from root-knot nematode Meloidogyne enterolobii manipulates plant immunity to promote parasitism

Meloidogyne spp.is an economically important plant-parasitic nematode distributed worldwide.To fight with host immune system for successful parasitism,plant parasitic nematodes secrete effectors to promote infection.In this study,we identified one chorismate mutase(CM)effector from M.enterolobii,named Me-CM.Spatial and temporal expression assays exhibited Me-cm is expressed in esophageal glands and up-regulated at parasitic-stage juveniles.Me-CM affects the pathogenicity of M.enterolobii based on the reduced infection rate,number of galls,egg masses,eggs per mass and multiplication rate collected from RNA silencing experiments.We showed that Me-CM localized in the cytoplasm and nucleus of plant cells and decreased the expression level of the marker gene PR1 of salicylic acid(SA)pathway.Besides,constitutive expression of Me-cm in Arabidopsis thaliana significantly reduced salicylic acid concentration.These results suggested that M.enterolobii may secrete effector Me-CM to fight with plantimmunesystemsvia regulating SA signaling pathway when interacting with host plants,ultimately facilitating parasitism.

Protective mechanism of quercetin compounds against acrylamide-induced hepatotoxicity

Quercetin compounds have antioxidant,anti-inflammatory and anticancer pharmacological functions.Longterm exposure to acrylamide(AA)can cause liver injury and endanger human health.However,whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear.Here,we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro.In vivo studies found that quercetin-like compounds protect against AAinduced liver injury by reducing oxidative stress levels,activating the Akt/m TOR signaling pathway to attenuate autophagy,and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis.In vitro studies found that quercetin compounds protected Hep G2 cells from AA by attenuating the activation of AA-induced autophagy,lowering reactive oxygen species(ROS)levels by exerting antioxidant effects and thus attenuating oxidative stress,increasing mitochondrial membrane potential(MMP),and improving apoptosis-related proteins,thus attenuating AA-induced apoptosis.Furthermore,the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity,with quercetin showing the best protective capacity due to its strongest antioxidant activity.In conclusion,quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress,autophagy and apoptosis,and their protective capacity correlates with antioxidant activity.

Harnessing immunity:Immunomodulatory therapies in COVID-19

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.

Targeting the chromatin structural changes of antitumor immunity

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.