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.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

PIKA Provides an Adjuvant Effect to Induce Strong Mucosal and Systemic Humoral Immunity Against SARS-CoV

Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly （I：C）, was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly （I：C） derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.

A Novel Chitosan CpG Nanoparticle Regulates Cellular and Humoral Immunity of Mice

Objective To develop a safe and novel immunoadjuvant to enhance the immunity and resistance of animals against E. coli infection. Methods An 88-base immunostimulatory oligodeoxynuleotide containing eleven CpG motifs （CpG ODN） was synthesized and amplified by PCR. The chitosan nanoparticle （CNP） was prepared by ion linking method to entrap the CpG ODN that significantly promotes the proliferation of lymphocytes of pig in vitro. Then the CpG- CNP was inoculated into 21-day old Kunming mice, which were orally challenged with virulent K88/K99 E. Coil 35 days after inoculation. Blood was collected from the tail vein of mice on days 0, 7, 14, 21, 28, 35, 42, and 49 after inoculation to detect the changes and content of immunoglobulins, cytokines and immune cells by ELISA, such as IgG, IgA, IgM, IL-2, IL-4, and IL-6. Results The CpG provoked remarkable proliferation of lymphocytes of pig in vitro in comparison with that of control group （P〈0.05）. The inoculation with CpG-CNP significantly raised the content of IgG, IgM, and IgA in the sera of immunized mice （P〈0.05）. The levels of IL-2, 1L-4, and IL-6 in the mice significantly increased in comparison with those in controls （P〈0.05）, so was the number of white blood cells and lymphocytes in immunized mice. The humoral and cellular immunities were significantly enhanced in immunized mice, which resisted the infection of E coli and survived, while the control mice manifested evident symptoms and lesions of infection. Conclusions CpG-CNP can significantly promote cellular and humoral immunity and resistance of mice against E. coli infection, and can be utilized as an effective adjuvant to improve the immunoprotection and resistance of porcine against infectious disease.

Effects of dissolved oxygen on intestinal bacterial community and immunity of Atlantic salmon Salmo salar

Dissolved oxygen(DO)is one of most important factors which affect wide range physiologic features of including immune responses and intestinal bacterial community.However,the underlying mechanisms remain enigmatic.To address this question,the intestinal bacterial community compositions and the immune features of Atlantic salmon(Salmo salar)grown in recirculating aquaculture systems(RAS)were characterized.Fish were reared under different DO saturation levels,e.g.,200% saturation named high group(H),100%saturation named control group(CK),and 60%saturation named lower group(L).Large variations in the operational taxonomic units(OTUs)frequency distribution for the intestinal bacterial community of Atlantic salmon were observed.The intestinal bacterial community of all groups was dominated mainly by three phyla,e.g.,Proteobacteria.Firmicutes,and Bacteroidetes.Interestingly,Acinetobacter baumannii,an opportunistic pathogen of salmon was increased significantly in L group.We further monitored the immunity features of fish under different DO levels.The results show that leucocyte number,cortisol level,the expressions of interleukin-1β(IL-1β),Toll-like receptor 4(TLR4),and nucleotide-binding oligomerization domain like protein 2(NOD2)were higher at significant levels in the L group than those in the other two groups.TLR4 and NOD2 are usually related with the bacterial infections;therefore,it is reasonable to believe that the stronger immune responses observed in the L group might be related with the higher abundance of A.baumannii in the inte stine of Atlantic salmon.Overall,these findings demonstrated that low DO level may induce stronger immunity responses in Atlantic salmon.

Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis

AIM:To investigate the potential interactions of thymic stromal lymphopoietin(TSLP)with interleukin-4(IL-4)in adaptive immunity during fungal keratitis(FK).METHODS:An FK mouse model was induced with Aspergillus fumigatus(AF)hyphal infection.Mice were divided into several groups:untreated,phosphate buffer saline(PBS),infected with AF,and pretreated with a scrambled siRNA,a TSLP-specific siRNA(TSLP siRNA),murine recombinant TSLP(rTSLP),immunoglobulin G(IgG),murine recombinant IFN(rIFN-γ),murine recombinant IL-4(rI L-4),rIL-13,murine recombinant IL-17A(rIL-17A),and murine recombinant IL-17F(rIL-17F)groups.Quantitative realtime reverse transcription-polymerase chain reaction(qRTPCR)and enzyme-linked immunosorbent assay(ELISA)or Western blot were performed to determine mRNA and protein levels in the inflamed cornea.Cytokine locations were observed by immunofluoresence staining after AF hyphal infection.RESULTS:Compared to those in the untreated group,TSLP and T helper type 1(Th1)cytokine levels in the AF group were upregulated at 24 h post infection(hpi),and those of T helper type 2(Th2)and T helper type 17(Th17)cytokines were increased at 5 d post infection(dpi).Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF group.The TSLP level was increased in the rIL-4-pretreated group,but there were no significant changes among the other groups.Immunofluorescence staining showed cytokine locations after AF hyphal infection.CONCLUSION:TSLP induces a Th2 immune response and promots Th2 T cell differentiation in vivo.IL-4 promotes TSLP secretion.Therefore,TSLP with IL-4 regulates adaptive immunity in FK.

Research Progress on the Innate Immunity of Bactrocera dorsalis (Hendel) and the Regulation Mechanism of Parasitic Wasp Venom Protein

[Objectives]The use of natural enemies of living insects and their derivatives can effectively avoid the problems of pesticide residues,pest resistance,biodiversity decline,control effect weakening and so on.[Methods]Parasites inject various parasitic factors into hosts to inhibit the development of hosts,adjust the immunity of hosts,interfere with the growth and development of hosts,and reduce the nutrition metabolism of hosts,so as to ensure the growth and development of the offspring.Host pests can escape or conquer the parasitism of parasitic wasps through immune defense system in order to reproduce their own offspring.[Results]Under intense and strong selection pressure,in order to effectively ensure the success rate of parasitism,the adaptive diversity of parasitism strategies of parasitic wasps is finally caused.In the process of evolution and under the pressure of directional selection,the innate immunity and acquired immunity gradually evolve.[Conclusions]In-depth research on parasitic factors of parasitic wasps and their interaction with crop pests immunity and development can not only improve theoretical understanding of insect immunity and development biology,pest biological control and other disciplines,but also be expected to enable the application of some components of parasitic factors to agriculture,medicine and pharmacy.Bactrocera dorsalis is a destructive fruit and vegetable pest.This paper summarized the venom protein of B.dorsalis parasitoids and the immune interaction with hosts,in order to provide theoretical basis for biological control of plant pests by using parasitic natural enemies.

Innate Immunity of Phlomis purpurea against Phytophthora cinnamomi: A Transcriptomic Analysis

Phlomis purpurea L.grows spontaneously in dry and stony habitats from the south of Iberian Peninsula and in cork oak(Quercus suber L.)and holm oak(Q.ilex ssp.rotundifolia,Lam.)plantations infested with Phytophthora cinnamomi(Rands).The aim of this study is to understand the genetic basis of P.purpurea innate immunity to this pathogen.The transcriptome analysis of P.purpurea upon challenging with P.cinnamomi revealed a set of up-regulated genes,related to signaling,transcription factors and response to stress.Transcripts involved in the synthesis of a number of proteins,namely:ANKYRIN,AP2,AQUAPORIN,ARMADILLO,At1G69870-LIKE,BHLH,BON1,CALMODULIN,CALNEXIN,CALRETICULINE,CC-NBS-LRR,CHAPERONE,CYTOCHROME,DUF,GH3,GMP,G-TYPE,LIPOXYGENASE,MLO-LIKE,MYB,NAC,NBS-LRR,PENTATRICOPEPTIDE,SUBTILISIN,WAK,bZIP and hormones such as BRASSINOSTEROID,JASMONATE,SALICYLATE,ETHYLENE-RESPONSIVE were identified.P.purpurea ability to cope with P.cinnamomi attack is based on the expression of a set of transcription factors and signaling molecules targeted by the pathogen.The information gathered contributes to the elucidation of the overall response of P.purpurea to P.cinnamomi attempted infection which can be helpful for improving woody species resistance to pathogenic oomycetes.

Vaccines and autoimmunity during the COVID-19 pandemic

To control the pandemic,efficient vaccines must be applied to the population,including patients with autoimmune diseases.Therefore,one can expect that coronavirus disease 2019(COVID-19)vaccines may influence the underlying autoimmune processes in these patients.Additionally,it is essential to understand whether COVID-19 vaccines would be effective,safe,and provide long-lasting immunological protection and memory.However,the currently available and approved COVID-19 vaccines turned out to be safe,effective,and reliable in patients with autoimmune inflammatory and rheumatic diseases.Furthermore,most patients said they felt safer after getting vaccinations for COVID-19 and reported enhanced overall quality of life and psychological wellbeing.In general,the COVID-19 vaccines have been highly tolerated by autoimmune patients.Such findings might comfort patients who are reluctant to use COVID-19 vaccines and assist doctors in guiding their patients into receiving vaccinations more easily and quickly.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Probiotics: Shaping the gut immunological responses

Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate amounts.Among the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae,Bifidobacteriaceae and yeasts.Most of them have been shown,both in vitro and in vivo studies of intestinal inflammation models,to provide favorable results by means of improving the gut microbiota composition,promoting the wound healing process and shaping the immunological responses.Chronic intestinal conditions,such as inflammatory bowel diseases(IBD),are characterized by an imbalance in microbiota composition,with decreased diversity,and by relapsing and persisting inflammation,which may lead to mucosal damage.Although the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial,it is without doubt that these microorganisms and their metabolites,now named postbiotics,have a positive influence on both the host’s microbiota and the immune system,and ultimately alter the topical tissue microenvironment.This influence is achieved through three axes:(1)By dis-placement of potential pathogens via competitive exclusion;(2)by offering protection to the host through the secretion of various defensive mediators;and(3)by supplying the host with essential nutrients.We will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses,highlighting which species are the most beneficial against intestinal inflammation.

Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

Mutation in the Agrobacterium his I gene enhances transient expression in pepper

Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.

Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

Inflammation: Complexity and significance of cellular and molecular responses

Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.

Immune consequences of exercise in hypoxia:A narrative review

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual characteristics.Similarly,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia.How combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly popular.Therefore,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune system.We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional strategies.Mitochondrial,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune cells.This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions.Appropriate acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

Insights into the mechanism of L-malic acid on drip loss of chicken meat under commercial conditions

Background A deterioration in the meat quality of broilers has attracted much more attention in recent years.L-malic acid(MA)is evidenced to decrease meat drip loss in broilers,but the underlying molecular mechanisms are still unclear.It’s also not sure whether the outputs obtained under experimental conditions can be obtained in a com-mercial condition.Here,we investigated the effects and mechanisms of dietary MA supplementation on chicken meat drip loss at large-scale rearing.Results Results showed that the growth performance and drip loss were improved by MA supplementation.Meat metabolome revealed that L-2-aminoadipic acid,β-aminoisobutyric acid,eicosapentaenoic acid,and nicotinamide,as well as amino acid metabolism pathways connected to the improvements of meat quality by MA addition.The transcriptome analysis further indicated that the effect of MA on drip loss was also related to the proper immune response,evidenced by the enhanced B cell receptor signaling pathway,NF-κB signaling pathway,TNF signaling pathway,and IL-17 signaling pathway.Conclusions We provided evidence that MA decreased chicken meat drip loss under commercial conditions.Metabolome and transcriptome revealed a comprehensive understanding of the underlying mechanisms.Together,MA could be used as a promising dietary supplement for enhancing the water-holding capacity of chicken meat.

The immunomodulatory effects and mechanisms of magnesium-containing implants in bone regeneration:A review

Traditional designs and developments of bone biomaterials mostly concentrate on the positive regulation of osteoblast lineage cells,but often ignore the importance of immune responses and the equilibrium between bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts.Immune dysregulation is associated with an imbalance between pro-inflammatory and anti-inflammatory processes,which may influence the efficacy of bone therapy.Therefore,implanted biomaterials should appropriately and precisely modulate subsequent immune responses.Magnesium(Mg)has been used to fabricate various Mg alloys for bone repair because of its favorable attributes such as osteogenic potential,immune regulation characteristics,biodegradability,and biocompatibility.Various basic research and clinical trials have been already conducted in many countries to explore the physical properties of Mg-containing implants and their clinical outcomes in bone fracture and defect repair.Therefore,this review summarizes the immune response to Mg-containing implants,and further organizes the current research and development progress of Mg-containing implants.The review aims to offer an overview of the current knowledge on immunomodulation of Mg-containing implants and future challenges in their clinical application,which could provide further insight in the development of better strategies for the treatment of bone defect and fracture.

Effect of dietary supplement of inactivated Lactobacillus plantarum Ep-M 17 on growth performance,immune response,disease resistance,and intestinal microbiota in Penaeus vannamei

Our previous study found that feeding with Lactobacillus plantarum Ep-M17 could effectively affect the growth performance,immune response,and gut microbiota of Penaeus vannamei.However,high temperature and pressure during feed pelletizing is the main problem that can lead to a decrease in the activity of probiotics or cause their inactivation.Further investigation needs to investigate whether inactivated Ep-M17 can exert similar effects as live Ep-M17.Therefore,we evaluated the effects of inactivated L.plantarum Ep-M17 on growth performance,immune response,disease resistance,and gut microbiota in P.vannamei.Results show that adding inactivated Ep-M17 to the feed also promoted body weight gain and increased relative immune protection in shrimp.Also,histological examination revealed that the administration of inactivated Ep-M17 led to improvements in the density and distribution of microvilli in the intestines and enhancements in the abundance of B and R cells in the hepatopancreas.Additionally,the inactivated Ep-M17 supplementation resulted in increased activity levels of nutrient immune-related enzymes in both the shrimp hepatopancreas and intestines.Moreover,it stimulated the expression of Lvlec,PEN-3a,Crustin,LGBP,Lysozyme,and proPo genes in both the hepatopancreas and intestines.Furthermore,the inactivated Ep-M17 also increased bacterial diversity in the gut of shrimp and promoted the abundance of specific flora,facilitating the host organism’s metabolism and immunity to improve the disease resistance of shrimp.Therefore,supplementation of inactivated L.plantarum Ep-M17 in shrimp diets can exert similar effects as live L.plantarum Ep-M17 effectively improving growth performance,gut microbiota,immune response,and disease resistance in P.vannamei.