Monitoring humoral and cellular immunity over 6 months after mRNA-based bivalent COVID-19 vaccine administration

Dear Editor,Although the World Health Organization(WHO)has declared an end to the global emergency for coronavirus disease 2019(COVID-19)[1],the clinical burden of severe acute respiratory syndrome coronavirus disease(SARS-CoV-2)has not yet subsided[2,3],especially after the emergence of new variants such as EG.5 and BA.2.86,whose genetic leap is so large that it may contribute to increase the number of new COVID-19 cases,hospitalizations,and deaths[3].Some physical preventive measures,such as mask-wearing,hand hygiene,and isolation of positive cases,play an important role.However,widespread vaccination remains the cornerstone to contain the spread of the virus and mitigate the potential harm to human health.

Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma

Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.

Effect of Astragalus Injection on Serious Abdominal Traumatic Patients’ Cellular Immunity

Objective： To explore the change of serious abdominal traumatic patients＇ cellular immunity and the effect of Astragalus Injection （AI） on it. Methods： Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with Al20 ml was added into 250 ml of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored. Results： On the first day, in the conventional group and treated group, the levels of CD3^＋ , CD4^＋ , CD4^＋/CD8^＋ , 0D16^＋ , CD69^＋ and CD3^＋/homologous leucocytic antigen-DR （HLA-DR＋ ） were apparently lower than those in the healthy group （ P〈0.05）, while the CD8^＋ was significantly higher than that in the healthy group （P〈0.05）, and there was no significant difference between the conventional group and the treated group （P〉0.05） ; on the 14th days, the levels of CD3^＋, CD4^＋, CD4^＋/CD8^＋, CD16^＋, CD69^＋ and CD3^＋/HLA-DR^＋ of the treated group got closed to healthy subject value, and got even higher than those of conventional group （P〈0. 05）; CD8^＋ got close to that of healthy subjects, while obviously lower than that of conventional group （ P〈0. 05）. Conclusion： After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI was beneficial to the restoration of cellular immunity.

ACUPUNCTURE EFFECT ON CELLULAR IMMUNITY AND NEUROENDOCRINOIMMUNE NETWORK-A REVIEW OF OUR RESEARCH WORKS

The immune cells,mainly including lymphocytes,possessed tneir respective receptorsfor OLP,such as β-EP,MEK and LEK and for neurotransmitters,such as 5-HT,SP,SOMand VIP.The ligands released from the nervous system and endocrine APUD cells under stimulationof acupuncture,laser or TENS at the acupoint could exert analgesia and generally promotion of cellularimmunity with a dual regulation in individuals.The effects of immune cells preincubated with exogenousligands on cellular immunity were similar to that affected by endogenous ligands underacupuncture.Both effects of preincubation and acupuncture could be inhibited or reversed by naloxonewhich may compete with OLP and its related neurotransmitters at the same receptor slies.The ligands,primarily including OLP,may act as a link between the neuroendocrine system and immunecells or between analgesia and immune cell function.The acupuncture effect on cellular immunity maybe carried out through regulation of the neuroendocrinoimmune network in the organism.

Adjuvant activity of Pasteurella multocida A strain,Pasteurella multocida B strain and Salmonella typhimurium bacterial DNA on cellular and humoral immunity responses against Pasteurella multocida specific strain infections in Balb/c mice

Objective: To evaluate the effects of Pasteurella multocida(P. multocida) vaccines on the expression and release of antibodies, interleukin(IL)-6 and IL-12 by serum. Methods: Balb/c mice were immunized with two formalin and iron inactivated vaccine doses within 2 weeks. The vaccines were adjuvant with P. multocida A strain, P. multocida B strain and Salmonella typhimurium bacterial DNA(AbDNA, BbDNA and SbDNA for short, respectively). The animals were challenged 4 weeks after immunization. Blood of mice was collected to detect the change of specific antibody, IL-6, and IL-12 using ELISA. Results: The specific antibody and interleukins in the immunized group increased significantly compared to the control mice after vaccination and challenge(P<0.05). The highest release of these cytokines was obtained by P.multocida inactivated with iron and adjuvant with AbDNA at a concentration of 25 μg/mL. The antibody titer peak was 0.447 in mice vaccinated with iron-killed whole-cell antigen adjunct with AbDNA. The time-courses of release showed that bacterial DNA was able to stimulate IL-6 and IL-12 production more than alum(P<0.05). Conclusions: Our findings introduce that bacterial DNA is capable of releasing an immunological response with several cytokines.These indicate that bacterial DNA entrapped with killed P. multocida antigen is a new and effective adjuvant to enhance specific immunity and resistance of animal against the infectious pathogen, which could simplify the development of highly promising strong adjuvant.

Inflammatory factors, cellular immunity and humoral immunity in patients with secretory otitis media

Objective:To investigate the changes of inflammatory factors, cellular immunity and humoral immunity in patients with secretory otitis media.Methods:A total of 82 cases of secretory otitis media admitted in our hospital from January 2017 to December 2017 were selected as the observation group, and 80 healthy volunteers in our hospital were selected as the control group. The tumor necrosis factor-α (TNF-α), calcitonin (PCT), platelet activating factor (PAF), endothelin-1 (ET-1), CD3+, CD4+, CD8+, CD4+/CD8+, IgA, IgG, IgM. were detected and compared.Results: The levels of TNF-α, PCT, PAF and ET-1 in the observation group were (2.21 ± 0.13) ng/mL, (3.96 ± 0.81) ng/mL, (149.50 ± 21.08) ng/mL, and (1.67 ± 0.53) μg/L, which were all higher than those of the control group, the differences were significant. The levels of CD3+, CD4+ and CD4+/CD8+ in the observation group were (51.95 ± 4.47)%, (37.04 ± 3.94)% and (1.10 ± 0.04) respectively, which were all lower than those in the control group, the differences were significant. The level of CD8+ in the observation group was (33.63 ± 3.94)%, higher than that in the control group, the difference was significant. The levels of IgA, IgG and IgM in the observation group were (4.97 ± 0.22) g/L, (31.16 ± 2.53) g/L and (5.12 ± 0.17) g/L respectively, which were all higher than the control group, the differences were significant.Conclusion:Inflammatory factors and immune status of patients with secretory otitis media are abnormal. It is suggested to strengthen clinical monitoring of relevant indicators.

Effects of ulinastatin combined with thymopentin on cellular immunity, humoral immunity and stress response in severe pneumonia

Objective:To explore the effects of ulinastatin combined with thymopentin on cellular immunity, humoral immunity and stress response in severe pneumonia.Methods: A total of 102 cases of severe pneumonia treated in our hospital from February 2016 to November 2017 were collected as subjects and randomly divided into the control group (n=51) and the observation group (n=51), the two groups were treated with routine symptomatic treatment. The control group was treated with the ulinastatin on the basis of routine treatment, the observation group was treated with thymopentin on the basis of the control group. The changes of cellular immunity, humoral immunity, stress response and liver function in the two groups were compared.Results: Before treatment, there was no significant difference in the levels of CD4+, CD8+, CD4+/CD8+, IgA, IgM, IgG, SOD, MDA, T-AOC, AKP, TB and ALT between the two groups (P>0.05). After treatment, the two groups of CD4+ and CD4+ /CD8+ were significantly increased (P<0.05), CD8+ was significantly lower than before treatment (P<0.05), and CD4+ and CD4+ /CD8+ in the observation group were significantly increased compared with the control group (P<0.05), CD8+was significantly lower than the control group (P<0.05);the two groups of IgA, IgM and IgG were significantly increased compared with those before treatment (P<0.05), and the IgA, IgM and IgG in the observation group were significantly higher than those in the control group (P<0.05);two groups of SOD and T-AOC were significantly higher than before treatment (P<0.05), while MDA was significantly lower than before treatment (P<0.05), and SOD and T-AOC in the observation group were significantly increased (P<0.05), and MDA was significantly lower than that of the control group (P<0.05);two groups of AKP, TB and ALT were significantly lower than those before treatment (P<0.05), and the AKP, TB and ALT in the observation group were significantly lower than those in the control group (P<0.05).Conclusions: ulinastatin combined with thymopentin in patients with severe pneumonia can effectively enhance the cellular immunity and humoral immune function, reduce oxidative stress damage and protect the liver function, which has clinical significance.

The Regulatory Action of the Modified Yu Ping Feng Tang on Cellular Immunity in Mice under Amputation-Induced Stress

To approach the action of modified Yu Ping Feng Tang(玉屏风汤 Jade-Screen Decoction)on cellularimmunity,an experiment was conducted in mice under amputation-induced stress.On the 3rd dayafter amputation,acute atrophy was found in the thymus,the reactivities of T-and B-lymphocytes toCon-A and LPS were decreased,the IL-2 content and its activity reduced and the activity of NK cellslowered.The high,moderate and low concentrations of the modified Yu Ping Feng(YPF)Decoction allhave antagonistic action on the above manifestations of immune inhibition.

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.

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.

CONSECUTIVE IMMUNIZATION WITH RECOMBINANT FOWLPOX VIRUS AND PLASMID DNA FOR ENHANCING CELLULAR AND HUMORAL IMMUNITY

Objective: To investigate the influence of consecutive immunization on cellular and humoral immunity in mice. Methods: We evaluated a consecutive immunization strategy of priming with recombinant fowlpox virus vUTALG and boosting with plasmid DNA pcDNAG encoding HIV-1 capsid protein Gag. Results: In immunized mice, the number of CD 4 + T cells from splenic lymphocytes increased significantly and the proliferation response of splenocytes to ConA and LPS elevated markedly and HIV-1-specific antibody response could be induced. Conclusion: Consecutive immunization could increase cellular and humoral immunity responses in mice.

Role of cellular immunity in halothane hepatitis: an in vitro study

Objective: To explore the effect of cellular immunity in halothane hepatitis. Methods: Hepatotoxicity model was established by exposing male Hartley guinea pigs to 1% halothane via inspiration for 4 h each time for 1 or 3 times within a 42-day interval. Then their hepatocytes and lymphocytes were collected and divided into 2 parts for different cultures. Hepatocytes were cultivated with or without 1% halothane for 4 h and lymphocytes were cultivated with or without 12.5 μg/ml trifluoroacetylated guinea pig serum albumin (TFA-GSA). Then the 2 kinds of hepatocytes were co-cultivated with lymphocytes (1:100) with or without TFA-GSA induction respectively and the supernatant fluid was taken after 24, 48 and 72 h to determine the concentration of alanine aminotransferase (ALT). The halothane cultivated hepatocytes were co-cultivated with various proportion of TFA-GSA antigen induced lymphocytes and ALT was determined after 48 h to determine the proper proportion of hepatocytes and lymphocyte. Results: Lymphocytes of 3 times halothane induced guinea pigs caused a significant increase of ALT in hepatocytes with or without halothane induction. But the lymphocytes of 1 time halothane induced guinea pigs only caused a significant increase of ALT in hepatocytes with induction of halothane. The increase of ALT was only seen after 48- and 72-hour co-culture. The proper proportion of hepatocytes and lymphocytes was 1:100 for lymphocytes cytotoxicity. Conclusion: Lymphocytes is sensitized after inhalation of halothane and generates cytotoxicity to hepatocytes. The immune response of lymphocytes to hepatocytes will be enhanced by repeated inhalation of halothane. The cellular immunity may be one of the mechanisms of halothane induced hepatotoxicity.

Study of cellular immunity response of mB7-1 gene transfected mouse ovarian cancer cell line and its tumorigenecities in vivo

Objective:To investigate the cellular immunity response in vitro and the tumorigenecities in vivo of mB7 1 gene transfected murine ovarian cancer cell line.Methods:mB7 1 gene was transfected into the NuTu 19 cell line by retrovirus vector, and the expression of mB7 1 gene was confirmed by flow cytometry(FCM).NuTu 19/neo and NuTu 19/mB7 1 cells were injected subcutaneously into syngeneic Fischer 344 rats respectively,and their tumorigenecities were recorded.Proliferation indices of lymphocyte were assayed after syngenieic mixed tumor lymphocyte cultures(MTLCs).The lysis activity of CTL toward tumor cells was determined using methyl thiazolyl tetrazolium(MTT) assay.Results:Successful transfection of mB7 1 gene into NuTu 19 cell line was comfirmed with FCM.In vitro study showed that there was no obvious changes in cell growth of gene transfected cell line,compared with the cell line NuTu 19.NuTu 19/mB7 1 cells could induce more effective proliferation of effector lymphocytes(P<0.05). The lysis activity of CTL activated by NuTu 19/mB7 1 was stronger than that of NuTu 19/neo (P<0.01).Tumor sizes were smaller in the NuTu 19/mB7 1 receptance syngeneic Fischer 344 rats compared with those in the control group.Conclusion:mB7 1 genetically modified ovarian cancer cells could induce the cellular immunity response in vitro and the tumorigenecitiy of NuTu 19 cells was decreased after inoculation with the experimental vaccine.

Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.

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.

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.

Resource Allocation in Multi-User Cellular Networks:A Transformer-Based Deep Reinforcement Learning Approach

To meet the communication services with diverse requirements,dynamic resource allocation has shown increasing importance.In this paper,we consider the multi-slot and multi-user resource allocation(MSMU-RA)in a downlink cellular scenario with the aim of maximizing system spectral efficiency while guaranteeing user fairness.We first model the MSMURA problem as a dual-sequence decision-making process,and then solve it by a novel Transformerbased deep reinforcement learning(TDRL)approach.Specifically,the proposed TDRL approach can be achieved based on two aspects:1)To adapt to the dynamic wireless environment,the proximal policy optimization(PPO)algorithm is used to optimize the multi-slot RA strategy.2)To avoid co-channel interference,the Transformer-based PPO algorithm is presented to obtain the optimal multi-user RA scheme by exploring the mapping between user sequence and resource sequence.Experimental results show that:i)the proposed approach outperforms both the traditional and DRL methods in spectral efficiency and user fairness,ii)the proposed algorithm is superior to DRL approaches in terms of convergence speed and generalization performance.

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.

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.