Effects of Combined Application of NRTUAs and ABP on Growth and Humoral Immunity of Chicks

[Objectives]The paper was to study the effects of combined application of nonreplicating Toxoplasma uracil auxotrophs(NRTUAs)and Agaricus blazei Murill polysaccharide(ABP)on growth and humoral immunity of chicks.[Methods]A total of 120 one-day old female Hyline brown laying hens were randomly divided into 4 groups,30 hens for each group.The chicks in group 1 were subcutaneously injected with NRTUAs and fed on the diet containing with ABP;the chicks in group 2 were subcutaneously injected with NRTUAs;the chicks in group 3 were subcutaneously injected with equal volume of PBS,and fed on the diet containing with ABP;the chicks in group 4 were subcutaneously injected with equal volume of PBS.The body weight of chicks in each group was counted at the 21^(st),42^(nd),84^(th)and 112^(th)week.During this period,blood samples were collected from chicks in each group at 0,7,14,21,28 and 35 d post immunization against Newcastle disease(ND),and serum was separated to detect the antibody titer of ND.[Results]The combined application of NRTUAs and ABP had no effect on growth of chicks,but promoted the humoral immune response of chicks,significantly improved the ND antibody level of chicks,and could maintain high levels of antibodies in the body for a long time.[Conclusions]The study lays a theoretical foundation for further developing the clinical application of NRTUAs and ABP.

Evolution of Acquired Humoral Immunity after Full Vaccination against SARS-CoV-2. IgG Levels in Healthcare Workers at 6 and 9 Months

Background: The COVID-19 pandemic continues to be a major worldwide health problem. The present study aims to contribute to surveillance of the immune and clinical response of vaccines to SARS-CoV-2. Methods: Observational medication study on acquired immunity and effectiveness of vaccines. Population: 620 workers in the health service of Almansa (Spain). Representative sample of 150 individuals. Sociodemographic, clinical, and epidemiological data and samples were recorded to determine anti-SARS-CoV-2 serum IgG levels 6 and 9 months after vaccination with Pfizer. Results: Mean age 46.45 years;76% women;85.1% working in a hospital. 19.3% had had COVID-19 in the year prior to vaccination. 96.7% were fully vaccinated with Pfizer/BioNTech. At 6 months, 100% seropositivity and mean IgG levels of 3017.2 AU/ml. Significant variations in IgG levels in individuals with prior COVID-19 infection and smokers. At 9 months, 99.3% remained seropositive;2.8% infected after vaccination. The repeated measures analysis showed a difference in means of 669.0 AU/ml (significant decrease in IgG levels of 28.9%). Conclusion: Antibody levels remained positive 6 and 9 months after vaccination, although IgG levels were found to decay.

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.

STUDIES ON LYMPHOCYTE SUBSETS, HUMORAL IMMUNITY AND THEIR RELATIONSHIP WITH SELENIUM IN PATIENTS WITH KASHIN-BECK DISEASE

Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kashin-Beck Disease (KBD), and their relationship with erythrocyte selenium. Methods 23 X-ray diagnosed patients, 22 age- and sex- matched healthy children in KBD affected area (KAA), and 25 in KBD non-affected area (KNAA) were randomly selected. Immunohistochemistry with monoclonal antibodies anti-CD4, anti-CD8, anti-CD20 was conducted to analyze the lymphocyte subsets. Serum IgM, IgA, IgG, Complement C3 and C4 were assayed using rate nephelometry (Array 360 System, USA). The contents of erythrocyte selenium was determined by 2,3-diaminonaphthalene fluorescence assay. Results CD4+ and CD8+ cells percentage in PBMCs and serum IgA were significantly lower in KAA than those in KNAA(P< 0.05). CD20+ percentage in KAA displayed a decreasing trend compared to KNAA, although not statistically significantly. No statistical differences were found in CD4/CD8 ratio, serum IgG, IgM, C3 and C4 levels. Erythrocyte selenium level in KAA still showed a pronounced decrease compared to that in KNAA. Correlation analysis showed that erythrocyte selenium contents had a strong association with the CD4 cell percentage (r= 0.625, P< 0.05), as well as serum IgA (r= 0.462, P< 0.05). In addition, a moderate correlation between the serum IgA and CD4+ percentage (r= 0.130, P> 0.05) was found. Conclusion These results suggested that children in KAA had a comparably low cellular immunity level and their humoral immunity status was also in a state of moderate immune suppression. Of this immune disorder in Kashin-Beck disease patients, selenium deficiency probably played a critical role via affecting the distribution pattern of peripheral blood lymphocyte. Selenium-deficiency and immune impairment maybe both have something to do with the cause-effect chain of KBD.

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.

Evaluation of humoral immunity and peripheral blood T lymphocyte subset levels after Mycoplasma pneumoniae infection

Objective:To evaluate humoral immunity and peripheral blood T lymphocyte subset levels after Mycoplasma pneumoniae infection. Methods:118 cases of children with Mycoplasma pneumoniae infection were selected as observation group, and 98 cases of healthy children receiving medical examination in our hospital during the same period were selected as control group. The differences in humoral immunity, T lymphocyte subsets, anti-inflammatory and pro-inflammatory factors, Th1/Th2 balance state, etc were compared between two groups of children. Results:Serum IgA level of observation group was lower than that of control group (P<0.05), and IgM level was higher than that of control group (P<0.05). Peripheral blood CD3+and CD4+T lymphocyte levels as well as CD4+/CD8+ratio were lower than those of control group (P<0.05), while CD8+T lymphocyte level was higher than that of control group (P<0.05). Serum pro-inflammatory factors IL-8 and TNF-αlevels were higher than those of control group (P<0.05), while anti-inflammatory factors IL-10 and IL-13 levels were lower than those of control group (P<0.05). Serum IL-4, IFN-γand IL-4/IFN-γlevels were higher than those of control group (P<0.05). Conclusions:Humoral immune and cellular immune suppression, high inflammatory state and so on after Mycoplasma pneumoniae infection are the important mechanisms leading to disease progression.

Effect of adjuvant ganglioside sodium therapy on nerve injury degree as well as cytokines and humoral immunity in patients with acute severe craniocerebral injury

Objective:To study the effect of adjuvant ganglioside sodium therapy on nerve injury degree as well as cytokines and humoral immunity in patients with acute severe craniocerebral injury. Methods:94 patients with severe craniocerebral injury treated in our hospital between March 2013 and March 2016 were selected and randomly divided into the ganglioside sodium group (GM1 group) and control group. Before treatment as well as after 4 weeks and 8 weeks of treatment, serum levels of nerve injury molecules, nerve injury cytokines, inflammatory cytokines and humoral immune molecules were determined respectively.Results: After 4 weeks and 8 weeks of treatment, serum neuron-specific enolase (NSE), S100β protein (S100β), ubiquitin carboxy-terminal hydrolase L1 (UCH L1), glial fibrillary acid protein (GFAP), hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor α(TNF-α), and interleukin-6 (IL-6) content of both groups were significantly lower than those before treatment (P<0.05) while brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), IgG, IgM and IgA content were significantly higher than those before treatment (P<0.05), and serum NSE, S100β, UCH-L1, GFAP, hs-CRP, TNF-α and IL-6 content of GM1 group were significantly lower than those of control group (P<0.05) while BDNF, NGF, IgG, IgM and IgA content were significantly higher than those of control group (P<0.05).Conclusions: Adjuvant ganglioside sodium therapy can relieve the nerve injury, inhibit the inflammatory reaction and improve the humoral immune response in patients with acute severe craniocerebral injury.

Low-protein diets supplemented with casein hydrolysate favor the microbiota and enhance the mucosal humoral immunity in the colon of pigs

Background:High-protein diets can increase the colonic health risks.A moderate reduction of dietary crude-protein(CP)level can improve the colonic bacterial community and mucosal immunity of pigs.However,greatly reducing the dietary CP level,even supplemented with all amino acids(AAs),detrimentally affects the colonic health,which may be due to the lack of protein-derived peptides.Therefore,this study evaluated the effects of supplementation of casein hydrolysate(peptide source)in low-protein(LP)diets,in comparison with AAs supplementation,on the colonic microbiota,microbial metabolites and mucosal immunity in pigs,aiming to determine whether a supplementation of casein hydrolysate can improve colonic health under very LP level.Twenty-one pigs(initial BW 19.90±1.00 kg,63±1 days of age)were assigned to three groups and fed with control diet(16%CP),LP diets(13%CP)supplemented with free AAs(LPA)or casein hydrolysate(LPC)for 4 weeks.Results:Compared with control diet,LPA and LPC diet decreased the relative abundance of Streptococcus and Escherichia coli,and LPC diet further decreased the relative abundance of Proteobacteria.LPC diet also increased the relative abundance of Lactobacillus reuteri.Both LP diets decreased concentrations of ammonia and cadaverine,and LPC diet also reduced concentrations of putrescine,phenol and indole.Moreover,LPC diet increased total short-chain fatty acid concentration.In comparison with control diet,both LP diets decreased protein expressions of Toll-like receptor-4,nuclear factor-κB,interleukin-1βand tumor necrosis factor-α,and LPC diet further decreased protein expressions of nucleotide-binding oligomerization domain protein-1 and interferon-γ.LPC diet also increased protein expressions of G-protein coupled receptor-43,interleukin-4,transforming growth factor-β,immunoglobulin A and mucin-4,which are indicators for mucosal defense activity.Conclusions:The results showed that supplementing casein hydrolysate showed beneficial effects on the colonic microbiota and mucosal immunity and barrier function in comparison with supplementing free AAs in LP diets.These findings may provide new framework for future nutritional interventions for colon health in pigs.

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.

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.

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.

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.

Effects of Astragalus injection on chemokines, renal function and humoral immunity in patients with pulmonary tuberculosis

Objective:To investigate the effects of Astragalus Injection on inflammatory factors, chemokines, renal function and humoral immunity in patients with pulmonary tuberculosis. Methods:80 patients with pulmonary tuberculosis who were treated in the department of respiratory medicine in our hospital from October 2015 to October 2017 were randomly divided into control group and observation group, 40 cases in each group. Patients in the control group were given levofloxacin treatment;and patients in the observation group were given astragalus injection combined with levofloxacin treatment. Before and after treatment, procalcitonin (PCT), interferon-γ (INF-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1 ), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA) and immunoglobulin (IgA, IgM, IgG) levels were measured and compared between the patients in the two groups.Result: After treatment, the levels of PCT, INF-γ, MCP-1 and MIP-1 in serum of the patients in the two groups were significantly decreased, and the levels of IgA, IgM and IgG were significantly increased. The changes of the PCT, INF-γ, MCP-1, MIP-1 , IgA, IgM and IgG of patients in the observation group were significantly stronger than those in the control group (P<0.05). After treatment, the levels of BUN, SCr and UA in serum of patients in the two groups increased significantly. The serum levels of above indexes of patients in the observation group were significantly lower than those in the control group (P<0.05).Conclusion: Astragalus injection can significantly relieve the inflammatory state of patients with pulmonary tuberculosis, reduce the level of chemokines, enhance the renal function and immune function of patients. It has good clinical efficacy.

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.

Immunology of Kaschin-Beck Disease:Studies on lymphocyte subsets, humoral immunity and their relationship with selenium

Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kaschin-Beck Disease (KBD), and their relationship with erythrocyte selenium.Methods 23 X-ray diagnosed patients, 22 age- and sex- matched healthy children in KBD affected area (KAA), And 25 in KBD non-affected area (KNAA) were randomly selected. Immunohistochemistry with monoclonal antibodies anti-CD4, anti-CD8, anti-CD20 was conducted to analyze the lymphocyte subsets. Serum IgM, IgA, IgG, Complement C3 and C4 were assayed using rate nephelometry (Array 360 System, USA). The contents of erythrocyte selenium was determined by 2,3-diaminonaphthalene fluorescence assay. Results CD4+ and CD8+ cells percentage in PBMCs and serum IgA were significantly lower in KAA than those in KNAA(P<0.05). CD20+ percentage in KAA displayed a decreasing trend compared to KNAA, although not statistically significantly. No statistical differences were found in CD4/CD8 ratio, serum IgG, IgM, C3 and C4 levels. Erythrocyte selenium level in KAA still showed a pronounced decrease compared to that in KNAA. Correlation analysis showed that erythrocyte selenium contents had a strong association with the CD4 cell percentage (r=0.625,P<0.05), and also a close relationship with serum IgA (r=0.462,P<0.05). In addition, we detected a moderate correlation between the serum IgA and CD4+ percentage (r=0.130, P>0.05).Conclusion Taken together, our results suggested that children in KAA had a comparably low cellular immunity level manifested by the marked depression of CD4 and CD8 cells percentage, and their humoral immunity status was also in a state of moderate immune suppression. Of this immune disorder in KBD patients, selenium deficiency probably played a critical role via affecting the distribution pattern of peripheral blood lymphocyte. Selenium-deficiency and immune impairment maybe both have something to do with the cause-effect chain of KBD.

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.

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.

Humoral Response and Tolerance of Vaccination against SARS-CoV-2 in Adults Senegalese Patients Undergoing Hemodialysis: A Multicenter Prospective Study

Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to assess the immunological response to vaccination in Senegalese hemodialysis patients. Patients and Methods: We conducted a prospective study, in two dialysis centers in Dakar from March 30th to August 30th, 2021 including patients on hemodialysis for >6 months, vaccinated against SARS-CoV-2 according to the vaccination schedule recommended by WHO. A vaccine response was considered positive when seroconversion was observed after one dose of vaccine. The clinical efficacy of immunization was defined as the absence of new COVID-19 infection in patients who received a complete vaccination. Results: Among the 81 patients included in the study, 7.4% had anti-Spike IgM antibodies before their first vaccination. Seroprevalence of IgM antibodies was 38.3% one month after the first vaccine dose (at M1) and 8.6% one month after the second dose (at M4). Anti-Spike IgG antibodies were present in 40.3% of patients before vaccination, in 90.1% at M1, and in 59.7% at M4. Among patients previously infected with SARS-CoV-2, 10.2% had IgM antibodies at M0, 31.6% at M1, and 10.5% at M4 post-vaccination. Similarly, seroprevalences of IgG antibodies in this subgroup were 31.5%, 61.3%, and 50.0% respectively at M0, M1, and M4 post-vaccination. A comparison of seroconversion rates between M0 and M4 showed significant differences only for IgG in COVID-19 naive patients. Mean duration in dialysis and the existence of previous COVID-19 infection were associated with patients’ vaccinal response after the two doses. Age, gender and the use of immunosuppressive treatment did not influence post-vaccinal antibody production. Conclusion: Vaccination against COVID-19 in Senegalese hemodialysis patients induced a low seroconversion rate but it was well tolerated. Moreover, the induced protection was neither strong nor durable, particularly in patients with longer duration in dialysis.