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.

Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review

BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

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.

Cryoablation Combined with TACE for Treating Large Hepatocellular Carcinoma： Tumor Load and Cellular Immunity

OBJECTIVE To study the effectiveness on the tumor load and cellular immune function of percutaneous cryoablation （argon-helium cryoablative system, AHCS） combined with transarterial chemoembolization （TACE） for treating large hepatocellular carcinomas （HCCs） with diameters over 10 ca. METHODS A total of 48 HCC patients were treated with AHCS after TACE. Tumor sizes ranged from 10 to 14 cm. All cases were a hypervascular type. There were 38 Child A cases and 10 Child B cases. Forty were AFP positive and 8 negative. The patients were randomized with therapy group consisting of 26 cases and the control group 22 cases. The therapy group received AHCS 4 weeks following TACE treatment. Reexamination included pathology, tumor markers, T-lymphocyte subgroup levels and computed tomography or MRI. The necrosis rate of the tumor load was calculated by Cavalieri＇s theory. EORTC QLQ-C30 was used in quality of life evaluation. RESULTS The average tumor-load reduction rate （necrosis rate） was 8.07% after TACE, and 28.65% after AHCS. Coagulation necrosis was produced in the target area. The tumor markers deceased significantly after AHCS. Tumor-load reduction after AHCS was more significant than after TACE. Suppression of cellular immunity after TACE was significant. In contrast, CD3^＋, CD4^＋ and NK increased after AHCS and an abnormal T-lymphocyte distribution was corrected. Quality of life after AHCS increased according to the EORTC QLQ-C30 evaluation. No severe complications occurred. CONCLUSION Percutaneous AHCS cryoablation after TACE reduced the tumor load in the short term. At the same time, cellular immune function was increased after AHCS. TACE was critical in increasing the therapeutic efficacy of AHCS because of its embolisation of blood vessels preventing a Flow Effect. Reduction of the tumor load in the short term may conduce to increase cellular immunity. Percutaneous AHCS cryoablation combined with TACE can reduce the tumor load, improve cellular immunity and increase quality of life of HCC patients. This type of therapy deserves to be studied further research.

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.

Role of innate immunity in the development of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common form of liver cancer worldwide.It is caused by a variety of risk factors,most common ones being infection with hepatitis viruses,alcohol,and obesity.HCC often develops in the background of underlying cirrhosis,and even though a number of interventional treatment methods are currently in use,recurrence is fairly common among patients who have had a resection.Therefore,whole liver transplantation remains the most practical treatment option for HCC.Due to the growing incidence of HCC,intense research efforts are being made to understand cellular and molecular mechanisms of the disease so that novel therapeutic strategies can be developed to combat liver cancer.In recent years,it has become clear that innate immunity plays a critical role in the development of a number of liver diseases,including HCC.In particular,the activation of Toll-like receptor signaling results in the generation of immune responses that often results in the production of proinflammatory cytokines and chemokines,and could cause acute inflammation in the liver.In this review,the current knowledge on the role of innate immune responses in the development and progression of HCC is examined,and emerging therapeutic strategies based on molecular mechanisms of HCC are discussed.

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.

Cellular immunity augmentation in mainstream oncologic therapy

Anticancer immunotherapy has undergone a long evolving journey for decades, and has been dramatically applied to mainstream treatments in oncology in recent 5 years. This progress represents an advanced milestone following cytotoxic medicine and targeted therapy. Cellular immunity plays a pivotal role in the immune responses of hosts to tumor antigens. Such immunity is notably suppressed during neoplastic progression due to immuno-editing processes. Cellular immunity can also be selectively reactivated to combat malignancies while exploiting the advantages of contemporary scientific breakthroughs in molecular immunology and genetic engineering. The rapid advancement of cellular immunity-based therapeutic approaches has achieved high efficacy in certain cancer patients. Consequently, the landscape of oncologic medicine and pharmaceutical innovation has transformed recently. In this regard, we present a comprehensive update on clinically established anti-cancer treatments with cell immunity augmentation as the major mechanism of action.

Isolation, chemical characteristics and immunity activity of an extracellular polysaccharide EPS I isolated from Antarctic bacterium Pseudoalteromonas sp.S-15-13

A new extracelluar polysaccharide （EPS） was isolated and purified from Antarctic bacterium S-15-13, identified as Pseudoalteromonas sp. After being separated and purified by DEAE-Sephadex A-50 ionexchange and Sephadex G-100 gel chromatography, two mains fractions （EPS I and EPS Ⅱ ） were ob-tained. EPS I was composed of mannose, glucose and galactose with a molecular weight of 23kDa and EPS Ⅱ was composed of mannose only with a molecular weight of 62kDa. The effect of the polysaccharide EPS I on the cellular immune response of mice was investigated. Results demonstrated that EPS I could markedly facilitate lymphocyte proliferation, and might be a strong immunomodulator.

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.

Effects of Tai Chi Chuan training on cellular immunity in post-surgical non-small cell lung cancer survivors:A randomized pilot trial

Background： Although emerging evidence points to benefits from Tai Chi Chuan （TCC） in improving immune system function, its effects on cellular immune responses remain under-studied. The objective of this study was to evaluate the effects of TCC training on cellular immunity in non-small cell lung cancer patients. Methods： A 2-group randomized trial design in which post-surgical, non-small cell lung cancer survivors were randomly assigned to a TCC training group （n = 16） or a control group （n = 16）. The participants in the TCC group completed a 16-week intervention. The main immune response outcome measures assayed included the ratio of T-helper cells/T-suppressor cells （CD4＋：CD8＋ ratio） and complement regulatory proteins status （CRPs; CD55 and CD59）. Using repeated measures ANOVA, the data were analyzed for the participants who completed the study （n = 27）. Results： At 16 weeks, the TCC participants showed a significantly lower increment in the expression of CD55 （p 〈 0.05） as compared to the control group. No significant between-group differences were found in the CD4＋：CD8＋ ratio or CD59 expression. There were also no significant correlations among the changes in CRPs or T lymphocyte subpopulations, either. Conclusion： A 16-week TCC intervention caused no alterations in CD4＋：CD8＋ ratio, but significantly attenuated CD55 expression among post- surgical non-small cell lung cancer survivors.

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.

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.

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.

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.

Studies of the effects of dietary zinc on the immune organs and cellular immunity in the rat

The effects of dietary zinc on the immune organs and cellular immunity were investigated in the rats of zinc-deficient(ZD), zinc-excessive(ZE), paired feeding(PF) and ad libitus(AL) groups. The findings were as follows: (1) The weight of the thymus and spleen and the ratio with the body weight, the size of the cells,the production of thymic peptides and thymin activity were significantly lower in ZD and ZE groups than in PF and AL groups. (2) The total number of the cells in G_0/G_1 phase of T-and B-cells and bone marrow cells were significantly higher in ZD and ZF groups than in PF and AL groups while that of the cells in S and G_2/M phases were significantly lower in ZD and ZE groups than in PF and AL groups. (3) The cellular DNA, RNA and protein content in the thymus, spleen and bone marrow were significantly lower in ZD and ZE groups than in PF and AL groups.(4) The ￣3H-TdR incorporation rate of splenic T-and B-cells , IL-2 activity, plasma level of TNF and nitrogen oxide(NO) were significantly lower in ZD group than in PF group. (5) The leucocyte count of the perpheral blood,the percentage of lymphocytes, the bacteriocidal activity of phagocytes, and the phagocytic rate and index of abdominal phagocytes were significantly lower in ZD and ZE groups than in PF and AL groups. These findings indicate that an adequate amount of dietary zinc is essential for the development of immune organs and the promotion of cellular immunity while deficiency or excess of zinc is able to damage the immune function.

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.

Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.