Leukocyte modulation by natural products from herbal medicines and potential as cancer immunotherapy.

Cancer constitutes a kind of life-threatening disease that is prevalent throughout the world. In light of limitations in conventional chemotherapies or radiotherapies, cancer immunotherapy has emerged as a potent strategy in treating cancer. In cancer immunotherapy, preliminary studies have demonstrated that cancer immune surveillance serves a crucial role in tumor initiation, progression, and metastasis. Herbal medicines and natural products, which serve as alternative medicines, are involved in the modulation of tumor immunosurveillance to enhance antitumor activity. Accordingly, this review aimed to summarize the modulation function of herbal medicines and natural products on tumor immunosurveillance while providing scientific insight into further research on its molecular mechanism and potential clinical applications.

Is malaria immunity a possible protection against severe symptoms and outcomes of COVID-19?

Malaria-endemic areas of the world are noted for high morbidity and mortality from malaria. Also noted in these areas is the majority of persons in the population having acquired malaria immunity. Though this acquired malaria immunity does not prevent infection, it resists the multiplication of Plasmodium parasites, restricting disease to merely uncomplicated cases or asymptomatic infections. Does this acquired malaria immunity in endemic areas protect against other diseases, especially outbreak diseases like COVID-19? Does malaria activation of innate immunity resulting in trained or tolerance immunity contribute to protection against COVID-19? In an attempt to answer these questions, this review highlights the components of malaria and viral immunity and explores possible links with immunity against COVID-19. With malaria-endemic areas of the world having a fair share of cases of COVID-19, it is important to direct research in this area to evaluate and harness any benefits of acquired malaria immunity to help mitigate the effects of COVID-19 and any possible future outbreaks

Stimulator of interferon genes inhibits the development and progression of chronic liver diseases / 临床肝胆病杂志

Stimulator of interferon genes (STING) is an important congenital cytoplasmic cyclic dinucleotide sensor that regulates the internal environment of the liver. It activates IRF3/IRF7 and inhibits the development and progression of chronic liver diseases such as chronic hepatitis B, liver fibrosis, and hepatocellular carcinoma through innate immune response, specific T cell response, and autophagy. This article introduces the distribution, structural characteristics, biological functions, and signaling pathways of STING and its role in the development and progression of chronic liver diseases, in order to elaborate on the role of STING in the intervention of chronic liver diseases and provide new ideas for treatment.

Interaction between the stimulator of interferon genes signaling pathway and HBV / 临床肝胆病杂志

Stimulator of interferon genes (STING) is a newly discovered adaptor protein in the innate immune system and plays an important role in innate immune response mediated by cytoplasmic DNA. Double-stranded DNA recognition receptors in cells are mediated by STING protein to produce type I interferon and other cytokines. Inadequate innate immune response and anti-hepatitis B virus (HBV) specific immune response are important causes of chronic HBV infection. This article introduces the discovery of STING and the latest research advances in its structure, briefly elaborates on the mechanism of activation of the STING signaling pathway, summarizes the research advances in the interaction between the STING signaling pathway and HBV, and points out the potential value of STING in clinical treatment.

Immunosenescence and its role in cancer / 国际肿瘤学杂志

Immunosenescence is a biological process featured by the structural and functional decline of immunity in ageing people,which favors the carcinogenesis by rendering the body's immune surveillance and tumor escape.Decreasing clearance of tumor cells by macrophages and natural killer cell reflects the immunosenescence of innate immune,also,the tumor antigen presentation ability of dendritic cell is decreased.While,the decline of the CD8 + T cells cytotoxic effect and the secretion of tumor growth factor accounts for the immunosenescence of adaptive immunity.Intervention of immunosenescence may produce the novelty ideas of prevention and treatment of cancer.

Research advances in innate immunity against hepatitis B virus / 临床肝胆病杂志

When hepatitis B virus (HBV) invades the human body, innate immunity acts the earliest and plays an important role. When an adult is infected with HBV, HBV can often be eliminated spontaneously. However, if HBV infection occurs right after birth or when the patient is young, the disease tends to become chronic and affect the whole life. In the incipient stage of HBV infection, innate immune response plays an important role in inhibiting viral replication, and the prognosis of HBV infection depends on the combined effect of host and virus. This article briefly introduces the research advances in the cells, cytokines, and signaling pathways that play important roles in the host's innate immunity against HBV and their mechanisms of action, and points out their potential values in clinical treatment.

Research advances in innate immunity mechanism of nonalcoholic fatty liver disease / 临床肝胆病杂志

The pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD) are closely associated with the activation of the innate immune system. This article reviews how various types of immune cells, Toll-like receptors, and their downstream signaling pathways are involved in insulin resistance and mediate oxidative stress, inflammation, and fibrosis in the liver. Reduction or elimination of dendritic cells delays inflammatory responses and fibrosis in the liver. A decrease in natural killer T cells induces lipid accumulation at the stage of simple steatosis, but alleviates fibrosis at the inflammation stage. The mTOR signaling pathways for insulin and amino acids suppresses autophagy through short-term or long-term regulation, which leads to endoplasmic reticulum stress and altered insulin resistance, thereby modulating the development and progression of NAFLD. The research on the mechanisms by which traditional Chinese medicine offers therapeutic benefits for NAFLD increasingly focuses on the potential role of immunity.

Application prospects of research on pathogenesis of primary biliary cirrhosis / 临床肝胆病杂志

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the destruction of small intrahepatic bile ducts. Incomprehensible and complicated autoreactive responses participate in the development and progression of PBC, which involve various immune cells and inflammatory mediators. Based on the aspects of innate immunity and adaptive immunity, this article summarizes recent advances in the research on PBC pathogenesis at cellular and molecular levels and evaluates the clinical application of these studies. This article not only gives a feasible direction for researchers and clinicians in this study field, but also provides a theoretical basis for clinical diagnosis and novel therapeutic strategies.

Expression of mannose-binding lectin in lesions of psoriasis vulgaris / 中华皮肤科杂志

Objective To investigate the expression of mannose-binding lectin (MBL) in lesions of patients with psoriasis vulgaris,and to explore the relationship between MBL and psoriasis pathogenesis.Methods Immunohistochemistry and Western blot were performed to detect the expression of MBL in lesional and normalappearing perilesional skin of 30 patients with progressive psoriasis vulgaris,as well as in normal skin of 30 healthy human controls.Statistical analysis was carried out by t test using SPSS13.0 software.Results Immunohistochemistry showed that MBL was expressed in lesional psoriatic skin,but weakly expressed or absent in normalappearing perilesional skin and normal control skin,with the relative expression level of MBL in lesional skin significantly higher than that in perilesional skin and normal control skin (0.636 7 ± 0.515 1 vs.0.416 3 ± 0.160 1 and 0.381 6 ± 0.310 9,t =2.24,2.32,respectively,both P ＜ 0.05).Western blot revealed a positive expression of MBL protein in all the skin specimens,and the expression intensity of MBL protein in lesional psoriatic skin was significandy increased compared with perilesional psoriatic skin and normal control skin (0.273 1 ± 0.129 4 vs.0.186 3 ± 0.193 1 and 0.149 2 ± 0.268 7,t =2.05,2.28,respectively,both P＜ 0.05).No significant difference was shown in the expression of MBL protein between perilesional psoriatic skin and normal control skin by immunohistochemistry (t =1.51,P ＞ 0.05) or Western blot (t =0.61,P ＞ 0.05).Conclusion There is a high expression of MBL protein in lesions of patients with psoriasis vulgaris,which may be somewhat associated with the pathogenesis of psoriasis.

Immune -mediated liver failure / 临床肝胆病杂志

The primary causative factors of liver failure include direct damage and immune -mediated liver injury.Increasing evidence sug-gests that immune -mediated injury plays a pivotal role in the pathogenesis of liver failure.The new concepts concerning the mechanisms of immune -mediated liver injury in liver failure are reviewed with relevant basic and clinical studies in both humans and animals.The innate and adaptive immunity,particularly the interaction of various immune cells and molecules,as well as apoptosis -related molecules,are dis-cussed in detail.

Current status of research on liver innate immunity / 临床肝胆病杂志

Liver innate immunity plays an important role in the defense against pathogen invasion.The mechanisms of liver innate immunity for defending against pathogen invasion are reviewed,including the special anatomical and physiological characteristics of the liver,the fea-tures of innate immune cells in the liver (liver-settled cells and cells raised from blood circulation)and their function and relationship with each other in pathogen invasion,the process of pathogen identification and effect of liver innate immune cells,and the mechanism of liver immune injury and immune tolerance.Given current research on innate immune cells and innate immune molecules in the liver,further stud-ies should be conducted to understand the connection and difference between liver innate immunity and systemic immunity,thus promoting the diagnosis and treatment of liver diseases and deeper research.

Advances for toll-like receptors in cancer immunotherapy / 国际肿瘤学杂志

Toll like receptors(TLRs) , a pattern conservative receptor superfamily are found on mammalian cell surface over the last decade. TLRs recognize distinct pathogen - associated molecular patterns, which can lead not only to the responses of the innate immunity but also to the development of the antigenspecific adaptive immunity. The expression of TLRs have changed in some carcinomas, besides, microbial composition and drugs mediate the tumor immunotherapy by the way of TLRs signal transduction. Consequently , deep studies on TLRs will provide new approaches for tumor immunotherapy.

Study on specific humoral immune response in children with rotavirus diarrhea / 中国医师进修杂志

Objective To apply the theory basis for effectively preventing and treating rotavirus infection by studying on specific humoral immune response in children with rotavirus diarrhea. Methods Seventy-five patients of children (diarrhea group ) and 45 controls (control group) were selected. The antigen and specific antibody in plasma and stool were detected by ELISA method;the type of viral gene was confirmed by reverse transcription PCR method;the expression of mRNA in peripheral blood mononuclear cell was measured by fluorescent light quantitation PCR method. Results In diarrhea group, rotavirus G typing to G3 dominated, accounting for 77.3% (58/75), P sub-type to P8 mainly, accounting for 82.7% (62/75). Rotavirus-specific antibody titers of plasma in diarrhea group were significantly higher than those in control group, IgA antibody titers of stool increased significantly, not only higher than that in control group and plasma. The percentage of CD19+ cells in diarrhea group [(30.8 ± 7.9)%] was significantly higher than that in control group [(23.1 ± 7.7 )%] (P = 0.009 ). And the proportion of CD4+ cells decreased significantly (P = 0.005 ), the expression level of IL- 12p40 mRNA in the entire process in diarrhea group was significantly higher than that in control group(P＜ 0.01 ). Conclusion Children with acute rotavirus infection early in the immune response to specific humoral immunity, especially mucosal immune to significantly improve the main features.

The regulation mechanism of RIG-Ⅰ-like receptors in antiviral innate immune responses / 军事医学科学院院刊

Immune and tissue cells usually express pattern-recognition receptors (PRRs) to detect viruses and other microorganisms, thereby inducing signal cascade amplification and host innate immune responses. Since PRRs have strain-specific substrates and mechanisms of recognition, the identification of PRRs and mechanisms of PRRs-mediated responses is highly challenging. Besides, the research on RLRs-mediated immune responses has become more popular in cellular immunology recently. Accumulating evidence shows that post-translation modifications, such as ubiquitination, deubiquitination and ISGylation, play an important role in regulating host innate immune responses. In parallel, these approaches may be used by viruses to evade PRRs-mediated responses or to actively subvert these pathways for their own benefit. It was identified that STING (also called MITA/MPYS/ERIS) plays an important role in RIG-Ⅰ-like receptor(RLR) signaling as a type Ⅰ IFN stimulator, providing a special method for the research on complex host antiviral innate immune responses.

The reconstitutional profiles of peripheral blood natural killer cell,γδT lymphocyte and CD4+T cell in human immunodeficiency virus infected patients during one-year antiretroviral therapy / 中华内科杂志

To investigate the different reconstitutional profiles for acquired(CD4+ T cell)and innate(NK cell,γδT lymphocyte)immunity after highly active antiretroviral therapy(HAART).Methods The CD4+ CD4+,CD3+ CD4- CD8-,CD3- CD16/CD56+,CD4+ CD45 RA+ CD62 L+ and CD4+ CD45 RA- subsets were measured by flow cytometry.The dynamic changes of these subsets after HAART initiation were assessed in 59 patients who were followed for 12 months in resular 3-month visits.Results At baseline the cell counts of CD4+ T cells including its na(I)ve and memory subsets,NK cell and γδT cells in HIV/AIDS patients were all significantly lower than those of healthy individuals.There was a decrease of 2.33 lg copies/ml in HIV-1 RNA from baseline noted 1 month after initiation of treatment which was sustained through 12 months.CD4+ T cell count showed a bi-phase increase during treatment.The first rapid increase was mainly memory CD4+T cells and this followed by the second slow but steady increase of na(I)ve CD4+ T cells.Increases in NK cell and γδT cell were noted at 3 months of HAART and this restoration were different quantitatively when compared with the oge in CD4+ T cells.Conclusion HAART could induce a different quantitative restorational patterns in peripheral CD4+ T cells,NK cells and γδT cells.

Changes of natural killer cells and γδT lymphocytes in human immunodeficiency virus infected patients with different disease status / 中华传染病杂志

Objective To study the profile of peripheral natural killer cells(NK cells)and γδT lymphocytes in human immunodeficiency virus(HIV)infected patients with different disease status and to explore the pathogenesis of acquired immunodeficiency syndrome(AIDS).Methods Three hundred and eleven HIV/AIDS patients without antiviral treatment were enrolled in this study.The percentages and absolute numbers of CD4+T lymphocytes,NK cells,and γδT ceils were measured by flow cytometry.The patients were divided into 3 groups based to their CD4+T lymphocytes counts:low CD4+T lymphocytes group(L),patients with CD4+T lymphocytes <0.20×109L;middle CD4+T lymphocytes group(M),CD4+T lymphocytes counts between 0.20×109and 0.35×109L;high CD4+T lymphocytes group(H),patients with CD4+T lymphocytes counts >0.35×109L.Rank sum test of independent samples of two-group and multiple-group was performed using Mann-Whitney U test and Kruskal-Wallis test.Correlation analysis was done by Spearman and Pearson test. Results The median percentage and cell counts of NK cells(8.4%,103×106L) and γδT cells(3.4%,41×106L)in HIV/AIDS patients were all significantly lower than those of healthy individuals(Z=-5.029,Z=-7.723,Z=-2.437,Z=-6.063;all P<0.01).The median cell counts of CD4+T lymphocytes in L,M,H groups were 0.062×109L,0.276×109L and 0.482×109L,respectively.The median cell counts of NK cells in these 3 groups were 89×106L,97×106L and 146×106L,respectively.NK cell counts were not significantly different between L and M groups,whereas both of them were much lower than that of H group(Z=-3.392,P=-0.001,Z=-4.849,P<0.01,respectively).The median γδT cell counts of L,M and H group were 29×106L,43×106L and 59×106L,respectively.The differences between any 2 groups were not significant.Conclusion These data suggest that the decreasing levels of peripheral NK cells and γδT cells are different after HIV infection.

Toll-like receptor signal transduction

Toll-like receptors (TLRs) are the archetypal pattern recognition receptors in sensing exogenous pathogens. Activation of TLRs is a first line of defense of the immune system, leading to the activation and recruitment of neutrophils and macrophages to sites of infection and enhances antimicrobial activity. The TLR signaling through different intracellular molecules, such as MAP kinases and IkappaB kinases which are conserved signaling elements for many receptors, leads to a distinct set of proinflammatory gene expressions. However, how these pathways differentially and precisely control the transcription of identical genes remains largely unknown. Our review focuses on the details of up-to- date signaling molecules including negative regulators and their role in controlling innate immune response. We also stress the importance of developing systemic approaches for the global understanding of TLR signaling so that appropriate drug therapeutic targets can be identified for regulating inflammatory diseases.

Effect of Atorvastatin, a HMG-CoA Reductase Inhibitor, in Experimental Colitis in Mice

BACKGROUND: The statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are approved for cholesterol reduction, and may also be beneficial in the treatment of inflammatory disease. In this study, atorvastatin was tested in experimental colitis, a disease model of inflammatory bowel disease. METHODS: To induce colitis, dextran sodium sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS) were administrated to C57BL/6 or BALB/c mice. Mice were monitored daily for loss of body weight and survival for indicated days. Colon length and histology were examined after sacrifice. RESULTS: The administration of DSS induced marked colonic inflammation and shortening, and resulted in a loss of body weight. DSSinduced colitis was not affected by atorvastatin treatment, but in contrast, the administration of atorvastatin relieved TNBS-induced colitis with a resultant rapid recovery of weight loss and a reduction in colonic length shortening. Histologically, inflammatory cell infiltration in the colonic wall, mucosal ulceration and crypt disruption were also suppressed in atorvastatin treated mice. CONCLUSION: These results suggest that atorvastatin preserves intestinal integrity in colitis, probably via the modulation of Th cell-mediated immune response, in a manner independent of innate immunity.

Naturally occurring IgG anti-HLA alloantibody does not correlate with HIV type 1 resistance in Nairobi prostitutes.

In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV. In fact, 12% of the women were found to have serum IgG antibodies against class I alloantigens. However, this alloantibody did not correlate with the HIV status of the women and was found in a similar proportion of HIV-positive and HIV-resistant women. The observed levels of alloantibody did not increase with HIV infection in susceptible individuals, suggesting that potential antigenic mimicry between HIV and host HLA class I antigens does not significantly increase levels of anti-class I antibodies. The lack of correlation between serum anti-allo-class I HLA antibodies and the risk of sexual transmission indicates that this humoral immune response is unlikely to be the natural mechanism behind the HIV-resistance phenotype of persistently HIV-seronegative women. This result, however, does not preclude the further investigation of alloimmunization as an artificial HIV immunization strategy.

AIDS: nature's last laugh?

PIP: HIV has already shown that it can control population more effectively than any other discovery or invention over the past 2 centuries. Condom use can both block the transmission of HIV and prevent pregnancy, while the fear of contracting HIV will drive people to become more monogamous in their sexual relations. Early successes with antibiotics and vaccines led us to believe that humans could defy nature, and we continue to challenge the forces of nature, routinely choosing diseases to eradicate. AIDS, however, should teach humankind that every time it eradicates one disease, nature delivers 2 new ones. Unless humankind realizes and accepts its fallibility, it will be doomed. Mankind should try to increase individual immunity to pathogens, coexist with microscopic pathogens, and believe in the wisdom of our ancestors.^ieng