Regulation of T cells by myeloid-derived suppressor cells: emerging immunosuppressor in lung cancer.

Myeloid-derived suppressor cells (MDSCs), major components maintaining the immune suppressive microenvironment in lung cancer, are relevant to the invasion, metastasis, and poor prognosis of lung cancer, through the regulation of epithelial-mesenchymal transition, remodeling of the immune microenvironment, and regulation of angiogenesis. MDSCs regulate T-cell immune functions by maintaining a strong immunosuppressive microenvironment and promoting tumor invasion. This raises the question of whether reversing the immunosuppressive effect of MDSCs on T cells can improve lung cancer treatment. To understand this further, this review explores the interactions and specific mechanisms of different MDSCs subsets, including regulatory T cells, T helper cells, CD8 + T cells, natural killer T cells, and exhausted T cells, as part of the lung cancer immune microenvironment. Second, it focuses on the guiding significance confirmed via clinical liquid biopsy and tissue biopsy that different MDSC subsets improve the prognosis of lung cancer. Finally, we conclude that targeting MDSCs through action targets or signaling pathways can help regulate T-cell immune functions and suppress T-cell exhaustion. In addition, immune checkpoint inhibitors targeting MDSCs may serve as a new approach for enhancing the efficiency of immunotherapy and targeted therapy for lung cancer in the future, providing better comprehensive options for lung cancer treatment.

Protective effects of oridonin against osteoporosis by regulating immunity and activating the Wnt3a/ß-catenin/VEGF pathway in ovariectomized mice.

This study was performed with the aim of investigating the effect of oridonin (ORI) on estrogen deprivation-induced osteoporosis in mice and its mechanism. Animal experiments were used in this work to validate the anti-osteoporotic efficacy of ORI. Morphometric analysis was performed by micro-CT. A special protein meter was used to detect the content of immunoglobulin lgM, immunoglobulin lgG, complement C3 and C4 in the serum of mice. The expression of CD4+CD25+Foxp3+ Treg cell and CD4+/CD8+ lymphocyte subsets in mice was detected by flow cytometry. ELISA was used to detect the content of insulin-like growth factor (IGF-1), tumor necrosis factor (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6). In addition, key signaling molecules in the Wnt3a/ß-catenin signaling pathway were detected by Western blotting. The results showed that compared with the model group, the contents of calcium and phosphorus in the femurs of mice in the ORI groups were increased, and the spleen coefficient was decreased. The ALP activity in the serum of mice in the high and medium dose ORI groups was decreased, and the uterine coefficient was increased. ORI significantly increased the maximum bending load and the maximum bending stress of the femurs of mice, increased the number of trabeculae, and repaired the bone microstructure. At the same time, ORI could significantly increase the levels of immunoglobulin (lgG and lgM) and complement (C3 and C4), increase the activity of peritoneal macrophages in mice, increase the expression of CD4+CD25+Foxp3+ Tregs and CD4+/CD8+ in the spleen, increase the content of IGF-1, reduce the content of TNF-α, IL-1 and IL-6 and increase the expression levels of VEGF, Wnt3a, p-GSK3ß/GSK3ß and ß-catenin/Lamin in the femoral tissue. These results indicated that ORI might regulate the expression of VEGF through the Wnt3a/ß-catenin signaling pathway, improve the immunity of mice, maintain the balance of the immune system, and promote angiogenesis, thereby improving the bone mineral density and bone tissue morphology of mice and playing an anti-osteoporotic role.

Insights into health promoting effects and myochemical profiles of pine mushroom Tricholoma matsutake.

Tricholoma matsutake (TM) is a valuable edible mushroom that has attracted increasing attention due to its potential medicinal values and functional uses. However, the chemical composition and molecular mechanisms behinds TM are not specifically summarized yet. Hence, this review aims to systematically analyze the research progress on the characterization of chemical compositions and the reported health effects of TM in the last 20 years. The myochemical profiles of TM consist of proteins with amino acids, fatty acids, nucleic acids with their derivatives, polysaccharides, minerals, volatile components, phenolic compounds, and steroids. The bioactive substances in TM exert their health effects mainly by regulating body immunity and restoring the balance of the redox system. NF-κB signaling pathway and its downstream cytokines such as TNF-α and IL-6 are the key molecular mechanisms. In addition, MAPK, PI3K-Akt, and JAK-STAT are also involved. NF-κB, MAPK, and PI3K-Akt are also highly related to cancer regulation and thus TM has great anticancer potential. Considering that most studies have only investigated the dosage and inhibition rate of TM on cancer cell lines, more extensive studies need to focus on the specific molecular mechanisms behind these anticancer effects in the future.

Glycolysis in tumor microenvironment as a target to improve cancer immunotherapy.

Cancer cells and immune cells all undergo remarkably metabolic reprogramming during the oncogenesis and tumor immunogenic killing processes. The increased dependency on glycolysis is the most typical trait, profoundly involved in the tumor immune microenvironment and cancer immunity regulation. However, how to best utilize glycolytic targets to boost anti-tumor immunity and improve immunotherapies are not fully illustrated. In this review, we describe the glycolytic remodeling of various immune cells within the tumor microenvironment (TME) and the deleterious effects of limited nutrients and acidification derived from enhanced tumor glycolysis on immunological anti-tumor capacity. Moreover, we elucidate the underlying regulatory mechanisms of glycolytic reprogramming, including the crosstalk between metabolic pathways and immune checkpoint signaling. Importantly, we summarize the potential glycolysis-related targets that are expected to improve immunotherapy benefits. Our understanding of metabolic effects on anti-tumor immunity will be instrumental for future therapeutic regimen development.

Anti-miR33 therapy improved hepatopancreatic lipid and immune metabolism disorders in grass carp, Ctenopharyngodon idella.

Lipid metabolism disorders are found ubiquitously in farmed fish and occur as a result of excessive fat accumulation. Previous studies have found that miR-33 is involved in lipid metabolism; however, its role in fish lipid metabolism is unclear. We sought to clarify this relationship in grass carp in vivo and in vitro. Our findings revealed the length of miR-33 to be 65 bp. Phylogenetic tree analysis showed that grass carp miR-33 was most closely related to fish miR-33 (Siganus canaliculatus). Hepatocytes transfected with miR-33 mimic displayed markedly raised TG content (P < 0.05) as well as increased levels of lipid synthesis-related transcription factors (P < 0.05). Compared with blank and saline groups, total serum cholesterol, AST, and LDL levels were suppressed in groups treated with the miR-33 antagomir (P < 0.05). Moreover, the expression levels of PPARγ and SREBP-1c mRNA were significantly decreased in contrast to those found in the control group (P < 0.05). Similar findings were noted in the expression of immune-related proinflammatory molecules (TNFα, IL-1ß, IL-6, and NF-κB), which also demonstrated decreased levels (P < 0.05). Conversely, high expressions of anti-inflammatory factors (TGF-ß1 and IL-10) were noted (P < 0.05). This investigation strongly supports the role of miR-33 in hepatopancreas-based lipid metabolism and immunity. miR-33 may have been highly conserved in early vertebrates in order to facilitate liver-specific metabolic and immunomodulatory functions. Our findings provide a basis for further investigations exploring the mechanisms surrounding fish lipid metabolism and may aid in preventing and treating immunocompromised fish as well as fish with fatty hepatopancreas, and other metabolic diseases.

Changes in the MicroRNA Profile of the Giant Panda After Canine Distemper Vaccination and the Integrated Analysis of MicroRNA-Messenger RNA.

Canine distemper (CD) is a significant threat to wild and captive giant panda populations. Captive giant pandas are inoculated with canine distemper virus (CDV) vaccination to prevent the infection with the CDV. As an important regulator, microRNA (miRNA) plays a crucial role in regulating gene expression, including in disease immunity. To understand the role of miRNA in immune response to CDV vaccination, we investigated the miRNA expression profile in five giant panda cubs after two inoculations, 21 days apart. A total of 187 conserved miRNAs and 96 novel miRNAs were identified. Among the 187 conserved miRNAs, 29 differentially expressed miRNAs were found postinoculation. The upregulation of miR-16, miR-182, miR-30b, and miR-101 indicated that the innate immune may be enhanced, whereas the upregulation of miR-142 and miR-19a are probably involved in the enhanced cellular immune response. However, the downregulated miR-155 and miR-181a might indicate the giant panda has weak ability to produce antibodies and memory B cells. Integrated analysis of miRNA-messenger RNA (mRNA) found 20 negatively regulated miRNA-mRNA pairs, where downregulated miR-204 might enhance giant panda cub innate immunity by increasing TLR6 expression, and downregulated miR-330 might activate macrophages and regulate the immune response by increasing TMEM106A expression. Our research provides key information for future development to enhance the immune response of giant pandas and potentially improve the survival of captive and wild giant panda populations threatened by CD.

Mechanism of Chinese Medicine Against Sjögren Syndrome： A Review / 中国实验方剂学杂志

Sjögren syndrome （SS） is a chronic autoimmune disease characterized by immune cell infiltration and progressive destruction of salivary and lacrimal glands. It not only affects the lacrimal and salivary glands， manifested as dry eyes and dry mouth， but also involves heart， lung，kidney，and central nervous system， seriously affecting human physical and mental health. Although western medicine has made extensive and in-depth research on the diagnosis and treatment of this disease in recent years，there is no effective treatment targeting the potential causes. Chinese medicine emphasizes the concept of holism，treatment and prescription formulation based on syndrome differentiation， and effect exertion via multiple targets，multiple levels，and multiple pathways，exhibiting great advantages in the treatment of SS. This paper reviews the mechanisms of Chinese medicine in treating SS from the perspectives of immunity regulation，aquaporin up-regulation， and anti-oxidative stress reported in the related literature，so as to provide more theoretical basis for the research and clinical treatment of SS.

Effect of Fuzheng Kangai Decoction on Immune Regulation and Inhibition of Tumor Growth in Rats with Ovarian Carcinoma / 中国实验方剂学杂志

Objective:To explore the effect of Fuzheng Kangai decotion （FZKAD） on the immune regulation and the inhibition of tumor growth in rats with ovarian carcinoma. Method:Kunming mice were randomly divided into normal group， lentinan （0.05 g·kg^-1） group， and high （27.3 g·kg^-1）， medium （13.65 g·kg^-1） and low （6.825 g·kg^-1） dose groups of FZKAD， with 10 mice in each group， serum hemolytic value （HC₅₀）， antibody-forming cells and the phagocytosis of mononuclear macrophages were measured. Fischer 344 rat xenograft model was established through inoculation of NUTU-19 cell in the right axilla， and the model rats were randomly divided into model group， cisplatin group （0.002 g·kg^-1）， and high （18.9 g·kg^-1）， medium （9.45 g·kg^-1）， and low （4.725 g·kg^-1） dose groups of FZKAD， with 10 rats in each group， in addition， 10 healthy rats were randomly selected as the normal group. Tumor quality， tumor inhibition rate， T lymphocyte subsets， and expressions of serum cytokines， enhancer binding protein homologous protein 1（XBP1） and enhancer binding protein homologous protein （CHOP） protein in tumor tissues were detected after 14 days of administration. Result:Compared with normal group， HC₅₀， level of antibody-forming cells， phagocytic index and phagocytic activity of mice in high， medium and low-dose groups of FZKAD were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Tumor quality and XBP1 protein expression in high， medium and low-dose groups of FZKAD were significantly decreased （<italic>P</italic><0.01） compared with the model group， while the tumor inhibition rate， CD4⁺， CD8⁺ T cell ratio， CD4⁺/CD8⁺ ratio， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-2 （IL-2）， <italic>γ-</italic>interferon （IFN-<italic>γ</italic>） expression and CHOP protein expression were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:FZKAD can improve the immune function of normal mice and inhibit the tumor growth in rats with ovarian carcinoma， and the immunity regulation effect is the main mechanism.

Network pharmacology reveals the multiple mechanisms of Xiaochaihu decoction in the treatment of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver (NAFLD) is a chronic disease worldwide, which poses a huge threat to human health. Xiaochaihu decoction is a well-known traditional Chinese medicine prescription. It has been proven effective in treating NAFLD but its mechanism is still unclear. OBJECTIVE: Multiple mechanisms of Xiaochaihu decoction are explored by identifying and connecting potential targets and active ingredients in the treatment of NAFLD. METHODS: Active ingredients and related targets of seven herbs were collected from TCMSP database. The related targets of NAFLD were obtained from Genes cards database, TDD and OMIM database. The intersected targets of disease targets and drug targets were input into STRING database to construct protein-protein interaction network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis. RESULTS: After screening and removal of duplicates, a total of 145 active ingredients and 105 potential targets were obtained. PPI network manifested that AKT1, IL6, JUN MAPK8 and STAT3 were the key target proteins. The results of GO enrichment analysis mainly involved cytokine receptor binding, cytokine activity, and heme binding. The results of KEGG analysis suggested that the mechanism mainly involved in AGE-RAGE signaling pathway in diabetic complications, Hepatitis C, fluid shear stress and atherosclerosis. The signaling pathways were further integrated as network manner, including AGE-RAGE signaling pathway in diabetic complications, Fluid shear stress and atherosclerosis, Insulin resistance, HIF-1 signaling pathway, Th17 cell differentiation and IL-17 signaling pathway. The network contained immunity regulation, metabolism regulation and oxidative stress regulation. CONCLUSION: Xiaochaihu decoction plays a key role in the treatment of NAFLD with multiple targets and pathways. Immunity regulation, metabolism regulation and oxidative stress regulation consist of the crucial regulation cores in mechanism. GRAPHICAL ABSTRACT: Design and workflow of this study.

Discovery of dihydropyrrolidones as novel inhibitors against influenza A virus.

More effective prophylactic and therapeutic strategies to combat influenza viruses are urgently required worldwide because the conventional anti-influenza drugs are facing drug resistance. Here, dihydropyrrolidones (DHPs), the products of an efficient multi-components reaction, were found to possess good activities against influenza A virus (IAV). Primary structure-activity relationship indicated that the activities of DHPs were greatly influenced by substituents and four of them had IC50 values lower than 10 µM (DHPs 5-2, 8, 14 and 19: IC50 = 3.11-9.23 µM). The activities against multiple IAV strains and mechanism of DHPs were further investigated by using 5-2 (IC50 = 3.11 µM). It was found that 5-2 possessed antiviral effects against all the investigated subtypes of IAVs with the IC50 values from 3.11 to 7.13 µM. Moreover, 5-2 showed very low cytotoxicity with CC50 > 400 µM. Results of mechanism study indicated that 5-2 could efficiently inhibit replication of IAV, up-regulate the expression of key antiviral cytokines IFN-ß and antiviral protein MxA, and suppress the production of the NDAPH oxidase NOX1 in MDCK cells. These results indicated that 5-2 could be used as a potential inhibitor against wide subtypes of IAVs.

MicroRNAs and microbiota: Is there a cross talk?

MicroRNAs (miRNAs) are a form of single-stranded RNA molecules with a length that varies between 18 and 23 nucleotides and which are synthesized in the nucleus but function in the cytoplasm. miRNAs function endogenously and bind to complementary sequences in either the coding regions or the 3' untranslated regions (UTRs) of target messenger RNAs (mRNAs). This indicates that miRNAs operate in a post-transcriptional manner. miRNAs play essential roles in various biological events, and have thus been found extracellularly in different body fluids such as saliva, urine and plasma. miRNAs are distinguished in the gut mainly by examining content from intestines and feces. The gastrointestinal tract is infested with a variety of microorganisms that are initially inherited from the mother; however, those microorganisms develop as a result of changes in dietary intakes and environmental factors. The gut microbiota are therefore shaped differently in different individuals due to several contributing factors such as genetics, diet and state of disease, and have a great impact on the host during phases of disease and homeostasis.

MicroRNAs involved in innate immunity regulation in the sea cucumber: A review.

The sea cucumber is one of the most economically significant echinoderms. The immunity against exogenous stimulation of sea cucumber is of great academic and economic importance. MicroRNAs (miRNAs) are a class of short endogenous non-coding RNAs (ncRNAs) that are considered as vital regulators of both innate and adaptive immune responses in most eukaryotes. In sea cucumbers, some miRNAs (such as miR-133, miR-137, and miR-2008, among others) that participate in the regulation of innate immunity have been recently identified and characterized. This review focuses on those known miRNAs and their corresponding target genes that participate in the regulation of the complement system, Toll-like receptor (TLR) pathway, reactive oxygen species (ROS) production and apoptosis pathways in sea cucumbers. Moreover, we cover immune-related miRNA investigations in sea cucumbers that provide insights into developing more miRNA-based biomarkers and therapeutic strategies for sea cucumber diseases.

Research progress on anti-aging pharmacological effects and mechanisms of plant essential oil / 中草药

Plant essential oil not only has functions of anti-oxidative and scavenging free radicals activities, piliation promotion, osteoporosis prevention, body immunity regulation and other anti-physiological aging effects, but also has anti-pathogenic aging effects such as regulating neurodegenerative diseases, cardiovascular and cerebrovascular diseases, osteoarthritis and cancer. This paper introduces the research and progress of the pharmacological effects and mechanisms of anti-aging effects of plant essential oils by introducing the concept and mechanism of aging, and discusses the application prospects, development advantages and existing problems of plant essential oils in the anti-aging field.

New progress in pharmacological action of paeoniflorin / 中草药

Paeoniflorin is the main effective component of Paeoniae lactiflora and Paeonia suffruticosa. A large number of studies have proven that paeoniflorin has many pharmacological effects, such as anti-depression, anti-inflammation, analgesia, anti-tumor, liver protection, nerve protection, sedation and hypnosis, immunomodulation and so on. It has little toxic and side effects and has been highly concerned by people. At present, paeoniflorin is rarely used in clinical practice in the form of monomers. This article mainly refers to the related research literatures on paeoniflorin pharmacological action in recent three years, combs and summarizes the new progress of its pharmacological action research. The relationship between the drug effect and the prescription of traditional Chinese medicine was discussed, in order to provide a reference for further development and clinical application of paeoniflorin.

Anti-tumor Effect of Astragaloside by Inducing M1 Macrophage Polarization / 中国实验方剂学杂志

Objective:To investigate the effect of astragaloside on the macrophage polarization and the possible anti-tumor immunity mechanism of astragaloside. Method:The cytotoxic effect of different concentrations of astragaloside at different time points on macrophage was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT), in order to choose the suitable concentration of astragaloside, macrophages were co-cultured with tumor cells at the ratio 1:1, and the effect of astragaloside on macrophage-mediated lysis of tumor cells was performed by biophotonic cytotoxicity assay after the mixed cells were effected with 0.1 mg·L-1 astragaloside for 24 h. Macrophages were dealt with 0.1 mg·L-1 astragaloside for 24h, the expressions of CD16/32 and CD206 in macrophages were performed by flow cytometry, the mRNA expressions of macrophage inducible nitric oxide synthase (iNOS), Arginine-1 (Arg-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were measured by Real-time PCR, the protein expressions of macrophage signal transducers and activators of transcription 1 (STAT1) and phosphorylation signal transducers and activators of transcription 1 (p-STAT1) were determined by Western blot. Result:Astragaloside had no effect on the viability of macrophages with 0.1 mg·L-1. Compared with control group, astragaloside obviously enhanced the macrophage-mediated lysis of tumor cells according to the biophotonic cytotoxicity assay, induced the M1 macrophage marker CD16/32 expression according to flow cytometry, increased the mRNA expressions of iNOS, IL-1β, TNF-α and IL-12 according to the Real-time PCR, and promoted the phosphorylation of STAT1 in macrophages on the basis of Western blot. Conclusion:Astragaloside could induce M1 macrophage polarization by increasing the phosphorylation of STAT1, and initiate macrophage-related anti-tumor immunity response.

Advances in pharmacological research on Dendrobii Caulis based on strengthening enterogastric function / 中草药

Dendrobii Caulis was traditionally used for promoting middle energizer, strengthening enterogastric function to light body weight, and prolonging life according to Shennong's Classic of Materia Medica and many other previous ancient books of traditional Chinese medicine. The stomach and intestine tonic effect is still approved in modern society and broadly applied in clinic, whose efficacy has been featured as replenishing yin for maintaining gastric tonicity, enhancing the production of body fluid, and clearing away heat in Chinese Pharmacopoeia 2015. This review firstly made a summary of ancient literature on strengthening enterogastric function of Dendrobii Caulis, combined with literature of modern pharmacological research and clinical application from literature search system, such as CNKI, etc. It was summarized that Dendrobii Caulis had broad bioactivities in enterogastric system including gastric mucosa protection, digest-promotion, intestinal flora modulation, intestinal immunity regulation, stimulation of digestive juice secretion, etc. Furthermore, present situation of product development was analyzed based on patent and health product search system. This review could provide a reference for further development and clinical application of Dendrobii Caulis.

Experimental Study on Antitumor Activities and Immunity Regulation of Hedyotis Diffusa Willd Injection / 中国中医药信息杂志

Objective To study the antitumor activities and immunity regulation of Hedyotis diffusa Willd injection. Methods Inhibitory effects of Hedyotis diffusa Willd injection on cell proliferation was detected with MTT method. Then the inhibitive rate was calculated. The immunomdulatory effects of Hedyotis diffusa Willd injection were investigated. Results Hedyotis diffusa Willd injection inhibited the proliferation of A549, SGC-7901, HEP-G2, Helacells in the dose of 100～20 ?g/mL, and enhance the immunity regulation on S180 tumor transplanted in mice. Conclusion Hedyotis diffusa Willd injection has the antitumor activities and can enhance the immunity.