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1.
Microb Pathog ; 190: 106614, 2024 May.
Article in English | MEDLINE | ID: mdl-38492825

ABSTRACT

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.


Subject(s)
Aeromonas hydrophila , Antioxidants , Carps , Eleutherococcus , Fermentation , Fish Diseases , Lacticaseibacillus rhamnosus , Probiotics , Animals , Lacticaseibacillus rhamnosus/metabolism , Carps/microbiology , Probiotics/pharmacology , Probiotics/administration & dosage , Antioxidants/metabolism , Fish Diseases/prevention & control , Fish Diseases/microbiology , Fish Diseases/immunology , Gram-Negative Bacterial Infections/veterinary , Gram-Negative Bacterial Infections/prevention & control , Gram-Negative Bacterial Infections/immunology , Animal Feed , Inflammation/prevention & control , Cytokines/metabolism , Aquaculture
2.
Heliyon ; 9(7): e18224, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37539255

ABSTRACT

Background: Folic acid and zinc supplements have been used to treat male infertility, but their efficacy is still debated. Objective: To systematically evaluate the effects of folic acid and folic acid plus zinc supplements on sperm characteristics and pregnancy outcomes of infertile men. Methods: An online systematic search was performed using PubMed, Cochrane Library, and EMBASE databases from inception to August 1, 2022. The goal was to identify randomized controlled trials (RCTs) that used folic acid or folic acid plus zinc to improve sperm characteristics of infertile men. Data were extracted by two investigators who independently screened the literature and assessed for quality according to the criteria. The meta-analysis was performed using RevMan 5.4 software. Results: A total of 8 RCT studies involving 2168 patients were included. The results showed that compared with the controls, folic acid significantly increased sperm motility (MD, 3.63; 95% CI, -1.22 to 6.05; P = 0.003), but did not affect the sperm concentration (MD, 2.53; 95% CI, -1.68 to 6.73; P = 0.24) and sperm morphology (MD, -0.02; 95% CI, -0.29 to 0.24; P = 0.86) in infertile men. Folic acid plus zinc did not affect sperm concentration (MD, 1.87; 95% CI, -1.39 to 5.13; P = 0.26), motility (MD, 1.67; 95% CI, -1.29 to 4.63; P = 0.27), and morphology (MD, -0.05; 95% CI, -0.27 to 0.18; P = 0.69) in infertile men. Secondary results showed that compared with a placebo, folic acid alone had a higher rate of pregnancy in transferred embryos (35.6% vs. 20.4%, P = 0.082), but the difference was not significant. Folic acid plus zinc did not affect pregnancy outcomes. Conclusions: Based on the meta-analysis, no significant improvements in sperm characteristics with folic acid plus zinc supplements were seen. However, folic acid alone has demonstrated the potential to improve sperm motility and in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) outcomes. This indicates that folic acid supplements alone may be a viable treatment option for male infertility.

3.
Cancer Cell ; 41(6): 1134-1151.e10, 2023 06 12.
Article in English | MEDLINE | ID: mdl-37172581

ABSTRACT

Glioblastomas are aggressive brain tumors that are largely immunotherapy resistant. This is associated with immunosuppression and a dysfunctional tumor vasculature, which hinder T cell infiltration. LIGHT/TNFSF14 can induce high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), suggesting that its therapeutic expression could promote T cell recruitment. Here, we use a brain endothelial cell-targeted adeno-associated viral (AAV) vector to express LIGHT in the glioma vasculature (AAV-LIGHT). We found that systemic AAV-LIGHT treatment induces tumor-associated HEVs and T cell-rich TLS, prolonging survival in αPD-1-resistant murine glioma. AAV-LIGHT treatment reduces T cell exhaustion and promotes TCF1+CD8+ stem-like T cells, which reside in TLS and intratumoral antigen-presenting niches. Tumor regression upon AAV-LIGHT therapy correlates with tumor-specific cytotoxic/memory T cell responses. Our work reveals that altering vascular phenotype through vessel-targeted expression of LIGHT promotes efficient anti-tumor T cell responses and prolongs survival in glioma. These findings have broader implications for treatment of other immunotherapy-resistant cancers.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Mice , Animals , Glioma/genetics , Glioma/therapy , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Brain Neoplasms/blood supply , Glioblastoma/genetics , Phenotype , Brain , Tumor Microenvironment
4.
Front Nutr ; 10: 1158158, 2023.
Article in English | MEDLINE | ID: mdl-37090775

ABSTRACT

Cyclocarya paliurus (C. paliurus), a nutritional and nutraceutical resource for human and animal diets, has been constantly explored. The available biological components of C. paliurus were triterpenoids, polysaccharides, and flavonoids. Recent studies in phytochemical-phytochemistry; pharmacological-pharmacology has shown that C. paliurus performed medicinal value, such as antihypertensive, antioxidant, anticancer, antimicrobial, anti-inflammatory and immunological activities. Furthermore, C. paliurus and its extracts added to drinks would help to prevent and mitigate chronic diseases. This review provides an overview of the nutritional composition and functional applications of C. paliurus, summarizing the research progress on the extraction methods, structural characteristics, and biological activities. Therefore, it may be a promising candidate for developing functional ingredients in traditional Chinese medicine. However, a more profound understanding of its active compounds and active mechanisms through which they perform biological activities is required. As a result, the plant needs further investigation in vitro and in vivo.

5.
Acta Pharmaceutica Sinica ; (12): 1464-1474, 2023.
Article in Chinese | WPRIM | ID: wpr-978739

ABSTRACT

Plasma nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving kidney deficient in mice of Polygoni Multiflori Radix Praeparata. Thirty-five ICR mice were randomly divided into the control group, the model group, the BB24 h (braising with black bean sauce for 24 hours) group, the BB32 h group, and the BB40 h group. Biochemical indices in blood plasma of mice were measured by collecting eye blood after modeling. Changes in plasma endogenous metabolites of mice from each group were determined by ultra-performance liquid chromatography-linear trap quadrupole-orbitrap XL (UPLC-LTQ-orbitrap XL), and differential metabolites were screened. The results of pharmacodynamic investigation showed that compared to the model group, the levels of estradiol increased obviously in the BB24 h (P < 0.05), and the levels of cortisol increased obviously in BB32 h (P < 0.05). The hormone level of mice with kidney deficiency was significantly improved after taking processed Polygonum multiflorum. A total of 70 differential endogenous metabolites in blood plasma of mice were identified from all treatment groups, which mainly involved glycerophospholipid meta-bolism, arachidonic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism. The study indicated that Polygoni Multiflori Radix Praeparata may play the role of tonifying liver and kidney by improving the disorder of hypothalamic-pituitary-adrenal axis and regulating lipid metabolism in mice. Correlation analysis on differential metabolites in blood plasma and the chemical constituents showed that stilbene glycosides and saccharides may be the key pharmacodynamic material basis. The present study provides a new reference and theoretical foundation for revealing the potential pharmacodynamic material basis and mechanism investigation on tonifying liver and kidney of Polygoni Multiflori Radix Praeparata. This study was carried out following the ethical guidelines and regulations for the use of laboratory animals of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and passed the animal experimental ethical review [No. SYXK (Jing) 2019-0003].

6.
Phytother Res ; 37(5): 1823-1838, 2023 May.
Article in English | MEDLINE | ID: mdl-36581492

ABSTRACT

Total saponins of Panax ginseng (TSPG) have antidepressant effects. However, the underlying antidepressant mechanism of TSPG remains not clear. This study aimed to predict the mechanism of TSPG by bioinformatics analysis and to verify it experimentally. Bioinformatics analysis showed that the antidepressant effects of TSPG may be related to inflammation, and CX3CL1/CX3CR1 may play a key mediating role. Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and TSPG (50 mg/kg/d, 100 mg/kg/d) was administered throughout the modeling period. It was found that TSPG improves depressive behavior and reduces neuropathic damage in the hippocampus in rats. Meanwhile, TSPG decreased mRNA and protein expression of pro-inflammatory cytokines and CX3CL1/CX3CR1 and inhibited P38 and JNK protein phosphorylation in the hippocampus. Rat astrocytes were employed to explore further the potential mechanism of TSPG in regulating CX3CL1/CX3CR1. The results showed that CX3CL1 small interfering RNA (siRNA-CX3CL1) and CX3CR1 inhibitor (JMS-17-2) had similar effects to TSPG, that is, reduced inflammatory response, reactive oxygen species (ROS), and phosphorylation of P38 and JNK proteins, while overexpression of CX3CL1 (pcDNA-CX3CL1) counteracted the above effects of TSPG. It is suggested that the antidepressant effect of TSPG may be achieved through inhibition of CX3CL1/CX3CR1.


Subject(s)
Panax , Saponins , Rats , Animals , Saponins/pharmacology , Neuroinflammatory Diseases , Panax/metabolism , Rats, Wistar , Cytokines/metabolism , Chemokine CX3CL1 , CX3C Chemokine Receptor 1/metabolism
7.
Front Pharmacol ; 13: 1033919, 2022.
Article in English | MEDLINE | ID: mdl-36386126

ABSTRACT

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments. Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR). Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum. Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence.

8.
Fish Shellfish Immunol ; 131: 682-696, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36341871

ABSTRACT

Aeromonas hydrophila, a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila, regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection.


Subject(s)
Carps , Fish Diseases , Gram-Negative Bacterial Infections , Probiotics , Sanguisorba , Animals , Aeromonas hydrophila/physiology , Disease Resistance , Goldfish , Immunity , Plant Extracts , Probiotics/pharmacology
10.
J Clin Invest ; 132(9)2022 05 02.
Article in English | MEDLINE | ID: mdl-35499082

ABSTRACT

The trace element iron affects immune responses and vaccination, but knowledge of its role in autoimmune diseases is limited. Expansion of pathogenic T cells, especially T follicular helper (Tfh) cells, has great significance to systemic lupus erythematosus (SLE) pathogenesis. Here, we show an important role of iron in regulation of pathogenic T cell differentiation in SLE. We found that iron overload promoted Tfh cell expansion, proinflammatory cytokine secretion, and autoantibody production in lupus-prone mice. Mice treated with a high-iron diet exhibited an increased proportion of Tfh cell and antigen-specific GC response. Iron supplementation contributed to Tfh cell differentiation. In contrast, iron chelation inhibited Tfh cell differentiation. We demonstrated that the miR-21/BDH2 axis drove iron accumulation during Tfh cell differentiation and further promoted Fe2+-dependent TET enzyme activity and BCL6 gene demethylation. Thus, maintaining iron homeostasis might be critical for eliminating pathogenic Th cells and might help improve the management of patients with SLE.


Subject(s)
Iron , Lupus Erythematosus, Systemic , Animals , Cell Differentiation , Epigenesis, Genetic , Humans , Hydroxybutyrate Dehydrogenase/genetics , Mice , T-Lymphocytes, Helper-Inducer
11.
Biol Trace Elem Res ; 200(4): 1750-1762, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34185276

ABSTRACT

Mastitis caused by Staphylococcus aureus infection not only causes serious economic losses, but also affects human health. Se plays an important role in body immunity. However, the mechanisms by which Se regulates mastitis induced by S. aureus are still principally unknown. The purpose of this study is to investigate whether Se can inhibit mastitis induced by S. aureus through regulation of MerTK. Sixty BALB/c female mice were fed low, normal, or high Se concentrations for 7 weeks and then randomly divided into six groups (Se-Low Control group (LSN), Se-Normal Control group (NSN), Se-High Control group (HSN), Se-Low S. aureus group (LSS), Se-Normal S. aureus group (NSS), Se-High S. aureus group (HSS)). The regulation of Se on MerTK was detected via histopathological staining, western blot analysis, enzyme-linked immunosorbent assay, and qRT-PCR. With increased selenium concentrations, the levels of IL-1ß, IL-6, and TNF-α decreased, while the phosphorylation levels of MerTK, PI3K, AKT, and mTOR increased. Therefore, this study showed that Se could alleviate S. aureus mastitis by activating MerTK and PI3K/AKT/mTOR pathway.


Subject(s)
Mastitis , Selenium , Staphylococcal Infections , Animals , Female , Humans , Inflammation/drug therapy , Inflammation/metabolism , Mastitis/metabolism , Mice , Mice, Inbred BALB C , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Selenium/metabolism , Selenium/pharmacology , Staphylococcal Infections/metabolism , Staphylococcus aureus/metabolism , TOR Serine-Threonine Kinases , c-Mer Tyrosine Kinase
12.
Phytomedicine ; 93: 153792, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34735906

ABSTRACT

BACKGROUND: Kai Xin San (KXS) was widely applied for the treatment of depression for thousands of years. However, the underlying antidepressant mechanism of KXS remains not clear. PURPOSE: This study aimed to investigate whether NLRP3 inflammasome and autophagy are involved in inflammation-induced depression and antidepressant mechanism of KXS. METHODS: Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and KXS (3, 5, and 10 g/kg/d) was administrated during the last 2 weeks of CUMS procedure. The effects of KXS on depressive-like behaviors, neuroinflammation, NLRP3 inflammasome activation, and autophagy were investigated in CUMS rats. Rat astrocytes were employed to further explore the potential mechanism of KXS in regulating NLRP3 inflammasome and autophagy. Autophagy inhibitor 3-methyladenine (3-MA, 5 mM) was used in vitro to elucidate the role of autophagy in the antidepressant mechanism of KXS. RESULTS: In vivo, KXS improved depressive-like behaviors of CUMS rats in sucrose preference test, open field test and forced swimming test. Moreover, KXS inhibited the neuroinflammation induced by CUMS and promoted autophagy in prefrontal cortex of rats. The results in vitro further validated the anti-inflammatory and proautohapgic effects of KXS. More importantly, autophagy inhibitor 3-MA diminished the inhibitory effect of KXS on NLRP3 inflammasome activation in rat astrocytes. CONCLUSION: KXS ameliorated CUMS-induced depressive behaviors in rats and inhibited the NLRP3 inflammasome-mediated inflammation in vivo and in vitro. These effects might be regulated by KXS-induced autophagy.


Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Antidepressive Agents/pharmacology , Autophagy , Disease Models, Animal , Drugs, Chinese Herbal , Rats , Rats, Wistar , Stress, Psychological
13.
Clin Transl Immunology ; 10(9): e1338, 2021.
Article in English | MEDLINE | ID: mdl-34584694

ABSTRACT

OBJECTIVE: The benefit of Se supplementation in rheumatoid arthritis (RA) has been tested in clinical trials, but results remain inconclusive. The objective of this study was to specifically investigate the potential benefit of supranutritional Se by examining human samples from an area with supranutritional Se intake and testing a mouse model of RA. METHODS: Peripheral blood mononuclear cells (PBMCs) from RA patients (N = 57) and healthy controls (HC, N = 71) from an area of supranutritional Se intake (Enshi, Hubei, China) were analysed by flow cytometry. Serum cytokine and Se levels were measured by cytometric beads array (CBA) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. With sufficient or supranutritional selenium intake, mice were induced with collagen-induced arthritis (CIA) and examined for disease activity and immunopathology. The influence of Se supplementation in the generation of RANKL-expressing osteoclastogenic CD4+ T cells was investigated by in vitro assays. RESULTS: In Enshi city, HC showed the above-normal concentrations of serum Se concentrations while RA patients were enriched in the normal range (70-150 ng mL-1) or below. RA patients with higher Se levels demonstrated milder disease and lower levels of C-reactive protein, IL-6, RANKL and Th17 cells. In the mouse CIA model, supranutritional Se supplementation delayed disease onset, ameliorated joint pathology and reduced CD4+CD44+RANKL+ T cells. Se supplementation could suppress RANKL expression in cultured mouse Th17 cells. CONCLUSION: Supranutritional Se suppresses RANKL-expressing osteoclastogenic CD4+ T cells and could be beneficial to RA, which warrants formal testing in randomised clinical trials.

14.
Front Pharmacol ; 12: 726035, 2021.
Article in English | MEDLINE | ID: mdl-34531749

ABSTRACT

Atopic dermatitis (AD), also known as atopic eczema, is one of the most common skin diseases and is characterized by allergic skin inflammation, redness, and itchiness and is associated with a hyperactivated type 2 immune response. The leading causes of AD include an imbalance in the immune system, genetic predisposition, or environmental factors, making the development of effective pharmacotherapies complex. Steroids are widely used to treat AD; however, they provide limited efficacy in the long term and can lead to adverse effects. Thus, novel treatments that offer durable efficacy and fewer side effects are urgently needed. Here, we investigated the therapeutic potential of Huangbai Liniment (HB), a traditional Chinese medicine, using an experimental AD mouse model, following our clinical observations of AD patients. In both AD patient and the mouse disease model, HB significantly improved the disease condition. Specifically, patients who received HB treatment on local skin lesions (3-4 times/day) showed improved resolution of inflammation. Using the 1-Chloro-2,4-dinitrobenzene (DNCB)-induced AD model in BALB/c mice, we observed that HB profoundly alleviated severe skin inflammation and relieved the itching. The dermatopathological results showed markedly reversed skin inflammation with decreased epidermal thickness and overall cellularity. Correspondingly, HB treatment largely decreased the mRNA expression of proinflammatory cytokines, including IL-1ß, TNF-α, IL-17, IL-4, and IL-13, associated with declined gene expression of IL-33, ST2, and GATA3, which are connected to the type 2 immune response. In addition, HB restored immune tolerance by promoting regulatory T (TREG) cells and inhibiting the generation of TH1, TH2, and TH17 cells in vitro and in the DNCB-induced AD mouse model. For the first time, we demonstrate that HB markedly mitigates skin inflammation in AD patients and the DNCB-induced AD mouse model by reinvigorating the T cell immune balance, shedding light on the future development and application of novel HB-based therapeutics for AD.

15.
Nat Immunol ; 22(9): 1127-1139, 2021 09.
Article in English | MEDLINE | ID: mdl-34413521

ABSTRACT

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.


Subject(s)
Ferroptosis/physiology , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Selenium/pharmacology , T Follicular Helper Cells/physiology , Adolescent , Adult , Animals , Cell Survival/immunology , Child , Female , Germinal Center/cytology , Germinal Center/immunology , Homeostasis/drug effects , Homeostasis/genetics , Humans , Immunity, Humoral/immunology , Influenza Vaccines/immunology , Lipid Peroxidation/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/physiology , Ovalbumin , T Follicular Helper Cells/immunology , Vaccination , Young Adult
16.
Front Pharmacol ; 12: 624404, 2021.
Article in English | MEDLINE | ID: mdl-33912044

ABSTRACT

Diabetic nephropathy (DN), a common microvascular complication of diabetes, is one of the main causes of end-stage renal failure (ESRD) and imposes a heavy medical burden on the world. Yiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine formula, which has been widely used in the treatment of DN and has achieved stable and reliable therapeutic effects. However, the mechanism of YJHD in the treatment of DN remains unclear. This study aimed to investigate the mechanism of YJHD in the treatment of DN. Sprague-Dawley rats were randomly divided into a normal control group, a diabetic group, an irbesartan group, and three groups receiving different doses of YJHD. Animal models were constructed using streptozotocin and then treated with YJHD for 12 consecutive weeks. Blood and urine samples were collected during this period, and metabolic and renal function was assessed. Pathological kidney injury was evaluated according to the kidney appearance, hematoxylin-eosin staining, Masson staining, periodic-acid Schiff staining, periodic-acid Schiff methenamine staining, and transmission electron microscopy. The expression levels of proteins and genes were detected by immunohistochemistry, western blotting, and real-time qPCR. Our results indicate that YJHD can effectively improve renal function and alleviate renal pathological injury, including mesangial matrix hyperplasia, basement membrane thickening, and fibrosis. In addition, YJHD exhibited podocyte protection by alleviating podocyte depletion and morphological damage, which may be key in improving renal function and reducing renal fibrosis. Further study revealed that YJHD upregulated the expression of the autophagy-related proteins LC3II and Beclin-1 while downregulating p62 expression, suggesting that YJHD can promote autophagy. In addition, we evaluated the activity of the mTOR pathway, the major signaling pathway regulating the level of autophagy, and the upstream PI3K/Akt and AMPK pathways. YJHD activated the AMPK pathway while inhibiting the PI3K/Akt and mTOR pathways, which may be crucial to its promotion of autophagy. In conclusion, our study shows that YJHD further inhibits the mTOR pathway and promotes autophagy by regulating the activity of the PI3K/Akt and AMPK pathways, thereby improving podocyte injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research into YJHD.

17.
Zhongguo Zhong Yao Za Zhi ; 46(3): 614-619, 2021 Feb.
Article in Chinese | MEDLINE | ID: mdl-33645027

ABSTRACT

To standardize the processing technology of Polygoni Multiflori Radix Praeparata and stabilize its quality, the similar change laws of Polygoni Multiflori Radix Praeparata with different processing methods and time were analyzed. The processing time of Polygoni Multiflori Radix Praeparata was studied at 24, 32, 40, 48 h, and 4 different processing methods were studied, namely stewed with black bean sauce, steamed, steamed with black bean sauce, and steamed with black bean sauce and rice wine. The content of stilbene glycosides and anthraquinones were determined by HPLC-DAD method. UV method was used to determine the content of polysaccharides, and HPLC-ELSD method was used to determine the monosaccharides and oligosaccharides. The comparative chart of content determination, cluster analysis and entropy weight TOPSIS model was used to find the similar change laws and time interval of different processing methods of Polygoni Multiflori Radix Praeparata. The results demonstrated that around 32 h, the content of nine components in Polygoni Multiflori Radix Praeparata with different processing methods had similar change laws, and the decoction pieces had a high quality, indicating that the four processing methods of Polygoni Multiflori Radix Praeparata are likely to be used as one type of decoction piece with the same name.


Subject(s)
Drugs, Chinese Herbal , Polygonum , Chromatography, High Pressure Liquid , Glycosides , Plant Roots
18.
Immunology ; 163(4): 448-459, 2021 08.
Article in English | MEDLINE | ID: mdl-33738807

ABSTRACT

In contrast to humans or rabbits, in which maternal IgG is transmitted to offspring prenatally via the placenta or the yolk sac, large domestic animals such as pigs, cows and sheep transmit IgG exclusively through colostrum feeding after delivery. The extremely high IgG content in colostrum is absorbed by newborns via the small intestine. Although it is widely accepted that the neonatal Fc receptor, FcRn, is the receptor mediating IgG transfer across both the placenta and small intestine, it remains unclear whether FcRn also mediates serum IgG transfer across the mammary barrier to colostrum/milk, especially in large domestic animals. In this study, using a FcRn knockout pig model generated with a CRISPR-Cas9-based approach, we clearly demonstrate that FcRn is not responsible for the IgG transfer from serum to colostrum in pigs, although like in other mammals, it is involved in IgG homeostasis and mediates IgG absorption in the small intestine of newborns.


Subject(s)
Colostrum/metabolism , Histocompatibility Antigens Class I/metabolism , Intestine, Small/metabolism , Placenta/metabolism , Receptors, Fc/metabolism , Swine/immunology , Animals , Animals, Genetically Modified , Animals, Newborn , Breast Feeding , CRISPR-Cas Systems , Cattle , Female , Gene Knockout Techniques , Histocompatibility Antigens Class I/genetics , Homeostasis , Humans , Immunity, Maternally-Acquired , Immunoglobulin G/metabolism , Pregnancy , Rabbits , Receptors, Fc/genetics , Sheep
19.
J Sports Med Phys Fitness ; 61(2): 301-309, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32734755

ABSTRACT

INTRODUCTION: Dance therapy is a non-conventional aerobic exercise in cardiovascular rehabilitation. This meta-analysis aimed to update and assess evidence from randomized controlled trials of dance therapy on patients with hypertension. EVIDENCE ACQUISITION: PubMed, web of science, EBSCO, EMBESE, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases in English or Chinese were searched and randomized controlled trials were conducted for this meta-analysis to investigate the effects of dance therapy on blood pressure in hypertension patients. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed by I2 test. EVIDENCE SYNTHESIS: Five studies were included according to the eligibility criteria. Dance therapy could significantly reduce the systolic/diastolic pressure of hypertension individuals (SBP:WMD -11.07mmHg; 95%CI, -14.3 to -8.12mmHg, P<0.00001;DBP:WMD-4.16mmHg;95% CI, -6.44to-1.88mmHg, P=0.0004) when compared with the control group. low heterogeneity was observed in this research (P=0.65; I2=0% to SBP; P=0.57; I2 =0% to DBP). Subgroup analysis results showed that the subgroup of less than 12 weeks intervention group reduce the blood pressure more than those of 12 weeks intervention. Dance therapies reduce the SPB of hypertension individuals in African region better than Europe and America hypertension population. CONCLUSIONS: Despite the limited number of studies and people involved, the meta-analysis further demonstrated that dance therapy could reduce SBP and DBP in patients with hypertension. The effect of dance therapy intervention on hypertension might be related to duration of intervention and population gene.


Subject(s)
Blood Pressure/physiology , Dance Therapy , Hypertension/therapy , China , Diastole , Europe , Exercise , Humans , Systole
20.
Article in Chinese | WPRIM | ID: wpr-878886

ABSTRACT

To standardize the processing technology of Polygoni Multiflori Radix Praeparata and stabilize its quality, the similar change laws of Polygoni Multiflori Radix Praeparata with different processing methods and time were analyzed. The processing time of Polygoni Multiflori Radix Praeparata was studied at 24, 32, 40, 48 h, and 4 different processing methods were studied, namely stewed with black bean sauce, steamed, steamed with black bean sauce, and steamed with black bean sauce and rice wine. The content of stilbene glycosides and anthraquinones were determined by HPLC-DAD method. UV method was used to determine the content of polysaccharides, and HPLC-ELSD method was used to determine the monosaccharides and oligosaccharides. The comparative chart of content determination, cluster analysis and entropy weight TOPSIS model was used to find the similar change laws and time interval of different processing methods of Polygoni Multiflori Radix Praeparata. The results demonstrated that around 32 h, the content of nine components in Polygoni Multiflori Radix Praeparata with different processing methods had similar change laws, and the decoction pieces had a high quality, indicating that the four processing methods of Polygoni Multiflori Radix Praeparata are likely to be used as one type of decoction piece with the same name.


Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Glycosides , Plant Roots , Polygonum
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