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1.
Antioxidants (Basel) ; 10(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34679643

RESUMO

As a well-known hepatoprotective and antioxidant agent, dimethyl diphenyl bicarboxylate (DDB) has frequently been employed to remedy various liver diseases. However, it is still uncertain whether DDB exerts consistent hepatoprotective and antioxidative activities against varying degrees of hepatic damage. Therefore, DDB (100, 25, 5, or 50 mg/kg depending on the model) was administered to animals in four representative models of liver injury (CCl4 chemical acute model, DMN subchronic model, TAA chronic model, and restraint stress psychological acute model). Horizontal comparative analysis indicated that DDB significantly lowered the excess serum AST and ALT levels in the CCl4 and DMN models but not in the TAA and restraint stress models. In accordance with this result, DDB markedly reduced oxidative stress indices (hepatic MDA and ROS) but restored five main antioxidant components (GSH content, GSH-peroxidase, GSH-reductase, SOD, and catalase activity) in the CCl4 and DMN models. DDB failed to normalize oxidative stressors in the restraint stress-induced injury model and restore these five antioxidant components in the TAA model. Overall, our results produced a comprehensive overview of the effects of DDB on oxidative stressors and the main antioxidative components using four animal models. These findings will provide valuable clues to guide therapeutic clinical applications.

2.
Front Pharmacol ; 12: 753153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630123

RESUMO

Background: Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available. Aim of the study: To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model. Materials and methods: BALB/C mice were pretreated with Yeokwisan (100, 200, and 400 mg/kg, po) or mosapride (3 mg/kg, po) for 5 days and then treated with loperamide (10 mg/kg, ip) after 20 h of fasting. A solution of 0.05% phenol red (500 µL) or diet of 5% charcoal (200 µL) was orally administered, followed by assessment of gastric emptying or intestinal transit. Plasma acyl-ghrelin (ELISA), C-kit (immunofluorescence and western blotting), nNOS (western blotting) and gastric contraction- and ghrelin-related gene/protein expression levels were examined in stomach and small intestine tissues. Results: Loperamide injection substantially delayed gastric emptying, while Yeokwisan pretreatment (especially 200 and 400 mg/kg Yeokwisan) significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of phenol red retained in the stomach (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The levels of plasma acyl-ghrelin and expression of gastric ghrelin-related genes, such as growth hormone secretagogue receptor (GHSR), ghrelin-O-acyltransferase (GOAT), adrenergic receptor ß1 (ADRB1) and somatostatin receptor (SSTR), were significantly normalized (p < 0.05 or 0.01) by Yeokwisan (400 mg/kg). Yeokwisan (400 mg/kg) significantly tempered the loperamide-induced alterations in the c-kit and nNOS levels (p < 0.01) as well as the expression of contraction- and ghrelin-related genes, such as 5-HT4 receptor (5-HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK), in the stomach, but not in the small intestine. Conclusion: The present results showed the clinical relevance of Yeokwisan, in treating FD, especially in promoting gastric emptying but not small intestinal transit. The main mechanisms corresponding to these effects may involve the modulation of the ghrelin pathway and activation of interstitial cells of Cajal in stomach tissue.

3.
FEBS J ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34528400

RESUMO

Injury or disease in the somatosensory nervous system may cause broad molecular changes and lead to neuropathic pain. Excitatory synaptic transmission in somatosensory pathways conveys the somatosensory information from the peripheral to the central nervous system. Long-term effects of excitatory synaptic transmission on the pain pathway contribute to neuropathic pain hypersensitivity. Synaptic strength is dynamically regulated and undergoes bidirectional changes, manifested by two primary forms of synaptic plasticity, long-term potentiation and long-term depression (LTD), which are mediated by insertion and endocytosis of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), respectively. Molecular mechanisms of LTP have been extensively studied; on the other hand, the role of AMPAR endocytosis in the pain-related synaptic enhancement is less well known. Recent research in the anterior cingulate cortex reveals that loss of LTD contributes to the maintenance of neuropathic pain, which provides the novel perspective of the mechanism of LTD also being critical for maintaining neuropathic pain. More importantly, exploring the molecular mechanism of LTD may help with the development of novel analgesic strategies to manage neuropathic pain.

4.
J Pers Med ; 11(4)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33918059

RESUMO

In contrast to nonalcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD) as an innovative definition can coexist with significant alcohol consumption. Massive clinical observations have indicated that high-fat/-calorie diet induced metabolic dysfunction along with alcohol intake deteriorates steatotic liver injury. To explore the potential mechanisms of fatty diet together with alcohol-induced steatohepatitis, we adopted a rat model by comparing a half-dose combination of fat diet (20%) and alcohol (10%) with their corresponding double dose of 40% fat diet and 20% alcohol for 8 weeks. The notable alterations in histopathology, acceleration in the oxidation parameters (ROS, NO and lipid peroxidation) and serum transaminase levels were shown in the concomitant group. Concomitant use of a high-fat diet and alcohol provoked hepatic endoplasmic reticulum stress, but did not activate mitochondria-mediated apoptosis parameters compared to F. In contrast, the notable activation of caspase-12 and nuclear translocation of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) were observed only in the combined treatment group. The concomitant dietary fat intake and alcohol consumption lead to liver injury initially and later to steatohepatitis by the overdose of fat or alcohol, and in which the CHOP and caspase-12 might be involved in synergistic acceleration of steatohepatitis through a mitochondria-independent manner.

5.
Molecules ; 26(4)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567750

RESUMO

Rhus verniciflua Stokes (RVS) has been traditionally used as an herbal remedy to support the digestive functions in traditional Korean medicine. Additionally, the pharmacological effects of RVS, including antioxidative, antimicrobial and anticancer activities, have been well-reported. The genotoxicity of RVS, however, is elusive; thus, we evaluated the genotoxicity of RVS without bark (RVX) for safe application as a resource of functional food or a medical drug. To evaluate the genotoxicity of RVX, we used a bacterial reverse mutation test, chromosomal aberration test and comet assay, according to the "Organization for Economic Co-operation and Development" (OECD) guidelines. Briefly, for the reverse mutation test, samples (5000, 1667, 556, 185, 62 and 0 µg/plate of RVX or the positive control) were treated with a precultured strain (TA98, TA100, TA1535, TA1537 or WP2µvrA) with or without the S9 mix, in which RVX partially induced a reverse mutation in four bacterial strains. From the chromosomal aberration test and comet assay, the RVX samples (556, 185, 62, 20 and 0 µg/mL of RVX or the positive control) were treated in a Chinese hamster ovary cell line (CHO-K1 cells) in the conditions of the S9 mix absent or S9 mix present and in Chang liver cells and C2C12 myoblasts, respectively. No chromosomal aberrations in CHO-K1 or DNA damage in Chang liver cells and C2C12 myoblasts was observed. In conclusion, our results suggest the non-genotoxicity of RVX, which would be helpful as a reference for the safe application of bark-removed Rhus verniciflua Stokes as functional raw materials in the food, cosmetics or pharmaceutical fields.


Assuntos
Casca de Planta/química , Extratos Vegetais/química , Rhus/química , Água/química , Animais , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Humanos , Camundongos , Testes de Mutagenicidade , Extratos Vegetais/toxicidade
6.
Antioxidants (Basel) ; 10(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33435626

RESUMO

Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity and the extent of hepatic fibrosis, fifty-four subjects with liver fibrosis (5.5 ≤ liver stiffness measurement (LSM) score ≤ 16.0 kPa) by chronic hepatitis B virus (HBV) were analyzed. From the analysis of eight kinds of serum oxidative stress/antioxidant profiles and liver fibrosis degrees, the level of total antioxidant capacity (TAC) reflected a negative correlation with the severity of hepatic fibrosis (Pearson correlation, r = -0.35, p = 0.01). Moreover, TAC showed higher sensitivity (73.91%) than the aspartate transaminase (AST) to platelet ratio index (APRI, 56.52%) in the receiver operating characteristic (ROC) curves. Interestingly, the TAC level finely reflected the fibrosis degree in inactive carriers (HBV DNA < 2000 IU/mL), while the APRI did in active carriers (HBV DNA > 2000 IU/mL). In conclusion, TAC is a promising biomarker for evaluating the progression of liver fibrosis in patients with HBV, and this finding may indicate the involvement of TAC-composing factors in the pathogenesis of hepatic fibrosis in chronic HBV carriers.

7.
Clin Res Hepatol Gastroenterol ; 45(4): 101526, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32919911

RESUMO

AIMS: We aimed to conduct a systematic review and a meta-analysis to estimate NAFLD prevalence and its change in Korea. METHODS: We searched the literature involving NAFLD prevalence in Korea in PubMed, RISS, and KMBASE from inception to June 2017. Studies with subjects with certain disorders, population limitations, or subjects who consume alcohol were excluded. Analysis was stratified by publication year, age, gender, severity, body mass index (BMI), and diagnostic technique. Random-effects models were used to provide point estimates (95% confidence interval) of prevalence with subgroup analysis to account for heterogeneity. RESULTS: A total of 61 studies (837,897 participants) were included. The overall NAFLD prevalence in Korea was 30.3% (men: 41.1%, women: 20.3%), with a slight increase from 29.0% to 31.0% over an approximately 10-year period. BMI significantly affected NAFLD prevalence (≤ or > 25 kg/m2, 12.3% vs. 41.7%, p < 0.001), while women were significantly affected by aging (< or ≥ 50 years, 17.0% vs. 25.8%, p < 0.01). The prevalence of steatosis by severity was 22.6% for mild, 9.8% for moderate to severe and 2.2% for nonalcoholic steatohepatitis (NASH), with different patterns by gender. CONCLUSION: The current study is the first systematic analysis on NAFLD prevalence in Korea and found a change in NAFLD prevalence during the recent decade.

8.
Cells ; 11(1)2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-35011585

RESUMO

Cynanchum atratum, a medicinal herb, is traditionally used as an antidote, diuretic, and antipyretic in eastern Asia. The current study aimed to investigate the anti-fatty liver capacity of the ethanol extract of Cynanchum atratum (CAE) using a 10-week high-fat, high-fructose diet mouse model. A six-week treatment of CAE (from the fifth week) significantly attenuated the weights of the body, liver, and mesenteric fat without a change in diet intake. CAE also considerably restored the alterations of serum aminotransferases and free fatty acid, fasting blood glucose, serum and hepatic triglyceride, and total cholesterol, as well as platelet and leukocyte counts. Meanwhile, CAE ameliorated hepatic injury and lipid accumulation, as evidenced by histopathological and immunofluorescence observations. Additionally, CAE significantly lowered the elevation of hepatic TNF-α, the TNF-α/IL-10 ratio, fecal endotoxins, and the abundance of Gram-negative bacteria. Hepatic lipogenesis and ß-oxidation-related proteins and gene expression, including PPAR-α, SREBP-1, SIRT1, FAS, CTP1, etc., were normalized markedly by CAE. In particular, the AMPK, a central regulator of energy metabolism, was phosphorylated by CAE at an even higher rate than metformin. Overall, CAE exerts anti-hepatic steatosis effects by reducing lipogenesis and enhancing fatty acid oxidation. Consequently, Cynanchum atratum is expected to be a promising candidate for treating chronic metabolic diseases.

9.
Cell Rep ; 33(6): 108369, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33176141

RESUMO

Nerve injury in somatosensory pathways may lead to neuropathic pain, which affects the life quality of ∼8% of people. Long-term enhancement of excitatory synaptic transmission along somatosensory pathways contributes to neuropathic pain. Caspase 3 (Casp3) plays a non-apoptotic role in the hippocampus and regulates internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. Whether Casp3-AMPAR interaction is involved in the maintenance of peripheral hypersensitivity after nerve injury remained unknown. Here, we show that nerve injury suppresses long-term depression (LTD) and downregulates Casp3 in the anterior cingulate cortex (ACC). Interfering with interactions between Casp3 and AMPAR subunits or reducing Casp3 activity in the ACC suppresses LTD induction and causes peripheral hypersensitivity. Overexpression of Casp3 restores LTD and reduces peripheral hypersensitivity after nerve injury. We reveal how Casp3 is involved in the maintenance of peripheral hypersensitivity. Our findings suggest that restoration of LTD via Casp3 provides a therapeutic strategy for neuropathic pain management.


Assuntos
Caspase 3/metabolismo , Depressão/genética , Giro do Cíngulo/fisiopatologia , Neuralgia/fisiopatologia , Humanos
10.
Am J Chin Med ; 48(6): 1409-1433, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32907360

RESUMO

Scutellaria baicalensis (SB), a herbal medicine, is commonly used to treat metabolic diseases, while Metformin (MF) is a widely used drug for type 2 diabetes. The purpose of this study was to investigate whether co-treatment of SB with MF could produce a potential therapeutic effect on high-fat and high-fructose diet (HFFD)-induced metabolic dysregulation. First, we optimized the dose of SB (100, 200, 400, and 800[Formula: see text]mg/kg) with MF (200[Formula: see text]mg/kg) in HFFD-induced C57BL6J mice. Next, the optimized dose of SB (400[Formula: see text]mg/kg) was co-administered with MF (50, 100, and 200[Formula: see text]mg/kg) in a similar animal model to find the effective combinations of SB and MF. Metabolic markers were determined in serum and tissues using different assays, histology, gene expression, and gut microbial population. The SB and MF co-treatment significantly decreased the body, liver, and VAT weights. The outcome of OGTT was improved, and the fasting insulin, HbA1c, TG, TC, LDL-c, AST, and ALT were decreased, while HDL-c was significantly increased. Histological analyses revealed maintained the integrity of liver, adipose tissue, and intestine prevented lipid accumulation in the liver and intestine and combated neuronal damage in the brain. Importantly, controlled the expression of PPAR[Formula: see text], and IL-6 genes in the liver, and expression of BDNF, Glut1, Glut3, and Glut4 genes in the brain. Treatment-specific gut microbial segregation was observed in the PCA chart. Our findings indicate that SB and MF co-treatment is an effective therapeutic approach for HFFD-induced metabolic dysregulation which is operated through the gut-liver-brain axis.


Assuntos
Encéfalo/metabolismo , Microbioma Gastrointestinal , Fígado/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Metformina/administração & dosagem , Metformina/farmacologia , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Quimioterapia Combinada , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/microbiologia , Camundongos Endogâmicos C57BL , PPAR gama/genética , PPAR gama/metabolismo , Scutellaria baicalensis
11.
World J Stem Cells ; 12(8): 879-896, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32952864

RESUMO

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 EVs-delivered 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.

12.
World J Gastroenterol ; 26(32): 4846-4856, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32921961

RESUMO

BACKGROUND: The Helicobacter pylori (H. pylori) eradication rate is decreasing in the general population of China. AIM: To evaluate the H. pylori eradication status in real-world clinical practice and to explore factors related to eradication failure. METHODS: Patients with H. pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Multivariate analysis was performed to identify predictors of eradication failure. RESULTS: Of 2610 patients enrolled, eradication was successful in 1999 (76.6%) patients. Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens (83.0% vs 69.0%, P < 0.001). The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate (83.5%). Primary therapy had a higher eradication rate than rescue therapy (78.3% vs 66.5%, P < 0.001). In rescue therapy, the amoxicillin- and furazolidone-containing regimens achieved the highest eradication rate (80.8%). Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors (81.8% vs 74.9%, P = 0.001). Multivariate regression analysis found that older age, prior therapy, and use of omeprazole or pantoprazole were associated with an increased risk of eradication failure. CONCLUSION: The total eradication rate is 76.6%. Amoxicillin-containing regimens are superior to other regimens. Age, prior therapy, and use of omeprazole or pantoprazole are independent risk factors for eradication failure.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Idoso , Amoxicilina/uso terapêutico , Antibacterianos/efeitos adversos , China/epidemiologia , Claritromicina/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco
13.
World J Stem Cells ; 12(7): 688-705, 2020 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-32843922

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have been widely investigated in rheumatic disease due to their immunomodulatory and regenerative properties. Recently, mounting studies have implicated the therapeutic potency of MSCs mostly due to the bioactive factors they produce. Extracellular vesicles (EVs) derived from MSCs have been identified as a promising cell-free therapy due to low immunogenicity. Rheumatic disease, primarily including rheumatoid arthritis and osteoarthritis, is a group of diseases in which immune dysregulation and chronic progressive inflammation lead to irreversible joint damage. Targeting MSCs and MSC-derived EVs may be a more effective and promising therapeutic strategy for rheumatic diseases. AIM: To evaluate the potential therapeutic effectiveness of MSCs and EVs generated from MSCs in rheumatic diseases. METHODS: PubMed was searched for the relevant literature using corresponding search terms alone or in combination. Papers published in English language from January 1999 to February 2020 were considered. Preliminary screening of papers concerning analysis of "immunomodulatory function" or "regenerative function" by scrutinizing the titles and abstracts of the literature, excluded the papers not related to the subject of the article. Some other related studies were obtained by manually retrieving the reference lists of papers that comply with the selection criteria, and these studies were screened to meet the final selection and exclusion criteria. RESULTS: Eighty-six papers were ultimately selected for analysis. After analysis of the literature, it was found that both MSCs and EVs generated from MSCs have great potential in multiple rheumatic diseases, such as rheumatoid arthritis and osteoarthritis, in repair and regeneration of tissues, inhibition of inflammatory response, and regulation of body immunity via promoting chondrogenesis, regulating innate and adaptive immune cells, and regulating the secretion of inflammatory factors. But EVs from MSCs exhibit much more advantages over MSCs, which may represent another promising cell-free restorative strategy. Targeting MSCs and MSC-derived EVs may be a more efficient treatment for patients with rheumatic diseases. CONCLUSION: The enormous potential of MSCs and EVs from MSCs in immunomodulation and tissue regeneration offers a new idea for the treatment of rheumatism. However, more in-depth exploration is needed before their clinical application.

14.
Kaohsiung J Med Sci ; 36(9): 721-731, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32627922

RESUMO

Our study aimed to explore the molecular mechanisms involved in the improvement of postoperative cognitive dysfunction (POCD) by dexmedetomidine (DEX). BV2 microglia cells were cultured under normal condition, DEX exposure (0.1 µg/mL), and lipopolysacchride (LPS) treatment (0.1 µg/mL) or with pretreatment of DEX before LPS incubation. For BV2 microglia cells, LPS induced markedly increased release of pro-inflammatory cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-alpha [TNF-α]) and expressions of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB), while DEX pretreatment inhibited the LPS-induced production of pro-inflammatory cytokines and expressions of TLR4 and NF-κB. The spatial memory function was impaired in the aged mice following partial hepatectomy since the percentage of time spent in the target quadrant and the number of crossings over the former platform location were reduced. Pretreatment of DEX may attenuate neuroinflammation and improve POCD in aged mice through inhibiting the TLR4-NF-κB signaling pathway in the hippocampus.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Envelhecimento/genética , Dexmedetomidina/farmacologia , Hipocampo/efeitos dos fármacos , Complicações Cognitivas Pós-Operatórias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Envelhecimento/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Fígado/inervação , Fígado/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/genética , Complicações Cognitivas Pós-Operatórias/fisiopatologia , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
FASEB J ; 34(6): 8686-8701, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32356337

RESUMO

Thyroid hormones are essential for the regulation of energy homeostasis and metabolic processes. However, the relationship between thyroid function and host gut microbial communities is not properly understood. To determine whether and how gut microbiota is associated with thyroid function, metagenomics analysis of the bacterial population in fecal samples of rat models of hyperthyroidism (induced by levothyroxine) and hypothyroidism (induced by propylthiouracil or thyroidectomy) was conducted through 16S rRNA gene sequencing. Our results revealed that all thyroid dysfunction models were definitely established and gut microbial composition varied according to different thyroid functional status. The relative abundance of Ruminococcus was significantly higher in the hyperthyroidism group (HE) vs both the normal and hypothyroidism groups (HO) while S24-7 was significantly higher in the HO group. The population of Prevotellaceae and Prevotella were significantly lower in the HO group vs the normal. Firmicutes and Oscillospira were significantly higher in the SHO (surgery-induced hypothyroidism) group, while Prevotellaceae and Prevotella showed lower abundance in the SHO group than the SHAM group. Present results suggest that thyroid functions may have the potential to influence the profile of gut microbiota and could be used as foundation to investigate interaction mechanism between thyroid and gut microbiome.


Assuntos
Microbioma Gastrointestinal/genética , Glândula Tireoide/microbiologia , Glândula Tireoide/patologia , Animais , Bactérias/genética , Bacteroidetes/genética , Modelos Animais de Doenças , Fezes/microbiologia , Hipotireoidismo/microbiologia , Hipotireoidismo/patologia , Masculino , Metagenômica/métodos , Microbiota/genética , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley
16.
J Biosci ; 452020.
Artigo em Inglês | MEDLINE | ID: mdl-32345786

RESUMO

Patients affected by pulmonary tuberculosis (PTB) manifest deficiencies in innate cellular immunity. The Tim3/Galectin-9 axis is an important regulator of Th1 cell immunity, leading to Th1 cell apoptosis. Herein, this study aims to clarify the underlying roles of the Tim-3/Galectin-9 axis in T-cell immunity in PTB. Peripheral blood mononuclear cells (PBMCs) were extracted from subjects with and without PTB to examine the expression of CD4, CD8, CD25, and Tim-3 under the stimulation of Mycobacterium tuberculosis (MTB) and purified protein derivative (PPD). In addition, the expression of Tim-3 and Galectin-9 in PBMCs was determined. The Tim-3/Galectin-9 axis in the PBMCs was activated or blocked to detect the secreted levels of IFN-γ, TNF-α, IL-2, and IL-22. MTB stimulation increased the expression of CD4, CD8, CD25, Tim-3, and Galectin-9 in PBMCs. The blockade of Tim-3/Galectin-9 axis resulted in reduced secretion of IFN-γ, TNF-α, IL-2, and IL-22 from T-cells. Moreover, Tim-3+CD4+T, Tim-3+CD8+, and Tim-3+CD25+T cells exhibited a greater ability to inhibit the replication of MTB in macrophages. Taken conjointly, the blockade of Tim-3/ Galectin-9 axis inhibits the secretion of inflammatory cytokines in T-cells to regulate the T-cell immunity in PTB.


Assuntos
Galectinas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Células Th1/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Imunidade Celular , Leucócitos Mononucleares/imunologia , Ativação Linfocitária/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/fisiologia , Linfócitos T Reguladores/imunologia , Células Th1/metabolismo , Tuberculose Pulmonar/genética
18.
World J Pediatr ; 16(1): 19-30, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30796732

RESUMO

BACKGROUND: Systemic lupus erythematosis (SLE) is a complex and clinically heterogeneous autoimmune disease. A variety of immunological defects contribute to SLE, including dysregulated innate and adaptive immune response. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved SLE-personalized approaches to treatment. The aim of this review was to clarify the immunological pathogenesis and treatment of SLE. DATA SOURCES: Literature reviews and original research articles were collected from database, including PubMed and Wanfang. Relevant articles about SLE were included. RESULTS: Breakdown of self-tolerance is the main pathogenesis of SLE. The innate and adaptive immune networks are interlinked with each other through cytokines, complements, immune complexes and kinases of the intracellular machinery. Treatments targeted at possible targets of immunity have been assessed in clinical trials. Most of them did not show better safety and efficacy than traditional treatments. However, novel targeting treatments are still being explored. CONCLUSIONS: Dysregulated immune response plays a critical role in SLE, including innate immunity and adaptive immunity. Biologic agents that aim to specifically target abnormal immune processes were assessing and may bring new hope to SLE patients.


Assuntos
Antirreumáticos/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Imunidade Adaptativa , Criança , Humanos , Imunidade Inata
19.
Front Microbiol ; 10: 1292, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231354

RESUMO

Changes in environmental and genetic factors are vital to development of obesity and its complications. Induction of obesity and type 2 diabetes by both leptin deficiency (ob/ob) and high fat diet (HFD) has been verified in animal models. In the present experiment, three types of diets (normal diet; ND, HFD and high sucrose diet; HSD) and two types of genetic mice (Wild type: WT and ob/ob) were used to explore the relationship among diet supplements, gut microbiota, host genetics and metabolic status. HFD increased the body, fat and liver weight of both ob/ob and WT mice, but HSD did not. HFD also resulted in dyslipidemia, as well as increased serum transaminases and fasting glucose in ob/ob mice but not in WT mice, while HSD did not. Moreover, HFD led to brain BDNF elevation in WT mice and reduction in ob/ob mice, whereas HSD did not. Both HFD and HSD had a greater influence on gut microbiota than host genotypes. In detail, both of HFD and HSD alteration elucidated the majority (≥63%) of the whole structural variation in gut microbiota, however, host genetic mutation accounted for the minority (≤11%). Overall, diets more intensively disturbed the structure of gut microbiota in excess of genetic change, particularly under leptin deficient conditions. Different responses of host genotypes may contribute to the development of metabolic disorder phenotypes linked with gut microbiota alterations.

20.
Zhongguo Zhen Jiu ; 39(6): 588-92, 2019 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-31190493

RESUMO

OBJECTIVE: To explore the effect of acupuncture at the "reflection points" of affected side on the peripheral facial paralysis in acute phase. METHODS: Ninety patients with peripheral facial paralysis in acute phase were randomly divided into a reflection group (group A), a conventional acupuncture group (group B) and a physiotherapy group (group C), 30 cases in each group. The same basic medication were given in all three groups. In the group A, acupuncture at "reflection points" of the affected side and local acupoints in acute phase, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group B, acupuncture at Yifeng (TE 17) of the affected side in acute phase and local acupoints, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group C, ultrashort wave on Yifeng (TE 17) of the affected side in acute phase was applied, and the treatment in the stationary phase and the recovery phase was the same as the group B. The treatment was given once every day, 5 times as one course for 4 courses. The House-Brackmann (H-B) grading scale, facial disability index scale, the symptom and physical score integral scale were used to score before and after treatment, and the clinical effects of the three groups were compared. RESULTS: After treatment, the functional grade of H-B facial nerve was better than that before treatment in the three groups (P<0.01). There was no significant difference among the three groups after treatment (P>0.05). After treatment, the course of treatment required to reflect the healing in the group A was shorter than that in the group B and the group C (P<0.01); the body function scores and social function scores in the three groups were better than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). The scores of symptoms and signs in the three groups were lower than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). H-B facial nerve function grading scale and facial disability index (FDI) scale were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B and 46.7% (14/30) in the group C, the curative rate in the group A was better than the other two groups (P<0.05). The curative and markedly effective rate in the group A was 83.3% (25/30), 70.0% (21/30) in the group B and 63.3% (19/30) in the group C, the curative and markedly effective rate in the group A was better than the other two groups (P<0.05). The scores of symptoms and signs were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B, and 46.7% (14/30) in the group C. The curative rate in the group A was better than the other two groups (P<0.05). CONCLUSION: Compared with general acupuncture and physiotherapy, acupuncture at the "reflection points" of the affected side on the peripheral facial paralysis in acute phase could shorten the course of treatment and improve the curative effect.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Paralisia Facial , Pontos de Acupuntura , Paralisia Facial/terapia , Humanos
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