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1.
Pharmacol Res ; 177: 106121, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35143971

RESUMO

BACKGROUND AND AIMS: Metabolic diseases are globally popular, and a systematic review and meta-analysis of turmeric and curcuminoids on glucose metabolism among people with metabolic diseases was performed. DESIGN: We comprehensively searched Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, the Cochrane Library and two Chinese databases, Wanfang and CNKI for RCTs that focused on the effects of turmeric and curcuminoids on fasting blood glucose (FBG), hemoglobin A1C (HbA1c), fasting serum insulin (FSI) and HOMA-IR among patients with metabolic diseases. The FBG and HbA1c were the main outcomes to be analyzed. With random-effects models, separate meta-analyses were conducted by inverse-variance and reported as WMD with 95% CIs. RESULTS: Evidence from 17 RCTs including 22 trials showed that turmeric and curcuminoids lowered FBG by - 7.86 mg/dL (95% CI: -12.04, -3.67 mg/dL; P = 0.0002), HbA1c by - 0.38% (95% CI: -0.52%, -0.23%; P < 0.00001) and HOMA-IR by - 1.01 (95% CI: -1.6, -0.42; P = 0.0008). Moreover, they decreased fasting serum insulin by - 1.69 mU/L (95% CI: -3.22, -0.16 mU/L; P = 0.03) after more than 8 weeks of intervention in a subgroup analysis. CONCLUSIONS: Turmeric and curcuminiods decrease FBG, HbA1c and HOMA-IR significantly among subjects with metabolic disease. Additionally, they may have an effect on FSI concentrations if the intervention period is more than 8 weeks. However, attention should be paid to these outcomes due to the significant heterogeneity.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças Metabólicas , Glicemia/metabolismo , Curcuma , Diarileptanoides , Hemoglobina A Glicada/metabolismo , Humanos , Insulina , Doenças Metabólicas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Clin Transl Med ; 12(2): e746, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35220680

RESUMO

BACKGROUND: Aging-associated osteoporosis is frequently seen in the elderly in clinic, but efficient managements are limited because of unclear nosogenesis. The current study aims to investigate the role of melatonin on senescent bone marrow stromal cells (BMSCs) and the underlying regulating mechanism. METHODS: Melatonin levels were tested by ELISA. Gene expression profiles were performed by RNA-sequencing, enrichment of H3K36me2 on gene promoters was analyzed by Chromatin Immunoprecipitation Sequencing (ChIP-seq), and chromatin accessibility was determined by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). Osteogenesis of BMSCs in vitro was measured by Alizarin Red and Alkaline Phosphatase staining, and in vivo effects of melatonin was assessed by histological staining and micro computed tomography (micro-CT) scan. Correlation of NSD2 expression and severity of senile osteoporosis patients were analyzed by Pearson correlation. RESULTS: Melatonin levels were decreased during aging in human bone marrow, accompanied by downregulation of the histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2) expression in the senescent BMSCs. Melatonin stimulated the expression of NSD2 through MT1/2-mediated signaling pathways, resulting in the rebalancing of H3K36me2 and H3K27me3 modifications to increase chromatin accessibility of the osteogenic genes, runt-related transcription factor 2 (RUNX2) and bone gamma-carboxyglutamate protein (BGLAP). Melatonin promoted osteogenesis of BMSCs in vitro, and alleviates osteoporosis progression in the aging mice. In clinic, severity of senile osteoporosis (SOP) was negatively correlated with melatonin level in bone marrow, as well as NSD2 expression in BMSCs. Similarly, melatonin remarkably enhanced osteogenic differentiation of BMSCs derived from SOP patients in vitro. CONCLUSIONS: Collectively, our study dissects previously unreported mechanistic insights into the epigenetic regulating machinery of melatonin in meliorating osteogenic differentiation of senescent BMSC, and provides evidence for application of melatonin in preventing aging-associated bone loss.


Assuntos
Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Histona-Lisina N-Metiltransferase/farmacologia , Melatonina/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Proteínas Repressoras/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Diferenciação Celular/efeitos dos fármacos , Montagem e Desmontagem da Cromatina/genética , Montagem e Desmontagem da Cromatina/fisiologia , Modelos Animais de Doenças , Feminino , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Masculino , Melatonina/uso terapêutico , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL/metabolismo , Pessoa de Meia-Idade , Osteoblastos/fisiologia , Proteínas Repressoras/metabolismo
3.
Aging Cell ; 21(2): e13551, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35032339

RESUMO

Senescence of bone marrow mesenchymal stem cells (BMSCs) impairs stemness and osteogenic differentiation, but the key regulators for senescence and the related osteogenesis are not well defined. Herein, we screened the gene expression profiles of human BMSCs from young and old donors and identified that elevation of the nucleosome assembly protein 1-like 2 (NAP1L2) expression was correlated with BMSC senescence and impaired osteogenesis. Elevated NAP1L2 expression was observed in replicative cell senescence and induced cell senescence in vitro, and in age-related senescent human and mouse BMSCs in vivo, concomitant with significantly augmented chromatin accessibility detected by ATAC-seq. Loss- and gain-of-functions of NAP1L2 affected activation of NF-κB pathway, status of histone 3 lysine 14 acetylation (H3K14ac), and chromatin accessibility on osteogenic genes in BMSCs. Mechanistic studies revealed that NAP1L2, a histone chaperone, recruited SIRT1 to deacetylate H3K14ac on promoters of osteogenic genes such as Runx2, Sp7, and Bglap and suppressed the osteogenic differentiation of BMSCs. Importantly, molecular docking analysis showed a possible bond between NAP1L2 and an anti-aging reagent, the nicotinamide mononucleotide (NMN), and indeed, administration of NMN alleviated senescent phenotypes of BMSCs. In vivo and clinical evidence from aging mice and patients with senile osteoporosis also confirmed that elevation of NAP1L2 expression was associated with suppressed osteoblastogenesis. Taken together, our findings suggest that NAP1L2 is a regulator of both BMSC cell senescence and osteogenic differentiation, and provide a new theoretical basis for aging-related disease.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Envelhecimento/genética , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Cultivadas , Senescência Celular/genética , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Osteogênese/genética
4.
Phytomedicine ; 83: 153487, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33636476

RESUMO

BACKGROUND: Excessive hepatic glucose production (HGP) largely promotes the development of type 2 diabetes mellitus (T2DM), and the inhibition of HGP significantly ameliorates T2DM. Huanglian-Renshen-Decoction (HRD), a classic traditional Chinese herb medicine, is widely used for the treatment of diabetes in clinic for centuries and proved effective. However, the relevant mechanisms of HRD are not fully understood. PURPOSE: Based on that, this study was designed to identify the potential effects and underlying mechanisms of HRD on HGP by a comprehensive investigation that integrated in vivo functional experiments, network pharmacology, molecular docking, transcriptomics and molecular biology. METHODS: After confirming the therapeutic effects of HRD on T2DM mice, the inhibitory role of HRD on HGP was evaluated by pyruvate and glucagon tolerance tests, liver positron emission tomography (PET) imaging and the detection of gluconeogenic key enzymes. Then, network pharmacology and transcriptomics approaches were used to clarify the underlying mechanisms. Molecular biology, computational docking analysis and in vitro experiments were applied for final mechanism verification. RESULTS: Here, our results showed that HRD can decrease weight gain and blood glucose, increase fasting insulin, glucose clearance and insulin sensitivity in T2DM mice. Dysregulated lipid profile was also corrected by HRD administration. Pyruvate, glucagon tolerance tests and liver PET imaging all indicated that HRD inhibited the abnormal HGP of T2DM, and the expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) were significantly suppressed by HRD as expected. Network pharmacology and transcriptomics approaches illustrated that PI3K/Akt/FoxO1 signaling pathway may be responsible for the inhibitory effect of HRD on HGP. Afterward, further western blot and immunoprecipitation found that HRD did activate PI3K/Akt/FoxO1 signaling pathway in T2DM mice, which confirmed previous results. Additionally, the conclusion was further supported by molecular docking and in vitro experiments, in which identified HRD compound, oxyberberine, was proven to exert an obvious effect on Akt. CONCLUSION: Our data demonstrated that HRD can treat T2DM by inhibiting hepatic glucose production, the underlying mechanisms were associated with the activation of PI3K/Akt/FoxO1 signaling pathway.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glucose/metabolismo , Animais , Glicemia/metabolismo , Biologia Computacional , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Proteína Forkhead Box O1/metabolismo , Perfilação da Expressão Gênica , Gluconeogênese/efeitos dos fármacos , Células Hep G2 , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Obesos , Panax/química , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/química , Proteínas Proto-Oncogênicas c-akt/metabolismo
5.
Biomed Pharmacother ; 134: 111129, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33348308

RESUMO

Ulcerative colitis (UC) is an inflammatory bowel disease with complex pathogenesis, which is affected by genetic factors, intestinal immune status and intestinal microbial homeostasis. Intestinal epithelial barrier defect is crucial to the development of UC. Berberine, extracted from Chinese medicine, can identify bitter taste receptor on intestinal Tuft cells and activate IL-25-ILC2-IL-13 immune pathway to impair damaged intestinal tract by promoting differentiation of intestinal stem cells, which might be a potential approach for the treatment of UC.


Assuntos
Anti-Inflamatórios/uso terapêutico , Berberina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Animais , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/imunologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Células-Tronco/imunologia , Células-Tronco/metabolismo , Células-Tronco/patologia
6.
Phytomedicine ; 76: 153258, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32563018

RESUMO

BACKGROUND: Wu-Mei-Wan, a classic traditional Chinese herb medicine, is one of the most important formulations to treat digestive diseases from ancient times to the present. Our previous study showed that WMW treatment can prevent T2DM in db/db mice, which motivating the application of WMW on metabolic disorders. PURPOSE: Obesity and its comorbid diseases have increased dramatically and are now a worldwide health problem. There is still a lack of satisfactory treatment strategies for obesity. This work was designed to assess the effect and related mechanism of WMW on high fat diet (HFD)-induced obese mice model. METHODS: Obese mice were induced by HFD. Thetherapeutic effect of WMW were analyzed by examining body and adipose tissue weight, metabolic profile and energy expenditure. Adipose tissue phenotype was determined by histological staining and the mitochondrial content was examined by transmission electron microscopy (TEM). Immunohistochemical and immunofluorescence staining, RT-qPCR and Western blot analysis were used to evaluate expression of key molecules in adipose tissue. RESULTS: WMW treatment significantly protects HFD-induced obesity. Here we showed that WMW limits weight gain, improves metabolic profile and increases energy expenditure. WMW inhibits the hypertrophy and hyperplasia of white adipocytes, the mechanism involving the inhibition of TLR3/IL-6/JAK1/STAT3 pathway. In brown adipose tissue (BAT), WMW promotes thermogenicprogramme without affecting cell proliferation. The activated BMP7/ Smad1/5/9 pathway is considered to be one of the explanations for the effect of WMW on BAT. CONCLUSION: Our results suggested that WMW can prevent obesity and its underlying mechanisms are associated with reducing white adipose tissue and enhancing brown adipose tissue function.

8.
J Ethnopharmacol ; 252: 112580, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31972322

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Mei-Wan (WMW), a classic traditional Chinese herb medicine, is one of the most important formulations to treat digestive diseases from ancient times to the present. Previous study showed that WMW has satisfactory curative effects on experimental colitis, which motivating the application of WMW on colitis-associated complications. AIM OF THE STUDY: Intestinal fibrosis is usually considered to be a common complication of inflammatory bowel disease (IBD), particularly Crohn's disease (CD). Currently, no effective preventive measures or medical therapies are available for that. This work was designed to evaluate the effect and related mechanism of WMW on chronic colitis-associated intestinal fibrosis mice model. MATERIALS AND METHODS: The chronic colitis-associated intestinal fibrosis mice model was established by weekly intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The mice survival rate, disease activity index (DAI), colon length and histological score were examined to assess the therapeutic effect of WMW. Masson's trichrome staining, hydroxyproline assay, immunohistochemical staining and western blot analysis were used to evaluate fibrosis level. Colon inflammation was determined by ELISA and immunofluorescence staining. Immunofluorescence staining was used to evaluate fibroblasts proliferation and epithelial to mesenchymal transition (EMT), and the expression of key molecules in fibrosis was analyzed by western blot. RESULTS: Here we showed that WMW alleviates chronic colitis with improved survival rate, DAI, colon length and histological score. WMW inhibited the progression of intestinal fibrosis, decreased the expression of various fibrosis markers, such as α-SMA, collagen I, MMP-9 and fibronectin. In addition, WMW treatment reduced cytokines IL-6 and IFN-γ, and downregulated proinflammatory NF-κBp65 and STAT3 signaling pathways. Importantly, administration of WMW led to the inhibition of colon fibroblast proliferation and EMT, which are important mediators during fibrosis. Several key profibrotic pathways, including TGF-ß/Smad and Wnt/ß-catenin pathways, were downregulated by WMW treatment. CONCLUSION: Our work demonstrated that WMW can prevent intestinal fibrosis and the mechanisms involved may be related to the inhibition of colon fibroblasts activation.


Assuntos
Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Animais , Doença Crônica , Colite/complicações , Colite/imunologia , Colite/patologia , Colo/imunologia , Colo/patologia , Citocinas/sangue , Citocinas/imunologia , Fibrose , Masculino , Medicina Tradicional Chinesa , Camundongos Endogâmicos C57BL
9.
BMC Complement Altern Med ; 19(1): 314, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744490

RESUMO

BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear. METHODS: The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80+ ratio and CD11c+ ratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking. RESULTS: Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80+CD11c+ M1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding. Molecular docking suggested that BBR might interact with TLR4. CONCLUSIONS: Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.


Assuntos
Berberina/farmacologia , Macrófagos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Berberina/química , Polaridade Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/química , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/química , Fator 88 de Diferenciação Mieloide/genética , Ligação Proteica/efeitos dos fármacos , Células RAW 264.7 , Receptor 4 Toll-Like/química , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Adv Nutr ; 10(5): 791-802, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31212316

RESUMO

Dyslipidemia is a global health problem and a high risk factor for atherosclerosis, which can lead to serious cardiovascular disease (CVD). Existing studies have shown inconsistent effects of turmeric and curcuminoids on blood lipids in adults. We performed this systematic review and meta-analysis to evaluate the effects of turmeric and curcuminoids on blood triglycerides (TG), total cholesterol (TC), LDL cholesterol, and HDL cholesterol. We searched the English databases of the Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, and the Cochrane Library and 2 Chinese databases, Wanfang Data and China National Knowledge Infrastructure, for randomized controlled trials (RCTs) that studied the effects of turmeric and curcuminoids on blood TG, TC, LDL cholesterol, and HDL cholesterol in subjects with metabolic diseases. With random-effects models, separate meta-analyses were conducted by using inverse-variance. The results are presented as the mean difference with 95% CIs. Evidence from 12 RCTs for TG, 14 RCTs for TC, 13 RCTs for LDL cholesterol, and 16 RCTs for HDL cholesterol showed that turmeric and curcuminoids could lower blood TG by -19.1 mg/dL (95% CI: -31.7, -6.46 mg/dL; P = 0.003), TC by -11.4 mg/dL (95% CI: -17.1, -5.74 mg/dL; P < 0.0001), and LDL cholesterol by -9.83 mg/dL (95% CI: -15.9, -3.74 mg/dL; P = 0.002), and increase HDL cholesterol by 1.9 mg/dL (95% CI: 0.31, 3.49 mg/dL; P = 0.02). In conclusion, turmeric and curcuminoids can significantly modulate blood lipids in adults with metabolic diseases. However, these findings should be interpreted cautiously because of the significant heterogeneity between included studies (I2 > 50%). There is a need for further RCTs in future.


Assuntos
Curcuma , Diarileptanoides/administração & dosagem , Suplementos Nutricionais , Dislipidemias/sangue , Lipídeos/sangue , Doenças Metabólicas/sangue , Adulto , Doenças Cardiovasculares/etiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/complicações , Dislipidemias/terapia , Feminino , Humanos , Masculino , Doenças Metabólicas/complicações , Doenças Metabólicas/terapia , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
11.
Artigo em Inglês | MEDLINE | ID: mdl-31015847

RESUMO

Huanglian-Renshen-Decoction (HRD) is widely used to treat type 2 diabetes mellitus (T2DM) in China. However, the underlying mechanism is unclear. We aimed to investigate the mechanism by which HRD regulates the glucose level. Forty 7-8-week-old db/db (BSK) mice were randomly assigned to the following four groups: model, low dose HRD (LHRD), high dose HRD (HHRD), and saxagliptin (SAX). Additionally, 10 db/m mice were assigned to control group. The experimental mice were administered 3.03g/kg/d and 6.06g/kg/d of HRD in the LHRD and HHRD groups, respectively, and 10mg/kg/d saxagliptin in the SAX group for 8 weeks. The control and model groups were supplied with distilled water. After the intervention, the pancreas and blood were collected and tested. Compared with that of model group, the fasting blood glucose (FBG) was significantly decreased in all intervention groups (p < 0.05 or 0.01), whereas fasting serum insulin (FINS) was increased significantly in both HHRD and SAX groups. The immunofluorescence images showed that the mass of insulin+ cells was increased and that of glucagon+ cells was reduced obviously in experimental groups compared to those of the model group. In addition, the coexpression of insulin, glucagon, and PDX1 was decreased in HHRD group, and the level of caspase 12 in islet was decreased significantly in all intervention groups. However, little difference was found in the number and morphology of islet, and the expression of ki67, bcl2, bax, caspase 3, and cleaved-caspase 3 in the pancreas among groups. Interestingly, the cleaved-Notch1 level was increased and the Ngn3 level in islet was decreased significantly in HHRD group. The HRD showed dose-dependent effects on glucose metabolism improvement through maintenance of ß cell identity via a mechanism that might involve the Notch1/Ngn3 signal pathway in db/db mice.

12.
Sci Rep ; 9(1): 2278, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30783119

RESUMO

A topless potential energy with inverse square root is introduced to solve the energy spectrum equations and the bound state wave functions of the static Schrödinger equation by coordinate variation and combining the extraordinary coefficients of the confluent hypergeometric functions. Furthermore, the model of optical rectification (OR) and absorption coefficients (AC) with this special potential energy V(x) will appear regular changes. In this work, we explore the specific characteristics of the OR and AC with the inverse square root potential through multiple factors such as energy intervals and matrix elements.

13.
Stem Cells Int ; 2018: 7961962, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30515223

RESUMO

Background and Objective: This study investigated the effects and underlying mechanisms of azithromycin (AZM) treatment on the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) after their stimulation with TNF-α in vitro. Methods. PDLSCs were isolated from periodontal ligaments from extracted teeth, and MTS assay was used to evaluate whether AZM and TNF-α had toxic effects on PDLSCs viability and proliferation. After stimulating PDLSCs with TNF-α and AZM, we analyzed alkaline phosphatase staining, alkaline phosphatase activity, and alizarin red staining to detect osteogenic differentiation. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the mRNA expression of osteogenic-related genes, including RUNX2, OCN, and BSP. Western blotting was used to measure the NF-κB signaling pathway proteins p65, phosphorylated p65, IκB-α, phosphorylated IκB-α, and ß-catenin as well as the apoptosis-related proteins caspase-8 and caspase-3. Annexin V assay was used to detect PDLSCs apoptosis. Results: TNF-α stimulation of PDLSCs decreased alkaline phosphatase and alizarin red staining, alkaline phosphatase activity, and mRNA expression of RUNX2, OCN, and BSP in osteogenic-conditioned medium. AZM enhanced the osteogenic differentiation of PDLSCs that were stimulated with TNF-α. Western blot analysis showed that ß-catenin, phosphorated p65, and phosphorylated IκB-α protein expression decreased in PDLSCs treated with AZM. In addition, pretreatment of PDLSCs with AZM (10 µg/ml, 20 µg/ml) prevented TNF-α-induced apoptosis by decreasing caspase-8 and caspase-3 expression. Conclusions: Our results showed that AZM promotes PDLSCs osteogenic differentiation in an inflammatory microenvironment by inhibiting the WNT and NF-κB signaling pathways and by suppressing TNF-α-induced apoptosis. This suggests that AZM has potential as a clinical therapeutic for periodontitis.

14.
Cancer Manag Res ; 10: 2945-2952, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214289

RESUMO

Introduction: Although remarkable progress has been made to determine the prognosis of patients with colorectal cancer (CRC), it is inadequate to identify the subset of high-risk TNM stage II and stage III patients that have a high potential of developing tumor recurrence and may experience death. In this study, we aimed to develop biomarkers as a prognostic signature for the clinical outcome of CRC patients with stage II and stage III. Materials and methods: We performed a systematic and comprehensive discovery step to identify recurrence-associated genes in CRC patients through publicly available GSE41258 (n=253) and GSE17536 (n=107) datasets. We subsequently determined the prognostic relevance of candidate genes in stage II and III patients and developed a triple-biomarker for predicting RFS in GSE17536, which was later validated in an independent cohort GSE33113 dataset (n=90). Results: Based upon mRNA expression profiling studies, we identified 45 genes which differentially expressed in recurrent vs non-recurrent CRC patients. By using Cox proportional hazard models, we then developed a triple-marker model (THBS2, SERPINE1, and FN1) to predict prognosis in GSE17536, which successfully identified poor prognosis in stage II and stage III, particularly high-risk stage II CRC patients. Discussion: Notably, we found that our triple-marker model once again predicted recurrence in stage II patients in GSE33113. Kaplan-Meier survival analysis demonstrated that patients with high scores have a poor outcome compared to those with low scores. Our triple-marker model is a reliable predictive tool for determining prognosis in CRC patients with stage II and stage III, and might be able to identify high-risk patients that are candidates for more targeted personalized clinical management and surveillance.

15.
Opt Lett ; 43(15): 3550-3553, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30067707

RESUMO

Nonlinear optical refractive index changes (RICs) with polaron effects are studied in this Letter. The energy levels and wave functions of the polaron Schrödinger equation are calculated and brought into the nonlinear RICs to analyze the difference between the effects of the presence and absence of polarons, as well as the specific representation of RICs with polarons.

16.
Artigo em Inglês | MEDLINE | ID: mdl-30622603

RESUMO

Berberine (BBR) is the main active ingredient of a traditional Chinese herb Coptis chinensis. It has been reported to exhibit beneficial effects in treating diabetes and obesity. However, the underlying mechanism has not been fully elucidated. Adipose tissue fibrosis is a hallmark of obesity-associated adipose tissue dysfunction. HIF-1α plays a key role in adipose tissue fibrosis, which closely linked to metabolic dysfunction in obese state. We hypothesized that BBR may alleviate obesity-induced adipose tissue fibrosis and associated metabolic dysfunction through inhibition of HIF-1α. To test this hypothesis, we treated high fat diet (HFD) feeding mice with different dose of BBR (100 mg/kg, 200 mg/kg, and 300 mg/kg) for 8 weeks. We found that BBR treatment greatly decreased the body weight gain and reduced insulin resistance induced by HFD. Data also revealed that BBR improved histologic fibrous of epididymal white adipose tissue (eWAT) and was accompanied with inhibition of the abnormal synthesis and deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin. We also found that BBR treatment suppressed the expression of HIF-1α and decreased the mRNA expression of LOX in epididymal adipose tissue, which plays a key role in fibrosis development. Taken together, these results suggest that BBR can regulate metabolic homeostasis and suppress adipose tissue fibrosis through inhibiting the expression of HIF-1α.

17.
Mol Nutr Food Res ; 62(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28730734

RESUMO

SCOPE: This study aimed to systematically investigate whether sugarcane policosanol was effective and safe on dyslipidemia. METHODS AND RESULTS: A total of 11 databases including the PubMed, Web of science, Embase, Scopus, the Cochrane library and SinoMed databases were searched for available studies investigating the effects of policosanol on dyslipidemia. A total of 22 studies including 1886 subjects were included in the analysis. The pooled results showed that compared with placebo, sugarcane policosanol could significantly reduce total cholesterol (TC, 95% CI: -0.87 to -0.30 mmol/L) and low density lipoprotein cholesterol (LDL-c, 95% CI: -1.02 to -0.40 mmol/L) and increase high density lipoprotein cholesterol; however, no significant effects were observed on triglyceride (TG) and body weight. Subgroup analysis suggested the studies from Cuba obtained more effective data than those outside this country, and the effects were not proportional to the dose. The adverse effects analysis demonstrated that sugarcane policosanol was safer than the control agents. CONCLUSION: The pooled results supported the lipid-lowering effects and safety of policosanol. Because of the high heterogeneity, the better treatment effects observed in the Cuban studies and the inconsistent dose-response relationship, more clinical trials are needed to further confirm the efficacy of policosanol on dyslipidemia.


Assuntos
Anticolesterolemiantes/uso terapêutico , Dislipidemias/tratamento farmacológico , Álcoois Graxos/uso terapêutico , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Álcoois Graxos/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
18.
Front Pharmacol ; 8: 42, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28217099

RESUMO

Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages.

19.
J Ethnopharmacol ; 194: 260-268, 2016 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-27496582

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fenugreek is a widely used herb for the treatment of diabetes mellitus (DM) but the effects in randomized controlled trials (RCTs) were controversial. Therefore, a meta-analysis was conducted to estimate the overall effects of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes. MATERIALS AND METHODS: PubMed, EMBASE, web of science, Chinese Biomedical Literature database (CBM), the Cochrane library, China Doctor Dissertations Full-text Database (CDFD), Wan Fang medical database, China Proceedings of Conference Full-text Database (CPCD), China national knowledge internet (CNKI) and China Master's Theses Full-text Database (CMFD) were searched to find the available literatures. RCTs with regard to the efficacy and safety of fenugreek on prediabetes or DM were included. The data of fasting blood glucose (FBG), postprandial 2h blood glucose (2hBG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c) were extracted to appraise the net change with fixed or randomized effect model. RESULTS: A total of 10 articles (12 studies) were included in the analysis. Pooled results showed fenugreek significantly decreased the levels of FBG (MD -0.84mmol/L; 95% CI -1.38 to -0.31; p=0.002), 2hBG (MD -1.30mmol/L; 95% CI -1.78 to -0.83; p<0.0001), HbA1c (MD -1.16; 95% CI -1.23 to -1.09; p<0.00001) and TC (MD -0.30mmol/L; 95% CI-0.56 to -0.03; p=0.03). In spite of the reductive trends in the TG or LDL-c levels and incremental trends of HDL-c, these results were not statistically significant or need further verification for fenugreek in the treatment of DM and prediabetes. Some studies were of low quality. No liver and kidney toxicity were found in all included studies, and the main side effects were gastrointestinal discomfort. CONCLUSIONS: The results suggest fenugreek has the hypoglycaemic and TC-lowering efficacy; however, the effects on TG, LDL-c and HDL-c need further confirmations.


Assuntos
Diabetes Mellitus/terapia , Hiperglicemia/terapia , Hiperlipidemias/terapia , Estado Pré-Diabético/terapia , Trigonella , Diabetes Mellitus/sangue , Humanos , Estado Pré-Diabético/sangue
20.
ACS Appl Mater Interfaces ; 8(8): 5124-36, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26863404

RESUMO

Bacterial adhesion and biofilm formation are the primary causes of implant-associated infection, which is difficult to eliminate and may induce failure in dental implants. Chimeric peptides with both binding and antimicrobial motifs may provide a promising alternative to inhibit biofilm formation on titanium surfaces. In this study, chimeric peptides were designed by connecting an antimicrobial motif (JH8194: KRLFRRWQWRMKKY) with a binding motif (minTBP-1: RKLPDA) directly or via flexible/rigid linkers to modify Ti surfaces. We evaluated the binding behavior of peptides using quartz crystal microbalance (QCM) and atomic force microscopy (AFM) techniques and investigated the effect of the modification of titanium surfaces with these peptides on the bioactivity of Streptococcus gordonii (S. gordonii) and Streptococcus sanguis (S. sanguis). Compared with the flexible linker (GGGGS), the rigid linker (PAPAP) significantly increased the adsorption of the chimeric peptide on titanium surfaces (p < 0.05). Concentration-dependent adsorption is consistent with a single Langmuir model, whereas time-dependent adsorption is in line with a two-domain Langmuir model. Additionally, the chimeric peptide with the rigid linker exhibited more effective antimicrobial ability than the peptide with the flexible linker. This finding was ascribed to the ability of the rigid linker to separate functional domains and reduce their interference to the maximum extent. Consequently, the performance of chimeric peptides with specific titanium-binding motifs and antimicrobial motifs against bacteria can be optimized by the proper selection of linkers. This rational design of chimeric peptides provides a promising alternative to inhibit the formation of biofilms on titanium surfaces with the potential to prevent peri-implantitis and peri-implant mucositis.


Assuntos
Materiais Revestidos Biocompatíveis/uso terapêutico , Implantes Dentários/microbiologia , Peptídeos/química , Titânio/química , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Implantes Dentários/efeitos adversos , Humanos , Microscopia de Força Atômica , Peptídeos/uso terapêutico , Técnicas de Microbalança de Cristal de Quartzo , Streptococcus gordonii/efeitos dos fármacos , Propriedades de Superfície , Titânio/uso terapêutico
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