Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.966
Filtrar
1.
Arch Biochem Biophys ; 694: 108613, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010228

RESUMO

Cancer-associated fibroblasts (CAFs) play an important role in tumorigenesis, development, and migration. Eliminating CAFs or reducing their tumor-promoting activity is beneficial for tumor immunotherapy. Curcumin is a natural polyphenol derived from turmeric, which has been shown to inhibit the growth of many types of tumor. In this study, we explored the effect of curcumin on prostate-CAFs and its underlying molecular mechanism. The effect of curcumin on CAFs was measured using MTT assay and plate colony formation assay. Flow cytometry was used to detect cell apoptosis, ROS, Cell cycle, and mitochondrial membrane potential (ΔΨm) changes after curcumin treatment. Western Blot was used to detect changes in expression levels of related proteins in CAFs after curcumin stimulation. Colorimetry was used to detect the change of caspase 3 activity. The mRNA levels of Bims, Puma, ATF4 and CHOP were determined by qRT-PCR. We found that curcumin induced the apoptosis and cell cycle arrest of CAFs, which is mainly caused by the ROS-mediated endoplasmic reticulum stress pathway. For mechanism, the up-regulation of ROS caused by curcumin triggers endoplasmic reticulum stress of CAFs through the PERK-eIF2α-ATF4 axis. Our study suggests that curcumin selectively inhibits prostate-CAFs by inducing apoptosis and cell cycle arrest in G2-M phase, indicating a novel application of curcumin in tumor therapy.

2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1009-1014, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051413

RESUMO

OBJECTIVES: To investigate the effect of HBV infection on PTEN expression, and to explore the possible molecular mechanisms. METHODS: HepG2 cells and HepG2.2.15 cells were cultured under suitable conditions for 48 hours, and the expressions of PTEN, Nrf2 and pGSK3ß in HepG2 and HepG2.2.15 cells were detected by Western blotting. After the blank plasmid (EV) and the plasmid pWXL-Nrf2 were transiently transfected into HepG2 and HepG2.2.15 cells, respectively, the HepG2 and HepG2.2.15 cells were treated with the selective inhibitor of GSK3ß (25 nmol/L LiCl). After 48 h, the expressions of Nrf2, pGSK3ß and PTEN in HepG2 and HepG2.2.15 cells were examined by Western blotting. RESULTS: Expression of PTEN was reduced and the levels of Nrf2 and pGSK3ß were increased in HepG2.2.15 cells compared with those in the HepG2 cells (all P<0.05). After transfection with pWXL-Nrf2, the protein expression of Nrf2 and pGSK3ß in cells were significantly increased while the protein expression of PTEN was decreased (all P<0.05). Furthermore, LiCl treatment up-regulated the protein expression of Nrf2 and pGSK3ß, and eventually suppressed the production of PTEN (all P<0.05). CONCLUSIONS: HBV may down-regulate PTEN expression via Nrf2/GSK3ß signaling pathway, which may provide new ideas for the targeting therapy of hepatocellular carcinoma.


Assuntos
Neoplasias Hepáticas , Fator 2 Relacionado a NF-E2 , PTEN Fosfo-Hidrolase , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Vírus da Hepatite B/genética , Humanos , Fator 2 Relacionado a NF-E2/genética , PTEN Fosfo-Hidrolase/fisiologia , Transdução de Sinais
3.
Animals (Basel) ; 10(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066354

RESUMO

cAMP response element binding protein 1 (CREB1) is a member of the leucine zipper transcription factor family of DNA binding proteins. Although studies in non-ruminants have demonstrated a crucial role of CREB1 in lipid synthesis in liver and adipose tissue, it is unknown if this transcription regulator exerts control of fatty acid synthesis in ruminant mammary cells. To address this question, we first defined the expression dynamics of CREB1 in mammary tissue during lactation. Analysis of CREB1 in mammary tissue revealed higher mRNA abundance in mammary tissue harvested at peak lactation. Overexpression of CREB1 markedly upregulated sterol regulatory element binding transcription factor 1 (SREBP1), fatty acid synthase (FASN), acetyl-coenzyme A carboxylase α (ACACA), elongase of very long chain fatty acids 6 (ELOVL6), lipoprotein lipase (LPL), fatty acid binding protein 3 (FABP3), lipin 1 (LPIN1) and diacylglycerol acyltransferase 1 (DGAT1), but had no effect on glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) or 1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6). In addition, overexpressing CREB1 led to a significant increase in the concentration and desaturation index of C16:1 (palmitoleic acid) and C18:1 (oleic acid), along with increased concentration of triacylglycerol. Taken together, these results highlight an important role of CREB1 in regulating lipid synthesis in goat mammary epithelial cells. Thus, manipulation of CREB1 in vivo might be one approach to improve the quality of goat milk.

4.
Cancer Med ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067872

RESUMO

This study aimed to explore the roles of ERCC1/XPF gene polymorphisms in the occurrence of breast cancer in the Uygur and Han ethnic groups in Xinjiang, China. Single nucleotide polymorphisms (SNPs) were detected by TaqMan real-time PCR. The rs11615 G>A and rs2276466 C>G variant frequencies were higher in Uygur patients with breast cancer than in Han patients, while the frequency of rs2298881 C>A was higher in Han patients. We found that rs2298881 C>A (CA vs. CC: OR = 0.35, 95% CI = 0.20-0.60; AA vs. CC: OR = 0.13, 95% CI = 0.04-0.34; CA + AA vs. CC: OR = 0.33, 95% CI = 0.18-0.51; AA vs. CA + CC: OR = 0.24, 95% CI = 0.08-0.62; CA vs. AA + CC: OR = 0.49, 95% CI = 0.29-0.82) was associated with a reduced breast cancer risk and rs3212986 C>A (AA vs. CC: OR = 4.80, 95% CI = 1.79-15.29,; CA+AA vs. CC: OR = 1.71, 95% CI = 1.06-2.77; AA vs. CA+CC: OR = 4.12, 95% CI =1.58-12.89) and rs11615 G > A (AA vs. GG: OR = 3.49, 95% CI =1.54-8.55; GA + AA vs. GG: OR = 1.98, 95% CI = 1.21-3.27; AA vs. GA+GG: OR = 2.87, 95% CI = 1.30-6.85) were associated with an elevated breast cancer risk among Uygur individuals. In addition, Uygur patients with breast cancer with 2-3 combined risk genotypes of ERCC1 had a higher risk than patients with 0-1 risk genotypes (OR = 2.91; 95% CI = 1.54-5.71, p = 0.001). However, we failed to detect a statistically significant association between ERCC1/XPF polymorphisms and breast cancer risk in five genetic models among Han individuals. Our results showed that ERCC1/XPF gene polymorphisms predispose Uygur individuals to breast cancer; this finding should be verified by further large-scale analyses.

5.
Diabetes Metab ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058967

RESUMO

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is considered both a cause and consequence of the metabolic syndrome (MetS). While emerging evidence has indicated that testosterone is associated with MetS, the relationship between testosterone and NAFLD in women remains unclear. Therefore, this study investigated the associations between serum testosterone levels and NAFLD prevalence risk in a community-based cross-sectional study. METHODS: A total of 2117 adult women were included in the analysis. Serum total testosterone (TT) was measured by chemiluminescence immunoassay, and other testosterone-related indices, such as concentrations and percentages of calculated free testosterone (cFT) and bioavailable testosterone (BioT), and free androgen index (FAI), were also calculated. NAFLD was diagnosed by clinical criteria. Logistic regression was used to explore these associations. RESULTS: There were significant differences in TT, FAI, cFT and BioT between women with and without NAFLD (all P < 0.001). Multivariate logistic-regression analyses demonstrated that both absolute concentrations and percentages of cFT and BioT were positively associated with NAFLD risk prevalence in all models. Adjusted ORs (95% CI) for quartile 4 vs quartile 1 of % cFT and % BioT were 5.94 (4.29-8.22) and 5.21 (3.79-7.17) in model 2, and 4.35 (3.07-6.18) and 3.58 (2.55-5.03) in model 3 (all P < 0.001 for trend). In addition, quartiles of TT, FAI, cFT and BioT were significantly correlated with degree of hepatic steatosis. ROC analysis also showed that % cFT and % BioT were more accurate for predicting NAFLD prevalence than was TT. CONCLUSION: Serum cFT and BioT were positively associated with NAFLD risk, and elevated levels of cFT and BioT could be independent risk factors of NAFLD prevalence in middle-aged and elderly women.

6.
Mol Cell Biochem ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000352

RESUMO

Mitochondria have various cellular functions, including ATP synthesis, calcium homeostasis, cell senescence, and death. Mitochondrial dysfunction has been identified in a variety of disorders correlated with human health. Among the many underlying mechanisms of mitochondrial dysfunction, the opening up of the mitochondrial permeability transition pore (mPTP) is one that has drawn increasing interest in recent years. It plays an important role in apoptosis and necrosis; however, the molecular structure and function of the mPTP have still not been fully elucidated. In recent years, the abnormal opening up of the mPTP has been implicated in the development and pathogenesis of diverse diseases including ischemia/reperfusion injury (IRI), neurodegenerative disorders, tumors, and chronic obstructive pulmonary disease (COPD). This review provides a systematic introduction to the possible molecular makeup of the mPTP and summarizes the mitochondrial dysfunction-correlated diseases and highlights possible underlying mechanisms. Since the mPTP is an important target in mitochondrial dysfunction, this review also summarizes potential treatments, which may be used to inhibit pore opening up via the molecules composing mPTP complexes, thus suppressing the progression of mitochondrial dysfunction-related diseases.

7.
Int J Biol Sci ; 16(15): 3050-3061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061817

RESUMO

Our previous studies demonstrated that MEG3 was significantly downregulated in neuroblastoma (NB) and its expression was negatively associated with the INSS stage. Overexpression of MEG3 promoted apoptosis and inhibited proliferation in NB cells. In this study, we discovered more potential functions and molecular mechanisms of MEG3 in NB. According to the database, MEG3 positively correlated with the NB survival rate and was negatively associated with malignant clinical features. Moreover, we determined that MEG3 was mainly located in the nucleus by nuclear-cytoplasmic separation and RNA fish assays. Upregulation of MEG3 in stably transfected cell lines was accomplished, and CCK8, colony formation, and EDU assays were performed, which indicated that MEG3 significantly suppressed cell proliferation. Both wound healing and transwell experiments demonstrated that MEG3 decreased cell migration and invasion. CHIRP enrichments showed the anticancer effects of MEG3 were probably linked to autophagy and the mTOR signaling pathway. LC3 fluorescence dots and western blots showed that MEG3 attenuated autophagy by inhibiting FOXO1, but not the mTOR signaling pathway. Furthermore, MEG3 inhibited metastasis through epithelial-mesenchymal transition via the mTOR signaling pathway. Consistent with the above results, downregulation of MEG3 facilitated NB malignant phenotypes. Mechanistically, MEG3 and EZH2 regulated each other via a negative feedback loop and promoted NB progression together. In conclusion, our findings suggested that MEG3 was a tumor suppressor in NB and could be a potential target for NB treatment in the future.

8.
Medicine (Baltimore) ; 99(42): e22681, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080713

RESUMO

Button batteries are the second most frequently-ingested foreign bodies and can lead to serious clinical complications within hours of ingestion. The purpose of this study was to analyze the outcomes of 14 children with button batteries lodged in the upper gastrointestinal tract.Totally 14 children with button batteries lodged in the upper gastrointestinal tract were included. The diagnosis was made primarily by the history of button battery ingestion, physical examination and chest-abdomen X-ray examination.The button batteries lodged in the esophagus were removed by esophagoscope, and those in the gastrointestinal tract were under observation. Among 10 children with batteries in the first esophageal stenosis, 9 were cured and 1 suffered from tracheoesophageal fistula. One case of battery in the second esophageal stenosis was dead due to intercurrent aortoesophageal fistula. Two cases of batteries in the third esophageal stenosis were cured after removal, and 1 case of the battery in the gastrointestinal tract discharged spontaneously.Ingested button batteries are mainly lodged in the esophageal stenoses and are easy to cause esophageal injury and severe complications. Early detection, prompt treatment, strengthening observation and regular follow-up after discharge may help to decrease the incidence of complications and improve the outcomes.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33092212

RESUMO

Cadmium presence in soil is considered a significant threat to human health. Biochar is recognized as an effective method to immobilize Cd ions in different soils. However, obtaining effective and viable biochar to remove elevated Cd from postmining soil remains a challenge. More modifiers need to be explored to improve biochar remediation capacity. In this investigation, pot experiments were conducted to study the effects of poplar-bark biochar (PBC600) and thiourea-modified poplar-bark biochar (TPBC600) on Cd speciation and availability, as well as on soil properties. Our results showed that the addition of biochar had a significant influence on soil properties. In the presence of TPBC600, the acid-soluble and reducible Cd fractions were transformed into oxidizable and residual Cd fractions. This process effectively reduced Cd bioavailability in the soil system. Compared to PBC600, TPBC600 was more effective in improving soil pH, electrical conductivity (EC), organic matter (SOM), total nitrogen (TN), ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3--N), available potassium (AK), available phosphorus (AP), and available sulfur (AS). However, this improvement diminished as incubation time increased. Results of Pearson correlation analysis, multivariate linear regression analysis, and principal component analysis showed that soil pH and available phosphorus played key roles in reducing the available cadmium in soil. Therefore, TPBC600 was shown to be an effective modifier that could be used in the remediation of soil polluted with Cd.

10.
J Hazard Mater ; : 124224, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33092882

RESUMO

The prevalence of various antibiotic resistance genes (ARGs) and resistant bacteria has caused global public health risks. The carrier transport mediated by phages or membrane vesicles is an important way for horizontal transfer of ARGs. Nano metal oxide particles (NMOPs), which can enter cell through the cell membrane, may be used as the carriers of genes. However, whether they can be used as transmembrane delivery vectors for the horizontal ARG transfer remains unknown. Here, we set up a model of MONPs-mediated transfer of ARGs, and demonstrate that NMOPs, especially for nano-Al2O3, can act as carriers mediating the transduction-like ARG transformation in water. The highest transfer rate mediated by nano-Al2O3 is 4.53 × 104 cfu/mmol, and it is 104 times higher than that of control. Nano-Al2O3 can combine with plasmid coding for ARGs to form high-density package and prevent ARGs from degradation by endonuclease. The results of superresolution fluorescence microscopy and transmission electron microscopy show that nano-Al2O3 can carry ARGs for transmembrane transport. Genome-wide transcription microarray and qPCR indicate that SOS response was closely related to transduction-like ARG transformation mediated by nano-Al2O3. This study is the first to demonstrate that as a new transmembrane carrier, nano-Al2O3 can also cause ARGs diffusion in water.

11.
Cancer Epidemiol ; 69: 101801, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33017728

RESUMO

OBJECTIVE: To evaluate the performance of low-dose computed tomography (LDCT) on lung cancer screening in high-risk populations in Sichuan. METHODS: From April 2014 to July 2018, LDCT was performed annually on 3185 subjects aged 50-74 years who had smoked ≥ 20 pack-years (or subjects having quit smoking within 5 years). Information about all deaths and lung cancer diagnoses were obtained by active investigation, or passive matching to disease surveillance system. RESULTS: The screening population had a median age of 60 years. 62.4 % of which were current smokers and had smoked 30 pack-years. After participating in the baseline screening, the compliance rates of subjects consecutively completing one round, two rounds, three rounds, and four rounds of annual screening were 67.22 %, 52.84 %, 43.24 %, and 40.04 %, respectively. The positive rates in baseline and annual screening were 6.53 % and 5.79 %, respectively. During the 5 rounds, a total of 9522 person-times were screened by LDCT with a screening sensitivity of 89.13 % (95 % CI: 76.96-95.27), specificity of 94.36 % (95 % CI: 93.88-94.81), positive predictive value of 7.13 % (95 % CI: 5.30-9.53), and negative predictive value of 99.94 % (95 % CI: 99.87-99.98). There were no statistically significant performance differences between baseline and annual screening. The difference in the proportion of screen-detected stage I lung cancer between baseline screening and annual screening was not statistically significant, neither. CONCLUSION: The application of LDCT on lung cancer screening in high-risk populations shows favorable compliance and a high screening performance in the project area of Sichuan,China.

12.
Biomater Sci ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33103167

RESUMO

Traditional antimicrobial therapies always rely on antibiotics, which have led to the overuse of antibiotics and caused the emergence of multidrug-resistant (MDR) bacteria in recent years. In this study, an efficient and broad-spectrum antimicrobial system based on chitosan (CS)-encapsulated multifunctional metal-organic nanoparticles (Fe-TCPP@CS NPs) was constructed to integrate the electrostatic targeting property and photodynamic and photothermal antimicrobial therapies. Tetrakis (4-carboxyphenyl) porphyrin (TCPP) coordinated with Fe3O clusters to form nanoparticles, Fe3O clusters enabled low-temperature photothermal therapy as well as avoiding the porphyrins self-aggregation to ensure the singlet oxygen yield under irradiation, and CS as the outer layer covered on Fe-TCPP nanoparticles could improve the dispersibility in aqueous solution and enhance the electrostatic binding with bacterial cell membranes to improve the antibacterial activities. After simple synthesis, we successfully obtained ideal and biocompatible multifunctional nanoparticles and verified their antimicrobial properties. Under light irradiation, Fe-TCPP@CS NPs could produce enough ROS and heat to kill S. aureus, E. coli and methicillin-resistant S. aureus with a synergistic effect. Therefore, Fe-TCPP@CS NPs would be an efficient and broad-spectrum antimicrobial agent, providing a novel approach to bacterial infection therapy.

13.
J Am Heart Assoc ; : e016352, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33103569

RESUMO

Background Managing risk factors is crucial to prevent stroke. However, few cohort studies have evaluated socioeconomic factors together with conventional factors affecting incident stroke and its subtypes in China. Methods and Results A 2014 to 2016 prospective study from the China National Stroke Screening and Intervention Program comprised 437 318 adults aged ≥40 years without stroke at baseline. There were 2429 cases of first-ever stroke during a median follow-up period of 2.1 years, including 2206 ischemic strokes and 237 hemorrhagic strokes. The multivariable Cox regression analysis indicated that age 50 to 59 years (versus 40-49 years), primary school or no formal education (versus middle school), having >1 child (versus 1 child), living in Northeast, Central, East, or North China (versus Southwest China), physical inactivity, hypertension, diabetes mellitus, and obesity were positively associated with the risk of total and ischemic stroke, whereas age 60 to 69 years and living with spouse or children (versus living alone) were negatively associated with the risk of total and ischemic stroke. Men, vegetable-based diet, underweight, physical inactivity, hypertension, living in a high-income region, having Urban Resident Basic Medical Insurance, and New Rural Cooperative Medical System were positively associated with the risk of hemorrhagic stroke, whereas age 60 to 69 years was negatively associated with the risk of hemorrhagic stroke. Conclusions We identified socioeconomic factors that complement traditional risk factors for incident stroke and its subtypes, allowing targeting these factors to reduce stroke burden.

14.
Pharmacol Res ; : 105234, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33053446

RESUMO

Although it is feared that diabetes-induced cognitive impairment (DCI) will become a major clinical problem worldwide in the future, its detailed pathological mechanism is not well known. Because patients with diabetes have various complications of vascular disease, vascular disorders in the brain are considered to be one of the main mechanisms of DCI. Mounting evidence suggests that the vascular endothelial growth factor (VEGF) family plays a crucial role in the development of DCI. In this review, we summarized the changes and functions of VEGF during the development of DCI, and speculated that it was characterized by spatiotemporal variations in DCI progression. Considering the complexity of DCI pathogenesis and the diversity of VEGF function, we focused on the interrelationship of DCI and VEGF spatiotemporal variations during DCI development. During the progression of DCI, hyperglycemia, abnormal brain insulin signals, advanced glycation end products (AGEs) and consequently hypoxia, oxidative stress, and inflammation are the main pathophysiological changes; hypoxia-inducible factor (HIF), reactive oxygen species (ROS), and nuclear factor kappa beta (NF-κB) play major roles in DCI-related VEGF spatiotemporal regulation. Furthermore, spatiotemporal variations in VEGF-mediated pathological cerebral neovascularization, repair and regeneration of dural lymphatic vessels, increased blood-brain barrier (BBB) permeability and slight neuroprotection are increasing emphasized as potential targets in the treatment of DCI.

15.
Chemistry ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107654

RESUMO

Chiral α-amino acids play critical roles in the metabolic process in nearly all life forms. So far, chiral recognitions of α-amino acids have mainly focused on the determination of L / D enantiomers. Herein, selection of planar chiral conformations between water-soluble pillar[5]arene WP5 and pillar[6]arene WP6 was observed due to α -side chain or ethyl ester moieties of L - α -amino acid ethyl ester hydrochlorides binding with WP5 and WP6 , respectively. Therefore, α -side chain and ethyl ester moieties of L - α -amino acid ethyl ester hydrochlorides were recognized by observing the induced CD signal and its inversion. It is the rare example that the chiral region around α -carbon of a chiral α -amino acid molecule could be detected.

16.
Int J Mol Sci ; 21(20)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066688

RESUMO

Soybean (Glycine max) is an important crop providing oil and protein for both human and animal consumption. Knowing which biological processes take place in specific tissues in a temporal manner will enable directed breeding or synthetic approaches to improve seed quantity and quality. We analyzed a genome-wide transcriptome dataset from embryo, endosperm, endothelium, epidermis, hilum, outer and inner integument and suspensor at the global, heart and cotyledon stages of soybean seed development. The tissue specificity of gene expression was greater than stage specificity, and only three genes were differentially expressed in all seed tissues. Tissues had both unique and shared enriched functional categories of tissue-specifically expressed genes associated with them. Strong spatio-temporal correlation in gene expression was identified using weighted gene co-expression network analysis, with the most co-expression occurring in one seed tissue. Transcription factors with distinct spatiotemporal gene expression programs in each seed tissue were identified as candidate regulators of expression within those tissues. Gene ontology (GO) enrichment of orthogroup clusters revealed the conserved functions and unique roles of orthogroups with similar and contrasting expression patterns in transcript abundance between soybean and Arabidopsis during embryo proper and endosperm development. Key regulators in each seed tissue and hub genes connecting those networks were characterized by constructing gene regulatory networks. Our findings provide an important resource for describing the structure and function of individual soybean seed compartments during early seed development.

17.
Nat Commun ; 11(1): 5015, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024120

RESUMO

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).

19.
Artigo em Inglês | MEDLINE | ID: mdl-32995892

RESUMO

CONTEXT: Up to 40% polycystic ovary syndrome (PCOS) patients have prediabetes, an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established. OBJECTIVE: To evaluate clinical efficacy of exenatide (EX), metformin (MET) or combination (COM) for prediabetes in PCOS. DESIGN: Randomized, open-label, parallel-group controlled trial. SETTING: Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. PATIENTS: PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2-h post glucose 7.8-11.0 mmol/L on OGTT). 150 out of 183 eligible enrollees completed the study. INTERVENTION: EX (10-20 µg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks. MAIN OUTCOME MEASURES: Sustained remission rate of prediabetes (primary endpoint, a normal OGTT after 12 weeks of treatment followed by 12 weeks of washout on no drug treatment) along with anthropometric, hormonal, metabolic, and pancreatic ß-cell function parameters (secondary endpoints) and potential mechanisms were assessed. RESULTS: IGT was found the dominant prediabetes phenotype. Overall sustained prediabetes remission rate was 50.7%. Remission rate of COM group (64%, 32/50) or EX group (56%, 28/50) was significantly higher than that of MET group (32%, 16/50) (p = 0.003 and 0.027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A two-step hyperglycemic clamp study further revealed that EX had led to higher postprandial insulin secretion as compared to MET, potentially explaining the higher remission rate. CONCLUSIONS: As compared to MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.

20.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867345

RESUMO

Dalbergia benthami Prain (D.benthami) is an important legume species of the Dalbergia family, due to the use of its trunk and root heart in traditional Chinese medicine (TCM). In the present study, we reported the isolation, characterization and pharmacological activities of robustic acid (RA) from the ethyl acetate extract of D. benthami Prain. The SwissADME prediction showed that the RA satisfied the Lipinski's rule of five (molecule weight (MW): 380.39 g/mol, lipid-water partition coefficient (log P): 3.72, hydrogen bond donors (Hdon): 1, hydrogen bond acceptors (Hacc): 6, rotatable bonds (Rbon): 3. Other chemical and pharmacological properties of this RA were also evaluated, including topological polar surface area (TPSA) = 78.13 Šand solubility (Log S) = -4.8. The probability values of the antineoplastic, anti-free radical activities and topoisomerase I (TopoⅠ) inhibitory activity were found to be 0.784, 0.644 and 0.379, respectively. The molecular docking experiment using the Surflex-Dock showed that the Total Score and C Score of RNA binding with the human DNA-Topo I complex were 7.80 and 4. The MTS assay experiment showed that the inhibitory rates of RA on HL-60, MT4, Hela, HepG2, SK-OV-3 and MCF-7 cells were 37.37%, 97.41%, 81.22%, 34.4%, 32.68% and 51.4%, respectively. In addition, RA exhibited an inhibitory effect on the angiogenesis of zebrafish embryo, a good TopoⅠ inhibitory activity at a 10 mM concentration and in a dose-dependent manner, excellent radical scavenging in the DPPH and ABTS assays, and the free radical scavenging rate was close to the positive control (BHT) at different concentrations (0.5-2.0 mg/mL). Furthermore, 18 potential targets were found for this RA by PharmMapper, including ANXA3, SRC, FGFR2, GSK3B, CSNK2B, YARS, LCK, EPHA2, MAPK14, RORA, CRABP2, PPP1CC, METAP2, MME, TTR, MET and KDR. The GO and KEGG pathway analysis revealed that the "protein tyrosine kinase activity", "rap1 signaling pathway" and "PI3K-Akt signaling pathway" were significantly enriched by the RA target genes. Our results will provide new insights into the pharmaceutical use of this species. More importantly, our data will expand our understanding of the molecular mechanisms of RA functions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA