Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 225
Filtrar
1.
Diabetes Metab J ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33752319

RESUMO

Background: Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. Methods: Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. Results: Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=-0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=-0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. Conclusion: Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

2.
FEMS Microbiol Lett ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33693611

RESUMO

Russula griseocarnosa is one of the uncultivable important mycorrhizal edible fungi. Currently, there is a limited insight into the dynamic composition of the microbial communities associated with Russula. Here, the microbiota in the root and mycorrhizosphere from Russula-Fagaceae nature areas of Fujian province were identified by Illumina MiSeq high-throughput sequencing. First, we compared three types of fungal communities associated with Russula-Fagaceae root mycelia-running stage (stage-1), Russula sporocarping stage-2 (stage-2), and Russula -free Fagaceae root (stage-3). Fungal diversity negatively correlated with Russula. Russula, Tomentella, and Lactarius were core EcM in Fagaceae roots. Eight genera, including Boletus, are likely a positive indicator of Russula sporocarp production in Russula-Fagaceae roots, while Tomentella and Elaphomyces for Russula symbiosis. Secondly, analysis of fungal and bacterial communities within rhizosphere soils from the three stages revealed six genera, including Dacryobolus and Acidocella, as possible indicator species associated with sporocarping in Russula. Elaphomyces, Tomentella, Sorangium, Acidicaldus, Acidobacterium, and Haliangium occurred more frequently in the Russula rhizosphere. Furthermore, operational taxonomic unit (OTU) network analysis showed a positive correlation between Russula, Tomentella, Elaphomyces, and Sorangium. Overall, our results revealed a relationship between micro-community and Russula, which may provide a new strategy for improving Russula symbiosis and sporocarp production.

3.
Zhongguo Zhen Jiu ; 41(1): 31-5, 2021 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-33559439

RESUMO

OBJECTIVE: To compare the therapeutic effect between acupuncture combined with ibuprofen sustained-release capsule and simple ibuprofen sustained-release capsule on chronic pelvic pain (CPP) after pelvic inflammatory disease (PID). METHODS: A total of 144 patients were randomized into an observation group (72 cases, 10 cases dropped off) and a control group (72 cases, 9 cases dropped off). Ibuprofen sustained-release capsule was given orally in the control group, one capsule a time. On the basis of the treatment in the control group, acupuncture was applied at Guanyuan (CV 4), Shuidao (ST 28), Guilai (ST 29), Shenshu (BL 23) and Ciliao (BL 32), and Shuidao (ST 28), Guilai (ST 29), Shenshu (BL 23) and Ciliao (BL 32) were connected to electroacupuncture in the observation group. The treatment was given 10 days before menstruation, once a day for 3 menstrual cycles in both groups, and the follow-up was adopted 3 menstrual cycles after treatment. The visual analogue scale (VAS) scores of hypogastrium and lumbosacral region before treatment, after treatment, and at the follow-up, the score of local signs and the score of World Health Organization quality of life questionnaire-brief version (WHOQOL-BREF) before and after treatment were observed in the both groups. RESULTS: After treatment and at the follow-up, the VAS scores of hypogastrium and lumbosacral region were decreased compared before treatment in both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, except for the score of uterosacral ligament tenderness in the control group, the scores of local signs were decreased compared before treatment in both groups (P<0.05), and the score of uterine appendages tenderness, the total score of local signs in the observation group were lower than the control group (P<0.05). Compared before treatment, the physiological scores of WHOQOL-BREF were increased in both groups (P<0.05), the scores of psychology, social relations and environment were increased in the observation group (P<0.05), and the physiological score was higher than the control group (P<0.05). CONCLUSION: Acupuncture combined with ibuprofen sustained-release capsule can effectively improve the symptoms, signs and quality of life in patients with CPP after PID, the therapeutic effect is superior to simple ibuprofen sustained-release capsule.


Assuntos
Terapia por Acupuntura , Doença Inflamatória Pélvica , Pontos de Acupuntura , Feminino , Humanos , Doença Inflamatória Pélvica/tratamento farmacológico , Doença Inflamatória Pélvica/etiologia , Dor Pélvica/tratamento farmacológico , Dor Pélvica/etiologia , Qualidade de Vida , Resultado do Tratamento
4.
Sci Rep ; 11(1): 655, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436935

RESUMO

The coexistence of HBV infection and hepatic steatosis is a novel characteristic of liver disease. Silibinin capsules (SC) is a silybin-phospholipid complex containing silybin as the bioactive component, which exerts a remarkable biological effect on various liver diseases, including nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to investigate (1) the prevalence of hepatic steatosis in the general population and patients with chronic hepatitis B (CHB) and (2) to evaluate the effect of SC combined with therapeutic lifestyle changes (TLC) compared with TLC alone on hepatic steatosis in patients with CHB. A total of 16,451 individuals underwent transient elastography (TE) with the control attenuation parameter (CAP) measurement, among which the prevalence of hepatic steatosis was 31.1% in patients with CHB and 42.2% in the general population. The prevalence of hepatic steatosis differed between patients with CHB and the general population at an age of 40 years or older but was similar in individuals aged 39 years or younger (p < 0.05). Furthermore, in patients with CHB presenting hepatic steatosis, the post-6-month relative reduction in CAP in the SC combined with TLC group (p = 0.001) was significantly greater than in the TLC alone group (p = 0.183). The CAP distribution of different steatosis grades (S1, S2, and S3) in the SC combined with TLC group was decreased and S0 (CAP < 248 dB/m) increased significantly, but not significant in the TLC group. Thus, SC combined with TLC may effectively improve hepatic steatosis in patients with CHB.

5.
J Ethnopharmacol ; 266: 113443, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33022344

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chansu, dried secretions from Bufonidae, has long been used for cancer treatment as a traditional Chinese medicine. In searching for effective anti-hepatoma agents from Chansu, our preliminary drug screening found that a bufadienolide, namely 1ß-hydroxyl-arenobufagin (1ß-OH-ABF), displays anti-hepatoma activities. However, the anti-hepatoma effects and molecular mechanisms of 1ß-OH-ABF have not been defined. AIM OF THE STUDY: To evaluate the anti-hepatoma activity of 1ß-OH-ABF against liver cancer Hep3B and HepG2 cells in vitro and in vivo, as well as explore the underlying mechanisms. MATERIALS AND METHODS: The anti-proliferative effects of 1ß-OH-ABF on liver cancer Hep3B, HepG2, HuH7, SK-HEP-1 and normal hepatocyte LO2 cells were examined by MTT assay and colony formation assay. Hoechst 33258 staining and Annexin V-FITC/PI staining assay were used to analyze apoptosis induced by 1ß-OH-ABF. The collapse of the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining assay. Western blotting was used to examine the expression levels of targeted proteins. The role of mTOR in 1ß-OH-ABF-induced apoptosis was investigated using small interfering RNA (siRNA) transfection. Zebrafish xenograft model was established to evaluate the anti-hepatoma effects of 1ß-OH-ABF in vivo. RESULTS: We found that 1ß-OH-ABF inhibits the proliferation of Hep3B, HepG2, HuH7, SK-HEP-1 cells but has little cytotoxicity towards LO2 cells. 1ß-OH-ABF induces mitochondria dysfunction and triggers mitochondria apoptotic pathway, which is accompanied by the loss of ΔΨm, upregulation and translocation of Bax, as well as cleavages of caspase-9, caspase-3 and PARP. Mechanistically, 1ß-OH-ABF markedly decreases the expression level of p-AKT/AKT and p-mTOR (Ser2248 and Ser2481)/mTOR in a time-dependent manner. Inhibition of mTOR by siRNA strengthens 1ß-OH-ABF-mediated apoptosis. Critically, 1ß-OH-ABF shows a marked in vivo anti-hepatoma effect on human Hep3B cell xenografts in zebrafish model. CONCLUSION: 1ß-OH-ABF induces mitochondrial apoptosis through the suppression of mTOR signaling in vitro and in vivo, indicating that 1ß-OH-ABF may serve as a potential agent for the treatment of liver cancer.


Assuntos
Antineoplásicos/farmacologia , Bufanolídeos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Bufanolídeos/química , Bufanolídeos/isolamento & purificação , Carcinoma Hepatocelular/patologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Mitocôndrias/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
6.
Bioresour Technol ; 320(Pt B): 124336, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33217692

RESUMO

The impacts of magnesium-ammonium-phosphate (MAP) precipitation on the performance and microbial dynamics in an anaerobic continuously stirred tank reactor (CSTR) coupled with sequencing batch reactor (SBR) for swine wastewater treatment were investigated. In CSTR-SBR systems, an overall higher removal efficiency for COD, NH4+ and PO43-as 98.6%, 98.7% and 97.9% was achieved with MAP precipitation, compared to CSTR-SBR without MAP pretreatment (i.e., 97.5, 74.3% and 19.9% for COD, NH4+ and PO43-, respectively). With MAP precipitation, the high C/N ratio of 6.6 after anaerobic CSTR was observed. The increase in the richness and diversity of microbial communities in CSTR with MAP was conducive to nitrogen and phosphorus removal, as well as biogas production. The core community was affiliated with bacterial phyla Firmicutes, Bacteroidetes, Proteobacteria, Cloacimonetes, and Spirochaetae. The study provide a new insight into the potential application of MAP precipitation as pretreatment for dealing with nutrient recovery from high-strength swine wastewater.

7.
Mol Cell Endocrinol ; : 111079, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33189863

RESUMO

High fructose is considered a causative factor for oxidative stress and autophagy imbalance that cause kidney pathogenesis. Antioxidant polydatin isolated from Polygonum cuspidatum has been reported to protect against kidney injury. In this study, polydatin was found to ameliorate fructose-induced podocyte injury. It activated mammalian target of rapamycin complex 1 (mTORC1) and suppressed autophagy in glomeruli of fructose-fed rats and in fructose-exposed conditionally immortalized human podocytes (HPCs). Polydatin also enhanced nuclear factor-E2-related factor 2 (Nrf2)-dependent antioxidant capacity to suppress fructose-induced autophagy activation in vivo and in vitro, with the attenuation of fructose-induced up-regulation of cellular light chain 3 (LC3) II/I protein levels. This effect was abolished by Raptor siRNA in fructose-exposed HPCs. These results demonstrated that polydatin ameliorated fructose-induced autophagy imbalance in an mTORC1-dependent manner via improving Nrf2-dependent antioxidant capacity during podocyte injury. In conclusion, polydatin with anti-oxidation activity suppressed autophagy to protect against fructose-induced podocyte injury.

8.
Signal Transduct Target Ther ; 5(1): 214, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033232

RESUMO

Epidermal growth factor receptor (EGFR) activation plays a pivotal role in EGFR-driven non-small cell lung cancer (NSCLC) and is considered as a key target of molecular targeted therapy. EGFR tyrosine kinase inhibitors (TKIs) have been canonically used in NSCLC treatment. However, prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs. Therefore, the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance. Here, we identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel EGFR small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR. Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR. DPBA did not induce EGFR dimerization, phosphorylation, and ubiquitination, but it significantly promoted EGFR degradation and repressed downstream survival pathways. Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs. Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation. The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC, particularly NSCLC with innate or acquired EGFR TKI resistance. DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.

9.
Anal Methods ; 12(42): 5097-5102, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33047756

RESUMO

Carbon dots (CDs) with blue fluorescence were synthesized using indole-3-butyric acid and l-tryptophan using a one-step hydrothermal method. The CDs were further employed as a fluorescent sensor with high selectivity for colorimetric and ratiometric detection of tetracycline (TC) in water. The limit of detection (LOD) was found to be 0.33 µM for TC with R2 = 0.98387. Besides, the CDs could be applied in practical water samples and showed good recovery.

10.
Chin J Nat Med ; 18(9): 696-703, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32928513

RESUMO

Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α (HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evidence has demonstrated that HIF-1α promotes tumor angiogenesis, metastasis, metabolism, and immune evasion. Natural products are an important source of antitumor drugs and numerous studies have highlighted the crucial role of these agents in modulating HIF-1α. The present review describes the role of HIF-1α in tumor progression, summarizes natural products used as HIF-1α inhibitors, and discusses the potential of developing natural products as HIF-1α inhibitors for the treatment of cancer.

11.
Fish Physiol Biochem ; 46(6): 2227-2242, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32948974

RESUMO

Environmental changes in intensive aquaculture commonly lead to hypoxic stress for cultured largemouth bass (Micropterus salmoides). To better to understand the hypoxic stress response mechanisms, the miRNA expression profiles of the livers of largemouth bass exposed for 24 h to three different dissolved oxygen levels (7.0 ± 0.2 mg/L as control, 3.0 ± 0.2 mg/L and 1.2 ± 0.2 mg/L) were compared. In this study, a total of 266 known miRNAs were identified, 84 of which were differentially expressed compared with the control group. Thirteen of the differentially expressed miRNAs (miR-15b-5p, miR-30a-3p, miR-133a-3p, miR-19d-5p, miR-1288-3p, miR456, miR-96-5p, miR-23a-3p, miR-23b-5p, miR-214, miR-24, miR-20a-3p, and miR-2188-5p) were significantly enriched in VEGF signaling pathway, MAPK signaling pathway, and phosphatidylinositol signaling system. These miRNAs were significantly downregulated during stress, especially after a 4-h exposure to hypoxia. In contrast, their target genes (vegfa, pla2g4a, raf1a, pik3c2a, clam2a, inpp1, pi4k2b, mtmr14, ip6k, itpkca, map3k7, and Jun) were significant upregulated after 4 h of hypoxic stress. Moreover, two potential hypoxia-tolerance signal transduction pathways (MAPK signaling pathway and phosphatidylinositol signaling system) were revealed, both of which may play important roles in responding to acute hypoxic stress. We see that miRNAs played an important role in regulating gene expression related to physiological responses to hypoxia. Potential functional network regulated by miRNAs under hypoixic stress in the liver of largemouth bass (Micropterus salmoides). Blue boxes indicated that the expression of miRNA or target genes were down-regulated. Red boxes indicated that the expression of miRNA or target genes wasere up-regulated.

12.
Sheng Li Xue Bao ; 72(4): 499-505, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32820312

RESUMO

The transforming growth factor-ß-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family. TAK1 plays important roles in many biological functions. Cardiac hypertrophy can be identified as physiological or pathological myocardial hypertrophy. TAK1 not only participates in the development of normal myocardium, but also plays an important role in regulating the occurrence and development of pathological myocardial hypertrophy. Angiotensin II (Ang II) or pressure overload induces pathological cardiac hypertrophy through different ways, such as hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional expression of TAK1, or transforming growth factor-ß1 (TGF-ß1)-, thyroid hormone-, ubiquitin protease-mediated TAK1 phosphorylation or ubiquitination. This article reviews the role of TAK1 in the occurrence and development of pathological myocardial hypertrophy and discusses the potential of TAK1 as an important target for the prevention and treatment of clinical myocardial hypertrophy.


Assuntos
MAP Quinase Quinase Quinases/genética , Fator de Crescimento Transformador beta1 , Cardiomegalia , Humanos , Miocárdio , Fosforilação , Fator de Crescimento Transformador beta
13.
Eur J Pharmacol ; 887: 173379, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758567

RESUMO

Bufadienolides are cardioactive C24 steroids with an α-pyrone ring at position C17. In the last ten years, accumulating studies have revealed the anticancer activities of bufadienolides and their underlying mechanisms, such as induction of autophagy and apoptosis, cell cycle disruption, inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and stemness, and multidrug resistance reversal. As Na+/K+-ATPase inhibitors, bufadienolides have inevitable cardiotoxicity. Short half-lives, poor stability, low plasma concentration and oral bioavailability in vivo are obstacles for their applications as drugs. To improve the drug potency of bufadienolides and reduce their side effects, prodrug strategies and drug delivery systems such as liposomes and nanoparticles have been applied. Therefore, systematic and recapitulated information about the antitumor activity of bufadienolides, with special emphasis on the molecular or cellular mechanisms, prodrug strategies and drug delivery systems, is of high interest. Here, we systematically review the anticancer effects of bufadienolides and the molecular or cellular mechanisms of action. Research advancements regarding bufadienolide prodrugs and their tumor-targeting delivery strategies are critically summarized. This work highlights recent scientific advances regarding bufadienolides as effective anticancer agents from 2011 to 2019, which will help researchers to understand the molecular pathways involving bufadienolides, resulting in a selective and safe new lead compound or therapeutic strategy with improved therapeutic applications of bufadienolides for cancer therapy.

14.
PLoS One ; 15(8): e0237947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833961

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Inflammation has been proven to be one of the characteristics of malignant tumors. Chronic inflammatory response mediated by cytokines in the tumor microenvironment is an important factor in tumorigenesis. The purpose of this study was to observe and evaluate the value of red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin-to-red blood cell distribution width ratio (HRR) in the progression of NSCLC. METHODS: A total of 245 patients with NSCLC, 97 patients with benign pulmonary nodules, and 94 healthy volunteers were included in this study. Factors, such as age, gender, smoking history, histological type, lymph node metastasis, distant metastasis, TNM stage, and differentiation degree were statistically analyzed. The correlation of RDW, NLR, and HRR of patients with NSCLC with other clinical experimental parameters were also analyzed. Then, the diagnostic value of RDW, NLR, and HRR in the progression of NSCLC was evaluated. RESULTS: RDW, NLR, and HRR could be used to distinguish patients with NSCLC from healthy controls (p < 0.05). In addition, only the RDW in the NSCLC group with III-IV stage was significantly different from that in the benign pulmonary nodules group (p = 0.033), while NLR and HRR could significantly distinguish patients with NSCLC and benign pulmonary nodules (p < 0.001). RDW and NLR were positively correlated with NSCLC stage, whereas HRR was negatively correlated with NSCLC stage. RDW, NLR, and HRR were also significantly associated with the differentiation degree of NSCLC (p < 0.05). The ROC curve analysis showed that the combination of RDW with NLR, HRR, and CEA could show significantly higher diagnostic value than any one marker alone (AUC = 0.925, 95% CI: 0.897-0.954, and sensitivity and specificity of 79.60% and 93.60%, respectively). CONCLUSION: RDW, NLR, and HRR can be utilized as simple and effective biomarkers for the diagnosis and evaluation of NSCLC progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Progressão da Doença , Eritrócitos/citologia , Hemoglobinas/metabolismo , Neoplasias Pulmonares/imunologia , Linfócitos/citologia , Neutrófilos/citologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Contagem de Células , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
J Nat Prod ; 83(8): 2313-2319, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32683864

RESUMO

Six new structurally diverse indole alkaloids, melohemsines J-M (1-4), 11-hydroxy-Δ14-vincamine (5), and 11-hydroxy-16-epi-Δ14-vincamine (6), and 15 known alkaloids were isolated from the leaves and twigs of Melodinus hemsleyanus Diels. These new compounds and their absolute configurations were determined through spectroscopic data analyses, X-ray diffraction, and computational methods. Melohemsine J (1) is the first example of a melodinus-type alkaloid possessing a 6/6/5/5/6/5 hexacyclic skeleton and containing a tetrahydrofuro[2,3-b]pyridine-2(3H)-one unit. Melohemsine K (2) is an unusual aspidosperma-type alkaloid possessing a 6/5/6/5/5 pentacyclic architecture with a contracted E ring (loss of CH2). Compounds 5-10 and 16 exhibited vasorelaxant activities with EC50 values of 0.8-3.8 µM. In addition, compound 4 displayed moderate cytotoxicity toward the tumor cell lines HepG2 and A-549 with EC50 values of 18.7 and 28.7 µM, respectively.

16.
Endocr J ; 67(11): 1107-1117, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-32684527

RESUMO

Type 2 diabetes (T2D) is characterized by islet ß-cell dysfunction and impaired suppression of glucagon secretion of α-cells in response to oral hyperglycaemia. Bile acid (BA) metabolism plays a dominant role in maintaining glucose homeostasis. So we evaluated the association of fasting serum total bile acids (S-TBAs) with insulin sensitivity, islet ß-cell function and glucagon levels in T2D. Total 2,952 T2D patients with fasting S-TBAs in the normal range were recruited and received oral glucose tolerance tests for determination of fasting and postchallenge glucose, C-peptide and glucagon. Fasting and systemic insulin sensitivity were assessed by homeostasis model assessment (HOMA) and Matsuda index using C-peptide, i.e., ISHOMA-cp and ISIM-cp, respectively. Islet ß-cell function was assessed by the insulin-secretion-sensitivity-index-2 using C-peptide (ISSI2cp). The area under the glucagon curve (AUCgla) was used to assess postchallenge glucagon. The results showed ISHOMA-cp, ISIM-cp and ISSI2cp decreased, while AUCgla notably increased, across ascending quartiles of S-TBAs but not fasting glucagon. Moreover, S-TBAs were inversely correlated with ISHOMA-cp, ISIM-cp and ISSI2cp (r = -0.21, -0.15 and -0.25, respectively, p < 0.001) and positively correlated with AUCgla (r = 0.32, p < 0.001) but not with fasting glucagon (r = 0.033, p = 0.070). Furthermore, after adjusting for other clinical covariates by multiple linear regression analyses, the S-TBAs were independently associated with ISHOMA-cp (ß = -0.04, t = -2.82, p = 0.005), ISIM-cp (ß = -0.11, t = -7.05, p < 0.001), ISSI2cp (ß = -0.15, t = -10.26, p < 0.001) and AUCgla (ß = 0.29, t = 19.08, p < 0.001). Increased fasting S-TBAs are associated with blunted fasting and systemic insulin sensitivity, impaired islet ß-cell function and increased glucagon levels in response to glucose challenge in T2D.

17.
J Leukoc Biol ; 108(2): 493-508, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32678943

RESUMO

A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid-derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF-κB, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.

18.
Sleep Breath ; 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32592022

RESUMO

PURPOSE: The current study was conducted to explore the clinical features and risk factors of patients with asthma complicated by obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Patients with asthma who underwent polysomnography in our hospital from August 2017 to December 2019 were enrolled in the study. Data on demographics, pulmonary function testing, polysomnography, blood gases, mean pulmonary artery pressure, and vascular endothelial growth factor (VEGF) were compared between the two groups. RESULTS: Of 238 patients with asthma, 93 who also had OSAHS formed the observation group and were subclassified into mild (n = 33), moderate (n = 41), and severe (n = 19) categories, while 145 patients with asthma alone were assigned to the control group. No significant differences were found in sex, age, course of disease, or pulmonary function between the two groups (P > 0.05), while the observation group showed more frequent allergic rhinitis and had greater BMI, neck circumference, mean pulmonary artery pressure (mPAP), and VEGF than those in the control group (P < 0.001). The peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC in the mild group and the moderate group were higher than those in the severe group (P < 0.001). The durations of AHI and SaO2 < 90% in the mild group and the moderate group were shorter than that in the severe group, and the lowest level of SaO2 in the mild group and the moderate group was higher than that in the severe group (P <  0.05). The mPAP and VEGF of the mild and moderate groups were lower than those of severe group (P < 0.001), with mild group lower than moderate group (P < 0.001). CONCLUSION: Significant differences in allergic rhinitis, BMI, neck circumference, AHI, SaO2, mPAP, and VEGF were observed in patients with asthma complicated by OSAHS. These parameters are risk factors associated with asthma complicated by OSAHS.

19.
Diabetol Metab Syndr ; 12: 44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477430

RESUMO

Background: The role of serum fibroblast growth factor 19 (FGF19) in arteriosclerosis is not well known. In the present study, we aimed to explore whether serum FGF19 levels were related to arteriosclerosis parameters, including arterial stiffness and atherogenic index of plasma (AIP), in patients with type 2 diabetes (T2D). Methods: A total of 200 patients with type 2 diabetes and 50 healthy controls were recruited for this study from Apr 2017 to Oct 2018. Serum FGF19 levels, arterial stiffness assessed by brachial ankle pulse wave velocity (baPWV), and AIP assessed by the triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio were measured in those subjects. In addition, other relevant clinical data were also collected. Results: Serum FGF19 levels in T2D patients were significantly lower than those in healthy controls (p < 0.05). The arteriosclerosis parameters, including baPWV and AIP, significantly decreased across ascending tertiles of serum FGF19 levels (all p for trend < 0.001). Moreover, the baPWV and AIP were all inversely correlated with serum FGF19 levels (r = - 0.351 and - 0.303, respectively, p < 0.001). Furthermore, after adjusting for other clinical covariates by multiple linear regression analyses, the serum FGF19 levels were independently associated with baPWV (ß = - 0.20, t = - 2.23, p = 0.029) and AIP (ß = - 0.28, t = - 2.66, p = 0.010). Conclusions: The serum FGF19 levels were independently and inversely associated with baPWV and AIP, which indicate that serum FGF19 may have a protective role in atherosclerosis in patients with T2D.

20.
Plant Dis ; 104(7): 1986-1993, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32441579

RESUMO

Potato common scab is an important soilborne disease worldwide that can significantly reduce the quality and economic values of potato. The disease is caused by multiple species of Streptomyces, which are not well controlled due to lack of effective strategies. Streptomyces galilaeus has been recently identified as a dominant species causing potato common scab in Inner Mongolia, China. This study was focused on screening and characterizing antagonists for biological control against pathogenic S. galilaeus. Bacterial strain PBSH9 was isolated from a potato tuber. PBSH9 was identified as a Streptomyces sp. on the basis of morphological, physiological, and biochemical characteristics, as well as DNA sequence analysis. PBSH9 inhibited S. galilaeus with a diameter of inhibitory zone of 19.8 mm on agar plates. The extracellular filtrate of PBSH9 also inhibited S. galilaeus growth with a diameter of inhibition zone of 10.0 mm. Furthermore, PBSH9 promoted potato sprouting and emergence. Disease control was up to 81.88% in greenhouse trials, and from 47.64 to 73.97% in 3-year field trials. Among the tested inoculation methods, seed treatment was more effective than soil drenching for PBSH9 application. PBSH9 not only effectively controlled potato common scab but also increased potato growth. Thus, it can be a potential candidate for biocontrol agent.


Assuntos
Solanum tuberosum , Streptomyces , China , Doenças das Plantas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...