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1.
FASEB J ; 35(5): e21504, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33913563

RESUMO

Cell death-inducing DFFA-like effector C (CIDEC) is responsible for metabolic disturbance and insulin resistance, which are considered to be important triggers in the development of diabetic cardiomyopathy (DCM). To investigate whether CIDEC plays a critical role in DCM, DCM rat model was induced by a high-fat diet and a single injection of low-dose streptozotocin (27.5 mg/kg). DCM rats showed severe metabolic disturbance, insulin resistance, myocardial hypertrophy, interstitial fibrosis, ectopic lipid deposition, inflammation and cardiac dysfunction, accompanied by CIDEC elevation. With CIDEC gene silencing, the above pathophysiological characteristics were significantly ameliorated accompanied by significant improvements in cardiac function in DCM rats. Enhanced AMP-activated protein kinase (AMPK) α activation was involved in the underlying pathophysiological molecular mechanisms. To further explore the underlying mechanisms that CIDEC facilitated collagen syntheses in vitro, insulin-resistant cardiac fibroblast (CF) model was induced by high glucose (15.5 mmol/L) and high insulin (104  µU/mL). We observed that insulin-resistant stimulation dramatically raised CIDEC expression and promoted CIDEC nuclear translocation in CFs. Meanwhile, AMPKα2 was observed to distribute almost completely inside CF nucleus. The results further proved that CIDEC biochemically interacted and co-localized with AMPKα2 rather than AMPKα1 in CF nucleus, which provided a novel mechanism of CIDEC in promoting collagen syntheses. This study suggested that CIDEC gene silencing alleviates DCM via AMPKα signaling both in vivo and in vitro, implicating CIDEC may be a promising target for treatment of human DCM.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Regulação da Expressão Gênica , Inativação Gênica , Proteínas/antagonistas & inibidores , Animais , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Resistência à Insulina , Masculino , Fosforilação , Proteínas/genética , Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley
2.
J Vasc Access ; 22(6): 969-978, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33752495

RESUMO

The objective of this systematic review is to evaluate the safety ad feasibility of the totally implantable vascular access devices (TIVADs) flushed more than 4 weeks. We searched the following electronic databases from the date their build-up to February 2020: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL. The final selection resulted in 14 trials fulfilling the inclusion criteria and being included in our review. A pooled frequency of port-related late complications with longer flushing intervals (>4 weeks) was 8.0%, and the pooled frequency of occlusions, infections, and mechanical complications was 5.0%, 2.0%, and 3.0%, respectively. Then, we compared the frequency of port-related complications between standard and longer flushing intervals. There were no differences between the group's changes in the frequency of total late complications, occlusions, infections, and mechanical complications. This systematic review and meta-analysis demonstrates that longer flushing intervals for ports are safe. However, more prospective, power appropriated randomized trials are needed to explore the specific flushing time for ports.


Assuntos
Cateterismo Venoso Central , Neoplasias , Dispositivos de Acesso Vascular , Cateterismo Venoso Central/efeitos adversos , Humanos , Estudos Prospectivos
3.
Huan Jing Ke Xue ; 42(2): 1004-1012, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742897

RESUMO

Ground-level ozone (O3) pollution frequently co-occurs with drought and nitrogen (N) deposition during the growing season. It is important to understand how the carbon dynamics of plants respond to O3 pollution in drier and N-enriched environments. Here we present the patterns of non-structural carbohydrates and its components (soluble sugar and starch) in the leaves and fine roots in poplar clone 546 (Populus deltoides cv. '55/56'×P. deltoides cv. 'Imperial') for one growing season at two O3 concentrations (control, charcoal-filtered air, and elevated O3, non-filtered air+40 nmol·mol-1 of O3), two watering regimes (well-watered and reduced watering at 40% of well-watered irrigation), and two soil nitrogen addition treatments[no addition and the addition of 50 kg·(hm2·a)-1]. The results showed that O3 stress significantly increased the content of soluble sugar in leaves and starch in fine roots but decreased the content of starch and total non-structural carbohydrate (NSC) in leaves. Drought stress significantly reduced the content of starch and total NSC in leaves but increased the contents of soluble sugar and total NSC in fine roots. Nitrogen addition had no significant effect on NSC and its components in leaves and fine roots. NSC and its components in leaves and fine roots were positively correlated with photosynthetic rate and biomass. With an increase in the number of environmental stress factors, NSC in leaves showed a significant downward trend while NSC in fine roots showed a significant upward trend. The study demonstrates that environmental stress can promote the transformation of starch into soluble sugars in plant leaves and the transfer of NSC from leaves to roots for storage, which may be a coping strategy for plants exposed to environmental stress.


Assuntos
Ozônio , Populus , Carboidratos , Secas , Nitrogênio , Folhas de Planta , Raízes de Plantas
4.
Acta Pharmacol Sin ; 42(11): 1900-1912, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33536604

RESUMO

Ras-GTPase activating SH3 domain-binding protein 1 (G3BP1) is a multifunctional binding protein involved in the development of a variety of human cancers. However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer. Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulating ß-catenin signaling, which upregulates a number of proliferation-related genes. We further show that G3BP1 improves the stability of ß-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription of ß-catenin. Mechanistically, elevated G3BP1 interacts with and inactivates GSK-3ß to suppress ß-catenin phosphorylation and degradation. Disturbing the G3BP1-GSK-3ß interaction accelerates the degradation of ß-catenin, impairing the proliferative capacity of breast cancer cells. Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3ß/ß-catenin axis may be a potential therapeutic target for breast cancer.

5.
J Drug Target ; 29(6): 576-591, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33554661

RESUMO

Mitophagy is a selective form of macroautophagy in which dysfunctional and damaged mitochondria can be efficiently degraded, removed and recycled through autophagy. Selective removal of damaged or fragmented mitochondria is critical to the functional integrity of the entire mitochondrial network and cells. In past decades, numerous studies have shown that mitophagy is involved in various diseases; however, since the dual role of mitophagy in tumour development, mitophagy role in tumour is controversial, and further elucidation is needed. That is, although mitophagy has been demonstrated to contribute to carcinogenesis, cell migration, ferroptosis inhibition, cancer stemness maintenance, tumour immune escape, drug resistance, etc. during cancer progression, many research also shows that to promote cancer cell death, mitophagy can be induced physiologically or pharmacologically to maintain normal cellular metabolism and prevent cell stress responses and genome damage by diminishing mitochondrial damage, thus suppressing tumour development accompanying these changes. Signalling pathway-specific molecular mechanisms are currently of great biological significance in the identification of potential therapeutic targets. Here, we review recent progress of molecular pathways mediating mitophagy including both canonical pathways (Parkin/PINK1- and FUNDC1-mediated mitophagy) and noncanonical pathways (FKBP8-, Nrf2-, and DRP1-mediated mitophagy); and the regulation of these pathways, and abovementioned pro-cancer and pro-death roles of mitophagy. Finally, we summarise the role of mitophagy in cancer therapy. Mitophagy can potentially be acted as the target for cancer therapy by promotion or inhibition.

6.
Eur J Clin Invest ; 51(1): e13405, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32926588

RESUMO

BACKGROUND: In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice. METHODS AND RESULTS: Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than 'applicability'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery. CONCLUSIONS: Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.


Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Terapia Antiplaquetária Dupla/métodos , Guias de Prática Clínica como Assunto , Aspirina/uso terapêutico , Desprescrições , Duração da Terapia , Procedimentos Cirúrgicos Eletivos , Emergências , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Hemorragia Pós-Operatória/prevenção & controle , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico
9.
Fitoterapia ; 147: 104755, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33069835

RESUMO

Hypersubones D-H (1-5), five new polycyclic polyprenylated acylphloroglucinols (PPAPs) type metabolites with intriguing adamantane and homo-adamantane skeletons, were characterized from aerial parts of Hypericum subsessile. Compounds 1-2 were elucidated to share an adamantane core with 28,29-expoxide moiety, while 3-5 were homo-adamantane type PPAPs sharing a1,2-dioxepane ring system. Their structures were determined on the basis of comprehensive NMR and MS spectroscopic data.The anti-adipogenesis activities of these isolates were evaluated through employing 3T3-L1 cells as an in vitro system using oil red O staining, and compounds 1, 2 and 5 were able to significant inhibit the adipocyte differentiation, which implied that these compounds possessed anti-adipogenic activity.


Assuntos
Adamantano/farmacologia , Adipócitos/efeitos dos fármacos , Hypericum/química , Células 3T3-L1 , Adamantano/isolamento & purificação , Animais , Diferenciação Celular/efeitos dos fármacos , China , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química
10.
Artigo em Inglês | MEDLINE | ID: mdl-32994225

RESUMO

INTRODUCTION: Long-term changes of fasting blood glucose (FBG) in relation to lower-extremity peripheral artery disease (lower-extremity PAD) in people without diabetes has barely been reported. Our study aimed to investigate the association between FBG variability and the incidence of lower-extremity PAD in people without diabetes. RESEARCH DESIGN AND METHODS: We included 7699 participants without prior lower-extremity PAD and diabetes from the Atherosclerosis Risk in Communities study in the final analysis. At least two measurements of FBG were required during follow-up. Variability of FBG was identified using SD, coefficient of variation (CV), variability independent of the mean (VIM) and average real variability. Lower-extremity PAD was defined as an ankle brachial index <0.9, or hospitalization with a lower-extremity PAD diagnosis. Cox regression model was used to calculate HR for incidence of lower-extremity PAD and FBG variability. RESULTS: During a median follow-up of 19.5 years, 504 (6.5 %) lower-extremity PAD events were observed, 54.4% (n=274) were male, and 17.5% (n=88) were African-American. FBG variability was positively associated with incident lower-extremity PAD, with a linear relationship. HRs for CV and VIM were 1.015 (95% CI: 1.001 to 1.03; p=0.023), and 1.032 (95% CI: 1.004 to 1.06; p=0.022) for lower-extremity PAD, respectively. Participants in the lowest quartile of CV were at lower lower-extremity PAD risk compared with the highest ones (HR: 1.499, 95% CI: 1.16 to 1.938; p=0.002). CONCLUSIONS: Higher FBG variability was independently associated with increased prevalence of lower-extremity PAD in people without diabetes. TRIAL REGISTRATION NUMBER: NCT00005131.


Assuntos
Diabetes Mellitus , Doença Arterial Periférica , Glicemia , Diabetes Mellitus/epidemiologia , Jejum , Feminino , Humanos , Masculino , Doença Arterial Periférica/epidemiologia , Fatores de Risco
11.
J Int Med Res ; 48(8): 300060520933810, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32776805

RESUMO

The sudden outbreak of severe acute respiratory syndrome coronavirus 2 pneumonia posed a significant challenge to medical professionals because treatment of critically ill patients requires the efforts of a multidisciplinary team. To highlight this principle, we examined acute kidney injury (AKI) in IgA-dominant infection-associated glomerulonephritis (GN) and menstrual toxic shock syndrome (mTSS). Both GN and mTSS are rare diseases caused by staphylococcal infection, and renal function is frequently impaired. The resulting AKIs are disparate pathological entities driven by distinct immune mechanisms. We begin by describing the case of a diabetic man with pyopneumothorax following methicillin-resistant Staphylococcus aureus (MRSA). He had endocapillary proliferative GN with in situ IgA-dominant immune-complex formation in the mesangium accompanied by complement C3 deposition in the glomerular capillary wall. By contrast, acute tubular necrosis was observed in a case of mTSS; the patient's immune response was stimulated differently by MRSA enterotoxin and exotoxin resulting in aberrant IgA deposition, complement activation, and insufficient antibody production. As a multidisciplinary communication covering the fields of nephrology, immunology, and pathology, this report may help clinicians to understand these distinct renal lesions and make optimal therapeutic decisions expeditiously.


Assuntos
Injúria Renal Aguda/patologia , Glomerulonefrite por IGA/patologia , Imunoglobulina A/imunologia , Distúrbios Menstruais/patologia , Choque Séptico/patologia , Infecções Estafilocócicas/patologia , Injúria Renal Aguda/microbiologia , Adolescente , Betacoronavirus , COVID-19 , Ativação do Complemento/imunologia , Infecções por Coronavirus/patologia , Enterotoxinas/metabolismo , Feminino , Glomerulonefrite por IGA/microbiologia , Humanos , Rim/patologia , Masculino , Distúrbios Menstruais/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Pneumotórax/microbiologia , Pneumotórax/patologia , SARS-CoV-2 , Choque Séptico/microbiologia
12.
Cancer Cell Int ; 20: 366, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774160

RESUMO

Background: Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that transgelin was up-regulated in node-positive colorectal cancer (CRC) versus node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms through which transgelin participates in the metastasis of colon cancer cells. Methods: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with transgelin. The 256 downstream transcripts regulated by transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with transgelin. The interaction between transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence. Results: Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven key genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1, which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with transgelin. The interaction between PARP1 and transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays. Conclusions: Our results suggest that transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.

13.
Int J Med Sci ; 17(10): 1345-1350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32624691

RESUMO

Background: Patients with Wilson disease (WD) progress to cirrhosis at an early age but have good prognoses. This study aimed to delineate hepatic features in WD patients with or without cirrhosis. Methods: Medical data were retrospectively collected from 27 July 2015 to 27 June 2018. WD patients were divided into two groups based on whether or not they progressed to cirrhosis. Liver function, portal hypertension features and hematocytopenia rates were compared between groups. Results: The study enrolled 119 WD patients with cirrhosis and 53 WD patients without cirrhosis. There were no differences between groups for liver enzyme levels or incidence rates of Kayser-Fleischer ring (all P > 0.05). Ascites and hepatic encephalopathy were nearly absent in both groups, and almost all patients were Child-Pugh group A. However, WD-associated cirrhotic patients had a higher prothrombin time (beta = 0.908, P = 0.004) and international normalized ratio (beta = 0.089, P = 0.040), wider portal vein diameter (beta = 1.330, P < 0.001), and an increased risk of splenomegaly/splenectomy (odds ratio [OR] = 4.36, 95% confidence interval [CI]: 2.15-8.84, P < 0.001). Moreover, WD-associated cirrhotic patients have significantly increased risks of leukopenia (OR = 2.30, 95% CI: 1.00-5.25, P = 0.049) and thrombocytopenia (OR = 6.89, 95% CI: 2.01-23.59, P = 0.002). Conclusions: Despite presenting good outcomes, mild hepatocyte injury, and good hepatic metabolic function, WD-associated cirrhotic patients show more serious impairment of hepatic synthetic function, wider portal vein diameter, and higher risk of splenomegaly due to portal hypertension.


Assuntos
Degeneração Hepatolenticular/patologia , Degeneração Hepatolenticular/fisiopatologia , Adulto , Feminino , Humanos , Hipertensão Portal/patologia , Hipertensão Portal/fisiopatologia , Leucopenia/patologia , Leucopenia/fisiopatologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Masculino , Prognóstico , Estudos Retrospectivos , Trombocitopenia/patologia , Trombocitopenia/fisiopatologia , Adulto Jovem
14.
Aging (Albany NY) ; 12(16): 16111-16125, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32717722

RESUMO

Low serum testosterone level is associated with aging-related vascular stiffness, but the underlying mechanism is unclear. The Growth arrest-specific protein 6 (Gas6) /Axl pathway has been proved to play important roles in cell senescence. In this study, we intend to explore whether Gas6/Axl is involved in the effect of testosterone on vascular aging amelioration. Vascular aging models of wild type and Axl-/- mice were established by natural aging. Mice of these two gene types were randomized into young group, aging group and testosterone undecanoate (TU) treatment group. Mice were treated with TU (37.9 mg/kg) in the TU group, which treated with solvent reagent served as control. The aging mice exhibited decreases in serum testosterone, Gas6 and Axl levels and an increase in cell senescence, manifested age-related vascular remodeling. Testosterone treatment induced testosterone and Gas6 levels in serum, and ameliorated cell senescence and vascular remodeling in aging mice. Furthermore, we uncover the underlying molecular mechanism and show that testosterone treatment restored the phosphorylation of Akt and FoxO1a. Axl knockout accelerated cell senescence and vascular remodeling, and resisted the anti-aging effect of testosterone. Testosterone might exert a protective effect on vascular aging by improving cell senescence and vascular remodeling through the Gas6/Axl pathway.


Assuntos
Aorta/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Testosterona/análogos & derivados , Remodelação Vascular/efeitos dos fármacos , Fatores Etários , Envelhecimento , Animais , Aorta/diagnóstico por imagem , Aorta/metabolismo , Pressão Arterial/efeitos dos fármacos , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/metabolismo , Fibrose , Proteína Forkhead Box O1/metabolismo , Masculino , Camundongos Knockout , Fosforilação , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Proteína Tirosina Quinases/deficiência , Receptores Proteína Tirosina Quinases/genética , Transdução de Sinais , Testosterona/farmacologia , Rigidez Vascular/efeitos dos fármacos
15.
Nat Prod Bioprospect ; 10(4): 269, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32548686

RESUMO

In the original publication of this article, we found an error under the section "Introduction". The first sentence of the fourth paragraph appears incorrectly. The corrected sentence is given below. Eriocalyxin B, isolated and identified in 1982 [1], is the major component in Chinese plant Isodon eriocalyx (Dunn.) Hara (family Lamiaceae) showing many pharmacological activities, such as inhibiting inflammatory response, regulating immune cell differentiation, inhibiting tumor cells proliferation, causing cell cycle arrest affecting angiogenesis and promoting cancer cells apoptosis.

16.
Nat Prod Bioprospect ; 10(3): 163-170, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32447748

RESUMO

Adamantane polycyclic polyprenylated acylphloroglucinols (PPAPs) with caged architecture, a special class of hybrid natural products, is specifically rich in the plant family Guttiferae, especially Hypericum or Garcinia genus. Hypersampsone P is one of Adamantane PPAPs compounds extracted from Hypericum subsessile. Here we have chosen, screened ten PPAPs and identified one of them showed an activity in inhibiting of adipocytes differentiation. Particularly, the compound, hypersampsone P, blunted the adipocyte differentiation dose-dependently. Moreover, hypersampsone P down-regulated the expressions of several key regulators for adipogenesis, including PPARγ and FABP4. The treatment of cells at the early stage of adipogenesis by hypersampsone P induced the greatest blunting of adipocyte differentiation and the effect might be involved in the LKB1-AMPK signaling pathway.

17.
J Agric Food Chem ; 68(17): 4865-4875, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32306731

RESUMO

Saponins of Panax notoginseng (Burk.) F.H. Chen have been classified as a type of composition in functional foods for numerous diseases. However, its mild effects and other characteristics limited clinical applications in diseases. Inspired by "nine steaming and nine processing" of P. notoginseng in traditional Chinese medicine, we developed a "steaming"-mimic protocol, which significantly changed the composition of saponins of P. notoginseng from the original, R1, Rg1, Re, Rb1, and Rd (raw-PNS), to the products after steaming, 20S/R-Rh1, Rk3, Rh4, 20S/R-Rg3, Rk1, and Rg5 (N-PNS). Surprisingly, N-PNS demonstrated promising activities in improving hyperlipidemia and reducing body weight and weight of white adipose tissue and the inhibition of adipogenesis in obese mice. In accordance with the results in vivo, N-PNS remarkably blunted adipogenesis at the early stage of differentiation dose-dependently in vitro. Moreover, we demonstrated that the activity may involve the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway by promoting phosphorylation of AMPKT172 and downregulating its downstream factors: sterol regulatory element binding protein 1c, stearoyl-CoA desaturase 1, and fatty acid synthase. Taken together, the steaming-induced eight compositions of saponins showed a very promising function in improving hyperlipidemia and obesity both in vivo and in vitro, providing fundamental evidence for future study and application in treatment of hyperlipidemia, obesity, and other lipid-related metabolic syndromes.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Obesidade/tratamento farmacológico , Panax notoginseng/química , Saponinas/administração & dosagem , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Medicamentos de Ervas Chinesas/química , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Fitoterapia , Saponinas/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
18.
Nat Prod Bioprospect ; 10(3): 131-140, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32314168

RESUMO

Eriocalyxin B, an ent-Kaurene diterpenoid extracted from a traditional Chinese herb Isodon eriocalyx, has been shown to possess multifunctional activities such as anti-cancer and anti-inflammatory. However, the function and mechanism of the compound in adipocyte differentiation is still unknown. Here we reported that eriocalyxin B blunted adipogenesis remarkably by inhibiting the accumulation of lipid droplets, triglycerides and the expressions of adipogenesis-related factors, including C/EBPß, C/EBPα, PPARγ, and FABP4. Moreover, we showed that the inhibition might be the consequence of cell cycle being arrested at the G2/M phase during the mitotic clonal expansion of adipocyte differentiation, most likely by suppressing mRNAs and proteins of CDK1, CDK2, Cyclin A and Cyclin B1. Overall, we conclude that eriocalyxin B is capable of inhibiting adipocyte differentiation at the early stage through downregulating the proteins involved in cell cycle progression.

19.
Medicine (Baltimore) ; 99(7): e18837, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049785

RESUMO

Patients with cirrhosis are known to develop small bowel mucosal lesions. However, the occurrence of mucosal lesions in patients with abnormal liver function test results in the absence of chronic liver disease has not been fully evaluated. This study aims to examine the association between small bowel endoscopic lesions and liver dysfunction in patients without confirmed chronic liver disease.Two hundred ninety six consecutive patients who met the selection criteria underwent capsule endoscopy. The severity of the small intestinal mucosal lesions was evaluated quantitatively using the Lewis scoring system, and hepatic dysfunction was evaluated using an algorithm-based combination scoring system with 8 individual serological markers.Small bowel lesions were observed in 121 patients (40.88%). Hepatic dysfunction was significantly more prevalent in patients with small bowel lesions than in those without lesions (33.1%; 40/121 and 5.7%; 10/175, respectively; P < .001). The mean serum ALT and AST levels were significantly higher in patients with small bowel lesions than in those without lesions (P = .007 and P = .004, respectively). The mean scores for AST to Platelet Ratio Index, Forns Index, S-Index, Fibrosis-4 Index and BARD were significantly higher in patients with small bowel lesions than those without lesions. The Lewis score significantly and positively correlated with the Forns Index (P = .008) and the FIB-4 Index (P = .006).There is a close correlation between small intestinal mucosal lesions and hepatic dysfunction. The severity of hepatic dysfunction is directly proportional to the severity of the small intestinal mucosal lesions in patients without confirmed chronic liver disease.


Assuntos
Mucosa Intestinal/patologia , Intestino Delgado/patologia , Hepatopatias/epidemiologia , Adulto , Idoso , Endoscopia por Cápsula , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Projetos de Pesquisa , Estudos Retrospectivos
20.
Chem Commun (Camb) ; 55(64): 9507-9510, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31329195

RESUMO

A novel palladium-catalyzed decarbonylative annulation for the synthesis of phenanthridinones from phthalimides and arynes has been developed. This catalytic system tolerates a broad range of functional groups. Mechanistic experiments demonstrate that the Pd(ii) complex B is the key intermediate, which has been confirmed by X-ray crystallography for the first time.

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