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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118884, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32898726

RESUMO

The 8-oxo-deoxyguanosine is the most abundant specie of the DNA oxidative damage. Despite the deleterious effects such as gene mutation it may cause, the 8-oxodG was also reported to have beneficial effect such as repairing the nearby cyclobutane pyrimidine dimer (CPD) after photoexcitation. Due to its strong biological relevance, the photoinduced excited state dynamics behavior of 8-oxo-deoxyguanosine is of particular interest. In this work, a theoretical investigation by combination of complete active space self-consistent field (CASSCF) ab initio calculations and on-the-fly nonadiabatic dynamics simulations are implemented to provide intrinsic deactivation mechanism of its free base 8-oxoguanine after being excited to the S1 and S2 states. Two minimum energy conical intersections (MECIs) characterized by the C3-puckered motion with attractive chiral character are located, which contribute appreciably to the S1 state deactivation process. When the system is being excited to the S2 state directly, a S2 â†’ S1 â†’ S0 two-step decay pattern is proposed. A nearly planar S2/S1 intersection plays a significant role in the S2 â†’ S1 decay process. The subsequent S1 state relaxation process is also dominated by the C3-puckered deformation motion. One decay time is estimated to be 704 fs, which compares well with the experimental observation of 0.9 ± 0.1 ps in solvents. Particular illustration is the fact that the MECIs configurations we located bear an exceptional resemblance with previous reported thymine, cytosine and guanine, suggesting that the current work could lend support for better understanding of the non-natural nucleobases and derivatives.

2.
Food Chem ; 334: 127567, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32707362

RESUMO

Fruit acidity is an important determinant of peach organoleptic quality, but its regulatory mechanism remains elusive. Measurement of organic acids in ripe fruits of seventy-five peach cultivars revealed the predominant components malate and citrate, accompanied by quinate. Organic acid accumulation increased at early stages of fruit growth, but exhibited a more dramatic reduction in low-acid cultivar during later stages of fruit development compared to high-acid cultivars. Low-acid cultivars showed citrate degradation and less transport of malate into the vacuole due to up- and down-regulation of a GABA pathway gene GAD and a malate transporter gene ALMT9, respectively. The NAD-MDH1 gene might control the rate-limiting step in malate synthesis, while three genes, PDK, PK, and ADH, could affect citrate synthesis through the pyruvate-to-acetyl-CoA-to-citrate pathway. Altogether, these results suggested that malate accumulation is controlled at the level of metabolism and vacuolar storage, while metabolism is crucial for citrate accumulation in peach.

3.
Dalton Trans ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084690

RESUMO

Two rare earth metal-organic frameworks (MOFs), [Y2(PTC)2(H2O)2]·3H2O (Y-PTC) and [Eu2(PTC)2(H2O)5]·H2O (Eu-PTC) together with the solid solutions [Eu2xY2(1-x)(PTC)2(H2O)5]·H2O (EuxY1-x-PTC, x = 0.013-0.82), were synthesized hydrothermally, and characterized by microanalysis, IR spectroscopy, TG, powder, and single crystal X-ray diffraction techniques. Eu-PTC and Y-PTC showed different crystal structures; however, all solid solutions were isomorphic to Eu-PTC even at x = 0.013, leading to the IR spectra and TG plots of the solid solutions to be similar to those of Eu-PTC but distinct from those of Y-PTC. DFT calculations for the crystal lattice energy demonstrated that the procedure for the crystallizing nucleation of Eu-PTC occurred prior to that of Y-PTC in the reaction solution, leading to the all solid solutions being isomorphic to Eu-PTC. The solid emission spectra at ambient condition showed that Y-PTC emitted ligand-based phosphorescence at 433 nm with a quantum yield (QY) of 27.02%, while Eu-PTC and EuxY1-x-PTC (x = 0.013-0.82) emitted the characteristic luminescence of Eu3+ ions, and most solid solutions showed higher QYs than Eu-PTC; in particular, the QY of Eu0.195Y0.805-PTC was up to 29.48%, i.e., increased by 10% regarding Eu-PTC (19.86%). Interestingly, solid solutions with x = 0.013-0.395 showed excitation-wavelength-dependent luminescence, and such type of luminescence MOFs have promising applications including the areas of precise temperature, gas sensing and information encryption or anti-counterfeiting materials.

4.
Nat Commun ; 11(1): 5205, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060564

RESUMO

Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). Malfunction in GHRHR signaling is associated with abnormal growth, making GHRHR an attractive therapeutic target against dwarfism (e.g., isolated growth hormone deficiency, IGHD), gigantism, lipodystrophy and certain cancers. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein at 2.6 Å. This high-resolution structure reveals a characteristic hormone recognition pattern of GHRH by GHRHR, where the α-helical GHRH forms an extensive and continuous network of interactions involving all the extracellular loops (ECLs), all the transmembrane (TM) helices except TM4, and the extracellular domain (ECD) of GHRHR, especially the N-terminus of GHRH that engages a broad set of specific interactions with the receptor. Mutagenesis and molecular dynamics (MD) simulations uncover detailed mechanisms by which IGHD-causing mutations lead to the impairment of GHRHR function. Our findings provide insights into the molecular basis of peptide recognition and receptor activation, thereby facilitating the development of structure-based drug discovery and precision medicine.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1694-1698, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067976

RESUMO

OBJECTIVE: To investigate the inducing effect of PKA inhibitor H89 of different concentrations on platelet apoptosis and its mechanism. METHODS: Platelets were isolated from peripheral venous blood of healthy volunteers. Different concentrations gradient PKA inhibitor H89 were co-incubated with washing platelets, and the effects of PKA inhibitor H89 at different concentrations on platelet mitochondrial membrane potential, phosphatidylserine and reactive oxygen species(ROS) were determined by ELISA and flow cytometry. RESULTS: Different concentration of PKA inhibitor H89 could induce the depolarization of mitochondrial membrane potential and PS exposure of platelet. However, high concentration(100 µmol/L) PKA inhibitor H89 could induce the production of ROS in platelets, but medium and low concentrations did not induce the production of ROS in platelets. And several ROS inhibitors could inhibit the apoptosis induced by high concentration PKA inhibitor H89. CONCLUSION: High concentration H89 can induce platelet apoptosis, however the mechanism of platelet apoptosis caused by H89 of high concentration is different from H89 at medium and low concentrations.


Assuntos
Plaquetas , Peptídeos e Proteínas de Sinalização Intracelular , Apoptose , Humanos , Potencial da Membrana Mitocondrial
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1704-1709, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067978

RESUMO

OBJECTIVE: To investigate the role of mitochonaria in the regulation of platelet membrane protein GPIbα shedding and its mechanisms. METHODS: The washed platelets were obtained from peripheral blood in healthy volunteers and co-incubated with mitochondrial inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP), mitochondrial protector cyclosporin A (CsA) or matrix metalloproteinases inhibitor GM6001. After the platelets was stimulated, the effect of mitochondria to the shedding in platelet membrane protein GPIbα was detected by flow cytometry. RESULTS: Depolarization of mitochondrial membrane potential and the respiratory function of mitochondrial could be induced and destroyed by the uncoupling agent CCCP. At the same time, the shedding of GPIbα was detected out, and the result showed a statistical significance, which showed that the shedding of GPIbα could be activated by the damaged of mitochondrial in platelets. After the mitochondrial was protected by CsA, the shedding of GPIbα was inhibited significantly. GM6001 could only inhibited the shedding of GPIbα, but showed no inhibitation to the function of mitochondrial, which showed that the shedding of GPIbα was regulated at the mitochondrial, and the regulatory enzyme of receptor shedding (ADAM17) was located in the pathway of downstream of mitochondria. After the oxidative damage in cells was inhibited by NAC, and the changes of GPIbα shedding was detected, the result showed that the GPIbα shedding could be inhibited by NAC, which showed a dose-dependent manner. CONCLUSION: The GPIbα shedding could be caused by abnormality function of metabolic, and the metabolic imbalance of ROS is caused by the abnormallity function of mitochondria.


Assuntos
Plaquetas , Proteínas de Membrana , Humanos , Proteínas de Membrana/metabolismo , Mitocôndrias
7.
PeerJ ; 8: e9995, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083118

RESUMO

Background: We used bioinformatic analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays to investigate the association between plasma microRNAs (miRNAs) and stable warfarin dosage in a Chinese Han population. Methods: Bioinformatics analysis was used to screen out potential warfarin dose-associated miRNAs. Three plasma miRNAs were validated in 99 samples by RT-qPCR. Kruskal-Wallis test and multivariate logistic regression were used to compare differences in plasma miRNAs expression levels between three warfarin dosage groups. Results: There were significant between-group differences among the three dose groups for hsa-miR-133b expression (p = 0.005), but we observed an "n-shaped" dose-dependent curve rather than a linear relationship. Expression levels of hsa-miR-24-3p (p = 0.475) and hsa-miR-1276 (p = 0.558) were not significantly different in the multivariate logistic regression. Conclusion: miRNAs have received extensive attention as ideal biomarkers and possible therapeutic targets for various diseases. However, they are not yet widely used in precision medicine. Our results indicate that hsa-miR-133b may be a possible reference factor for the warfarin dosage algorithm. These findings emphasize the importance of a comprehensive evaluation of complex relationships in warfarin dose prediction models and provide new avenues for future pharmacogenomics studies.

8.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1092-1099, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059806

RESUMO

OBJECTIVE: To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05). CONCLUSIONS: Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.

9.
Carbohydr Polym ; 250: 116844, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049812

RESUMO

Pullulan was successfully esterified with octenyl succinic anhydride (OSA) in aqueous alkaline solutions. The degree of substitution (DS) was regulated from 0.0163, 0.0346 to 0.0469 by changing the OSA concentration (3.0%, 6.0% and 9.0%, respectively). Meanwhile, the weight-average molecular weight (Mw) of OSA-pullulans varied from 2.050 × 105, 2.113 × 105 to 2.124 × 105. The chemical structures of OSA-pullulans were characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance spectroscopy (1H NMR), which indicated that OSA groups were successfully grafted into pullulan. The surface tension, interfacial tension and droplet size of the emulsions stabilized by OSA-pullulans significantly reduced with the increase of DS. Furthermore, the emulsion stability (ES) and viscosity dramatically increased with DS compared with those of emulsion stabilized by pullulan. These results indicated emulsifying properties of OSA-pullulans were improved by increasing DS. Additionally, OSA-pullulans had excellent emulsion stability when DS was higher than 0.0346.

10.
Pharmacogenomics J ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097827

RESUMO

The correlations between hydroxytryptamine receptor 2A (HTR2A) gene polymorphisms (1438A/G, 102T/C, and rs7997012G/A) and the safety and efficacy of antidepressants in depression patients were constantly reported, but conclusions are debatable. This meta-analysis ascertained forty-two studies on the efficacy (including response and remission) and side-effect issued before February 2020. Pooled analyses indicated significant associations of 1438A/G polymorphism (16 studies, 1931 subjects) and higher response within dominant model (OR: 1.40, 95% CI: 1.12-1.76); rs7997012G/A polymorphism (nine studies, 1434 subjects) and higher remission in overall models (dominant model: OR: 1.30, 95% CI: 1.01-1.66; recessive model: OR: 2.20, 95% CI: 1.53-3.16; homozygote model: OR: 2.73, 95% CI: 1.78-4.17); 102T/C polymorphism (eight studies, 804 subjects) and reduced risk of side-effect within recessive (OR: 0.57, 95% CI: 0.4-0.83) and homozygote models (OR: 0.54, 95% CI: 0.29-0.99). For depression patients, genotyping of HTR2A polymorphisms is a promising tool for estimating the outcome and side-effect of antidepressants.

11.
Scand J Gastroenterol ; : 1-6, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33076704

RESUMO

AIMS: The efficacy of somatostatin in altering splanchnic hemodynamics in cirrhotic portal hypertension is still controversial. We aimed to establish the dynamic effect of somatostatin on portal pressure in cirrhotic patients and compared its effect with Partial Splenic Embolization (PSE). METHODS: Eighteen patients with cirrhotic portal hypertension were prospectively recruited. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were repeatedly measured at baseline, 1-, 5-, 10- and 20-min after initiating somatostatin infusion. After somatostatin infusion cessation and washout, WHVP and FHVP were measured before and after PSE. The change in all the variables between time points was analyzed. RESULTS: Decreased hepatic venous pressure gradient (HVPG) 5-min after initiation of infusion was identified compared with baseline level (19.6%; p-value: .042), which was achieved through elevated FHVP (37.5%; p-value: 9.26e - 04). There was no significant decrease in WHVP at any time point during somatostatin infusion. The HVPG (17.4%; p-value: 1.27e - 04) and WHVP (10.4%; p-value: 3.00e - 03) post-PSE significantly decreased compared to the washout level. No significant distribution differences in the number of patients with HVPG decrease by a percentage relative to the baseline level were identified between the 5-min time point and post-PSE. CONCLUSION: Our study indicates that somatostatin administration does not decrease WHVP within 20 min at clinically recommended doses. While somatostatin did decrease HVPG, this effect was achieved through increased FHVP, providing a possible explanation for its unclear efficacy. In contrast, PSE decreases both the WHVP and the HVPG.

12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5220-5223, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019161

RESUMO

The aim of this study is to design an implantable Lower Esophageal Sphincter (LES) stimulator connected and controlled by an Android Bluetooth for the treatment of the gastroesophageal reflux disease (GERD). Then the animal experiments are carried out to evaluate the function of the system. The LES stimulator is composed of an external controller, an Android application (APP) via a smart phone and an implantable electronic device (IED). The external controller is designed to receive the settings parameters information sent by the Android APP via a Bluetooth module, and then is programmed to generate specific electrical stimulation pulses to the LES. The Android APP controls the start and stop of stimulation and the settings of stimulation parameters. The in vivo IED consists of a bipolar stimulating lead, a bipolar head connector and a receiving module. The bipolar stimulating lead is constructed of biocompatible materials: platinum-iridium electrodes which are coated with parylene and an outer silicone rubber sheathing. The size of the receiving module has been significantly decreased to 20×20×2 mm3, which is packaged by polydimethylsiloxane (PDMS) and proposed to deliver stimulation pulses from the external controller to the implantable lead. The one-month implantation experiment on rabbits has been performed to evaluate the LES stimulator. The results indicate that the proposed LES stimulator meets the requirements of the functions, effectiveness and safety.


Assuntos
Terapia por Estimulação Elétrica , Refluxo Gastroesofágico , Animais , Estimulação Elétrica , Esfíncter Esofágico Inferior , Refluxo Gastroesofágico/terapia , Próteses e Implantes , Coelhos
13.
Physiol Behav ; 228: 113190, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002497

RESUMO

BACKGROUND: Traumatic brain injury (TBI) can lead to cognitive dysfunction and motor dysfunction. TBI is a potential risk factor for subsequent dementia. Hyperphosphorylation of Tau and ApoE4 has been found in patients with TBI. A significant increase in miR-203 was also found in the peripheral blood of TBI mice. Thus, we hypothesize that miR-203 inhibitor protects against neuronal damage and behavioral deficits by inhibition of Tau phosphorylation, ApoE4 expression and apoptosis. METHODS: TBI mice were induced and treated with miR-203 inhibitor. Tau phosphorylation and ApoE4, hippocampal long-term potentiation (LTP), learning and memory, and motor function were separately detected by Western blot analysis, electrophysiology recording and behavioral assessments including Morris water maze test, beam-balance test, beam-walk test and rotarod test. Caspase-3 activity and bcl-2 expression were detected by ELISA. RESULTS: TBI induction led to increased phosphorylation of Tau and ApoE4 expression. Administration of miR-203 inhibitor suppressed TBI induced ApoE4 expression and Tau hyperphosphorylation, rescued TBI mediated hippocampal LTP deficits and hippocampus dependent learning and memory dysfunction. miR-203 inhibitor treatment also improved motor function. In addition, miR-203 inhibitor treatment inhibited neuronal apoptosis by inhibiting caspase-3 activity and increasing bcl-2 expression. CONCLUSION: miR-203 inhibitor treatment can rescue TBI-induced neural damage by inhibiting neuronal apoptosis and dementia markers like ApoE4 expression and Tau phosphorylation.

14.
J Food Biochem ; : e13511, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33103258

RESUMO

The whole plant of Clerodendranthus spicatus (Thunb.) is one of popular functional food in south of China, named as "kidney tea" and used to ameliorate renal inflammation. In order to verify this potential function and explore the accurate compounds responsible for inflammation, the ethanol extract, fractions, and subfractions of this plant were prepared to evaluate anti-inflammation effect on xylene-induced acute inflammatory mice model, and the results indicated that two subfractions from EtOAc fraction show potential activities. Subsequent bioassay-guided isolation of the bioactive subfractions led to isolation of 25 compounds. Among them, compounds 2, 4, 5, 9-11, 13, 16, 17, and 20-22 inhibited the productions of pro-inflammation factors TNF-α, IL-1ß, and IL-8 in lipopolysaccharide (LPS) -induced renal epithelia (HK-2) cells, respectively. Further anti-inflammation evaluation in vivo indicated that the major bioactive compounds 1, 2, 5-7, 17, 21, and 22 from C. spicatus were even better than aspirin. PRACTICAL APPLICATIONS: C. spicatus as a healthy tea has been available in the Chinese market and as a medicine for various disorders such as nephritis, rheumatism, inflammation, gout, and diabetes. Previous pharmacological investigation of the plant revealed the potential anti-inflammatory activities, but the material basis of anti-inflammatory activity remains to be elucidated. In our study, the anti-inflammatory fractions and compounds were obtained by the bioassay-guide isolation and the results showed that the highly oxygenated diterpenoids were major anti-inflammatory compounds, in which 1, 2, 5-7, 17, 21, and 22 were even better than aspirin. This information supported kidney tea as a functional food for treatment of renal inflammation reasonably and may add a new dimension to biological activity of this plant in the field of agriculture as a functional food were cultivated.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33012100

RESUMO

QF-036 is an HIV-1 maturation inhibitor in pre-clinical development, and its antiviral activity against a laboratory HIV-1 strain and two drug-resistant strains was determined in the C8166 line. QF-036 was also subjected to absorption, distribution and metabolism (ADM) assessment in vitro, and pharmacokinetic profiles were evaluated in rats and monkeys. The 50% effective concentrations (EC50 ) of QF-036 against the three strains were 20.36 nM, 0.39 µM and 2.11 nM, respectively, demonstrating better antiviral potential than the first-generation antiviral maturation inhibitor bevirimat. QF-036 demonstrated moderate cell permeability, high plasma protein binding ability and good metabolic stability in vitro. After oral QF-036 administration to rats and monkeys, both species exhibited moderate bioavailability, and the plasma drug exposure increased in an approximately dose-proportional manner. When administered orally (30 mg/kg) to monkeys, the QF-036 plasma concentration (Cmax ) peaked at 3671 ng/mL (4.82 µM), 12 to 2410 times higher than the EC50 of laboratory or resistant HIV-1 strains. Moreover, the plasma concentration of QF-036 at 12 hours after administration was 263 ng/mL (0.35 µM), which approximately matched the highest EC50 value of the three test strains. The favourable viral inhibitory activity and pharmacokinetic properties provide critical support for QF-036 as a promising anti-HIV therapeutic candidate.

16.
Chem Commun (Camb) ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107881

RESUMO

A Cs2CO3-mediated formal [4+3] cycloaddition involving benzofuran-derived azadienes (BDAs) and α-bromohydroxamates to afford benzofuran-fused 1,4-diazepinones is established. This is the first example of using BDAs for the construction of seven-membered dinitrogen-fused heterocycles. This strategy not only enriches the chemistry of BDAs but also provides an interesting class of bioisosteres of 1,4-benzodiazepine.

17.
BMC Infect Dis ; 20(1): 647, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883217

RESUMO

BACKGROUND: The family cluster is one of most important modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission throughout China, and more details are needed about how family clusters cause the spread of coronavirus disease 2019 (COVID-19). CASE PRESENTATION: We retrospectively reviewed 7 confirmed cases from one family cluster. Both clinical features and laboratory examination results were described. Patient 1 had been in close contact with someone who was later confirmed to have COVID-19 in Wuhan City before he returned back to his hometown. He had dinner with 6 other members in his family. All the persons developed COVID-19 successively except for one older woman who neither had dinner with them nor shared a sleeping room with her husband. Six patients had mild or moderate COVID-19 but one older man with underlying diseases progressed into the severe type. After general and symptomatic treatments, all the patients recovered. CONCLUSIONS: In a family cluster, having dinner together may be an important mode for the transmission of SARS-CoV-2. In this setting, most cases are mild with a favorable prognosis, while elderly patients with underlying diseases may progress into the severe type. For someone who has close contact with a confirmed case, 14-day isolation is necessary to contain virus transmission.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Saúde da Família , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Adolescente , Adulto , Idoso , Betacoronavirus/patogenicidade , Criança , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Estudos Retrospectivos
18.
Curr Top Med Chem ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901583

RESUMO

Indole, a heterocyclic organic compound, is one of the most promising heterocycles found in natural and synthetic sources since its derivatives possess fascinating structural diversity and various therapeutic properties. Indole alkaloids, synthetic dimers and hybrids could act on diverse targets in cancer cells, and consequently possess potential antiproliferative effects on various cancers both in vitro and in vivo. Vinblastine, midostaurin, and anlotinib as the representative of indole alkaloids, synthetic dimers and hybrids respectively have already been clinically applied to treat many types of cancers, demonstrating indole alkaloids, synthetic dimers and hybrids are useful scaffolds for the development of novel anticancer agents. Covering articles published between 2010 and 2020, this review emphasizes the recent development of indole alkaloids, synthetic dimers and hybrids with potential in vivo therapeutic application for cancers.

19.
Arch Toxicol ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32909075

RESUMO

Nuclear receptors (NRs) are key regulators of energy homeostasis, body development, and sexual reproduction. Xenobiotics binding to NRs may disrupt natural hormonal systems and induce undesired adverse effects in the body. However, many chemicals of concerns have limited or no experimental data on their potential or lack-of-potential endocrine-disrupting effects. Here, we propose a virtual screening method based on molecular docking for predicting potential endocrine-disrupting chemicals (EDCs) that bind to NRs. For 12 NRs, we systematically analyzed how multiple crystal structures can be used to distinguish actives and inactives found in previous high-throughput experiments. Our method is based on (i) consensus docking scores from multiple structures at a single functional state (agonist-bound or antagonist-bound), (ii) multiple functional states (agonist-bound and antagonist-bound), and (iii) multiple pockets (orthosteric site and alternative sites) of these NRs. We found that the consensus enrichment from multiple structures is better than or comparable to the best enrichment from a single structure. The discriminating power of this consensus strategy was further enhanced by a chemical similarity-weighted scoring scheme, yielding better or comparable enrichment for all studied NRs. Applying this optimized method, we screened 252 fatty acids against peroxisome proliferator-activated receptor gamma (PPARγ) and successfully identified 3 previously unknown fatty acids with Kd = 100-250 µM including two furan fatty acids: furannonanoic acid (FNA) and furanundecanoic acid (FUA), and one cyclopropane fatty acid: phytomonic acid (PTA). These results suggested that the proposed method can be used to rapidly screen and prioritize potential EDCs for further experimental evaluations.

20.
Medicine (Baltimore) ; 99(35): e21574, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871873

RESUMO

The prevalence of the metabolic syndrome (MS) is increasing in China, but there are disparities between urban and rural populations, and across different regions.To examine the prevalence and risk factors of MS in the rural area of Qianjiang (Southwest China).From March 2016 to June 2018, 6 townships in the Qianjiang District of Chongqing Municipality were selected for a cross-sectional study of the residents in rural areas. Demographics and medical history were collected using a questionnaire. Anthropometry and blood pressure were obtained by physical examination. Blood lipids, fasting plasma glucose, and 2-h postprandial glucose were measured.A total of 2949 (1067 males and 1882 females) were included. The mean age was 63.8 ±â€Š10.7 years. The prevalence of MS in the study population was 16.8% (496/2949). The prevalence of MS was 7.4% in men, 22.2% in women, 15.7% in Han, 18.1% in Tujia, and 14.8% in Miao. According to age, the prevalence of MS was 10.6%, 17.0%, and 18.3% in the 30-50, 50-69, and ≥ 70 years groups. The multivariable analysis showed that female sex (OR = 33.36, 95%CI: 17.0-65.53), dyslipidemia (OR = 4.71, 95%CI: 1.73-12.82), kidney diseases (OR = 2.32, 95%CI: 1.37-3.94), waistline (OR = 1.39, 95%CI: 1.33-1.46), high-density lipoprotein cholesterol (OR = 0.12, 95%CI: 0.06-0.23), triglycerides (OR = 1.52, 95%CI: 1.31-1.76), alanine aminotransferase (OR = 0.98, 95%CI: 0.97-1.00), γ-glutamyltransferase (OR = 1.00, 95%CI: 1.00-1.01), and glycated hemoglobin (OR = 1.31, 95%CI: 1.08-1.59) were independently associated with MS.The prevalence of MS was 16.8% in Qianjiang. Female sex, kidney diseases, alanine aminotransferase, and γ-glutamyltransferase were independent risk factors for MS.


Assuntos
Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , População Rural/tendências , Idoso , Alanina Transaminase/sangue , Antropometria , Glicemia/análise , Pressão Sanguínea/fisiologia , China/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/epidemiologia , Jejum/sangue , Feminino , Humanos , Nefropatias/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Triglicerídeos/sangue , gama-Glutamiltransferase/sangue
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