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1.
Org Biomol Chem ; 18(39): 7922-7931, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33001107

RESUMO

A novel method for the Rh(iii)-catalyzed oxime-directed C-H amidation of indoles with dioxazolones has been developed. This strategy provides an exclusive site selectivity and the directing group can be easily removed. This transformation features a wide substrate scope, good functional group tolerance and excellent yields, and may serve as a significant tool to construct structurally diverse indole derivatives for the screening of potential pharmaceuticals in the future.

2.
Acta Pharmacol Sin ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814818

RESUMO

Cardiac fibrosis is a typical pathological change in various cardiovascular diseases. Although it has been recognized as a crucial risk factor responsible for heart failure, there is still a lack of effective treatment. Recent evidence shows that microRNAs (miRNAs) play an important role in the development of cardiac fibrosis and represent novel therapeutic targets. In this study we tried to identify the cardiac fibrosis-associated miRNA and elucidate its regulatory mechanisms in mice. Cardiac fibrosis was induced by infusion of angiotensin II (Ang II, 2 mg·kg-1·d-1) for 2 weeks via osmotic pumps. We showed that Ang II infusion induced cardiac disfunction and fibrosis accompanied by markedly increased expression level of miR-99b-3p in heart tissues. Upregulation of miR-99b-3p and fibrotic responses were also observed in cultured rat cardiac fibroblasts (CFs) treated with Ang II (100 nM) in vitro. Transfection with miR-99b-3p mimic resulted in the overproduction of fibronectin, collagen I, vimentin and α-SMA, and facilitated the proliferation and migration of CFs. On the contrary, transfection with specific miR-99b-3p inhibitor attenuated Ang II-induced fibrotic responses. Similarly, intravenous injection of specific miR-99b-3p antagomir could prevent Ang II-infused mice from cardiac dysfunction and fibrosis. We identified glycogen synthase kinase-3 beta (GSK-3ß) as a direct target of miR-99b-3p. In CFs, miR-99b-3p mimic significantly reduced the expression of GSK-3ß, leading to activation of its downstream profibrotic effector Smad3, whereas miR-99b-3p inhibitor caused anti-fibrotic effects. GSK-3ß knockdown ameliorated the anti-fibrotic role of miR-99b-3p inhibitor. These results suggest that miR-99b-3p contributes to Ang II-induced cardiac fibrosis at least partially through GSK-3ß. The modulation of miR-99b-3p may provide a new approach for tackling fibrosis-related cardiomyopathy.

3.
Medicine (Baltimore) ; 99(30): e21346, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791734

RESUMO

RATIONALE: Papillary thyroid carcinoma (PTC) is the most common type of primary thyroid cancer with a low incidence of distant metastases. PTC represents more than 70% to -90% of thyroid malignancies. Distant metastases have only been observed in only 1% to 15% of patients with PTC. In this article, we reported the case of a patient with PTC and hyperthyroidism as well as simultaneous multiple metastases. PATIENT CONCERNS: A 47-year-old man was admitted to our hospital on February 22, 2019, with several neck masses that had been present for 12 months, low back pain for 9 months, and lower limb paraplegia for 3 months. DIAGNOSES: According to the patient physical examination, adjuvant examination (e.g., ultrasound, computed tomography, magnetic resonance imaging, blood test, and biopsy) and medical history, the clinical diagnosis was as follows: thyroid papillary carcinoma; cervical lymph node metastasis; multisite bone metastasis (6th and 7th cervical vertebrae, left clavicle proximal, right scapula bone, thoracic vertebrae, lumbar vertebrae, sacral vertebrae, bilateral ilium, and left pubic bone); muscular metastasis (the right medial femoral muscle, the vastus lateralis muscle, left thigh muscle, and the flexor superficialis of the left forearm); possible mediastinal lymph node metastasis; and paraplegia due to the soft-tissue metastasis around the 9th thoracic vertebral spine; and hyperthyroidism (free thyroxine: 36.59 pmol/L, free triiodothyronine: 9.58 pmol/L, thyroid-stimulating hormone: 0.005 µIU/mL, thyroid autoantibody: 2.53 IU/L). INTERVENTIONS AND OUTCOMES: The patient refused to undergo further intervention or follow-up. LESSONS: In summary, this is the 1st case of in which a patient with PTC and hyperthyroidism, as well as simultaneous multiple skeletal muscles and bone metastases, lymph node metastasis, and paraplegia was observed. In practice, in cases where patients have PTC and hyperthyroidism, practitioners should perform further examinations to rule out the presence of distant metastases. We believe that the use of ultrasound has a unique advantage in the diagnosis of PTC and skeletal muscle metastasis.


Assuntos
Carcinoma Papilar/patologia , Hipertireoidismo/diagnóstico , Paraplegia/etiologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Paraplegia/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Recusa do Paciente ao Tratamento , Ultrassonografia/métodos
4.
Int J Syst Evol Microbiol ; 70(9): 4883-4889, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32790603

RESUMO

A novel actinomycete, designated strain TRM 66233T, was isolated from Apocynum venetum L. collected from the Xinjiang Uygur Autonomous Region of China and characterized using a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain TRM 66233T with the genus Streptomyces. Strain TRM 66233T showed a high similarity value to Streptomyces bikiniensis NRRL B-1049T (98.07 %) based on the 16S rRNA gene phylogenetic tree. The whole-cell sugar pattern of TRM 66233T consisted of glucose, galactose, mannose and ribose. The predominant menaquinones were MK-9(H2), MK-9(H6), MK-9(H8) and MK-9(H10). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and four unidentified lipids. The major fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0, C16 : 0 and iso-C17 : 0. The G+C content of the DNA was 70.35 mol%. The DNA-DNA relatedness and average nucleotide identity values as well as evolutionary distances based on multilocus (atpD, gyrB, recA, rpoB and trpB) sequences between strain TRM 66233T and closely related type strains were significantly lower than the recommended threshold values. The whole-genome average nucleotide identity and digital DNA-DNA hybridization values between strain TRM 66233T and S. bikiniensis NRRL B-1049T were 78.86 and 23.2 %, respectively. On the basis of evidence from this polyphasic study, strain TRM 66233T should represent a novel species of the genus Streptomyces, for which the name Streptomyces apocyni sp. nov. is proposed. The type strain is TRM 66233T (=CCTCC AA 2019056T=LMG 31559T).

5.
Microvasc Res ; 132: 104060, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32818511

RESUMO

BACKGROUND: Cardiovascular diseases are associated with proliferation and phenotypic switch. Platelet-derived growth factor-BB (PDGF-BB) is a major initiating factor for proliferative vascular diseases, such as neointimal lesion formation, restenosis after angioplasty, and atherosclerosis. Ruxolitinib, a potent Janus kinase (JAK) 1 and 2 inhibitor, has been reported to significantly block the proliferation-related signaling pathway of JAK2/signal transducers and activators of transcription 3 (STAT3) and harbor a broad spectrum of anti-cancer activities, including proliferation inhibition, apoptosis induction, and anti-inflammation. However, the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation remains to be elucidated. Thus, this study investigates the role of ruxolitinib in regulating PDGF-BB-induced VSMC proliferation and its underlying mechanisms. METHODS: In vivo, the medial thickness of the carotid artery was evaluated using a mouse carotid ligation model, ruxolitinib was administered orally to the mice every other day, and the mice were euthanized on day 28 to evaluate the therapeutic effects of ruxolitinib. Cell proliferation markers were measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. In vitro, VSMCs were treated with ruxolitinib with or without PDGF-BB at an indicated time and concentration. Cell proliferation and apoptosis were measured using Cell Counting Kit-8 assay, MTS assays and flow cytometry. The JAK2/STAT3 signaling pathway involved in the effects of ruxolitinib on VSMCs was detected by western blotting with the specific pathway inhibitor AG490. RESULTS: In vivo, ruxolitinib significantly decreased the ratio-of-intima ratio (I/M ratio) by inhibiting the expression of PCNA and cyclinD1 (p <0.05). In vitro, ruxolitinib inhibited PDGF-BB-induced VSMC proliferation compared with the PDGF-BB treatment group (p <0.05). In addition, ruxolitinib inhibited the PDGF-BB-induced activation of the JAK2/STAT3 signaling pathway and decreased the expression of proliferation related-proteins cyclinD1 and PCNA in VSMCs (p <0.05). CONCLUSION: Our findings suggest that ruxolitinib inhibits VSMC proliferation in vivo and in vitro by suppressing the activation of the JAK2/STAT3 signaling pathway. Therefore, ruxolitinib has a therapeutic potential for proliferative vascular diseases.

6.
Int J Syst Evol Microbiol ; 70(7): 4358-4363, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32618556

RESUMO

A novel Gram-positive, aerobic and motile endophytic actinomycete, designated TRM 65233T, was isolated from the root of Peganum harmala L. collected from Xinjiang Uygur Autonomous Region of China. The isolate had white aerial mycelium and brown substrate mycelium on Gause's synthetic agar. Growth occurred at 10-40 °C, pH 6-9 with NaCl concentration of 0-6 % (w/v). Strain TRM 65233T contained meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell hydrolysates included glucose and galactose as the major whole-cell sugars. The menaquinones were MK-9 (H4) and MK-7. The major cellular fatty acids were iso-C16 : 0, iso-C15 : 0 and anteiso-C17 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phospholipids, phosphatidylinositol and one unidentified lipid. Strain TRM 65233T showed the highest 16S rRNA gene sequence similarity to Actinokineospora cianjurensis BTCC B-558T (98.13 %), Actinokineospora auranticolor IFO 16518T (98.06 %), Actinokineospora spheciospongiae EG49T (97.99 %), Actinokineospora baliensis ID03-0561T (97.97 %), Actinokineospora mzabensis PAL84T (97.95 %) and Actinokineospora bangkokensis 44EHWT (97.06 %). The isolate was distinguished from these phylogenetically related strains by digital DNA-DNA hybridization and average nucleotide identity analyses and by a range of physiological and biochemical characteristics. The G+C content of the genomic DNA was 72.6 mol%. On the basis of polyphasic taxonomic data, strain TRM 65233T represents a novel species of the genus Actinokineospora, for which the name Actinokineospora pegani sp. nov. is proposed. The type strain is TRM 65233T (KCTC 49342=CCTCC AA 2019050).


Assuntos
Actinobacteria/classificação , Peganum/microbiologia , Filogenia , Raízes de Plantas/microbiologia , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
7.
Psychooncology ; 29(8): 1321-1328, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32539164

RESUMO

OBJECTIVE: Suicidal ideation is common in cancer patients and may be associated with hopelessness, demoralization, and depression. This study aims to investigate the serial multiple mediation of demoralization and depression in the relationship between hopelessness and suicidal ideation in cancer patients. METHODS: A total of 244 cancer patients were investigated by using the following standardized self-reported questionnaires: self-rating idea of suicide scale, Beck hopelessness scale, demoralization scale-Mandarin version, and patient health questionnaire depression scale-9. The mediation hypothesis was tested with a serial multiple mediation model (PROCESS model 6). An exploratory graph analysis was performed to detect the correlations among the dimensions of the mental conditions measured by these instruments. RESULTS: Bootstrap analyzes indicate that there were direct and indirect effects of hopelessness on suicidal ideation mediated solely by demoralization (B = 2.3074, SE = 0.1724, P < .001) or by demoralization together with depression (B = 0.1605, SE = 0.0303, 95% confidence interval [CI] = 0.1102 to 0.2303). The mediation of depression alone in the relationship between hopelessness and suicidal ideation was insignificant (B = 0.1541, SE = 0.0519, 95% CI = -0.0565 to 0.0715). The exploratory graph analysis suggests that the strongest edge of dimensions between demoralization and suicidal ideation was desperation-disheartenment (0.62). CONCLUSIONS: The results of the study support the hypothesis that demoralization and depression mediate between hopelessness and suicidal ideation. The early identification of and interventions for hopelessness, demoralization, and depression may prevent cancer patients from developing suicidal ideation.

8.
Biomolecules ; 10(6)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32503302

RESUMO

In the submerged cultivation of filamentous microbes, including actinomycetes, complex morphology is one of the critical process features for the production of secondary metabolites. Ansamitocin P-3 (AP-3), an antitumor agent, is a secondary metabolite produced by Actinosynnema pretiosum ATCC 31280. An excessive mycelial fragmentation of A. pretiosum ATCC 31280 was observed during the early stage of fermentation. Through comparative transcriptomic analysis, a subtilisin-like serine peptidase encoded gene APASM_4178 was identified to be responsible for the mycelial fragmentation. Mutant WYT-5 with the APASM_4178 deletion showed increased biomass and improved AP-3 yield by 43.65%. We also found that the expression of APASM_4178 is specifically regulated by an AdpA-like protein APASM_1021. Moreover, the mycelial fragmentation was alternatively alleviated by the overexpression of subtilisin inhibitor encoded genes, which also led to a 46.50 ± 0.79% yield increase of AP-3. Furthermore, APASM_4178 was overexpressed in salinomycin-producing Streptomyces albus BK 3-25 and validamycin-producing S. hygroscopicus TL01, which resulted in not only dispersed mycelia in both strains, but also a 33.80% yield improvement of salinomycin to 24.07 g/L and a 14.94% yield improvement of validamycin to 21.46 g/L. In conclusion, our work elucidates the involvement of a novel subtilisin-like serine peptidase in morphological differentiation, and modulation of its expression could be an effective strategy for morphology engineering and antibiotic yield improvement in actinomycetes.

9.
Antonie Van Leeuwenhoek ; 113(7): 1023-1031, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32306135

RESUMO

A novel Streptomyces strain, designated TRM43335T, was isolated from the Taklimakan desert in Alar City, Xinjiang, north-west China. The strain was found to exhibit an inhibitory effect on biofilm formation by Candida albicans and Staphylococcus epidermidis. A polyphasic approach was used to determine its taxonomic status. The strain was observed to form abundant aerial mycelium, occasionally twisted and which differentiated into spiral spore chains. Spores of TRM43335T were observed to be oval-shaped, with a smooth surface. Strain TRM43335T was found to grow optimally at 37 °C, pH 8 and in the presence of 1% (w/v) NaCl. The major sugars were identified as ribose, xylose, glucose, mannose and galactose, and the principal phospholipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. The diagnostic cell wall amino acid was identified as LL-diaminopimelic acid. The predominant menaquinone was found to be MK-9(H6). The major cellular fatty acids were identified as iso-C16:1 H, anteiso-C15:0, iso-C16:0, anteiso-C17:0, anteiso-C17:1 w9c and iso-C15:0. Analysis of the 16S rRNA sequence showed that strain TRM43335T exhibits high sequence similarity to Streptomyces desertarenae SYSU D8023T 98.69%. A multilocus sequence analysis of five house-keeping genes (atpD, gyrB, rpoB, recA and trpB) also illustrated that strain TRM43335T should be assigned to the genus Streptomyces. The DNA G + C content of the strain was determined to be 72.8 mol%. The average nucleotide identity relatedness between strain TRM43335T and the phylogenetically related strain S. desertarenae SYSU D8023T was found to be 89.23%, and the in silico DNA-DNA hybridization value to be 36.70%. Therefore, it is concluded that strain TRM43335T represents a novel species of the genus Streptomyces, for which the name Streptomyces taklimakanensis sp. nov is proposed. The type strain is TRM43335T (CCTCC AA 2018052 T = KCTC 49254 T).

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(4): 361-367, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32312376

RESUMO

OBJECTIVE: To study the characteristics of vocalization during the still-face paradigm (SFP) before the age of 2 years and their correlation with the severity of autism spectrum disorder (ASD) symptoms at diagnosis in children with ASD. METHODS: A total of 43 children aged 7-23 months, who were suspected of ASD, were enrolled as the suspected ASD group, and 37 typical development (TD) children, aged 7-23 months, were enrolled as the TD group. The frequency and durations of vocalization in the SFP were measured. The children in the suspected ASD group were followed up to the age of 2 years, and 34 children were diagnosed with ASD. Autism Diagnostic Observation Schedule (ADOS) was used to assess the severity of symptoms. The correlation of the characteristics of vocalization before the age of 2 years with the severity of ASD symptoms was analyzed. RESULTS: Compared with the TD group, the ASD group had significant reductions in the frequency and durations of meaningful vocalization and vocalization towards people and a significant increase in the duration of vocalization toward objects (P<0.05). The Spearman correlation analysis showed that in the ASD group, the frequency and durations of total vocalization, non-speech vocalization, babbling, vocalization towards people, and vocalization towards objects were negatively correlated with the score of communication in ADOS (P<0.05). The frequency and durations of total vocalization, babbling, and vocalization towards people and the duration of vocalization towards objects were negatively correlated with the score of reciprocal social interaction in ADOS (P<0.05). The frequency of total vocalization, the duration of babbling, and the frequency and duration of vocalization towards people were negatively correlated with the score of play in ADOS (P<0.05). The frequency of total vocalization and non-speech vocalization and the frequency and durations of vocalization towards people were negatively correlated with the score of stereotyped behaviors and restricted interests in ADOS (P<0.05). The multiple linear regression analysis showed that the frequency of total vocalization was a negative predictive factor for the score of communication in ADOS (P<0.001), and the duration of vocalization towards people was a negative predictive factor for the score of reciprocal social interaction in ADOS (P<0.05). CONCLUSIONS: SFP can better highlight the abnormal vocalization of ASD children before the age of 2 years, and such abnormalities can predict the severity of ASD symptoms early.


Assuntos
Transtorno do Espectro Autista , Humanos , Lactente , Relações Interpessoais
11.
Neurosci Lett ; 729: 135003, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32335219

RESUMO

Hyperthyroidism may cause cognitive decline and increases the risk of Alzheimer's disease (AD), the major form of dementia; however, the underlying mechanism of this relationship is unclear. AD is associated with increased serum levels of tau. In this study, we investigated the relationship between serum thyroid hormones (THs) and tau. Fifty participants diagnosed with hyperthyroidism and fifty euthyroid counterparts were included and received clinical examinations. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and tau protein were assessed. The total tau protein level was significantly higher in hyperthyroidism participants than in their euthyroid counterparts. The level of circulating total tau had a significant positive association with the serum concentrations of FT3 and FT4. Total tau level was increased in the low TSH group and the serum THs decreased with the increase of age. These findings reveal that peripheral THs are associated with the serum concentration of tau, which may be involved in the pathogenesis of AD, suggesting a potential therapeutic target of AD via hyperthyroidism therapy.

12.
Zhongguo Zhong Yao Za Zhi ; 45(1): 202-208, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237431

RESUMO

To study the effect of dihydroartemisinin(DHA) on hepatic inflammation and lipid metabolism in weaned piglets, a liver injury model of weaned piglets was established by lipopolysaccharide(LPS)-induced method. In this study, 30 healthy weaned piglets were selected and randomly divided into control group(CON), model group(LPS) and treatment group(LD, LPS+DHA), with 10 in each group. The CON group and the LPS group were fed with a basal diet, and the LD group was fed with a basal diet+80 mg·kg~(-1) DHA. The test period was 21 days. The LPS group and the LD group were intraperitoneally injected with 100 µg·kg~(-1) LPS at 4 hours before slaughter, and the CON group was injected with the same dose of sterile physiological saline. The results showed that compared with the CON group, contents of TC, AST activity and AST/ALT ratio were significantly increased in the serum of LPS piglets(P<0.05), content of HDL-c was significantly decreased(P<0.05). In addition, in the liver, the levels of TG, NEFA, IL-1ß, IL-6 and TNF-α were increased significantly(P<0.05), and activities of LPL, HL and TL were decreased significantly(P<0.05). Compared with LPS group, content of TC, activities of AST and ALT and the AST/ALT ratio were decreased significantly(P<0.05), and HDL-c content increased significantly in the serum of LD piglets(P<0.05). The contents of TG, NEFA, IL-1ß, IL-6 and TNF-α and activity of FAS in the liver were decreased significantly(P<0.05), and the activities of LPL, HL and TL were increased significantly(P<0.05). Compared with the CON group, the mRNA expressions of IL-1ß, IL-6, TNF-α, ACCß and SREBP-1 c in the LPS group were significantly increased(P<0.05), the mRNA expressions of AMPKα, SIRT1, CPT-1 and SCD were decreased significantly(P<0.05). The above indicators were improved in the LD group compared with the LPS group. These results indicated that DHA had a certain effect in recovering LPS-induced liver inflammation and abnormal lipid metabolism.


Assuntos
Artemisininas/uso terapêutico , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Animais , Suplementos Nutricionais , Lipopolissacarídeos , Fígado/fisiopatologia , Suínos
13.
World J Gastroenterol ; 26(10): 1029-1041, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32205994

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global metabolism-associated liver disease. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly discovered secreted protein that is involved in metabolic homeostasis. However, much remains to be discovered about its function in hepatic lipid metabolism; thus, we assessed whether MANF could regulate hepatic metabolism. AIM: To establish in vivo and in vitro NAFLD models to explore the role of MANF in hepatic lipid metabolism. METHODS: HepG2 cells treated with free fatty acids (FFAs) and ob/ob mice were used as NAFLD models. Liver tissues collected from wild type and ob/ob mice were used to detect MANF expression. Cells were treated with FFAs for different durations. Moreover, we used lentiviral constructs to establish overexpression and knockdown cell models in order to interfere with MANF expression levels and observe whether MANF influences hepatic steatosis. Western blot analysis and quantitative real-time PCR were used to detect protein and gene expression, and oil red O staining was used to visualize intracellular lipid droplets. RESULTS: Hepatic MANF protein and mRNA expression in wild type mice were 10-fold and 2-fold higher, respectively, than those in ob/ob mice. The MANF protein was temporarily increased by 1.3-fold after stimulation with FFAs for 24 h and gradually decreased to 0.66-fold that of the control at the 72 h time point in HepG2 cells. MANF deficiency upregulated the expression of genes involved in fatty acid synthesis, cholesterol synthesis, and fatty acid uptake and aggravated HepG2 cell steatosis, while MANF overexpression inhibited fatty acid synthesis and uptake and cholesterol synthesis, and rescued HepG2 cells from FFAs-induced steatosis. Furthermore, a significant decrease in triglyceride levels was observed in the MANF overexpression group compared with the control group (0.4288 ± 0.0081 mmol/g vs 0.3746 ± 0.0121 mmol/g, P < 0.05) upon FFAs treatment. There was also a 17% decrease in intracellular total cholesterol levels between the MANF overexpression group and the control group (0.1301 ± 0.0059 mmol/g vs 0.1088 ± 0.0009 mmol/g, P < 0.05) upon FFAs treatment. Moreover, MANF suppressed lipid deposition in HepG2 cells. CONCLUSION: Our findings indicate that MANF improves the phenotype of liver cell steatosis and may be a potential therapeutic target in hepatic steatosis processes.

14.
Medicine (Baltimore) ; 99(9): e19418, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118796

RESUMO

Few studies on the individual and combined analysis between serum uric acid (SUA) and body mass index (BMI) and blood pressure (BP) were conducted in individuals aged ≥45 years. We aimed to assess the extent to which BMI and SUA and their interaction affect BP in Chinese middle-aged and older adults.Data were selected from the China Health and Retirement Longitudinal Study (CHARLS). A total of 5888 individuals aged 45 to 96 was included. Differences between BMI, or between categories of blood pressure were evaluated by t test or chi-square test. The trend of related variables according to four BMI categories was also tested using contrast analysis. The adjusted associations between various characteristics and BP status were first compared using linear regression models, as appropriate. Then, general linear models adjusting for related potential confounders were used to examine the synergistic effect of SUA and BMI level on BP for middle-aged and elderly individuals in China.Age-adjusted partial Pearson correlation coefficient showed that BMI was significantly and positively correlated with BP both in male and female, SUA positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in males with BMI <24.0 kg/m and females with BMI <24.0 kg/m. However, SUA level significantly and positively correlated with DBP, but not with SBP, in females with BMI ≥24.0 kg/m. Multiple linear regression analysis showed that BMI was independently associated with BP both in male and female, SUA significantly and positively associated with SBP in both males and females with BMI <24.0 kg/m, However, SUA level positively correlated with DBP in females with BMI <24.0 kg/m, but not with males with BMI <24.0 kg/m, independent of other confounding factors. A general linear model analysis adjusted for confounding factors did not reveal interaction between BMI, SUA levels and SBP (ß=-1.404, P = .686 in males; ß=-2.583, P = .575 in females) and DBP (ß=-2.544, P = .263 in males; ß=-2.619, P = .622 in females).No interaction between BMI, SUA levels, and BP was observed in either males or females; However, BMI was independently associated with BP both in male and female, SUA independently associated with SBP both in males and females with BMI <24.0 kg/m, and SUA independently associated with DBP in females with BMI ≥24.0 kg/m.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Ácido Úrico/análise , Adulto , Idoso , Determinação da Pressão Arterial/métodos , China , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
15.
Neurotox Res ; 37(4): 1029-1035, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32026360

RESUMO

Hyperphosphorylated tau is an important pathological agent in Alzheimer's disease (AD). Tau effluxes from the brain to the blood could potentially stimulate the production of naturally occurring antibodies (NAbs). We aimed to investigate whether NAbs to tau (NAbs-tau) was generated in human blood and to figure out the alteration of plasma NAbs-tau level in AD patients. About 192 AD patients and 192 age-matched and non-demented controls (NC) were enrolled in the present study. Immunofluorescence staining and western blot assays were used to confirm the existence of NAbs-tau in human blood. The plasma level of NAbs-tau in NC and AD group was analyzed by ELISA. Immunofluorescence staining and western blot assays confirmed the existence of NAbs-tau in human blood. However, no significant difference in the plasma level of NAbs-tau was observed between NC and AD group. Furthermore, the plasma level of NAbs-tau had no significant correlation with MMSE scores. The present study confirmed that NAbs-tau exists in human blood but does not differ in level between the NC and AD group. Plasma NAbs-tau is not a reliable biomarker for AD.

16.
Insect Sci ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32108430

RESUMO

Rice stripe virus (RSV) is the causative agent of rice stripe disease and is completely dependent on insect vectors for its plant-to-plant transmission. Laodelphax striatellus is the major insect vector for RSV. In this study, we explored the interactions between RSV infection and L. striatellus autophagy, a potential intrinsic antiviral mechanism in insects. We found that L. striatellus autophagic activity did not affect RSV infection; however, the autophagy-related-8 (Atg8) gene significantly enhanced virus infection. During RSV initial infection within the L. striatellus midgut, silencing of Atg8 expression significantly decreased the phosphorylation of c-Jun N-terminal kinase (p-JNK); however, when RSV infection is absent, silencing of Atg8 did not alter p-JNK levels. These results indicated that Atg8 might activate the JNK machinery by allowing more virus infection into cells. We further revealed that Atg8-deficiency significantly decreased RSV accumulation on the surface of the insect midgut epithelial cells, suggesting a receptor trafficking function of the γ-aminobutyric acid receptor-associated protein family. Using the RSV ovary entry as a model, in which vitellogenin receptor (VgR) mediates RSV cell entry, we clarified that Atg8-deficiency decreased the abundance of VgR localizing on the cytomembrane and disturbed the attachment of RSV in the germarium zones. Collectively, these results revealed an autophagy-independent function of L. striatellus Atg8 that enhances RSV initial infection by increasing virus attachment on the infection sites.

17.
Environ Sci Pollut Res Int ; 27(10): 11375-11386, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31965499

RESUMO

Understanding the mechanisms that lead various hydrological conditions to influence solute and carbon dynamics in karst rivers is a crucial issue. In this study, high-frequency sampling and analyses of water chemistry and ẟ13CDIC were conducted from October 2013 to September 2014 in a typical karst river, the Beipan River in southwestern China. The major ions (such as Ca2+, Mg2+, HCO3-, K+, SO42-, Na+, and Cl-) in the river are mainly from the weathering of carbonates and silicates and present temporal hydrological variabilities. Sr and U are mainly derived from carbonate weathering and show chemostatic behaviors responding to increasing discharge, similar to carbonate-sourced ions Ca2+, Mg2+, and HCO3-. Silicate weathering is the primary source of Al and Li, which show significant dilution effects similar to those of Na+ responding to high discharge. Meanwhile, most dissolved trace elements (such as Zn, Cu, Ba, Sb, Mn, Mo, and Pb) are strongly impacted by anthropogenic overprints and also exhibit a significant seasonal variability, which may be related with mining activities in the investigated area. A simultaneous increase of ẟ13CDIC and decrease in ∆DIC contents and pCO2 values suggests that photosynthesis is the primary control on riverine DIC variability during the high-flow season. Besides, the pCO2 values display significant chemostatic behaviors owing to the influx of biological CO2, which is produced by microbiological activities and ecological processes, and enhanced by monsoonal climatic conditions. A two-dimensional endmember mixing model demonstrates that carbonate weathering (averaging 62%) along with biological carbon (averaging 38%) are main sources to the riverine DIC, with temporal variability. Consequently, these results show that carbonate weathering and involved plant photosynthesis are the dominant processes controlling the riverine DIC contents under high discharge and temperature conditions. This work provides insight into the crucial influence of hydrological variability on solute sources and carbon dynamics under monsoonal climate for the karst rivers.


Assuntos
Carbono/análise , Rios , Carbonatos/análise , China , Monitoramento Ambiental , Hidrologia
18.
J Hazard Mater ; 381: 121208, 2020 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-31563672

RESUMO

Contaminated mining sites require ecological restoration work, of which phytoremediation using appropriate plant species is an attractive option. Our present study is focused on one typical contaminated mine site with indigenous plant cover. The X-ray absorption near edge structure (XANES) analysis indicated that Cu (the major contaminant) was primarily associated with goethite (adsorbed fraction), with a small amount of Cu oxalate-like species (organic fraction) in mine affected soil. With growth of plant species like Miscanthus floridulus and Stenoloma chusanum, the Cu-oxalate like organic species in rhizosphere soil significantly increased, with corresponding decrease in Cu-goethite. In the root cross-section of Miscanthus floridulus, synchrotron-based micro-X-ray fluorescence (µ-XRF) microscopy and micro-XANES results indicated that most Cu was sequestered around the root surface/epidermis, primarily forming Cu alginate-like species as a Cu-tolerance mechanism. From the root epidermis to the cortex and vascular bundle, more Cu(I)-glutathione was observed, suggesting reductive detoxification ability of Cu(II) to Cu(I) during the transport of Cu in the root. The observation of Cu-histidine in root internal cell layers showed another Cu detoxification pathway based on coordinating amino ligands. Miscanthus floridulus showed ability to accumulate phosphorous and nitrogen nutrients in rhizosphere and may be an option for in situ phytostabilization of metals in contaminated mining area.

19.
Nurs Sci Q ; 33(1): 65-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31795877

RESUMO

The authors focus on discussing the barriers in the use of physical assessment skills by RNs (Registered Nurses) in mainland China. This study was a multicenter, cross-sectional survey conducted in 6 cities with 1,115 RNs in mainland China. The results indicated that 15.36% of the skills were used regularly, where general and skin condition assessment skills are used most frequently. Lack of training and a unified documentation form were the top two barriers RNs faced. In conclusion, RNs are not performing assessment skills with required proficiency in mainland China and still need managerial attention in continuing education.

20.
Orthop Surg ; 11(5): 784-793, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663278

RESUMO

OBJECTIVE: For the purpose of providing evidence for the treatment of osteoporosis and osteopenia, this study retrospectively identified succinylation-modified sites and proteins in postmenopausal women, and bioinformatics analysis were performed. METHODS: From January 2016 to June 2018, a total of 30 postmenopausal women aged from 55 to 70 years old were assigned to three groups: 10 cases with osteoporosis; 10 cases with osteopenia; and 10 cases with normal bone mass. Subsequently, the serum samples were collected from all cases for succinyl-proteome. Measures comprised label-free quantitative analysis, succinylation enrichment techniques, the liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) methods, and bioinformatics. RESULTS: A total of 113 succinylation sites on 35 proteins were identified based on quantitative information. The variation of the different multiple folds were more than 1.2 times as a significant increase for up-regulated and less than 1/1.2 times as a significant decrease for down-regulated. Among the quantified succinylation sites, 66 were up-regulated and 11 down-regulated in the Osteopenia/Normal comparison group, 24 were up-regulated and 44 down-regulated in the Osteoporosis/Osteopenia comparison group, 45 were up-regulated and 32 down-regulated in the Osteoporosis/Normal comparison group. Among the quantified succinylation proteins, 24 were up-regulated and 7 down-regulated in the Osteopenia/Normal comparison group, 15 were up-regulated and 20 down-regulated in the Osteoporosis/Osteopenia comparison group, 20 were up-regulated and 17 down-regulated in the Osteoporosis/Normal comparison group. The percentage of proteins differed in immune response, signaling pathway, proteolysis, lymphocyte, leukocyte, and cell activation. Four differentially expressed proteins (apolipoprotein A-I, apolipoprotein A-II, hemoglobin subunit alpha, and haptoglobin) contained quantitative information; they were mediated with receptors, factors, mechanisms, that related to bone metabolism. Hemoglobin subunit alpha was screened for diagnosis of osteopenia. CONCLUSIONS: The succinyl-proteome experimental data indicated that apolipoprotein A-I, apolipoprotein A-II, hemoglobin subunit alpha, and haptoglobin were valuable for diagnosis and treatment in postmenopausal women with osteoporosis and osteopenia.


Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Osteoporose Pós-Menopausa/sangue , Proteoma/metabolismo , Ácido Succínico/sangue , Idoso , Cromatografia Líquida , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Espectrometria de Massas em Tandem
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