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1.
Oxid Med Cell Longev ; 2021: 3259238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721757

RESUMO

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.

2.
Nat Prod Res ; : 1-7, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822252

RESUMO

Phytochemical investigation of the fruits of Crataegus pinnatifida Bunge led to the isolation of four pairs enantiomeric benzofuran lignans (1a/1b-4a/4b) including four undescribed compounds (1a, 2b, 3b and 4b). Their structures were determined by extensive spectroscopic methods and the absolute configurations were further determined by the comparison of experimental and calculated ECD spectra. All the enantiomeric lignans were evaluated for their inhibitory activities to tyrosinase. Among them, compound 4a showed moderate inhibition activity (IC50 = 0.54 mM).

3.
Stroke ; 52(12): 3918-3925, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34404235

RESUMO

BACKGROUND AND PURPOSE: Researches on rare variants of NOTCH3 in the general Chinese population are lacking. This study aims to describe the spectrum of rare NOTCH3 variants by whole-exome sequencing in a Chinese community-based cohort and to investigate the association between rare NOTCH3 variants and age-related cerebral small vessel disease. METHODS: The cross-sectional study comprised 1065 participants who underwent whole-exome sequencing and brain magnetic resonance imaging. NOTCH3 variants with minor allele frequency<1% in all 4 public population databases (1000 Genomes, ESP6500siv2_ALL, GnomAD_ALL, and GnomAD_EAS) were defined as rare variants. Multivariable linear and logistic regressions were used to investigate the associations between rare NOTCH3 variants and volume of white matter hyperintensities and cerebral small vessel disease burden. Clinical and imaging characteristics of rare NOTCH3 variant carriers were summarized. RESULTS: Sixty-five rare NOTCH3 variants were identified in 147 of 1065 (13.8%) participants, including 57 missense single nucleotide polymorphisms (SNPs), 5 SNPs in splice branching sites, and 3 frameshift deletions. A significantly higher volume of white matter hyperintensities and heavier burden of cerebral small vessel disease was found in carriers of rare NOTCH3 EGFr (epidermal growth factor-like repeats)-involving variants, but not in carriers of EGFr-sparing variants. The carrying rate of rare EGFr-involving NOTCH3 variants in participants with dementia or stroke was significantly higher than those without dementia or stroke (12.4% versus 6.6%, P=0.041). Magnetic resonance imaging signs suggestive of CADASIL were found in 3.4% (5/145) rare EGFr cysteine-sparing NOTCH3 variant carriers but not in 2 cysteine-altering NOTCH3 variant carriers. CONCLUSIONS: Carriers of rare NOTCH3 variants involving the EGFr domain may be genetically predisposed to age-related cerebral small vessel disease in the general Chinese population.

4.
Ann Transl Med ; 9(8): 640, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987338

RESUMO

Background: Considerable evidence has been presented that heart and health-related quality of life are directly linked in patients with various diseases. This exploratory study investigated whether cardiac structure and function were associated with health-related quality of life in the general population. Methods: This cross-sectional study was performed in five villages of Shunyi, a suburban district of Beijing, from June 2013 to April 2016. All inhabitants aged 35 years or older living in five villages of Shunyi were invited to participate. Exclusion criteria were individuals who declined participation, who had incomplete Health-related quality of life (HRQoL) data, and who had suboptimal echocardiograms. HRQoL was evaluated by the Mandarin version of SF-36. The association between the echocardiography-derived cardiac structure and function and each domain of SF-36 was analyzed by the multivariate linear regression analysis after adjusted for conventional risk factors affecting HRQoL. Results: The baseline data of 990 individuals were analyzed. The median age of the participants was 57 (50-63) years, and 367 (37.1%) were male, the average physical and mental component summary scores were 89.3 (79.8-94.3) and 90 (83.5-95) respectively. Tricuspid annular plane systolic excursion, an echocardiography-derived right ventricular parameter, was associated with all the subscales and summarized scores of SF-36 (all P<0.05). The independent association between tricuspid annular plane systolic excursion and physical/mental component summary scores remained after adjusting for age, gender, body mass index, education level, annual personal income, smoking and drinking status, and comorbidities (ß=0.65, 95% confidence interval 0.30-1.01, P<0.01 and ß=0.49, 95% confidence interval 0.23-0.76, P<0.01 for physical and mental component summary scores respectively). Compared with the participants with tricuspid annular plane systolic excursion ≥21 mm, the participants with tricuspid annular plane systolic excursion <21 mm had lower adjusted scores of physical and mental component summary scores (81.8 vs. 84.5, P=0.015, and 85.5 vs. 88.1, P<0.01 for physical and mental component summary scores respectively). Conclusions: In this population-based study, right ventricular systolic function assessed by tricuspid annular plane systolic excursion was independently associated with health-related quality of life assessed by SF-36.

5.
Stroke Vasc Neurol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903177

RESUMO

BACKGROUND AND PURPOSE: This study aimed to investigate the association of metabolic syndrome (MetS) with both intracranial atherosclerotic stenosis (ICAS) and imaging markers of cerebral small vessel disease (CSVD) in a community-based sample. METHODS: This study included 943 participants (aged 55.6±9.2 years, 36.1% male) from the community-based Shunyi cohort study. MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score. ICAS was evaluated by brain magnetic resonance angiography. The MRI markers of CSVD, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVS), were assessed. Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers. RESULTS: We found that risk of ICAS (OR=1.75, 95% CI 1.39 to 2.21, p<0.001) increased consistently with MetS severity. MetS severity was significantly associated with higher risks of WMH volume (ß=0.11, 95% CI 0.01 to 0.20, p=0.02) and lacunes (OR=1.28, 95% CI 1.03 to 1.59, p=0.03) but not the presence of CMBs (OR=0.93, 95% CI 0.74 to 1.16, p=0.51) and PVS severity (EPVS in basal ganglia: OR=0.96, 95% CI 0.84 to 1.09, p=0.51 and EPVS in white matter: OR=1.09, 95% CI 0.96 to 1.23, p=0.21). CONCLUSIONS: Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery, whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.

6.
Hum Exp Toxicol ; 40(10): 1634-1645, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33779332

RESUMO

OBJECTIVE: To explore the effects of myocardin-related transcription factor A (MRTF-A) knockout on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat diet (HFD). METHODS: Normal-fat diet (NFD) or HFD was fed to MRTF-A-knockout (MRTF-A-/-) and wild-type (WT) mice for 16 weeks. Liver histopathological status was observed using Hematoxylin and Eosin (HE) staining, Oil Red O staining, Sirius Red staining, and Immunohistochemical staining. The mRNA and protein levels in liver tissues were measured through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: Compared with WT + HFD group, mice in MRTF-A-/- + HFD group were decreased in body weight, blood glucose, plasma insulin, liver TG and NAFLD activity score (NAS), with liver function recovery. Besides, compared with HFD-fed WT mice, HFD-fed MRTF-A-/- mice were improved in hepatic fibrosis, accompanied by decreased collagen content (%) and down-regulated expressions of α-SMA, COL1A2, TGFß1, and SMAD3. In mice fed with HFD, the expression of MCP-1, CCR2, F4/80 and CD68 declined in liver tissues of MRTF-A-/- mice as compared with WT mice. Besides, in hepatic macrophages isolated from HFD-fed mice, the observed increased expression of TNF-α, IL-1ß, MCP-1, as well as decreased expression of CCR2. Compared with WT + HFD group, MRTF-A-/- + HFD group mice were decreased regarding NF-κB p65 in liver tissues. CONCLUSION: MRTF-A knockout reduced macrophage infiltration, down-regulated NF-κB p65 expression, and ameliorated inflammation and fibrosis of liver tissues in mice, thereby becoming a potential therapeutic target for NASH treatment.

7.
Sci China Life Sci ; 64(9): 1473-1480, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33439457

RESUMO

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

8.
Phytochemistry ; 183: 112628, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33412403

RESUMO

Nine undescribed guaiane-type sesquiterpenoids stelleraterpenoids A‒I, along with seven reported congeners, were isolated and identified from the 70% EtOH extract of the roots of Stellera chamaejasme L. Their chemical structures were elucidated on the basis of various spectral data. The relative configurations were determined by their NOESY spectra and comparison between their experimental and calculated NMR data. The absolute configurations were established by the comparison between the experimental and calculated ECD spectra and further by X-ray single-crystal diffraction analysis. The neuroprotective effects of these compounds on the H2O2-induced damage in human neuroblastoma SH-SY5Y cells were evaluated. Stelleraguaianone B exhibited the better activity with 71.62% cell viability compared to the positive control Trolox (65.05%) at 12.5 µM, which might be achieved by inhibiting the apoptosis of SH-SY5Y cells based on an annexin V-FITC/PI staining experiment.


Assuntos
Fármacos Neuroprotetores , Sesquiterpenos , Thymelaeaceae , Peróxido de Hidrogênio , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano
9.
J Am Heart Assoc ; 10(3): e018003, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33496186

RESUMO

Background It was uncertain if direct endovascular thrombectomy (ET) was superior to bridging thrombolysis (BT) for patients with acute ischemic stroke caused by large-vessel occlusions. We aimed to examine real-world clinical outcomes of ET using nationwide registry data in China and to compare the efficacy and safety between BT and direct ET. Methods and Results Patients treated with ET from a nationwide registry study in China were included. Rapid neurological improvement, intracranial hemorrhage, and in-hospital mortality were compared between the 2 groups using multivariate logistic models and propensity-score matching analyses. A total of 7674 patients from 592 stroke centers were included. The median onset-to-puncture time, onset-to-door time, and door to puncture time were 290, 170, and 99 minutes, respectively. A total of 2069 (27.0%) patients received BT treatment. Patients in the BT group had a significantly shorter onset-to-puncture time (235 versus 323 minutes; P<0.001) and onset-to-door time (90 versus 222 minutes; P<0.001) compared with the direct ET group. The prior use of intravenous thrombolysis was associated with a higher rate of rapid neurological improvement (adjusted odds ratio [OR], 0.83; 95% CI, 0.71-0.96) and higher risk of intracranial hemorrhage (adjusted OR, 1.46; 95% CI, 1.18-1.80) in multivariate analyses and propensity-score matching analyses. Conclusions This study reflects the current application of ET in China. More patients received direct ET than BT. Our results suggested that favorable short-term outcomes could be achieved with BT compared with direct ET. Higher risk of intracranial hemorrhage was observed in the BT group.


Assuntos
Isquemia Encefálica/terapia , Procedimentos Endovasculares/métodos , Fibrinolíticos/uso terapêutico , Sistema de Registros , Terapia Trombolítica/métodos , Idoso , Isquemia Encefálica/mortalidade , China/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Trombectomia/métodos
10.
J Cereb Blood Flow Metab ; 41(3): 561-568, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32312169

RESUMO

Our aim is to investigate whether vascular risk factors are associated with cerebral deep medullary veins (DMVs) and whether DMVs are associated with MRI markers of cerebral small vessel disease (CSVD) or risk of stroke. In a community-based cohort of 1056 participants (mean age 55.7 years), DMVs were identified on susceptibility-weighted imaging (SWI) and counted in periventricular regions. Neuroimaging markers including lacunes, whiter matter hyperintensity (WMH), microbleeds, enlarged perivascular space, and brain atrophy were evaluated. The number of DMVs decreased with age (p = 0.007). After adjusting for age and sex, the number of DMVs was not associated with traditional vascular risk factors. Fewer DMVs was associated with increase of WMH and lacunes, but the association vanished after adjustment for vascular risk factors. However, fewer DMVs were independently associated with brain atrophy (p < 0.001). DMVs were not associated with three-year risk of stroke. Our results suggest that DMV is significantly different from other MRI markers of CSVD regarding risk factors, association with other CSVD markers, and risk of stroke. Nonetheless, the significant association between DMV and brain atrophy suggested the potential role of venules in age-related neurodegenerative process, which deserves further investigation.


Assuntos
Veias Cerebrais/fisiologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Encéfalo/irrigação sanguínea , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Veias Cerebrais/diagnóstico por imagem , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
Exp Neurol ; 336: 113532, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33245889

RESUMO

Increasing evidence suggests that microglial polarization plays an important role in the pathological processes of neuroinflammation following subarachnoid hemorrhage (SAH). Previous studies indicated that milk fat globule-epidermal growth factor-8 (MFG-E8) has potential anti-apoptotic and anti-inflammatory effects in cerebral ischemia. However, the effects of MFG-E8 on microglial polarization have not been evaluated after SAH. Therefore, the aim of this study was to explore the role of MFG-E8 in anti-inflammation, and its effects on microglial polarization following SAH. We established the SAH model via prechiasmatic cistern blood injection in mice. Double-immunofluorescence staining, western blotting and quantitative real-time polymerase chain reaction (q-PCR) were performed to investigate the expression and cellular distribution of MFG-E8. Two different dosages (1 and 5 µg) of recombinant human MFG-E8 (rhMFG-E8) were injected intracerebroventricularly (i.c.v.) at 1 h after SAH. Brain water content, neurological scores, beam-walking score, Fluoro-Jade C (FJC), and terminal deoxynucleotidyl transferase dUTP nick endlabeling staining (TUNEL) were measured at 24 h. Suppression of MFG-E8, integrin ß3 and phosphorylation of STAT3 were achieved by specific siRNAs (500 pmol/5 µl) and the STAT3 inhibitor Stattic (5 µM). The potential signaling pathways and microglial polarization were measured by immunofluorescence labeling and western blotting. SAH induction increased the levels of inflammatory mediators and the proportion of M1 cells, and caused neuronal apoptosis in mice at 24 h. Treatment with rhMFG-E8 (5 µg) remarkably decreased brain edema, improved neurological functions, reduced the levels of proinflammatory factors, and promoted the microglial to shift to M2 phenotype. However, knockdown of MFG-E8 and integrin ß3 via siRNA abolished the effects of MFG-E8 on anti-inflammation and M2 phenotype polarization. The STAT3 inhibitor Stattic further clarified the role of rhMFG-E8 in microglial polarization by regulating the protein levels of the integrin ß3/SOCS3/STAT3 pathway. rhMFG-E8 inhibits neuronal inflammation by transformation the microglial phenotype toward M2 and its direct protective effect on neurons after SAH, which may be mediated by modulation of the integrin ß3/SOCS3/STAT3 signaling pathway, highlighting rhMFG-E8 as a potential therapeutic target for the treatment of SAH patients.


Assuntos
Anti-Inflamatórios/farmacologia , Antígenos de Superfície/farmacologia , Encefalite/tratamento farmacológico , Encefalite/patologia , Microglia/patologia , Proteínas do Leite/farmacologia , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/patologia , Animais , Anti-Inflamatórios/administração & dosagem , Antígenos de Superfície/administração & dosagem , Apoptose/efeitos dos fármacos , Edema Encefálico/patologia , Edema Encefálico/prevenção & controle , Polaridade Celular , Encefalite/psicologia , Técnicas de Silenciamento de Genes , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Leite/administração & dosagem , Neurônios/patologia , Desempenho Psicomotor/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Hemorragia Subaracnóidea/psicologia
12.
Dermatol Ther ; 34(1): e14539, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33190373

RESUMO

Fractional CO2 laser is a good option for treating acne scars. However, the clinical efficacy of this treatment modality requires further evidence. To perform a meta-analysis to assess clinical improvements in acne scars with fractional CO2 laser and non-CO2 laser therapies. Databases (PubMed, Embase, Cochrane Library) were searched using the search strategy to identify eligible studies. All statistical analyses were performed using the Review Manager 5.0, and a meta-analysis was conducted to assess the effects of fractional CO2 laser used as a treatment for acne scars. Eight studies were included for further analysis. There was no significant difference between fractional CO2 laser and non-CO2 laser therapies in terms of clinical improvement, observer assessment (P = .19), patient assessment (P = .91), and incidence of post-inflammatory hyperpigmentation (P = .69). The subgroup analyses showed that the duration of follow-up had little effect on the evaluation of treatment effect. The efficacy of fractional CO2 laser therapy in acne scars appeared to be equal to that of non-CO2 laser therapies. More well designed randomized controlled trials and more credible and standard evaluation criteria are needed, and the efficiency of combination therapy requires further analysis.


Assuntos
Acne Vulgar , Lasers de Gás , Acne Vulgar/complicações , Acne Vulgar/diagnóstico , Dióxido de Carbono , Cicatriz/diagnóstico , Cicatriz/etiologia , Cicatriz/terapia , Humanos , Lasers de Gás/efeitos adversos , Resultado do Tratamento
13.
Basic Clin Pharmacol Toxicol ; 127(6): 488-494, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32564469

RESUMO

Studies on the effectiveness and mechanisms of reducing scar formation by interfering with the renin-angiotensin-aldosterone-system (RAAS) have been demonstrated in animals, but not in humans due to the lack of clinical support. Our aim was to investigate whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) could inhibit scar formation in humans. Thus, an observational and hypothesis-generating study using a designed questionnaire was carried out. A total of 347 patients with postoperative scars secondary to thyroid tumours were enrolled. They were divided into four groups: ACEI group, ARB group, other antihypertensive drugs control group and blank control group according to the administration of antihypertensive drugs. The width of scar was measured, and the Scar Cosmesis Assessment and Rating (SCAR) Scale was filled out. Results showed that patients of ACEI group (mean scar width 1.60 mm) and ARB group (mean scar width 1.57 mm) formed smaller scars than those of other antihypertensive drugs control group (mean scar width 2.09 mm) and blank control group (mean scar width 2.0 mm). Oral administration of ACEI and ARB may be associated with better post-surgical scar formation in humans. These two kinds of antihypertensive drugs may be active components of anti-scar medicine.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Cicatriz/tratamento farmacológico , Hipertensão/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Estudos de Casos e Controles , Cicatriz/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
14.
Int J Mol Sci ; 21(5)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120850

RESUMO

Few studies have been conducted regarding the biological function and regulation role of gga-miR-221-5p in the liver. We compared the conservation of miR-221-5p among species and investigated the expression pattern of gga-miR-221-5p, validating the direct target genes of gga-miR-221-5p by dual luciferase reporter assay, the biological function of gga-miR-221-5p in the liver was studied by gga-miR-221-5p overexpression and inhibition. Furthermore, we explored the regulation of gga-miR-221-5p and its target genes by treatment with estrogen and estrogen antagonists in vivo and in vitro. The results showed that miR-221-5p was highly conserved among species, expressed in all tested tissues and significantly downregulated in peak-laying hen liver compared to pre-laying hen liver. Gga-miR-221-5p could directly target the expression of elongase of very long chain fatty acids 6 (ELOVL6) and squalene epoxidase (SQLE) genes to affect triglyceride and total cholesterol content in the liver. 17ß-estradiol could significantly inhibit the expression of gga-miR-221-5p but promote the expression of ELOVL6 and SQLE genes. In conclusion, the highly conservative gga-miR-221-5p could directly target ELOVL6 and SQLE mRNAs to affect the level of intracellular triglyceride and total cholesterol. Meanwhile, 17ß-estradiol could repress the expression of gga-miR-221-5p but increase the expression of ELOVL6 and SQLE, therefore promoting the synthesis of intracellular triglyceride and cholesterol levels in the liver of egg-laying chicken.


Assuntos
Galinhas/metabolismo , Estrogênios/farmacologia , Elongases de Ácidos Graxos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , MicroRNAs/metabolismo , Esqualeno Mono-Oxigenase/metabolismo , Animais , Linhagem Celular , Galinhas/genética , Colesterol/metabolismo , Estradiol/administração & dosagem , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Estrogênios/administração & dosagem , Elongases de Ácidos Graxos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , MicroRNAs/genética , Esqualeno Mono-Oxigenase/genética , Triglicerídeos/metabolismo , Regulação para Cima
15.
Cancer Biother Radiopharm ; 35(4): 307-312, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32191497

RESUMO

Background: Long noncoding RNA (lncRNA) LUADT1 is a known oncogenic lncRNA in lung cancer. This study aimed to explore the roles of LUADT1 in melanoma. Materials and Methods: Sixty pairs of melanoma and nontumor tissues were obtained from 60 melanoma patients (37 men and 23 women, 38-68 years, 52.1 ± 4.9 years) at the First Affiliated Hospital of Zhejiang University School of Medicine. Gene expression was analyzed by quantitative polymerase chain reaction and western blot. Cell transfections were performed to analyze gene expression. Results: We found that LUADT1 was upregulated in melanoma and high levels of LUADT1 predicted poor survival. RNA interaction prediction showed that LUADT1 can form base pairing with miR-28-5p. In melanoma cells, LUADT1 overexpression mediated the upregulated Ras-related protein Rap-1b (RAP1B). Cell proliferation assay showed that LUADT1 and RAP1B overexpression mediated the increased proliferation rate of melanoma cells. In addition, miR-28-5p overexpression played opposite roles attenuating the effects of LUADT1 overexpression on both RAP1B expression and cancer cell proliferation. Conclusions: LUADT1 in melanoma and may sponge miR-28-5p to upregulate RAP1B, thereby promoting cancer cell proliferation.


Assuntos
Melanoma/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas rap de Ligação ao GTP/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Regulação para Cima
16.
Braz J Med Biol Res ; 53(1): e9144, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939600

RESUMO

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-ß plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-ß type II receptor (t-TGF-ßRII) is unable to continue signal transduction but is still capable of binding to TGF-ß, thereby blocking the TGF-ß signaling pathway. Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes tissue regeneration and wound healing. Theoretically, the combination of HGF and t-TGF-ßRII would be expected to exert a synergistic effect on promoting wound healing and reducing collagen formation. In the present study, lentivirus-mediated transfection of the two genes (t-TGF-ßRII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-ßRII and HGF in NIH-3T3 cells was successfully induced. The expression of both molecules significantly reduced collagen I and III expression, and also inhibited fibroblast proliferation. Furthermore, histological examination and scar quantification revealed less scarring in the experimental wound in a rat model. Moreover, on macroscopic inspection, the experimental wound exhibited less visible scarring compared with the control. Therefore, the present study demonstrated that the combination gene therapy of t-TGF-ßRII and HGF promoted wound healing, with less scarring and more epithelial tissue formation, not only by suppressing the overgrowth of collagen due to its antifibrotic effect, but also by promoting tissue regeneration.


Assuntos
Cicatriz/metabolismo , Colágeno/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Transfecção , Fator de Crescimento Transformador beta2/metabolismo , Animais , Proliferação de Células , Cicatriz/patologia , Camundongos , Modelos Animais , Ratos , Ratos Sprague-Dawley
17.
Braz. j. med. biol. res ; 53(1): e9144, Jan. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1055480

RESUMO

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-β plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-β type II receptor (t-TGF-βRII) is unable to continue signal transduction but is still capable of binding to TGF-β, thereby blocking the TGF-β signaling pathway. Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes tissue regeneration and wound healing. Theoretically, the combination of HGF and t-TGF-βRII would be expected to exert a synergistic effect on promoting wound healing and reducing collagen formation. In the present study, lentivirus-mediated transfection of the two genes (t-TGF-βRII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-βRII and HGF in NIH-3T3 cells was successfully induced. The expression of both molecules significantly reduced collagen I and III expression, and also inhibited fibroblast proliferation. Furthermore, histological examination and scar quantification revealed less scarring in the experimental wound in a rat model. Moreover, on macroscopic inspection, the experimental wound exhibited less visible scarring compared with the control. Therefore, the present study demonstrated that the combination gene therapy of t-TGF-βRII and HGF promoted wound healing, with less scarring and more epithelial tissue formation, not only by suppressing the overgrowth of collagen due to its antifibrotic effect, but also by promoting tissue regeneration.


Assuntos
Animais , Coelhos , Ratos , Transfecção , Colágeno/metabolismo , Cicatriz/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Cicatriz/patologia , Ratos Sprague-Dawley , Modelos Animais , Proliferação de Células
18.
Wound Repair Regen ; 28(3): 326-337, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31868976

RESUMO

Dressings are necessary during the process of wound healing. Since the early 1980s, several types of wound dressings have been produced, but they cannot always take into account some effects include antibacterial effect, wound healing promotion, and other properties. In this study, we would like to develop an effective dressing with the above properties, especially accelerating wound healing effect. A chitosan-calcium alginate dressing (CCAD) was developed by coating mixture of chitosan with high-low molecular weight on calcium alginate dressing (CAD). We investigated the structural characteristics of CCAD with Fourier-transform infrared spectroscopy (FTIR) and electron microscopy. The cytotoxicity and antibacterial property were evaluated in vitro using CCK-8 and inhibition zone method. Moisture retention was tested on the skin of Sprague-Dawley (SD) rats, and wound healing studies were performed on a full-thickness skin wound model in SD rats. CCAD showed good moisturizing and antibacterial properties with no cytotoxicity. CCAD could inhibit inflammation by decreasing IL-6, and it could also promote angiogenesis by increasing VEGF, resulting in better wound healing than CAD. CCAD is a better choice in wound care due to its antibacterial property, biocompatibility, moisture retention, healing promotion, and non-cytotoxicity characteristics.


Assuntos
Alginatos/ultraestrutura , Bandagens , Quitosana/uso terapêutico , Hemostáticos/uso terapêutico , Pele/lesões , Ferida Cirúrgica/terapia , Animais , Modelos Animais de Doenças , Masculino , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Ferida Cirúrgica/patologia , Ferida Cirúrgica/fisiopatologia , Cicatrização
19.
Front Neurol ; 9: 498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29997570

RESUMO

Background: Recent studies have shown that renal disease is associated with magnetic resonance imaging (MRI) markers of cerebral small vessel disease (CSVD), independent of traditional vascular risk factors. Although large artery lesions might be involved in the cerebrorenal association, evidence has been lacking. Methods: A total of 928 participants from a population-based cohort study were included. Kidney injury measurements included urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). CSVD was assessed on MRI by white matter hyperintensity volume (WMHV), lacunes, brain parenchymal fraction (BPF), cerebral microbleeds (CMBs), and perivascular space. Carotid plaques and brachial-ankle pulse wave velocity (baPWV) were used to assess large artery atherosclerosis and stiffness. Multivariable linear and logistic regression and additional interaction models were used for statistical analysis. Results: Individuals with elevated ACR had higher prevalence of lacunes and more WMHV (p = 0.001 and 0.000, respectively), those with decreased eGFR had smaller brain volume, higher prevalence of lacunes and deep CMBs (p = 0.009, p = 0.017) and p = 0.010 respectively). Interaction analysis revealed that carotid plaque and baPWV significantly enhanced the association between eGFR and BPF (p = 0.001 and p = 0.002, respectively), that is, the association of eGFR with BPF was only significant among participants with carotid plaque and higher baPWV. In addition, carotid plaque enhanced the association between ACR and WMHV (p = 0.034) and baPWV enhanced the association between ACR and the presence of lacunes (p = 0.027). Modifying effect of large vessel disease markers on the association between kidney injury measurements and CMBs was not significant. Conclusion: Evaluation of subclinical CVSD in individuals with kidney injury is warranted, especially in those with combined large artery disease.

20.
Mol Neurobiol ; 54(1): 755-767, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26768594

RESUMO

Subarachnoid hemorrhage (SAH) is a threatening and devastating neurological insult with high mortality and morbidity rates. Despite considerable efforts, the underlying pathophysiological mechanisms are still poorly understood. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been implicated in various pathological conditions. We previously showed that RAGE was upregulated and may be involved in pathophysiology of SAH. In the current study, we investigated its potential role in SAH. We found that the upregulation of RAGE after SAH was NF-κB-dependent positive feedback regulation. Further, pharmacological inhibition of RAGE attenuated neuroinflammation, indicating a possible contributive role of RAGE in inflammation-associated brain injury after SAH. Conversely, however, inhibition of RAGE sensitized neurons, exacerbating cell death, which correlated with augmented apoptosis and diminished autophagy, suggesting that activation of RAGE may protect against SAH-induced neuronal injury. Furthermore, we demonstrate that inhibition of RAGE significantly reduced brain edema and improved neurological function at day 1 but not at day 3 post-SAH. Taken together, these results suggest that RAGE exerts dual role after SAH. Our findings also suggest caution should be exercised in setting RAGE-targeted treatment for SAH.


Assuntos
Córtex Cerebral/metabolismo , Neurônios/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/biossíntese , Hemorragia Subaracnóidea/metabolismo , Animais , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/prevenção & controle
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