Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 143
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Gastroenterology ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906512

RESUMO

BACKGROUNDS & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1aΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

2.
Anal Bioanal Chem ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363305

RESUMO

Nanozyme technology has gained significant regard and been successfully implemented in various applications including chemical sensing, bio-medicine, and environmental monitoring. Fe-CDs were synthesized and characterized well in this study. As compared to HRP (3.7 mM), the Fe-CDs exhibited a higher affinity towards H2O2 (0.2 mM) using the steady-state kinetic assay and stronger catalytic capability by changing the color of TMB to the blue color of the oxidized state, oxTMB. Additionally, an efficient peroxidase mimic, Fe-CDs/GOx, based on the hybrid cascade system to produce in situ H2O2 for the visual detection of glucose (color change: colorless to blue, and then to green), has been developed in detail, with limits of detection (LODs) for H2O2 and glucose of 0.33 µM and 1.17 µM, respectively. The changes further demonstrate a linear relationship between absorbance and H2O2 concentration, ranging from 10 to 60 µM, and for glucose (1 to 60 µM). To assess the accuracy and detection capability of the Fe-CDs/GOx system, we evaluated a real human serum sample obtained from adult males in a local hospital. In conclusion, Fe-CDs serving as a peroxidase mimic have the potential for various applications in the fields of biomedicine and nanozymes.

3.
BMC Cardiovasc Disord ; 24(1): 345, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977943

RESUMO

BACKGROUND AND AIMS: H-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene. METHODS AND RESULTS: A multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073-1.094), 1.002(1.001-1.004), 1.240(1.050-1.464) and 2.274(1.432-3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004-2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model's results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease. CONCLUSION: The MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease.


Assuntos
Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2) , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Tibet/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Medição de Risco , Adulto , Prevalência , Fenótipo , Hipertensão Essencial/genética , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/epidemiologia , Hipertensão Essencial/fisiopatologia , Pressão Sanguínea/genética , Idoso , Incidência , Polimorfismo de Nucleotídeo Único , Homocisteína/sangue , Hiper-Homocisteinemia/genética , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Hiper-Homocisteinemia/sangue , Hipertensão/genética , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia
4.
Nucleic Acids Res ; 50(12): 6715-6734, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35736138

RESUMO

In Escherichia coli, transcription-translation coupling is mediated by NusG. Although chloroplasts are descendants of endosymbiotic prokaryotes, the mechanism underlying this coupling in chloroplasts remains unclear. Here, we report transcription-translation coupling through AtNusG in chloroplasts. AtNusG is localized in chloroplast nucleoids and is closely associated with the chloroplast PEP complex by interacting with its essential component PAP9. It also comigrates with chloroplast ribosomes and interacts with their two components PRPS5 (uS5c) and PRPS10 (uS10c). These data suggest that the transcription and translation machineries are coupled in chloroplasts. In the atnusg mutant, the accumulation of chloroplast-encoded photosynthetic gene transcripts, such as psbA, psbB, psbC and psbD, was not obviously changed, but that of their proteins was clearly decreased. Chloroplast polysomic analysis indicated that the decrease in these proteins was due to the reduced efficiency of their translation in this mutant, leading to reduced photosynthetic efficiency and enhanced sensitivity to cold stress. These data indicate that AtNusG-mediated coupling between transcription and translation in chloroplasts ensures the rapid establishment of photosynthetic capacity for plant growth and the response to environmental changes. Therefore, our study reveals a conserved mechanism of transcription-translation coupling between chloroplasts and E. coli, which perhaps represents a regulatory mechanism of chloroplast gene expression. This study provides insights into the underlying mechanisms of chloroplast gene expression in higher plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Cloroplastos , Cloroplastos , Arabidopsis/genética , Escherichia coli/genética , Fatores de Alongamento de Peptídeos , Fatores de Transcrição , Proteínas de Cloroplastos/metabolismo , Proteínas de Arabidopsis/metabolismo , Transcrição Gênica , Biossíntese de Proteínas
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 360-366, 2024 Mar 20.
Artigo em Zh | MEDLINE | ID: mdl-38645841

RESUMO

Objective: To investigate the prevalence and influencing factors of isolated diastolic hypertension (IDH) in the Tibetan population in Tibet and to provide some evidence for the prevention and control of hypertension and other related diseases in high-altitude areas. Methods: A multistage stratified whole-group random sampling method was used to enroll participants from Ngari Prefecture, Nagqu City, Shannan City, and Lhasa City, Tibet. A total of 3918 native Tibetans with complete data were enrolled in the survey between June 2020 and August 2023. The participants were aged from 18 to 80. The demographic data, life habits, and chronic disease prevalence of the participants were collected. Fasting venous blood samples were collected to perform the routine blood tests and blood biochemistry tests. The prevalence of IDH in subgroups with different characteristics was analyzed and the influencing factors were analyzed by multivariate logistic regression, accordingly. The predictive value of influencing factors on the prevalence of IDH was analyzed by the receiver operating characteristic (ROC) curve and the findings were compared with those of the previous prediction models for IDH. Results: The prevalence of hypertension in the participants was 33.7% (n=1321), among which, 395 had IDH, accounting for 29.9% of the hypertensive patients. The results of multivariate regression showed that age, heart rate, body mass index, waist circumference, hemoglobin, and low-density lipoprotein cholesterol were associated with risks of developing IDH (P<0.05). The area under the ROC curve (AUC) was 0.71, which indicated improved accuracy for predicting the risks for IDH in comparison with previous predictive models for IDH. Among the influencing factors, BMI showed the best predictive value for IDH risks. Conclusion: The prevalence of IDH is high among Tibetans in Tibet, suggesting the necessity for rational allocation of health resources in accordance. Compared with the previous IDH prediction models, the model proposed in this study is more suited for the Tibetan population. Targeted interventions should be carried out for the high-risk populations, such as young and middle-aged adults and populations suffering from overweight/obesity, central obesity, high-altitude polycythemia, and dyslipidemia, so as to effectively control the occurrence and development of IDH.


Assuntos
Hipertensão , Humanos , Tibet/epidemiologia , Pessoa de Meia-Idade , Prevalência , Hipertensão/epidemiologia , Adulto , Masculino , Feminino , Idoso , Fatores de Risco , Adolescente , Altitude , Adulto Jovem , Idoso de 80 Anos ou mais , Índice de Massa Corporal
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 176-182, 2024 Jan 20.
Artigo em Zh | MEDLINE | ID: mdl-38322533

RESUMO

Objective: To analyze the prevalence of hyperuricemia (HUA) among the Tibetan population in Nagqu City, Tibet and to uncover the relevant influencing factors. Methods: From July 2020 to August 2021, 763 Tibetan natives from Bangor County (specifically Xinji Township and Jiaqiong Township) and Seni District (specificially Sexiong Township), Nagqu City were investigated by multi-stage cluster random sampling method and the prevalence of HUA was studied by retrospective analysis. Chi-square test and multiple logistic regression were used to analyze the influencing factors of HUA prevalence. Results: The overall prevalence of HUA among the Tibetan population in the three townships of Nagqu City was 19.66% (150/763). In particular, the prevalence in men was 35.00%, while that in women was 8.58%, showing significant difference (P<0.05). According to the results of univariate analysis, there were significant differences in the distribution of sex, abnormal liver function, abnormal hemoglobin, hyperlipidemia, high level of low-density lipoprotein, hypertriglyceridemia, hypercholesterolemia, abnormal creatinine, hyperhomocysteinemia, obesity, and hypertension between HUA and non-HUA patients (P<0.05). Multiple logistic regression showed that female sex (odds ratio [OR]=0.195, 95% confidence interval [CI]: 0.120-0.315) was a protective factor for HUA, while abnormal liver function (OR=2.812, 95% CI: 1.685-4.692), abnormal creatinine (OR=7.374, 95% CI: 1.446-37.620), high level of low-density lipoprotein (OR=2.357, 95% CI: 1.011-5.492), and hyperlipidemia (OR=3.056, 95% CI: 1.886-4.951) were independent risk factors. Conclusion: The prevalence of HUA is relatively high in Nagqu city and the prevalence of HUA is much higher in men than that in women. Male sex, abnormal liver function, abnormal creatinine, elevated low-density lipoprotein, and hyperlipidemia may be the risk factors for HUA in the local Tibetan population.


Assuntos
Hiperlipidemias , Hiperuricemia , Humanos , Masculino , Feminino , Hiperuricemia/epidemiologia , Tibet , Estudos Retrospectivos , Creatinina , Ácido Úrico , Fatores de Risco , Lipoproteínas LDL , Prevalência , China/epidemiologia
7.
Anal Chem ; 95(51): 18880-18888, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38088834

RESUMO

Biocompatible fluorescent probes have emerged as essential tools in life sciences for visualizing subcellular structures and detecting specific analytes. Herein, we report the synthesis and characterization of a novel fluorescent probe (TPE-FdU), incorporated with hydrophilic 2'-fluoro-substituted deoxyuridine and hydrophobic ethynyl tetraphenylethene moieties, which possessed typical aggregation-induced emission (AIE) behavior. In comparison to the TPE-FdU (pKa 7.68) treated in neutral conditions, it performed well at pH 4, exhibiting an enhanced 450 nm emission signal of approximately four times stronger. As the pH value was increased to 10, the fluorescence intensity was completely quenched. The TEM images of TPE-FdU in an acidic environment (nanospherical morphology, AIE enhance, pH = 4) and in a basic environment (microrods, fluorescence quenching, pH = 9) revealed that it was a pH-dependent self-assembled probe, which was also illustrated by the interpretation of the NMR spectrum. Furthermore, the TPE-FdU probe exhibited a specific response to trace Hg2+ ions. Interestingly, the quenched fluorescence of the TPE-FdU probe caused by Hg2+ can be recovered by the addition of GSH due to the formation of the Hg-S bond being released away. MTT assay and CLSM images demonstrated that TPE-FdU was nontoxic and selectively visualized in the intracellular mitochondria. These results contributed to the development of advanced fluorescent probes with diverse applications in cell imaging, environment protection, and biomedical research.


Assuntos
Floxuridina , Corantes Fluorescentes , Corantes Fluorescentes/química , Mitocôndrias , Espectrometria de Fluorescência , Concentração de Íons de Hidrogênio
8.
BMC Public Health ; 23(1): 2100, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880645

RESUMO

BACKGROUND: This study aimed to provide a reference for the prevention and treatment of abnormal bone mass in postmenopausal women by analysing the current situation and influencing factors of bone mass abnormalities in Tibet. METHODS: A total of 229 postmenopausal Tibetan women were randomly selected from six counties by a multistage cluster random sampling method. Multiple logistic regression was utilized to analyse the status and influencing factors of bone mass abnormalities in postmenopausal Tibetan women. RESULTS: Among 229 postmenopausal Tibetan women, the prevalence of osteopenia and osteoporosis was 54.6% and 9.6%, respectively. Age {odds ratio (OR) = 0.022 [95% confidence interval (CI) = 0.003 ~ 0.163]}, BMI [OR = 441.902 (20.899,9343.717)], altitude [OR = 18.818 (1.391,254.585)], and creatinine (CREA) levels [OR = 0.895 (0.825 ~ 0.971)] were significantly associated with the risk of osteoporosis. CONCLUSION: Postmenopausal Tibetan women had high rates of abnormal bone mass. Age, BMI, altitude and CREA levels were associated with osteoporosis. It is suggested that relevant departments should take targeted measures to promote health education on the prevention of osteoporosis in the general population and increase the screening of high-risk groups for osteoporosis to improve the bone health of postmenopausal Tibetan women.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Humanos , Feminino , Densidade Óssea , Tibet/epidemiologia , Pós-Menopausa , Promoção da Saúde , Absorciometria de Fóton , Osteoporose/epidemiologia , Osteoporose/diagnóstico , China/epidemiologia , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/complicações , Fatores de Risco
9.
Regul Toxicol Pharmacol ; 139: 105342, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36731760

RESUMO

Fritillaria Cirrhosa bulbus (BFC) is a Chinese herbal medicine. In the present study, subchronic toxicities of the ethanol extract from cultivated Fritillaria Cirrhosa bulbus (ECBFC) were performed by oral daily administration in Sprague-Dawley rats. The subchronic toxicity test of ECBFC was conducted at doses of 0.34, 0.68, and 2.04 g/kg/day for 90 days (equivalent to the highest human clinical recommend dosage of 25, 50, and 150-fold) with a 4-week satellite group. No mortality or significant changes in behaviors, body weight and food consumption were observed during the experimental and recovery periods. According to the data from ematological analysis, biochemistry, organ coefficient and the results of histopathology, the ECBFC have toxicity to the spleen and liver at the highest (2.04 g/kg), medium (0.68 g/kg) dose and nephrotoxicity at the highest dose. Subchronic oral toxicity of ECBFC in SD rats (90 days) with NOAEL was 0.34 g/kg and LOAEL was 0.68 g/kg. In addition, the toxicity is gender neutral and reversible. The NOAEL value (0.34 g/kg) is 25-fold of the highest human clinical recommend dosage thus the ECBFC could be long-term used as Chinese patent medicine or functional food.


Assuntos
Fritillaria , Humanos , Ratos , Animais , Ratos Sprague-Dawley , Etanol/toxicidade , Extratos Vegetais/toxicidade , Testes de Toxicidade Subcrônica , Administração Oral
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(3): 585-590, 2023 May.
Artigo em Zh | MEDLINE | ID: mdl-37248588

RESUMO

Objective: To explore the possible interaction between overweight/obesity and dyslipidemia and to provide some evidence for the interaction of the risk of hypertension with overweight/obesity and dyslipidemia. Methods: By using multi-stage stratified cluster random sampling method, the subjects of the study were randomly selected from Naqu city, Shannan city, and Ali prefecture, Tibet. A total of 4047 Tibetans with complete data were included. Investigators obtained relevant information on the subjects through questionnaire surveys, measured their height, body mass index, and blood pressure, and collected fasting venous blood samples. The multivariate logistic regression model was used to analyze the independent effects of overweight/obesity and dyslipidemia and hypertension. Stratified analysis and an additive interaction model were used to evaluate the effect of two-factor interaction on the risk of hypertension. Results: The overall prevalence of hypertension, overweight/obesity, and dyslipidemia among Tibetans living in Tibet was 29.3%, 46.2%, and 40.9%, respectively. Overweight/obesity (odds ratio [ OR]=2.151) and dyslipidemia ( OR=1.240) were risk factors of hypertension. Evaluation results of the effect of additive interaction showed significant additive interaction of overweight/obesity and dyslipidemia on hypertension ( P=0.028), with the synergy index ( SI) being 1.318. Conclusion: Overweight/obesity and dyslipidemia are risk factors for having hypertension and there is an additive interaction between dyslipidemia and overweight/obesity.


Assuntos
Dislipidemias , Hipertensão , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Tibet/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Hipertensão/epidemiologia , Fatores de Risco , Dislipidemias/epidemiologia , Índice de Massa Corporal , Prevalência , China/epidemiologia
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(5): 985-993, 2023 Sep.
Artigo em Zh | MEDLINE | ID: mdl-37866957

RESUMO

Objective: To examine the differences and commonalities of factors influencing the utilization of health services among urban and rural residents in Tibet and to identify vulnerable populations in the utilization of health services, thereby providing references for the formulation of local health policies and the allocation of health resources. Methods: Using the Tibetan area data from the Sixth National Health Service Survey, we conducted statistical analysis of the health service utilization status of 8 297 residents of agro-pastoral areas and 2 179 residents of urban areas with χ 2 test and logistic regression model. Results: The two-week outpatient visit rates of residents in agro-pastoral areas and that of the urban residents were 65.3% and 57.1%, respectively, and the one-year hospitalization rates were 8.3% and 8.9%, respectively. The influencing factors of two-week outpatient visits for rural and pastoral residents included urban and rural health insurance coverage, Three Guarantees in One coverage, distance to medical facilities, chronic disease status, physical examination, family doctor contract status, employment status, and health status self-assessment. The influencing factors of two-week outpatient visit for urban residents included chronic disease status, urban and rural medical insurance coverage, health status self-assessment, health records, and physical examination. The factors influencing hospitalization for agro-pastoral residents were sex, age, marital status, urban and rural medical insurance coverage, Three Guarantees in One coverage, critical illness insurance, health self-assessment, mobility, health records, physical examination, and chronic disease status. The factors influencing the hospitalization of urban residents were sex, marital status, health status self-assessment, health records, urban employee medical insurance coverage, and chronic disease status. The factors influencing the hospitalization of urban residents were sex, marital status, health status self-assessment, health records, urban employee medical insurance coverage, and chronic disease status. Conclusion: The urban and rural residents in Tibet have relatively poor health and their awareness of seeking early medical help after they fall ill is relatively weak. The health institutions concerned should dedicate more attention to the vulnerable populations who have difficulty accessing health services, focus on the commonly shared influencing factors of health service utilization among urban and rural residents, take into account the differences, rationally allocate health resources, and improve the effective utilization rate of health services among residents in Tibet.


Assuntos
Serviços de Saúde , Medicina Estatal , Humanos , Tibet , Hospitalização , Doença Crônica , População Rural , China , População Urbana
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 357-360, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-36949698

RESUMO

Objective: To analyze the screening value of osteoporosis self-screening tool for Asia (OSTA) and body mass index (BMI) for osteoporosis (OP) in middle-aged and elderly Tibetan population in the Tibetan region. Methods: Data on demographic information, bone mineral density (BMD), and other information of 627 middle-aged and elderly people were collected. Analysis of the correlation between OSTA index, BMI and BMD, and receiver operating characteristic (ROC) curve was performed to evaluate the OP screening effects. Results: OSTA index and BMI were correlated with BMD in both female and male populations ( P<0.05). In both male and female populations, OSTA index screening results for OP yielded higher area under the curve ( AUC) than BMI did, with the AUC for female OSTA index being 0.886 and that for female BMI being 0.785, while that for male OSTA index being 0.957 and that for male BMI being 0.834. When comparing the different age groups, the AUC of OSTA index and BMI of the middle-age group was higher than those of the quasi-elderly group and the elderly group, with the AUC of OSTA index and BMI of the middle-age being 0.939 and 0.858, those of the quasi-elderly group being 0.860 and 0.813, and those of the elderly group being 0.750 and 0.650, respectively. When the optimal cut-off value of diagnosis with OSTA index was -2.20, the sensitivity and specificity were both 100%. When the optimal cut-off value for diagnosis with BMI was 17.512 kg/m2, the sensitivity and specificity were both 100%. Conclusion: OSTA index and BMI have different OP screening effects in different middle-aged and elderly Tibetan populations, and OSTA index shows better effects for OP screening than BMI does.


Assuntos
Osteoporose , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Absorciometria de Fóton/métodos , Índice de Massa Corporal , Densidade Óssea , Programas de Rastreamento/métodos , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Medição de Risco/métodos , Autoavaliação (Psicologia) , Tibet , População do Leste Asiático
13.
Angew Chem Int Ed Engl ; 62(24): e202303500, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37069464

RESUMO

Indoor detection of volatile organic compounds (VOCs) concentration is necessary due to the serious toxicity hazards even at trace level. However, physisorbents usually exhibit weak interactions especially in the presence of trace concentrations of VOCs, thus exhibiting poor responsive signal. Herein, we report a new flexible metal-organic framework (MOF) that exhibits interesting pore-opening behavior after immersing in H2 O. The pore-opening phase shows significant (≈116 folds) and extremely fast (<1 minute) fluorescence enhancement after being exposed to saturated benzene vapor. The limit of detection concentration for benzene vapor can be calculated as 0.133 mg L-1 . Thus this material represents the first MOF to achieve visual detection of trace benzene vapor by the naked eyes. Theoretical calculations and single-crystal structure reveal that the special "bilateral π-π stacking" interactions between the host and guest, which facilitate electron transfer and greatly enhance the intensity of fluorescence.

14.
Med Res Rev ; 42(4): 1607-1660, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35312190

RESUMO

The key proteins involved in transcriptional regulation play convergent roles in cellular homeostasis, and their dysfunction mediates aberrant gene expressions that underline the hallmarks of tumorigenesis. As tumor progression is dependent on such abnormal regulation of transcription, it is important to discover novel chemical entities as antitumor drugs that target key tumor-associated proteins involved in transcriptional regulation. Despite most key proteins (especially transcription factors) involved in transcriptional regulation are historically recognized as undruggable targets, multiple targeting approaches at diverse levels of transcriptional regulation, such as epigenetic intervention, inhibition of DNA-binding of transcriptional factors, and inhibition of the protein-protein interactions (PPIs), have been established in preclinically or clinically studies. In addition, several new approaches have recently been described, such as targeting proteasomal degradation and eliciting synthetic lethality. This review will emphasize on accentuating these developing therapeutic approaches and provide a thorough conspectus of the drug development to target key proteins involved in transcriptional regulation and their impact on future oncotherapy.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinogênese , Regulação da Expressão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo
15.
Bioorg Chem ; 129: 106154, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36137311

RESUMO

Reactive oxygen species (ROS)-responsive prodrugs have received significant attention due to their capacity to target tumors to relieve the side effects caused by chemotherapy. Herein, a series of novel H2O2-activated theranostic prodrugs (CPTSe1-CPTSe7) were developed containing allyl phenyl selenide moieties as H2O2 acceptors. Compared with conventional boronate ester-based prodrug CPT-B, CPTSe1 was more stable in human plasma and showed a more complete release of camptothecin (CPT) in H2O2 inducing experiment. The selectively activated fluorescence signals of CPTSe1 in tumor cells make it useful for real-time monitoring of CPT release and H2O2 detection. Furthermore, excellent selectivity of CPTSe1 was achieved for tumor cells over normal cells. Our results provide a new platform for the development of H2O2-responsive theranostic prodrugs.


Assuntos
Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Medicina de Precisão , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Linhagem Celular Tumoral
16.
Environ Res ; 214(Pt 2): 113865, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35835168

RESUMO

CONTEXT: Recent studies in specific population subgroups (e.g., pregnant women) have suggested PM exposure increases the risk of hyperuricemia. However, no studies have examined this in the general population. Furthermore, the underlying mechanism through which PM impacts hyperuricemia risk is poorly understood. OBJECTIVE: To assess the association between long-term exposure to PM and risk of hyperuricemia and whether this association is mediated by lipid profile. METHODS: We included 5939 participants in Southwest China from the China Multi-Ethnic Cohort (baseline 2018-2019, follow-up 2020-2021). Long-term PM pollutants (PM1, PM2.5, PM10) exposure for each individual was represented by the three-year average PM levels before the baseline survey. Hyperuricemia at follow-up was defined as the serum uric acid above 7.0 mg/dL in men and 6.0 mg/dL in women. Serum lipids were measured at baseline including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). The association of PM with hyperuricemia was accessed through logistic regression. The potential mediation effects of serum lipids were evaluated through causal mediation analyses. RESULTS: A total of 837 participants were newly diagnosed with hyperuricemia. The odds ratios of hyperuricemia associated with an interquartile range (IQR) increase in PM1, PM2.5, and PM10 (IQR: 21.10, 25.78, 30.43 µg m-3) were 1.72 (95% CI: 1.23, 2.39), 2.68 (95% CI: 1.59, 4.49), and 1.81 (95% CI: 1.20, 2.72), respectively. The association between PM2.5, PM1, and PM10 on hyperuricemia was mediated by HDL-C (10%) and LDL-C (3%). CONCLUSION: Higher particulate matter exposure was associated with higher hyperuricemia incidence. The decline in HDL-C and rise in LDL-C partially mediated this association. These findings were conducive to scientific research about the underlying mechanism of PM on hyperuricemia.


Assuntos
Poluentes Atmosféricos , Hiperuricemia , Poluentes Atmosféricos/análise , China/epidemiologia , LDL-Colesterol , Exposição Ambiental , Feminino , Humanos , Hiperuricemia/epidemiologia , Masculino , Material Particulado/análise , Material Particulado/toxicidade , Gravidez , Estudos Prospectivos , Ácido Úrico/análise
17.
J Sep Sci ; 45(14): 2717-2723, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35524724

RESUMO

A method is first established for the separation and determination of fenpropathrin enantiomer residues in apple puree, strawberry puree, and tomato puree considered a supplementary food for infants by supercritical fluid chromatography. After the sample was extracted with acetonitrile and cleaned up by a solid-phase extraction column, then it was separated by a CHIRALPAK AD-3 chiral column with gradient elution at a flow rate of 1.5 mL/min using methanol and supercritical carbon dioxide as the mobile phase, detected by ultraviolet detector at 230 nm wavelength and quantified with the external standard method. The limits of quantification of the two fenpropathrin enantiomers were both 0.2 mg/kg, the linear ranges were 1.0-20.0 mg/L with linear correlation coefficients greater than 0.9992, the recoveries in the spiked samples at 0.2, 0.4 and 2.0 mg/kg were from 80.6 to 105%, and the relative standard deviation reached 2.6-7.7%. This method has the advantages of convenient operation, good resolution, and environmental protection, which can satisfy the requirement of determination for fenpropathrin enantiomer residues in fruit and vegetable puree as supplementary food for infants.


Assuntos
Cromatografia com Fluido Supercrítico , Praguicidas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia com Fluido Supercrítico/métodos , Frutas/química , Humanos , Praguicidas/análise , Piretrinas , Estereoisomerismo , Verduras/química
18.
J Cell Physiol ; 236(4): 2572-2591, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32853412

RESUMO

Changes in immune responses to hepatocellular carcinoma (HCC) are closely related to the occurrence, development, and prognosis of this disease. Exploring the role of immune-related genes (IRGs) in HCC would provide insights into the mechanisms regulating this disease. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) provide a platform for such research, owing to a large number of HCC samples available for comprehensive and systematic immunogenomics analyses. We analyzed the IRGs expression profile and clinical information of patients with HCC based on the TCGA and ICGC database. Potential molecular mechanisms and properties of the screened IRGs were analyzed across multiple databases. And we analyzed the correlation between IRGs, single-nucleotide polymorphisms, and copy number variation. A novel prognostic index, based on IRGs, was developed using the LASSO Cox regression algorithm, followed by univariate and multivariate Cox regression analyses to analyze the prognostic index. Information in the ICGC database was used to verify the reliability of the prognostic index. A total of 54 differentially expressed IRGs were found to be significantly associated with HCC prognosis, and there is a significant correlation between their expression level and copy number variation. Functional enrichment analyses indicated that the genes play active roles in tumor and immune-related signaling pathways. In addition, five potential biomarkers namely IRG, MAPK3, HSP90AA1, HSP90AB1, HSPA4, and CDK4, were identified. Finally, a novel prognostic index, based on IRGs (PSMD14, FABP6, ISG20L2, HGF, BIRC5, IL17D, and STC2), was found useful as an independent prognostic factor, not only for prognosis but also to reflect levels of infiltration in a variety of immune cells. Our team conducted a genomics study of IRGs in HCC and screened several clinically significant IRGs, and our model provides an effective approach for stratification and characterization of patients using IRG-based immunolabeling tools to monitor the prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Fenômenos Imunogenéticos , Neoplasias Hepáticas/genética , Transcriptoma , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Feminino , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Prognóstico , Microambiente Tumoral
19.
Small ; 17(51): e2105439, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34802181

RESUMO

DNAzyme-nanomaterial bioconjugates are a popular hybrid and have received major attention for diverse biomedical applications, such as bioimaging, biosensor development, cancer therapy, and drug delivery. Therefore, significant efforts are made to develop different strategies for the preparation of inorganic and organic nanoparticles (NPs) with specific morphologies and properties. DNAzymes functionalized with metal-organic frameworks (MOFs), gold nanoparticles (AuNPs), graphene oxide (GO), and molybdenum disulfide (MoS2 ) are introduced and summarized in detail in this review. Moreover, the focus is on representative examples of applications of DNAzyme-nanomaterials over recent years, especially in bioimaging, biosensing, phototherapy, and stimulation response delivery in living systems, with their several advantages and drawbacks. Finally, the perspective regarding the future directions of research addressing these challenges is also discussed and highlighted.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , Nanoestruturas , Ouro
20.
Plant Physiol ; 182(1): 408-423, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31685645

RESUMO

Members of the mitochondrial transcription terminator factor (mTERF) family, originally identified in vertebrate mitochondria, are involved in the termination of organellular transcription. In plants, mTERF proteins are mainly localized in chloroplasts and mitochondria. In Arabidopsis (Arabidopsis thaliana), mTERF8/pTAC15 was identified in the plastid-encoded RNA polymerase (PEP) complex, the major RNA polymerase of chloroplasts. In this work, we demonstrate that mTERF8 is associated with the PEP complex. An mTERF8 knockout line displayed a wild-type-like phenotype under standard growth conditions, but showed impaired efficiency of photosystem II electron flow. Transcription of most chloroplast genes was not substantially affected in the mterf8 mutant; however, the level of the psbJ transcript from the psbEFLJ polycistron was increased. RNA blot analysis showed that a larger transcript accumulates in mterf8 than in the wild type. Thus, abnormal transcription and/or RNA processing occur for the psbEFLJ polycistron. Circular reverse transcription PCR and sequence analysis showed that the psbJ transcript terminates 95 nucleotides downstream of the translation stop codon in the wild type, whereas its termination is aberrant in mterf8 Both electrophoresis mobility shift assays and chloroplast chromatin immunoprecipitation analysis showed that mTERF8 specifically binds to the 3' terminal region of psbJ Transcription analysis using the in vitro T7 RNA polymerase system showed that mTERF8 terminates psbJ transcription. Together, these results suggest that mTERF8 is specifically involved in the transcription termination of the chloroplast gene psbJ.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Transcrição Gênica/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Cloroplastos/genética , Imunoprecipitação da Cromatina , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Ligação Proteica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA