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1.
Mil Med Res ; 11(1): 22, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622688

RESUMO

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.


Assuntos
Ferroptose , Traumatismo por Reperfusão , Animais , Camundongos , Diclorodifenil Dicloroetileno , Hepatócitos , Interferon-alfa , RNA , RNA Mensageiro
2.
Front Oncol ; 14: 1323650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590649

RESUMO

This case report describes an 80-year-old female patient admitted to the emergency department due to abdominal distension, abdominal pain, and hematemesis persisting for three days. Subsequent postoperative pathological examination confirmed the diagnosis of peritoneal cancer. The occurrence, diagnosis, treatment, and prognosis of primary peritoneal cancer (PPC) are presented in detail. PPC is a type of cancer originating from the primary peritoneal mesothelium organization, causing diffuse malignant tumors in the abdominal and pelvic regions. Due to the lack of specific clinical manifestations for this disease, the importance of early diagnosis and treatment is hereby emphasized. The article also mentions the histological source of this type of cancer and the advantages of preoperative intraperitoneal chemotherapy in improving the efficacy of PPC treatment. Finally, the importance of a comprehensive treatment approach and proficient use of targeted therapy techniques are highlighted to enhance the treatment outcomes of PPC.

3.
Medicine (Baltimore) ; 103(12): e36263, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517996

RESUMO

This study utilized network pharmacology to investigate the effects of Xiaoyaosan (XYS) on the intervention of hyperplasia of mammary glands (HMG) by targeting specific genes and signaling pathways. The active ingredients and targets of XYS, which consisted of 8 traditional Chinese medicines (TCM), were identified using TCMSP. The gene targets associated with HMG were obtained from the GeneCards Database, and the intersection data between the 2 was integrated. Cytoscape 3.8.1 software was used to construct a network diagram illustrating the relationship between compounds, drug active ingredients, target proteins, and the disease. The protein-protein interaction network diagram was generated using STRING, and the core targets were analyzed. A total of 133 active ingredients in XYS and 7662 active ingredient targets were identified. Among them, 6088 targets were related to HMG, and 542 were common targets between the active ingredients and the disease. The protein-protein interaction (PPI) core network contained 15 targets, with 5 key targets playing a crucial role. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses have indicated that XYS has the potential to treat HMG by interfering with the AGE-RAGE signaling pathway in diabetic complications, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Additionally, molecular docking studies have shown excellent binding properties between the drug components and key targets. Thus, this study provides a theoretical foundation for a better understanding of the pharmacological mechanism and clinical application of XYS in the comprehensive treatment of HMG.


Assuntos
Medicamentos de Ervas Chinesas , Glândulas Mamárias Humanas , Humanos , Farmacologia em Rede , Hiperplasia , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
4.
PLoS One ; 19(1): e0296749, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38232103

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic and progressive condition defined by hyperglycemia caused by abnormalities in insulin production, insulin receptor sensitivity, or both. Several studies have revealed that higher body mass index (BMI) is associated with increasing risk of developing diabetes. In this study, we perform a protocol for systematic review to explore metabolite biomarkers that could be used to identify T2DM in obese subjects. METHODS: The protocol of this review was registered in PROSPERO (CRD42023405518). Three databases, EMBASE, PubMed, and Web of Science were selected to collect potential literature from their inceptions to July December 2023. Data for collection will include title, authors, study subjects, publication date, sample size, detection and analytical platforms, participant characteristics, biological samples, confounding factors, methods of statistical analysis, the frequency and directions of changes in potential metabolic biomarkers, and major findings. Pathway analysis of differential metabolites will be performed with MetaboAnalyst 5.0 based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This systematic review will summarize the potential biomarkers and metabolic pathways to provide a new reference for the prevention and treatment of T2DM in obese subjects.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/complicações , Revisões Sistemáticas como Assunto , Obesidade/complicações , Projetos de Pesquisa , Biomarcadores , Literatura de Revisão como Assunto
5.
Nutrients ; 14(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36145208

RESUMO

Binge eating is a characteristic symptom observed in obese individuals that is related to dysfunction of dopaminergic neurons (DNs). Intermittent administration of a high-fat diet (HFD) is reported to induce binge-like eating, but the underlying mechanisms remain unclear. We generated dopaminergic neuron specific IKKß deficient mice (KO) to examine the effects of inflammation in DNs on binge-like eating under inflammatory conditions associated with HFD. After administration of HFD for 4 weeks, mice were fasted for 24 h, and then the consumption of HFD was measured for 2 h. We also evaluated that the mRNA expressions of inflammatory cytokines, glial markers, and dopamine signaling-related genes in the ventral tegmental area (VTA) and striatum. Moreover, insulin was administered intraventricularly to assess downstream signaling. The consumption of HFD was significantly reduced, and the phosphorylation of AKT in the VTA was significantly increased in female KO compared to wild-type (WT) mice. Analyses of mRNA expressions revealed that DNs activity and inflammation in the VTA were significantly decreased in female KO mice. Thus, our data suggest that HFD-induced inflammation with glial cell activation in the VTA affects DNs function and causes abnormal eating behaviors accompanied by insulin resistance in the VTA of female mice.


Assuntos
Transtorno da Compulsão Alimentar , Insulinas , Animais , Transtorno da Compulsão Alimentar/metabolismo , Citocinas/metabolismo , Dieta Hiperlipídica , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Feminino , Quinase I-kappa B/metabolismo , Inflamação/metabolismo , Insulinas/metabolismo , Insulinas/farmacologia , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Área Tegmentar Ventral/metabolismo
6.
Mycology ; 13(3): 212-222, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938082

RESUMO

3,4-Dihydroxy-2,2-dimethyl-chroman derivatives have diverse physiological properties. A polyketone (3S,4S)-3,4-Dihydroxy-6-methoxy-2,2-dimethylchromom (3S,4S-DMD) with antibacterial activity was isolated from the solid culture of rare edible fungus Panus lecomtei. However, the yield of 3S,4S-DMD in solid culture of P. lecomtei is very low and the production period are too long. In this work, efficient accumulation of 3S,4S-DMD in P. lecomtei by submerged fermentation is studied. The key fermentation factors of P. lecomtei for 3S,4S-DMD production were optimised by single-factor experiment successively, and then a Box-Behnken design (BBD) experiment was carried out to further enhance 3S,4S-DMD production. A maximum 3S,4S-DMD yield of 196.3 mg/L was obtained at 25.78 g/L glucose, 1.67 g/L MgSO4 · 7H2O, 40°C and 197 r/min, respectively, which increased by 1.3-fold in comparison with that in the non-optimised fermentation conditions. Furthermore, an enhanced yield of 3S,4S-DMD (261.6 mg/L) was obtained in 5-L agitated fermenter. The 3S,4S-DMD productivity in flask and fermenter reached to 7.26 and 8.07 mg/g per day, respectively, which considerably increased by over 121-fold in comparison with that in the solid fermentation (0.06 mg/g per day). This study presents a potential method for the production of 3S,4S-DMD by submerged fermentation.

7.
Food Funct ; 13(17): 9032-9048, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35943028

RESUMO

Oxidative stress causes chronic inflammation, and mediates various diseases. The discovery of antioxidants from natural sources is important to research. Here we identified a novel antioxidant peptide (GLP4) from Ganoderma lingzhi mycelium and investigated its antioxidant type and potential protective mechanisms. Through free radical scavenging assay, active site shielding validation, superoxide dismutase (SOD) activity assay, and lipid peroxidation assay, we demonstrated that GLP4 was a novel protective agent with both direct and indirect antioxidant activities. GLP4 could directly enter human umbilical vein endothelial cells (HUVECs) as an exogenous substance. Meanwhile, GLP4 promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and activated the Nrf2/antioxidant response element (ARE) signaling pathway, exhibiting antioxidant and anti-apoptotic cytoprotective effects on hydrogen peroxide (H2O2)-induced HUVECs. Pull-down experiments of GLP4 target proteins, bioinformatics analysis and molecular docking further revealed that GLP4 mediated Nrf2 activation through binding to phosphoglycerate mutase 5 (PGAM5). The results suggested that GLP4 is a novel peptide with dual antioxidant activity and has promising potential as a protective agent in preventing oxidative stress-related diseases.


Assuntos
Antioxidantes , Fator 2 Relacionado a NF-E2 , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ganoderma , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/metabolismo , Simulação de Acoplamento Molecular , Micélio/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
8.
Nutrients ; 14(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35276765

RESUMO

d-Allulose, a rare sugar, improves glucose metabolism and has been proposed as a candidate calorie restriction mimetic. This study aimed to investigate the effects of d-allulose on aerobic performance and recovery from exhaustion and compared them with the effects of exercise training. Male C57BL/6J mice were subjected to exercise and allowed to run freely on a wheel. Aerobic performance was evaluated using a treadmill. Glucose metabolism was analyzed by an intraperitoneal glucose tolerance test (ipGTT). Skeletal muscle intracellular signaling was analyzed by Western blotting. Four weeks of daily oral administration of 3% d-allulose increased running distance and shortened recovery time as assessed by an endurance test. d-Allulose administration also increased the maximal aerobic speed (MAS), which was observed following treatment for >3 or 7 days. The improved performance was associated with lower blood lactate levels and increased liver glycogen levels. Although d-allulose did not change the overall glucose levels as determined by ipGTT, it decreased plasma insulin levels, indicating enhanced insulin sensitivity. Finally, d-allulose enhanced the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase and the expression of peroxisome proliferator-activated receptor γ coactivator 1α. Our results indicate that d-allulose administration enhances endurance ability, reduces fatigue, and improves insulin sensitivity similarly to exercise training. d-Allulose administration may be a potential treatment option to alleviate obesity and enhance aerobic exercise performance.


Assuntos
Frutose , Resistência à Insulina , Animais , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Front Nutr ; 9: 1077893, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618689

RESUMO

Herein, we developed a dual fluorescent aptasensor based on mesoporous silica to simultaneously detect sulfadimethoxine (SDM) and oxytetracycline (OTC) in animal-derived foods. We immobilized two types of aptamers modified with FAM and CY5 on the silica surface by base complementary pairing reaction with the cDNA modified with a carboxyl group and finally formed the aptasensor detection platform. Under optimal conditions, the detection range of the aptasensor for SDM and OTC was 3-150 ng/mL (R 2 = 0.9831) and 5-220 ng/mL (R 2 = 0.9884), respectively. The limits of detection for SDM and OTC were 2.2 and 1.23 ng/mL, respectively. The limits of quantification for SDM and OTC were 7.3 and 4.1 ng/mL, respectively. Additionally, the aptasensor was used to analyze spiked samples. The average recovery rates ranged from 91.75 to 114.65% for SDM and 89.66 to 108.94% for OTC, and all coefficients of variation were below 15%. Finally, the performance and practicability of our aptasensor were confirmed by HPLC, demonstrating good consistency. In summary, this study was the first to use the mesoporous silica-mediated fluorescence aptasensor for simultaneous detection of SDM and OTC, offering a new possibility to analyze other antibiotics, biotoxins, and biomolecules.

10.
Otol Neurotol Open ; 2(1): e009, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38515811

RESUMO

Objectives: To describe outcomes after bilateral cochlear implantation (CI) in a patient with a pathologic PTPN11 variant associated with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML). Additionally, to assess the utility of CI in this specific population based on our outcome and previous reports. Study Design: Retrospective case report with literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Patients: A young boy with various multiorgan abnormalities, speech and language delay, and persistent hearing loss who was found to have a heterozygous PTPN11 gene mutation at age 2. Interventions: Bilateral tympanostomy tube placement, diagnostic imaging, and eventual staged bilateral CI. Main Outcome Measures: Objective audiometric testing and developmental milestone attainment. Results: Bilateral CI was successfully completed over a 2-month period. The patient illustrated significant improvement in objective audiologic measurement. However, he continues to sign as his main form of communication without significant speech progression. Conclusions: Early diagnostic and therapeutic intervention in patients with NS/NSML can help improve long-term audiologic and speech development. Given the heterogeneity of NS/NSML, a multidisciplinary approach is needed for optimal outcomes.

11.
Molecules ; 26(20)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34684891

RESUMO

BACKGROUND: d-Allulose is a rare sugar with antiobesity and antidiabetic activities. However, its direct effect on insulin sensitivity and the underlying mechanism involved are unknown. OBJECTIVE: This study aimed to investigate the effect of d-allulose on high-fat diet (HFD)-induced insulin resistance using the hyperinsulinemic-euglycemic (HE)-clamp method and intramuscular signaling analysis. METHODS: Wistar rats were randomly divided into three dietary groups: chow diet, HFD with 5% cellulose (HFC), and HFD with 5% d-allulose (HFA). After four weeks of feeding, the insulin tolerance test (ITT), intraperitoneal glucose tolerance test (IPGTT), and HE-clamp study were performed. The levels of plasma leptin, adiponectin, and tumor necrosis factor (TNF)-α were measured using the enzyme-linked immunosorbent assay. We analyzed the levels of cell signaling pathway components in the skeletal muscle using Western blotting. RESULTS: d-allulose alleviated the increase in HFD-induced body weight and visceral fat and reduced the area under the curve as per ITT and IPGTT. d-Allulose increased the glucose infusion rate in the two-step HE-clamp test. Consistently, the insulin-induced phosphorylation of serine 307 in the insulin receptor substrate-1 and Akt and expression of glucose transporter 4 (Glut-4) in the muscle were higher in the HFA group than HFC group. Furthermore, d-allulose decreased plasma TNF-α concentration and insulin-induced phosphorylation of stress-activated protein kinase/Jun N-terminal kinase in the muscle and inhibited adiponectin secretion in HFD-fed rats. CONCLUSIONS: d-allulose improved HFD-induced insulin resistance in Wistar rats. The reduction of the proinflammatory cytokine production, amelioration of adiponectin secretion, and increase in insulin signaling and Glut-4 expression in the muscle contributed to this effect.


Assuntos
Frutose/farmacologia , Resistência à Insulina/fisiologia , Músculo Esquelético/efeitos dos fármacos , Animais , Citocinas/metabolismo , Dieta Hiperlipídica , Glucose/metabolismo , Teste de Tolerância a Glucose/métodos , Hipoglicemiantes/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Insulina/metabolismo , Masculino , Músculo Esquelético/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
12.
Biotechnol Biofuels ; 14(1): 189, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563244

RESUMO

BACKGROUND: Lignin is a complex aromatic heteropolymer comprising 15-30% dry weight of the lignocellulose. The complex structural characteristic of lignin renders it difficult for value-added utilization. Exploring efficient lignin-degrading microorganisms and investigating their lignin-degradation mechanisms would be beneficial for promoting lignin valorization. In this study, a newly isolated white-rot basidiomycete, Trametes hirsuta X-13, with capacity to utilize alkaline lignin as the sole substrate was investigated. RESULTS: The analysis of the fermentation properties of T. hirsuta X-13 using alkaline lignin as the sole substrate, including the mycelial growth, activities of ligninolytic enzymes and the rates of lignin degradation and decolorization confirmed its great ligninolysis capacity. The maximum lignin degradation rate reached 39.8% after 11 days of T. hirsuta X-13 treatment, which was higher than that of reported fungi under the same condition. Fourier transform infrared spectrometry (FTIR), gas chromatography-mass spectrometry (GC-MS) scanning electron micrographs (SEM), two-dimensional heteronuclear single quantum coherence NMR analysis (2D-HSQC NMR) collaborated with pyrolysis gas chromatography-mass spectrometry (py-GC/MS) analyses proved that lignin structure was severely deconstructed along with amounts of monomer aromatics generated. Furthermore, according to those chemical analysis, in addition to canonical Cα-Cß breakage, the cleavage of lignin interunit linkages of ß-ß might also occur by T. hirsuta X-13. CONCLUSIONS: This study characterized a newly isolated white-rot basidiomycete T. hirsuta X-13 with impressive alkaline lignin degradation ability and provided mechanistic insight into its ligninolysis mechanism, which will be valuable for the development of lignin valorization strategies.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34206942

RESUMO

There is mixed evidence regarding whether video games affect executive function. The inconsistent results in this area may have to do with researchers' conceptualizations of executive function as a unified construct or as a set of independent skills. In the current study, 120 university students were randomly assigned to play a video game or to watch a screen record of the video game. They then completed a series of behavioral tasks to assess the shifting, updating and inhibiting subcomponents of executive function. Scores on these tasks were also used as indicators of a component-general latent variable. Results based on analysis of covariance showed that, as predicted, the inhibition subcomponent, but not the updating or the shifting subcomponent, was significantly enhanced after gaming. The component-general executive function was not enhanced after gaming once the results were controlled for other subcomponents. The results were unrelated to participants' self-reported positive and negative affect. The findings add key evidence to the literature on executive function and potentially contribute to the therapeutic use of video games to maintain executive function in the aged population.


Assuntos
Jogos de Vídeo , Idoso , Função Executiva , Humanos , Inibição Psicológica
14.
Life Sci ; 256: 117884, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502546

RESUMO

AIMS: Endothelial barrier dysfunction is associated with multiple diseases, and barrier repair may be a possible therapeutic target. Yes-associated protein and its pathway have been implicated in organ repair after injury. However, the mechanisms underlying barrier repair and any role YAP plays in the process are unclear. This study aimed to explore the role and mechanism of YAP in the repair of endothelial cell permeability after TNF-α-induced injury. MAIN METHODS: A trans-endothelial electrical resistance assay was performed to investigate changes in endothelial cell permeability. Lentivirus packaging by calcium phosphate transfection was used to construct endothelial cell lines with knocked down or overexpressed YAP. Western blotting, immunofluorescence, CO-IP, and real-time PCR were used to detect related protein and gene expression. KEY FINDINGS: YAP is involved in the repair process of TNF-α-induced endothelial cell permeability injury; its overexpression promotes repair of endothelial cell permeability, and knockdown weakens repair ability. Moreover, YAP may promote repair by down-regulating STAT3 activity, thereby inhibiting VEGF expression. SIGNIFICANCE: Elucidating the role of YAP in endothelial cell permeability repair process after injury might reveal mechanisms of endothelial barrier repair and provide therapeutic targets for treatment of vascular hyper-permeability disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Proteínas de Sinalização YAP
15.
Chin J Nat Med ; 18(4): 268-272, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32402403

RESUMO

Two new meroterpenoid compounds (1 and 2) together with five known meroterpenoid derivatives (3-7) were isolated from solid culture of mushroom Panus lecomtei. The structures of new compounds were confirmed by the analysis of NMR and HR-ESI-MS spectroscopic data. The biosynthetic pathway of 1-7 was postulated. All isolated compounds were evaluated for antibacterial activities against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Bacillus Calmette-Guérin. Compound 3 exhibited weak antibacterial activity against Bacillus Calmette-Guérin with the inhibition rate of 83.6% at 100 µmol·L-1. Other compounds showed no antibacterial activities against all tested pathogens at 100 µmol·L-1.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Extratos Vegetais/química , Polyporales/química , Terpenos/química , China , Estrutura Molecular , Terpenos/isolamento & purificação
16.
Soc Sci Med ; 256: 113062, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32464417

RESUMO

Diabetes is one of the most widespread global epidemics and has become the main component of the global disease burden. Based on data regarding the prevalence of diabetes in 203 countries and territories from 2013 to 2017, we employed the Bayesian space-time model to investigate the spatiotemporal trends in the global diabetes prevalence. The factors influencing the diabetes prevalence were assessed by the Bayesian LASSO regression model. We identified 77 (37.9%) hotspots with a higher diabetes prevalence than the global average, 10 (0.4%) warm spots with global average level and 116 (57.1%) cold spots with lower level than global average. Of the 203 countries and territories, 68 (33.5%), including 31 hotspots, 5 warm spots and 32 cold spots, exhibited an increasing trend. Of these, 60 experienced an annual increase of more than 0.25%, and 8 showed an increasing trend. Three populous countries, namely China, the USA and Mexico, exhibited a high prevalence and an increasing trend simultaneously. Three socioeconomic factors, body mass index (BMI), urbanization rate (UR) and gross domestic product per capita (GDP-PC), and PM2.5 pollution were found to significantly influence the prevalence of diabetes. BMI was the strongest factor; for every 1% increase in BMI, the prevalence of diabetes increased by 2.371% (95% confidence interval (95% CI): 0.957%, 3.890%) in 2013 and by 3.045% (95% CI: 1.803%, 4.397%) in 2015 and 2017. PM2.5 pollution could be a risk factor, and its influencing magnitude gradually increased as well. With an annual PM2.5 concentrations increase of 1.0% in a country, the prevalence of diabetes increased by 0.196% (95% CI: 0.020%, 0.356%). The UR, on the other hand, was found to be inversely associated with the prevalence of diabetes; with each UR increase of 1%, the prevalence of diabetes decreased by 0.006% (95% CI: 0.001%, 0.011%).


Assuntos
Diabetes Mellitus , Saúde Global , Teorema de Bayes , China/epidemiologia , Diabetes Mellitus/epidemiologia , Humanos , México/epidemiologia , Prevalência , Análise Espacial , Fatores de Tempo
17.
Stem Cell Res ; 43: 101730, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32062133

RESUMO

A human induced pluripotent stem cell (hiPSC) line (WMUi001-A) was generated from the aortic tissue of a 47-year-old donor with aortic dissection and normal blood pressure. Integration-free episomal vector-mediated reprogramming was used for the generation of this iPSC line. The established iPSC line was found to express pluripotency markers, exhibit a differentiation potential in vitro, as well as display a normal karyotype. We further identified that this iPSC line contained a mutation in collagen type IV (COL4A2, R131M), which may serve as a useful tool for the disease modeling of aortic dissection.


Assuntos
Dissecção Aórtica/genética , Linhagem Celular/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
18.
Int J Biochem Cell Biol ; 116: 105612, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31546020

RESUMO

BACKGROUND/AIMS: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, plays an important anti-tumor role and is involved in various other biological processes, such as, neuroprotection by prevention of aggregation of misfolded proteins generated because of genetic defects. Surfactant protein A2 mutations (G231V and F198S) have been identified to be associated with pulmonary fibrosis and lung cancer, and these mutations cause protein aggregation, instability as well as secretion deficiency. The present study focused on investigating the inhibitory effects of EGCG on aggregation of mutant SP-A2 and elucidating the potential mechanisms underlying this action. METHODS: Wild-type and mutant SP-A2 were transiently expressed in CHO-K1 cells. The aggregated and soluble proteins were separated into NP-40-insoluble and NP-40-soluble fractions. Protein stability was validated by chymotrypsin limited proteolysis assay. Western blot and RT-PCR were used to determine the protein and mRNA expression level, respectively. RESULTS: Mutant SP-A2 alone or wild-type SP-A2 co-expressed with G231V formed NP-40-insoluble aggregates in CHO-K1 cells. EGCG significantly suppressed this aggregation and alleviated mutant SP-A2 accumulation in the ER. When combined with 4-PBA, EGCG treatment completely blocked mutant SP-A2 aggregate formation. Though secretion of mutant protein was not affected, EGCG facilitated protein instability in both wild-type and mutant protein. Importantly, MG132, a proteasome inhibitor, reversed EGCG-induced aggregate reduction. CONCLUSIONS: EGCG inhibits aggregation of misfolded SP-A2 via induction of protein instability and activation of proteasomal pathway for aggregate degradation.


Assuntos
Catequina/análogos & derivados , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Agregados Proteicos/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Proteína A Associada a Surfactante Pulmonar/química , Animais , Butilaminas/farmacologia , Células CHO , Catequina/farmacologia , Cricetulus , Inibidores de Cisteína Proteinase/farmacologia , Detergentes/farmacologia , Expressão Gênica , Leupeptinas/farmacologia , Mutação , Octoxinol/farmacologia , Estabilidade Proteica , Fibrose Pulmonar/metabolismo , Proteína A Associada a Surfactante Pulmonar/genética , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Solubilidade
19.
Environ Int ; 128: 46-62, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31029979

RESUMO

Air pollution in the form of particulate matter (PM) is becoming one of the greatest current threats to human health on a global scale. This paper firstly presents a Bayesian space-time hierarch piecewise regression model (BSTHPRM) which can self-adaptively detect the transitions of local trends, accounting for spatial correlations. The spatiotemporal trends of the approximately anthropogenic PM2.5 removed natural dust (PM2.5_No Dust) concentrations and the corresponding population's PM2.5_No Dust exposure (PPM2.5E) in the global continent from 1998 to 2016 were investigated by the presented BSTHPRM. The total areas of the high and higher PM2.5_No Dust-polluted regions, whose spatial relative magnitude of PM2.5_NoDust pollution to the global continental overall level was between 1.89 and 14.68, accounted for about 13.4% of the global land area, and the corresponding exposed populations accounted for 56.0% of the global total population. The spatial heterogeneity of the global PM2.5_NoDust pollution increased generally from 1998 to 2016. The areas of hot, warm, and cold spots with increasing trends of PM2.5_NoDust concentration initially contracted and then later expanded. The local trends of the global continental PM2.5_NoDust concentrations and PPM2.5E can be parted into three changing stages, early, medium, and later stages, using the BSTHPRM. The area proportions of the regions experiencing a decreasing trend of PM2.5_NoDust concentrations and PPM2.5E were greater in the medium stage than in the early and later stages. The local trends of PM2.5_NoDust concentration and PPM2.5E in the two higher PM2.5_NoDust polluted areas, northern India and eastern and southern China, increased in the early stage and then decreased in the medium stage. In the later stage (recent years), northern India displayed a stronger increasing trend; nevertheless, the follow-up decreasing trend still occurred in eastern and southern China. In the first two stages, more than half of the areas in Europe experienced a decreasing trend of PM2.5_NoDust concentration and PPM2.5E; later, more than half of areas in Europe exhibited increasing trends in the later stage. North America and South America experienced a similar local trend of PPM2.5E to Europe. The PPM2.5E trend in Africa generally increased during the study period.


Assuntos
Exposição Ambiental/análise , Poluição Ambiental/análise , Material Particulado/análise , Poeira , Monitoramento Ambiental , Humanos
20.
BMC Public Health ; 19(1): 127, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30700286

RESUMO

BACKGROUND: Population ageing is an increasingly severe global issue. And this has been posing challenges for public health policies and medical resource allocation There are various features of population ageing in different regions worldwide. METHODS: All data were obtained from the health data of World Bank Open Data. Quantile linear regression was used to subtly measure the common variation tendency and strength of the global ageing rate and ageing population. The Bayesian space-time hierarchy model (BSTHM) was employed to assess the detailed spatial temporal evolution of ageing rate and ageing population in global 195 countries and regions. RESULTS: Annual growth of the ageing (65 and above) rate occurred on six continents: Europe (0.1532%), Oceania (0.0873%), Asia (0.0834%), South America (0.0723%), North America (0.0673%) and Africa (0.0069%). The coefficient of variation of the global ageing rate increased from 0.54 in 1960 to 0.69 in 2017. The global ageing rate and ageing population increased over this period, correlating positively with their quantiles. Most countries (37/39) in Europe belong to the top level with regard to the ageing rate, including the countries with the greatest degree of ageing-Sweden, Germany, Austria, Belgium and the UK-whose spatial relative risks of ageing are 3.180 (3.113-3.214), 3.071 (3.018-3.122), 2.951 (2.903-3.001), 2.932 (2.880-2.984) and 2.917 (2.869-2.967), respectively. Worldwide, 44 low ageing areas which were distributed mainly in Africa (26 areas) and Asia (15 areas) experienced a decreasing trend of ageing rates. The local trends of ageing population in the 195 areas increased. CONCLUSIONS: The differentiation of global population ageing is becoming increasingly serious. Globally, all 195 areas showed an increasing local ageing trend in absolute terms, although there were 44 low-ageing areas that experienced a decreasing local trend of ageing rate. The statistical results may provide some baseline reference for developing public health policies in various countries or regions, especially in less-developed areas.


Assuntos
Internacionalidade , Dinâmica Populacional/tendências , Idoso , Teorema de Bayes , Humanos , Análise Espaço-Temporal
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