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1.
Front Endocrinol (Lausanne) ; 15: 1294638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590820

RESUMO

As the incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly and its consequences are severe, effective intervention and prevention, including sleep-related interventions, are urgently needed. As a component of sleep architecture, naps, alone or in combination with nocturnal sleep, may influence the onset and progression of T2DM. Overall, napping is associated with an increased risk of T2DM in women, especially in postmenopausal White women. Our study showed that napping >30 minutes (min) increased the risk of T2DM by 8-21%. In addition, non-optimal nighttime sleep increases T2DM risk, and this effect combines with the effect of napping. For nondiabetic patients, napping >30 min could increase the risks of high HbA1c levels and impaired fasting glucose (IFG), which would increase the risk of developing T2DM later on. For diabetic patients, prolonged napping may further impair glycemic control and increase the risk of developing diabetic complications (e.g., diabetic nephropathy) in the distant future. The following three mechanisms are suggested as interpretations for the association between napping and T2DM. First, napping >30 min increases the levels of important inflammatory factors, including interleukin 6 and C-reactive protein, elevating the risks of inflammation, associated adiposity and T2DM. Second, the interaction between postmenopausal hormonal changes and napping further increases insulin resistance. Third, prolonged napping may also affect melatonin secretion by interfering with nighttime sleep, leading to circadian rhythm disruption and further increasing the risk of T2DM. This review summarizes the existing evidence on the effect of napping on T2DM and provides detailed information for future T2DM intervention and prevention strategies that address napping.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Feminino , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Sono , Ritmo Circadiano , Inflamação
2.
J Glob Health ; 14: 04069, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38515427

RESUMO

Background: China's fertility policy has dramatically changed in the past decade with the successive promulgation of the partial two-child policy, universal two-child policy and three-child policy. The trajectories of maternal and neonatal health accompanied the changes in fertility policy are unknown. Methods: We obtained data of 280 203 deliveries with six common pregnancy complications and thirteen perinatal outcomes between 2010 and 2021 in eastern China. The average annual percent change (AAPC) was calculated to evaluated the temporal trajectories of obstetric characteristics and adverse outcomes during this period. Then, the autoregressive integrated moving average (ARIMA) models were constructed to project future trend of obstetric characteristics and outcomes until 2027. Results: The proportion of advanced maternal age (AMA), assisted reproduction technology (ART) treatment, gestational diabetes mellitus (GDM), anaemia, thrombocytopenia, thyroid dysfunction, oligohydramnios, placental abruption, small for gestational age (SGA) infants, and congenital malformation significantly increased from 2010 to 2021. However, the placenta previa, large for gestational age (LGA) infants and stillbirth significantly decreased during the same period. The AMA and ART treatment were identified as independent risk factors for the uptrends of pregnancy complications and adverse perinatal outcomes. The overall caesarean section rate remained above 40%. Importantly, among multiparas, a previous caesarean section was found to be associated with a significantly reduced risk of hypertensive disorders of pregnancy (HDP), premature rupture of membranes (PROM), placenta previa, placental abruption, perinatal asphyxia, LGA infants, stillbirths, and preterm births. In addition, the ARIMA time series models predicted increasing trends in the ART treatment, GDM, anaemia, thrombocytopenia, postpartum haemorrhage, congenital malformation, and caesarean section until 2027. Conversely, a decreasing trend was predicted for HDP, PROM, and placental abruption premature, LGA infants, SGA infants, perinatal asphyxia, and stillbirth. Conclusions: Maternal and neonatal adverse outcomes became more prevalent from 2010 to 2021 in China. Maternal age and ART treatment were independent risk factors for adverse obstetric outcomes. The findings offered comprehensive trajectories for monitoring pregnancy complications and perinatal outcomes in China, and provided robust intervention targets in obstetric safety. The development of early prediction models and the implementation of prevention efforts for adverse obstetric events are necessary to enhance obstetric safety.


Assuntos
Descolamento Prematuro da Placenta , Anemia , Placenta Prévia , Complicações na Gravidez , Nascimento Prematuro , Trombocitopenia , Feminino , Humanos , Recém-Nascido , Gravidez , Asfixia , Cesárea , Estudos Transversais , Saúde do Lactente , Placenta , Placenta Prévia/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Natimorto
3.
Med Educ Online ; 28(1): 2272387, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37883485

RESUMO

BACKGROUND: Virtual simulation experiments have been rapidly applied to medical education curricula in recent years. China constructed a national virtual simulation experimental teaching center (iLAB-X), and this platform covered almost all of the virtual simulation experiment curricula of domestic colleges or universities. We aimed to comprehensively assess the characteristics and usages of virtual simulation experiments in medical education based on iLAB-X. METHODS: A total of 480 virtual simulation experiment courses had been constructed on iLAB-X (https://www.ilab-x.com/) by December 20, 2022, and the curriculum level, type and design were all searched in this platform. We also conducted an evaluation of curriculum usage and online tests, including the page view, frequency of participation, number of participants, duration of experimental learning and passing rate of the experimental test. RESULTS: The national and provincial high-quality virtual simulation experiment curricula accounted for 33.5% (161/480) and 35.8% (172/480), respectively. The curricula were mainly set as basic practice experiments (46.5%) and synthetic designing experiments (48.8%). Significantly, forensic medicine (100%), public health and preventive medicine (83%) and basic medical sciences (66%) focused on synthetic design experiments. In terms of usage experiments, the average duration of experimental learning was 25 minutes per course, and the average number of participants was just 1257. The average passing (score ≥60) rate of online tests was 80.6%, but the average rate of score ≥ 85 was only 58.5%. In particular, the average page views, the number of participants, the duration of learning and the test passing rate of clinical medicine were relatively low. CONCLUSIONS: The curriculum design features, construction level and utilization rate varied in different medical majors. Virtual simulation experiments are particularly underutilized in clinical medicine. There is a long way for virtual simulation experiments to go to become a supplement or alternative for traditional medical education in the future.


Assuntos
Educação Médica , Medicina , Humanos , Currículo , Aprendizagem , China
4.
Genomics ; 115(5): 110681, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37453476

RESUMO

This study conducted a high-throughput sequencing analysis of the T- and B- repertoires in the newly diagnosed GDM patients and evaluated the association between abnormal adaptive immunity and GDM. The unique TCR CDR3 clonotypes were mildly decreased in GDM patients, and the similarity of TCR V-J distributions was higher in the GDM group. Moreover, the usages of the V gene and V-J pair and the frequency distributions of some CDR3 amino acids (AAs) both in BCR and TCR were significantly different between groups. Moreover, the cytokines including IL-4, IL-6, IFN-γ and IL-17A were synchronously elevated in the GDM cases. Our findings provide a comprehensive view of BCR and TCR repertoires at newly diagnosed GDM patients, revealing the mild reduction in unique TCRB CDR3 sequences and slight alteration of the V gene, V-J combination and CDR3 (AA) usages of BCR and TCR. This work provides deep insight into the mechanism of maternal adaptive immunity in GDM and provides novel diagnostic biomarkers and potential immunotherapy targets for GDM.

5.
BMC Med Educ ; 23(1): 323, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37158861

RESUMO

BACKGROUND: Massive open online courses (MOOCs) have become innovative open-learning approach in medical education. This study aimed to evaluate the dynamic changes in the construction and application of medical MOOCs before and after the coronavirus disease 2019 (COVID-19) pandemic in China. METHODS: The dynamic changes of usages about medical MOOCs before and after 2020 were mainly searched on the Smart Education of China Higher Education platform, and the detailed learning profiles and outcome indicators were further analyzed using 40 national first-class medical MOOCs from 'zhihuishu' platform. RESULTS: A total of 2,405 medical MOOCs were exported from the Smart Education of China Higher Education platform, of which 1,313 (54.6%) were launched since 2020. The total and average numbers of participants of 141 national first-class medical MOOCs peaked during the initial spread of COVID-19 in 2020. We further analyzed the dynamic usage of MOOCs from 2018 to 2022 based on 40 national first-class medical MOOCs launched on the 'Zhihuishu' platform. The findings revealed that the number of registered learners (3,240 versus 2,654), questions and answers (27,005 versus 5,116) and students taking the final examination (2,782 versus 1,995) per semester were significantly higher since 2020 compared to these before 2020. Especially, the number of registered learners, registered schools, questions and answers, and students participating in online discussion, taking the unit quiz, taking final examinations and passing final examinations all peaked in the 2020 spring-summer semester. Pearson's correlation analysis found that the number of questions and answers and the number of learners who participated in online discussion were both positively correlated with the number of students who passed the final examination, and the correlation was especially strong since 2020. Moreover, the number of publications on medical MOOC research has soared since 2020 and has maintained a continuous upward trend. CONCLUSIONS: High-quality medical MOOCs have been launched rapidly since the COVID-19 pandemic in China. The number of participants and online interactions of medical MOOCs peaked during the initial spread of COVID-19 in 2020. MOOCs are reliable and valid digital sources that facilitate medical higher education and play irreplaceable roles in emergency management.


Assuntos
COVID-19 , Educação a Distância , Humanos , Pandemias , COVID-19/epidemiologia , Escolaridade , China/epidemiologia
6.
Nutrients ; 15(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36986139

RESUMO

Night-shift work and sleep disorders are associated with type 2 diabetes (T2DM), and circadian rhythm disruption is intrinsically involved. Studies have identified several signaling pathways that separately link two melatonin receptors (MT1 and MT2) to insulin secretion and T2DM occurrence, but a comprehensive explanation of the molecular mechanism to elucidate the association between these receptors to T2DM, reasonably and precisely, has been lacking. This review thoroughly explicates the signaling system, which consists of four important pathways, linking melatonin receptors MT1 or MT2 to insulin secretion. Then, the association of the circadian rhythm with MTNR1B transcription is extensively expounded. Finally, a concrete molecular and evolutionary mechanism underlying the macroscopic association between the circadian rhythm and T2DM is established. This review provides new insights into the pathology, treatment, and prevention of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Melatonina , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Receptor MT2 de Melatonina/genética , Receptor MT2 de Melatonina/metabolismo , Melatonina/metabolismo , Ritmo Circadiano , Secreção de Insulina
7.
Ecotoxicol Environ Saf ; 255: 114802, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36934545

RESUMO

OBJECTIVE: We aimed to evaluate the relationship between the composition of particulate matter (PM) and gestational diabetes mellitus (GDM) by a comprehensively review of epidemiological studies. METHODS: We systematically identified cohort studies related to air pollution and GDM risk before February 8, 2023 from six databases (PubMed, Embase, Web of Science Core Collection, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and Chongqing VIP Chinese Science and Technology Periodical databases). We calculated the relative risk (RR) and its 95% confidence intervals (CIs) to assess the overall effect by using a random effects model. RESULTS: This meta-analysis of 31 eligible cohort studies showed that exposure to PM2.5, PM10, SO2, and NO2 was associated with a significantly increased risk of GDM, especially in preconception and first trimester. Analysis of the components of PM2.5 found that the risk of GDM was strongly linked to black carbon (BC) and nitrates (NO3-). Specifically, BC exposure in the second trimester and NO3- exposure in the first trimester elevated the risk of GDM, with the RR of 1.128 (1.032-1.231) and 1.128 (1.032-1.231), respectively. The stratified analysis showed stronger correlations of GDM risk with higher levels of pollutants in Asia, except for PM2.5 and BC, which suggested that the specific composition of particulate pollutants had a greater effect on the exposure-outcome association than the concentration. CONCLUSIONS: Our study found that ambient air pollutant is a critical factor for GDM and further studies on specific particulate matter components should be considered in the future.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/induzido quimicamente , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Material Particulado/toxicidade , Material Particulado/análise , Estudos de Coortes , Exposição Ambiental/análise
8.
Ann Med ; 55(1): 1262-1286, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36974476

RESUMO

Disturbed circadian rhythms have been a risk factor for type 2 diabetes mellitus (T2DM). Melatonin is the major chronobiotic hormone regulating both circadian rhythm and glucose homeostasis. The rs10830963 (G allele) of the melatonin receptor 1B (MTNR1B) gene has the strongest genetic associations with T2DM according to several genome-wide association studies. The MTNR1B rs10830963 G allele is also associated with disturbed circadian phenotypes and altered melatonin secretion, both factors that can elevate the risk of diabetes. Furthermore, evolutionary studies implied the presence of selection pressure and ethnic diversity in MTNR1B, which was consistent with the "thrifty gene" hypothesis in T2DM. The rs10830963 G risk allele is associated with delayed melatonin secretion onset in dim-light and prolonged duration of peak melatonin. This delayed melatonin secretion may help human ancestors adapt to famine or food shortages during long nights and early mornings and avoid nocturnal hypoglycemia but confers susceptibility to T2DM due to adequate energy intake in modern society. We provide new insight into the role of MTNR1B variants in T2DM via disturbed circadian rhythms from the perspective of the "thrifty gene" hypothesis; these data indicate a novel target for the prevention and treatment of susceptible populations with the thrifty genotype.


Assuntos
Ritmo Circadiano , Diabetes Mellitus Tipo 2 , Melatonina , Receptor MT2 de Melatonina , Humanos , Glicemia/genética , Ritmo Circadiano/genética , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Receptor MT2 de Melatonina/genética
9.
Front Endocrinol (Lausanne) ; 13: 960877, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060951

RESUMO

Background: After the universal two-child policy has been fully implemented, challenges regarding pregnancy complications seemed to be more severe in China. This study aimed to evaluate the prevalence of gestational diabetes mellitus (GDM) and the main risk factors for GDM before and after the implementation of the universal two-child policy in China. Methods: A retrospective study was performed with 128,270 pregnant women who delivered at Ningbo Women & Children's Hospital from January 2010 to December 2020. Univariate and multivariate logistic regression analysis was applied to estimate the risk factors associated with GDM prevalence. Segmented regression analyses of interrupted time series (ITS) were conducted to assess the effect of the universal two-child policy on the trends of GDM. Results: The prevalence of GDM increased remarkably from 4% in 2010 to 21% in 2020. ITS analysis presented that the prevalence of GDM increased by 0.190% (ß1) per month from 2010 to 2016 (P<0.05), and by 0.044% (ß1+ß3) per month after the implementation of the universal two-child policy; the rate of elevation of GDM slowed down significantly (ß3=-0.146, P=0.004). Advanced maternal age (>30 years), multigravidity, multiparity, multiple gestation and gestational hypertension were significantly associated with GDM. Advanced age remained an independent risk factor for GDM even after cross stratification with gravidity and parity. The proportion of women with advanced maternal age (>30 years) increased by 0.161% per month before the implementation of the universal two-child policy and increased by 5.25% during the policy took effect month, and gradually increased by 0.124% (ß1+ß3) per month after then. Conclusions: The prevalence of GDM has sharply increased in the past decade. The growth rate of GDM slowed down after the implementation of the universal two-child policy in China, but the rate would maintain at a high plateau. The rise in the proportion of older pregnant women could increase the GDM rate. We recommend having children at a relatively optimal reproductive age when encouraging childbearing.


Assuntos
Diabetes Gestacional , Adulto , China/epidemiologia , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Políticas , Gravidez , Prevalência , Estudos Retrospectivos
10.
Diab Vasc Dis Res ; 19(4): 14791641221122918, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35989592

RESUMO

OBJECTIVES: We aimed to explore the shared and specific signalling pathways involved in diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN). METHODS: Differentially expressed mRNAs and lncRNAs were identified by high-throughput sequencing. Subsequently, functional enrichment analysis, protein-protein interaction (PPI) analysis and lncRNAs-mRNAs networks were conducted to determine the pathogenic mechanisms underlying DR, DPN and DN. RESULTS: Twenty-six biological pathways were shared among DR, DPN and DN groups compared to the type 2 diabetes mellitus (T2DM) group without complications, and most of the shared pathways and core proteins were involved in immune and inflammatory responses of microvascular damage. Cytokine‒cytokine receptor interactions and chemokine signalling pathway were the most significant and specific pathways for DR, and the lncRNA‒mRNA regulatory networks affected DR by targeting these pathways. Sphingolipid metabolism and neuroactive ligand-receptor pathways were found to be specific for the pathogenesis of DPN. Moreover, multiple amino acid metabolic pathways were involved in the occurrence and progression of DN. CONCLUSIONS: Diabetic retinopathy, DPN and DN exhibited commonality and heterogeneity simultaneously. The shared pathologic mechanisms underlying these diabetic complications are involved in diabetic microvascular damage via immune and inflammatory pathways. Our findings predict several biomarkers and therapeutic targets for these diabetic complications.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Neuropatias Diabéticas , Retinopatia Diabética , RNA Longo não Codificante , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/genética , Retinopatia Diabética/patologia , Sequenciamento de Nucleotídeos em Larga Escala , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
11.
Basic Clin Pharmacol Toxicol ; 129(3): 196-209, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34117726

RESUMO

Previous studies have confirmed that a dynamic change in circadian rhythm will affect platelet activity, resulting in clopidogrel resistance (CR). We attempted to evaluate whether polymorphisms of related circadian rhythm genes are involved in CR in stable coronary artery disease (SCAD) patients. A sum of 204 SCAD patients met our requirements and were recruited, and 96 patients were considered to have CR. After clinical data collection and platelet function evaluation, genomic DNA was isolated from human peripheral blood, and 23 tagSNPs from related circadian rhythm genes were genotyped by GenomeLab SNPstream Genotyping System. After RNA isolation, relative expression of related gene mRNAs (CLOCK, CRY1, CACNA1C and PRKCG) was measured by real-time PCR. The results showed that polymorphisms in CRY1, CACNA1C and PRKCG changed the response to clopidogrel. And then, the rs1801260 polymorphism might lead to higher mRNA expression in CLOCK and potentially induce the occurrence of CR. Additionally, the TC genotype of rs3745406 might lower mRNA expression of PRKCG, resulting in CR. These findings support the hypothesized role of circadian rhythm genes in CR and indicate probable biomarkers for CR susceptibility, providing new insight into individualized medicine for coronary heart disease.


Assuntos
Ritmo Circadiano/genética , Clopidogrel/farmacologia , Doença da Artéria Coronariana/genética , Resistência a Medicamentos/genética , Inibidores da Agregação Plaquetária/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas CLOCK/metabolismo , Canais de Cálcio Tipo L/metabolismo , Estudos de Coortes , Doença da Artéria Coronariana/tratamento farmacológico , Criptocromos/metabolismo , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Proteína Quinase C/metabolismo
13.
Front Endocrinol (Lausanne) ; 12: 774608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35046894

RESUMO

Objective: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and its pathogenesis is still unclear. Studies have shown that circular RNAs (circRNAs) can regulate blood glucose levels by targeting mRNAs, but the role of circRNAs in GDM is still unknown. Therefore, a joint microarray analysis of circRNAs and their target mRNAs in GDM patients and healthy pregnant women was carried out. Methods: In this study, microarray analyses of mRNA and circRNA in 6 GDM patients and 6 healthy controls were conducted to identify the differentially expressed mRNA and circRNA in GDM patients, and some of the discovered mRNAs and circRNAs were further validated in additional 56 samples by quantitative realtime PCR (qRT-PCR) and droplet digital PCR (ddPCR). Results: Gene ontology and pathway analyses showed that the differentially expressed genes were significantly enriched in T cell immune-related pathways. Cross matching of the differentially expressed mRNAs and circRNAs in the top 10 KEGG pathways identified 4 genes (CBLB, ITPR3, NFKBIA, and ICAM1) and 4 corresponding circRNAs (circ-CBLB, circ-ITPR3, circ-NFKBIA, and circ-ICAM1), and these candidates were subsequently verified in larger samples. These differentially expressed circRNAs and their linear transcript mRNAs were all related to the T cell receptor signaling pathway, and PCR results confirmed the initial microarray results. Moreover, circRNA/miRNA/mRNA interactions and circRNA-binding proteins were predicted, and circ-CBLB, circ-ITPR3, and circ-ICAM1 may serve as GDM-related miRNA sponges and regulate the expression of CBLB, ITPR3, NFKBIA, and ICAM1 in cellular immune pathways. Conclusion: Upregulation of T cell receptor signaling pathway components may represent the major pathological mechanism underlying GDM, thus providing a potential approach for the prevention and treatment of GDM.


Assuntos
Diabetes Gestacional/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Feminino , Ontologia Genética , Humanos , Análise em Microsséries , Gravidez , RNA Circular/metabolismo , RNA Mensageiro/metabolismo , Regulação para Cima
15.
Genomics Proteomics Bioinformatics ; 18(5): 489-500, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822870

RESUMO

Solar energy, which is essential for the origin and evolution of all life forms on Earth, can be objectively recorded through attributes such as climatic ambient temperature (CAT), ultraviolet radiation (UVR), and sunlight duration (SD). These attributes have specific geographical variations and may cause different adaptation traits. However, the adaptation profile of each attribute and the selective role of solar energy as a whole during human evolution remain elusive. Here, we performed a genome-wide adaptation study with respect to CAT, UVR, and SD using the Human Genome Diversity Project-Centre Etude Polymorphism Humain (HGDP-CEPH) panel data. We singled out CAT as the most important driving force with the highest number of adaptive loci (6 SNPs at the genome-wide 1 × 10-7 level; 401 at the suggestive 1 × 10-5 level). Five of the six genome-wide significant adaptation SNPs were successfully replicated in an independent Chinese population (N = 1395). The corresponding 316 CAT adaptation genes were mostly involved in development and immunity. In addition, 265 (84%) genes were related to at least one genome-wide association study (GWAS)-mapped human trait, being significantly enriched in anthropometric loci such as those associated with body mass index (χ2; P < 0.005), immunity, metabolic syndrome, and cancer (χ2; P < 0.05). For these adaptive SNPs, balancing selection was evident in Euro-Asians, whereas obvious positive and/or purifying selection was observed in Africans. Taken together, our study indicates that CAT is the most important attribute of solar energy that has driven genetic adaptation in development and immunity among global human populations. It also supports the non-neutral hypothesis for the origin of disease-predisposition alleles in common diseases.


Assuntos
Estudo de Associação Genômica Ampla , Desenvolvimento Humano , Imunidade , Temperatura , Alelos , Humanos , Polimorfismo de Nucleotídeo Único , Luz Solar , Raios Ultravioleta
16.
IUBMB Life ; 72(3): 384-400, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31675148

RESUMO

microRNAs (miRNAs) can be used as biomarkers for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI. Exosomes were isolated via ultracentrifugation after serum samples were collected. The exosomes were then identified by transmission electron microscopy, western blotting, and nanoparticle tracking analysis. The differential expression of miRNAs in exosomes from six AMI and six matching SCAD patients was screened using the Agilent Human miRNA Microarray Kit. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Further validation was conducted through quantitative real-time polymerase chain reaction with 60 exosome samples. The expression of 13 miRNAs was significantly downregulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling. Validation of the expression of candidate miRNAs indicated that exosomal miR-1915-3p, miR-4,507, and miR-3,656 were significantly less expressed in AMI samples than in SCAD samples, and area under the receiver-operating-characteristic curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miR-1915-3p (AUC: 0.772); miR-4,507 (AUC: 0.684); and miR-3,656 (AUC: 0.771)], suggesting that these serum exosomal miRNAs might be predictive for AMI at an early stage. Hence, exosomal miRNAs might play an important role in the pathophysiology of AMI and could serve as diagnostic biomarkers.


Assuntos
Biomarcadores/sangue , Exossomos/genética , MicroRNAs/genética , Infarto do Miocárdio/genética , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/fisiopatologia , Exossomos/metabolismo , Feminino , Expressão Gênica , Ontologia Genética , Humanos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos , Curva ROC , Reprodutibilidade dos Testes
17.
Front Genet ; 11: 583215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33519892

RESUMO

Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared the whole genomic methylation patterns of blood samples from patients with CR (n = 6) and non-CR (n = 6) with the Human Methylation 850K BeadChip assay. We explored differentially methylated CpG sites, genes, and pathways using bioinformatics profiling. The CR and control groups showed significantly different DNA methylation at 7,098 sites, with 979 sites showing hypermethylation and 6,119 sites showing hypomethylation. The pyrosequencing method was used to validate four differentially methylated CpG loci (cg23371584, cg15971518, cg04481923, cg22507406), confirming that DNA methylation was associated with the risk of CR (30 CR vs. 30 non-CR). The relative mRNA expression of the four genes (BTG2, PRG2, VTRNA2-1, PER3) corresponding to the loci above was also associated with CR, suggesting that alterations in DNA methylation may affect the expression of these four genes, eventually resulting in CR. Additionally, differentially methylated sites are partially related to genes and pathways that play key roles in process of circadian entrainment, insulin secretion, and so on. Hence, the mechanism and biological regulation of CR might be reflected through these epigenetic alterations, but future research will need to address the causal relationships.

18.
Toxicon ; 160: 1-7, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30639658

RESUMO

Okadaic acid (OA), a potent polyether marine toxin, accumulates in the digestive glands of marine mollusks and therefore can severely threaten the health of humans after ingestion of contaminated shellfish. In vivo and in vitro studies have revealed that exposure of various cells, including human embryonic amniotic cells, hepatocytes, neuroblastoma cells, to OA induces morphological and functional modifications as well as the death of cells. As the number of reports on OA poisoning has increased, this toxin has gradually attracted the public's attention, and researchers are trying to study it. This review summarizes the current literature on the toxicity effects of OA, in addition to its detection and detoxification.


Assuntos
Dinoflagelados/química , Ácido Okadáico/toxicidade , Animais , Humanos , Inativação Metabólica , Toxinas Marinhas/toxicidade , Moluscos/química , Ácido Okadáico/análise , Ácido Okadáico/metabolismo , Intoxicação por Frutos do Mar
19.
Toxicon ; 152: 16-22, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30003918

RESUMO

Okadaic acid (OA) is one of the most common and widespread marine toxins and causes acute gastrointestinal symptoms known as diarrheic shellfish poisoning (DSP) in humans. Although OA is not classified as a typical neurotoxin, an increasing number of studies have reported its neurotoxic effects. However, most of the available studies have focused on OA-induced inhibition of serine/threonine protein phosphatases, while the molecular mechanism of OA-induced neurotoxicity remains largely unclear. To better understand the potentially toxicological profile of OA, cell cycle arrest, DNA damage and alterations in gene expression in the human neuroblastoma cell line SHSY5Y upon OA exposure were determined using flow cytometry, comet assay, and transcriptome microarray. The results showed that OA could induce cell cycle arrest at S phase and might be involved in significant DNA strand breaks. Gene expression profiling indicated that the differentially expressed genes after OA exposure were significantly enriched in the "DNA replication" and "cell cycle" pathways. Real-time PCR result had further validated that down-regulation of the Cdc45/Mcm2-7/GINS complex might be the major factor regulating those alterations. These findings provide new insight into the molecular mechanisms of OA-induced neurotoxicity, and the current data may also provide a basis for future studies.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Ácido Okadáico/toxicidade , Fase S/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Toxinas Marinhas/toxicidade
20.
Cell Physiol Biochem ; 46(3): 1209-1217, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29672293

RESUMO

BACKGROUND/AIMS: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). Because of its controversial pathogenesis, DPN is still not diagnosed or managed properly in most patients. METHODS: In this study, human lncRNA microarrays were used to identify the differentially expressed lncRNAs in DM and DPN patients, and some of the discovered lncRNAs were further validated in additional 78 samples by quantitative realtime PCR (qRT-PCR). RESULTS: The microarray analysis identified 446 and 1327 differentially expressed lncRNAs in DM and DPN, respectively. The KEGG pathway analysis further revealed that the differentially expressed lncRNA-coexpressed mRNAs between DPN and DM groups were significantly enriched in the MAPK signaling pathway. The lncRNA/mRNA coexpression network indicated that BDNF and TRAF2 correlated with 6 lncRNAs. The qRT-PCR confirmed the initial microarray results. CONCLUSION: These findings demonstrated that the interplay between lncRNAs and mRNA may be involved in the pathogenesis of DPN, especially the neurotrophin-MAPK signaling pathway, thus providing relevant information for future studies.


Assuntos
Neuropatias Diabéticas/patologia , RNA Longo não Codificante/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Análise por Conglomerados , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/metabolismo , Regulação para Baixo , Teste de Tolerância a Glucose , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/genética , Fator 2 Associado a Receptor de TNF/metabolismo , Regulação para Cima
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