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OBJECTIVES: Adiponectin plays an important role in carbohydrate and lipid metabolism. However, the evidence regarding the association between adiponectin and diabetes mellitus in obese dogs is sparse. The aim of this study is to investigate the associations of adiponectin with the risk of diabetes mellitus in obese dogs on the basis of a prospective cohort study. MATERIALS AND METHODS: Serum adiponectin levels in obese dogs recruited from three small animal hospitals between 2015 and 2018 were measured by ELISA. Electronic health records were used to record the incidence of diabetes mellitus during follow-up for 3 years. RESULTS: A total of 862 dogs were included. Amongst the 862 dogs, 51 developed diabetes. Adiponectin levels were associated with diabetes mellitus after adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol. When adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol, the adjusted hazard ratios were 7.83 (95% confidence interval: 2.67 to 30.13) in the lowest adiponectin group and 1.96 (95% CI: 1.10 to 8.55) in the medium adiponectin group relative to that in the highest adiponectin group. The area under a curve of adiponectin's Receiver operating characteristic curve was 0.81 (95% CI: 0.76 to 0.86). CLINICAL SIGNIFICANCE: Low adiponectin is associated with diabetes mellitus and has a high risk of incident diabetes mellitus, implying the potential of adiponectin as a predictive biomarker of diabetes mellitus in obese dogs.
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OBJECTIVE: To explore whether the using of mimetic peptide Gap27, a selective inhibitor of connexin 43 (Cx43), could block the death of dopamine neurons and influence the expression of Cx43 in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease mouse models. METHODS: Eighteen C57BL/6 mice were randomly divided into control group, 6-OHDA group and 6-OHDA+Gap27 group, with 6 mice in each group. Bilateral substantia nigra stereotactic injection was performed. The control group was injected with ascorbate solution, 6-OHDA group was injected with 6-OHDA solution, and 6-OHDA+Gap27 group was injected with 6-OHDA and Gap27 mixed solution. Immuno-histochemical staining was used to detect the number of dopamine neurons, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Cx43 messenger ribonucleic acid (mRNA), immuno-fluorescence staining was used to detect the distribution of Cx43 protein, the contents of Cx43 protein and Cx43 phosphorylation at serine 368 (Cx43-ps368) in mouse midbrain were detected by Western blot. RESULTS: After injection of 6-OHDA, numerous dopamine neurons in substantia nigra died as Cx43 content increased, Cx43-ps368 content decreased. Mixing Gap27 while injecting 6-OHDA could reduce the number of death dopamine neurons and weaken the changes of Cx43 and Cx43-ps368 content caused by 6-OHDA. The number of tyrosine hydroxylase (TH) immunoreactive positive neurons in 6-OHDA group decreased to 27.7% ± 0.02% of the control group (P < 0.01); The number of TH immunoreactive positive neurons in 6-OHDA+Gap27 group was (1.64±0.16) times higher than that in 6-OHDA group (P < 0.05); The content of total Cx43 protein in 6-OHDA group was (1.44±0.07) times higher than that in 6-OHDA+Gap27 group (P < 0.05) while (1.68±0.07) times higher than that in control group (P < 0.01). In 6-OHDA group, the content of Cx43-ps368 protein and its proportion in total Cx43 protein were significantly lower than that in 6-OHDA+Gap27 group (P < 0.05). CONCLUSION: In 6-OHDA mouse models, mimetic peptide Gap27 played a protective role in reducing the damage to substantia nigra dopamine neurons, which was induced by 6-OHDA. The overexpression of Cx43 protein might have neurotoxicity to dopamine neuron. Meanwhile, decreasing Cx43 protein level and keeping Cx43-ps368 protein level may be the protective mechanisms of Gap27.
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Doença de Parkinson , Animais , Conexina 43/genética , Conexina 43/metabolismo , Conexina 43/farmacologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oxidopamina/efeitos adversos , Oxidopamina/metabolismo , Doença de Parkinson/metabolismo , Peptídeos/metabolismo , Peptídeos/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/farmacologiaRESUMO
OBJECTIVE: To analyze the effect of benzopyrene on the decrease of dopaminergic neurons, and the increase and aggregation of α-synuclein, which are the pathological features of Parkinson's disease, and to explore its possible mechanisms. METHODS: Eight-month-old transgenic mice with human SNCA gene were randomly divided into a BaP-exposed group and a control group. BaP and solvent corn oil were injected intraperitoneally to BaP-exposed group and control group respectively, once a day for 60 days. The motor dysfunction of mice was tested by rotarod test. The effects of BaP on the decrease of dopaminergic neurons and increase and aggregation of α-synuclein were observed by immunohistochemistry and Western blot experiments respectively, and the expression of related mRNA was detected by quantitative real-time PCR (qRT-PCR). Twenty genes were tested in the study, mainly related to neurotransmitter transporter (2 genes), neurotransmitter receptor function (10 genes), cellular autophagy (5 genes), and α-synuclein aggregation and degradation (3 genes). RESULTS: After BaP exposure, the movement time of the mice in the rotarod test was significantly reduced (P<0.05). The substantia nigra dopami-nergic neurons in the mice were significantly reduced, which was 62% of the control group (P<0.05), and the expression of α-synuclein in the midbrain increased, which was 1.36 times that of the control group (P<0.05). After BaP exposure, mRNA expressions of 14 genes in the midbrain of the mice were significantly down-regulated (P<0.05). Alpha-synuclein degradation and cell autophagy (5 genes), neuron transporters (2 genes), and neurotransmitter receptor functions (5 genes) were involved. The expression of one gene, Synphilin-1, was significantly up-regulated (P<0.01), which was related to α-synuclein aggregation. CONCLUSION: BaP exposure not only inhibited function of neurotransmitter receptor and dopamine transporter, but also interfered cell autophagy, thereby hindering the degradation of α-synuclein, which could lead to decrease of dopaminergic neurons in substantia nigra and increase and aggregation of α-synuclein in midbrain, as the significant pathology of Parkinson's disease. Therefore, BaP exposure may increase the risk of Parkinson's disease.
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Neurônios Dopaminérgicos , Animais , Benzo(a)pireno , Encéfalo , Dopamina , Humanos , Camundongos , alfa-SinucleínaRESUMO
Species of Diaporthe (syn. Phomopsis) are important endophytes, saprobes and pathogens, infecting a wide range of plants and resulting in important crop diseases. However, the species occurring on pear remain largely unresolved. In this study, a total of 453 Diaporthe isolates were obtained from branches of Pyrus plants (including P. bretschneideri, P. communis, P. pyrifolia and P. ussuriensis collected from 12 provinces in China) showing shoot canker symptoms. Phylogenetic analyses based on five loci (ITS, TEF, CAL, HIS, and TUB) coupled with morphology of 113 representative isolates revealed that 19 Diaporthe species were isolated, representing 13 known species (including D. caryae, D. cercidis, D. citrichinensis, D. eres, D. fusicola, D. ganjae, D. hongkongensis, D. padina, D. pescicola, D. sojae, D. taoicola, D. unshiuensis and D. velutina) and six new species described here as D. acuta, D. chongqingensis, D. fulvicolor, D. parvae, D. spinosa and D. zaobaisu. Although Koch's postulates confirmed all species to be pathogenic, a high degree of variation in aggressiveness was observed. Moreover, these species have a high diversity, plasticity, and prevalence related to the geographical location and pear species involved.
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Colletotrichum species are plant pathogens, saprobes, and endophytes on a range of economically important hosts. However, the species occurring on pear remain largely unresolved. To determine the morphology, phylogeny and biology of Colletotrichum species associated with Pyrus plants, a total of 295 samples were collected from cultivated pear species (including P. pyrifolia, P. bretschneideri, and P. communis) from seven major pear-cultivation provinces in China. The pear leaves and fruits affected by anthracnose were sampled and subjected to fungus isolation, resulting in a total of 488 Colletotrichum isolates. Phylogenetic analyses based on six loci (ACT, TUB2, CAL, CHS-1, GAPDH, and ITS) coupled with morphology of 90 representative isolates revealed that they belong to 10 known Colletotrichum species, including C. aenigma, C. citricola, C. conoides, C. fioriniae, C. fructicola, C. gloeosporioides, C. karstii, C. plurivorum, C. siamense, C. wuxiense, and two novel species, described here as C. jinshuiense and C. pyrifoliae. Of these, C. fructicola was the most dominant, occurring on P. pyrifolia and P. bretschneideri in all surveyed provinces except in Shandong, where C. siamense was dominant. In contrast, only C. siamense and C. fioriniae were isolated from P. communis, with the former being dominant. In order to prove Koch's postulates, pathogenicity tests on pear leaves and fruits revealed a broad diversity in pathogenicity and aggressiveness among the species and isolates, of which C. citricola, C. jinshuiense, C. pyrifoliae, and C. conoides appeared to be organ-specific on either leaves or fruits. This study also represents the first reports of C. citricola, C. conoides, C. karstii, C. plurivorum, C. siamense, and C. wuxiense causing anthracnose on pear.
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Our study demonstrated a high incidence of recollapse of the augmented vertebrae after PVP treatment for OVCFs. A risk score based on all significant factors can predict the rate of recollapse and gain clinical benefits to prevent recollapse in patients at high risk. BACKGROUND: Recollapse of the augmented vertebrae after percutaneous vertebroplasty (PVP) treatment for osteoporotic vertebral compression fractures (OVCFs) has obtained much attention. However, little is known about risk factors and score for recollapse of the augmented vertebrae. OBJECTIVE: To determine risk factors and furthermore develop a risk score related to recollapse of the augmented vertebrae after PVP treatment for OVCFs. METHODS: Patients who were treated with PVP for single OVCFs and met this study's inclusion criteria were retrospectively reviewed. The follow-up period was at least 2 years. Associations of recollapse with co-variates (age, gender, bone mass density [BMD] with a T-score, fracture level, intravertebral cleft [IVC], fracture type, cement volume, cement leakage, leakage into a disc, cement distribution pattern, Non-PMMA-endplate-contact [NPEC], preoperative fracture severity, reduction rate [RR], reduction angle [RA]) were analyzed and a risk score for recollapse was further developed to predict recollapse. RESULTS: A total of 152 patients were included. Recollapse group was found in 42 (27.6%) patients. Preoperative IVC, solid lump cement distribution pattern, more RR (a cutoff value of 7%) and larger RA (a cutoff value of 3°) was significantly associated with increased risk for recollapse of the augmented vertebrae. A risk score was developed based on the number of risk factors present in each patient. Patients with a score of 4 had an approximately ninefold increased risk of developing recollapse over patients with a score of 0. The receiver operating characteristic curve of the risk score generated an area under the curve of 0.899 (95% CI 0.642-0.836, P = 0.000). CONCLUSION: A risk score based on preoperative IVC, cement distribution pattern, reduction rate, and reduction angle predicts the rate of recollapse. Additional studies should aim to validate this score and inspect clinical benefits of recollapse prophylaxis in patients at high risk.
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Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Idoso , Cimentos Ósseos , Feminino , Seguimentos , Fraturas por Compressão/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico por imagem , Radiografia , Recidiva , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Falha de TratamentoRESUMO
The contraction of gastrointestinal (GI) smooth muscles is regulated by both Ca(2+)-dependent and Ca(2+) sensitization mechanisms. Proline-rich tyrosine kinase 2 (Pyk2) is involved in the depolarization-induced contraction of vascular smooth muscle via a Ca(2+) sensitization pathway. However, the role of Pyk2 in GI smooth muscle contraction is unclear. The spontaneous contraction of colonic smooth muscle was measured by using isometric force transducers. Protein and phosphorylation levels were determined by using western blotting. Pyk2 protein was expressed in colonic tissue, and spontaneous colonic contractions were inhibited by PF-431396, a Pyk2 inhibitor, in the presence of tetrodotoxin (TTX). In cultured colonic smooth muscle cells (CSMCs), PF-431396 decreased the levels of myosin light chain (MLC20) phosphorylated at Ser19 and ROCK2 protein expression, but myosin light chain kinase (MLCK) expression was not altered. However, Y-27632, a Rho kinase inhibitor, increased phosphorylation of Pyk2 at Tyr402 and concomitantly decreased ROCK2 levels; the expression of MLCK in CSMCs did not change. The expression of P(Tyr402)-Pyk2 and ROCK2 was increased when CSMCs were treated with Ach. Pyk2 is involved in the process of colonic smooth muscle contraction through the RhoA/ROCK pathway. These pathways may provide very important targets for investigating GI motility disorders.
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Colo/metabolismo , Quinase 2 de Adesão Focal/biossíntese , Contração Muscular/fisiologia , Músculo Liso/metabolismo , Proteínas rho de Ligação ao GTP/biossíntese , Quinases Associadas a rho/biossíntese , Animais , Técnicas de Cultura de Células , Colo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Quinase 2 de Adesão Focal/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos ICR , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTPRESUMO
BACKGROUND: A major complication related to gastrointestinal (GI) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility. In the present study, the contributions of PDGFRα+ cells to diabetes-induced colonic slow transit were investigated in streptozotocin (STZ)-induced diabetic mice. METHODS: Western blotting, quantitative PCR, contractile experiments, and intracellular recording were used in the present study. KEY RESULTS: The results demonstrated that the colon length was increased in STZ-treated mice. The colonic transit of artificial fecal pellets in vitro was significantly delayed in STZ-treated mice. The mRNA and protein expression of PDGFRα, small-conductance Ca2+ -activated K channels (SK3), and P2Y1 receptors were increased in the colons of STZ-treated mice. In contractile experiments, the colonic smooth muscles were more sensitive to the SK3 agonist and antagonist (CyPPA and apamin) and the P2Y1 agonist and antagonist (MRS2365 and MRS2500) in STZ-treated mice. Intracellular recordings showed the responses of membrane potentials in colonic smooth muscle cells to CyPPA, apamin, MRS2365, and MRS2500 were more sensitive in STZ-treated mice. The electric field stimulation-induced P2Y1/SK3-dependent fast inhibitory junctional potentials (fIJPs) of colonic smooth muscles were more significantly hyperpolarized in STZ-treated mice. CONCLUSIONS AND INFERENCES: These results suggest that the purinergic neurotransmitters/P2Y1/SK3 signaling pathway is up-regulated in the diabetic colons, thereby mediating diabetes-induced colonic slow transit.
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BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.
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Esvaziamento Gástrico , Mucosa Gástrica/metabolismo , Receptores da Neurocinina-2/fisiologia , Estômago/fisiopatologia , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Fundo Gástrico/fisiopatologia , Regulação da Expressão Gênica , Intestino Delgado/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Fenótipo , Antro Pilórico/fisiopatologia , Receptores da Neurocinina-2/genética , Receptores da Neurocinina-2/metabolismo , Transdução de Sinais , Estômago/patologia , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Objective: To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated. Results: (1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD. Conclusions: APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension and smoke, while a negative additive interaction with diabetes mellitus in the occurrence of CHD.
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Apolipoproteínas B/genética , Doença das Coronárias/genética , Polimorfismo de Nucleotídeo Único , Alelos , Estudos de Casos e Controles , Diabetes Mellitus , Feminino , Genótipo , Humanos , Hipertensão , Lipídeos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
A novel disease characterized by small brown-black spots (1 to 2 mm in diameter) on tender tea leaves (Camellia sinensis) has been observed in many regions of Hubei Province, China, which severely affects the yield and quality of tea. Tea leaf samples with typical symptoms were collected from three major tea-cultivation regions of Hubei, and were subjected to pathogen isolation for etiological analysis. As a result, 34 Pestalotiopsis isolates were obtained from 20 samples, and they were identified as Pestalotiopsis theae (14 isolates), P. camelliae (12), and P. clavispora (8), determined by morphologies and phylogenetic analysis based on internal transcribed spacer, and partial ß-tubulin and translation elongation factor 1-alpha genes. Pathogenicity tests on detached tea leaves showed that no matter what mycelial discs or conidium suspensions were used, inoculation of the Pestalotiopsis fungi could result in small brown-black spots (1 to 2 mm in diameter) on wounded leaves, similar to those observed in the field in the sizes and colors. It also revealed that only P. theae had pathogenicity on unwounded tea leaves, and P. theae and P. clavispora showed significantly higher virulence than P. camelliae. Inoculation test with conidium suspension on intact tea leaves in the field further confirmed that P. theae as the pathogen of brown-black spots. Reisolation of the pathogens from diseased leaves confirmed that the symptom was caused by the inoculation of Pestalotiopsis fungi. The P. theae isolates responsible for brown-black spots were also compared with those for tea gray blight disease in growth rate, pathogenicity, and molecular characteristics in parallel. To our knowledge, this is the first report that the Pestalotiopsis fungi cause brown-black spot disease on tender tea leaves. The results provide important implications for the prevention and management of this economically important disease.
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Ascomicetos , Camellia sinensis , Doenças das Plantas , Folhas de Planta , Ascomicetos/classificação , Ascomicetos/isolamento & purificação , Ascomicetos/fisiologia , Camellia sinensis/microbiologia , China , Filogenia , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologiaRESUMO
OBJECTIVE: To investigate the impact of particulate matter 2.5 (PM2.5) on the blood pressure of urban residents in Shanghai, China. METHODS: A panel study was conducted from May 27(th) to June 5(th) 2014 in a cohort of 30 adults in an urban community. Participants were 50-80 years old, had lived in the community for at least 5 years, and had a good health status. Key exclusion criteria were current smoking, smoking during the last 3 years, passive smoking, alcohol consumption, and severe cardiopulmonary disease. A total of 28 participants were eligible. Information on demographic characteristics, including of age, sex, height, weight, education, income and chronic comorbidities were collected. Participants were requested to have six weekly blood pressure measurements. Real-time concentrations of PM2.5 and gaseous pollutants were obtained from a nearby air quality monitor during 40 d. Pearson correlation was applied to analyze the correlation between PM2.5 and SO2, NO2, CO and O3. Linear mixed models were applied to analyze the association between PM2.5 and blood pressure, after controlling for time-related trends, day of the week, mean temperature, relative humidity and individual characteristics. RESULTS: The mean systolic and diastolic blood pressure was (124.0±15.0) mmHg (1 mmHg=0.133 kPa) and (74.0±7.7) mmHg, respectively. At 24 h before blood pressure measurement, the mean PM2.5, SO2, NO2, O3 and CO concentration were (8.3±4.9), (46.6±12.9) , (79.2±27.4) µg/m(3) and (0.8±0.2) mg/m(3). The Pearson correlation coefficient R, between PM2.5 and O3, SO2, NO2 and CO was 0.79, 0.59, 0.34 and 0.45, respectively, with corresponding P-values of <0.001, 0.006, 0.012 and 0.009, respectively. The significant correlation between PM2.5 and systolic blood pressure occurred at lag 1 day, was strongest at lag 3 day, but attenuated thereafter. A 10 µg/m(3) increase in 3-day average concentrations of PM2.5 was associated with changes of 1.86 (95%CI: 0.62-3.09) mmHg in systolic blood pressure and -0.05 (95%CI: 0.59-0.50) mmHg in diastolic blood pressure. CONCLUSION: Short-term exposure to PM2.5 may significantly elevate the systolic blood pressure of urban residents in Shanghai.
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Poluentes Atmosféricos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , China , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Temperatura , Fatores de Tempo , População UrbanaRESUMO
Ulmus chenmoui (Ulmaceae) is an endangered tree found on Langya Mountain, eastern China. To better understand the population genetics of U. chenmoui and conserve the species, we developed microsatellite markers. Using a suppression-polymerase chain reaction technique, 74 compound microsatellite primer pairs were designed. Twelve microsatellite markers were polymorphic in 39 individuals, and the number of alleles per locus ranged from 3 to 9. The observed and expected heterozygosities ranged from 0.051 to 0.769 and from 0.533 to 0.768, respectively. Significant linkage disequilibrium was detected for three pairs of loci (P < 0.01), which may be due to a recent population bottleneck and the small population size. Nine of the 12 loci deviated from the Hardy-Weinberg equilibrium (P < 0.01), which could be explained by significant inbreeding rather than the presence of null alleles. These markers will provide a solid basis for future efforts in population genetic studies of U. chenmoui, which in turn will contribute to species conservation.
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Árvores/genética , Ulmus/genética , Alelos , China , Conservação dos Recursos Naturais , Loci Gênicos , Genética Populacional , Desequilíbrio de Ligação , Repetições de Microssatélites , Polimorfismo GenéticoRESUMO
The classic renin-angiotensin system (RAS) is a complex system in which angiotensin II (Ang II) has been identified as an important endogenous regulator that influences both smooth muscle contraction and cell growth. Although a local RAS is known to exist in the gastrointestinal tract, it is unclear whether Ang II is involved in the loss of gastric interstitial cells of Cajal (ICC) in diabetic mice. The present study was designed to investigate the effect of Ang II on ICC survival in streptozotocin (STZ)-induced diabetic mice. Western blot, immunofluorescence, isometric muscle recording, enzyme-linked immunosorbent assay (ELISA) and a cell counting kit-8 were used in this research. Our results demonstrate that the c-Kit and membrane-bound stem cell factor (mSCF) protein expression levels in gastric smooth muscle were decreased in STZ-induced diabetic mice. However, the angiotensin receptor type 1 (AT1R) expression levels in gastric smooth muscle and angiotensin-converting enzyme (ACE) expression levels in gastric mucosa were increased. The effect of Ang II on the tonic contraction of gastric smooth muscle was potentiated in diabetic mice, and the plasma Ang II level was enhanced. Ang II increased mSCF expression, cell proliferation, and Akt-Ser473 phosphorylation in cultured gastric smooth muscle cells (GSMCs). These effects were reduced by specific inhibitors ZD7155 (an AT1R antagonist) and LY294002 (a PI3-kinase inhibitor). Our results suggest that Ang II increases mSCF expression and cell proliferation in cultured GSMCs in a PI3K/Akt signaling-dependent manner. ACE and AT1R up-regulation in the stomach may help compensate for ICC loss in STZ-induced diabetic mice.
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Diabetes Mellitus Experimental/metabolismo , Células Intersticiais de Cajal/fisiologia , Receptor Tipo 1 de Angiotensina/metabolismo , Angiotensina II/fisiologia , Animais , Proliferação de Células , Células Cultivadas , Diabetes Mellitus Experimental/patologia , Mucosa Gástrica/metabolismo , Masculino , Camundongos Endogâmicos ICR , Miócitos de Músculo Liso/fisiologia , Peptidil Dipeptidase A/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antro Pilórico/patologia , Receptor Tipo 1 de Angiotensina/genética , Transdução de Sinais , Estreptozocina , Regulação para CimaRESUMO
Distension is a regular mechanical stimulus in gastrointestinal (GI) tract. This study was designed to investigate the effect of hypotonic stress on pacemaking activity and determine whether actin microfilament is involved in its mechanism in cultured murine intestinal interstitial cells of Cajal (ICCs) by using whole-cell patch-clamp and calcium imaging techniques. Hypotonic stress induced sustained inward holding current from the baseline to -650+/-110 pA and significantly decreased amplitudes of pacemaker current. Hypotonic stress increased the intensity of basal fluorescence ratio (F/F0) from baseline to 1.09+/-0.03 and significantly increased Ca(2+) oscillation amplitude. Cytochalasin-B (20 microM), a disruptor of actin microfilaments, significantly suppressed the amplitudes of pacemaker currents and calcium oscillations, respectively. Cytochalasin-B also blocked hypotonic stress-induced sustained inward holding current and hypotonic stress-induced increase of calcium oscillations. Phalloidin (20 microM), a stabilizer of actin microfilaments, significantly enhanced the amplitudes of pacemaker currents and calcium oscillations, respectively. Despite the presence of phalloidin, hypotonic stress was still able to induce an inward holding current and increased the basal fluorescence intensity. These results suggest that hypotonic stress induces sustained inward holding current via actin microfilaments and the process is mediated by alteration of intracellular basal calcium concentration and calcium oscillation in cultured intestinal ICCs.
Assuntos
Citoesqueleto de Actina/metabolismo , Relógios Biológicos/fisiologia , Sinalização do Cálcio/fisiologia , Motilidade Gastrointestinal/fisiologia , Pressão Osmótica/fisiologia , Telócitos/fisiologia , Animais , Células Cultivadas , Feminino , Masculino , Mecanotransdução Celular/fisiologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
OBJECTIVE: To investigate the value of myocardial performance index (MPI) in assessing LV function in patients with primary hypertension (HP). METHODS: We studied 130 patients with HP (mean age 54.9±13.3 years)and 155 healthy control subjects (mean age 52.4±11.6 years). MPI was determined by tissue doppler imaging using the following formula: MPI=(isovolumic contraction time + isovolumic relaxation time)/ ejection time. The HP group was divided into hypertrophy subgroup( LVMI≥115 g/m(2) in males, or ≥95 g/m(2) in females) and normal mass subgroup(LVMI <115 g/m(2) in males, or<95 g/m(2) in females). RESULTS: MPI was significantly different in control group, normal mass subgroup and hypertrophy subgroup(0.72±0.23 vs. 0.54± 0.17 vs. 0.45±0.11, P<0.001). Hypertrophy subgroup had significant higher MPI than normal mass subgroup(P =0.046), and both the groups had significant higher MPI than control group(all P<0.001). MPI was positively associated with age(r=0.369,P<0.001), Left ventricular end diastolic diameter(r=0.169, P<0.05), Sm(r=-0.211, P<0.001) and Em(r=-0.383, P<0.001) in control group. In multiple linear regression analysis, MPI was independently related to age (ß=0.492, t=7.222,P<0.001) in control group. Among the HP patients, MPI was positively associated with left atrial area (r=0.293, P<0.001),intra ventricular septum(IVS) diameter (r=0.453, P<0.001), LVMI (r=0.453, P<0.001), relative wall thickness(r=0.458, P<0.001), and negatively associated with Sm(r=-0.414, P<0.001), Em(r=-0.508, P<0.001), left ventricular ejection fraction (r=-0.305, P<0.001) in bivariate analysis. In the multiple linear regression analysis, MPI was independently related to Em (ß=0.401, t=4.256,P<0.001) and IVS diameter (ß=-0.365, t=-3.878,P<0.001) in the HP patients. CONCLUSION: The HP patients had elevated MPI, especially in the ones with LV hypertrophy. Tissue doppler imaging (TDI) derived MPI could be a useful index to evaluate the overall cardiac function in HP patients.
Assuntos
Hipertensão , Função Ventricular Esquerda , Adulto , Idoso , Estudos de Casos e Controles , Ecocardiografia Doppler , Hipertensão Essencial , Feminino , Humanos , Hipertrofia Ventricular Esquerda , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
BACKGROUND: Hydrogen sulfide (H2 S) has been shown to have an excitatory effect on gastric motility, but the underlying molecular mechanism is unclear. In this study, we aimed to investigate the possible targets of H2 S and determine how H2 S affects its target proteins during H2 S-induced contraction. METHODS: Patch-clamp and potentiometric fluorescence dye were utilized to measure the electrophysiological changes. The Biotin-switch assay was utilized to detect the protein S-sulfhydration. The isometric tension measurement was conducted too. KEY RESULTS: Exogenous H2 S enhanced the tonic contraction of gastric antral smooth muscle, and voltage-dependent potassium channel (KV ) blocker and Dithiothreitol (DTT, a reducing agent) abolished the excitatory effect of NaHS. Exogenous H2 S inhibited the fast inactivation component of the voltage-dependent potassium channel current (IKVfast ) in isolated gastric antral smooth muscle cells. H2 S inhibited the KV 4.3 current in H293 cells with heterologous expression of KV 4.3, but did not inhibit the KV 4.1 and KV 4.2 currents, which together contribute greatly to IKVfast . NaHS significantly decreased the membrane potential in cultured gastric smooth muscle cells, but the NaHS-induced depolarization was suppressed by knockdown of KV 4.3 and N-ethylamaleimide (NEM), a free thiol group blocker. In addition, NaHS sulfhydrated KV 4.3 in H293 cells and in gastric smooth muscle tissue. However, this S-sulfhydration was inhibited by NEM and DTT. Meanwhile the NaHS-induced inhibition of IKVfast and KV 4.3 was also blocked by NEM and DTT. CONCLUSIONS & INFERENCES: These results suggest that exogenous H2 S sulfhydrates KV 4.3 to decrease the membrane potential, thereby enhancing the basal tension of gastric antral smooth muscle.
Assuntos
Mucosa Gástrica/metabolismo , Sulfeto de Hidrogênio/metabolismo , Tono Muscular/fisiologia , Músculo Liso/metabolismo , Canais de Potássio Shal/metabolismo , Animais , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Células HEK293 , Humanos , Sulfeto de Hidrogênio/farmacologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Tono Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Técnicas de Patch-Clamp , Estômago/efeitos dos fármacosRESUMO
Worldwide, many plant species are experiencing an earlier onset of spring phenophases due to climate warming. Rapid recent temperature increases on the Tibetan Plateau (TP) have triggered changes in the spring phenology of the local vegetation. However, remote sensing studies of the land surface phenology have reached conflicting interpretations about green-up patterns observed on the TP since the mid-1990s. We investigated this issue using field phenological observations from 1990 to 2006, for 11 dominant plants on the TP at the levels of species, families (Gramineae-grasses and Cyperaceae-sedges) and vegetation communities (alpine meadow and alpine steppe). We found a significant trend of earlier leaf-out dates for one species (Koeleria cristata). The leaf-out dates of both Gramineae and Cyperaceae had advanced (the latter significantly, starting an average of 9 days later per year than the former), but the correlation between them was significant. The leaf-out dates of both vegetation communities also advanced, but the pattern was only significant in the alpine meadow. This study provides the first field evidence of advancement in spring leaf phenology on the TP and suggests that the phenology of the alpine steppe can differ from that of the alpine meadow. These findings will be useful for understanding ecosystem responses to climate change and for grassland management on the TP.
Assuntos
Mudança Climática , Cyperus , Pradaria , Desenvolvimento Vegetal , Poaceae , Ecossistema , Temperatura , TibetRESUMO
MicroRNAs (miRNAs) are small non-coding RNA molecules that play a fundamental role in controlling a variety of biological functions. Emerging evidence has shown that common genetic polymorphisms in miRNAs may be associated with the development of liver cancer; however, several individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the association between functional polymorphisms in miRNAs and susceptibility to liver cancer. A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before May 1, 2012. Crude odds ratios with 95% confidence intervals were calculated. Fourteen case-control studies were included with a total of 6824 liver cancer patients and 7674 healthy controls. Nine single nucleotide polymorphisms in miRNAs were assessed, including miR-146a G>C (rs2910164), miR-499 T>C (rs3746444), miR-218 A>G (rs11134527), miR-let-7c Ins/Del (rs6147150), miR-106b-25 A>G (rs999885), miR-34b/c T>C (rs4938723), miR-196a-2 C>T (rs11614913), miR-920 Ins/Del (rs16405), and miR-122 Ins/Del (rs3783553). The meta-analysis results showed that miR-let-7c Del, miR-34b/c C, and miR-122 Del variants may be associated with increased liver cancer risk. Conversely, miR-920*Del variant may decrease the risk of liver cancer. However, miR-146a G>C, miR-196a-2 C>T, miR-499 T>C, and miR-218 A>G polymorphisms showed no significant association with liver cancer risk. In conclusion, the current meta-analysis suggests that miR-let- 7c Del, miR-34b/c C and miR-122 Del variants may be associated with increased liver cancer risk, while miR-920 Del variant may be a protective factor against liver cancer.