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1.
Diabetes Obes Metab ; 25(6): 1714-1722, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36811214

RESUMO

AIM: To assess whether the beta-cell function of inpatients undergoing antidiabetic treatment influences achieving time in range (TIR) and time above range (TAR) targets. MATERIALS AND METHODS: This cross-sectional study included 180 inpatients with type 2 diabetes. TIR and TAR were assessed by a continuous glucose monitoring system, with target achievement defined as TIR more than 70% and TAR less than 25%. Beta-cell function was assessed by the insulin secretion-sensitivity index-2 (ISSI2). RESULTS: Following antidiabetic treatment, logistic regression analysis showed that lower ISSI2 was associated with a decreased number of inpatients achieving TIR (OR = 3.10, 95% CI: 1.19-8.06) and TAR (OR = 3.40, 95% CI: 1.35-8.55) targets after adjusting for potential confounders. Similar associations still existed in those participants treated with insulin secretagogues (TIR: OR = 2.91, 95% CI: 0.90-9.36, P = .07; TAR, OR = 3.14, 95% CI: 1.01-9.80) or adequate insulin therapy (TIR: OR = 2.84, 95% CI: 0.91-8.81, P = .07; TAR, OR = 3.24, 95% CI: 1.08-9.67). Furthermore, receiver operating characteristic curves showed that the diagnostic value of the ISSI2 for achieving TIR and TAR targets was 0.73 (95% CI: 0.66-0.80) and 0.71 (95% CI: 0.63-0.79), respectively. CONCLUSIONS: Beta-cell function was associated with achieving TIR and TAR targets. Stimulating insulin secretion or exogenous insulin treatment could not overcome the disadvantage of lower beta-cell function on glycaemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Automonitorização da Glicemia , Estudos Transversais , Pacientes Internados , Glicemia/análise , Insulina/uso terapêutico
2.
Cardiovasc Diabetol ; 21(1): 283, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536433

RESUMO

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels. METHODS: This is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function. RESULTS: After adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053-0.402), an association specific to participants with < 1 year duration of diabetes. RCS analyses demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 144 mmHg corresponding to the best beta-cell function. This higher SBP was "paradoxically" associated with lower 2 h postprandial blood glucose (PBG) when SBP < 150 mmHg that was almost exclusively mediated by ISSI2 (mediating effect = - 0.043, 95%CI - 0.067 to - 0.018; mediating effect percentage = 94.7%, P < 0.01). SBP was however not associated with improvement in ISSI2 or 2 h PBG in participants with HbA1c < 10%. CONCLUSIONS: In early stage of diabetes, a slightly elevated SBP (140-150 mmHg) was transiently associated with better beta-cell function in T2DM patients with HbA1c ≥ 10% but not in those with HbA1c < 10%.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Glicemia/análise , Pressão Sanguínea , Hemoglobinas Glicadas , Estudos Transversais
3.
Cell Biol Int ; 46(12): 2075-2084, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36040750

RESUMO

Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is believed to be involved in many gynecological and obstetrics disorders. Nevertheless, the role of NEAT1 in polycystic ovary syndrome (PCOS) is scarcely investigated. Our study aimed to investigate the role of NEAT1, microRNA (miR)-324-3p, and bromodomain containing 3 (BRD3) in PCOS. First, 80 women with PCOS and 80 healthy (non-PCOS) women were included, and their serum hormone levels were tested. Next, the PCOS mouse model was established by dehydroepiandrosterone injection, and then NEAT1, miR-324-3p, and BRD3 expression levels were detected in the PCOS mice. Lentivirus carrying short hairpin-NEAT1 or miR-324-3p agomir was injected into the PCOS mice to determine the change in biochemical indices and pathology. Moreover, a rescue experiment was conducted, after which, the binding relationships among NEAT1, miR-324-3p, and BRD3 were analyzed. NEAT1 and BRD3 were expressed at a high level while miR-324-3p was expressed at a low level in women with PCOS and PCOS mice. Reduced levels of NEAT1 or elevated levels of miR-324-3p mitigated metabolic disorders and alleviated ovarian pathological changes in PCOS mice. Mechanistically, NEAT1 sponged miR-324-3p and miR-324-3p targeted BRD3. In the rescue experiment, elevated miR-324-3p or reduced BRD3 level reversed the effects of the enhanced NEAT1 on metabolic disorders and ovarian pathological changes in PCOS mice. NEAT1 exacerbates metabolic disorders and ovarian pathological changes in PCOS mice by downregulating miR-324-3p and upregulating BRD3. This study gives a novel direction in PCOS treatment.


Assuntos
MicroRNAs , Síndrome do Ovário Policístico , RNA Longo não Codificante , Humanos , Feminino , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Fatores de Transcrição/genética
4.
Acta Pharmacol Sin ; 43(6): 1473-1483, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34654875

RESUMO

Most studies regarding the beneficial effect of sulforaphane (SFN) on non-alcoholic fatty liver disease (NAFLD) have focused on nuclear factor E2-related factor 2 (Nrf2). But the molecular mechanisms underlying the beneficial effect of SFN in the treatment of NAFLD remain controversial. Fibroblast growth factor (FGF) 21 is a member of the FGF family expressed mainly in liver but also in adipose tissue, muscle and pancreas, which functions as an endocrine factor and has been considered as a promising therapeutic candidate for the treatment of NAFLD. In the present study we investigated whether FGF21 was involved in the therapeutic effect of SFN against NAFLD. C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to generate NAFLD and continued on the HFD for additional 6 weeks with or without SFN treatment. We showed that administration of SFN (0.56 g/kg) significantly ameliorated hepatic steatosis and inflammation in NAFLD mice, along with the improved glucose tolerance and insulin sensitivity, through suppressing the expression of proteins responsible for hepatic lipogenesis, while enhancing proteins for hepatic lipolysis and fatty acids oxidation. SFN administration significantly increased hepatic expression of FGFR1 and fibroblast growth factor 21 (FGF21) in NAFLD mice, along with decreased phosphorylation of p38 MAPK (the downstream of FGF21). HepG2 cells were treated in vitro with FFAs (palmitic acid and oleic acid) followed by different concentrations of SFN. We showed that the effects of SFN on FGF21 and FGFR1 protein expression were replicated in FFAs-treated HepG2 cells. Moreover, the increased FGFR1 protein occurred earlier than increased FGF21 protein. Interestingly, the rapid effect of SFN on FGFR1 protein was not regulated by the FGFR1 gene transcription. Knockdown of FGFR1 and p38 genes weakened SFN-reduced lipid deposition in FFAs-treated HepG2 cells. SFN administration in combination with rmFGF21 (1.5 mg/kg, i.p., every other day) for 3 weeks further suppressed hepatic steatosis in NAFLD mice. In conclusion, SFN ameliorates lipid metabolism disorders in NAFLD mice by upregulating FGF21/FGFR1 pathway. Our results verify that SFN may become a promising intervention to treat or relieve NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Ácidos Graxos não Esterificados/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Isotiocianatos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Sulfóxidos
5.
Nutr Metab Cardiovasc Dis ; 32(2): 447-455, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34893412

RESUMO

BACKGROUND AND AIMS: Previous studies have indicated that the association of elevated low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) varies greatly with age, with the association being much stronger in younger than older individuals. To estimate the relationship between LDL-C and CVD risk in a contemporary population aged over 70 years in China. METHODS AND RESULTS: In this analysis, participants of China Health and Retirement Longitudinal Study (CHARLS) who did not take statins and did not have heart disease and stroke in 2011 were include and were followed up to 2018. The outcome of this analysis was the occurrence of CVD. Cox regression was used to assess the effect of LDL-C on CVD. We calculated E-values to quantify the effect of unmeasured confounding. In the 9,631 participants, 15.2% (N = 1,463) were aged over 70 years. During follow-up of 7 years, 1,437 participants had a first CVD attack. The Risk of CVD increased with each 10 mg/mL elevation in LDL-C in whole participants and all age groups. We noted a U-shaped relationship between LDL-C and risk of CVD in group over 70 years old, however, we further found that in the left side of U-shape curve, LDL-C was not associated with CVD, which indicated that a lower level of LDL-C could not increase the risk of CVD. E-value analysis suggested robustness to unmeasured confounding. CONCLUSIONS: In a contemporary society of China, elevated the level of LDL-C also increased the risk of CVD in participants over 70 years old. These results should strengthen guideline recommendations for the use of lipid-lowering therapies in those elderly.


Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol , LDL-Colesterol , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Estudos Longitudinais , Estudos Prospectivos , Fatores de Risco
6.
Gen Physiol Biophys ; 41(2): 159-164, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35416179

RESUMO

Our study aimed to detect the effects of polyphyllin I (PPI) on relieving gestational diabetes mellitus (GDM), and the possible mechanism. A mouse model of GDM was constructed. The effects of PPI on GDM mice were evaluated by detecting blood glucose, insulin level, glucose tolerance test, and insulin tolerance test. The inflammation response in GDM and GDM+PPI group were evaluated by enzyme-linked immunosorbent assay (ELISA). The effect of PPI on the offspring of GDM mice was analyzed. In addition, immunoblot assays were performed to investigate the effects of PPI on the AMPK pathway. We found that PPI improved diabetes-related symptoms and decreased serum inflammatory response in GDM mice. In addition, we also found that PPI reduced the tissue damage of GDM mice. We noticed that PPI alleviated inflammatory injury in GDM mice through targeting AMPK pathway. Our findings showed that PPI has the potential to be explored as the drug for GDM treatment.


Assuntos
Diabetes Gestacional , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicemia/metabolismo , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/metabolismo , Diosgenina/análogos & derivados , Feminino , Insulina/metabolismo , Camundongos , Gravidez , Transdução de Sinais
7.
BMC Vet Res ; 16(1): 86, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156273

RESUMO

BACKGROUND: Wild Amur tigers are a sparsely populated species, and the conservation of this species is of great concern worldwide, but as an important health risk factor, parasite infection in them is not fully understanding. RESULTS: In this study, sixty-two faecal samples were collected to investigate the frequency and infection intensity of Toxocara cati and Toxascaris leonina in wild Amur tigers. The T. cati and T. leonina eggs were preliminary identified by microscopy, and confirmed by molecular techniques. Infection intensity was determined by the modified McMaster technique. Phylogenetic trees demonstrated that T. cati of wild Amur tiger had a closer relationship with which of other wild felines than that of domestic cats. T. leonina of Amur tiger and other felines clustered into one clade, showing a closer relationship than canines. The average frequency of T. cati was 77.42% (48/62), and the frequency in 2016 (100%) were higher than those in 2013 (P = 0.051, < 0.1; 66.6%) and 2014 (P = 0.079, < 0.1; 72.2%). The infection intensity of T. cati ranged from 316.6 n/g to 1084.1 n/g. For T. leonina, only three samples presented eggs when the saturated sodium chloride floating method was performed, indicating that the frequency is 4.83% (3/62). Unfortunately, the egg number in faecal smears is lower than the detective limitation, so the infection intensity of T. leonina is missed. CONCLUSIONS: This study demonstrated that ascarids are broadly prevalent, and T. cati is a dominant parasite species in the wild Amur tiger population.


Assuntos
Tigres/parasitologia , Toxascaríase/veterinária , Toxocaríase/epidemiologia , Animais , China/epidemiologia , Contagem de Ovos de Parasitas/veterinária , Filogenia , Toxascaríase/epidemiologia , Toxascaris/classificação , Toxascaris/isolamento & purificação , Toxocara/classificação , Toxocara/isolamento & purificação
8.
Lipids Health Dis ; 19(1): 226, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059672

RESUMO

BACKGROUND: Prediabetes has become a pandemic. This study aimed to identify a better predictor for the incidence of prediabetes, which we hypothesize to be the triglyceride-glucose (TyG) index, a simplified insulin resistance index. We compared its predictive value with the other common risk factors of prediabetes. METHODS: The participants of this analysis were derived from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 4543 participants without initial prediabetes or diabetes were followed up for 3.25 years. Using multivariate logistic regression model, the associations between baseline obesity, lipid profiles and non-insulin-based insulin resistance indices with the incidence of prediabetes were analyzed. To assess which is better predictor for the incidence of prediabetes, the area under curves (AUCs) calculated from the receiver operating characteristic curve analyses were used to evaluate and compare with the predictive value of the different indices. RESULTS: During the 3.25 years, 1071 out of the 4543 participants developed prediabetes. Using the logistic regression analysis adjusted for some potential confounders, the risk of incidence of prediabetes increased 1.38 (1.28-1.48) fold for each 1-SD increment of TyG index. The predictive ability (assessed by AUCs) of TyG index for predicting prediabetes was 0.60 (0.58-0.62), which was superior to the indices of obesity, lipid profiles and other non-insulin-based insulin resistance indices. Although the predictive ability of the TyG index was overall similar to fasting plasma glucose (FPG) (P = 0.4340), TyG index trended higher than FPG in females (0.62 (0.59-0.64) vs. 0.59 (0.57-0.61), P = 0.0872) and obese subjects (0.59 (0.57-0.62) vs. 0.57 (0.54-0.59), P = 0.1313). TyG index had superior predictive ability for the prediabetic phenotype with isolated impaired glucose tolerance compared with FPG (P <  0.05) and other indices. Furthermore, TyG index significantly improved the C statistic (0.62 (0.60-0.64)), integrated discrimination improvement (1.89% (1.44-2.33%)) and net reclassification index (28.76% (21.84-35.67%)) of conventional model in predicting prediabetes than other indices. CONCLUSIONS: TyG could be a potential predictor to identify the high risk individuals of prediabetes.


Assuntos
Glicemia/análise , Estado Pré-Diabético/sangue , Triglicerídeos/sangue , China/epidemiologia , Jejum/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Estado Pré-Diabético/epidemiologia , Estudos Prospectivos , Curva ROC , Fatores de Risco
9.
Development ; 141(24): 4697-709, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25468938

RESUMO

The balance between self-renewal and differentiation of adult neural stem cells (aNSCs) is essential for the maintenance of the aNSC reservoir and the continuous supply of new neurons, but how this balance is fine-tuned in the adult brain is not fully understood. Here, we investigate the role of SIRT1, an important metabolic sensor and epigenetic repressor, in regulating adult hippocampal neurogenesis in mice. We found that there was an increase in SIRT1 expression during aNSC differentiation. In Sirt1 knockout (KO) mice, as well as in brain-specific and inducible stem cell-specific conditional KO mice, the proliferation and self-renewal rates of aNSCs in vivo were elevated. Proliferation and self-renewal rates of aNSCs and adult neural progenitor cells (aNPCs) were also elevated in neurospheres derived from Sirt1 KO mice and were suppressed by the SIRT1 agonist resveratrol in neurospheres from wild-type mice. In cultured neurospheres, 2-deoxy-D-glucose-induced metabolic stress suppressed aNSC/aNPC proliferation, and this effect was mediated in part by elevating SIRT1 activity. Microarray and biochemical analysis of neurospheres suggested an inhibitory effect of SIRT1 on Notch signaling in aNSCs/aNPCs. Inhibition of Notch signaling by a γ-secretase inhibitor also largely abolished the increased aNSC/aNPC proliferation caused by Sirt1 deletion. Together, these findings indicate that SIRT1 is an important regulator of aNSC/aNPC self-renewal and a potential mediator of the effect of metabolic changes.


Assuntos
Células-Tronco Adultas/fisiologia , Proliferação de Células/fisiologia , Giro Denteado/citologia , Regulação da Expressão Gênica/fisiologia , Células-Tronco Neurais/fisiologia , Sirtuína 1/metabolismo , Células-Tronco Adultas/metabolismo , Animais , Western Blotting , Bromodesoxiuridina , Proliferação de Células/efeitos dos fármacos , Desoxiglucose/efeitos adversos , Fluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Knockout , Análise em Microsséries , Microscopia Confocal , Células-Tronco Neurais/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Sirtuína 1/genética , Estatísticas não Paramétricas , Tamoxifeno
10.
Exp Parasitol ; 183: 13-22, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29054823

RESUMO

Small heat shock proteins (sHsps) are ubiquitous and diverse molecular chaperones. Found in almost all organisms, they regulate protein refolding and protect cells from stress. Until now, no sHsp has been characterized in Eimeria tenella. In this study, the novel EtsHsp20.4 gene was cloned from E. tenella by rapid amplification of cDNA ends based on a previously identified expressed sequence tag. The full-length cDNA was 1019bp in length and contained an open reading frame of 558bp that encoded a 185-amino acid polypeptide with a calculated molecular weight of 20.4 kDa. The EtsHsp20.4 protein contained a distinct HSP20/alpha-crystallin domain that is the key determinant of their function as molecular chaperones and belongs to the HSP20 protein family. EtsHsp20.4 mRNA levels were higher in sporulated oocysts than in sporozoites or second-generation merozoites by real-time quantitative PCR, the transcription of EtsHsp20.4 was barely detectable in unsporulated oocysts. Immunolocalization with EtsHsp20.4 antibody showed that EtsHsp20.4 was mainly located on the surface of sporozoites, first-generation merozoites and second-generation merozoites. Following the development of parasites in DF-1 cells, EtsHsp20.4 protein was uniformly dispersed in trophozoites, immature schizonts, and mature schizonts. Malate dehydrogenase thermal aggregation assays indicated that recombinant EtsHsp20.4 had molecular chaperone activity in vitro. These results suggested that EtsHsp20.4 might be involved in sporulation in external environments and intracellular growth of the parasite in the host.


Assuntos
Eimeria tenella/metabolismo , Proteínas de Choque Térmico HSP20/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Galinhas , Clonagem Molecular , DNA Complementar/química , Eimeria tenella/classificação , Eimeria tenella/genética , Eimeria tenella/fisiologia , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP20/química , Proteínas de Choque Térmico HSP20/classificação , Masculino , Chaperonas Moleculares/classificação , Chaperonas Moleculares/genética , Oocistos/fisiologia , Filogenia , RNA de Helmintos/análise , RNA de Helmintos/genética , RNA de Helmintos/isolamento & purificação , RNA Mensageiro/análise , Coelhos , Alinhamento de Sequência , Análise de Sequência de DNA , Esporos de Protozoários/genética
11.
J Integr Neurosci ; 16(4): 385-400, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28891528

RESUMO

Alzheimer's Disease (AD) is one of the commonest neural degeneration in aging population, and has become a global health challenge. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) was reported to effectively improved the damage of patients with neuropathological disorders. In the present study, we investigated the effect of 2-BFI on the improvement of antioxidative, inflammation, and apoptosis in AD rats. Sprague-Dawley rats (2 months old, n=40) were used in this study and after injection of Aß1-42 into hippocampal CA1 (Cornu Ammonis) region, the rats were given high, moderate and low dose of 2-BFI though intraperitoneal (i.p.) injection. Then spatial memory and navigation ability were analyzed by Morrize Water Maze. For the molecular testing, chemical colorimetry, ELISA and immunoblotting were performed to measure the activities of antioxidative enzymes, the abundance of immune cytokines and expression of apoptotic proteins, respectively. Hematoxylin and Eosin staining was used to analyze the pathological changes. We observed that 2-BFI significantly ameliorated the learning and memory abilities in rat models with AD by dosage treatment, as demonstrated by the shorten learning latency and greater times of travel across the platform quadrant. Additionally, reactive oxygen species (ROS) and malondialdehyde (MDA), were decreased after treatment of 2-BFI with dosage dependency, while the activities of superoxidase dismutase (SOD) and (GPX) Glutathione peroxidase were in turn enhanced, suggesting that 2-BFI could protect the antioxidative enzymes and reduce the oxidative stress in the hippocampus. Moreover, the expression of inflammatory factors including TNF-a and IL-1ß were decreased after 2-BFI treatment. Additionally, the neuronal apoptosis was also attenuated, as shown by Western blot results. Taken together, the cognitive impairment in AD rats could be significantly improved by 2-BFI in a dose-dependent manner through suppressing oxidants accumulation, inhibiting of inflammatory response, as well as enhancing the neural viability.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Apoptose/efeitos dos fármacos , Benzofuranos/farmacologia , Imidazóis/farmacologia , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação/patologia , Inflamação/fisiopatologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Nootrópicos/farmacologia , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos , Distribuição Aleatória , Ratos Sprague-Dawley , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Navegação Espacial/efeitos dos fármacos , Navegação Espacial/fisiologia
12.
Exp Parasitol ; 154: 118-26, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25888243

RESUMO

The initiation of translation in eukaryotic cells is stimulated by proteins known as initiation factors (eIFs). A structurally complex eIF composed of multiple subunits, eIF3 has been shown to have various functions in translation in a variety of eukaryotes. Until now, little is known about eIF3 in Eimeria tenella. Based on a previously identified expressed sequence tag(EST), we cloned the eIF3 subunit 7 gene (EteIF3s7) from E. tenella by rapid amplification of the cDNA ends(RACE). The 2278-bp full-length complementary DNA of EteIF3s7 contained a 1716-bp open reading frame (ORF) that encoded a 571-amino acid (aa) polypeptide. The EteIF3s7 protein contained the subunit 7 domain that is characteristic of members of the eIF3 zeta superfamily. The levels of EteIF3s7 messenger RNA and protein were higher in second generation merozoites than in sporulated oocysts, unsporulated oocysts, or sporozoites, and the EteIF3s7 protein was barely detectable in unsporulated oocysts. Our immunofluorescence analysis showed that the EteIF3s7 protein was uniformly distributed throughout the cytoplasm of sporozoites. After sporozoites were incubated in complete medium, the EteIF3s7 protein localized to the anterior region of the parasite. Following the first schizogenous division, the protein was uniformly dispersed in trophozoites, immature schizonts, and mature schizonts, and the EteIF3s7 protein was observed to be closely associated with the parasitophorous vacuole membrane. An anti-rEteIF3s7 polyclonal antibody inhibited the ability of E. tenella to invade DF-1 cells, which suggested that EteIF3s7 might be involved in host cell invasion and required for the growth of the parasite in the host.


Assuntos
Eimeria tenella/química , Fator de Iniciação 3 em Eucariotos/fisiologia , Sequência de Aminoácidos , Animais , Anticorpos Antiprotozoários/imunologia , Sequência de Bases , Linhagem Celular , Embrião de Galinha , Galinhas , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , Relação Dose-Resposta Imunológica , Eimeria tenella/genética , Eimeria tenella/imunologia , Fator de Iniciação 3 em Eucariotos/química , Fator de Iniciação 3 em Eucariotos/genética , Fator de Iniciação 3 em Eucariotos/imunologia , Fibroblastos/parasitologia , Dados de Sequência Molecular , RNA Mensageiro/análise , RNA Mensageiro/isolamento & purificação , RNA de Protozoário/análise , RNA de Protozoário/isolamento & purificação , Coelhos , Organismos Livres de Patógenos Específicos
13.
Arch Orthop Trauma Surg ; 135(2): 209-221, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25519181

RESUMO

INTRODUCTION: This study aimed to investigate the surgical techniques and the clinical efficacy of combined approaches for the treatment of Schatzker type II tibial plateau fractures involving the posterolateral column [lateral and posterolateral columns (LPCs) fractures] in a prospective cohort. MATERIALS AND METHODS: From January 2007 through December 2010, a total of 65 patients with LPCs underwent dual-plate fixation via a combined anterior and posterior approach. The anterior and posterior approaches were the conventional anterolateral approach and a posteromedial inverted L-shaped approach, respectively, with the patients in a floating position. RESULTS: Ultimately, 41 patients were followed up for a mean period of 52.5 months. All fractures healed. The mean time to radiographic bony union was 15.2 weeks and the mean time to full weight-bearing was 18.7 weeks. No parameter associated with knee alignment changed significantly between immediately postoperation and 2 years postoperation. No collapse of the reduced articular surface was detected. Two years postoperation, the mean Hospital for Special Surgery score was 92.3; the mean Short Form-36 score was 90.1, and the mean range of knee motion was 1.7°-123.6° (extension-flexion). Two patients suffered dehiscence of the anterolateral incision and another suffered partial necrosis at the margin of the posteromedial incision postoperatively. All healed in response conservative treatment. Another two patients experienced numbness in the posteromedial inferior region of the calf. No implant loosening, breakage, fixation failure, or other complication was observed during follow-up. CONCLUSIONS: LPCs are not uncommon. Careful preoperative analysis of computed tomography images and impeccable preparation are necessary to avoid neglecting a posterolateral column fracture. It is inappropriate to generalize one scenario for all Schatzker type II fractures: a single approach cannot address all subtypes of these fractures. Dual-plate fixation via a combined approach is an effective treatment for LPCs.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Adulto , Idoso , Placas Ósseas , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
14.
Arch Orthop Trauma Surg ; 134(10): 1369-80, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25077782

RESUMO

OBJECTIVES: The aim of our study is to evaluate the incidence and pathoanatomy of posterolateral fragments and analyze the associated fracture mechanism in bicondylar tibial plateau fractures. METHODS: From 1.1.2008 to 3.15.2012, all patients suffering bicondylar tibial plateau fractures were identified, scanned and analyzed at the Shanghai Clinical Trauma Center. Furthermore cadaver knees were selected into three groups of 30/60/90 knee flexion to simulate the posterolateral tibial plateau fracture by an impact device. RESULTS: One hundred and sixty-four (44.32 %) bicondylar tibial plateau fractures finally satisfied our requirements. Fifty-three and ninety-four cases were measured eventually in the groups of posterolateral split and depression. The posterolateral articular fragment proportion was 15.43 %. The posterolateral articular fragment angle showed an average of 12.94°. The posterolateral fragment cortical height was on average 2.96 cm. The posterolateral sagittal fragment angle averaged at 72.06°. Ninety-four cases were measured in the posterolateral depression group. The average posterolateral articular depression proportion was 16.74 %. The average posterolateral articular depression height was 2.47 cm. In the biomechanical modeling of such kinds of fracture patterns, posterolateral split fractures in 30° and 60° flexion are significantly more than those in 90° flexion. Posterolateral splits combined with anterolateral depression fractures in 30° flexion are significantly more than those in 90° flexion. CONCLUSION: The incidence of posterolateral fractures is 44.32 % in bicondylar tibial plateau fractures. The morphology of posterolateral area can be referenced for the surgeon in the future clinical work. The information is also helpful for the design of locking plate and fracture modeling in biomechanical test. In addition, that posterolateral split and posterolateral depression might be caused by different injury mechanisms. Different angles of knee flexion under the axial impact loading are possibly the interpretations for these two fracture patterns.


Assuntos
Traumatismos do Joelho/patologia , Fraturas da Tíbia/patologia , Adulto , Idoso , Fenômenos Biomecânicos , China/epidemiologia , Feminino , Humanos , Incidência , Traumatismos do Joelho/diagnóstico por imagem , Traumatismos do Joelho/epidemiologia , Traumatismos do Joelho/fisiopatologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Químicos , Tomografia Computadorizada Multidetectores , Amplitude de Movimento Articular , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/epidemiologia , Fraturas da Tíbia/fisiopatologia
15.
Poult Sci ; 103(10): 104146, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39128391

RESUMO

The fatal gouty disease caused by goose astrovirus genotype 2 (GAstV-2) still seriously endangers the goose industry in China, causing great economic losses. However, research on its infection mechanism has progressed relatively slowly. VP70 is the structural protein of GAstV-2 and is closely related to virus invasion and replication. To better understand the role of VP70 during GAstV-2 infection, we used immunoprecipitation and mass spectrometry to identify host proteins that interact with VP70. Here, we report that cellular vimentin (VIM) is a host binding partner of VP70. Site-directed mutagenesis showed that amino acid residues 399 to 413 of VP70 interacted with VIM. Using reverse genetics, we found that VP70 mutation disrupts the interaction of VP70 with VIM, which is essential for viral replication. Overexpression of VIM significantly promoted GAstV-2 replication, while knockdown of VIM significantly inhibited GAstV-2 replication. Laser confocal microscopy showed that VP70 protein expression induced the rearrangement of VIM, gradually aggregating from the original uniform grid to the side of the nucleus, and aggregated the originally dispersed GAstV-2 RNA in VIM. This rearrangement was associated with increased VIM phosphorylation caused by GAstV-2. Meanwhile, blocking VIM rearrangement with acrylamide substantially inhibited viral replication. These results indicate that VIM interacts with VP70 and positively regulates GAstV-2 replication, and VIM-VP70 interaction and an intact VIM network are needed for GAstV-2 replication. This study provides a theoretical basis and novel perspective for the further characterization of the pathogenic mechanism of GAstV-2-induced gouty disease in goslings.


Assuntos
Avastrovirus , Gansos , Doenças das Aves Domésticas , Vimentina , Replicação Viral , Animais , Gansos/virologia , Doenças das Aves Domésticas/virologia , Vimentina/metabolismo , Vimentina/genética , Avastrovirus/genética , Avastrovirus/fisiologia , Avastrovirus/metabolismo , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Genótipo , Proteínas Aviárias/metabolismo , Proteínas Aviárias/genética
16.
Poult Sci ; 103(10): 104143, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39128392

RESUMO

Goose astrovirus (GAstV) has been widespread in China since 2016, causing significant growth inhibition and gout symptoms in goslings and leading to substantial economic losses in the goose industry. To better understand the epidemiological characteristics of GAstV in Guangdong Province, 682 samples were collected from geese with suspected GAstV infection across different regions of Guangdong Province from January 2022 to January 2024. Virus isolation, identification, and genetic evolution analysis were performed. The results showed that all samples were GAstV positive, with 52.64% co-infected with GAstV-1 and GAstV-2, and 42.38% positive for GAstV-2 alone, indicating that GAstV-2 remains the most prevalent subtype. Additionally, three GAstV isolates were identified using molecular detection, immunofluorescence, and transmission electron microscopy on LMH cells or goose embryos. Compared with GDYJ2304 and other reported GAstV-2 strains, the ORF2 region of the GDYJ2210 isolates lacked 3 bases, and the replication ability of GDYJ2210 was significantly higher than that of GDYJ2304. Whole genome sequence alignment and genetic evolution analysis revealed that the GDFS2209 isolate was located in the GAstV-1 branch, with a sequence similarity of 89.70 to 99.00% to GAstV-1 reference strains. The GDYJ2210 and GDYJ2304 isolates were located in the GAstV-2 branch, showing a sequence similarity of 96.80 to 98.90% to GAstV-2 reference strains. These results demonstrated that the GAstV isolates were highly similar to each other despite being prevalent in 5 different regions of Guangdong Province. These findings enhance the understanding of the genetic diversity and evolution of GAstV and may facilitate the development of effective preventive strategies.


Assuntos
Infecções por Astroviridae , Avastrovirus , Gansos , Filogenia , Doenças das Aves Domésticas , Animais , Gansos/virologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Infecções por Astroviridae/epidemiologia , China/epidemiologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/epidemiologia , Avastrovirus/genética , Avastrovirus/isolamento & purificação , Avastrovirus/fisiologia , Gota/veterinária , Gota/virologia , Gota/epidemiologia
17.
Poult Sci ; 103(1): 103177, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37980763

RESUMO

In recent years, the occurrence of fowl adenovirus 2 (FAdV-2) has been on the rise in China, posing a significant threat to the poultry industry. This study aimed to investigate the epidemiology, phylogenetic relationship, genomic characteristics, and pathogenicity of FAdV-2. The epidemiological analysis revealed the detection of multiple FAdV serotypes, including FAdV-1, FAdV-2, FAdV-3, FAdV-4, FAdV-8a, FAdV-8b, and FAdV-11 serotypes. Among them, FAdV-2 exhibited the highest proportion, accounting for 21.05% (8/38). The complete genomes of these 8 FAdV-2 strains were sequenced. Genetic evolution analysis indicated that these FAdV-2 strains formed a separate branch within the FAdV-D group, sharing 94.60 to 97.90% nucleotide similarity with the reference FAdV-2 and FAdV-11 strains. Notably, the recombination analysis revealed that 5 out of the 8 FAdV-2 strains, exhibited recombination events between FAdV-2 and FAdV-11. The recombination regions involved Hexon, Fiber, ORF19 genes and 3' end. Furthermore, pathogenicity experiments demonstrated that recombinant FAdV-2 XX strain is capable of inducing mortality rate of 66.70% and causing more severe hepatitis hydropericardium syndrome (HHS) in 6-wk-old specific-pathogen-free chickens. These findings contribute to our understanding of the prevalence, genomic characteristics, and the pathogenicity of FAdV-2, providing foundations for FAdV-2 vaccine development.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Doenças das Aves Domésticas , Animais , Virulência , Filogenia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/veterinária , Prevalência , Galinhas , Genômica , China/epidemiologia , Doenças das Aves Domésticas/prevenção & controle , Sorogrupo
18.
Heliyon ; 9(11): e22248, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034599

RESUMO

Self-Biased Magnetic Pendulum Array (SBMPA) is an efficient and portable transmitter in ultralow frequency (ULF). The resonance frequency of SBMPA is affected by the magnetic field of the radially magnetized cylindrical permanent magnets. In order to calculate the resonance frequency, the magnetic field model of a single radially magnetized cylindrical permanent magnet is derived based on the concept of magnetic charge. Then, the influence of the demagnetizing field and external magnetic field on the magnetization of permanent magnets is analyzed, and the magnetic field model of SBMPA is established. The results of the magnetic field model are verified through simulation. The average deviation of magnetic field intensity is determined as 0.021%; thus, the magnetic field model and simulation have consistent results. Finally, the influence of the size and distance of permanent magnets on the resonance frequency is analyzed, which could provide theoretical guidance for the dynamic analysis of SBMPA.

19.
Vet Sci ; 10(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37888577

RESUMO

Lumpy skin disease virus (LSDV) infection, accompanied by loss of hide quality, poor reproductive efficiency, consistent degenerative emaciation, and milk yield reduction of animals, causes severe economic implications in endemic zones. The heterologous attenuated goat pox (GTPV) vaccine (AV41 strain) was used in China to prevent LSDV infection. Only a few LSDV detection methods that distinguish LSDV from GTPV vaccine strains have been reported before. For simple, rapid, and specific detection of LSDV, the real-time recombinase polymerase amplification (RPA) method was established with the specific primers and probes designed according to the conserved regions of ORF132 gene sequences. The assay could be finished within 20 min at a constant temperature (39 °C). This method had a limit of detection (LOD) of 15 copies/µL for LSDV and no cross-reaction with the nucleic acids of goat pox virus, infectious bovine rhinotracheitis virus, Pasteurella multocida, and bovine healthy tissue. Furthermore, 43 clinical samples were detected by this method and the real-time PCR recommended by the World Organisation for Animal Health (WOAH), with a kappa value, was 0.94. These results demonstrated that the real-time RPA method for detecting LSDV developed in this study was characterized by high sensitivity and specificity, which has wide application value in the clinical diagnosis and detection of LSDV in China.

20.
Vet Microbiol ; 279: 109677, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36764218

RESUMO

While blocking inflammation is an effective way to ease the symptoms of gout disease in humans, the treatment and prevention of gout in goslings infected with goose astrovirus (GAstV), a recently emergent condition, remain unclear. In this study, we investigated the reprogramming of the host genes as a result of GAstV infection by combining analysis of the global transcriptome and metabolic network pathways in the kidneys of goslings infected with GAstV. We showed that as GAstV replication increased in vivo, the regulation of key enzymes in the host metabolism progressively increased, flowing metabolites into the purine/pyrimidine biosynthesis pathways. Furthermore, we found that GAstV: 1) inhibits the host oxidation-reduction response by inhibiting the expression of the catalase gene; 2) activates the Toll-like receptor 2 pathway to enhance the immune inflammatory response; and 3) activates the key enzyme in lactic acid synthesis to produce lactate accumulation which inhibits the host's antiviral response, so as to facilitate the replication of the virus itself. This study provided the first insight into the overall metabolic requirements of GAstV for replication in vivo by combining transcriptome with metabolic network pathway information.


Assuntos
Infecções por Astroviridae , Avastrovirus , Gota , Doenças das Aves Domésticas , Humanos , Animais , Gansos , Transcriptoma , Filogenia , Avastrovirus/genética , Infecções por Astroviridae/veterinária , Gota/veterinária
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