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OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.
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OBJECTIVE: Children with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) are characterized by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT), lupus anticoagulant positivity and low prothrombin (factor II, FII) levels. Bleeding or thrombosis tendencies related to LAHPS in children can occur due to the development of anti-prothrombin antibodies that are usually linked to autoimmune or infectious diseases. METHODS: We report three pediatric cases of LAHPS and describe details on their clinical symptoms, laboratory characteristics, treatment. PubMed, Medline, and Web of Science searches were conducted on LAHPS in children between 1960 and 2023; articles in English were included. RESULTS: The coagulation profile revealed prolonged PT and APTT, with low prothrombin levels (19.4%, 21.0% and 12.9%, respectively) and positive lupus anticoagulant in 3 pediatric cases. Fifty-nine relevant articles reported 93 pediatric LAHPS cases (mean age: 9 years (0.8-17 years)); 63 females and 30 males, 87 patients presented with minor to severe bleeding diathesis, and 3 patients presented with thrombosis events. Among 48 patients ≥9 years old, 36 had SLE; among 45 patients <9 years, 29 had viral infection. When all patients were divided into two groups based on age, associated disease, and factor II level, Pearson's χ2 tests were performed, p =.00, and there was clinical significance between autoimmune and infectious disease in patients ≥9 years old and <9 years old, and in patients FII level ≤10% and >10%. LAHPS patients with autoimmune disease had a protracted course and needed prolonged treatment with immune-modulating therapy, while those patients with infectious disease resolved spontaneously or needed short-term immune-modulating therapy. CONCLUSION: LAHPS caused by autoimmune disease are common in patients ≥9 years old, especially SLE, and FII level ≤10% is often reported in patients caused by autoimmune disease, suggesting that children ≥9 years old diagnosed with LAHPS-related autoimmune disease should pay special attention to the FII level. While LAHPS caused by infectious disease is more frequently observed in patients <9 years, especially viral infection. Early diagnostic investigations are critical to differentiating LAHPS caused by autoimmune or infectious disease, as the prognosis, treatment and outcome are distinct.
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Síndrome Antifosfolipídica , Doenças Autoimunes , Hipoprotrombinemias , Lúpus Eritematoso Sistêmico , Feminino , Masculino , Humanos , Criança , Pré-Escolar , Hipoprotrombinemias/diagnóstico , Inibidor de Coagulação do Lúpus , Protrombina , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Doenças Autoimunes/diagnósticoRESUMO
Rosacea is a chronic inflammatory skin disease characterized by facial erythema, papules, pustules, telangiectasia, and flushing. The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway appears to play a role in the pathogenesis of rosacea. Our study preliminarily explored the efficacy of JAK inhibitor tofacitinib in the treatment of rosacea. We retrospectively reviewed the cases of 21 patients with rosacea who were treated with oral tofacitinib. Patients received oral tofacitinib 5 mg as either monotherapy or adjunctive therapy. We have observed that 15 out of 21 patients (71.4%) patients experienced significant regression of erythema on the face (IGA ≤ 1), and a mean change of -2.24 in the Investigator's Global Assessment (IGA) score was significant improvement from baseline. Treatment with oral tofacitinib might be a potentially effective treatment to ameliorate the symptoms of rosacea.
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Rosácea , Humanos , Estudos Retrospectivos , Rosácea/diagnóstico , Rosácea/tratamento farmacológico , Rosácea/patologia , Eritema/diagnóstico , Imunoglobulina ARESUMO
BACKGROUND: Social isolation, i.e., the deprivation of social contact, is a highly stressful circumstance that affects behavioral and functional brain development in social animals. Cognitive flexibility, one of the essential executive brain function that facilitates survival problem solving, was reported to be impaired after social isolation rearing. However, most of the previous studies have focused on the constrained aspect of flexibility and little is known about the unconstrained aspect. In the present study, the unconstrained cognitive flexibility of Kunming mice (Mus musculus, Km) reared in isolation was examined by a novel digging task. The exploratory behavior of the mice was also tested utilizing the hole-board and elevated plus maze tests to explain the differences in cognitive flexibility between the mice reared socially and in isolation. RESULTS: The results demonstrated that the isolated mice had a higher success rate in solving the novel digging problem and showed a higher rate of exploratory behavior compared with the controls. Linear regression analysis revealed that the time it took the mice to solve the digging problem was negatively associated with exploratory behavior. CONCLUSIONS: The data suggest that social isolation rearing improves unconstrained cognitive flexibility in mice, which is probably related to an increase in their exploratory behavior. Such effects may reflect the behavioral and cognitive evolutionary adaptations of rodents to survive under complex and stressful conditions.
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Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disease. Mitochondrial modifiers are proposed to modify the phenotypic expression of primary LHON-associated mitochondrial DNA (mtDNA) mutations. In this study, we demonstrated that the LHON susceptibility allele (m.14502T > C, p. 58I > V) in the ND6 gene modulated the phenotypic expression of primary LHON-associated m.11778G > A mutation. Twenty-two Han Chinese pedigrees carrying m.14502T > C and m.11778G > A mutations exhibited significantly higher penetrance of optic neuropathy than those carrying only m.11778G > A mutation. We performed functional assays using the cybrid cell models, generated by fusing mtDNA-less ρo cells with enucleated cells from LHON patients carrying both m.11778G > A and m.14502T > C mutations, only m.14502T > C or m.11778G > A mutation and a control belonging to the same mtDNA haplogroup. These cybrids cell lines bearing m.14502T > C mutation exhibited mild effects on mitochondrial functions compared with those carrying only m.11778G > A mutation. However, more severe mitochondrial dysfunctions were observed in cell lines bearing both m.14502T > C and m.11778G > A mutations than those carrying only m.11778G > A or m.14502T > C mutation. In particular, the m.14502T > C mutation altered assemble of complex I, thereby aggravating the respiratory phenotypes associated with m.11778G > A mutation, resulted in a more defective complex I. Furthermore, more reductions in the levels of mitochondrial ATP and increasing production of reactive oxygen species were also observed in mutant cells bearing both m.14502T > C and m.11778G > A mutation than those carrying only 11778G > A mutation. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between primary and secondary mtDNA mutations.
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DNA Mitocondrial/genética , Genes Modificadores/genética , Predisposição Genética para Doença , Mutação/genética , Atrofia Óptica Hereditária de Leber/genética , Adolescente , Adulto , Alelos , Povo Asiático , Criança , Pré-Escolar , Complexo I de Transporte de Elétrons/genética , Feminino , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/patologia , NADH Desidrogenase/biossíntese , NADH Desidrogenase/genética , Atrofia Óptica Hereditária de Leber/patologia , Linhagem , FenótipoRESUMO
Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2.
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DNA Mitocondrial/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Mutação , Atrofia Óptica Hereditária de Leber/genética , Tirosina-tRNA Ligase/genética , Alelos , Sequência de Bases , Estudos de Casos e Controles , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , DNA Mitocondrial/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Exoma , Regulação da Expressão Gênica , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Neurônios/enzimologia , Neurônios/patologia , Atrofia Óptica Hereditária de Leber/enzimologia , Atrofia Óptica Hereditária de Leber/patologia , Linhagem , Fenótipo , Tirosina-tRNA Ligase/química , Tirosina-tRNA Ligase/metabolismoRESUMO
StkP and PhpP of Streptococcus pneumoniae have been confirmed to compose a signaling couple, in which the former is a serine/threonine (Ser/Thr) kinase while the latter was annotated as a phosphotase. StkP has been reported to be involved in penicillin-binding protein (PBP)-independent penicillin resistance of S. pneumoniae. However, the enzymatic characterization of PhpP and the role of PhpP in StkP-PhpP couple remain poorly understood. Here we showed that 1/4 minimal inhibitory concentration (MIC) of penicillin (PCN) or cefotaxime (CTX), the representatives of ß-lactam antibiotics, could induce the expression of stkP and phpP genes and phosphorylation of StkP in PCN/CTX-sensitive strain ATCC6306 and three isolates of S. pneumoniae (MICs: 0.02-0.5⯵g/ml). The product of phpP gene hydrolyzed PP2C type Ser/Thr phosphotase-specific RRA (pT)VA phosphopeptide substrate with the Km and Kcat values of 277.35⯵moL/L and 0.71â¯S-1, and the hydrolytic activity was blocked by sodium fluoride, a PP2C type Ser/Thr phosphatase inhibitor. The phosphorylation levels of StkP in the four phpP gene-knockout (ΔphpP) mutants were significantly higher than that in the wild-type strains. In particular, the MICs of PCN and CTX against the ΔphpP mutants were significantly elevated as 4-16⯵g/ml. Therefore, our findings confirmed that sublethal PCN and CTX act as environmental inducers to cause the increase of phpP and stkP gene expression and StkP phosphorylation. PhpP is a PP2C type Ser/Thr protein phosphatase responsible for dephosphorylation of StkP. Knockout of the phpP gene results in a high level of StkP phosphorylation and PBP-independent PCN/CTX resistance of S. pneumoniae.
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Antibacterianos/farmacologia , Cefotaxima/farmacologia , Penicilinas/farmacologia , Fosfoproteínas Fosfatases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Streptococcus pneumoniae/efeitos dos fármacos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Perfilação da Expressão Gênica , Testes de Sensibilidade Microbiana , Fosfoproteínas Fosfatases/genética , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Streptococcus pneumoniae/metabolismoRESUMO
Angiotensin II (Ang II), an effective component of renin-angiotensin system, plays a pivotal role in cardiac fibrosis, which may further contribute to heart failure. Single-stranded DNA-binding protein 1 (SSBP1), a DNA damage response protein, regulates both mitochondrial function and extracellular matrix remodeling. In this study, we aim to investigate the role of SSBP1 in cardiac fibrosis that is induced by Ang II. We infused C57BL/6J mice with vehicle or Ang II and valsartan using implanted osmotic mini-pumps. Moreover, heart function was examined by echocardiography and cardiac fibrosis was analyzed via picrosirus red staining. The expression of COL1A1, COL3A1, SSBP1, p53, Nox1, and Nox4 was analyzed via qRT-PCR and/or immunoblots. The SSBP1 expression was manipulated via SSBP1 shRNA and pcDNA3.1/SSBP1 plasmids, while the p53 expression was enhanced via AdCMV-p53 infection. The exposure to Ang II increased the mouse heart weight, systolic blood pressure, interventricular septal thickness diastolic (IVSTD) and left ventricular end posterior wall dimension diastolic (LVPWD), which were counteracted by valsartan. While cardiac fibrosis was induced with Ang II treatment, it was relieved using valsartan. Furthermore, Ang II treatment caused mitochondrial dysfunction, oxidative stress, and down-regulated SSBP1 expression. The knockdown of SSBP1 increased cardiac fibroblast proliferation, collagen expression, and decreased p53 expression, which was impeded via SSBP1 overexpression. Moreover, the forced expression of p53 abated the fibroblast proliferation and collagen expression that was induced by Ang II. To summarize, SSBP1 was down-regulated by Ang II and implicated in cardiac fibroblast proliferation and collagen expression partly via the p53 protein.
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Angiotensina II/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Colágenos Fibrilares/metabolismo , Coração/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Miofibroblastos/efeitos dos fármacos , Vasoconstritores/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Biomarcadores/metabolismo , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Colágeno Tipo III/metabolismo , Fibrose , Coração/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Miofibroblastos/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Valsartana/farmacologiaRESUMO
CONTEXT: Cryptoporus volvatus (Peck) Hubb grows wild in China, and its fruiting bodies have been used traditionally to treat asthma and bronchitis. OBJECTIVES: This study evaluates the anti-inflammatory effect of Cryptoporus polysaccharides (CP) extracted from fruiting bodies of C. volvatus on lipopolysaccharide (LPS)-induced pro-inflammatory factors and the signaling pathways involved in human alveolar epithelial cells. MATERIALS AND METHODS: To evaluate the effects of CP on LPS-induced pro-inflammatory factors, A549 cells were pre-incubated with CP 1, 10, and 100 µg/ml for 1 h and then stimulated with LPS 10 µg/ml for 24 h. The expression of pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), Toll-like receptor 2 (TLR2), and phosphorylation of ERK1/2, p38, and NF-κB p65 were measured by q-PCR, ELISA, and western blotting. RESULTS: CP decreased LPS-induced mRNA expression of MCP-1, TNF-α, and IL-1ß (IC50 = 83.3, 85.2, and 91.6 µg/ml, respectively) and their correspondent protein expression (IC50 = 88.6, 76.4, and 81.6 µg/ml, respectively). Investigation of potential mechanisms indicated that CP 100 µg/ml reduced LPS-induced expression of TLR2 mRNA (66.9%, p < 0.01) and protein (63.2%, p < 0.01) that was a result of the decreased pro-inflammatory factors. LPS induction increased the expression of TLR2 and the phosphorylation of p38 and ERK1/2, NF-kB p65 concomitantly. CP 100 µg/ml inhibited the LPS-induced phosphorylation of the signaling proteins (p < 0.05). CONCLUSIONS: This suggests that CP pretreatment down-regulates LPS-mediated inflammation in lung epithelial cells. This study further confirmed that CP is a potential anti-inflammatory drug for the treatment of airway inflammatory diseases.
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Anti-Inflamatórios/farmacologia , Coriolaceae/química , Citocinas/genética , Células Epiteliais/efeitos dos fármacos , Polissacarídeos Fúngicos/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Receptor 2 Toll-Like/metabolismo , Anti-Inflamatórios/isolamento & purificação , Western Blotting , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/imunologia , Relação Dose-Resposta a Droga , Células Epiteliais/imunologia , Polissacarídeos Fúngicos/isolamento & purificação , Humanos , Lipopolissacarídeos/farmacologia , Alvéolos Pulmonares/citologia , Alvéolos Pulmonares/imunologia , Transdução de Sinais , Fatores de TempoRESUMO
BACKGROUND: Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT. METHODS: EMT was induced in mice and pulmonary epithelial cells by exposure of CS and cigarette smoke extract (CSE) respectively. RESULTS: Treatment of pulmonary epithelial cells with CSE elevated Rac1 expression associated with increased TGF-ß1 release. Blocking TGF-ß pathway restrained CSE-induced changes in EMT-related markers. Pharmacological inhibition or knockdown of Rac1 decreased the CSE exposure induced TGF-ß1 release and ameliorated CSE-induced EMT. In CS-exposed mice, pharmacological inhibition of Rac1 reduced TGF-ß1 release and prevented aberrations in expression of EMT markers, suggesting that Rac1 is a critical signaling molecule for induction of CS-stimulated EMT. Furthermore, Rac1 inhibition or knockdown abrogated CSE-induced Smad2 and Akt (PKB, protein kinase B) activation in pulmonary epithelial cells. Inhibition of Smad2, PI3K (phosphatidylinositol 3-kinase) or Akt suppressed CSE-induced changes in epithelial and mesenchymal marker expression. CONCLUSIONS AND GENERAL SIGNIFICANCE: Altogether, these data suggest that CS initiates EMT through Rac1/Smad2 and Rac1/PI3K/Akt signaling pathway. Our data provide new insights into the fundamental basis of EMT and suggest a possible new course of therapy for COPD and lung cancer.
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Transição Epitelial-Mesenquimal , Neuropeptídeos/fisiologia , Nicotiana/efeitos adversos , Alvéolos Pulmonares/patologia , Fumaça/efeitos adversos , Proteínas rac1 de Ligação ao GTP/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteína Smad2/fisiologia , Fator de Crescimento Transformador beta1/análise , Fator de Crescimento Transformador beta1/biossínteseRESUMO
Metacercariae of Clonorchis sinensis (20 per mouse) were given orally to Kunming mice. The mice were sacrificed at 0.5, 1, 2, 4, 8, 16, 32, and 64 h after infection. The results showed that the excystation of the metacercariae occurred in the stomach and small intestine, mainly in the duodenum. Excystation occurred mainly at 2, 4, 8, and 16 h post-infection. Juveniles were found in hepatic duct on 0.5 h post-infection. The number of juveniles increased with the extension of infection time, which kept unchanged in hepatic duct from 32 h after infection.
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Clonorchis sinensis , Metacercárias , Animais , Clonorquíase , CamundongosRESUMO
Cigarette smoke contains reactive oxygen (ROS) that can cause oxidative stress. It increases the number of apoptotic and necrotic lung cells and further induces the development of chronic airway disease. In this study, we investigated the effects of cigarette smoke extract (CSE) on apoptosis in human bronchial epithelial cells (BEAS-2B). CSE exposure induced ROS generation and p38 mitogen-activated protein kinase (MAPK) activation that are associated with the activation of apoptosis-regulating signal kinase 1 (ASK-1). N-acetylcysteine (a general antioxidant) attenuated the CSE-induced ASK-1 and p38 MAPK activation and cell apoptosis, suggesting a triggering role of ROS in ASK-1/p38 MAPK activation during apoptotic progression. In contrast, the inhibition and knockdown of p38 attenuated the expression of anti-oxidant master NF-E2-related factor 2 (Nrf-2) and CSE-induced apoptosis, suggesting that p38 MAPK modulates Nrf-2 expression and presumably prevents cell apoptosis. Taken together, the data presented in this manuscript demonstrate that the ROS-dependent ASK-1/p38 signaling cascade regulates CSE-induced BEAS-2B cell apoptosis. In addition, anti-oxidative Nrf-2 is also up-regulated by the ROS/p38 signaling cascade in this progression.
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Apoptose/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/agonistas , Mucosa Respiratória/efeitos dos fármacos , Fumar/efeitos adversos , Regulação para Cima/efeitos dos fármacos , Acetilcisteína/farmacologia , Elementos de Resposta Antioxidante/efeitos dos fármacos , Antioxidantes/farmacologia , Brônquios/enzimologia , Brônquios/metabolismo , Linhagem Celular , Misturas Complexas/antagonistas & inibidores , Misturas Complexas/toxicidade , Ativação Enzimática/efeitos dos fármacos , Inativação Gênica , Humanos , MAP Quinase Quinase Quinase 5/antagonistas & inibidores , MAP Quinase Quinase Quinase 5/química , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Mucosa Respiratória/enzimologia , Mucosa Respiratória/metabolismo , Fumaça , Produtos do Tabaco , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/química , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
From May to November 2013, a total of 1175 wild freshwater fishes were collected from the rivers of Chuoer, Yalu, Wuyuer, Alun, and Yin in Nenjiang River basin Qiqihaer City, and examined for metacercariae by direct compression method. The metacercariae were collected by artificial digestion method. Forty Kunming mice were infected with 30-40 metacercariae of Clonorchis sinensis. The mice were sacrificed 36 days after infection, and the adult worms were collected from bile duct, and observed under microscope. The results showed that a total of 1 175 fishes, belonging to nine species were taken from the Nenjiang basin of Qiqihaer region. The infection rate of Clonorchis sinensis metacercariae was 51.2% (602/1 175). All the species were infected besides Silurus asotus, and the highest prevalence (82.7%, 91/149) was found in Longnose gudgeon and the lowest (7.1%, 6/84) in Perccottus glenii. Among the rivers, the highest prevalence of metacercariae was in Wuyuer River. (65.7%, 218/332), and the lowest was in Alun River and Yin River (24.1%, 67/278) (P<0.05). Each part of the body in the Carassius auratus and Pseudorasbora parva were susceptible for metacercariae. The main infection site in Longnose gudgeon was the fish scales, and C. sinensis metacercaria was first discovered in the brain tissue of Phoxinus lagowskii. The experimental results showed that the adult worms of C. sinensis were found in the hepatic bile duct of the mice, with an infection rate of 85.0% (34/40). The suckers, digestive system and reproductive system of C. sinensis were visible clearly.
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Clonorquíase/epidemiologia , Clonorchis sinensis , Doenças dos Peixes/epidemiologia , Metacercárias , Animais , Doenças dos Peixes/parasitologia , Peixes , Camundongos , Prevalência , RiosRESUMO
Freshwater fish were caught from Nenjiang River in Qiqihaer City, and examined for metacercariae of Clonorchis sinensis by the artificial digestion (pepsin-HCl) method. The metacercariae (35-40) were given orally into stomach to each Kunming mouse of infection group (50 mice). The mice in control group were given the same amount of normal saline. The mice were sacrificed on the 5th, 10th, 15th, 20th, 25th, and 30th day after infection. Worms were collected, fixed and stained with carmine acetate, and observed under microscope. The egg-laying capacity of C. sinensis was observed in mice. 96%(48/50) mice were infected with metacercariae of C. sinensis. The recovery rate of adult worms on the 5th, 10th, 15th, 20th, 25th, and 30th day post-infection was 42.1%, 52.6%, 63.2%, 62.2%, 63.3%, and 63.2%, respectively. The first appearance of eggs in utero and feces was on the 15th and 20th day after infection, respectively. The branch of testis in worms was observed after 20 days of infection.
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Clonorquíase , Animais , Clonorchis sinensis , Fezes , Peixes , Masculino , Camundongos , Rios , TestículoRESUMO
AIM: To investigate the relationship between maternal overweight and fetal insulin resistance. MATERIAL AND METHODS: Nineteen overweight and 30 lean pregnant women were recruited in the present study. Maternal and fetal insulin resistance were determined by measuring sex hormone binding globulin (SHBG) concentrations in maternal venous or umbilical cord serum, respectively. Maternal age, gestational age, height, pre-gravidity weight, pre-partum weight, as well as fetal gender, birth weight, birth height, and head circumference were collected as clinical data. RESULTS: Fetuses of overweight mothers had larger birth weight (3.58±0.55kg vs 3.32±0.42, adjusted P=0.006) and lower SHBG concentrations (26.64±3.65 vs 34.36±7.84, adjusted P=0.007) than those of lean mothers after values were adjusted for potential cofactors. Fetal SHBG level was negatively correlated with pre-gravidity body mass index (R=-0.392, adjusted P=0.025) and weight gain during pregnancy (R=-0.332, adjusted P=0.026) even with adjustment for potential cofactors. Among the 29 pregnant women with gestational diabetes mellitus, the overweight mothers had higher H1AC levels than their lean counterparts (6.47±0.44 vs 5.74±0.52, adjusted P=0.004). CONCLUSION: Intrauterine insulin resistance is more prominent in fetuses of overweight mothers, an effect that is decreased by weight gain control during pregnancy.
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Peso ao Nascer/fisiologia , Diabetes Gestacional/metabolismo , Feto/metabolismo , Resistência à Insulina/fisiologia , Sobrepeso/metabolismo , Adulto , Índice de Massa Corporal , Feminino , Idade Gestacional , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , GravidezRESUMO
Background: Previous studies have reported that the incidence of pediatric inflammatory bowel disease (IBD) is related to vitamin D, but it is still unclear. This study intends to calculate the relationship between pediatric IBD and vitamin D. Methods: A comprehensive literature search from inception to January 2023 was performed in the PubMed, EMBASE, Medline, Web of Science, and Google Scholar databases. Relevant data were extracted as required and used for subsequent calculations. Results: Sixteen papers were included, and there was no significant difference between the average vitamin D level in IBD patients and healthy controls. In addition, the overall pooled results showed that C-reactive protein (CRP) was 2.65 higher before vitamin D supplementation than after supplementation [SMD = 2.65, 95% CI = (2.26, 3.04)]. Moreover, patients with IBD in remission were 0.72 higher before vitamin D supplementation than after supplementation [OR = 0.72, 95% CI = (0.52, 1.00)]. Conclusion: This study suggested that there was no obvious relationship between pediatric IBD and vitamin D, while vitamin D supplementation can improve disease activity. Therefore, follow-up still needs many prospective studies to confirm the relationship between pediatric IBD and vitamin D.
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We reported here the clinical, genetic, and molecular characterization of Leber's hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families.
Assuntos
DNA Mitocondrial/genética , Mitocôndrias/genética , Mutação , Atrofia Óptica Hereditária de Leber/genética , RNA de Transferência/genética , Adolescente , Adulto , Animais , Povo Asiático/genética , Sequência de Bases , Bovinos , Criança , Feminino , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Linhagem , RNA de Transferência/química , Análise de Sequência , Xenopus laevis , Adulto JovemRESUMO
OBJECTIVE: To investigate the clinical characteristics of Leber hereditary optic neurology (LHON) patients with different primary site mutation. METHODS: Four hundred and fourteen patients with optic neuropathy were divided into three groups: clinically diagnosed LHON group (group A), probable LHON group (group B), optic neuropathy of unknown reason group (group C). Visual acuity (VA), colour vision, Intraocular pressure (IOP), virtual field and visual evoked potential (VEP) were tested for all the patients. Some (64 cases) had optical coherence tomography (OCT) measurement. Mutations of mtDNA were detected for all the groups, and clinical analysis were carried out emphatically in the patients with the 11778 mutation confirmed by gene assessment. T paired test was used to evaluate two group patients of different Mitochondrial DNA mutation. RESULTS: Gene mutations were found in 215 of the 414 patients (52%). Approximately 93% (199/255) of the patients were caused by the common primary mutations (11778, 14484, 3460 mutation), in which 100% mutation (106/106) in group A, 65% (91/139) in group B, and 11% (18/169) in group C. No cases were diagnosed with confirmed LHON in the patients with unilateral optic neuropathy. Fundus examination in 334 eyes of 167 cases showed pseudo papilledema (54 eyes), normal (67 eyes), pale disc or pale on the temporal side of the optic disc (213 eyes). On the basis data of OCT from 64 patients and 84 normal person, RNFL was found thickening at the early stage and thinning gradually at the later stage in the LHON patients. But, the RNFL thickness of patients with 1-2 years history was not significantly different from the patients with over 2 years history(P = 0.051), and there was no difference among the patients with different mitochondrial DNA mutations. The initial mean VA of patients with the 14484 mutation and 11778 mutation were 3.6 ± 0.65, 3.75 ± 0.54 (t = 0.536, P > 0.05), but the follow-up VA were 4.29 ± 0.55 (t = 4.034, P < 0.001) and 3.93 ± 0.49 respectively (t = 1.857, P > 0.05). CONCLUSIONS: The symptoms and fundus manifestation were similar in the LHOH patients with different primary site mutation. Gene mutation analysis is helpful to assess the prognosis of visual acuity.
Assuntos
DNA Mitocondrial , Atrofia Óptica Hereditária de Leber/diagnóstico , Atrofia Óptica Hereditária de Leber/genética , Adolescente , Adulto , Análise Mutacional de DNA , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Acuidade Visual , Adulto JovemRESUMO
To clarify the mechanisms underlying the improvement of Trichoderma on Chinese wolfberry (Lycium chinense) growth under saline stress, we analyzed the effects of application of organic fertilizer, Trichoderma agent and fertilizer on nitrogen uptake, assimilation, accumulation and use efficiency in Chinese wolfberry, based on a pot experiment with coastal saline soil. The organic fertilizer was the sterilization substance of Trichoderma fertilizer without viable Trichoderma, without any difference in the content of nutrients (such as nitrogen, phosphorus and potassium) between them. The results showed that the application of organic fertilizer, Trichoderma agent and ferti-lizer significantly increased NO3- and NH4+ influx rate in meristematic zone and NO3- influx rate in maturation zone of roots. The magnitude of such enhancement was greater in the application with Trichoderma fertilizer than organic fertilizer. Compared with the control, the application of Trichoderma agent and fertilizer significantly increased root, stem and leaf biomass and nitrogen content as well as plant nitrogen accumulation, strengthened root and leaf nitrate reductase, nitrite reductase and glutamine synthetase activities, and elevated nitrogen uptake efficiency, photosynthetic rate, stable carbon isotope abundance and photosynthetic nitrogen use efficiency. For all those variables, the beneficial effect was obviously stronger in the application with Trichoderma fertilizer than organic fertilizer. Therefore, Trichoderma facilitated nitrogen uptake, assimilation and accumulation in Chinese wolfberry under saline stress, improved photosynthetic carbon fixation ability and nitrogen use efficiency, and ultimately promoted plant growth.
Assuntos
Lycium , Trichoderma , Isótopos de Carbono , Fertilizantes/análise , Glutamato-Amônia Ligase , Nitrito Redutases , Nitrogênio/análise , Fósforo , Potássio , SoloRESUMO
BACKGROUND: Elderly patients tend to have poor self-efficacy and poor confidence in postoperative rehabilitation for hip fractures, and are prone to negative emotions, which affect treatment compliance. AIM: To evaluate the effects of evidence-based intervention on postoperative fear, compliance, and self-efficacy in elderly patients with hip fractures. METHODS: A total of 120 patients with hip fracture surgically treated from June 2018 to June 2020 at the orthopedic department of our hospital were selected and divided into intervention and routine groups (n = 60 each) according to different nursing methods. The basic rehabilitation methods of the two groups were consistent, but patients in the intervention group received evidence-based nursing interventions at the same time. Differences between groups in the scores of motion phobia, pain fear, rehabilitation training compliance, self-efficacy, nursing satisfaction, and hip joint function were compared before and after the intervention. RESULTS: Before the intervention, there were no statistically significant differences in motion phobia and pain fear scores between the groups (all P > 0.05). However, motion phobia scores at 1 wk after intervention initiation (P < 0.05), and pain fear scores at 1 wk and 2 wk after intervention initiation (all P < 0.05), were significantly lower in the intervention group than in the routine group. On the first day of intervention, there was no significant difference in rehabilitation treatment compliance between the groups (P > 0.05); however, at 2 wk after intervention initiation, rehabilitation compliance was significantly better in the intervention group than in the routine group (P < 0.05). Before the intervention, there were no statistically significant differences in the scores for the two self-efficacy dimensions (overcoming difficulties and rehabilitation exercise self-efficacy) and the total self-efficacy score between the groups (all P > 0.05). After 2 wk of intervention, the scores for these two dimensions of self-efficacy and the total self-efficacy score were significantly higher in the intervention group than in the routine group (all P < 0.05). At 3 and 6 mo after surgery, hip function as evaluated by the Harris hip score, was significantly better in the intervention group than in the routine group (P < 0.05). Additionally, overall nursing satisfaction was significantly higher in the intervention group than in the routine group (P < 0.05). CONCLUSION: Evidence-based nursing intervention can alleviate fear of postoperative rehabilitation in elderly patients who underwent hip fracture surgery, and improve rehabilitation treatment compliance and patient self-efficacy, which promote hip function recovery.