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1.
Angew Chem Int Ed Engl ; : e202412825, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119836

RESUMO

It is well-established that Pt-based catalysts suffer from the unfavorable linear scaling relationship (LSR) between *OOH and *OH (ΔG(*OOH) = ΔG(*OH) + 3.2 ± 0.2 eV) for the oxygen reduction reaction (ORR), resulting in a great challenge to significantly reduced ORR overpotentials. Herein, we propose a universal and feasible strategy of fluorine-doped carbon supports, which optimize interfacial microenvironment of Pt-based catalysts and thus significantly enhance their reactive kinetics. The introduction of C-F bonds not only weakens the *OH binding energy, but also stabilizes the *OOH intermediate, resulting in a break of LSR. Furthermore, fluorine-doped carbon constructs a local super-hydrophobic interface that facilitates the diffusion of H2O and the mass transfer of O2. Electrochemical tests show that the F-doped carbon-supported Pt catalysts exhibit over 2-fold higher mass activities than those without F modification. More importantly, those catalysts also demonstrate excellent stability in both rotating disk electrode (RDE) and membrane electrode assembly (MEA) tests. This study not only validates the feasibility of tuning the electrocatalytic microenvironment to improve mass transport and to break the scaling relationship, but also provides a universal catalyst design paradigm for other gas-involving electrocatalytic reactions.

2.
Pediatr Infect Dis J ; 43(9): 869-871, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39163300

RESUMO

This is the first reported case of a pediatric patient with tuberculous pleurisy and glucose-6-phosphate dehydrogenase deficiency treated with contezolid concomitantly with other antituberculous drugs. The patient responded well to treatment, and no adverse events were observed. These findings suggest that contezolid may be a potential therapeutic option for tuberculous pleurisy in children and adolescents with glucose-6-phosphate dehydrogenase deficiency.


Assuntos
Antituberculosos , Deficiência de Glucosefosfato Desidrogenase , Tuberculose Pleural , Humanos , Tuberculose Pleural/tratamento farmacológico , Tuberculose Pleural/diagnóstico , Antituberculosos/uso terapêutico , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/tratamento farmacológico , Masculino , Criança , Resultado do Tratamento , Adolescente , Feminino
3.
Heliyon ; 10(13): e33769, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39050432

RESUMO

Objective: Frailty is a significant public health issue facing aging societies and can be reduced by physical activity (PA), but the dose-response relationship between PA and frailty is not clear. This systematic review and dose-response meta-analysis aimed to assess the effect of PA on frailty in adults by aggregating data from observational studies. Methods: PubMed, Embase, Web of Science, Cochrane Library, Scopus, SAGE Reference Online, SinoMed, CINAHL and CNKI were retrieved for articles published before May 2024. After quality evaluation, data on PA and the risk of frailty were extracted. Stata/MP 17.0 was used for dose-response meta-analysis. Results: A total of 15 articles were included, involving 34,754 participants, including 4250 subjects with frailty or pre-frailty. The consequence of the dose-response meta-analysis revealed that compared with those who were not active at all, a 22 % (95 % CI, 16 %-28 %) reduction in the risk of frailty in individuals with 11.25 MET h/week of cumulative activity and a 55 % (95 % CI, 44 %-63 %) reduction in the risk of frailty in those with 22.5 MET h/week of cumulative activity; for higher activity levels (36.75 MET h/week), the risk of frailty was reduced by 68 % (95 % CI, 58 %-76 %) and continued to be reduced as PA volum increased. Conclusions: There is a non-linear dose-response relationship between PA and frailty risk. Even small amounts of PA could reduce the risk of frailty. Meeting the minimum recommended PA target could reduce some risks, and doubling the recommended PA volumes could reduce most risks, which continue to increase as the volum of PA accumulates.

4.
Sci Rep ; 14(1): 13867, 2024 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879665

RESUMO

Fever and diarrhea are key causes of malnutrition, growth and development disorders, and death among children. At present, most studies on the associated factors of fever and diarrhea in children are concentrated in African and South Asian countries, but relevant research in China is very limited. This study was aimed to analyze the two-week prevalence of fever, diarrhea, and coexisting fever and diarrhea among children aged 6-23 months in rural areas of Hunan Province and to explore the associated factors. The survey data of the Nutrition Improvement Program for Children in Poor Areas (NIPCPA) from 2016 to 2023 was used here. NIPCPA is a cross-sectional survey completed annually in Hunan to collect children's nutrition and health indicators. The two-week prevalence rates of fever, diarrhea, and coexisting fever and diarrhea among children aged 6-23 months were 12.2% (2066/16,985), 9.6% (1634/16,985), and 3.2% (542/16,985), respectively. Multivariate logistic regression analysis showed the risks of fever, diarrhea, and coexisting fever and diarrhea were higher among younger children. The high educational level of caregivers, effective consumption of Yingyangbao (a complementary food supplement containing iron, zinc, calcium, vitamins A, D, B1, B2, B12, folic acid, and other micronutrients), and complementary feeding meeting minimum dietary diversity and meeting minimum acceptable diet were protective factors against fever in children, with adjusted odds ratios (aORs) of 0.87 (95%CI: 0.78-0.98), 0.78 (0.69-0.87), 0.73 (0.65-0.82), and 0.74 (0.66-0.84), respectively. Effective consumption of Yingyangbao, and complementary feeding meeting the minimum dietary diversity and meeting minimum acceptable diet were protective factors against diarrhea in children, with aORs of 0.72 (95%CI: 0.63-0.83), 0.79 (0.70-0.91), and 0.80 (0.70-0.92), respectively. Effective consumption of Yingyangbao, and complementary feeding meeting the minimum dietary diversity and meeting minimum acceptable diet were protective factors against coexisting fever and diarrhea among children, with aORs of 0.53 (95%CI: 0.43-0.66), 0.71 (0.58-0.89), and 0.70 (0.56-0.88), respectively. Fever, diarrhea, and the coexisting fever and diarrhea affect one in eight, one in ten, and one in thirty children respectively in rural areas of Hunan. Effective interventions should be actively taken, such as improving the education level of caregivers, enhancing their scientific feeding skills for children, and promoting children's compliance with Yingyangbao consumption, to further reduce the prevalence of fever and diarrhea in children.


Assuntos
Diarreia , Febre , População Rural , Humanos , Lactente , Masculino , Feminino , Febre/epidemiologia , China/epidemiologia , Prevalência , Diarreia/epidemiologia , Estudos Transversais , Fatores de Risco
5.
J Microbiol Methods ; 221: 106928, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583783

RESUMO

The bicistronic expression system that utilizes fluorescent reporters has been demonstrated to be a straightforward method for detecting recombinant protein expression levels, particularly when compared to polyacrylamide gel electrophoresis and immunoblot analysis, which are tedious and labor-intensive. However, existing bicistronic reporter systems are less capable of quantitative measurement due to the lag in reporter expression and its negative impact on target protein. In this work, a plug and play bicistronic construct using mCherry as reporter was applied in the screening of optimal replicon and promoter for Sortase expression in Escherichia coli (E. coli). The bicistronic construct allowed the reporter gene and target open reading frame (ORF) to be co-transcribed under the same promoter, resulting in a highly positive quantitative correlation between the expression titer of Sortase and the fluorescent intensity (R2 > 0.97). With the correlation model, the titer of target protein can be quantified by noninvasively measuring the fluorescent intensity. On top of this, the expression of reporter has no significant effect on the yield of target protein, thus favoring a plug and play design for removing reporter gene to generate a plain plasmid for industrial use.


Assuntos
Escherichia coli , Genes Reporter , Proteínas Luminescentes , Plasmídeos , Regiões Promotoras Genéticas , Proteínas Recombinantes , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Luminescentes/genética , Plasmídeos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteína Vermelha Fluorescente , Fases de Leitura Aberta , Expressão Gênica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Vetores Genéticos , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Regulação Bacteriana da Expressão Gênica , Replicon/genética
6.
Am J Physiol Endocrinol Metab ; 326(6): E856-E868, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38656128

RESUMO

Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.


Assuntos
Doenças Ósseas Metabólicas , Pancreatite Crônica , Humanos , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/metabolismo , Pancreatite Crônica/complicações , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Vitamina K/metabolismo , Animais
7.
Front Pharmacol ; 15: 1342947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348395

RESUMO

Background: Due to the heterogeneity of critically ill patients, the pharmacokinetics of tigecycline are unclear, and the optimal dosing strategy is controversial. Methods: A single-center prospective clinical study that included critically ill patients who received tigecycline was performed. Blood samples were intensively sampled (eight samples each), and plasma drug concentrations were determined. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis and visual predictive checks. Monte Carlo simulation was conducted to optimize the dosage regimen. Results: Overall, 751 observations from 98 patients were included. The final PPK model was a two-compartment model incorporating covariates of creatinine clearance on clearance (CL), body weight on both central and peripheral volumes of distribution (V1 and V2), γ-glutamyl transferase and total bilirubin on intercompartment clearance (Q), and albumin on V2. The typical values of CL, Q, V1 and V2 were 3.09 L/h, 39.7 L/h, 32.1 L and 113 L, respectively. A dosage regimen of 50 mg/12 h was suitable for complicated intra-abdominal infections, but 100 mg/12 h was needed for community-acquired pneumonia, skin and skin structure infections and infections caused by less-susceptive bacteria. Conclusion: The Tigecycline PPK model was successfully developed and validated. Individualized dosing of tigecycline could be beneficial for critically ill patients.

9.
Technol Health Care ; 32(1): 163-179, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37092194

RESUMO

BACKGROUND: Jingshen Xiaoke decoction (JS) was prepared by studying the classic prescriptions of famous scholars in the past dynasties to prevent and treat diabetes. The related mechanism of JS against hyperlipidemia has yet to be revealed. OBJECTIVE: To investigate the mechanism of action of JS in treating diabetes mellitus by using bioinformatics methods. METHODS: A database was used to search the active ingredients and targets of the JS and targets for type 2 diabetes mellitus (T2DM). The protein interaction between the intersection targets, and the constructed the PPI network diagram was analyzed using the STRING database. Furthermore, the gene annotation tool DAVID was used to enrich the intersecting targets for the Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway. Finally, Maestro software was used for molecular docking to verify the binding ability of the active ingredients to the core target genes. RESULTS: A total of 45 active ingredients in JS were screened out corresponding to 239 effective targets, of which 64 targets were potential targets for treating T2DM. The analysis of PPI network diagram analysis revealed that the ingredients' active components are quercetin, ß-sitosterol, stigmasterol, luteolin, and 7-Methoxy-2-methyl isoflavone. GO functional enrichment analysis indicated 186 biological processes (BP), 23 molecular functions (MF) and 13 cellular components (CC). KEGG pathway enrichment analysis revealed the enrichment of 59 signal pathways. The molecular docking results demonstrated that the active ingredients and core targets had a good docking affinity with a binding activity less than -7 kcal/mol. Finally, the western blotting illustrated that JS could up-regulate the liver PI3K/AKT-signaling pathway. CONCLUSION: JS can regulate glucolipid metabolism, reduce the inflammatory response, improve insulin resistance and modulate the immune response through PI3K/AKT signaling pathway treating of T2DM and its complications effects.


Assuntos
Diabetes Mellitus Tipo 2 , Animais , Camundongos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
10.
Gene ; 895: 148028, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38007160

RESUMO

Spastic paraplegia 7 (SPG7) is an m-AAA protease subunit involved in mitochondrial morphology and physiology. However, its function in animal reproduction is yet to be evaluated. In this study, its molecular features, subcellular localization, and expression dynamics were investigated to analyze its potential function in the reproduction of male Phascolosoma esculenta, an economically important marine species in China. The full-length cDNA of P. esculenta spg7 (Pe-spg7) measures 3053 bp and encodes an 853-amino acid protein (Pe-SPG7). Pe-SPG7 includes two transmembrane domains, an AAA domain and a proteolytic domain. Amino acid sequence alignment revealed that SPG7 was conserved during evolution. The mRNA and protein expression of spg7 indicated its involvement in reproduction. Its expression was the highest in coelomic fluid, where spermatids develop, and it was significantly higher in the breeding stage than in the nonbreeding stage. SPG7 was mainly found in the mitochondria of spermatids in the coelomic fluid, indicating that it functions in this organelle in spermatids. Immunofluorescence experiments showed that SPG7 was expressed and colocalized in the mitochondria during spermiogenesis, suggesting its involvement in P. esculenta spermiogenesis. Therefore, SPG7 may participate in spermiogenesis by functioning in the mitochondria and regulate the reproduction of male P. esculenta. This study provided insights into the function of SPG7 in animal reproduction and P. esculenta gametogenesis.


Assuntos
Mitocôndrias , Paraplegia Espástica Hereditária , Animais , Masculino , ATPases Associadas a Diversas Atividades Celulares/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Espermatogênese/genética , Paraplegia Espástica Hereditária/genética , Metaloendopeptidases/genética
11.
Wei Sheng Yan Jiu ; 52(6): 972-978, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38115668

RESUMO

OBJECTIVE: To estimate the status of complementary feeding among infants and young children aged 6-23 months in rural areas of Hunan Province. The association between infant and young child feeding indicators and child undernutrition were assessed. METHODS: A total of 1220 infants and young children aged 6-23 months from 24 investigated places of 6 cities in Hunan Province were selected by multi-stage stratified sampling for physical measurement, hemoglobin(Hb) test and caregiver interview. Complementary diet was analyzed according to the World Health Organization's definition of infant and young child feeding indicators. Z-scores were used to elevate nutrition status. Logistic regression models were used to explore the influencing factors of the nutritional status. RESULTS: The prevalence rates of underweight, stunting, wasting, overweight, obesity and anemia were 3.6%, 4.8%, 2.7%, 10.5%, 2.0% and 16.3%. The percentage of infants and young children aged 6-23 months in rural areas of Hunan Province who get minimum dietary diversity, minimum meal frequency, and minimum acceptable diet was 43.3%, 68.5% and 28.1%. None of the individual infant and young child feeding indicators showed significant association with undernutrition, except minimum meal frequency for obesity and anemia. CONCLUSION: The nutritional status of infants and young children in rural areas of Hunan Province has improved, but the anemia problem is still serious. Complementary feeding frequency is closely associated with anemia for infants and young children.


Assuntos
Anemia , Desnutrição , Lactente , Criança , Humanos , Pré-Escolar , Feminino , Estado Nutricional , População Rural , Fenômenos Fisiológicos da Nutrição do Lactente , Desnutrição/epidemiologia , Anemia/epidemiologia , Hemoglobinas , Obesidade , Comportamento Alimentar , Aleitamento Materno
12.
Sci Rep ; 13(1): 13003, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563290

RESUMO

The effect of double filtration plasma apheresis (DFPP) on improving the outcomes of patients with hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains unclear. The aim of this study was to evaluate the relationship between the initiation time of DFPP and the risk of persistent organ failure (POF) in an HTG-AP cohort in China. We retrospectively evaluated data from HTG-AP patients treated with DFPP 48 h after diagnosis between January 2017 and January 2022. Comparisons across tertiles of the interval from diagnosis to completion of one DFPP session (DTD) were analysed. Logistic regression models and restricted cubic splines (RCS) were used to determine the correlation between the DTD time and risk of POF. Of the 89 patients enrolled, 46 patients (51.69%) suffered POF in the first week of HTG-AP. DFPP was initiated at a median of 17 h after the diagnosis was confirmed. The patients in the highest tertile of DTD time had a significantly increased prevalence of POF. After multivariate adjustment, the logistic regression models found a significant decrease in the odds ratios (OR) of POF from the highest to the lowest DTD tertile (P for trend = 0.006). Moreover, the RCS curves showed a nonlinear relationship in the adjusted OR of POF and DTD time, which remained relatively low and flat during the early DTD time but increased sharply afterwards. Early initiation of DFPP treatment correlates with a reduced risk of POF in HTG-AP patients.


Assuntos
Remoção de Componentes Sanguíneos , Hiperlipidemias , Hipertrigliceridemia , Pancreatite , Humanos , Pancreatite/etiologia , Pancreatite/terapia , Estudos Retrospectivos , Doença Aguda , Insuficiência de Múltiplos Órgãos/epidemiologia , Hipertrigliceridemia/complicações , Hipertrigliceridemia/terapia
13.
Int J Mol Sci ; 23(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36555170

RESUMO

Mitochondria can fuse or divide, a phenomenon known as mitochondrial dynamics, and their distribution within a cell changes according to the physiological status of the cell. However, the functions of mitochondrial dynamics during spermatogenesis in animals other than mammals and fruit flies are poorly understood. In this study, we analyzed mitochondrial distribution and morphology during spermiogenesis in Sipuncula (Phascolosoma esculenta) and investigated the expression dynamics of mitochondrial fusion-related protein MFN2 and fission-related protein DRP1 during spermiogenesis. The mitochondria, which were elliptic with abundant lamellar cristae, were mainly localized near the nucleus and distributed unilaterally in cells during most stages of spermiogenesis. Their major axis length, average diameter, cross-sectional area, and volume are significantly changed during spermiogenesis. mfn2 and drp1 mRNA and proteins were most highly expressed in coelomic fluid, a spermatid development site for male P. esculenta, and highly expressed in the breeding stage compared to in the non-breeding stage. MFN2 and DRP1 expression levels were higher in components with many spermatids than in spermatid-free components. Immunofluorescence revealed that MFN2 and DRP1 were consistently expressed and that MFN2 co-localizes with mitochondria during spermiogenesis. The results provide evidence for an important role of mitochondrial dynamics during spermiogenesis from morphology and molecular biology in P. esculenta, broadening insights into the role of mitochondrial dynamics in animal spermiogenesis.


Assuntos
GTP Fosfo-Hidrolases , Mitocôndrias , Animais , Masculino , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Espermatogênese/genética , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Hidrolases/metabolismo , Dinâmica Mitocondrial , Dinaminas/genética , Dinaminas/metabolismo , Mamíferos/metabolismo
14.
Comput Intell Neurosci ; 2022: 2721490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602624

RESUMO

Grey wolf optimizer (GWO) is a global search algorithm based on grey wolf hunting activity. However, the traditional GWO is prone to fall into local optimum, affecting the performance of the algorithm. Therefore, to solve this problem, an equalized grey wolf optimizer with refraction opposite learning (REGWO) is proposed in this study. In REGWO, the issue about the low swarm population variety of GWO in the late iteration is well overcome by the opposing learning of refraction. In addition, the equilibrium pool strategy reduces the likelihood of wolves going to the local extremum. To investigate the effectiveness of REGWO, it is evaluated on 21 widely used benchmark functions and IEEE CEC 2019 test functions. Experimental results show/ that REGWO performs better than the other competitors on most benchmarks.


Assuntos
Algoritmos , Aprendizagem , Simulação por Computador , Probabilidade
15.
Gastroenterol Res Pract ; 2022: 8333794, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340692

RESUMO

Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as a surrogate marker of inflammation with prognostic value in various diseases. Our objective was to investigate the predictive value of the NLR as an indicator of persistent organ failure (POF) in patients with hypertriglyceridemic pancreatitis (HTGP). Methods: We retrospectively reviewed the data from patients with HTGP between 2016 and 2019. The NLR was obtained at admission. The diagnostic performance of the NLR for POF was evaluated by the area under the receiver operator characteristics curve (AUROC). Multivariate logistic regression determined whether elevated NLR was independently associated with POF. Results: Of the 446 patients enrolled, 89 (20.0%) developed POF. Patients with POF showed a significantly higher NLR than those without POF (P < 0.001). A positive trend for the association across increasing NLR quartiles and the incidence of POF was observed (P trend < 0.001). The AUROC of NLR to predict POF was 0.673 (95% confidence interval, 0.627-0.716). With a cut-off of NLR > 6.56, the sensitivity and specificity were 73.0% and 55.7%, respectively. Multivariate analysis suggested that high NLR (>6.56) was independently associated with POF (odds ratio, 2.580; 95% confidence interval, 1.439-4.626; P = 0.001). Patients with a high NLR (>6.56) had a worse overall clinical course in HTGP. Conclusion: Elevated NLR was significantly associated with an increased risk of developing POF and could be an early independent predictor of POF in patients with HTGP.

16.
Front Endocrinol (Lausanne) ; 13: 1068555, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36589810

RESUMO

Objective: Codonopsis Radix and Polygonati Rhizoma (CRPR) has a good hypoglycemic effect. The aims of the present study were to investigate the effect of CRPR on high-fat/high-sugar diet (HFHSD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) mice as well as to investigate the involved mechanism. Methods: A T2DM mouse model was generated by combining HFHSD and STZ. After the model was established, normal and model groups received the same volume of normal saline intragastrically, and the negative control group was treated with metformin (200 mg/kg·BW). The low, medium, and high CRPR groups received four consecutive weeks of oral gavage with CRPR doses of 2.5, 5, and 10 g/kg·BW, respectively, during the course of the study. Body weight and fasting blood glucose (FBG) were measured on a weekly basis. Enzyme-linked immunosorbent assay (ELISAs) were used to evaluate the serum and liver samples. Hematoxylin and eosin (H&E) staining was utilized to observe the pathological status of the liver and pancreas. Western blot (WB) analysis was performed to evaluate the protein expression levels of PI3K, p-PI3K, AKT, and p-AKT. Results: Compared to model mice, each treatment group had significantly elevated levels of FBG, total cholesterol (TC), and triacylglycerol (TG) (P<0.01 and P<0.05, respectively). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced in the treatment groups compared to the model group (P<0.01). Compared to the model group, fasting insulin (FINS) levels were elevated in all groups of CRPR (P<0.05), and there were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) in both the low-dose and high-dose CRPR groups (P<0.05). H&E staining indicated that CRPR treatment reduced organ enlargement, improved liver lipid accumulation, and repaired islet injury in T2DM mice. Moreover, WB analysis demonstrated that all CRPR groups significantly upregulated the protein expression of IRS1, p-GSK3ß, PI3K, p-Akt and p-FOXO1(P<0.05) as well as significantly downregulated p-IRS1 and FOXO1 protein expression (P<0.05). Conclusion: The present study demonstrated that CRPR effectively improves the metabolic disturbance of lipids, repairs damaged liver tissues, repairs damaged pancreatic tissues, and reduces insulin resistance (IR) in T2DM mice. The mechanism of action may be associated with upregulation of the IRS1/PI3K/AKT signaling pathway and inhibition of IRS1 phosphorylation.


Assuntos
Codonopsis , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Codonopsis/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Transdução de Sinais , Colesterol/efeitos adversos
17.
Medicine (Baltimore) ; 101(49): e32165, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36626523

RESUMO

Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.


Assuntos
Neoplasias da Mama , Medicamentos de Ervas Chinesas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Simulação de Acoplamento Molecular , Gynostemma , Farmacologia em Rede , Mapas de Interação de Proteínas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
18.
Reprod Fertil Dev ; 33(7): 455-465, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33858563

RESUMO

Vitellogenesis is essential for oocyte maturation. Vitellogenin (Vtg), a yolk precursor protein, plays an important role in oogenesis and vitellogenesis. Chinese hook snout carp Opsariichthys bidens is an economically important freshwater fish in China whose reproductive and developmental biology are not well understood. In this study, we undertook histological analysis to examine ovary development and oogenesis in O. bidens. The ovaries were divided into Stages II-V and oocytes were divided into perinuclear oocytes, cortical alveoli oocytes, vitellogenic oocytes and mature oocytes. Full-length cDNA sequences were cloned of two vtg genes from the liver of O. bidens, namely Ob-vtgAo1 and Ob-vtgC. Ob-vtgAo1 and Ob-vtgC cDNA are made up of 4136 and 4392 bases respectively and encode proteins containing 1335 and 1250 amino acids respectively. Ob-vtgAo1 contains three yolk protein domains: lipovitellin heavy chain (LvH), phosvitin (Pv) and lipovitellin light chain (LvL), whereas Ob-VtgC contains LvH and LvL, which are incomplete Vtgs. Ob-vtgAo1 and Ob-vtgC mRNA expression was significantly higher in the liver of O. bidens than in all other tissues. In oocytes of Stage II-III ovaries, yolk granules are almost absent and ovarian and hepatic Ob-vtgAo1 and Ob-vtgC expression is low. At Stage IV, the oocyte is filled with yolk granules and ovarian and hepatic Ob-vtgAo1 and Ob-vtgC expression is significantly increased. Collectively, these findings help us better understand vitellogenesis in O. bidens.


Assuntos
Carpas/metabolismo , Clonagem Molecular , Proteínas de Peixes/metabolismo , Oócitos/metabolismo , Oogênese , Ovário/metabolismo , Vitelogênese , Vitelogeninas/metabolismo , Animais , Carpas/genética , Carpas/crescimento & desenvolvimento , Feminino , Proteínas de Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Ovário/crescimento & desenvolvimento , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima , Vitelogênese/genética , Vitelogeninas/genética
19.
ACS Appl Mater Interfaces ; 13(13): 15168-15177, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33760597

RESUMO

Single-atom catalysts effectively integrate the respective advantages of homogeneous and heterogeneous catalysts and are a pioneering research frontier in catalysis by virtue of their maximized utility of metal atoms and distinct atomic configuration. However, development of such catalysts is still in the early stages. Herein, atomically dispersed vanadium (V) sites that are coordinated by N atoms and inlaid within N-incorporated porous carbon networks were prepared through a top-down strategy by annealing a V-containing metal-organic framework, NH2-MIL-101(V), followed by acid etching. The resulting V-N-C-600 catalyst exhibits unexpected catalytic reactivity, selectivity, and robust stability for the direct aerobic oxidation of benzylamine to generate N-benzylidene benzylamine with molecular oxygen under mild conditions. The turnover frequency reaches 53.9 h-1, which is much superior to those achieved over the commercial V2O5 and state-of-the-art non-noble metal heterogeneous catalysts reported in the literature. Kinetic analysis reveals a low activation energy barrier (37 kJ mol-1) for the benzylamine oxidation and indicates that a carbocationic intermediate is involved in the reaction mechanism. The synergistic effect between the isolated V single-atomic sites and N-doped hierarchically porous carbon network boosts the performance of V-N-C-600. Moreover, V-N-C-600 exhibits a wide generality for the efficient synthesis of a set of symmetrical imines, unsymmetrical imines, and imine derivatives.

20.
Anim Reprod Sci ; 222: 106608, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33039822

RESUMO

Spermatogenesis is important for male fertility, but has not been well-studied in Opsariichthys bidens, an economically important freshwater fish in China. In this study, there was investigation of the cytological features of spermatogenesis in O. bidens using light microscopy, transmission electron microscopy, and immunofluorescence detection of microtubules. O. bidens has tubular testis. Spermatogenesis in O. bidens is of the cystic type, in which the spermatogenic cells develop into spermatozoa in cysts. There was asynchronous development of primary spermatocytes within a single cyst. Spermiogenesis was classified as Type I, which develops into a Type I aquasperm with an oval nucleus, a small and simple midpiece, a flagellum and no acrosome. There was a nuage in spermatogonia, spermatocytes, and spermatids in different developmental stages of spermatids which may have important functions in fish spermatogenesis. Furthermore, microtubule dynamics may be involved in spermatid reshaping, material transport, and polar distribution of organelles during spermiogenesis.


Assuntos
Cyprinidae/fisiologia , Espermatogênese/fisiologia , Espermatozoides/citologia , Testículo/citologia , Animais , Aquicultura , China , Citoesqueleto/fisiologia , Água Doce , Masculino , Meiose , Microscopia Eletrônica , Microtúbulos/ultraestrutura , Células de Sertoli/citologia , Células de Sertoli/ultraestrutura , Espermátides/citologia , Espermátides/ultraestrutura , Espermatócitos/citologia , Espermatócitos/ultraestrutura , Espermatogônias/citologia , Espermatogônias/ultraestrutura , Espermatozoides/ultraestrutura , Testículo/ultraestrutura
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