Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 192
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34571535

RESUMO

In recent years, synthesizing drugs powered by artificial intelligence has brought great convenience to society. Since retrosynthetic analysis occupies an essential position in synthetic chemistry, it has received broad attention from researchers. In this review, we comprehensively summarize the development process of retrosynthesis in the context of deep learning. This review covers all aspects of retrosynthesis, including datasets, models and tools. Specifically, we report representative models from academia, in addition to a detailed description of the available and stable platforms in the industry. We also discuss the disadvantages of the existing models and provide potential future trends, so that more abecedarians will quickly understand and participate in the family of retrosynthesis planning.


Assuntos
Inteligência Artificial , Aprendizado Profundo
2.
Int J Clin Pract ; 2024: 5113990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322112

RESUMO

Objective: We conducted a meticulous bioinformatics analysis leveraging expression data of 226 PANRGs obtained from previous studies, as well as clinical data from AML patients derived from the HOVON database. Methods: Through meticulous data analysis and manipulation, we were able to categorize AML cases into two distinct PANRG clusters and subsequently identify differentially expressed genes (PRDEGs) with prognostic significance. Furthermore, we organized the patient data into two corresponding gene clusters, allowing us to investigate the intricate relationship between the risk score, patient prognosis, and the immune landscape. Results: Our findings disclosed significant associations between the identified PANRGs, gene clusters, patient survival, immune system, and cancer-related biological processes and pathways. Importantly, we successfully constructed a prognostic signature comprising nineteen genes, enabling the stratification of patients into high-risk and low-risk groups based on individually calculated risk scores. Furthermore, we developed a robust and practical nomogram model, integrating the risk score and other pertinent clinical features, to facilitate accurate patient survival prediction. Our comprehensive analysis demonstrated that the high-risk group exhibited notably worse prognosis, with the risk score proving to be significantly correlated with infiltration of most immune cells. The qRT-PCR results revealed significant differential expression patterns of LGR5 and VSIG4 in normal and human leukemia cell lines (HL-60 and MV-4-11). Conclusions: Our findings underscore the potential utility of PANoptosis-based molecular clustering and prognostic signatures as predictive tools for assessing patient survival in AML.


Assuntos
Leucemia Mieloide Aguda , Humanos , Imunoterapia , Aprendizado de Máquina , Análise de Dados , Bases de Dados Factuais , Prognóstico
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 435-443, 2024 Jun.
Artigo em Zh | MEDLINE | ID: mdl-38953268

RESUMO

With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on diseases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in modification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing factors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the research progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.


Assuntos
Doenças Cardiovasculares , Lisina , Processamento de Proteína Pós-Traducional , Doenças Cardiovasculares/metabolismo , Humanos , Lisina/metabolismo , Ácido Succínico/metabolismo
4.
Toxicol Appl Pharmacol ; 472: 116570, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37268026

RESUMO

Bone cancer pain is a difficult-to-treat pathologic condition that impairs the patient's quality of life. The effective therapy options for BCP are restricted due to the unknown pathophysiology. Transcriptome data were obtained from the Gene Expression Omnibus database and differentially expressed gene extraction was performed. DEGs integrated with pathological targets found 68 genes in the study. Butein was discovered as a possible medication for BCP after the 68 genes were submitted to the Connectivity Map 2.0 database for drug prediction. Moreover, butein has good drug-likeness properties. To collect the butein targets, we used the CTD, SEA, TargetNet, and Super-PRED databases. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed butein's pharmacological effects, indicating that butein may aid in treating BCP by altering the hypoxia-inducible factor, NF-kappa B, angiogenesis, and sphingolipid signaling pathways. Moreover, the pathological targets integrated with drug targets were obtained as the shared gene set A, which was analyzed by ClueGO and MCODE. Biological process analysis and MCODE algorithm further analyzed that BCP related targets were mainly involved in signal transduction process and ion channel-related pathways. Next, we integrated targets related to network topology parameters and targets of core pathways, identified PTGS2, EGFR, JUN, ESR1, TRPV1, AKT1 and VEGFA as butein regulated hub genes by molecular docking, which play a critical role in its analgesic effect. This study lays the scientific groundwork for elucidating the mechanism underlying butein's success in the treatment of BCP.


Assuntos
Neoplasias Ósseas , Dor do Câncer , Medicamentos de Ervas Chinesas , Osteossarcoma , Humanos , Farmacologia em Rede , Simulação de Acoplamento Molecular , Qualidade de Vida , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Biologia Computacional
5.
Mol Cell Biochem ; 478(12): 2695-2719, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36913150

RESUMO

Since ferroptosis was first described as an iron-dependent cell death pattern in 2012, there has been increasing interest in ferroptosis research. In view of the immense potential of ferroptosis in treatment efficacy and its rapid development in recent years, it is essential to track and summarize the latest research in this field. However, few writers have been able to draw on any systematic investigation into this field based on human body organ systems. Hence, in this review, we provide a comprehensive description of the latest progress in unveiling the roles and functions, as well as the therapeutic potential of ferroptosis, in treating diseases from the aspects of 11 human body organ systems (including the nervous system, respiratory system, digestive system, urinary system, reproductive system, integumentary system, skeletal system, immune system, cardiovascular system, muscular system, and endocrine system) in the hope of providing references for further understanding the pathogenesis of related diseases and bringing an innovative train of thought for reformative clinical treatment.


Assuntos
Ferroptose , Humanos , Corpo Humano , Morte Celular , Ferro
6.
World J Surg ; 47(6): 1548-1561, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36882637

RESUMO

BACKGROUND: Liver cancer resection is an effective but complex way to treat liver cancer, and complex anatomy is one of the reasons for the difficulty of surgery. The use of 3D technology can help surgeons cope with this dilemma. This article intends to conduct a bibliometric analysis of the role of 3D technology in liver cancer resection. METHODS: (TS = (3D) OR TS = (three-dimensional)) AND (TS = (((hepatic) OR (liver)) AND ((cancer) OR (tumor) OR (neoplasm)))) AND (TS = (excision) OR TS = (resection)) was used as a search strategy for data collection in the Web of Science (WoS) Core Collection. CiteSpace, Carrot2 and Microsoft Office Excel were used for data analysis. RESULTS: Three hundred and eighty-eight relevant articles were obtained. Their annual and journal distribution maps were produced. Countries/regions and institutions collaboration, author collaboration, references co-citations and their clusters and keywords co-occurrences and their clusters were constructed. Carrot2 cluster analysis was performed. CONCLUSIONS: There was an overall upward trend in the number of publications. China's contribution was greater, and the USA had greater influence. Southern Med Univ was the most influential institution. However, the cooperation between institutions still needs to be further strengthened. Surgical Endoscopy and Other Interventional Techniques was the most published journal. Couinaud C and Soyer P were the authors with the highest citations and centrality, respectively. "Liver planning software accurately predicts postoperative liver volume and measures early regeneration" was the most influential article. 3D printing, 3D CT and 3D reconstruction may be the mainstream of current research, and augmented reality (AR) may be a future hot spot.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Tecnologia , Bibliometria
7.
Aging Clin Exp Res ; 35(10): 2039-2049, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37368163

RESUMO

BACKGROUND: Osteoporosis is a degenerative disease defined by low bone mineral density, has a high prevalence, and causes fractures at multiple sites throughout the body, greatly affecting the quality of patients. α-Klotho is an endocrine factor involved in the regulation of various metabolic processes in humans, and its role in bone metabolism has attracted widespread attention. The relationship between α-klotho and bone mineral density has not been uniformly recognized, and no large-scale correlation analysis has been conducted in the middle-aged and elderly population. OBJECTIVE: To determine the relationship between α-klotho and bone mineral density in middle-aged and elderly people. METHODS: Population data of 3120 individuals aged 40-79 years were obtained from the NHANES database for the period 2011-2016. Regression analysis was performed using a general linear model with serum α-klotho as the independent variable and total bone mineral density, thoracic bone mineral density, lumbar bone mineral density, pelvic bone mineral density, and trunk bone mineral density as the dependent variables, respectively. The generalized additive model was also used for smoothing curve fitting and threshold effect analysis. RESULTS: Serum α-klotho was positively correlated with total bone mineral density at lg (Klotho) < 2.97 and with thoracic bone mineral density at lg (Klotho) > 2.69 (ß = 0.05, p = 0.0006), and negatively correlated (ß = -0.27, p = 0.0341) with lumbar bone mineral density at lg (Klotho) < 2.69. It also positively correlated with trunk bone mineral density (ß = 0.027, p = 0.03657) and had no segmental effect but did not correlate with pelvic bone mineral density. The positive association of serum α-klotho with those aged 40-49 years, female, non-Hispanic White, and without hypertension was clearer. In the population with diabetes, a significantly positive association between total (ß = 0.15, p = 0.01), thoracic (ß = 0.23, p = 0.0404), and lumbar (ß = 0.22, p = 0.0424) bone mineral density and α-klotho was observed. CONCLUSIONS: α-Klotho has different relationships with total, thoracic, lumbar, and trunk bone mineral density. Among them, the positive correlation between α-klotho and trunk bone mineral density is more valuable for predicting osteoporosis. The significant effect of α-klotho on bone mineral density in diabetes patients suggests its potential as a predictive marker of diabetes progression.


Assuntos
Densidade Óssea , Osteoporose , Humanos , Idoso , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Densidade Óssea/fisiologia , Estudos Transversais , Absorciometria de Fóton , Inquéritos Nutricionais , Vértebras Lombares
8.
Neurochem Res ; 47(7): 1791-1798, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35426597

RESUMO

Gangliosides are important components of the neuronal cell membrane and play a vital role in the development of neurons and the brain. They participate in neurotransmission and are considered as the structural basis of learning and memory. Gangliosides participate in several and important physiological processes, such as cell differentiation, cell signaling, neuroprotection, nerve regeneration and apoptosis. The stability of ion concentration in excitable cells is particularly important in the maintenance of a steady state of cells and in the regulation of physiological functions. Ion concentration has been found to be related to the ganglioside's regulation in many neurological diseases, and several studies have found that they can stabilize intracellular ion concentration by regulating ion channels, which highlights their important regulatory role in neuronal excitability and synaptic transmission. Gangliosides can influence some forms of ion transport, by directly binding to ion transporters or through indirect binding and activation of transport proteins via appropriate signaling pathways. Therefore, the important and special role of gangliosides in the homeostasis of ion concentration is becoming a hot topic in the field and a theoretical basis in promoting help gangliosides use as key drugs for the treatment of nervous system diseases.


Assuntos
Gangliosídeos , Doenças do Sistema Nervoso , Encéfalo/metabolismo , Gangliosídeos/metabolismo , Humanos , Regeneração Nervosa , Doenças do Sistema Nervoso/metabolismo , Neurônios/metabolismo , Transdução de Sinais
9.
J Nanobiotechnology ; 20(1): 201, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473604

RESUMO

Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from ß-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing.


Assuntos
Células Endoteliais , Hidrogéis , Animais , Becaplermina , Colágeno/metabolismo , Células Endoteliais/metabolismo , Epitopos , Camundongos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Cicatrização
10.
BMC Pediatr ; 22(1): 697, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36471266

RESUMO

BACKGROUND AND OBJECTIVES: Vaccine is the most essential avenue to prevent hepatitis B virus (HBV) infection in infants and preschool children in China, with the largest populations carrying HBV in the world. This study aimed to evaluate the factors associating the response level of anti-HBs in children, providing instructions for HBV prevention clinically. METHODS: The children taking physical examinations in the Third Xiangya Hospital from January 2013 to April 2020 were recruited. Telephone follow-up were adopted to collect further information. Univariate logistic regression was used to analyse the relationship between age and anti-HBs expression. Grouping by age and anti-HBs expression, we used chi-square test and T test to compare qualitative and quantitative data between positive group and negative group in each age subgroup. The meaningful variables (P < 0.10) in chi-square test or T test were further assessed with collinearity and chosen for univariate and multivariate logistic regression analysis by the stepwise backward maximum likelihood method (αin = 0.05, αout = 0.10). RESULTS: A total of 5838 samples (3362 males, 57.6%) were enrolled. In total, the incidence of negative anti-HBs increased with age[OR = 1.037(1.022-1.051)]. Multivariate logistic regression analysis illustrated that anemia[OR = 0.392(0.185-0.835)], age[OR = 2.542(1.961-3.295)] and Vit D[OR = 0.977(0.969-0.984)] in 0.5-2.99 years subgroup, Zinc deficiency[OR = 0.713(0.551-0.923] and age[OR = 1.151(1.028-1.289)] in 3-5.99 years subgroup, Vit D[OR = 0.983(0.971-0.995)] in 12-18 years subgroup had significant association with anti-HBs. CONCLUSIONS: This retrospective study illustrated that age, anemia status, zinc deficiency and vitamin D were associated with anti-HBs expression in specific age groups of children, which could serve as a reference for the prevention of HBV.


Assuntos
Vacinas contra Hepatite B , Hepatite B , Masculino , Lactente , Pré-Escolar , Humanos , Antígenos de Superfície da Hepatite B , Estudos Retrospectivos , Anticorpos Anti-Hepatite B , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , China/epidemiologia , Zinco , Vírus da Hepatite B
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(3): 463-471, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35791945

RESUMO

Lipid droplet (LD) are multifunctional organelles which take part into intracellular lipid metabolism,mainly consisting of a neutral lipid core,a single-layer phospholipid shell,and LD-related protein (LRP).LRP on the shell can regulate the storage,transport,and metabolism of lipid.The imbalance of LD regulation could cause the abnormality of lipid metabolism,leading to the blood lipid changes and immune disorders.The available studies have demonstrated that LRP are capable of influencing the lipid metabolism in heart and atherosclerosis (AS) by regulating the physical processes in myocardial and vascular cells.This article reviewed the recent studies about LD in heart and vessels,and illustrated the effects of LD on myocardial cells,the formation of foam cells,and the development of atherosclerosis.Furthermore,we summarized the relationship between LD and cardiovascular diseases,providing new insights for the treatment of such diseases based on LD.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Gotículas Lipídicas , Miócitos Cardíacos , Perilipinas
12.
J Nanobiotechnology ; 19(1): 417, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903236

RESUMO

Clinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core-shell structure was designed. Metal-organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS.


Assuntos
Anti-Inflamatórios , Materiais Biomiméticos , Osso e Ossos/efeitos dos fármacos , Nanomedicina , Síndrome Nefrótica/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Cloreto de Cálcio/química , Cloreto de Cálcio/metabolismo , Resistência a Medicamentos , Feminino , Ácido Glicirrízico/química , Ácido Glicirrízico/metabolismo , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Osteoporose/metabolismo
13.
Med Sci Monit ; 27: e930032, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33820904

RESUMO

In December 2019, pneumonia of unknown cause broke out, and currently more than 150 countries around the world have been affected. Globally, as of 5: 46 pm CET, 6 November 2020, the World Health Organization (WHO) had reported 48 534 508 confirmed cases of COVID-19, including 1 231 017 deaths. The novel coronavirus disease (COVID-19) outbreak, caused by the SARS-CoV-2 virus, is the most important medical challenge in decades. Previous research mainly focused on the exploration of lung changes. However, with development of the disease and deepening research, more and more patients showed cardiovascular diseases, even in those without respiratory symptoms, and some researchers have found that underlying cardiovascular diseases increase the risk of infection. Although the related mechanism is not thoroughly studied, based on existing research, we speculate that the interaction between the virus and its receptor, inflammatory factors, various forms of the stress response, hypoxic environment, and drug administration could all induce the development of cardiac adverse events. Interventions to control these pathogenic factors may effectively reduce the occurrence of cardiovascular complications. This review summarizes the latest research on the relationship between COVID-19 and its associated cardiovascular complications, and we also explore possible mechanisms and treatments.


Assuntos
COVID-19/epidemiologia , Doenças Cardiovasculares/epidemiologia , COVID-19/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/virologia , Humanos , Pulmão/patologia , Miocárdio/patologia , Pandemias , SARS-CoV-2/isolamento & purificação , Organização Mundial da Saúde
14.
Aging Clin Exp Res ; 33(11): 3123-3134, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32141009

RESUMO

BACKGROUND: HSPC (hematopoietic stem/progenitor cell) aging was closely associated with the organism aging, senile diseases and hematopoietic related diseases. Therefore, study on HSPC aging is of great significance to further elucidate the mechanisms of aging and to treat hematopoietic disease resulting from HSPC aging. Little attention had been paid to mRNA splicing as a mechanism underlying HSPC senescence. RESULTS: We used our lab's patented in vitro aging model of HSPCs to analyze mRNA splicing relevant protein alterations with iTRAQ-based proteomic analysis. We found that not only the notable mRNA splicing genes such as SR, hnRNP, WBP11, Sf3b1, Ptbp1 and U2AF1 but also the scarcely reported mRNA splicing relevant genes such as Rbmxl1, Dhx16, Pcbp2, Pabpc1 were significantly down-regulated. We further verified their gene expressions by qRT-PCR. In addition, we reported the effect of Spliceostatin A (SSA), which inhibits mRNA splicing in vivo and in vitro, on HSPC aging. CONCLUSIONS: It was concluded that mRNA splicing emerged as an important factor for the vulnerability of HSPC aging. This study improved our understanding of the role of mRNA splicing in the HSPC aging process.


Assuntos
Células-Tronco Hematopoéticas , Proteômica , RNA Mensageiro/genética
15.
Genomics ; 112(6): 4000-4008, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32634468

RESUMO

Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) that lack a 5' end cap or a 3' end poly-(A) tail and form a circular structure through covalent bonds. Compared to linear RNAs, circRNAs are more conservative and stable, and their distribution is spatiotemporally regulated. circRNAs, as a new type of competitive endogenous RNA (ceRNA), are involved in many disease processes and are also related to the occurrence and development of tumors. Over the past three years, the role of circRNAs in hematological malignancies has received increasing attention. Related research has shown that circRNAs may regulate the occurrence and development of hematological malignancies and contribute to drug resistance through a variety of molecular mechanisms. Therefore, to lay the foundation and point out directions for further research on circRNAs, this article systematically reviews the research progress on circRNAs in leukemia, lymphoma, and myeloma.


Assuntos
Neoplasias Hematológicas/fisiopatologia , RNA Circular/fisiologia , Humanos
16.
Pharm Biol ; 59(1): 1045-1057, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34362291

RESUMO

CONTEXT: HuoXue QianYang QuTan Recipe (HQQR) is used to manage hypertension and cardiac remodelling, but the mechanism is elusive. OBJECTIVE: To determine the mechanism of HQQR on obesity hypertension (OBH)-related myocardial fibrosis. MATERIALS AND METHODS: OBH models were prepared using spontaneously hypertensive rats (SHRs) and divided (n = 6) into saline, low-dose (19.35 g/kg/d) HQQR, high-dose (38.7 g/kg/d) HQQR, and valsartan (30 mg/kg/d) groups for 10 weeks. Systolic blood pressure (SBP), and Lee's index were measured. Heart tissues were examined by histology. HQQR's effects were examined on cardiac fibroblasts (CFs) stimulated with angiotensin II and treated with HQQR, a caspase-1 inhibitor, siNLRP3, and oeNLRP3. RESULTS: HQQR(H) reduced SBP (201.67 ± 21.00 vs. 169.00 ± 10.00), Lee's index (321.50 ± 3.87 vs. 314.58 ± 3.88), and left ventricle mass index (3.26 ± 0.27 vs. 2.71 ± 0.12) in vivo. HQQR reduced percentage of fibrosis area (18.99 ± 3.90 vs. 13.37 ± 3.39), IL-1ß (10.07 ± 1.16 vs. 5.35 ± 1.29), and inhibited activation of NLRP3/caspase-1/IL-1ß pathway. HQQR also inhibiting the proliferation (1.09 ± 0.02 vs. 0.84 ± 0.01), fibroblast to myofibroblast transition (14.74 ± 3.39 vs. 3.97 ± 0.53), and collagen deposition (Col I; 0.50 ± 0.02 vs. 0.27 ± 0.05 and Col III; 0.48 ± 0.21 vs. 0.26 ± 0.11) with different concentrations selected based on IC50 in vitro (all ps < 0.05). NLRP3 interference further confirmed HQQR inhibiting NLRP3 inflammasome signalling. CONCLUSION: HQQR blunted cardiac fibrosis development in OBH and suppressed CFs proliferation by directly interfering with the NLRP3/caspase-1/IL-1ß pathway.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fibrose/tratamento farmacológico , Coração/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Angiotensina II/farmacologia , Animais , Caspase 1/metabolismo , Inibidores de Caspase , Proliferação de Células/efeitos dos fármacos , Fibrose/induzido quimicamente , Hidroxiprolina/sangue , Hidroxiprolina/metabolismo , Hipertensão/metabolismo , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Masculino , Miocárdio/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Cultura Primária de Células , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
17.
Cell Mol Neurobiol ; 40(8): 1405-1416, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32162200

RESUMO

Voltage-gated sodium channels are crucial mediators of neuronal damage in ischemic and excitotoxicity disease models. Fenamates have been reported to have anti-inflammatory properties following a decrease in prostaglandin synthesis. Several researches showed that fenamates appear to be ion channel modulators and potential neuroprotectants. In this study, the neuroprotective effects of tolfenamic acid, flufenamic acid, and mefenamic acid were tested by glutamate-induced injury in SH-SY5Y cells. Following this, fenamates' effects were examined on both the expression level and the function of hNav1.1 and hNav1.2, which were closely associated with neuroprotection, using Western blot and patch clamp. Finally, the effect of fenamates on the expression of apoptosis-related proteins in SH-SY5Y cells was examined. The results showed that both flufenamic acid and mefenamic acid exhibited neuroprotective effects against glutamate-induced injury in SH-SY5Y cells. They inhibited peak currents of both hNav1.1 and hNav1.2. However, fenamates exhibited decreased inhibitory effects on hNav1.1 when compared to hNav1.2. Correspondingly, the inhibitory effect of fenamates was found to be consistent with the level of neuroprotective effects in vitro. Fenamates inhibited glutamate-induced apoptosis through the modulation of the Bcl-2/Bax-dependent cell death pathways. Taken together, Nav1.2 might play a part in fenamates' neuroprotection mechanism. Nav1.2 and NMDAR might take part in the neuroprotection mechanism of the fenamates. The fenamates inhibited glutamate-induced apoptosis through modulation of the Bcl-2/Bax-dependent cell death pathways.


Assuntos
Fenamatos/farmacologia , Ácido Glutâmico/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , ortoaminobenzoatos/farmacologia , Ácido Glutâmico/metabolismo , Humanos , Fármacos Neuroprotetores , Técnicas de Patch-Clamp/métodos , Canais de Sódio Disparados por Voltagem/metabolismo
18.
Med Sci Monit ; 26: e923767, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32294078

RESUMO

BACKGROUND During February 2020, the coronavirus disease 2019 (COVID-19) epidemic in Hubei Province, China, was at its height, requiring isolation of the population. This study aimed to compare the emotional state, somatic responses, sleep quality, and behavior of people in Hubei Province with non-endemic provinces in China during two weeks in February 2020.  MATERIAL AND METHODS Questionnaires were completed by 939 individuals (357 men; 582 women), including 33 from Hubei and 906 from non-endemic provinces. The Stress Response Questionnaire (SRQ) determined the emotional state, somatic responses, and behavior. The Pittsburgh Sleep Quality Index (PSQI) was used to measure the duration of sleep and sleep quality. RESULTS There were 939 study participants, aged 18-24 years (35.89%) and 25-39 years (35.57%); 65.92% were university students. During a two week period in February 2020, the emotional state and behavior of participants in Hubei improved, but the quality of sleep did not. Health workers and business people became increasingly anxious, but other professionals became less anxious. The data showed that most people in Hubei Province developed a more positive attitude regarding their risk of infection and the chances of surviving the COVID-19 epidemic. CONCLUSIONS During a two-week period, front-line health workers and people in Hubei Province became less anxious about the COVID-19 epidemic, but sleep quality did not improve. Despite public awareness, levels of anxiety exist that affect the quality of life during epidemics, including periods of population quarantine. Therefore, health education should be combined with psychological counseling for vulnerable individuals.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Estresse Psicológico , Adolescente , Adulto , Ansiedade , COVID-19 , Infecções por Coronavirus/psicologia , Surtos de Doenças , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/psicologia , SARS-CoV-2 , Sono , Adulto Jovem
19.
Med Sci Monit ; 26: e924457, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32559181

RESUMO

BACKGROUND Early interventions have been believed to have a positive influence on the neurodevelopment of infants. Our Child Health Center has carried out parenting training for parents of infants for several years to promote the neurobehavioral development of infants at an early stage. MATERIAL AND METHODS We enrolled 117 families with term infants age 0-3 months who had completed a parenting training class at the Child Health Center of the Department of Pediatrics, the Third Xiangya Hospital. Parenting training included 4 parts: nursing, intelligence, social contact, and physical ability. A nurse practitioner demonstrated procedures to parents, who then performed them at home for 1 month. The Neonatal Behavioral Neurological Assessment (NBNA) was used to evaluate infants before and 1 month after parenting training. RESULTS In the comparative analysis before and after parenting training, there was a significant increase in the NBNA scores. For the infants whose parents received parenting training, the NBNA scores in total score (33.74±0.19 before parenting training vs. 36.69±0.20 after 1 month), neonatal behavioral capacity (10.19±0.14 before parenting training vs. 11.26±0.10 after 1 month), passive muscle tension (7.28±0.07 before parenting training vs. 7.82±0.04 after 1 month), and initiative muscle tension (4.29±0.08 before the parenting training vs. 5.61±0.13 after 1 month) were significantly higher one month before (P<0.01). CONCLUSIONS Term infant neurobehavior was associated with participation in parenting training, suggesting that these practices of parenting training support better early neurobehavioral development of infants.


Assuntos
Desenvolvimento Infantil , Comportamento do Lactente , Tono Muscular , Pais/educação , Reflexo , Intervenção Educacional Precoce , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Poder Familiar , Comportamento Social
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(2): 198-203, 2020 Feb 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-32386048

RESUMO

Rubinstein-Taybi syndrome (RSTS), also known as broad thumb-great toe syndrome or broad digits syndrome, is a rare autosomal dominant genetic disease. The main features of the patients are craniofacial dysmorphisms, skeletal malformations, and delay of growth and psychomotor development. In this case, the child has a typical RSTS specific face and growth retardation, with atypical indirect inguinalhemia. A heterozygous mutation, C. 4492 C>T (p. Arg1498Ter), was found in the exon of CREBBP gene by gene sequencing. It was a nonsense mutation, which leads to the premature termination of peptide synthesis. The mutation was not observed in the child's parents, which may be a de Novo mutation. The disease is lack of effective therapy so far.


Assuntos
Proteína de Ligação a CREB/genética , Síndrome de Rubinstein-Taybi , Códon sem Sentido , Éxons , Humanos , Lactente , Mutação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA