Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 140
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 184(21): 5405-5418.e16, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34619078

RESUMO

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment.


Assuntos
Antibacterianos/uso terapêutico , Doença de Lyme/tratamento farmacológico , Animais , Borrelia burgdorferi/efeitos dos fármacos , Calibragem , Cinamatos/química , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Fezes/microbiologia , Feminino , Células HEK293 , Células Hep G2 , Humanos , Higromicina B/análogos & derivados , Higromicina B/química , Higromicina B/farmacologia , Higromicina B/uso terapêutico , Doença de Lyme/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Microbiota/efeitos dos fármacos
2.
J Cogn Neurosci ; : 1-14, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38940732

RESUMO

Our perception of objects depends on non-oculomotor depth cues, such as pictorial distance cues and binocular disparity, and oculomotor depth cues, such as vergence and accommodation. Although vergence eye movements are always involved in perceiving real distance, previous studies have mainly focused on the effect of oculomotor state via "proprioception" on distance and size perception. It remains unclear whether the oculomotor command of vergence eye movement would also influence visual processing. To address this question, we placed a light at 28.5 cm and a screen for stimulus presentation at 57 cm from the participants. In the NoDivergence condition, participants were asked to maintain fixation on the light regardless of stimulus presentation throughout the trial. In the WithDivergence condition, participants were instructed to initially maintain fixation on the near light and then turn their two eyes outward to look at the stimulus on the far screen. The stimulus was presented for 100 msec, entirely within the preparation stage of the divergence eye movement. We found that participants perceived the stimulus as larger but were less sensitive to stimulus sizes in the WithDivergence condition than in the NoDivergence condition. The earliest visual evoked component C1 (peak latency 80 msec), which varied with stimulus size in the NoDivergence condition, showed similar amplitudes for larger and smaller stimuli in the WithDivergence condition. These results show that vergence eye movement planning affects the earliest visual processing and size perception, and demonstrate an example of the effect of motor command on sensory processing.

3.
Circ Res ; 131(11): 926-943, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36278398

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a growing health problem without effective therapies. Epidemiological studies indicate that diabetes is a strong risk factor for HFpEF, and about 45% of patients with HFpEF are suffering from diabetes, yet the underlying mechanisms remain elusive. METHODS: Using a combination of echocardiography, hemodynamics, RNA-sequencing, molecular biology, in vitro and in vivo approaches, we investigated the roles of SIRT6 (sirtuin 6) in regulation of endothelial fatty acid (FA) transport and HFpEF in diabetes. RESULTS: We first observed that endothelial SIRT6 expression was markedly diminished in cardiac tissues from heart failure patients with diabetes. We then established an experimental mouse model of HFpEF in diabetes induced by a combination of the long-term high-fat diet feeding and a low-dose streptozocin challenge. We also generated a unique humanized SIRT6 transgenic mouse model, in which a single copy of human SIRT6 transgene was engineered at mouse Rosa26 locus and conditionally induced with the Cre-loxP technology. We found that genetically restoring endothelial SIRT6 expression in the diabetic mice ameliorated diastolic dysfunction concurrently with decreased cardiac lipid accumulation. SIRT6 gain- or loss-of-function studies showed that SIRT6 downregulated endothelial FA uptake. Mechanistically, SIRT6 suppressed endothelial expression of PPARγ through SIRT6-dependent deacetylation of histone H3 lysine 9 around PPARγ promoter region; and PPARγ reduction mediated SIRT6-dependent inhibition of endothelial FA uptake. Importantly, oral administration of small molecule SIRT6 activator MDL-800 to diabetic mice mitigated cardiac lipid accumulation and diastolic dysfunction. CONCLUSIONS: The impairment of endothelial SIRT6 expression links diabetes to HFpEF through the alteration of FA transport across the endothelial barrier. Genetic and pharmacological strategies that restored endothelial SIRT6 function in mice with diabetes alleviated experimental HFpEF by limiting FA uptake and improving cardiac metabolism, thus warranting further clinical evaluation.


Assuntos
Diabetes Mellitus Experimental , Insuficiência Cardíaca , Sirtuínas , Humanos , Camundongos , Animais , Volume Sistólico/fisiologia , Insuficiência Cardíaca/metabolismo , PPAR gama , Modelos Animais de Doenças , Sirtuínas/genética , Lipídeos
4.
Acta Pharmacol Sin ; 45(1): 23-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37644131

RESUMO

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.


Assuntos
Insuficiência Cardíaca , Hipertensão , Animais , Humanos , Volume Sistólico/fisiologia , Comorbidade , Descoberta de Drogas
5.
Cell Biol Toxicol ; 39(4): 1433-1452, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36121554

RESUMO

T helper (Th) 17 cells highly contribute to the immunopathology of rheumatoid arthritis. Morin, a natural flavonoid, owns well anti-arthritic action but unclear effect on Th17 differentiation. This study tried to solve this issue and explore the mechanisms in view of cellular metabolism. Naïve CD4+ T cells were treated with anti-CD3/CD28 along with Th17-inducing cytokines. Morin was shown to block Th17 differentiation without affecting cell viability even when Foxp3 was dampened. The mechanisms were ascribed to the limited fatty acid synthesis by restricting FASN transcription, as indicated by metabolomics analysis, nile red staining, detection of triglycerides, FASN overexpression, and addition of palmitic acid. Moreover, morin had slight effect on cell apoptosis and protein palmitoylation during Th17 differentiation, but blocked the binding of RORγt to promoter and CNS2 region of Il17a gene. Oleic acid rescued the inhibition of morin on RORγt function, and Th17-inducing cytokines could not induce RORγt function in SCD1-defficient cells, suggesting that oleic acid but not palmitic acid was the direct effector in the action of morin. Then, PPARγ was identified as the target of morin, and GW9662 or PPARγ CRISPR/Cas9 KO plasmid weakened its above-mentioned effects. The transrepression of FASN by morin was owing to physical interaction between PPARγ and Sp1, and the importance of Sp1 in Th17 differentiation was confirmed by siSp1. Finally, the effects and mechanisms for morin-dampened Th17 responses were confirmed in collagen-induced arthritis (CIA) mice. Collectively, morin inhibited Th17 differentiation and alleviated CIA by limiting fatty acid synthesis subsequent to PPARγ activation.


Assuntos
Artrite Experimental , Camundongos , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , PPAR gama/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Agonistas PPAR-gama , Ácido Oleico , Diferenciação Celular , Citocinas , Flavonoides/farmacologia
6.
Acta Pharmacol Sin ; 44(2): 321-331, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35655094

RESUMO

Metabolic cardiomyopathy (MC) is characterized by intracellular lipid accumulation and utilizing fatty acids as a foremost energy source, thereby leading to excess oxidative stress and mitochondrial dysfunction. There is no effective therapy available yet. In this study we investigated whether defective mitophagy contributed to MC and whether urolithin A (UA), a naturally occurring microflora-derived metabolite, could protect against MC in experimental obese mice. Mice were fed high fat diet for 20 weeks to establish a diet-induced obese model. We showed that mitochondrial autophagy or mitophagy was significantly downregulated in the heart of experimental obese mice. UA (50 mg·kg-1·d-1, for 4 weeks) markedly activated mitophagy and ameliorated MC in obese mice by gavage. In PA-challenged H9C2 cardiomyocytes, UA (5 µM) significantly increased autophagosomes and decreased autolysosomes. Furthermore, UA administration rescued PINK1/Parkin-dependent mitophagy and relieved mitochondrial defects in the heart of obese mice, which led to improving cardiac diastolic function and ameliorating cardiac remodelling. In PA-challenged primarily isolated cardiomyocytes, both application of mitophagy inhibitor Mdivi-1 (15 µM) and silencing of mitophagy gene Parkin blunted the myocardial protective effect of UA. In summary, our data suggest that restoration of mitophagy with UA ameliorates symptoms of MC, which highlights a therapeutic potential of UA in the treatment of MC.


Assuntos
Cardiomiopatias , Mitofagia , Camundongos , Animais , Camundongos Obesos , Proteínas Quinases/metabolismo , Cardiomiopatias/metabolismo , Miócitos Cardíacos/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
7.
BMC Med Imaging ; 23(1): 24, 2023 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-36739392

RESUMO

BACKGROUND: To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS: Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS: A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION: ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.


Assuntos
Degeneração Hepatolenticular , Cirrose Hepática , Humanos , Criança , Adolescente , Cirrose Hepática/patologia , Degeneração Hepatolenticular/diagnóstico por imagem , Estudos Retrospectivos , Biomarcadores , Testes de Função Hepática , Curva ROC , Fígado/diagnóstico por imagem , Fígado/patologia
8.
J Med Internet Res ; 25: e45051, 2023 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-37058349

RESUMO

BACKGROUND: The COVID-19 vaccine is an effective tool in the fight against the COVID-19 outbreak. As the main channel of information dissemination in the context of the epidemic, social media influences public trust and acceptance of the vaccine. The rational application of health behavior theory is a guarantee of effective public health information dissemination. However, little is known about the application of health behavior theory in web-based COVID-19 vaccine messages, especially from Chinese social media posts. OBJECTIVE: This study aimed to understand the main topics and communication characteristics of hot papers related to COVID-19 vaccine on the WeChat platform and assess the health behavior theory application with the aid of health belief model (HBM). METHODS: A systematic search was conducted on the Chinese social media platform WeChat to identify COVID-19 vaccine-related papers. A coding scheme was established based on the HBM, and the sample was managed and coded using NVivo 12 (QSR International) to assess the application of health behavior theory. The main topics of the papers were extracted through the Latent Dirichlet Allocation algorithm. Finally, temporal analysis was used to explore trends in the evolution of themes and health belief structures in the papers. RESULTS: A total of 757 papers were analyzed. Almost all (671/757, 89%) of the papers did not have an original logo. By topic modeling, 5 topics were identified, which were vaccine development and effectiveness (267/757, 35%), disease infection and protection (197/757, 26%), vaccine safety and adverse reactions (52/757, 7%), vaccine access (136/757, 18%), and vaccination science popularization (105/757, 14%). All papers identified at least one structure in the extended HBM, but only 29 papers included all of the structures. Descriptions of solutions to obstacles (585/757, 77%) and benefit (468/757, 62%) were the most emphasized components in all samples. Relatively few elements of susceptibility (208/757, 27%) and the least were descriptions of severity (135/757, 18%). Heat map visualization revealed the change in health belief structure before and after vaccine entry into the market. CONCLUSIONS: To the best of our knowledge, this is the first study to assess the structural expression of health beliefs in information related to the COVID-19 vaccine on the WeChat public platform based on an HBM. The study also identified topics and communication characteristics before and after the market entry of vaccines. Our findings can inform customized education and communication strategies to promote vaccination not only in this pandemic but also in future pandemics.


Assuntos
COVID-19 , Mídias Sociais , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Disseminação de Informação , Comunicação , Surtos de Doenças
9.
J Med Internet Res ; 25: e45019, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37733396

RESUMO

BACKGROUND: Social networks have become one of the main channels for obtaining health information. However, they have also become a source of health-related misinformation, which seriously threatens the public's physical and mental health. Governance of health-related misinformation can be implemented through topic identification of rumors on social networks. However, little attention has been paid to studying the types and routes of dissemination of health rumors on the internet, especially rumors regarding health-related information in Chinese social media. OBJECTIVE: This study aims to explore the types of health-related misinformation favored by WeChat public platform users and their prevalence trends and to analyze the modeling results of the text by using the Latent Dirichlet Allocation model. METHODS: We used a web crawler tool to capture health rumor-dispelling articles on WeChat rumor-dispelling public accounts. We collected information from health-debunking articles posted between January 1, 2016, and August 31, 2022. Following word segmentation of the collected text, a document topic generation model called Latent Dirichlet Allocation was used to identify and generalize the most common topics. The proportion distribution of the themes was calculated, and the negative impact of various health rumors in different periods was analyzed. Additionally, the prevalence of health rumors was analyzed by the number of health rumors generated at each time point. RESULTS: We collected 9366 rumor-refuting articles from January 1, 2016, to August 31, 2022, from WeChat official accounts. Through topic modeling, we divided the health rumors into 8 topics, that is, rumors on prevention and treatment of infectious diseases (1284/9366, 13.71%), disease therapy and its effects (1037/9366, 11.07%), food safety (1243/9366, 13.27%), cancer and its causes (946/9366, 10.10%), regimen and disease (1540/9366, 16.44%), transmission (914/9366, 9.76%), healthy diet (1068/9366, 11.40%), and nutrition and health (1334/9366, 14.24%). Furthermore, we summarized the 8 topics under 4 themes, that is, public health, disease, diet and health, and spread of rumors. CONCLUSIONS: Our study shows that topic modeling can provide analysis and insights into health rumor governance. The rumor development trends showed that most rumors were on public health, disease, and diet and health problems. Governments still need to implement relevant and comprehensive rumor management strategies based on the rumors prevalent in their countries and formulate appropriate policies. Apart from regulating the content disseminated on social media platforms, the national quality of health education should also be improved. Governance of social networks should be clearly implemented, as these rapidly developed platforms come with privacy issues. Both disseminators and receivers of information should ensure a realistic attitude and disseminate health information correctly. In addition, we recommend that sentiment analysis-related studies be conducted to verify the impact of health rumor-related topics.


Assuntos
Educação em Saúde , Mídias Sociais , Humanos , Dieta Saudável , Governo , Comunicação , China
10.
Molecules ; 28(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37049943

RESUMO

This study aimed to optimize the brewing conditions of Shanlan rice wine (SRW) and select a suitable sterilization method. The response surface method experiment was used to optimize the brewing process of SRW. LC-MS/MS (liquid chromatography-tandem mass spectrometry) and GC-MS (gas chromatography-mass spectrometry) were used to analyze the physicochemical components, free amino acids, and flavor metabolites of the thermal-sterilized SRW and the SRW sterilized by intense pulsed light (IPL), respectively. Results showed that the optimum fermentation conditions of SRW were as follows: fermentation temperature, 24.5 °C; Qiuqu amount (the traditional yeast used to produce SRW), 0.78%; water content, 119%. Compared with the physicochemical properties of the control, those of the SRWs separately treated with two sterilization methods were slightly affected. The 60 s pulse treatment reduced the content of bitter amino acids, maintained sweet amino acids and umami amino acids in SRW, and balanced the taste of SRW. After pasteurization, the ester content in wine decreased by 90%, and the alcohol content decreased to different degrees. IPL sterilization slightly affected the ester content and increased the alcohol content. Further analysis of the main flavor metabolites showed that 60 s pulse enhanced the important flavor-producing substances of SRW. In conclusion, 60 s pulse is suitable for sterilizing this wine.


Assuntos
Oryza , Vinho , Vinho/análise , Cromatografia Líquida , Oryza/química , Espectrometria de Massas em Tandem , Aminoácidos/análise , Esterilização , Fermentação
11.
Vet Med (Praha) ; 68(10): 392-402, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38028206

RESUMO

Rongchang piglets were easily induced to cold stress and diarrhoea in the winter when raised in an open hog house. However, they also gradually recovered under mid-cold stress. Other studies have suggested gut microbiome might be involved in the host energy metabolism to relieve stress. To study how to adapt Rongchang piglets to cold stress by gut microbiome, thirty Rongchang piglets were randomly divided into a mild cold stress group and a control group for 30 consecutive days. The findings revealed that the piglets had low growth performance and a high diarrhoea rate and mortality rate during the first half of the cold treatment, but subsequently stabilised. The level of cortisol (COR) also displayed a similar trend. In the mild cold stress group, the relative abundance of Muribaculaceae significantly increased on day 15, and the predominant bacterial on day 30 was Lactobacillus sp. Our results indicated that the Rongchang piglet's production performance and health were impaired at the start of the mild cold stress. However, as time passed, the body could progressively adapt to the low temperature, and Lactobacillus sp. participated in this process. This study provides new insight into how to alleviate health damage caused by cold stress.

12.
Nature ; 538(7625): 350-355, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27680706

RESUMO

Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium.


Assuntos
Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Colo/metabolismo , Epitélio/metabolismo , Receptores Frizzled/metabolismo , Animais , Antígenos/metabolismo , Proteínas de Bactérias/química , Toxinas Bacterianas/química , Sítios de Ligação , Células CHO , Sistemas CRISPR-Cas , Linhagem Celular , Clostridioides difficile/patogenicidade , Cricetulus , Feminino , Receptores Frizzled/química , Receptores Frizzled/deficiência , Receptores Frizzled/genética , Técnicas de Inativação de Genes , Humanos , Masculino , Camundongos , Camundongos Knockout , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Organoides/metabolismo , Domínios Proteicos , Proteoglicanas/metabolismo , Fatores de Virulência/metabolismo , Proteínas Wnt/metabolismo
13.
Psychol Health Med ; 27(4): 925-930, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34402336

RESUMO

To investigate post-traumatic growth induced by COVID-19 pandemic in certain Yunnan residents and to analyze its influencing factors. A total of 581 permanent residents of Yunnan province completed the electronic questionnaire from 18 April 2020 to 26 April 2020. Logistic regression analysis showed that the educational levels, self-perceived health status, family history of infectious diseases, family history of infectious diseases, personality and frequency of going through COVID-19 related news were influencing factors of PTG (P < 0.05). As a traumatic event, the threat of COVID-19 may enable some people to gain positive psychological development in adversity. This will provide reference for public psychological crisis intervention following the COVID-19 pandemic.


Assuntos
COVID-19 , Crescimento Psicológico Pós-Traumático , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Humanos , Pandemias , SARS-CoV-2
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(5): 899-905, 2022 Oct.
Artigo em Zh | MEDLINE | ID: mdl-36325789

RESUMO

Gastric cancer ranks as the fifth most common malignant tumor worldwide and the fourth leading cause of cancer-related deaths.Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a special type of gastric adenocarcinoma,the prognosis of which can be improved by trastuzumab plus cytotoxic chemotherapy such as cisplatin and fluorouracil.Pembrolizumab on the basis of Tmabplus chemotherapy can further improve the overall response rate,which has become the first-line standardized therapy against HER2-positive gastric cancer.However,there are still some obstacles such as the innate resistance to Tmab in specific populations.The research on HER2-targeted therapy provides clues for clinical decision-making.This review documents the current neoadjuvant and adjuvant therapies against late-stage HER2-positive gastric cancer,as well as the progress in novel HER2 pathway-targeted drugs.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2 , Trastuzumab/uso terapêutico
15.
Med Res Rev ; 41(1): 314-341, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32969064

RESUMO

The global incidence of cardiac diseases is expected to increase in the coming years, imposing a substantial socioeconomic burden on healthcare systems. Autophagy is a tightly regulated lysosomal degradation mechanism important for cell survival, homeostasis, and function. Accumulating pieces of evidence have indicated a major role of autophagy in the regulation of cardiac homeostasis and function. It is well established that dysregulation of autophagy in cardiomyocytes is involved in cardiac hypertrophy, myocardial infarction, diabetic cardiomyopathy, and heart failure. In this sense, autophagy seems to be an attractive therapeutic target for cardiac diseases. Recently, multiple natural products/phytochemicals, such as resveratrol, berberine, and curcumin have been shown to regulate cardiomyocyte autophagy via different pathways. The autophagy-modifying capacity of these compounds should be taken into consideration for designing novel therapeutic agents. This review focuses on the role of autophagy in various cardiac diseases and the pharmacological basis and therapeutic potential of reported natural products in cardiac diseases by modifying autophagic processes.


Assuntos
Produtos Biológicos , Cardiopatias , Autofagia , Produtos Biológicos/farmacologia , Cardiopatias/tratamento farmacológico , Humanos , Lisossomos , Miócitos Cardíacos
16.
J Clin Microbiol ; 59(9): e0058521, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34132582

RESUMO

Metronidazole resistance in clinical Clostridioides difficile is often described as unstable, since resistant strains reportedly appear susceptible following freezer storage or brief passage. This has presented a conundrum for adopting susceptibility testing to accurately evaluate the connection between metronidazole resistance and decreased clinical efficacy of metronidazole in patients with C. difficile infections (CDIs). We discovered that supplementation of microbiological media with the metalloporphyrin heme is crucial for detection of metronidazole-resistant C. difficile using the agar dilution susceptibility testing method. Known metronidazole-resistant strains appeared susceptible to metronidazole in media lacking heme. Similarly, these resistant strains exhibited increased susceptibility to metronidazole when tested on heme-containing agars that were exposed to room light for more than 1 day, likely due to heme photodecomposition. In parallel experiments, resistance was reproducibly detected when heme-containing agars were either prepared and used on the same day or protected from light and then used on subsequent days. Notably, heme did not influence the susceptibilities of drug-susceptible strains that were of the same ribotype as the resistant strains. These findings firmly show that the consistent detection of metronidazole-resistant C. difficile is dependent upon heme and its protection from light. Studies are warranted to determine the extent to which this heme-associated metronidazole-resistant phenotype affects the clinical efficacy of metronidazole in CDI and the underlying genetic and biochemical mechanisms.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Ágar , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Clostridioides , Clostridioides difficile/genética , Infecções por Clostridium/tratamento farmacológico , Heme , Humanos , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana
17.
BMC Pregnancy Childbirth ; 21(1): 275, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794797

RESUMO

BACKGROUND: Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations. RESULTS: Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P < 0.001) and from 1.1 to 0.0% (P = 0.090). Other, there was no statistical difference with respect to the T-retrieved ova (total retrieved ova), high quality embryos, cultured blastocyst and blastocyst number in high responders. For normal responders and poor ovary responders, T-Gn, Gn days, T-retrieved ova, high quality embryos, cultured blastocyst and blastocysts number in oral medications group all apparently decreased. Clinical pregnancy rate per fresh cycle of poor responders with prior oral medications was significantly decreased (25.7% vs. 50.8%, P = 0.005), and no significant differences in high responders and normal responders were expressed (52.5% vs. 44.2%, P = 0.310; 51.9% vs. 42.4%, P = 0.163) between two groups of participants. The numbers of cumulative pregnancy rates were lower in the conventional group compared to the add group for high (75.90% versus 81.03%, P = 0.279), normal (62.69% versus 71.36%, P = 0.016) and poor (39.74% versus 68.21%, P < 0.001) responders. CONCLUSIONS: The addition of CC/LE to the ovulation induction during IVF has certain efficacy in terms of low cost, low OHSS incidence. CC/LE deserves more recommendations as a responsible strategy in high responders due to advantageous pregnancy outcomes. For normal responders, the strategy needs to be considered with more comprehensive factors.


Assuntos
Clomifeno/administração & dosagem , Gonadotropinas/administração & dosagem , Letrozol/administração & dosagem , Síndrome de Hiperestimulação Ovariana/epidemiologia , Indução da Ovulação/métodos , Administração Oral , Adulto , Clomifeno/efeitos adversos , Relação Dose-Resposta a Droga , Transferência Embrionária , Estudos de Viabilidade , Feminino , Gonadotropinas/efeitos adversos , Humanos , Incidência , Infertilidade/terapia , Injeções Intramusculares , Letrozol/efeitos adversos , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/efeitos adversos , Gravidez , Taxa de Gravidez , Resultado do Tratamento , Adulto Jovem
18.
Tohoku J Exp Med ; 255(3): 247-256, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34840225

RESUMO

As the most common tumor of central nervous system in adults, glioma is characterized with poor prognosis. Tac2-N (TC2N) is a newly discovered protein that play potential roles in lung cancer and breast cancer progression. Here we aimed to investigate the expression, clinical significance, and function of TC2N in glioma. The mRNA level of TC2N in glioma patients was extracted from TCGA datasets. Immunohistochemistry staining was conducted to test protein expression of TC2N in glioma tissues. Chi-square test was used to assess correlations between TC2N expression and patients' clinicopathological characteristics. Kaplan-Meier method was used to plot survival curves. The prognostic predictive role of TC2N was evaluated by univariate and multivariate analyses. Knockdown assays were performed in U87 and U251 cell lines, respectively. Cell proliferation, colony formation, and subcutaneous mice xenografts were used to reveal the tumor-related role of TC2N in glioma. Compared with normal brain tissues, the mRNA level of TC2N was significantly higher in glioma tissues, whose dysregulated higher mRNA level was correlated with poorer overall survival. Similarly, higher protein expression of TC2N was observed in cases with larger tumor size and advanced WHO grades. Univariate and multivariate analyses identified TC2N as a novel independent prognostic factor of gliomas. In vitro and in vivo data demonstrated that TC2N interference can remarkably prevent glioma cell proliferation and tumor growth. In conclusion, high TC2N expression is significantly correlated with poor overall survival of glioma patients via enhancing tumor growth.


Assuntos
Neoplasias Encefálicas , Glioma , Animais , Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Imuno-Histoquímica , Camundongos , Prognóstico
19.
J Med Internet Res ; 23(5): e27811, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33970865

RESUMO

BACKGROUND: COVID-19 has spread around the world and has increased the public's need for health information in the process. Meanwhile, in the context of lockdowns and other measures for preventing SARS-CoV-2 spread, the internet has surged as a web-based resource for health information. Under these conditions, social question-and-answer communities (SQACs) are playing an increasingly important role in improving public health literacy. There is great theoretical and practical significance in exploring the influencing factors of SQAC users' willingness to adopt health information. OBJECTIVE: The aim of this study was to establish an extended unified theory of acceptance and use of technology model that could analyze the influence factors of SQAC users' willingness to adopt health information. Particularly, we tried to test the moderating effects that different demographic characteristics had on the variables' influences. METHODS: This study was conducted by administering a web-based questionnaire survey and analyzing the responses from a final total of 598 valid questionnaires after invalid data were cleaned. By using structural equation modelling, the influencing factors of SQAC users' willingness to adopt health information were analyzed. The moderating effects of variables were verified via hierarchical regression. RESULTS: Performance expectation (ß=.282; P<.001), social influence (ß=.238; P=.02), and facilitating conditions (ß=.279; P=.002) positively affected users' willingness to adopt health information, whereas effort expectancy (P=.79) and perceived risk (P=.41) had no significant effects. Gender had a significant moderating effect in the structural equation model (P<.001). CONCLUSIONS: SQAC users' willingness to adopt health information was evidently affected by multiple factors, such as performance expectation, social influence, and facilitating conditions. The structural equation model proposed in this study has a good fitting degree and good explanatory power for users' willingness to adopt health information. Suggestions were provided for SQAC operators and health management agencies based on our research results.


Assuntos
Gestão da Informação em Saúde/métodos , Uso da Internet/tendências , Adolescente , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , Características de Residência , Inquéritos e Questionários , Adulto Jovem
20.
BMC Med Inform Decis Mak ; 21(1): 257, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479566

RESUMO

BACKGROUND: Although middle-aged and elderly users are the main group targeted by health maintenance-oriented WeChat official accounts (HM-WOAs), few studies have explored the relationship of these accounts and their users. Exploring the factors that influence the continuous adoption of WOAs is helpful to strengthen the health education of middle-aged and elderly individuals. OBJECTIVE: We developed a new theoretical model and explored the factors that influence middle-aged and elderly individuals' continuous usage intention for HM-WOA. Performance expectancy mediated the effects of the model in explaining continuous usage intention and introduced health literacy into the model. METHODS: We established a hybrid theoretical model on the basis of the unified theory of acceptance and use of technology 2 model (UTAUT2), the health belief model (BHM), protection motivation theory (PMT), and health literacy. We collected valid responses from 396 middle-aged and elderly users aged ≥ 45 years in China. To verify our hypotheses, we analyzed the data using structural equation modeling. RESULTS: Performance expectancy (ß = 0.383, P < 0.001), hedonic motivation (ß = 0.502, P < 0.001), social influence (ß = 0.134, P = 0.049), and threat appraisal (ß = 0.136, P < 0.001) positively influenced middle-aged and elderly users' continuous usage intention. Perceived health threat (ß = - 0.065, P = 0.053) did not have a significant effect on continuous usage intention. Both threat appraisal (ß = 0.579, P < 0.001) and health literacy (ß = 0.579, P < 0.001) positively affected performance expectancy. Threat appraisal indirectly affected continuous usage intention through performance expectancy mediation. CONCLUSIONS: Our new theoretical model is useful for understanding middle-aged and elderly users' continuous usage intention for HM-WOA. Performance expectancy plays a mediation role between threat appraisal and continuous usage intention, and health literacy positively affects performance expectancy.


Assuntos
Intenção , Motivação , Idoso , China , Humanos , Análise de Classes Latentes , Pessoa de Meia-Idade , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA