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BACKGROUND: An mHealth-based school health education platform (EduSaltS) was promoted in real-world China to reduce salt intake among children and their families. This progress evaluation explores its implementation process and influencing factors using mixed methods. METHODS: The mixed-methods process evaluation employed the RE-AIM framework. Quantitative data were collected from a management website monitoring 54,435 third-grade students across two cities. Questionnaire surveys (n = 27,542) assessed pre- and post-education effectiveness. Mixed-effects models were used to control cluster effects. Qualitative interviews (23 individuals and 8 focus groups) identified program performance, facilitators, and barriers. Findings were triangulated using the RE-AIM framework. RESULTS: The program achieved 100% participation among all the third-grade classes of the 208 invited primary schools, with a 97.7% registration rate among all the 54,435 families, indicating high "Reach." Qualitative interviews revealed positive engagement from children and parents through the "small hands leading big hands" strategy. The high completion rate of 84.9% for each health cloud lesson and the significant improvement in salt reduction knowledge and behaviors scores from 75.0 (95%CI: 74.7-75.3) to 80.9 (95%CI: 80.6-81.2) out of 100 demonstrated the "Effect" of EduSaltS. The program's "Adoption" and "Implementation" were supported by attractive materials, reduced workload via auto-delivered lessons/activities and performance evaluation, and high fidelity to recommended activities, with medians 3.0 (IQR: 2.0-8.0)/class and 9.0 (IQR: 5.0-14.0)/school. Stable course completion rates (79.4%-93.4%) over one year indicated promising "Maintenance." Apart from the facilitating features praised by the interviewees, government support was the basis for the scaling up of EduSaltS. Barriers included the lack of smartphone skills among some parents and competing priorities for schools. Unhealthy off-campus environments, such as excessive use of salt in pre-packaged and restaurant foods, also hindered salt reduction efforts. The program's scalability was evident through its integration into existing health education, engagement of local governments and adaptation across various mobile devices. CONCLUSIONS: The mHealth-based school health education program is scalable and effective for public salt reduction in China. Identified barriers and facilitators can inform future health program scale-ups. The program's successful implementation demonstrates its potential for broader application in public health initiatives aimed at reducing dietary salt intake.
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Avaliação de Programas e Projetos de Saúde , Serviços de Saúde Escolar , Cloreto de Sódio na Dieta , Telemedicina , Humanos , China , Masculino , Criança , Feminino , Cloreto de Sódio na Dieta/administração & dosagem , Educação em Saúde/métodos , Pesquisa Qualitativa , Grupos Focais , Inquéritos e QuestionáriosRESUMO
The recent acceleration of industrialization and urbanization has brought significant attention to N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ), an emerging environmental pollutant from tire wear, due to its long-term effects on the environment and organisms. Recent studies suggest that 6-PPDQ can disrupt neurotransmitter synthesis and release, impact receptor function, and alter signaling pathways, potentially causing oxidative stress, inflammation, and apoptosis. This review investigates the potential neurotoxic effects of prolonged 6-PPDQ exposure, the mechanisms underlying its cytotoxicity, and the associated health risks. We emphasize the need for future research, including precise exposure assessments, identification of individual differences, and development of risk assessments and intervention strategies. This article provides a comprehensive overview of 6-PPDQ's behavior, impact, and neurotoxicity in the environment, highlighting key areas and challenges for future research.
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Poluentes Ambientais , Síndromes Neurotóxicas , Humanos , Poluentes Ambientais/toxicidade , Síndromes Neurotóxicas/etiologia , Animais , Estresse Oxidativo/efeitos dos fármacos , Fenilenodiaminas/toxicidade , Medição de Risco , Exposição Ambiental/efeitos adversos , Apoptose/efeitos dos fármacosRESUMO
Red swamp crayfish, Procambarus clarkii (P. clarkii), is an important model crustacean organism used in many types of research. However, the effects of different doses of aminomethylphosphonic acid (AMAP) on the transcriptome and metabolites of P. clarkii have not been explored. Thus, this study investigated the molecular and metabolic mechanisms activated at the different exposure dosages of AMAP in P. clarkii to provide new insights into the strategies of P. clarkii in response to the high concentrations of AMAP in the environment. In the present study, the P. clarkii were divided into three groups (control group; low-dosage AMAP exposure; high-dosage AMAP exposure), and hepatopancreatic tissue samples were dependently taken from the three groups. The response mechanisms at the different dosages of AMAP were investigated based on the transcriptome and metabolome data of P. clarkii. Differentially expressed genes and differentially abundant metabolites were identified in the distinct AMAP dosage exposure groups. The genes related to ribosome cell components were significantly up-regulated, suggesting that ribosomes play an essential role in responding to AMAP stress. The metabolite taurine, involved in the taurine and hypotaurine metabolism pathway, was significantly down-regulated. P. clarkii may provide feedback to counteract different dosages of AMAP via the upregulation of ribosome-related genes and multiple metabolic pathways. These key genes and metabolites play an important role in the response to AMAP stress to better prepare for survival in high AMAP concentrations.
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Astacoidea , Organofosfonatos , Transcriptoma , Animais , Astacoidea/genética , Metaboloma , TaurinaRESUMO
Colorectal cancer (CRC) is identified as a primary cause of death around the world. The current chemotherapies are not cost-effective. Therefore, finding novel potential therapeutic target is urgent. Titin (TTN) is a muscle protein that is critical in hypertrophic cardiomyopathy. However, its role in CRC is not well understood. The study focused on exploring the possible role of TTN in CRC carcinogenesis. TTN mRNA and protein expression levels presented an obvious downregulation in CRC tissue samples, relative to normal control (p < 0.05). TTN expression significantly correlated with the clinical stage (normal vs. Stage 1, p < 0.05; normal vs. Stage 4, p < 0.05), node metastasis (normal vs. N1, p < 0.05; N1 vs. N2, p < 0.05), histological type (normal vs. adenocarcinoma, p < 0.05), race (Caucasian vs. Asian, p < 0.05; African-American vs. Asian, p < 0.05) and TP53 mutation (normal vs. TP53 mutation, p < 0.05), considering The Cancer Genome Atlas database. However, for patients who had higher TTN expression, the overall survival was remarkably shorter than patients who had low TTN expression. Furthermore, TTN was lowly expressed in four CRC cell lines. TTN overexpression facilitated CRC cells in terms of the proliferation, metastasis and invasion. Based on gene set enrichment analysis, the ERB pathway might be responsible for TTN-related CRC. Besides, TTN was involved in the response to azacitidine. Overall, TTN might serve as a potential novel therapeutic target for treating and overcoming chemotherapy resistance in CRC.
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Neoplasias Colorretais , MicroRNAs , Humanos , Conectina/genética , Conectina/metabolismo , MicroRNAs/genética , Proteínas Musculares/genética , Mutação/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismoRESUMO
Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury via vascular injury. There is still a lack of effective pharmaceutical preparations for cerebral I/R injury under hyperglycemia. This study aimed to investigate the effects of oxymatrine (OMT) on hyperglycemia-exacerbated cerebral I/R injury in vitro and in vivo. The middle cerebral artery occlusion (MCAO) and reperfusion was established in the rats under hyperglycemia. Meanwhile, oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose was used as an in vitro model of hyperglycemic cerebral I/R injury. The results showed that the neurological deficit score, mortality, infarct volume and penumbra apoptosis in hyperglycemia group were significantly higher than those in normal glucose group. OMT pre-treated obviously reduced the degree of neurological deficit, mortality, infarct volume, improve cerebral blood flow after I/R in rats with hyperglycemia, and increase the survival rate of human brain microvascular endothelial cells (HBMECs) in high glucose and OGD/R group. OMT significantly improved the ultrastructure changes of endothelial cells, and maintain the migration and angiogenesis potency of HBMECs in high glucose and OGD/R group. OMT obviously alleviated the down-regulating CD31 and CD105 expression in cerebral microvessels caused by hyperglycemia. It is concluded that OMT treatment might alleviate cerebral I/R injury under hyperglycemia via protecting microvessels.
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Alcaloides , Isquemia Encefálica , Quinolizinas , Traumatismo por Reperfusão , Alcaloides/uso terapêutico , Animais , Apoptose , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Células Endoteliais/metabolismo , Humanos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Microvasos/metabolismo , Quinolizinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismoRESUMO
BACKGROUND: Dyslipidaemia is a risk factor for abnormal blood glucose. However, studies on the predictive values of lipid markers in prediabetes and diabetes simultaneously are limited. This study aimed to assess the associations and predictive abilities of lipid indices and abnormal blood glucose. METHODS: A sample of 7667 participants without diabetes were enrolled in this cross-sectional study conducted in 2016, and all of them were classified as having normal glucose tolerance (NGT), prediabetes or diabetes. Blood glucose, blood pressure and lipid parameters (triglycerides, TG; total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; and triglyceride glucose index, TyG) were evaluated or calculated. Logistic regression models were used to analyse the association between lipids and abnormal blood glucose. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the discriminatory power of lipid parameters for detecting prediabetes or diabetes. RESULTS: After adjustment for potential confounding factors, the TyG was the strongest marker related to abnormal blood glucose compared to other lipid indices, with odds ratios of 2.111 for prediabetes and 5.423 for diabetes. For prediabetes, the AUCs of the TG, TC, HDL-C, LDL-C, TC/HDL-C, TG/HDL-C, non-HDL-C and TyG indices were 0.605, 0.617, 0.481, 0.615, 0.603, 0.590, 0.626 and 0.660, respectively, and the cut-off points were 1.34, 4.59, 1.42, 2.69, 3.39, 1.00, 3.19 and 8.52, respectively. For diabetes, the AUCs of the TG, TC, HDL-C, LDL-C, TC/HDL-C, TG/HDL-C, non-HDL-C and TyG indices were 0.712, 0.679, 0.440, 0.652, 0.686, 0.692, 0.705, and 0.827, respectively, and the cut-off points were 1.35, 4.68, 1.42, 2.61, 3.44, 0.98, 3.13 and 8.80, respectively. CONCLUSIONS: The TyG, TG and non-HDL-C, especially TyG, are accessible biomarkers for screening individuals with undiagnosed diabetes.
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Diabetes Mellitus , Estado Pré-Diabético , Biomarcadores/sangue , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Triglicerídeos/sangueRESUMO
OBJECTIVE: Patients with liver cirrhosis (LC) commonly exhibit hypercoagulability and tend to develop thrombosis. Neutrophil extracellular traps (NETs) are associated with a variety of thrombotic conditions, but their possible value in portal vein thrombosis (PVT) is not known. We assessed whether NETs promote thrombosis and contribute to the procoagulant state in patients with LC. METHODS: The circulating levels of NETs markers (myeloperoxidase, neutrophil elastase, citrullinated histone H3) were measured in 72 patients (median age, 55 years; 48 [66.7%] men) with LC from September 2020 to February 2021. Then they were divided into two groups: patients with or without PVT. NETs procoagulant activity was assessed based on thrombin-antithrombin complex (TAT complex) and Factor X. The levels of plasma markers were determined by ELISA. RESULTS: There were 28 patients with PVT and 44 patients without PVT. The levels of NETs markers and hypercoagulability markers in the plasma of cirrhosis patients with PVT were significantly higher than those of cirrhosis patients without PVT (p < 0.05). Additionally, the levels of the NETs markers correlated with TAT complex and Factor X (Spearman correlation rho >0.73, p < 0.0001). CONCLUSIONS: Neutrophil extracellular traps seem to enhance procoagulant activity in LC patients with PVT; thus, they may be a practical predictor of PVT as well as a rapid and easy-to-use diagnostic and treatment guide for PVT in patients with cirrhosis.
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Armadilhas Extracelulares , Trombofilia , Trombose , Trombose Venosa , Fator X , Feminino , Humanos , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Trombose Venosa/complicaçõesRESUMO
Fritillaria cirrhosa, the most valuable source of the precious Chinese medicinal material Fritillariae Cirrhosae Bulbus, suffers from various stresses during growth which influence the yield and quality of the medicinal part. This study aims to explore the genes related to stress resistance in this medicinal species. To be specific, based on the transcriptome data of F. cirrhosa, a gene encoding the late embryogenesis abundant(LEA) protein was obtained, which was named as FcLEA-D29. The gene sequence and protein structure were analyzed with bioinformatics methods and qRT-PCR was used to detect the expression of the gene in different tissues and in response to temperature stress. The low-temperature tolerance of FcLEA-D29 was verified by the prokaryotic expression system. The results showed that FcLEA-D29 contained an open reading frame of 777 bp, encoding 258 amino acids. Multiple sequence alignment revealed that FcLEA-D29 protein belonged to LEA-D29 subfamily of LEA3 family. qRT-PCR results showed that FcLEA-D29 was specifically expressed in bulbs and responded to low temperature. The strain with the recombinant plasmid demonstrated better growth status than the control strain in the instance of low temperature stress, suggesting that FcLEA-D29 may play a role in bulb development and low temperature response of F. cirrhosa. This study laid a basis for further research on the role of FcLEA-D29 in the accumulation of secondary metabolites in F. cirrhosa, especially alkaloids, under low temperature and provided evidence for the low-temperature adaptation of F. cirrhosa.
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Alcaloides , Fritillaria , Fritillaria/química , Reação em Cadeia da Polimerase , Clonagem MolecularRESUMO
Background: Ultrasound (US)- or computed tomography-guided drainage for abdominal abscess is currently the first-line options for drainage, but both options have disadvantages. Patients without adequate windows for drainage mostly undergo surgical drainage. However, surgical drainage is invasive and expensive. Endoscopic US (EUS)-guided drainage is a minimally invasive alternative for abdominal abscess, but there is less consensus on its efficacy, safety and complications. This meta-analysis aims to evaluate EUS-guided drainage for abdominal abscess. Materials and Methods: We retrieved relevant papers on EUS-guided drainage for abdominal abscess from the PubMed, Cochrane Library, Web of Science and EMBASE databases. Each paper was reviewed, and data were extracted. We used R software version 3.6.3 to perform the meta-analysis. Fixed effects models were used for merging data. Results: A total of 11 papers met the inclusion criteria, with a total sample population of 264 patients. The meta-analysis showed that the pooled clinical success rate was 90% (95% confidence interval [CI], 0.85-0.95), the technical success rate was 99% (95% CI, 0.97-1.00) and the recurrence rate was 1% (95% CI, 0.00-0.03). Three studies reported the complications, including perforation, bleeding and stent migration; none of the other eight studies reported complications. There were no significant differences between subgroups. There was no publication bias in either the clinical or the technical success rates. Conclusions: This meta-analysis showed that EUS-guided drainage for abdominal abscess was effective and safe, with an excellent technical success rate. In addition, EUS-guided drainage could be used for abscesses with complex anatomy. Nevertheless, complications and stent type should be considered.
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BACKGROUND: When the risk of lymph node metastasis (LNM) is considered minimal in patients with early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is an effective alternative to radical resection. This study aims to estimate the feasibility of ESD for EGC with ulceration. PATIENTS AND METHODS: We retrospectively reviewed data from 691 patients who underwent gastrectomy for EGC with ulceration. Subsequently, a stratification system for lesions was created based on the expanded ESD criteria, and the associations between the subgroups and the rate of LNM were analyzed. RESULTS: LNM was confirmed in 16.5% (114/691) of patients. Univariate analysis demonstrated that age, sex, tumor size, macroscopic features, depth of invasion, tumor differentiation, Lauren type, lymphovascular invasion (LVI), and perineural invasion were associated with LNM. Multivariate analysis showed that LVI [odds ratio (OR) = 16.761, P < 0.001], SM1 invasion (OR = 2.159, P = 0.028), and SM2 invasion (OR = 3.230, P < 0.001) were independent risk factors for LNM. LNM occurred in undifferentiated mucosal tumors, with ulceration being 1.7% (2/116) when the lesion was smaller than 20 mm. Further stratification revealed that among lesions < 30 mm in size, undifferentiated tumors with SM1 invasion had a higher rate of LNM and a lower disease-free survival rate than differentiated tumors with SM1 invasion and tumors limited to the mucosal layer. CONCLUSIONS: Depth of invasion and LVI were strongly associated with LNM in ulcerative EGC. Endoscopic resection may be applicable for undifferentiated mucosal ulcerative EGC < 30 mm in size, and additional investigation is needed to evaluate its safety.
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Neoplasias Gástricas , Estudos de Viabilidade , Gastrectomia , Mucosa Gástrica , Humanos , Excisão de Linfonodo , Metástase Linfática , Invasividade Neoplásica , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgiaRESUMO
Mitochondrial uncoupling protein 2 (UCP2) deficiency exacerbates brain damage following cerebral ischemia/reperfusion (I/R). The Nod-like receptor protein-3 (NLRP3) inflammasome also plays a vital role in cerebral I/R damage. However, the effect of UCP2 on NLRP3 inflammasome-mediated hyperglycemia and I/R damage is not clear. In the present study, UCP2-knockout (UCP2-/-) and wild-type (WT) mice were used to establish a model of middle cerebral artery occlusion (MCAO) and reperfusion under normo- and hyperglycemic conditions. HT22 cells were established as a model of oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose to mimic hyperglycemia and I/R in vitro. HT22 cells were treated with/without different concentrations of the UCP2-specific inhibitor genipin for different periods of time. The results showed that UCP2 deficiency significantly increased histopathological changes and apoptosis after cerebral I/R damage in hyperglycemic mice. Moreover, UCP2 deficiency enhanced NLRP3 inflammasome activation in neurons when cerebral I/R damage was exacerbated by hyperglycemia. Furthermore, UCP2 deficiency enhanced NLRP3 inflammasome activation and reactive oxygen species (ROS) production in HT22 cells under OGD/R and high-glucose conditions. UCP2 deficiency aggravated hyperglycemia-induced exacerbation of cerebral I/R damage. UCP2 deficiency also enhanced NLRP3 inflammasome activation and ROS production in neurons in vitro and in vivo. These findings suggest that UCP2 deficiency enhances NLRP3 inflammasome activation following hyperglycemia-induced exacerbation of cerebral I/R damage in vitro and in vivo. UCP2 may be a potential therapeutic target for hyperglycemia-induced exacerbation of cerebral I/R damage.
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Hiperglicemia/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteína Desacopladora 2/deficiência , Animais , Apoptose/fisiologia , Encéfalo/patologia , Linhagem Celular , Feminino , Glucose/deficiência , Glucose/farmacologia , Hiperglicemia/patologia , Hipóxia/fisiopatologia , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
Grass carp is one of the most common farmed fish and its growth rate has been the focus of various studies. However, the impact of long-term exercise on growth rate of juvenile grass carp has not been clearly established. In this study, a four-month exercise trial and liver transcriptome analysis were performed to investigate changes in growth, liver molecular regulatory network and key genes in grass carp. When compared to the non-exercised grass carp (N-EXF), the exercised grass carp (EXF) showed a significant improvement in growth. Liver transcriptome analysis revealed 1714 significantly up-regulated and 1672 significantly down-regulated genes. These genes were enriched in various signaling pathways. These pathways included: those associated with growth, such as the PI3K-Akt and mTOR signaling pathways; those associated with glucose metabolism, such as glycolysis/gluconeogenesis, insulin and AMPK signaling pathways as well as those associated with oxygen transport, such as HIF-1, PI3K-Akt, PPAR and MAPK signaling pathways. In addition, growth-associated genes, such as ghr, igf1 and igf1r; glucose metabolism-associated genes, such as ins and insr as well as oxygen transport-associated genes, such as vhl, pdha and epo were identified. In conclusion, long-term moderate exercise improved the growth rate of grass carp. Our findings elucidate on changes in the liver molecular regulatory network and functional genes that occur during moderate exercise in fish.
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Carpas/genética , Metabolismo Energético/genética , Perfilação da Expressão Gênica , Glucose/metabolismo , Fígado/metabolismo , Oxigênio/metabolismo , Condicionamento Físico Animal , Transdução de Sinais/genética , Transcriptoma , Animais , Carpas/crescimento & desenvolvimento , Carpas/metabolismo , Regulação da Expressão Gênica , Esforço Físico , RNA-Seq , Fatores de TempoRESUMO
Copper sulfides have attracted great attention recently in the thermoelectric community due to the liquid-like behavior of Cu ions. Among the numerous copper sulfides, digenite Cu1.80S has a poorer thermoelectric performance but better stability than the state-of-the-art binary copper sulfide Cu1.97S. In this study, good stability and high thermoelectric performance were simultaneously obtained in Fe-doped Cu1.80S. Because Fe ions will not form a concentration gradient under an external field to change the critical voltage, Fe-doped Cu1.80S samples inherit the good stability of the pristine Cu1.80S. The critical voltage for Cu1.80Fe0.064S is 0.16 V at 750 K, which has been the largest value reported so far. Likewise, the Fe dopants can significantly improve the thermoelectric performance by suppressing the too high electrical conductivity of Cu1.80S. The peak dimensionless figure of merit (zT) for Cu1.80Fe0.064S is around 0.8 at 750 K, about four times that of Cu1.80S. The average zT for Cu1.80Fe0.064S is 0.40 in 300-750 K, which is amongst the highest values in reported thermoelectric sulfides. Combining the good stability and high thermoelectric performance, the present Cu1.80Fe0.064S has great potential to be used in the application of waste heat harvesting in the middle temperature range.
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Circular RNAs (circRNA) are endogenous noncoding RNAs and play important roles in cancer; however, the roles of circRNAs in colon cancer are far from clear. The circRNA expression profile in colon cancer tissues was analyzed by microarray. The data from microarray showed that there were 198 upregulated and 136 downregulated circRNAs in colon cancer tissues. Among the top 10 upregulated circRNAs, hsa_circ_0055625 (circ_0055625) was confirmed to be significantly upregulated in colon cancer tissues. Further analysis demonstrated that circ_0055625 might get involved in the pathogenesis of colon cancer by functioning as miRNA sponges and performed bioinformatics analysis of the predicted circ_0055625/miR-106b-5p (miR-106b)/ITGB8 network. Moreover, we found that circ_0055625 expression was associated with pathological TNM stage and metastasis. These data indicated that circ_0055625/miR-106b/ITGB8 played a role in promoting tumor growth and metastasis, which suggested that circ_0055625 was a potential biomarker of colon cancer.
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Neoplasias do Colo/patologia , Perfilação da Expressão Gênica/métodos , Cadeias beta de Integrinas/genética , Cadeias beta de Integrinas/metabolismo , MicroRNAs/genética , RNA Circular/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Análise de Sequência com Séries de OligonucleotídeosRESUMO
Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA-21 (miR-21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up-regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR-21 overexpression (p < .05 or p < .01). On the other side, miR-21 silence showed contrary results (p < .05) as relative to miR-21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down-regulating miR-21.
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Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MicroRNAs/genética , Neoplasias Gástricas/patologia , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metástase Neoplásica , Triterpenos Pentacíclicos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias Gástricas/genéticaRESUMO
A highly diastereo- and enantioselective cascade annulation reaction of Morita-Baylis-Hillman (MBH) maleimides of isatins with ortho-hydroxychalcones was achieved by a chiral N,N'-dioxide/Mg(II) complex Lewis acid catalyst. This strategy provides a concise and efficient route to densely functionalized spiro[cyclopentane-1,3'-oxindole] compounds with five consecutive stereocenters. The reaction itself features mild conditions, good functional group compatibility, and broad substrate scope (62 examples, up to 99% yield, up to >20:1 dr, 97% ee). In addition, an obvious ligand acceleration effect and chiral amplification effect were observed. DFT calculations were performed to elucidate the stereoselectivity observed. The gram-scale synthesis and the inhibitory effect of two products on the viability of A549 cells demonstrate the potential utility of the current method.
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Exosomes are a type of cell-derived vesicles that range in size from 30 to 100 nm. They are widely present in various organisms and participate in diverse biological processes, playing crucial roles in tumorigenesis and progression. This study aimed to investigate whether LINC01480 in tumor-derived exosomes is involved in the molecular mechanism of gastric cancer by competitively upregulating the VCAM1 expression through binding miR-204-5p. The study analyzed transcriptome data related to gastric cancer from the cancer genome atlas database and constructed a risk-scoring model for epithelial-mesenchymal transition (EMT)-related lncRNAs to identify eight EMT-related lncRNAs associated with prognosis. EMT-related mRNAs positively correlated with LINC01480 were screened in the ExoRBase database. In vitro cell experiments showed that exosomal LINC01480 can promote the proliferation, migration, invasion, and EMT of gastric cancer cells by upregulating VCAM1 expression through competitive binding with miR-204-5p. In vivo experiments on nude mice showed that exosomal LINC01480 promotes the development of gastric cancer. These results suggest that exosomal LINC01480 could be a potential therapeutic target for gastric cancer.
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MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Animais , Camundongos , MicroRNAs/genética , Neoplasias Gástricas/genética , RNA Endógeno Competitivo , Camundongos Nus , RNA Longo não Codificante/genética , Proliferação de Células/genética , Linhagem Celular TumoralRESUMO
Frailty syndrome refers to the nonspecific state of increased body vulnerability and decreased antistress and recovery abilities after stress during aging. Sarcopenia is the major component of frailty and is characterized by the gradual loss of muscle mass, strength, and function with age. Inflammaging is the gradual increase in inflammatory status during aging, and it disrupts immune tolerance, causes physiological changes in tissues, organs, and normal cells, and is related to frailty and sarcopenia. The gut microbiota is an extremely complex and diverse microbial community that coevolves with the host. The composition and structure of the gut microbiota and the metabolism of tryptophan (Trp) significantly change in older adults with frailty and sarcopenia. The gut microbiota participates in regulating the Trp metabolic pathways of kynurenine (Kyn), 5-hydroxytryptamine (5-HT), and indole in the gastrointestinal tract. The Trp metabolites derived from the gut microbiota may synergistically promote the occurrence of age-related frailty and sarcopenia by promoting inflammation in the intestines, nervous system, and muscles. The role and mechanisms of the gut microbiota, Trp metabolism, and inflammaging in age-related frailty and sarcopenia may be a worthwhile research direction to help promote healthy aging.
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Fragilidade , Microbioma Gastrointestinal , Sarcopenia , Humanos , Idoso , Triptofano/metabolismo , Microbioma Gastrointestinal/fisiologia , Idoso FragilizadoRESUMO
RATIONALE: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes. PATIENT CONCERNS: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation. DIAGNOSES: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy. INTERVENTIONS: The patient was given methylprednisolone and VDZ cessation. OUTCOMES: The patient's symptoms improved and remained symptom-free after nearly 2 years. LESSONS: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ.
Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Fármacos Gastrointestinais , Doenças Pulmonares Intersticiais , Humanos , Colite Ulcerativa/tratamento farmacológico , Masculino , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Metilprednisolona/uso terapêuticoRESUMO
OBJECTIVE: The intestine is responsible for approximately one-third of uric acid (UA) excretion. The effect of commensal Enterococcus faecalis (E. faecalis), one of the most colonized bacteria in the gut, on UA excretion in the intestine remains to be investigated. The aim of this study was to evaluate the effect of commensal E. faecalis on UA metabolism and gut microbiota. METHODS: The 16S rRNA gene sequencing was used to examine the species of Enterococcus in mouse fecal content. E. faecalis strain was isolated from mouse feces and identified to be E. faecalis W5. The hyperuricemia (HUA) animal model was established with yeast-rich forage and 250 mg·kg-1 ·day-1 potassium oxonate. Oral administration of E. faecalis W5 was given for 20 days, serving as the Efa group. RESULTS: Disrupted intestinal barrier, activated proinflammatory response and low UA excretion in the intestine were found in HUA mice. After E. faecalis W5 treatment, the gut barrier was restored and serum UA level was decreased. Additionally, fecal and intestinal UA levels were elevated, intestinal urate transporter ABCG2 and purine metabolism were upregulated. Moreover, short-chain fatty acid levels were increased, and intestinal inflammation was ameliorated. CONCLUSIONS: Commensal E. faecalis W5 ameliorated HUA through reversing the impaired gut barrier, promoting intestinal UA secretion by regulating ABCG2 expression, and decreasing intestinal UA synthesis by regulating purine metabolism. The results may provide the potential for developing treatments for HUA through the intestine.