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1.
Heliyon ; 10(18): e37624, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39309918

RESUMO

Introduction: Previous studies have suggested a potential correlation between psoriasis (PS) and ulcerative colitis (UC). However, studies exploring the shared mechanisms of both diseases remain limited. Current treatments primarily involve using immunosuppressive drugs, which can lead to potential side effects and drug resistance. Traditional Chinese medicine has demonstrated favorable efficacy in treating UC and PS with fewer side effects. This study aims to elucidate the shared biological mechanisms underlying UC and PS and to predict natural compounds effective for treating both disorders. Method: We collected and validated differentially expressed genes associated with UC and PS from the Gene Expression Omnibus database. A protein-protein interaction network was constructed using the STRING database, aiding in identifying core targets. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were utilized to analyze the functions and genomic enrichment of the identified core targets. The CIBERSORT method was employed to assess the correlation of core targets with immune cells. Compounds with potential therapeutic values were selected from the Coremine and TCMSP databases, and their therapeutic efficacy was predicted via molecular docking. Results: In UC and PS, 20 common core targets were identified, with matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 1 (MMP1), cluster of differentiation 274 (CD274), C-X-C motif chemokine ligand 10 (CXCL10), and topoisomerase II alpha (TOP2A) emerging as the most relevant targets shared between both conditions. Elevated levels of macrophages and dendritic cells were observed in UC and PS, with CXCL10 exhibiting the closest association with macrophages. UC and PS shared common signaling pathways, including IL-17, TNF, and chemokine signaling pathways, among others. Molecular docking revealed that quercetin, baicalen, irisolidone, rutaecarpine, epigallocatechin-3-gallate, and others held potential as natural compounds for treating both disorders. Conclusion: MMP9, MMP1, and CXCL10, central mediators in the inflammatory pathways of UC and PS, establish a shared mechanism by triggering cytokine and chemokine activation, leading to tissue damage and positioning them as promising therapeutic targets for both conditions. Compounds such as quercetin, luteolin, irisolidone, rutaecarpine, and so on may be key drugs for treating both conditions. These findings suggest the potential advancement of therapeutic strategies and the enhancement of patient care by exploring shared mechanisms and predicting promising natural compounds for treating UC and PS.

2.
Front Neurol ; 15: 1431127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233685

RESUMO

Objectives: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing condition linked to the accelerated onset of mild cognitive impairment (MCI). However, the prevalence of undiagnosed MCI among OSA patients is high and attributable to the complexity and specialized nature of MCI diagnosis. Timely identification and intervention for MCI can potentially prevent or delay the onset of dementia. This study aimed to develop screening models for MCI in OSA patients that will be suitable for healthcare professionals in diverse settings and can be effectively utilized without specialized neurological training. Methods: A prospective observational study was conducted at a specialized sleep medicine center from April 2021 to September 2022. Three hundred and fifty consecutive patients (age: 18-60 years) suspected OSA, underwent the Montreal Cognitive Assessment (MoCA) and polysomnography overnight. Demographic and clinical data, including polysomnographic sleep parameters and additional cognitive function assessments were collected from OSA patients. The data were divided into training (70%) and validation (30%) sets, and predictors of MCI were identified using univariate and multivariate logistic regression analyses. Models were evaluated for predictive accuracy and calibration, with nomograms for application. Results: Two hundred and thirty-three patients with newly diagnosed OSA were enrolled. The proportion of patients with MCI was 38.2%. Three diagnostic models, each with an accompanying nomogram, were developed. Model 1 utilized body mass index (BMI) and years of education as predictors. Model 2 incorporated N1 and the score of backward task of the digital span test (DST_B) into the base of Model 1. Model 3 expanded upon Model 1 by including the total score of digital span test (DST). Each of these models exhibited robust discriminatory power and calibration. The C-statistics for Model 1, 2, and 3 were 0.803 [95% confidence interval (CI): 0.735-0.872], 0.849 (95% CI: 0.788-0.910), and 0.83 (95% CI: 0.763-0.896), respectively. Conclusion: Three straightforward diagnostic models, each requiring only two to four easily accessible parameters, were developed that demonstrated high efficacy. These models offer a convenient diagnostic tool for healthcare professionals in diverse healthcare settings, facilitating timely and necessary further evaluation and intervention for OSA patients at an increased risk of MCI.

3.
Am J Cancer Res ; 14(8): 3800-3815, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267661

RESUMO

Aberrant RSPO1 expression is implicated in tumor progression across various cancers and correlates with anti-cancer immune cell characteristics. However, the specific role of R-spondin 1 (RSPO1) in lung adenocarcinoma (LUAD) remains unclear. In this study, we utilized data from The Cancer Genome Atlas (TCGA) to assess RSPO1 expression across 33 tumor types. Kaplan-Meier (K-M) analysis revealed the prognostic significance of RSPO1 in various cancers. Using statistical software R, we examined RSPO1's associations with immune cell infiltration, methylation, mutation, and competing endogenous RNA (ceRNA) networks. Exploration via the Tumor Immune Single Cell Hub (TISCH) database uncovered RSPO1's link to the tumor microenvironment (TME) and identified potential small molecule drug targets. We further investigated RSPO1's impact on LUAD cell proliferation, metastasis, and the Wnt pathway in vitro. Our findings highlight RSPO1's role in cancer progression and suggest its potential as both a prognostic marker and therapeutic target in LUAD, implicating the modulation of the Wnt pathway.

4.
Nat Immunol ; 25(9): 1565-1579, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39103576

RESUMO

Nucleophosmin 1 (NPM1) is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Concurrent inflammatory bowel diseases (IBD) and MDS are common, indicating a close relationship between IBD and MDS. Here we examined the function of NPM1 in IBD and colitis-associated colorectal cancer (CAC). NPM1 expression was reduced in patients with IBD. Npm1+/- mice were more susceptible to acute colitis and experimentally induced CAC than littermate controls. Npm1 deficiency impaired the function of interleukin-22 (IL-22)-producing group three innate lymphoid cells (ILC3s). Mice lacking Npm1 in ILC3s exhibited decreased IL-22 production and accelerated development of colitis. NPM1 was important for mitochondrial biogenesis and metabolism by oxidative phosphorylation in ILC3s. Further experiments revealed that NPM1 cooperates with p65 to promote mitochondrial transcription factor A (TFAM) transcription in ILC3s. Overexpression of Npm1 in mice enhanced ILC3 function and reduced the severity of dextran sulfate sodium-induced colitis. Thus, our findings indicate that NPM1 in ILC3s protects against IBD by regulating mitochondrial metabolism through a p65-TFAM axis.


Assuntos
Colite , Imunidade nas Mucosas , Camundongos Knockout , Mitocôndrias , Proteínas Nucleares , Nucleofosmina , Fosforilação Oxidativa , Animais , Mitocôndrias/metabolismo , Camundongos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Humanos , Colite/imunologia , Colite/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Interleucina 22 , Imunidade Inata , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Sulfato de Dextrana , Masculino , Interleucinas/metabolismo , Interleucinas/genética , Interleucinas/imunologia , Feminino
5.
Diabetes Metab Syndr Obes ; 17: 2967-2974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139742

RESUMO

Objective: Visceral fat area (VFA) levels have been found to exhibit a strong association with various conditions such as insulin resistance (IR), inflammation, oxidative stress, metabolic syndrome (MetS), hyperlipidemia, diabetes, and its vascular complications. These complications include hypertension, cardiovascular disease, diabetic retinopathy (DR), albuminuria, and cardiovascular autonomic dysfunction, which is considered one of the main types of diabetic neuropathy. This study aimed to investigate the correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes (T2DM). Methods: A retrospective analysis of clinical data of patients diagnosed with type 2 diabetes admitted to our hospital was conducted. After excluding 28 cases, a total of 488 patients were included, divided into the group with peripheral neuropathy (207 cases) and the control group without peripheral neuropathy (281 cases). The correlation between VFA and the presence of DPN was assessed using correlation and multiple logistic regression analyses. Results: In terms of general information, the group with peripheral neuropathy had lower BMI but longer duration of diabetes compared to the control group. Regarding biochemical indicators, VFA were lower in the group with peripheral neuropathy, while FPG and HbA1c levels were higher (all P<0.05). Spearman correlation analysis showed a negative correlation between VFA, and the presence of peripheral neuropathy in patients with type 2 diabetes (P<0.05). Logistic regression analysis indicated that VFA, duration of diabetes, and HbA1c level were influencing factors for the occurrence of peripheral neuropathy in patients with type 2 diabetes (P<0.05). Conclusion: This study revealed a correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes, highlighting the importance of monitoring visceral fat in such patients. In addition to lower levels of VFA, factors such as duration of diabetes and glycated hemoglobin (HbA1c) level were also associated with peripheral neuropathy in patients with T2DM.

6.
Front Mol Neurosci ; 17: 1394932, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39169952

RESUMO

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer's disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood-brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid ß (Aß) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress.

7.
Cell Death Differ ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107495

RESUMO

Erk signaling is indispensable for the self-renewal and differentiation of mouse embryonic stem cells (ESCs), as well as telomere homeostasis. But how Erk regulates these biological processes remains unclear. We identified 132 Erk2 interacting proteins by co-immunoprecipitation and mass spectrometric analysis, and focused on Ddx39 as a potential Erk2 substrate. We demonstrated that Erk2 phosphorylates Ddx39 on Y132 and Y138. Ddx39 knockout (KO) ESCs are defective in differentiation, due to reduced H3K27ac level upon differentiation. Phosphorylation of Ddx39 promotes the recruitment of Hat1 to acetylate H3K27 and activate differentiation genes. In addition, Ddx39 KO leads to telomere elongation in ESCs. Ddx39 is recruited to telomeres by the telomere-binding protein Trf1, consequently disrupting the DNA loop formed by Trf1 and suppressing the alternative lengthening of telomeres (ALT). Phosphorylation of Ddx39 weakens its interaction with Trf1, releasing it from telomeres. Thus, ALT activity is enhanced, and telomeres are elongated. Altogether, our studies reveal an essential role of Ddx39 in the differentiation and telomere homeostasis of ESCs.

8.
Health Qual Life Outcomes ; 22(1): 68, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39180073

RESUMO

BACKGROUND: Individuals with sensory processing sensitivity (SPS) tend to be overreactive in response to negative environmental stimuli. More is known about the positive relationship between SPS and quality of life (QoL); nevertheless, less is known regarding the roles of resilience and social determinants in this association. This research aimed to investigate the potential mediation effect of resilience and the moderation effect of social determinants on the relationship between SPS and QoL in a large sample of Chinese cancer patients. METHODS: We used the most recent datasets from an ongoing project conducted in southwest China. A two-stage random sampling strategy with a probability proportionate to sample size (PPS) design was adopted. The associations between resilience, SPS, and QoL were evaluated using a linear regression model. Path analysis was adopted to examine the mediation of resilience. RESULTS: Resilience was positively associated with quality of life, while increased sensory processing sensitivity was negatively associated with quality of life. The restricted cubic spline analysis revealed that as resilience increased, the coefficients of quality of life rapidly increased across all domains. Conversely, the coefficients for quality of life gradually decreased with the escalation of sensory processing sensitivity. Resilience was a significant mediator, accounting for 21.88% of the total SPS-QoL association. The mediation effect of resilience varied across ethnicity and sex. CONCLUSION: Sensory processing sensitivity was significantly associated with quality of life in cancer patients, and promoting resilience could mitigate this negative impact. However, the effect of resilience varies across sex and ethnicity. Therefore, targeted resilience promotion interventions, especially those integrating social characteristics, should be considered for implementation.


Assuntos
Neoplasias , Qualidade de Vida , Resiliência Psicológica , Humanos , Qualidade de Vida/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias/psicologia , China , Adulto , Determinantes Sociais da Saúde , Idoso , Inquéritos e Questionários
9.
BMC Public Health ; 24(1): 2219, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148035

RESUMO

BACKGROUND: Evidence on the prevalence of smoking in China remains insufficient, with most previous studies focusing on a single region. However, smoking prevalence exhibits significant inequalities across the entire country. This study aimed to evaluate the risk of tobacco prevalence across the country, taking into account spatial inequalities. METHODS: The data used in this study were collected in 23 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in 2022. Large population survey data were used, and a Bayesian geostatistical model was employed to investigate smoking prevalence rates across multiple spatial domains. FINDINGS: Significant spatial variations were observed in smokers and exposure to secondhand smoke across China. Higher levels of smokers and secondhand smoke exposure were observed in western and northeastern regions. Additionally, the autonomous region of Tibet, Shanghai municipality, and Yunnan province had the highest prevalence of smokers, while Tibet, Qinghai province, and Yunnan province had the highest prevalence of exposure to secondhand smoke. CONCLUSION: We have developed a model-based, high-resolution nationwide assessment of smoking risks and employed rigorous Bayesian geostatistical models to help visualize smoking prevalence predictions. These prediction maps provide estimates of the geographical distribution of smoking, which will serve as strong evidence for the formulation and implementation of smoking cessation policies. HIGHLIGHTS: Our study investigated the prevalence of smokers and exposure to secondhand smoke in different spatial areas of China and explored various factors influencing the smoking prevalence. For the first time, our study applied Bayesian geostatistical modeling to generate a risk prediction map of smoking prevalence, which provides a more intuitive and clear understanding of the spatial disparities in smoking prevalence across different geographical regions, economic levels, and development status. We found significant spatial variations in smokers and secondhand smoke exposure in China, with higher rates in the western and northeastern regions.


Assuntos
Teorema de Bayes , Poluição por Fumaça de Tabaco , Humanos , China/epidemiologia , Estudos Transversais , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Prevalência , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fumar/epidemiologia , Fumantes/estatística & dados numéricos , Medição de Risco , Análise Espacial , Epidemias , Adulto Jovem
10.
Biomed Chromatogr ; : e5984, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39152775

RESUMO

P-glycoprotein (P-gp)-mediated herb-drug interactions (HDIs) may impact drug efficacy and safety. Tenacissoside G (Tsd-G), a major active component of Marsdenia tenacissima, exhibits anticancer activity. To analyze the effect of Tsd-G on the pharmacokinetics of paclitaxel (PTX), researchers selected 30 Sprague-Dawley (SD) rats, randomized into a solvent control group, a verapamil positive control group, and 20, 40, and 60 mg/kg Tsd-G groups. After seven consecutive days of intraperitoneal injection of verapamil or Tsd-G, a single dose of 6 mg/kg PTX was injected intravenously. Plasma samples were collected at different time points, and proteins were precipitated using a methanol-acetonitrile solution. An ultrahigh-performance liquid chromatography-tandem mass spectrometry method was developed, with docetaxel as an internal standard, and quantified using positive ion multiple reaction monitoring (MRM) mode. This analytical method's specificity, accuracy, precision, recovery, matrix effect, and sample stability meet the requirements for biological sample determination. After Tsd-G administration in rats, the mean residence time of PTX was significantly prolonged. And Tsd-G can stably bind to P-gp by forming hydrogen bonds and inhibiting the expression of P-gp in rat liver. Although the metabolites of PTX were not detected in this study, the above results still indicate the existence of HDIs between Tsd-G and PTX, and P-gp may be the main target to mediate HDIs.

11.
Nutrition ; 126: 112485, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39096779

RESUMO

OBJECTIVES: The combined impact of sleep quality and diet habits on ischemic stroke remains unclear, particularly in rural populations. Therefore, this study aimed to estimate the individual and joint associations of sleep quality and diet habits with nonfatal ischemic stroke among rural adults. METHODS: A total of 22 536 participants free of stroke were enrolled from the Henan Rural Cohort. Sleep quality and diet habits were evaluated with the Pittsburgh Sleep Quality Index and food frequency questionnaire, respectively. The ischemic stroke incidence was analyzed using Kaplan-Meier curves. Cox regression and restricted cubic spline were employed to estimate the correlation of sleep quality or diet habits with ischemic stroke. RESULTS: During an average 3.92 y of follow-up, 665 ischemic stroke patients were identified. The adjusted hazard ratio (95% confidence interval) of ischemic stroke risk compared with good sleep quality was 1.276 (1.057-1.542). The hazard ratio (95% confidence interval) of nonfatal ischemic stroke compared with unhealthy diet habits was 0.693 (0.589-0.814). The restricted cubic spline indicated that the risk of ischemic stroke increased with the increase of the Pittsburgh Sleep Quality Index. And the higher the diet quality score, the lower the risk of ischemic stroke. (Ptrend < 0.05). Further analysis indicated that the association of poor sleep quality with ischemic stroke was alleviated by healthy diet habits (P < 0.05). Additionally, a robust correlation remained after excluding individuals with ischemic stroke in the first year. CONCLUSIONS: Poor sleep quality was positively associated with nonfatal ischemic stroke among rural adults, and healthy diet habits attenuated this relationship. Developing healthy diet and sleep habits may have potential health implications for preventing ischemic stroke. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (registration no. ChiCTR-OOC-15006699). Date of registration: July 6, 2015.


Assuntos
Dieta Saudável , Comportamento Alimentar , AVC Isquêmico , População Rural , Qualidade do Sono , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Estudos Prospectivos , AVC Isquêmico/epidemiologia , AVC Isquêmico/prevenção & controle , AVC Isquêmico/etiologia , China/epidemiologia , Dieta Saudável/estatística & dados numéricos , Dieta Saudável/métodos , Fatores de Risco , Incidência , Idoso , Adulto , Inquéritos e Questionários , Estudos de Coortes , Modelos de Riscos Proporcionais
13.
J Ethnopharmacol ; 335: 118697, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39154669

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum (Epling and Játiva) is a psychoactive plant traditionally used by the Latinos for various medicinal purposes. Salvinorin A (Sal A), the main bioactive constituent of S. divinorum, is a natural highly selective kappa opioid receptor (KOR) agonist. Considering the anti-inflammatory effect of S. divinorum and endogenous hippocampal dynorphin/kappa opioid receptor (KOR) system playing an anticonvulsant function, we hypothesis that Sal A can be a potential candidate to treat epilepsy. Here, we identified whether Sal A ameliorated epileptic seizures and neuronal damages in animal model and in vitro model and investigated its underlying mechanisms. MATERIALS AND METHODS: Mice epilepsy model was induced by pilocarpine following seizures assessed by Racine classification. Hippocampus tissues were obtained for genetic, protein, and histological investigation. Furthermore, lipopolysaccharide (LPS)-activated BV2 microglial cells were utilized to validate the anti-inflammatory and microglia polarization regulation effects of Sal A. RESULTS: Sal A treatment significantly prolonged the latency to status epileptics (SE) and shortened the duration of SE in the pilocarpine-induced model. It also alleviated neuronal damages via activation of the AMPK/JNK/p-38 MAPK pathway and inhibition of apoptosis-related protein in hippocampus tissues. Furthermore, Sal A dose-dependently reduced microglia-mediated expression of pro-inflammatory cytokines and increased anti-inflammatory factors levels in SE mice and LPS-activated BV2 microglial cells by regulating microglia polarization. In addition, the effect of Sal A in vitro was totally blocked by KOR antagonist nor-BNI. CONCLUSION: Sal A treatment protects against epileptic seizures and neuronal damages in pilocarpine-induced models by suppressing the inflammation response through regulating microglial M1/M2 polarization. This study might serve as a theoretical basis for clinical applications of Sal A and its analogs and provide a new insight into the development of anti-seizure drugs.


Assuntos
Diterpenos Clerodânicos , Hipocampo , Microglia , Pilocarpina , Convulsões , Animais , Microglia/efeitos dos fármacos , Microglia/metabolismo , Pilocarpina/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/uso terapêutico , Masculino , Camundongos , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Anticonvulsivantes/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/isolamento & purificação
15.
Artigo em Inglês | MEDLINE | ID: mdl-39030705

RESUMO

In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal (5 mM) and high (25 mM) glucose conditions. Protein and gene expression levels are assessed by western blot analysis and qPCR respectively, while ROS levels are measured via flow cytometry. ZIPK expression is manipulated using overexpression plasmids, siRNAs, and shRNAs. The effects of the ZIPK inhibitor TC-DAPK6 are evaluated in a diabetic rat model. Our results show that high glucose significantly upregulates ZIPK, STAT5A, p53, and NOS2 expressions in HUVECs, thus increasing oxidative stress. Silencing of STAT5A reduces p53 and NOS2 expressions and reactive oxygen species (ROS) accumulation. ZIPK is essential for high glucose-induced p53 expression and ROS accumulation, while silencing of ZIPK reverses these effects. Overexpression of ZIPK combined with STAT5A silencing attenuates glucose-induced alterations in p53 and NOS2 expression, thereby preventing cell damage. Coimmunoprecipitation reveals a direct interaction between ZIPK and STAT5A in the nucleus under high-glucose condition. In diabetic rats, TC-DAPK6 treatment significantly decreases ZIPK, p53, and NOS2 expressions. Our findings suggest that ZIPK plays a critical role in high glucose-induced vascular injury via STAT5A-mediated pathways, proposing that ZIPK is a potential therapeutic target for diabetic vascular complications.

16.
Infect Drug Resist ; 17: 3113-3124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050825

RESUMO

Purpose: The mortality rate from pulmonary tuberculosis (PTB) complicated by severe community-acquired pneumonia (SCAP) in the intensive care unit (ICU) remains high. We aimed to develop a rapid and simple model for the early assessment and stratification of prognosis in these patients. Patients and Methods: All adult patients with PTB complicated by SCAP admitted to the ICU of a tertiary hospital in Chengdu, Sichuan, China between 2019 and 2021 (development cohort) and 2022 (validation cohort) were retrospectively included. Data on demographics, comorbidities, laboratory values, and interventions were collected. The outcome was the 28-day mortality. Stepwise backward multivariate Cox analysis was used to develop a mortality risk prediction score model. Receiver operating characteristic (ROC) and calibration curves were used to evaluate the model's predictive efficiency. Decision curve analysis (DCA) was used to validate the model's clinical value and impact on decision making. Results: Overall, 357 and 168 patients were included in the development and validation cohorts, respectively. The Pulmonary Tuberculosis Severity Index (PTSI) score included long-term use of glucocorticoid, body mass index (BMI) <18.5 kg/m2, diabetes, blood urea nitrogen (BUN) ≥7.14 mmol/L, PO2/FiO2 <150 mmHg, and vasopressor use. The area under the ROC curve (AUC) values were 0.817 (95% CI: 0.772-0.863) and 0.814 for the development and validation cohorts, respectively. The PTSI score had a higher AUC than the APACHE II, SOFA, and CURB-65 score. The calibration curves indicated good calibration in both cohorts. The DCA of the PTSI score indicated the high clinical application of the model compared with the APACHE II and SOFA scores. Conclusion: This prognostic tool was designed to rapidly evaluate the 28-day mortality risk in individuals with PTB complicated by SCAP. It can stratify this patient group into relevant risk categories, guide targeted interventions, and enhance clinical decision making, thereby optimizing patient care and improving outcomes.

17.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3348-3355, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39041098

RESUMO

To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD). A total of 100 4-month-old Wistar male rats were randomly selected as a blank group, and 10 rats were taken as a sham operation group and injected with 1 µL of normal saline on both sides of the hippocampus. The other rats were injected with Aß_(1-42) solution in the hippocampus to replicate the AD model. Fifty successfully modeled rats were selected and randomly divided into the model group, Aricatio group(0.5 mg·kg~(-1)), and high, medium, and low dose groups of Hei Xiaoyaosan(15.30, 7.65, and 3.82 g·kg~(-1)), with 10 rats in each group. The rats were administered by continuous gavage for 42 days. Morris water maze was used to detect the learning and memory ability of rats, and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region. The mRNA expression of p38MAPK, Beclin-1, and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK, Beclin-1, Bcl-2, APP, and related proteins. The level of Aß_(1-42) in the hippocampus was detected by ELISA, and the expression level of LC3Ⅱ in the hippocampus was detected by immunohistochemistry. The experimental results showed that compared with the blank group, the learning and memory ability of rats in the model group decreased(P<0.01). The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged. The mRNA expression of p38MAPK was up-regulated, and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were increased, while those of Beclin-1, Bcl-2, and p-Bcl-2 were decreased(P<0.01). The expression of Aß_(1-42) was increased(P<0.01). The relative expression of LC3Ⅱ decreased(P<0.01). Compared with the model group, the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01). The nuclei in the CA1 region of the hippocampus gradually became clear, showing light blue. The mRNA expression of p38MAPK was down-regulated(P<0.01), and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were down-regulated, while those of Beclin-1, Bcl-2, and p-Bcl-2 were up-regulated(P<0.05 or P<0.01). The expression of Aß_(1-42) was decreased(P<0.01). The relative expression of LC3Ⅱ was increased(P<0.01). It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats, and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway, increasing the level of autophagy, and reducing the accumulation of Aß_(1-42).


Assuntos
Doença de Alzheimer , Autofagia , Proteína Beclina-1 , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos Wistar , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Masculino , Ratos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Autofagia/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Humanos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
China CDC Wkly ; 6(26): 629-634, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38966307

RESUMO

Introduction: This study investigated the lagged correlation between Baidu Index for influenza-related keywords and influenza-like illness percentage (ILI%) across regions in China. The aim is to establish a scientific foundation for utilizing Baidu Index as an early warning tool for influenza-like illness epidemics. Methods: In this study, data on ILI% and Baidu Index were collected from 30 provincial-level administrative divisions (PLADs) spanning April 2014 to March 2019. The Baidu Index was categorized into Overall Index, Ordinary Index, Prevention Index, Symptom Index, and Treatment Index based on search query themes. The lagged correlation between the Baidu Index and ILI% was examined through the cross-correlation function (CCF) method. Results: Correlating the Baidu Overall Index of 30 PLADs with ILI% revealed CCF values ranging from 0.46 to 0.86, with a median lag of 0.5 days. Subcategory analysis indicated that the Prevention Index and Symptom Index exhibited quicker responses to ILI%, with median lags of -9 and -0.5 days, respectively, compared to 0 and 3 days for the Ordinary and Treatment Indexes. The median lag days between the Baidu Index and the ILI% were earlier in the northern PLADs compared to the southern PLADs. Discussion: The Prevention and Symptom Indexes show promising predictive capabilities for influenza-like illness epidemics.

19.
China CDC Wkly ; 6(26): 635-641, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38966311

RESUMO

Introduction: Respiratory infectious diseases, such as influenza and coronavirus disease 2019 (COVID-19), present significant global public health challenges. The emergence of artificial intelligence (AI) and big data offers opportunities to improve traditional disease surveillance and early warning systems. Methods: The study analyzed data from January 2020 to May 2023, comprising influenza-like illness (ILI) statistics, Baidu index, and clinical data from Weifang. Three methodologies were evaluated: the adaptive dynamic threshold method (ADTM) for dynamic threshold adjustments, the machine learning supervised method (MLSM), and the machine learning unsupervised method (MLUM) utilizing anomaly detection. The comparison focused on sensitivity, specificity, timeliness, and warning consistency. Results: ADTM issued 37 warnings with a sensitivity of 71% and a specificity of 85%. MLSM generated 35 warnings, with a sensitivity of 82% and a specificity of 87%. MLUM produced 63 warnings with a sensitivity of 100% and specificity of 80%. The initial warnings from ADTM and MLUM preceded those from MLSM by five days. The Kappa coefficient indicated moderate agreement between the methods, with values ranging from 0.52 to 0.62 (P<0.05). Discussion: The study explores the comparison between traditional methods and two machine learning approaches for early warning systems. It emphasizes the validation of machine learning's reliability and underscores the unique advantages of each method. Furthermore, it stresses the significance of integrating machine learning models with various data sources to enhance public health preparedness and response, alongside acknowledging limitations and the need for broader validation.

20.
JMIR Res Protoc ; 13: e54376, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083341

RESUMO

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common chronic inflammatory skin disease that manifests as itching and wheals, seriously affecting quality of life. Clinical observations and previous research trials have shown that acupuncture is safe and effective for the treatment of CSU. However, there are problems, such as a short duration of action and frequent treatment. Compared with traditional acupuncture, acupoint catgut embedding (ACE) has the advantages of a longer effect and higher compliance. Clinical trials are needed to prove its efficacy and mechanism of action. OBJECTIVE: This trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE. METHODS: This is a randomized, double-blind, placebo-controlled trial. In this trial, 108 participants aged 18-60 years with a diagnosis of CSU and no history of ACE will be randomly assigned to 2 groups (1:1 ratio) using the Statistical Analysis System: treatment (ACE) and control (sham ACE). The participants and efficacy evaluators will be blinded to the grouping. Both the ACE and sham ACE groups will undergo acupuncture, but the sham ACE group will not receive catgut sutures. Treatment will be performed twice weekly for 8 weeks, with a 1-week run-in period and a 16-week follow-up period. Twenty patients will be randomly selected to undergo functional magnetic resonance imaging before and after the treatment period. The primary outcome will be the urticaria activity score over 7 days (UAS7). We will use R (version 4.0.1; R Project for Statistical Computing) to perform ANOVA and independent samples t tests to compare the differences within and between groups before and after treatment by judging the rejection range based on a significance level of .05. RESULTS: The study protocol has been approved by the Ethics Committee of Guang'anmen Hospital on September 7, 2022, and has been registered on November 30, 2022. Recruitment began on March 1, 2023. A total of 4-6 participants are expected to be recruited each month. The recruitment is planned to be completed on March 1, 2025, and we expect to publish our results by the winter of 2025. As of November 1, 2023, we have enrolled 25 participants with CSU. CONCLUSIONS: This randomized, double-blind, placebo-controlled trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE. We hypothesize that wheals and itching will show greater improvement in participants receiving active therapy than in those receiving sham treatment. The limitations of this study include its single-center trial design, small sample size, and short treatment duration, which may have certain impacts on the research results. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200066274; https://www.chictr.org.cn/showprojEN.html?proj=179056. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54376.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Categute , Urticária Crônica , Humanos , Método Duplo-Cego , Adulto , Urticária Crônica/terapia , Terapia por Acupuntura/métodos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Feminino , Masculino , Resultado do Tratamento
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