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1.
World J Gastrointest Oncol ; 16(9): 3771-3780, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39350992

RESUMO

The microbiota is strongly association with cancer. Studies have shown significant differences in the gastric microbiota between patients with gastric cancer (GC) patients and noncancer patients, suggesting that the microbiota may play a role in the development of GC. Although Helicobacter pylori (H. pylori) infection is widely recognized as a primary risk factor for GC, recent studies based on microbiota sequencing technology have revealed that non-H. pylori microbes also have a significant impact on GC. A recent study discovered that Streptococcus anginosus (S. anginosus) is more prevalent in the gastric mucosa of patients with GC than in that of those without GC. S. anginosus infection can spontaneously induce chronic gastritis, mural cell atrophy, mucoid chemotaxis, and heterotrophic hyperplasia, which promote the development of precancerous lesions of GC (PLGC). S. anginosus also disrupts the gastric barrier function, promotes the proliferation of GC cells, and inhibits apoptosis. However, S. anginosus is underrepresented in the literature. Recent reports suggest that it may cause precancerous lesions, indicating its emerging pathogenicity. Modern novel molecular diagnostic techniques, such as polymerase chain reaction, genetic testing, and Ultrasensitive Chromosomal Aneuploidy Detection, can be used to gastric precancerous lesions via microbial markers. Therefore, we present a concise summary of the relationship between S. anginosus and PLGC. Our aim was to further investigate new methods of preventing and treating PLGC by exploring the pathogenicity of S. anginosus on PLGC.

2.
Digit Health ; 10: 20552076241277030, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224796

RESUMO

Objective: Readmission to the coronary care unit (CCU) has significant implications for patient outcomes and healthcare expenditure, emphasizing the urgency to accurately identify patients at high readmission risk. This study aims to construct and externally validate a predictive model for CCU readmission using machine learning (ML) algorithms across multiple hospitals. Methods: Patient information, including demographics, medical history, and laboratory test results were collected from electronic health record system and contributed to a total of 40 features. Five ML models: logistic regression, random forest, support vector machine, gradient boosting, and multilayer perceptron were employed to estimate the readmission risk. Results: The gradient boosting model was selected demonstrated superior performance with an area under the receiver operating characteristic curve (AUC) of 0.887 in the internal validation set. Further external validation in hold-out test set and three other medical centers upheld the model's robustness with consistent high AUCs, ranging from 0.852 to 0.879. Conclusion: The results endorse the integration of ML algorithms in healthcare to enhance patient risk stratification, potentially optimizing clinical interventions, and diminishing the burden of CCU readmissions.

3.
J Neurosci ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227159

RESUMO

Targeting altered expression and/or activity of GABA transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABAA inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon (IFN I)-independent manner. Stimulation of the STING-GAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GATs expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits.Significance Statement GABA concentration in extracellular space is maintained by GABA release and clearance of GABA back to brain cells for degradation. GABA clearance from the synaptic cleft predominantly depends on level and activity of GABA transporters (GATs) in the brain. Insufficient GABA clearance resulted to an aberrant tonic GABAA inhibition in brain. In this study, we have identified an unusually high GABA content in brain of STING-deficient mice, resulting in cognitive impairment. Our results show that STING regulates GATs expression through STING-TBK1-IRF3 pathway and thus regulates GABAergic tone. This is the first study that indicates that the STING-TBK1-IRF3 signaling pathway maintains GABA homeostasis in brain, which may offer a novel therapeutic target for modulating GABAergic tone in cases of cognitive dysfunction.

4.
Heliyon ; 10(17): e36815, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39263147

RESUMO

Backgrounds: Risk stratification for major adverse cardiovascular events (MACE) within one year in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) remains a challenge. Although several predictive models based on machine learning have emerged, they are difficult to understand. This study aimed to develop a machine learning prediction model that is easy to understand and trustworthy by lay people to assess the risk of MACE in ACS patients undergoing PCI within one year of the procedure. Methods: This retrospective cohort study used medical data from 1105 patients to construct a machine-learning model. To ensure thoroughness and multidimensionality of model parsing, Shapley Additive explanations (SHAP) analysis and Local interpretable model-agnostic explanations (LIME) interpretation techniques were used to systematically and deeply interpret the constructed models from a global to a detailed level. Results: The study assessed 12 machine learning methods' prediction models and found that the Random Forest model was the most effective in predicting the risk of MACE in ACS patients after undergoing PCI. The model achieved an AUC value of 0.807 in the validation set, with an accuracy of 0.82, and a stable F1 score of 0.51. SHAP analysis ranked eight key feature variables, such as LVEF, in global importance. The weights of each feature range in the prediction model were revealed using LIME analysis. Conclusion: The machine learning prediction model we developed is capable of accurately predicting the likelihood of patients with ACS experiencing a MACE within one year of surgery.

5.
BMC Neurol ; 24(1): 328, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243002

RESUMO

BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Progressão da Doença , Humanos , Masculino , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Constrição Patológica/epidemiologia , Adulto , Idoso , Hipertensão/epidemiologia , Hipertensão/complicações
6.
J Cancer ; 15(17): 5839-5840, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308688

RESUMO

[This corrects the article DOI: 10.7150/jca.19723.].

7.
Free Radic Biol Med ; 224: 630-643, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299527

RESUMO

Ectopic lipid accumulation induced lipotoxicity plays a crucial role in exacerbating the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of the worldwide population and 85% of the obese population. The growing demand for effective therapeutic agents highlights the need for high-efficacy lipotoxicity ameliorators and relevant therapeutic targets in the fight against MASLD. This study aimed to discover natural anti-lipotoxic and anti-MASLD candidates and elucidate the underlying mechanism and therapeutic targets. Utilizing palmitic acid (PA)-induced HepG-2 and primary mouse hepatocyte models, we identified linoleic acid (HN-002), a ligand of fatty acid binding protein 4 (FABP4), from the marine fungus Eutypella sp. F0219. HN-002 dose-dependently prevented lipid overload-induced hepatocyte damage and lipid accumulation, inhibited fatty acid esterification, and ameliorated oxidative stress. These beneficial effects were associated with improvements in mitochondrial adaptive oxidation. HN-002 treatment enhanced lipid transport into mitochondria and oxidation, inhibited mitochondrial depolarization, and reduced mitochondrial ROS (mtROS) level in PA-treated hepatocytes. Mechanistically, HN-002 treatment disrupted the interaction between KEAP1 and NRF2, leading to NRF2 deubiquitylation and nuclear translocation, which activated beneficial metabolic regulation. In vivo, HN-002 treatment (20 mg/kg/per 2 days, i. p.) for 25 days effectively reversed hepatic steatosis and liver injury in the fast/refeeding plus high-fat/high-cholesterol diet induced MASLD mice. These therapeutic effects were associated with enhanced mitochondrial adaptive oxidation and activation of NRF2 signaling in the liver. These data suggest that HN-002 would be an interesting candidate for MASLD by improving mitochondrial oxidation via the FABP4/KEAP1/NRF2 axis. The discovery offers new insights into developing novel anti- MASLD agents derived from marine sources.

8.
Sci Total Environ ; 953: 175980, 2024 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-39236823

RESUMO

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R2 = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment.


Assuntos
Disponibilidade Biológica , Cádmio , Microbioma Gastrointestinal , Oryza , Oryza/metabolismo , Cádmio/metabolismo , Humanos , Animais , Camundongos , Células CACO-2 , Contaminação de Alimentos/análise , Poluentes do Solo/metabolismo , Poluentes do Solo/análise
9.
Am J Clin Pathol ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39290045

RESUMO

Epstein-Barr Virus (EBV) positive primary cutaneous marginal zone lymphoma (PCMZL) is uncommon and subsequent transformation is rare. METHODS: We report a patient with EBV positive PCMZL with subsequent transformation to plasmablastic lymphoma and review the literature for transformed PCMZL to assess clinical and pathologic characteristics. In the case we describe, the patient presented with multifocal PCMZL, developed large B cell transformation with plasmacytic differentiation, followed by plasmablastic transformation (PBL), and ultimately died of disease progression despite multiple lines of therapy. Past history was significant for psoriatic arthritis (multiple prior lines of immunomodulatory therapy). The lymphomas and non-involved bone marrow share the same somatic DNMT3A and TET2 mutations, suggesting clonal relatedness and an association with clonal hematopoiesis (CH). RESULTS: Eighteen cases complied the cohort (seventeen cases from the literature and the case reported herein). Nearly half of the eighteen cases of PCMZL with transformation died of progressive disease (44%). Transformed cases were more commonly seen in patients with >2 sites at initial diagnosis. EBV was assessed in 5 patients, 3 were positive (all died of disease). Two patients with NGS studies demonstrated TET2 and DNMT3A mutations. CONCLUSIONS: Transformation of EBV positive PCMZL appears to be a poor prognostic indicator, with our reported case being the first well defined case transformed to PBL, suspected to arise from myeloid-CH.

10.
Prostaglandins Other Lipid Mediat ; 175: 106900, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39265778

RESUMO

Several interventional studies have revealed the beneficial impact of curcumin supplementation on blood pressure and endothelial function, but the findings are conflicting. Therefore, this study was conducted to investigate the effects of curcumin supplementation on blood pressure and endothelial function. A meta-analyses of randomized clinical trials were performed by searching PubMed, Embase, Scopus, and Web of Science were searched up to March 31, 2024. Random effects models were used to calculate weighted mean differences (WMD). Pooled estimates of 10 studies revealed that curcumin decreased diastolic blood pressure (DBP) [WMD = -0.94, 95 % CI: -1.59, -0.30; p = 0.004], pulse wave velocity (PWV) [WMD = -45.60, 95 % CI: -88.16, -3.04; p = 0.03, I2 = 0.0 %, p = 0.59], and vascular cell adhesion molecule-1 (VCAM-1) [WMD = -39.19; 95 % CI: -66.15, -12.23, p =0.004; I2=73.0 %, p = 0.005] significantly, and increased flow-mediated dilation (FMD) [WMD = 1.64, 95 % CI: 1.06, 2.22; p < 0.001, I2 = 0.0 %, p = 0.61. However, curcumin did not significantly change systolic blood pressure (SBP) [WMD = -0.64, 95 % CI: -1.96, 0.67; p =0.34, I2 = 83.5 %, p <0.001], and Intercellular Adhesion Molecule 1 (ICAM1) [WMD = -17.05; 95 % CI: -80.79, 46.70, p =0.601; I2=94.1 %, p < 0.001]. These results suggest that curcumin has a beneficial effect on DBP, PWV, VCAM-1 and FMD levels and may be an effective adjunctive therapy for improving blood pressure and endothelial function.

11.
Patient Prefer Adherence ; 18: 2007-2017, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39345758

RESUMO

Objective: The objective of this study is to systematically explore and summarize the best evidence on intervention programs for patients with kinesophobia following percutaneous coronary intervention (PCI) to provide a comprehensive reference for clinical practice interventions. Methods: Evidence on interventions for kinesophobia post-PCI was retrieved from Chinese and international integrated databases, treatment guidelines, and websites of professional associations, including systematic reviews and expert consensuses. The evidence considered in this study extends up to May 2022, encompassing information available since the inception of the databases. Two researchers independently evaluated the articles included in the review and extracted and summarized the available evidence. Results: By extracting and integrating data from the 14 articles included in this review, we identified six categories: pre-intervention assessment, psychological intervention, health education, rehabilitation training, social support, and quality control. A total of 21 pieces of evidence were summarized, including mental health assessment, physical fitness evaluation, timing and content of health education, development of personalized exercise prescriptions, and risk control. Conclusion: In clinical settings, using evidence-based practices requires developing feasible intervention programs based on comprehensive consideration of hospital resources, allocation of medical personnel, and consideration of patients' preferences to reduce the kinesophobia of patients post-PCI and improve their compliance with exercise rehabilitation.

12.
Int J Mol Sci ; 25(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39337700

RESUMO

The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.


Assuntos
Mutação , Doenças Mieloproliferativas-Mielodisplásicas , Proteínas Proto-Oncogênicas , Humanos , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Mieloproliferativas-Mielodisplásicas/genética , Doenças Mieloproliferativas-Mielodisplásicas/classificação , Idoso de 80 Anos ou mais , Proteínas Proto-Oncogênicas/genética , Adulto , Dioxigenases , Fatores de Processamento de Serina-Arginina/genética , Janus Quinase 2/genética , Proteínas de Ligação a DNA/genética , Genômica/métodos , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/patologia , Síndromes Mielodisplásicas/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/diagnóstico , Proteínas Repressoras/genética , Fatores de Processamento de RNA/genética , Proteínas de Transporte , Proteínas Nucleares
14.
Front Physiol ; 15: 1459031, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39282085

RESUMO

Introduction: The trend of human migration to terrestrial high altitudes (HA) has been increasing over the years. However, no published prospective studies exist with follow-up periods exceeding 1 month to investigate the cardiac change. This prospective study aimed to investigate the changes in cardiac structure and function in healthy young male lowlanders following long-term migration to HA. Methods: A total of 122 Chinese healthy young males were divided into 2 groups: those migrating to altitudes between 3600 m and 4000 m (low HA group, n = 65) and those migrating to altitudes between 4000 m and 4700 m (high HA group, n = 57). Traditional echocardiographic parameters were measured at sea level, 1 month and 1 year after migration to HA. Results: All 4 cardiac chamber dimensions, areas, and volumes decreased after both 1 month and 1 year of HA exposure. This reduction was more pronounced in the high HA group than in the low HA group. Bi-ventricular diastolic function decreased after 1 month of HA exposure, while systolic function decreased after 1 year. Notably, these functional changes were not significantly influenced by altitude differences. Dilation of the pulmonary artery and a progressive increase in pulmonary artery systolic pressure were observed with both increasing exposure time and altitude. Additionally, a decreased diameter of the inferior vena cava and reduced bicuspid and tricuspid blood flow velocity indicated reduced blood flow following migration to the HA. Discussion: 1 year of migration to HA is associated with decreased blood volume and enhanced hypoxic pulmonary vasoconstriction. These factors contribute to reduced cardiac chamber size and slight declines in bi-ventricular function.

15.
Front Bioeng Biotechnol ; 12: 1458362, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295845

RESUMO

Urinary cell-free DNA (UcfDNA) is gaining recognition as an important biomarker for diagnosing bladder cancer. UcfDNA contains tumor derived DNA sequences, making it a viable candidate for non-invasive early detection, diagnosis, and surveillance of bladder cancer. The quantification and qualification of UcfDNA have demonstrated high sensitivity and specificity in the molecular characterization of bladder cancer. However, precise analysis of UcfDNA for clinical bladder cancer diagnosis remains challenging. This review summarizes the history of UcfDNA discovery, its biological properties, and the quantitative and qualitative evaluations of UcfDNA for its clinical significance and utility in bladder cancer patients, emphasizing the critical role of UcfDNA in bladder cancer diagnosis. Emerging bioactive technologies and materials currently offer promising tools for multiple UcfDNA analysis, aiming to achieve more precise and efficient capture of UcfDNA, thereby significantly enhancing diagnostic accuracy. This review also highlights breakthroughs in detection technologies and substrates with the potential to revolutionize bladder cancer diagnosis in clinic.

16.
Phytomedicine ; 134: 155988, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39226708

RESUMO

BACKGROUND: Endometrial cancer (EC) as one of the most prevalent malignancies in the female reproductive system, usually has a poor diagnosis and unfavorable health effects. Neferine (Nef), derived from the edible and medicinal lotus seed, has been known for its functional activity; however, its anti-cancer mechanism for EC remains elusive. PURPOSE: We explored the potential anti-cancer effects and underlying molecular mechanisms of Nef on EC. METHODS: The cytotoxicity was tested using MTT, and the cell cycle, apoptosis, Ca2+ levels, and the mitochondrial membrane potential (MMP) were observed through flow cytometry. After Nef treatment, differences in miRNA expression were identified using miRNA-seq data. Furthermore, western blot and immunohistochemistry (IHC) were employed to identify the proteins associated with apoptosis in both mice and cells. RESULTS: Nef treatment led to Ishikawa cell apoptosis and blocked cell proliferation in the G2/M phase. In total, 101 significantly different miRNA (p 〈 0.05 and |logFC| 〉 1) were obtained and subjected to GO and KEGG enrichment analysis, which revealed the Ca2+ and PI3K/AKT signaling pathways pertaining to apoptosis. Nef treatment significantly changed intracellular Ca2+ levels and MMP, activating the endoplasmic reticulum stress (ERS) pathway and the expression of key proteins in the mitochondrial pathway. In addition, Nef also inhibited the expression of key proteins in the PI3K/AKT pathway, causing cell apoptosis. Moreover, in mouse tumor tissues, the expression of CHOP, Bcl-2, Caspase 3, Cyto-c, and p-AKT was also consistent with the results in vitro. CONCLUSION: Nef could block the cell cycle and induce the activation of the mitochondrial apoptotic pathway involving the Ca2+-mediated ERS pathway and the PI3K/AKT pathway, thereby inducing apoptosis in EC cells, confirming the potential role of Nef in the prevention and treatment of EC.


Assuntos
Apoptose , Benzilisoquinolinas , Cálcio , Neoplasias do Endométrio , Estresse do Retículo Endoplasmático , MicroRNAs , Feminino , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Cálcio/metabolismo , Linhagem Celular Tumoral , Camundongos , Benzilisoquinolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Nelumbo/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos Fitogênicos/farmacologia
17.
Fitoterapia ; 178: 106174, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39122119

RESUMO

Under the guidance of MS/MS-based molecular networking, five new clerodane diterpenoid glucosides, tinosinesides R-V (1-5), along with 15 known diterpenoids (6-20), were isolated from the stems of Tinospora sinensis. Compound 1 represents the first example of diterpenoid bearing a thio sugar and compound 5 is the first 18,19-dinor-clerodane with cis-fused A/B ring. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. Selected compounds were evaluated for their immunomodulatory effect and several compounds could enhance the proliferation of B lymphocytes. Preliminary mechanistic studies disclosed that 3 could promote B cell generation and inhibit B cell differentiation.


Assuntos
Linfócitos B , Diterpenos Clerodânicos , Compostos Fitoquímicos , Tinospora , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/isolamento & purificação , Diterpenos Clerodânicos/química , Tinospora/química , Estrutura Molecular , Linfócitos B/efeitos dos fármacos , Animais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Caules de Planta/química , China , Camundongos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/química
19.
Acta Pharmacol Sin ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152295

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15 (5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15 was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15 significantly reduced Aß accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15 and the necessity of the CaMKIIα/Fos for FO-4-15 was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15 and mGluR1 was displayed by Ca2+ flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15 was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15 may hold promise as a potential treatment for Alzheimer's disease.

20.
Rev Cardiovasc Med ; 25(7): 238, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39139427

RESUMO

Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.

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