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1.
Biol Reprod ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832713

RESUMO

Forkhead box L2 (FOXL2) is an indispensable key regulator of female follicular development, and it plays important roles in the morphogenesis, proliferation, and differentiation of follicle granulosa cells (GCs), such as establishing normal estradiol signaling and regulating steroid hormone synthesis. Nevertheless, the effects of FOXL2 on GC morphology and the underlying mechanism remain unknown. Using FOXL2 ChIP-seq analysis, we found that FOXL2 target genes significantly enriched in the actin cytoskeleton-related pathways. We confirmed that FOXL2 inhibited the expression of RhoA, a key gene for actin cytoskeleton rearrangement, by binding to TCATCCATCTCT in RhoA promoter region. In addition, the overexpression of FOXL2 in GCs induced the depolymerization of F-actin and the disordered of the actin filaments, resulting in a slowdown in the expansion of GCs, while silencing FOXL2 inhibited F-actin depolymerization and stabilized the actin filaments, thereby accelerating GC expansion. RhoA/ROCK pathway inhibitor Y-27632 exhibited similar effects to FOXL2 overexpression, even reversed the actin polymerization in FOXL2 silencing GCs. This study revealed for the first time that FOXL2 regulated GC actin cytoskeleton by RhoA/ROCK pathway, thus affecting GC expansion. Our findings provide new insights for constructing the regulatory network of FOXL2 and propose a potential mechanism for facilitating rapid follicle expansion, thereby laying a foundation for further understanding follicular development.

2.
Biochem Pharmacol ; 226: 116338, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38848780

RESUMO

ITFG2, as an immune-modulatory intracellular protein that modulate the fate of B cells and negatively regulates mTORC1 signaling. ITFG2 is highly expressed in the heart, but its pathophysiological function in heart disease is unclear. In this study, we found that in MI mice, overexpression of ITFG2 via an AAV9 vector significantly reduced the infarct size and ameliorated cardiac function. Knockdown of endogenous ITFG2 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In cardiac-specific ITFG2 transgenic (TG) mice, myocardial infarction size was smaller, eject fraction (EF) and fractional shortening (FS) was higher compared to those in wild-type (WT) mice, suggesting ITFG2 reversed cardiac dysfunction induced by MI. In hypoxic neonatal cardiomyocytes (NMCMs), overexpression of ITFG2 maintained mitochondrial function by increasing intracellular ATP production, reducing ROS levels, and preserving the mitochondrial membrane potential (MMP). Overexpression of ITFG2 reversed the mitochondrial respiratory dysfunction in NMCMs induced by hypoxia. Knockdown of endogenous ITFG2 by siRNA did the opposite. Mechanism, ITFG2 formed a complex with NEDD4-2 and ATP 5b and inhibited the binding of NEDD4-2 with ATP 5b leading to the reduction ubiquitination of ATP 5b. Our findings reveal a previously unknown ability of ITFG2 to protect the heart against ischemic injury by interacting with ATP 5b and thereby regulating mitochondrial function. ITFG2 has promise as a novel strategy for the clinical management of MI.

3.
Obstet Gynecol Surv ; 79(6): 343-347, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38896430

RESUMO

Importance: Polycystic ovary syndrome (PCOS) is a common endocrine syndrome with multiple causes and polymorphic clinical manifestations, which is one of the important causes of menstrual disorders in women of childbearing age. It has been found that branched-chain amino acids (BCAAs), a class of essential amino acids that cannot be synthesized by the human body, play a significant role in the metabolic changes of PCOS, which may be involved in the pathogenesis of PCOS. Objective: The purpose of this review is to summarize the relevance between BCAAs and metabolic abnormalities in PCOS and to explore their possible mechanisms. Evidence Acquisition: The evidence is mainly obtained by reviewing the literature on PubMed related to PCOS, BCAAs, and related metabolic abnormalities and conducting summary analysis. Results: The metabolism of BCAAs can affect the homeostasis of glucose metabolism, possibly by disrupting the balance of gut microbiota, activating mTORC1 targets, producing mitochondrial toxic metabolites, and increasing the expression of proinflammatory genes. The correlation between obesity and BCAAs in PCOS patients may be related to the gene expression of BCAA metabolism-related enzymes in adipose tissue. The association between BCAA metabolic changes and nonalcoholic fatty liver disease in PCOS patients has not been fully clarified, which may be related to the lipid accumulation caused by BCAAs. At present, it is believed that hyperandrogenism in patients with PCOS is not related to BCAAs. However, through the study of changes in BCAA metabolism in prostate cancer caused by hyperandrogenism, we speculate that the relationship between BCAAs and hyperandrogenism may be mediated by mTORC1 and amino acid transporters. Conclusions and Relevance: Review of prior articles reveals that BCAAs may be related to insulin resistance, obesity, nonalcoholic fatty liver, and hyperandrogenism in PCOS patients, and its mechanisms are complex, diverse, and interrelated. This review also discussed the mechanism of BCAAs and these metabolic disorders in non-PCOS patients, which may provide some help for future research.


Assuntos
Aminoácidos de Cadeia Ramificada , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/complicações , Aminoácidos de Cadeia Ramificada/metabolismo , Feminino , Hiperandrogenismo/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Obesidade/complicações , Resistência à Insulina
4.
Innov Aging ; 8(6): igae040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859823

RESUMO

Background and Objectives: Social networks are crucial to personal health, particularly among caregivers of individuals with dementia; however, different types of social networks among caregivers of those with dementia and how these differences are associated with caregiver burden and positive appraisal, remain underexamined. This study aims to depict dementia caregivers' social network types, related factors, and impact on caregiving experiences. Research Design and Methods: A questionnaire-based survey was conducted with a total of 237 family caregivers of individuals with dementia nested additional semistructured interviews conducted with 14 caregivers in Chongqing, China. A quantitative study was designed to collect data on personal and situational information, social networks, caregiver burden, and positive aspects of caregiving. Qualitative data were collected via semistructured interviews. Latent class analysis and multivariate regression analyses were applied to quantitative data, and inductive content analysis to qualitative data. Results: The 3 social network types-family-limited (n = 39, 16.46%), family-dominant (n = 99, 41.77%), and diverse network (n = 99, 41.77%)-differed in age and sex of caregivers and individuals with dementia, stage of dementia, and caregiving intensity. Caregivers in family-dominant networks had a lower caregiver burden (ß= -0.299, p = .003) and greater positive aspects of caregiving (ß= 0.228, p = .021) than those in family-limited networks. Three themes-accessibility, reciprocity, and reliance-emerged as facilitators and barriers when asking for support. Caregivers frequently cited the perception of economic, practical, and emotional support, yet reported a lack of adequate formal support from healthcare providers. Discussion and Implication: Family caregivers of individuals with dementia have different social network types that vary considerably among sociocultural contexts and perceive various types of support from social networks. Solid family networks and diverse social networks are contributors to long-term dementia care.

5.
Langmuir ; 40(24): 12755-12766, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38848303

RESUMO

Coke oven gas (COG) is considered to be one of the most likely raw materials for large-scale H2 production in the near or medium term, with membrane separation technologies standing out from traditional technologies due to their less energy-intensive structures as well as simple operation and occupation. Based on the "MOF-in/on-COF" pore modification strategy, the COF membrane (named the PBD membrane) and ZIF-67 were used as assembly elements to design advanced molecular sieving membranes for hydrogen separation. The composition and microstructure of membranes before and after ZIF-67 loading as well as ZIF-67-in-PBD membranes under different preparation conditions (metal ion concentration, metal-ligand ratio, and reaction time) were investigated by various characterizations to reveal the synthesis regularity and microstructure regulation. Furthermore, H2/CH4 separation performances and separation mechanisms were also analyzed and compared. Finally, a dense, continuous, ultrathin, and self-supporting ZIF-67-in-PBD membrane with a Co2+ concentration of 0.02 mol/L, a metal-ligand ratio of 1:4, and a reaction time of 6 h exhibited the largest specific surface area, micropore proportion, and the best H2/CH4 separation selectivity (α = 33.48), which was significantly higher than the Robeson upper limit and was in a leading position among reported MOF membranes. The separation mechanism was mainly size screening, and adsorption selectivity also contributed a little.

6.
Nutrients ; 16(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38794754

RESUMO

Alcohol consumption significantly impacts disease burden and has been linked to various diseases in observational studies. However, comprehensive meta-analyses using Mendelian randomization (MR) to examine drinking patterns are limited. We aimed to evaluate the health risks of alcohol use by integrating findings from MR studies. A thorough search was conducted for MR studies focused on alcohol exposure. We utilized two sets of instrumental variables-alcohol consumption and problematic alcohol use-and summary statistics from the FinnGen consortium R9 release to perform de novo MR analyses. Our meta-analysis encompassed 64 published and 151 de novo MR analyses across 76 distinct primary outcomes. Results show that a genetic predisposition to alcohol consumption, independent of smoking, significantly correlates with a decreased risk of Parkinson's disease, prostate hyperplasia, and rheumatoid arthritis. It was also associated with an increased risk of chronic pancreatitis, colorectal cancer, and head and neck cancers. Additionally, a genetic predisposition to problematic alcohol use is strongly associated with increased risks of alcoholic liver disease, cirrhosis, both acute and chronic pancreatitis, and pneumonia. Evidence from our MR study supports the notion that alcohol consumption and problematic alcohol use are causally associated with a range of diseases, predominantly by increasing the risk.


Assuntos
Consumo de Bebidas Alcoólicas , Predisposição Genética para Doença , Análise da Randomização Mendeliana , Humanos , Masculino , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Artrite Reumatoide/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/epidemiologia , Doença de Parkinson/genética , Doença de Parkinson/epidemiologia , Doença de Parkinson/etiologia , Fatores de Risco , Feminino
7.
Transl Oncol ; 46: 101985, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38805774

RESUMO

BACKGROUND: Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection. METHODS: The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms. RESULTS: A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49-18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS. CONCLUSIONS: Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.

8.
PLoS One ; 19(4): e0294227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564630

RESUMO

Current evidence suggests that DEP domain containing 1 (DEPDC1) has an important effect on non-small-cell lung cancer (NSCLC). However, the diagnostic value and the regulatory function within NSCLC are largely unclear. This work utilized publicly available databases and in vitro experiments for exploring, DEPDC1 expression, clinical features, diagnostic significance and latent molecular mechanism within NSCLC. According to our results, DEPDC1 was remarkably upregulated in the tissues of NSCLC patients compared with non-carcinoma tissues, linked with gender, stage, T classification and N classification based on TCGA data and associated with smoking status and stage according to GEO datasets. Meanwhile, the summary receiver operating characteristic (sROC) curve analysis result showed that DEPDC1 had a high diagnostic value in NSCLC (AUC = 0.96, 95% CI: 0.94-0.98; diagnostic odds ratio = 99.08, 95%CI: 31.91-307.65; sensitivity = 0.89, 95%CI: 0.81-0.94; specificity = 0.92, 95%CI: 0.86-0.96; positive predictive value = 0.94, 95%CI: 0.89-0.98; negative predictive value = 0.78, 95%CI: 0.67-0.90; positive likelihood ratio = 11.77, 95%CI: 6.11-22.68; and negative likelihood ratio = 0.12, 95%CI: 0.06-0.22). Subsequently, quantitative real-time PCR (qRT-PCR) and western blotting indicated that DEPDC1 was high expressed in NSCLC cells. According to the in vitro MTS and apoptotic assays, downregulated DEPDC1 expression targeting P53 signaling pathway inhibited the proliferation of NSCLC cells while promoting apoptosis of NSCLC cells. Moreover, DEPDC1 was significantly correlated with immune cell infiltrating levels in NSCLC based on TCGA data, which were primarily associated with T cells CD4 memory activated, macrophages M1, B cells memory, mast cells resting, T cells regulatory, monocytes, and T cells CD4 memory resting. Compared with the group with high expression of DEPDC1, the group with low expression level had higher scores for immune checkpoint inhibitors (ICIs) treatment. GSEA confirmed that DEPDC1 was involved in gene expression and tumor-related signaling pathways. Finally, DEPDC1 and its associated immune-related genes were shown to be enriched in 'receptor ligand activity', 'external side of plasma membrane', 'regulation of innate immune response', and 'Epstein-Barr virus infection' pathways. The present study demonstrates that DEPDC1 may contribute to NSCLC tumorigenesis and can be applied as the biomarker for diagnosis and immunology.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Infecções por Vírus Epstein-Barr , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Herpesvirus Humano 4/metabolismo , Transdução de Sinais , Proteínas de Neoplasias/genética , Proteínas Ativadoras de GTPase/metabolismo
9.
Angew Chem Int Ed Engl ; : e202402028, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656658

RESUMO

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

10.
World J Psychiatry ; 14(2): 255-265, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38464771

RESUMO

BACKGROUND: Cancer patients often suffer from severe stress reactions psychologically, such as anxiety and depression. Prostate cancer (PC) is one of the common cancer types, with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis. Therefore, attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment. AIM: To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model. METHODS: A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022. The patient cohort was divided into a training group (n = 84) and a validation group (n = 36) at a ratio of 7:3. The patients' anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), respectively. Logistic regression was used to analyze the risk factors affecting negative mood, and a risk prediction model was constructed. RESULTS: In the training group, 35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50, respectively. Based on the scores, we further subclassified patients into two groups: a bad mood group (n = 35) and an emotional stability group (n = 49). Multivariate logistic regression analysis showed that marital status, castration scheme, and postoperative Visual Analogue Scale (VAS) score were independent risk factors affecting a patient's bad mood (P < 0.05). In the training and validation groups, patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients (P < 0.0001). The area under the curve (AUC) of the risk prediction model for predicting bad mood in the training group was 0.743, the specificity was 70.96%, and the sensitivity was 66.03%, while in the validation group, the AUC, specificity, and sensitivity were 0.755, 66.67%, and 76.19%, respectively. The Hosmer-Lemeshow test showed a χ2 of 4.2856, a P value of 0.830, and a C-index of 0.773 (0.692-0.854). The calibration curve revealed that the predicted curve was basically consistent with the actual curve, and the calibration curve showed that the prediction model had good discrimination and accuracy. Decision curve analysis showed that the model had a high net profit. CONCLUSION: In PC patients, marital status, castration scheme, and postoperative pain (VAS) score are important factors affecting postoperative anxiety and depression. The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

11.
J Ovarian Res ; 17(1): 31, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310251

RESUMO

BACKGROUND: Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia. METHODS: We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation. RESULTS: Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein. CONCLUSIONS: Our research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.


Assuntos
Hiperinsulinismo , Infertilidade , Síndrome do Ovário Policístico , Animais , Feminino , Humanos , Ratos , Endométrio/metabolismo , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Insulina/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Fosfatidilinositol 3-Quinases/metabolismo , Síndrome do Ovário Policístico/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
Theranostics ; 14(4): 1430-1449, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389836

RESUMO

Rationale: Osteosarcoma (OS), a common malignant bone tumor, calls for the investigation of novel treatment strategies. Low-intensity vibration (LIV) presents itself as a promising option, given its potential to enhance bone health and decrease cancer susceptibility. This research delves into the effects of LIV on OS cells and mesenchymal stem cells (MSCs), with a primary focus on generating induced tumor-suppressing cells (iTSCs) and tumor-suppressive conditioned medium (CM). Methods: To ascertain the influence of vibration frequency, we employed numerical simulations and conducted experiments to determine the most effective LIV conditions. Subsequently, we generated iTSCs and CM through LIV exposure and assessed the impact of CM on OS cells. We also explored the underlying mechanisms of the tumor-suppressive effects of LIV-treated MSC CM, with a specific focus on vinculin (VCL). We employed cytokine array, RNA sequencing, and Western blot techniques to investigate alterations in cytokine profiles, transcriptomes, and tumor suppressor proteins. Results: Numerical simulations validated LIV frequencies within the 10-100 Hz range. LIV induced notable morphological changes in OS cells and MSCs, confirming its dual role in inhibiting OS cell progression and promoting MSC conversion into iTSCs. Upregulated VCL expression enhanced MSC responsiveness to LIV, significantly bolstering CM's efficacy. Notably, we identified tumor suppressor proteins in LIV-treated CM, including procollagen C endopeptidase enhancer (PCOLCE), histone H4 (H4), peptidylprolyl isomerase B (PPIB), and aldolase A (ALDOA). Consistently, cytokine levels decreased significantly in LIV-treated mouse femurs, and oncogenic transcript levels were downregulated in LIV-treated OS cells. Moreover, our study demonstrated that combining LIV-treated MSC CM with chemotherapy drugs yielded additive anti-tumor effects. Conclusions: LIV effectively impeded the progression of OS cells and facilitated the transformation of MSCs into iTSCs. Notably, iTSC-derived CM demonstrated robust anti-tumor properties and the augmentation of MSC responsiveness to LIV via VCL. Furthermore, the enrichment of tumor suppressor proteins within LIV-treated MSC CM and the reduction of cytokines within LIV-treated isolated bone underscore the pivotal tumor-suppressive role of LIV within the bone tumor microenvironment.


Assuntos
Neoplasias Ósseas , Células-Tronco Mesenquimais , Osteossarcoma , Animais , Camundongos , Vibração/uso terapêutico , Células-Tronco Mesenquimais/metabolismo , Osteossarcoma/patologia , Citocinas/metabolismo , Neoplasias Ósseas/patologia , Proteínas Supressoras de Tumor/metabolismo , Microambiente Tumoral
13.
Heliyon ; 10(3): e24562, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38318046

RESUMO

Sustained myocardial injury due to hypertension and diabetes mellitus leads to production of endogenous reactive oxygen species (ROS) and insufficient myocardial antioxidant capacity, increasing the risk of cardiomyocyte ferroptosis. Ferroptosis is a nonapoptotic form of cell death driven by unrestricted lipid peroxidation. Dysfunction of the glutathione peroxidase 4 (GPX4) antioxidant system also plays an important role in ferroptosis. Cardiomyocyte ferroptosis ultimately leads to myocardial deterioration, such as inflammation, fibrosis, and cardiac remodeling, resulting in structural and functional changes. Pterostilbene (PTS), a demethylated derivative of resveratrol, exhibits strong anti-inflammatory and antioxidative activities. In this study, we used in vitro experiments to explore ferroptosis induced by angiotensin II (Ang II) of primary cardiac myocytes (CMs) and in vivo experiments to prepare a transverse aortic constriction (TAC)-induced cardiac dysfunction mouse model. PTS can significantly ameliorate Ang II-induced cardiomyocyte ferroptosis in vitro and reduce cardiac remodeling, while improving cardiac function in mice after TAC in vivo. Further mechanistic investigations revealed that PTS exerts its protective effect through the SIRT1/GSK-3ß/GPX4 pathway. After siRNA-mediated knockdown of SIRT1 or GPX4 in CMs, the protective effects of PTS on cardiomyocytes were abolished. This study provides important theoretical support for the potential of PTS to attenuate pathological cardiac remodeling and heart failure and provides a preliminary exploration of the molecular pathways involved in its protective mechanism.

14.
J Chem Inf Model ; 64(7): 2454-2466, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38181418

RESUMO

High-quality protein-ligand complex structures provide the basis for understanding the nature of noncovalent binding interactions at the atomic level and enable structure-based drug design. However, experimentally determined complex structures are scarce compared with the vast chemical space. In this study, we addressed this issue by constructing the BindingNet data set via comparative complex structure modeling, which contains 69,816 modeled high-quality protein-ligand complex structures with experimental binding affinity data. BindingNet provides valuable insights into investigating protein-ligand interactions, allowing visual inspection and interpretation of structural analogues' structure-activity relationships. It can also be used for evaluating machine-learning-based scoring functions. Our results indicate that machine learning models trained on BindingNet could reduce the bias caused by buried solvent-accessible surface area, as we previously found for models trained on the PDBbind data set. We also discussed strategies to improve BindingNet and its potential utilization for benchmarking the molecular docking methods and ligand binding free energy calculation approaches. The BindingNet complements PDBbind in constructing a sufficient and unbiased protein-ligand binding data set and is freely available at http://bindingnet.huanglab.org.cn.


Assuntos
Desenho de Fármacos , Proteínas , Simulação de Acoplamento Molecular , Ligantes , Proteínas/química , Ligação Proteica
15.
PLoS One ; 19(1): e0295812, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38166121

RESUMO

Touch cultures have both differences and commonalities in different regions. The Touch Experiences and Attitudes Questionnaire (TEAQ) is a widely applicable self-report tool. The purpose of our research was to examine the validity and reliability of the Chinese version of TEAQ for Chinese college students. We translated the 57 items of the original TEAQ into Chinese and assessed its cultural and linguistic adaptation in Chinese context. Two samples were recruited for the assessment of validity and reliability. The Social Support Rating Scale, Index of Well-being Scale and Security Questionnaire were chosen as criterion-related validity indicators. Item analysis, principal component analysis and confirmatory factor analysis indicated that the simplified Chinese version of TEAQ contained 18 items in three factors: Attitude to Intimate Touch, Childhood Touch and Current Positive Touch, with a cumulative variance contribution rate of 57.12%. The 3-factor model had good validity and reliability. The TEAQ was positively correlated with social support, sense of security and well-being. There were demographic differences in sex and left-behind experience. We anticipate the simplified TEAQ will be a valuable tool for the research of touch among Chinese college students.


Assuntos
Atitude , Inquéritos e Questionários , Tato , Humanos , China , Psicometria , Reprodutibilidade dos Testes , Estudantes
16.
Exp Gerontol ; 185: 112348, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38128847

RESUMO

BACKGROUND: Little is known about the association between sarcopenia and multimorbidity among middle-aged and older adults. This study investigated whether sarcopenia is associated with multimorbidity in middle-aged and older Chinese individuals. MATERIALS AND METHODS: A total of 12,760 participants from China Health and Retirement Longitudinal Study (CHARLS) 2015, with data on 14 specified chronic diseases and sarcopenia status were included in the cross-sectional analysis. A total of 7345 participants without multimorbidity from the CHARLS 2015 were included and followed up in 2018 in the longitudinal analysis. Logistic regression models were used in a cross-sectional investigation to assess the association between sarcopenia status and multimorbidity. In a longitudinal analysis, the relationships between sarcopenia status and multimorbidity were investigated using Cox proportional hazards models. RESULTS: Multimorbidity was prevalent in the no sarcopenia, possible sarcopenia, and sarcopenia groups at 38.8 % (3765/9713), 56.6 % (1199/2118), and 48.5 % (451/929), respectively. Multivariable regression revealed that both possible sarcopenia (ß = 0.088, P<0.001) and sarcopenia (ß = 0.028, P = 0.009), contributed to the number of chronic diseases. Logistic regression revealed that possible sarcopenia (OR: 1.56, 95 % CI: 1.39-1.76) was associated with multimorbidity. In the longitudinal analysis, participants in the possible sarcopenia group (HR: 1.19, 95 % CI:1.03-1.38) were more prone to experience new onset multimorbidity than did participants in the no sarcopenia group. CONCLUSIONS: Possible sarcopenia is associated with the development of multimorbidity in middle-aged and older Chinese populations. Health screening of populations with possible sarcopenia can facilitate early detection of multimorbidity.


Assuntos
Multimorbidade , Sarcopenia , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Estudos Longitudinais , Aposentadoria , Sarcopenia/epidemiologia , China/epidemiologia , Doença Crônica
17.
Sci Total Environ ; 912: 169192, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38097085

RESUMO

Trace activated carbon (AC) and diatomaceous earth (DE) were used as structural promoters to be incorporated into Ce-Mn-based solid-solution catalysts by the redox precipitation method. The modified catalysts exhibit superior reducibility, with abundant Ce3+, Mn3+and reactive oxygen species, which are facilitated to the migration of oxygen and the generation of oxygen vacancies. In particular, the catalytic combustion temperatures of 90 % toluene (3000 ppm) on Ce1Mn3Ox-AC/DE were 84 °C (dry) and 123 °C (10 vol% H2O), respectively. The role of lattice oxygen and adsorbed oxygen was revealed by in situ DRIFTS. Additionally, in situ DRIFTS was employed to verify that the degradation of toluene by Ce1Mn3Ox-AC/DE satisfied the Langmuir-Hinshelwood (L-H) mechanism and the Mars-Van Krevelen (MvK) mechanism. The possible reaction pathway was elucidated (toluene → benzyl alcohol → benzoic acid → maleic anhydride → CO2 + H2O). Furthermore, final products attributed to toluene oxidation were detected by in situ DRIFTS at 50 °C in the absence of oxygen, confirming that the catalyst possessed outstanding performance at low temperatures beyond mere adsorption.

18.
RSC Adv ; 13(48): 33644-33653, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38020032

RESUMO

2-Amino-2-methyl-1-propanol (AMP) is often used as a moderator to enhance the CO2 capture capacity of absorbents due to its unique spatial site resistance structure, and relatively few studies have been conducted on the enhancement of AMP aqueous solutions by nanoparticles for CO2 capture. In order to investigate the effect of nanoparticles on the CO2 capture performance of AMP aqueous solution, different nanofluids were formulated in this paper using a two-step method, and a bubbling reactor and an oil bath were used as the experimental setup for absorption/desorption, and through comparative experiments, it was found that the type of nanoparticles, the solid content, and the different parameters have great influences on the CO2 absorption load and desorption rate. The experimental results show that the addition of TiO2 nanoparticles to the AMP base solution can accelerate the absorption-desorption mass transfer rate of CO2, and there exists an optimal solid content of 1 g L-1 (±1.0%, ±2.5%); after multiple absorption-desorption experiments, good cycling performance can still be achieved. The experimental results of the nanofluid-promoted mass transfer mechanism are also illustrated and analyzed in this paper.

19.
Expert Rev Respir Med ; 17(9): 805-813, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37787485

RESUMO

BACKGROUND: Real-time thoracic ultrasound-guided pleural biopsy (TUSPB) is an important diagnostic method for pleural diseases. Traditional two-dimensional thoracic ultrasound, as well as newly developed contrast-enhanced ultrasound (CEUS) and ultrasound elastography (UE), are all used as guidance tools for pleural biopsies. Herein, we aimed to determine the diagnostic yield of real-time TUSPB for pleural diseases to better inform the decision-making process. METHODS: A literature search of the MEDLINE/PubMed, Embase, and Cochrane Library databases was performed up to June 2023. A binary random-effects model was applied to determine the pooled diagnostic yield. RESULTS: Fifteen studies comprising 1553 patients with pleural diseases were included and analyzed. The overall diagnostic yield of TUSPB for pleural diseases was 85.58% (95% confidence interval [CI]: 81.57-89.58%). The sensitivity was 77.56% for pleural malignancy and 80.13% for tuberculous pleurisy. The sub-analysis result revealed that CEUS-guided pleural biopsy provided a pooled diagnostic yield of 98.24%, which was higher than that of conventional TUSPB (78.97%; p < 0.01). The overall proportion of adverse events for TUSPB was 6.68% (95% CI: 5.31-8.04%). CONCLUSION: Conventional TUSPB has good pooled diagnostic yields and high safety. CEUS and UE are promising guidance tools for pleural biopsy with the potential to increase diagnostic yield.


Assuntos
Pleura , Tuberculose Pleural , Humanos , Pleura/diagnóstico por imagem , Ultrassonografia/métodos , Biópsia Guiada por Imagem/métodos , Tuberculose Pleural/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos
20.
Inorg Chem ; 62(39): 16122-16130, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37717260

RESUMO

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Irídio/farmacologia , Irídio/química
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