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1.
Artigo em Inglês | MEDLINE | ID: mdl-38609654

RESUMO

PURPOSE: Tyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance. METHODS: The GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer. The expression of PARP1 in lung cancer TKI resistant cell PC9-ER and TKI sensitive cell PC9 was analyzed by qPCR and western blot. After knocking down of PARP1, CCK-8 assays, colony formation, flow cytometry were used to investigate its impact on erlotinib sensitivity, cell survival, cell cycle, and apoptosis. RNA-seq was used to investigate the mechanism by which PARP1 participates in EGFR-TKI resistance, and the results were validated in vitro and in vivo studies. RESULTS: PARP1 was highly expressed in both lung cancer tissues and cells. Subsequently, increased PARP1 expression was observed in PC9-ER compared with its parental cell line. Knockdown of PARP1 increased erlotinib sensitivity, promoted cell apoptosis, and suppressed cell growth. RNA-seq and previous studies have shown that the PI3K/AKT/mTOR/P70S6K pathway is involved in PARP1-mediated TKI resistance, and these results were confirmed by Western blot in vitro and in vivo. CONCLUSION: PARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.

2.
Talanta ; 274: 126022, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574538

RESUMO

In this work, a highly sensitive lung cancer biomarkers detection probe was developed based on Ag and MXene co-functionalized magnetic microspheres. By using carboxyl magnetic microspheres as carrier, MXene was coated repeatedly by Poly (allylamine hydrochloride) (PAH) as interlayer adhesive, and silver particles grown on the surface of MXene in situ can efficiently improve the sensitivity of the probe. The detection of neuron specific enolase (NSE) is mainly through the formation of a specific complex between NSE antigen and antibody, and the release of antibody labeled with amino carbon quantum dots (CQDs) from the surface of Ag nanoparticles (AgNPs), so that the fluorescence is restored and "OFF-ON" is formed. The biosensor exhibits excellently wide linear range (0.0001-1500 ng/mL) and the limit of detection (LOD) is up to 0.03 pg/mL, which is superior to most tumor marker probes based on fluorescence mechanism. Furthermore, we constructed dual detection strategy for NSE and carcinoembryonic antigen (CEA) simultaneously.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38571296

RESUMO

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

4.
Clin Exp Med ; 24(1): 79, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634972

RESUMO

BACKGROUND: Natural killer cells (NKs) may be involved in multiple myeloma (MM) progression. The present study elucidated the correlation between NKs and the progression of MM using single-cell binding transcriptome probes to identify NK cell-related biomarkers. METHODS: Single-cell analysis was performed including cell and subtype annotation, cell communication, and pseudotime analysis. Hallmark pathway enrichment analysis of NKs and NKs-related differentially expressed genes (DEGs) were conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction (PPI) networks. Then, a risk model was structured based on biomarkers identified through univariate Cox regression analysis and least absolute shrinkage and selection operator regression analysis and subsequently validated. Additionally, correlation of clinical characteristics, gene set enrichment analysis, immune analysis, regulatory network, and drug forecasting were explored. RESULTS: A total of 13 cell clusters were obtained and annotated, including 8 cell populations that consisted of NKs. Utilizing 123 PPI network node genes, 8 NK-related DEGs were selected to construct a prognostic model. Immune cell infiltration results suggested that 11 immune cells exhibited marked differences in the high and low-risk groups. Finally, the model was used to screen potential drug targets to enhance immunotherapy efficacy. CONCLUSION: A new prognostic model for MM associated with NKs was constructed and validated. This model provides a fresh perspective for predicting patient outcomes, immunotherapeutic response, and candidate drugs.


Assuntos
Mieloma Múltiplo , Humanos , Prognóstico , Biomarcadores , Células Matadoras Naturais , Imunoterapia
5.
Front Pharmacol ; 15: 1359319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584597

RESUMO

The α2-adrenoceptor agonist dexmedetomidine is a commonly used drug for sedatives in clinics and has analgesic effects; however, its mechanism of analgesia in the spine remains unclear. In this study, we systematically used behavioural and transcriptomic sequencing, pharmacological intervention, electrophysiological recording and ultrasound imaging to explore the analgesic effects of the α2-adrenoceptor and its molecular mechanism. Firstly, we found that spinal nerve injury changed the spinal transcriptome expression, and the differential genes were mainly related to calcium signalling and tissue metabolic pathways. In addition, α2-adrenoceptor mRNA expression was significantly upregulated, and α2-adrenoceptor was significantly colocalised with markers, particularly neuronal markers. Intrathecal dexmedetomidine suppressed neuropathic pain and acute inflammatory pain in a dose-dependent manner. The transcriptome results demonstrated that the analgesic effect of dexmedetomidine may be related to the modulation of neuronal metabolism. Weighted gene correlation network analysis indicated that turquoise, brown, yellow and grey modules were the most correlated with dexmedetomidine-induced analgesic effects. Bioinformatics also annotated the involvement of metabolic processes and neural plasticity. A cardiovascular-mitochondrial interaction was found, and ultrasound imaging revealed that injection of dexmedetomidine significantly enhanced spinal cord perfusion in rats with neuropathic pain, which might be regulated by pyruvate dehydrogenase kinase 4 (pdk4), cholesterol 25-hydroxylase (ch25 h) and GTP cyclohydrolase 1 (gch1). Increasing the perfusion doses of dexmedetomidine significantly suppressed the frequency and amplitude of spinal nerve ligation-induced miniature excitatory postsynaptic currents. Overall, dexmedetomidine exerts analgesic effects by restoring neuronal metabolic processes through agonism of the α2-adrenoceptor and subsequently inhibiting changes in synaptic plasticity.

6.
Clin Interv Aging ; 19: 289-301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434576

RESUMO

Purpose: The purpose of this study is to compare the refracture rate of the cemented vertebral body of percutaneous curved vertebroplasty (PCVP) and bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCF). Methods: Ninety-four patients with single segment thoracolumbar OVCF were randomly divided into two groups (47 patients in each) and underwent PCVP or bilateral PKP surgery, respectively. Refracture of cemented vertebral body, bone cement injection volume and cement pattern, cement leakage rate, total surgical time, intraoperative fluoroscopy time, preoperative and postoperative Cobb angles and anterior vertebral height, Oswestry disability index questionnaire (ODI) and visual analog scales (VAS) were recorded. Results: The PCVP group had significantly lower refracture incidence of the cemented vertebral than the bilateral PKP group (p<0.05). There was a significant postoperative improvement in the VAS score and ODI in both group (p<0.01), and no significant difference was found between two groups. The operation time and intraoperative fluoroscopy times were significantly less in the PCVP group than in the bilateral PKP group (p<0.01). The mean kyphosis angle correction and vertebral height restoration in the PCVP group was significantly less than that in the bilateral PKP group (p<0.01). Conclusion: Both PCVP and PKP were safe and effective treatments for OVCF. The PCVP had lower refracture rate of the cemented vertebral than the bilateral PKP group, and PCVP entailed less exposure to fluoroscopy and shorter operation time than bilateral PKP.


Assuntos
Fraturas por Compressão , Cifoplastia , Cifose , Fraturas da Coluna Vertebral , Humanos , Fraturas da Coluna Vertebral/cirurgia , Fraturas por Compressão/cirurgia , Coluna Vertebral , Cifose/cirurgia , Cimentos Ósseos/uso terapêutico
7.
J Immunol Res ; 2024: 5722548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481988

RESUMO

Purpose: NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Methods: Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Results: Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Conclusions: Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.


Assuntos
Produtos Biológicos , Síndromes Periódicas Associadas à Criopirina , Criança , Humanos , Lactente , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/genética , Mutação , Variação Genética
8.
Pediatr Rheumatol Online J ; 22(1): 38, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504360

RESUMO

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data. METHODS: We conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment. RESULTS: Seven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period. CONCLUSIONS: Canakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.


Assuntos
Anticorpos Monoclonais Humanizados , Artrite Juvenil , Criança , Humanos , Masculino , Feminino , Artrite Juvenil/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Estudos Retrospectivos , Corticosteroides/uso terapêutico
9.
BMC Med Educ ; 24(1): 265, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459539

RESUMO

BACKGROUND: The Tibetan area is one of China's minority regions with a shortage of general practice personnel, which requires further training and staffing. This research helps to understand the current condition and demand for general practitioner (GP) training in Tibetan areas and to provide a reference for promoting GP education and training. METHODS: We conducted a cross-sectional survey using stratified sampling targeting 854 GPs in seven cities within the Tibetan Autonomous Region, utilizing an online questionnaire. Achieving a high response rate of 95.1%, 812 GPs provided invaluable insights. Our meticulously developed self-designed questionnaire, available in both Chinese and Tibetan versions, aimed to capture a wide array of data encompassing basic demographics, clinical skills, and specific training needs of GPs in the Tibetan areas. Prior to deployment, the questionnaire underwent rigorous development and refinement processes, including expert consultation and pilot testing, to ensure its content validity and reliability. In our analysis, we employed descriptive statistics to present the characteristics and current training needs of GPs in the Tibetan areas. Additionally, chi-square tests were utilized to examine discrepancies in training needs across various demographic groups, such as age, job positions, and educational backgrounds of the participating GPs. RESULTS: The study was completed by 812 (812/854, 95.1%) GPs, of whom 62.4% (507/812) were female. The top three training needs were hypertension (81.4%, 661/812), pregnancy management (80.7%, 655/812), and treatment of related patient conditions and events (80.5%, 654/812). Further research shows that the training required by GPs of different ages in "puncturing, catheterization, and indwelling gastric tube use" (64.6% vs. 54.8%, p = 9.5 × 10- 6) varies statistically. GPs in various positions have different training needs in "community-based chronic disease prevention and management" (76.6% vs. 63.9%, p = 0.009). The training needs of GPs with different educational backgrounds in "debridement, suturing, and fracture fixation" (65.6% vs. 73.2%, p = 0.027) were also statistically significant. CONCLUSIONS: This study suggests the need for targeted continuing medical education activities and for updating training topics and content. Course developers must consider the needs of GPs, as well as the age, job positions, and educational backgrounds of GPs practicing in the Tibetan Plateau region. TRIAL REGISTRATION: Not applicable.


Assuntos
Clínicos Gerais , Humanos , Feminino , Masculino , Clínicos Gerais/educação , Estudos Transversais , Tibet , Educação Médica Continuada , Reprodutibilidade dos Testes , China , Inquéritos e Questionários
10.
Cancer Lett ; 589: 216795, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556106

RESUMO

The immune microenvironment constructed by tumor-infiltrating immune cells and the molecular phenotype defined by hormone receptors (HRs) have been implicated as decisive factors in the regulation of breast cancer (BC) progression. Here, we found that the infiltration of mast cells (MCs) informed impaired prognoses in HR(+) BC but predicted improved prognoses in HR(-) BC. However, molecular features of MCs in different BC remain unclear. We next discovered that HR(-) BC cells were prone to apoptosis under the stimulation of MCs, whereas HR(+) BC cells exerted anti-apoptotic effects. Mechanistically, in HR(+) BC, the KIT ligand (KITLG), a major mast cell growth factor in recruiting and activating MCs, could be transcriptionally upregulated by the progesterone receptor (PGR), and elevate the production of MC-derived granulin (GRN). GRN attenuates TNFα-induced apoptosis in BC cells by competitively binding to TNFR1. Furthermore, disruption of PGR-KITLG signaling by knocking down PGR or using the specific KITLG-cKIT inhibitor iSCK03 potently enhanced the sensitivity of HR(+) BC cells to MC-induced apoptosis and exerted anti-tumor activity. Collectively, these results demonstrate that PGR-KITLG signaling in BC cells preferentially induces GRN expression in MCs to exert anti-apoptotic effects, with potential value in developing precision medicine approaches for diagnosis and treatment.


Assuntos
Neoplasias da Mama , Fator de Células-Tronco , Humanos , Feminino , Fator de Células-Tronco/genética , Fator de Células-Tronco/metabolismo , Mastócitos/patologia , Neoplasias da Mama/patologia , Retroalimentação , Apoptose , Microambiente Tumoral
11.
Science ; 383(6689): 1337-1343, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38513024

RESUMO

The introduction of molecularly woven three-dimensional (3D) covalent organic framework (COF) crystals into polymers of varying types invokes different forms of contact between filler and polymer. Whereas the combination of woven COFs with amorphous and brittle polymethyl methacrylate results in surface interactions, the use of the liquid-crystalline polymer polyimide induces the formation of polymer-COF junctions. These junctions are generated by the threading of polymer chains through the pores of the nanocrystals, thus allowing for spatial arrangement of polymer strands. This offers a programmable pathway for unthreading polymer strands under stress and leads to the in situ formation of high-aspect-ratio nanofibrils, which dissipate energy during the fracture. Polymer-COF junctions also strengthen the filler-matrix interfaces and lower the percolation thresholds of the composites, enhancing strength, ductility, and toughness of the composites by adding small amounts (~1 weight %) of woven COF nanocrystals. The ability of the polymer strands to closely interact with the woven framework is highlighted as the main parameter to forming these junctions, thus affecting polymer chain penetration and conformation.

12.
ACS Biomater Sci Eng ; 10(4): 2270-2281, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38536862

RESUMO

Tumor hypoxia-associated drug resistance presents a major challenge for cancer chemotherapy. However, sustained delivery systems with a high loading capability of hypoxia-inducible factor-1 (HIF-1) inhibitors are still limited. Here, we developed an ultrastable iodinated oil-based Pickering emulsion (PE) to achieve locally sustained codelivery of a HIF-1 inhibitor of acriflavine and an anticancer drug of doxorubicin for tumor synergistic chemotherapy. The PE exhibited facile injectability for intratumoral administration, great radiopacity for in vivo examination, excellent physical stability (>1 mo), and long-term sustained release capability of both hydrophilic drugs (i.e., acriflavine and doxorubicin). We found that the codelivery of acriflavine and doxorubicin from the PE promoted the local accumulation and retention of both drugs using an acellular liver organ model and demonstrated significant inhibition of tumor growth in a 4T1 tumor-bearing mouse model, improving the chemotherapeutic efficacy through the synergistic effects of direct cytotoxicity with the functional suppression of HIF-1 pathways of tumor cells. Such an iodinated oil-based PE provides a great injectable sustained delivery platform of hydrophilic drugs for locoregional chemotherapy.


Assuntos
Antineoplásicos , Neoplasias , Animais , Camundongos , Emulsões/uso terapêutico , Acriflavina/farmacologia , Acriflavina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Quimioterapia Combinada , Hipóxia/tratamento farmacológico
13.
Proc Natl Acad Sci U S A ; 121(14): e2321645121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38527201

RESUMO

Central Asia (CA) is one of the world's most significant arid regions, which is markedly impacted by global warming. A better understanding of the dynamical processes governing its Holocene climate variability is critical for a better understanding of possible future impacts of climate change in the region. To date, most of the existing CA paleoclimate records are from the summer precipitation-dominated eastern CA (ECA), with few records from the winter precipitation-dominated western CA (WCA). Here, we present a precisely dated (~6‰) and highly resolved (<4-y) record of hydroclimatic variations from the WCA covering the period between 7,774 and 656 y BP. Utilizing multiple proxies (δ18O, δ13C, and Sr/Ca) derived from a stalagmite from the Fergana Valley, Kyrgyzstan, we reveal a long-term drying trend in WCA, which is in contrast with the wetting trend in ECA. We propose that different responses of winter and summer westerly jets to seasonal solar insolation over the past 8,000 y may have resulted in an antiphased precipitation relationship between the WCA and ECA. Our data contain dominant quasiperiodicities of 1,400, 50 to 70, and 20 to 30 y, indicating close connections between the WCA climate and the North Atlantic. We further identified a series of droughts and pluvials on centennial-to-decadal timescales, which may have influenced regional societies and trans-Eurasian culture exchanges during historical and prehistorical times.

14.
J Transl Med ; 22(1): 176, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369466

RESUMO

BACKGROUND: The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated. RESULTS: Here, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization. CONCLUSIONS: In conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner.


Assuntos
Interleucina-33 , Lesões por Radiação , Humanos , Idoso , Interleucina-33/farmacologia , Pele , Colágeno/farmacologia , Fibroblastos , Macrófagos , Senescência Celular
15.
J Adolesc Health ; 74(5): 971-979, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38323970

RESUMO

PURPOSE: Use of social networking sites (SNS) is highly prevalent among college and university students. Conflicting findings were found on the effects of SNS use on well-being, and very few studies examined the effects of social interaction with strong ties and weak ties on SNS on online and offline social support. The present study examined the association between social interaction with weak ties and strong ties on SNS and life satisfaction among Chinese college and university students. The mediating role of online social support and offline social support was also examined. METHODS: A cross-sectional survey was conducted among 26,547 students from 30 colleges/universities in Shanxi province, China. RESULTS: Social interaction with strong ties on SNS was associated with increased offline social support but had no significant association with online support. Social interaction with weak ties on SNS was associated with higher level of online support, but lower level of offline social support. Both offline and online social support were associated with life satisfaction. The direct effects of social interaction with strong ties and weak ties on life satisfaction were not significant. Mediation analyses supported the full mediating effect of offline social support in the relationship between social interaction with strong ties and life satisfaction, while online and offline support mediated the relationship between social interaction with weak ties and life satisfaction. DISCUSSION: Social interaction with strong ties and weak ties on the SNS was associated with life satisfaction through different pathways. Interventions to maximize the benefits of SNS use are warranted.


Assuntos
Rede Social , Apoio Social , Humanos , Estudos Transversais , Universidades , Comunicação , Estudantes , Satisfação Pessoal
16.
Shock ; 61(3): 442-453, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411611

RESUMO

ABSTRACT: Potential radiation exposure is a general concern, but there still lacks radioprotective countermeasures. Here, we found a small molecular near-infrared dye IR-780, which promoted hematopoietic stem cells (HSCs) into quiescence to resist stress. When mice were treated with IR-780 before stress, increased HSC quiescence and better hematopoietic recovery were observed in mice in stress conditions. However, when given after radiation, IR-780 did not show obvious benefit. Transplantation assay and colony-forming assay were carried out to determine self-renewal ability and repopulation capacity of HSCs. Furthermore, IR-780 pretreatment reduced the generation of reactive oxygen species (ROS) and DNA damage in HSCs after radiation. In homeostasis, the percentage of Lineage - , Sca-1 + , and c-Kit + cells and long-term HSCs (LT-HSCs) were improved, and more HSCs were in G0 state after administration of IR-780. Further investigations showed that IR-780 selectively accumulated in mitochondria membrane potential high LT-HSCs (MMP-high LT-HSCs). Finally, IR-780 promoted human CD34 + HSC reconstruction ability in NOD-Prkdc scid Il2rg null mice after transplantation and improved repopulation capacity in vitro culture. Our research showed that IR-780 selectively entered MMP-high LT-HSCs and promoted them into dormancy, thus reducing hematopoietic injury and improving regeneration capacity. This novel approach might hold promise as a potential countermeasure for radiation injury.


Assuntos
Células-Tronco Hematopoéticas , Indóis , Camundongos , Humanos , Animais , Camundongos Endogâmicos NOD , Espécies Reativas de Oxigênio
17.
Clin Nutr ; 43(2): 484-493, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38194788

RESUMO

BACKGROUND & AIMS: Epidemiologic studies have examined the association between dietary fatty acids and type 2 diabetes risk in general populations. Evidence regarding their associations with gestational diabetes mellitus (GDM) risk remains limited. This study aimed to evaluate prepregnancy fatty acids intake in relation to GDM risk. METHODS: 3,725 pregnant women from the Xi'an Birth Cohort Study who were free of previous GDM or pre-existing chronic diseases were included. Dietary intake of total fat and individual fatty acids (including saturated fatty acids [SFA], monounsaturated fatty acids [MUFA], polyunsaturated fatty acids [PUFA], and trans fatty acids) during the year preceding pregnancy was assessed by a validated food-frequency questionnaire before 16 weeks of gestation. GDM was confirmed based on the 75-g oral glucose tolerance test. Log-binomial or modified Poisson regression models were applied to estimate the relative risks (RRs) and 95 % confidence intervals (95%CIs) of GDM for fatty acids intake. Generalized linear regression was adopted for blood glucose levels with fatty acids intake. RESULTS: 644 (17.3 %) incident GDM cases were confirmed in our study. Participants in the highest intake of total fat substituting for carbohydrates had a 33 % reduced risk of GDM than those in the lowest intake (RR:0.67; 95%CI:0.55,0.81). For individual fatty acids, only PUFA intake was associated with a lower risk of GDM, with RR comparing extreme tertiles of 0.61 (95%CI:0.49,0.76). Each 2 % increase in energy from total fat and PUFA replacing carbohydrates decreased the risk of GDM by 6 % (95%CI:3 %,9 %) and 15 % (95%CI:9 %,21 %), respectively. Similar inverse associations with intake of total fat and PUFA were observed for blood glucose levels. Further analyses of SFA substitution showed that replacement of 2 % energy from SFA with PUFA and MUFA was associated with 26 % (RR:0.74; 95%CI:0.62,0.88) and 30 % (RR:0.70; 95%CI:0.50, 0.98) decreased risk of GDM, respectively. CONCLUSIONS: Greater intake of total fat and PUFA before pregnancy was associated with lower risk of GDM when replacing carbohydrates. Substitution SFA with PUFA and MUFA was also inversely associated with GDM risk. These findings support the important role of optimal dietary fatty acids composition in the prevention of GDM.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Humanos , Feminino , Gravidez , Diabetes Gestacional/epidemiologia , Estudos de Coortes , Dieta/efeitos adversos , Estudos Prospectivos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Glicemia , Gorduras na Dieta/efeitos adversos , Ácidos Graxos , Ácidos Graxos Insaturados , Ácidos Graxos Monoinsaturados
18.
Nutr J ; 23(1): 8, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38195532

RESUMO

BACKGROUND: Abnormal blood potassium levels are associated with an increased risk of cardiometabolic diseases and mortality in the general population; however, evidence regarding the association between dyskalemia and mortality among patients with cardiovascular disease (CVD) remains inconclusive. This study aimed to evaluate the association of potassium levels with all-cause and cardiovascular mortality among patients with CVD. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to August 2023 to identify relevant cohort studies among patients with CVD, such as myocardial infarction, stroke, and heart failure. Abnormal potassium levels were considered as hypokalemia or hyperkalemia. The primary outcomes were all-cause mortality based on follow-up length (including in-hospital, short-term and long-term mortality) and cardiovascular mortality. The methodological quality of included studies was assessed by using the Newcastle-Ottawa Scale. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Restricted cubic splines were applied to explore the dose-response relationship. RESULTS: Thirty-one cohort studies involving 227,645 participants with an average age of 68.3 years were included in the meta-analysis, all of which achieved moderate to high quality. Hyperkalemia was significantly associated with an approximately 3.0-fold increased risk of all-cause in-hospital mortality (RR:2.78,95CI%:1.92,4.03), 1.8-fold of all-cause short-term mortality (RR:1.80, 95CI%:1.44,2.27), 1.3-fold of all-cause long-term mortality (RR:1.33, 95CI%:1.19,1.48) and 1.2-fold of cardiovascular mortality (RR:1.19, 95CI%:1.04,1.36). Similar positive associations were also observed between hypokalemia and risk of all-cause mortality and cardiovascular mortality. The RRs of all-cause in-hospital, short-term, long-term mortality and cardiovascular mortality with hyperkalemia were attenuated to 2.21 (95CI%:1.60,3.06), 1.46(95CI%:1.25,1.71), 1.23 (95CI%:1.09,1.39) and 1.13 (95CI%:1.00,1.27) when treating hypokalemia together with normokalemia as the reference group. A U-shaped association was observed between potassium levels and mortality, with the lowest risk at around 4.2 mmol/L. CONCLUSIONS: Both hypokalemia and hyperkalemia were positively associated with the risk of mortality in patients with CVD. Our results support the importance of potassium homeostasis for improving the CVD management. REGISTRATION: PROSPERO, CRD42022324337.


Assuntos
Doenças Cardiovasculares , Hiperpotassemia , Hipopotassemia , Humanos , Idoso , Estudos de Coortes , Potássio
19.
J Integr Neurosci ; 23(1): 6, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38287855

RESUMO

BACKGROUND: Metformin has been shown to have potent analgesic effects; however, the underlying mechanism of synaptic plasticity mediating analgesia remained ambiguous. METHODS: In this study, animal behavioral tests, whole-cell patch­clamp recording, immunofluorescence staining, and network pharmacology techniques were applied to elucidate the mechanisms and potential targets of metformin-induced analgesia. RESULTS: Single or consecutive injections of metformin significantly inhibited spinal nerve ligation (SNL)-induced neuropathic pain, and formalin-induced acute inflammatory pain. Network pharmacology analysis of metformin action targets in pain database-related targets revealed 25 targets, including five hub targets (nitric oxide synthase 1 (NOS1), NOS2, NOS3, epidermal growth factor receptor (EGFR), and plasminogen (PLG)). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that metformin-induced analgesia was markedly correlated with calcium signaling and synaptic transmission. Intrathecal injection of metformin significantly reversed nerve injury-induced c-Fos (neural activity biomarker) mRNA and protein expression in neuropathic rats by regulating NOS2 expression. In addition, whole-cell recordings of isolated spinal neurons demonstrated that metformin dose-dependently inhibited the enhanced frequency and amplitude of miniature excitatory synaptic currents (mEPSCs) but did not affect those of miniature inhibitory synaptic currents (mIPSCs) in neuropathic pain. CONCLUSIONS: This study further demonstrated that metformin might inhibit spinal glutamatergic transmission and abnormal nociceptive circuit transduction by monitoring synaptic transmission in pain. Results of this work provide an in-depth understanding of metformin analgesia via synaptic plasticity.


Assuntos
Neuralgia , Transmissão Sináptica , Ratos , Animais , Ratos Sprague-Dawley , Transmissão Sináptica/fisiologia , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Nervos Espinhais/metabolismo , Neurônios/metabolismo
20.
Food Chem ; 441: 138352, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38199098

RESUMO

Heavy metal ions (HMIs) can lead to serious harm to human health and ecological environment. Thus, developing an efficient detection method for HMIs is extremely necessary. Herein, a new thiacalix[4]arene-based metal-organic framework (MOF) [Co2(L1)(TPA)2]·DMA·3CH3OH·H2O (Co-LTPA) (L1 = thiacalix[4]arene-based ligand and H2TPA = terephthalic acid) was successfully synthesized. The electrochemical detection platform (Co-LTPA/GCE) was acquired, and Co-LTPA/GCE featured ultrasensitive detection of HMIs with greatly low limits of detection (LODs) of 0.119 nM for Cd2+ and 0.279 nM for Pb2+ as well as wide linear ranges of 0.08-5.8 µM for Cd2+ and 0.01-6.0 µM for Pb2+. More importantly, the Co-LTPA/GCE sensor was employed to detect foods (milk, honey and orange juice) and water samples (tap water, lake water and drinking water) with satisfactory recoveries, proving the sensor reliability in practical applications. This work provided an example that the functional electrochemical Co-LTPA/GCE sensor was employed for Cd2+ and Pb2+ detection.


Assuntos
Estruturas Metalorgânicas , Metais Pesados , Humanos , Cádmio , Chumbo , Reprodutibilidade dos Testes , Íons , Água
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