Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 190
Filtrar
1.
J Adolesc Health ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033455

RESUMO

PURPOSE: Existing studies found that school closure during the COVID-19 pandemic negatively influenced adolescents' mental health. Yet, it remains unclear how adolescent mental health changed during the transition of school reopening as well as the academic-related risk and protective factors. METHODS: Immediately before (April 2020) and three months (July 2020) after school reopening, 879 adolescents in Shanghai, China (mean age = 13.14 years, standard deviation = 1.31, 51% girls) completed online surveys and reported on their mental health (i.e., depressive symptoms, anxiety symptoms, and anger problems). Adolescents also reported perceived academic stress and academic orientations (i.e., performance orientation and mastery orientation) before school reopening. RESULTS: Adolescents reported decreased depressive symptoms, anxiety symptoms, and anger problems three months after school reopening. Adolescents who reported higher perceived academic stress and performance orientation showed elevated mental health symptoms after school reopening, whereas those reported higher mastery orientation showed decreased anger problems. Higher mastery orientation buffered the negative influence of academic stress on mental health. DISCUSSION: The findings not only demonstrate the positive influence of school reopening on Chinese adolescents' mental health but also highlight the role of perceived academic stress and academic orientations in contributing to individual differences during this transition.

2.
Clin Cosmet Investig Dermatol ; 17: 1519-1526, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948921

RESUMO

Vitiligo has been reported to occur in association with lupus erythematosus (LE) and other autoimmune diseases. However, it remains unclear whether this association occurs because of shared immunopathogenesis. We hereby describe a case of discoid lupus erythematosus (DLE) in a 51-year-old man with a 3 years history of skin lesions on his face, arms, and the V zone of the neck, and with the coexistence of vitiligo for 12 years, who developed from DLE to hypertrophic discoid lupus erythematosus (HDLE) after 10 months. We reviewed the previously reported cases to summarize the clinical characteristics of these patients and hope it may provide a reference for dermatologists.

3.
Eur J Med Res ; 29(1): 330, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879523

RESUMO

BACKGROUND: Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients. METHODS: This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches. RESULTS: Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5-86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P < 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32-2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47-2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16-1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15-1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients. CONCLUSIONS: Our results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation.


Assuntos
Pontuação de Propensão , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , China/epidemiologia , Fatores de Risco , Transtornos Cerebrovasculares/mortalidade , AVC Isquêmico/mortalidade , AVC Isquêmico/epidemiologia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/complicações , Causas de Morte , Prognóstico , Comorbidade , População do Leste Asiático
6.
J Phys Chem B ; 128(20): 4959-4974, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38742764

RESUMO

Simulating chemically reactive phenomena such as proton transport on nanosecond to microsecond and beyond time scales is a challenging task. Ab initio methods are unable to currently access these time scales routinely, and traditional molecular dynamics methods feature fixed bonding arrangements that cannot account for changes in the system's bonding topology. The Multiscale Reactive Molecular Dynamics (MS-RMD) method, as implemented in the Rapid Approach for Proton Transport and Other Reactions (RAPTOR) software package for the LAMMPS molecular dynamics code, offers a method to routinely sample longer time scale reactive simulation data with statistical precision. RAPTOR may also be interfaced with enhanced sampling methods to drive simulations toward the analysis of reactive rare events, and a number of collective variables (CVs) have been developed to facilitate this. Key advances to this methodology, including GPU acceleration efforts and novel CVs to model water wire formation are reviewed, along with recent applications of the method which demonstrate its versatility and robustness.

7.
ACS Nano ; 18(17): 11165-11182, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38626338

RESUMO

Glioblastoma (GBM) is an aggressive brain cancer that is highly resistant to treatment including chimeric antigen receptor (CAR)-T cells. Tumor-associated microglia and macrophages (TAMs) are major contributors to the immunosuppressive GBM microenvironment, which promotes tumor progression and treatment resistance. Hence, the modulation of TAMs is a promising strategy for improving the immunotherapeutic efficacy of CAR-T cells against GBM. Molecularly targeting drug pexidartinib (PLX) has been reported to re-educate TAMs toward the antitumorigenic M1-like phenotype. Here, we developed a cell-drug integrated technology to reversibly conjugate PLX-containing liposomes (PLX-Lip) to CAR-T cells and establish tumor-responsive integrated CAR-T cells (PLX-Lip/AZO-T cells) as a combination therapy for GBM. We used a mouse model of GBM to show that PLX-Lip was stably maintained on the surface of PLX-Lip/AZO-T cells in circulation and these cells could transmigrate across the blood-brain barrier and deposit PLX-Lip at the tumor site. The uptake of PLX-Lip by TAMs effectively re-educated them into the M1-like phenotype, which in turn boosted the antitumor function of CAR-T cells. GBM tumor growth was completely eradicated in 60% of the mice after receiving PLX-Lip/AZO-T cells and extended their overall survival time beyond 50 days; in comparison, the median survival time of mice in other treatment groups did not exceed 35 days. Overall, we demonstrated the successful fusion of CAR-T cells and small-molecule drugs with the cell-drug integrated technology. These integrated CAR-T cells provided a superior combination strategy for GBM treatment and presented a reference for the construction of integrated cell-based drugs.


Assuntos
Aminopiridinas , Neoplasias Encefálicas , Glioblastoma , Microglia , Receptores de Antígenos Quiméricos , Glioblastoma/terapia , Glioblastoma/patologia , Glioblastoma/imunologia , Glioblastoma/tratamento farmacológico , Animais , Camundongos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Humanos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/tratamento farmacológico , Lipossomos/química , Pirróis/química , Pirróis/farmacologia , Imunoterapia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Imunoterapia Adotiva , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos
8.
STAR Protoc ; 5(2): 103023, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38640064

RESUMO

Social cooperation is fundamentally important for group animals but rarely studied in mice because of their natural aggressiveness. Here, we present a new water-reward assay to investigate mutualistic cooperative behavior in mice. We describe the construction of the apparatus and provide details of the procedures and analysis for investigators to characterize and quantify the mutualistic cooperative behavior. This protocol has been validated in mice and can be used for investigating mechanisms of cooperation. For complete details on the use and execution of this protocol, please refer to Zhang et al. and Wang et al.1,2.


Assuntos
Comportamento Animal , Comportamento Cooperativo , Recompensa , Animais , Camundongos , Comportamento Animal/fisiologia , Água , Masculino
9.
Adv Sci (Weinh) ; 11(25): e2401100, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634209

RESUMO

Due to multidimensional complexity of solid tumor, development of rational T-cell combinations and corresponding formulations is still challenging. Herein, a triple combination of T cells are developed with Indoleamine 2,3-dioxygenase inhibitors (IDOi) and Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). To maximize synergism, a spatiotemporally controlled T-cell engineering technology to formulate triple drugs into one cell therapeutic, is established. Specifically, a sequentially responsive core-shell nanoparticle (SRN) encapsulating IDOi and CDK4/6i is anchored onto T cells. The yielded SRN-T cells migrated into solid tumor, and achieved a 1st release of IDOi in acidic tumor microenvironment (TME). Released IDOi restored tryptophan supply in TME, which activated effector T cells and inhibited Tregs. Meanwhile, 1st released core is internalized by tumor cells and degraded by glutathione (GSH), to realize a 2nd release of CDK4/6i, which induced up-regulated expression of C-X-C motif chemokine ligand 10 (CXCL10) and C-C motif chemokine ligand 5 (CCL5), and thus significantly increased tumor infiltration of T cells. Together, with an enhanced recruitment and activation, T cells significantly suppressed tumor growth, and prolonged survival of tumor-bearing mice. This study demonstrated rationality and superiority of a tri-drug combination mediated by spatiotemporally controlled cell-engineering technology, which provides a new treatment regimen for solid tumor.


Assuntos
Linfócitos T , Microambiente Tumoral , Animais , Camundongos , Linfócitos T/imunologia , Microambiente Tumoral/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Quinase 4 Dependente de Ciclina/metabolismo , Linhagem Celular Tumoral , Nanopartículas , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética
10.
Acta Pharmacol Sin ; 45(6): 1237-1251, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38472317

RESUMO

Both epidemiological and animal studies suggest that adverse environment during pregnancy can change the offspring development programming, but it is difficult to achieve prenatal early warning. In this study we investigated the impact of prenatal dexamethasone exposure (PDE) on sperm quality and function of blood-testis barrier (BTB) in adult offspring and the underlying mechanisms. Pregnant rats were injected with dexamethasone (0.1, 0.2 and 0.4 mg·kg-1·d-1, s.c.) from GD9 to GD20. After weaning (PW4), the pups were fed with lab chow. At PW12 and PW28, the male offspring were euthanized to collect blood and testes samples. We showed that PDE significantly decreased sperm quality (including quantity and motility) in male offspring, which was associated with impaired BTB and decreased CX43/E-cadherin expression in the testis. We demonstrated that PDE induced morphological abnormalities of fetal testicle and Sertoli cell development originated from intrauterine. By tracing to fetal testicular Sertoli cells, we found that PDE dose-dependently increased expression of histone lysine demethylases (KDM1B), decreasing histone 3 lysine 9 dimethylation (H3K9me2) levels of follistatin-like-3 (FSTL3) promoter region and increased FSTL3 expression, and inhibited TGFß signaling and CX43/E-cadherin expression in offspring before and after birth. These results were validated in TM4 Sertoli cells following dexamethasone treatment. Meanwhile, the H3K9me2 levels of FSTL3 promoter in maternal peripheral blood mononuclear cell (PBMC) and placenta were decreased and its expression increased, which was positively correlated with the changes in offspring testis. Based on analysis of human samples, we found that the H3K9me2 levels of FSTL3 promoter in maternal blood PBMC and placenta were positively correlated with fetal blood testosterone levels after prenatal dexamethasone exposure. We conclude that PDE can reduce sperm quality in adult offspring rats, which is related to the damage of testis BTB via epigenetic modification and change of FSTL3 expression in Sertoli cells. The H3K9me2 levels of the FSTL3 promoter and its expression in the maternal blood PBMC can be used as a prenatal warning marker for fetal testicular dysplasia.


Assuntos
Barreira Hematotesticular , Dexametasona , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais , Animais , Masculino , Feminino , Gravidez , Dexametasona/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Barreira Hematotesticular/efeitos dos fármacos , Barreira Hematotesticular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ratos Sprague-Dawley , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia
11.
Asia Pac J Clin Nutr ; 33(1): 11-22, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494683

RESUMO

BACKGROUND AND OBJECTIVES: Sichuan cuisine is characterized by high salt and oil content. We aimed to evaluate the effects of the Sichuan cuisine version of Chinese heart-healthy diet (CHH diet-SC) on blood pressure reduction among hypertensive adults. METHODS AND STUDY DESIGN: The Chinese heart-healthy diet (CHH) trial was a multicenter randomized controlled feeding trial among Chinese hypertensive people. We conducted a secondary analysis of the CHH trial using data from the Sichuan center in Southwest China. Fifty-three people aged 25 to 75 years with a mean systolic blood pressure (SBP) between 130 and 159 mmHg were enrolled. Eligible participants underwent a 1-week run-in period with the typical local diet and were randomized 1:1 to consume the CHH diet-SC (n=27) or typical local diet (n=26) for the next 4-week. The primary outcome was the net change in SBP, the secondary outcomes included diastolic blood pressure (DBP), mean arterial pressure (MAP), and the rate of BP control. RESULTS: Compared with the control group, the CHH diet-SC decreased cooking salt, oil, and red meat content and increased inclusion of whole grains, fruits, seafood, low-fat dairy, soybean, and nuts; the SBP experienced reductions of 7.54, 8.60, 9.14, and 10.1 mmHg at the end of weeks 1 through 4; the DBP was reduced 4.01 mmHg at week 4; the MAP was significantly reduced 6.02 mmHg finally; and rate of BP control significantly increased (p<0.05). CONCLUSIONS: Adoption of the CHH diet-SC for 4 weeks can significantly reduce BP and increase the rate of BP control in hypertensive adults.


Assuntos
Hipertensão , Hipotensão , Adulto , Humanos , Pressão Sanguínea , Dieta , Dieta Saudável , Cloreto de Sódio na Dieta , Pessoa de Meia-Idade , Idoso
12.
Int J Stroke ; : 17474930241241994, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38472157

RESUMO

BACKGROUND: Hyperglycemia is associated with worse stroke outcomes, but it is uncertain whether tight glycemic control during the acute stroke period is associated with a better outcome. We conducted a meta-analysis to compare the effect of tight glycemic control versus loose glycemic control in the acute phase of stroke patients. METHODS: A literature search was performed to identify randomized controlled trials comparing the safety and efficacy of tight glycemic control with a relatively loose control of blood glucose of acute stroke (ischemic or hemorrhagic) patients within 24 h after stroke onset. We required that the blood glucose level of the patients should not be lower than 6.11 mmol/L at the time of enrollment, and for the intensive blood glucose control range, we defined the blood glucose level as lower than that of the control group. The primary efficacy outcome measure was deaths from any cause at 90 days. Secondary efficacy outcomes comprised the number of participants with modified Rankin score (mRS). We define mRS scores 0-2 as favorable scores, recurrent stroke, and the National Institute of Health Stroke Scale or the European Stroke Scale scores. We defined the number of participants with hypoglycemia as our primary safety outcome. Subgroup analysis was performed according to age, the variety of interventions, maintained glucose level, and status of hypoglycemia on National Institute of Health Stroke Scale (NIHSS) scores or European Stroke Scale (ESS) scores. RESULTS: Fifteen randomized controlled trials (RCTs) with 2957 participants meeting the including criteria were identified and included in this meta-analysis, although not all included data on every outcome measure. Data on the primary efficacy endpoint, mortality at 90 days, was available in 11 RCTs, a total of 2575 participants. There was no significant difference between the intervention and control groups (odds ratio (OR): 1.00; 95% confidence interval (CI): 0.81-1.23; P = 0.99). For secondary endpoints, there was no difference between intervention and control groups for a mRS from 0 to 2 (OR: 0.96; 95% CI: 0.80-1.15; P = 0.69; data from 9 RCTs available), or recurrent stroke (OR: 1.34; 95% CI: 0.92-1.96; P = 0.13; data from 3 RCTs available). For NIHSS scores or ESS scores, there was a small difference in favor of intensive controls (standardized mean difference: -0.29; 95% CI: -0.54 to -0.04; P = 0.02). There was a marked increase in hypoglycemia with tight control: (OR of 9.46 (95% CI: 4.59-19.50; P < 0.00001; data from 9 RCTs available). CONCLUSION: There was no difference between tight and loose glycemic control on mortality, independence, or recurrent stroke outcome in acute stroke, but an increase in hypoglycemia. There was a small effect improvement on neurological scales, but the relevance of this needs to be confirmed in future adequately powered studies.

13.
Angew Chem Int Ed Engl ; 63(20): e202403140, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38393614

RESUMO

The rising prevalence of global antibiotic resistance evokes the urgent need for novel antimicrobial candidates. Cationic lipopeptides have attracted much attention due to their strong antimicrobial activity, broad-spectrum and low resistance tendency. Herein, a library of fluoro-lipopeptide amphiphiles was synthesized by tagging a series of cationic oligopeptides with a fluoroalkyl tail via a disulfide spacer. Among the lipopeptide candidates, R6F bearing six arginine moieties and a fluorous tag shows the highest antibacterial activity, and it exhibits an interesting fluorine effect as compared to the non-fluorinated lipopeptides. The high antibacterial activity of R6F is attributed to its excellent bacterial membrane permeability, which further disrupts the respiratory chain redox stress and cell wall biosynthesis of the bacteria. By co-assembling with lipid nanoparticles, R6F showed high therapeutic efficacy and minimal adverse effects in the treatment of MRSA-induced sepsis and chronic wound infection. This work provides a novel strategy to design highly potent antibacterial peptide amphiphiles for the treatment of drug-resistant bacterial infections.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Sepse , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Sepse/tratamento farmacológico , Sepse/microbiologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Animais , Camundongos , Infecções Estafilocócicas/tratamento farmacológico , Tensoativos/química , Tensoativos/farmacologia , Tensoativos/síntese química , Lipopeptídeos/farmacologia , Lipopeptídeos/química , Lipopeptídeos/uso terapêutico
14.
Plant Physiol ; 195(2): 924-939, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38366641

RESUMO

Far-red radiation affects many plant processes, including reproductive organ abortion. Our research aimed to determine the role of apical dominance in far-red light-induced flower and fruit abortion in sweet pepper (Capsicum annuum L.). We conducted several climate room experiments where plants were grown under white- or red-rich LED light, with or without additional far-red light. Additional far-red light enhanced apical dominance: it increased auxin levels in the apices of dominant shoots, and caused a greater difference in internode length and apical auxin levels between dominant and subordinate shoots. Additional far-red light stimulated fruit abortion in intact plants but not in decapitated plants, suggesting a crucial role of shoot apices in this effect. However, reducing basipetal auxin transport in the stems with N-1-naphthylphthalamic acid did not influence far-red light-stimulated fruit abortion, although auxin levels in the stem were largely reduced. Applying the synthetic auxin 1-naphthaleneacetic acid on decapitated apices did not influence fruit abortion. However, applying the auxin biosynthesis inhibitor yucasin to shoot apices reduced fruit abortion regardless of the light conditions, accompanied by slight shoot growth retardation. These findings suggest that the basipetal auxin stream does not mediate far-red light-stimulated fruit abortion. Far-red light-stimulated fruit abortion was associated with reduced sucrose accumulation and lower invertase activities in flowers. We suggest that under additional far-red light conditions, increased auxin levels in shoot apices promote fruit abortion probably through enhanced competition for assimilates between apices and flowers, which limits assimilate import into flowers.


Assuntos
Capsicum , Flores , Frutas , Ácidos Indolacéticos , Luz , Capsicum/crescimento & desenvolvimento , Capsicum/fisiologia , Capsicum/efeitos da radiação , Capsicum/metabolismo , Flores/fisiologia , Flores/crescimento & desenvolvimento , Flores/efeitos da radiação , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Frutas/efeitos da radiação , Frutas/fisiologia , Ácidos Indolacéticos/metabolismo , Luz Vermelha
15.
Ecotoxicology ; 33(2): 151-163, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38329639

RESUMO

Suspended particulate matter (SPM), an important component of the natural water environment, can act as a carrier of many pollutants that affect aquatic organisms. In the present study, the effect of SPM obtained from Jinjiang Estuary on the physiological, biochemical, and photosynthetic properties of typical freshwater algae (Chlorella pyrenoidosa) was investigated. The results showed that under different concentrations of SPM treatment, the superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde (MDA) content of C. pyrenoidosa increased, but the soluble protein content decreased. SPM with different particle sizes had less effect on SOD of C. pyrenoidosa, but showed a promoting effect on CAT and MDA as well as soluble protein content. In terms of photosynthetic activity, high concentrations (70, 90 mg/L) and small particle sizes (0-75, 75-120 µm) of SPM had a greater effect on the chlorophyll a content of C. pyrenoidosa. In addition, different concentrations of SPM had no significant effect on the potential photosynthetic activity of PS II (Fv/F0) and the maximum quantum yield of PS II (Fv/Fm), but the inhibition of the initial slope (alpha), the maximum photosynthetic rate (ETRmax) and the semi-light saturation point (Ik) increased with the increase of SPM concentration. Fv/F0, ETRmax, and Ik of C. pyrenoidosa showed some degree of recovery after inhibition in the presence of SPM of different particle sizes.


Assuntos
Chlorella , Poluentes Químicos da Água , Clorofila A/metabolismo , Clorofila A/farmacologia , Material Particulado/toxicidade , Material Particulado/metabolismo , Estuários , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/análise
16.
Free Radic Biol Med ; 214: 54-68, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311259

RESUMO

Peritoneal mesothelial cell senescence promotes the development of peritoneal dialysis (PD)-related peritoneal fibrosis. We previously revealed that Brahma-related gene 1 (BRG1) is increased in peritoneal fibrosis yet its role in modulating peritoneal mesothelial cell senescence is still unknown. This study evaluated the mechanism of BRG1 in peritoneal mesothelial cell senescence and peritoneal fibrosis using BRG1 knockdown mice, primary peritoneal mesothelial cells and human peritoneal samples from PD patients. The augmentation of BRG1 expression accelerated peritoneal mesothelial cell senescence, which attributed to mitochondrial dysfunction and mitophagy inhibition. Mitophagy activator salidroside rescued fibrotic responses and cellular senescence induced by BRG1. Mechanistically, BRG1 was recruited to oxidation resistance 1 (OXR1) promoter, where it suppressed transcription of OXR1 through interacting with forkhead box protein p2. Inhibition of OXR1 abrogated the improvement of BRG1 deficiency in mitophagy, fibrotic responses and cellular senescence. In a mouse PD model, BRG1 knockdown restored mitophagy, alleviated senescence and ameliorated peritoneal fibrosis. More importantly, the elevation level of BRG1 in human PD was associated with PD duration and D/P creatinine values. In conclusion, BRG1 accelerates mesothelial cell senescence and peritoneal fibrosis by inhibiting mitophagy through repression of OXR1. This indicates that modulating BRG1-OXR1-mitophagy signaling may represent an effective treatment for PD-related peritoneal fibrosis.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Animais , Humanos , Camundongos , Senescência Celular/genética , Proteínas Mitocondriais/metabolismo , Mitofagia/genética , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/genética , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Peritônio/metabolismo , Peritônio/patologia
17.
J Ethnopharmacol ; 324: 117704, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38176664

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and arthritic pain. Sinomenine (SIN), derived from the rhizome of Chinese medical herb Qing Teng (scientific name: Sinomenium acutum (Thunb.) Rehd. Et Wils), has a longstanding use in Chinese traditional medicine for treating rheumatoid arthritis. It has been shown to possess anti-inflammatory, analgesic, and immunosuppressive effects with minimal side-effects clinically. However, the mechanisms governing its effects in treatment of joint pathology, especially on fibroblast-like synoviocytes (FLSs) dysfunction, and arthritic pain remains unclear. AIM: This study aimed to investigate the effect and underlying mechanism of SIN on arthritic joint inflammation and joint FLSs dysfunctions. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) was induced in rats and the therapeutic effects of SIN on joint pathology were evaluated histopathologically. Next, we conducted a series of experiments using LPS-induced FLSs, which were divided into five groups (Naïve, LPS, SIN 10, 20, 50 µg/ml). The expression of inflammatory factors was measured by qPCR and ELISA. The invasive ability of cells was detected by modified Transwell assay and qPCR. Transwell migration and cell scratch assays were used to assess the migration ability of cells. The distribution and content of relevant proteins were observed by immunofluorescence and laser confocal microscopy, as well as Western Blot and qPCR. FLSs were transfected with plasmids (CRMP2 T514A/D) to directly modulate the post-translational modification of CRMP2 protein and downstream effects on FLSs function was monitored. RESULTS: SIN alleviated joint inflammation in rats with CIA, as evidenced by improvement of synovial hyperplasia, inflammatory cell infiltration and cartilage damage, as well as inhibition of pro-inflammatory cytokines release from FLSs induced by LPS. In vitro studies revealed a concentration-dependent suppression of SIN on the invasion and migration of FLSs induced by LPS. In addition, SIN downregulated the expression of cellular CRMP2 that was induced by LPS in FLSs, but increased its phosphorylation at residue T514. Moreover, regulation of pCRMP2 T514 by plasmids transfection (CRMP2 T514A/D) significantly influenced the migration and invasion of FLSs. Finally, SIN promoted nuclear translocation of pCRMP2 T514 in FLSs. CONCLUSIONS: SIN may exert its anti-inflammatory and analgesic effects by modulating CRMP2 T514 phosphorylation and its nuclear translocation of FLSs, inhibiting pro-inflammatory cytokine release, and suppressing abnormal invasion and migration. Phosphorylation of CRMP2 at the T514 site in FLSs may present a new therapeutic target for treating inflammatory joint's destruction and arthritic pain in RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Morfinanos , Sinoviócitos , Ratos , Animais , Fosforilação , Lipopolissacarídeos/farmacologia , Movimento Celular , Artrite Reumatoide/patologia , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Citocinas/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Fibroblastos , Dor/tratamento farmacológico , Células Cultivadas , Proliferação de Células
18.
J Am Chem Soc ; 146(2): 1612-1618, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38170906

RESUMO

Amino acid ionic liquids (AAILs) are promising green materials for CO2 capture and conversion due to their large chemical structural tunability. However, the structural understanding of the AAILs underlying the CO2 reaction dynamics remains uncertain. Herein, we examine the steric effects of AAIL anions with various chemical structures on CO2 capture behavior. Based on ab initio free-energy sampling, we assess reaction mechanisms for carbamate formation via a two-step reaction pathway with a zwitterion intermediate undergoing dynamic proton transfer. Our results show that free-energy barriers for carbamate formation can be significantly reduced as the degree of steric hindrance of the anions decreases. Further analyses reveal that reduced steric hindrance of anions causes markedly stronger intermolecular interactions between zwitterion and anions, leading to an increased kinetically favorable intermolecular proton transfer for carbamate production. We also describe the correlation strength between intramolecular interactions within the zwitterion and intermolecular interactions between the zwitterion and anions. We conclude that the favored structural flexibility due to the less steric hindrance of the zwitterion leads to enhanced intermolecular interactions, facilitating proton transfer to nearby AAIL anions for carbamate formation. Our study provides invaluable insight into the influence of various degrees of steric hindrance of the AAIL anions governing CO2 chemisorption. These findings may aid in the design of optimal AAIL solvents for the CO2 capture process.

19.
J Integr Neurosci ; 23(1): 22, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38287857

RESUMO

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive technique that has demonstrated potential in modulating cortical neuron excitability. The objective of this paper is to investigate the effects of tDCS on characteristic parameters of brain functional networks and muscle synergy, as well as to explore its potential for enhancing motor performance. METHODS: By applying different durations of tDCS on the motor cortex of the brain, the 32-lead electroencephalogram (EEG) of the cerebral cortex and 4-lead electromyography (EMG) signals of the right forearm were collected for 4 typical hand movements which are commonly used in rehabilitation training, including right-hand finger flexion, finger extension, wrist flexion, and wrist extension. RESULTS: The study showed that tDCS can enhance the brain's electrical activity in the beta band of the C3 node of the cerebral cortex during hand movements. Furthermore, the structure of muscle synergy remains unaltered; however, the associated muscle activity is amplified (p < 0.05). CONCLUSIONS: Based on the study results, it can be inferred that tDCS enhances the control strength between the motor area of the cerebral cortex and the muscles during hand movements.


Assuntos
Córtex Motor , Estimulação Transcraniana por Corrente Contínua , Estimulação Transcraniana por Corrente Contínua/métodos , Músculos , Mãos , Encéfalo , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana
20.
Ther Apher Dial ; 28(2): 255-264, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37873689

RESUMO

INTRODUCTION: To assess the relationship between the rate of residual renal function (RRF) decline in the first year and all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients. METHODS: Incident PD patients were divided into two groups by the corresponding RRF decline value, when hazard ratio (HR) = 1 was found by the restricted cubic spline. The associations of rate of decline of RRF in the first year with mortality were evaluated. RESULTS: Of 497 PD patients, 122 patients died. After adjusting for confounding factors, patients in fast-decline group had a significant increase risk of all-cause and cardiovascular mortality (HR: 1.97 and 2.09, respectively). Each 0.1-mL/min/1.73 m2 /month decrease in RRF in the first year of PD was associated with a 19% and 20% higher risk of all-cause and cardiovascular mortality, respectively. CONCLUSIONS: Faster decline of RRF in the first year was independently associated with all-cause and cardiovascular mortality in PD patients.


Assuntos
Doenças Cardiovasculares , Falência Renal Crônica , Diálise Peritoneal , Humanos , Taxa de Filtração Glomerular , Rim , Doenças Cardiovasculares/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...