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1.
J Nanobiotechnology ; 22(1): 495, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164753

RESUMO

BACKGROUND: The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. RESULTS: In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. CONCLUSION: Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Lipossomos , Camundongos Nus , RNA Interferente Pequeno , Verteporfina , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Lipossomos/química , Verteporfina/farmacologia , Verteporfina/uso terapêutico , Animais , Humanos , Linhagem Celular Tumoral , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Proteínas de Sinalização YAP , Nanopartículas/química , Camundongos Endogâmicos BALB C , Fatores de Transcrição/metabolismo , Angiomotinas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Peptídeos
2.
J Environ Sci (China) ; 144: 1-14, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38802222

RESUMO

Nanoscale zero-valent iron (NZVI), which has the advantages of small particle size, large specific surface area, and high reactivity, is often injected into contaminated aquifers in the form of slurry. However, the prone to passivation and agglomeration as well as poor stability and mobility of NZVI limit the further application of this technology in fields. Therefore, sulfided NZVI loaded on reduced graphene oxide (S-NZVI/rGO) and guar gum (GG) with shear-thinning properties as stabilizers were used to synthesize S-NZVI/rGO@GG slurries. SEM, TEM, and FT-IR confirmed that the dispersion and anti-passivation of NZVI were optimized in the coupled system. The stability and mobility of the slurry were improved by increasing the GG concentration, enhancing the pH, and decreasing the ionic strength and the presence of Ca2+ ions, respectively. A modified advection-dispersion equation (ADE) was used to simulate the transport experiments considering the strain and physicochemical deposition/release. Meanwhile, colloidal filtration theory (CFT) demonstrated that Brownian motion plays a dominant role in the migration of S-NZVI/rGO@GG slurry, and the maximum migration distance can be increased by appropriately increasing the injection rate. Extended-Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory showed that the excellent stability and migration of S-NZVI/rGO@GG slurry mainly came from the GG spatial forces. This study has important implications for the field injection of S-NZVI/rGO@GG slurry. According to the injection parameters, the injection range of S-NZVI/rGO@GG slurry is effectively controlled, which lays the foundation for the promotion of application in actual fields.


Assuntos
Galactanos , Grafite , Ferro , Mananas , Gomas Vegetais , Grafite/química , Gomas Vegetais/química , Galactanos/química , Mananas/química , Ferro/química , Modelos Químicos , Nanopartículas Metálicas/química
3.
Int J Med Sci ; 19(8): 1254-1264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928721

RESUMO

Mammalian cardiomyocytes (CMs) maintain a low capacity for self-renewal in adulthood, therefore the induction of CMs cycle re-entry is an important approach to promote myocardial repair after injury. Recently, photobiomodulation (PBM) has been used to manipulate physiological activities of various tissues and organs by non-invasive means. Here, we demonstrate that conditioned PBM using light-emitting diodes with a wavelength of 630 nm (LED-Red) was capable of promoting the proliferation of neonatal CMs. Further studies showed that low-power LED-Red affected the expression of miR-877-3p and promoted the proliferation of CMs. In contrast, silencing of miR-877-3p partially abolished the pro-proliferative actions of LED-Red irradiation on CMs. Mechanistically, GADD45g was identified as a downstream target gene of miR-877-3p. Conditioned LED-Red irradiation also inhibited the expression of GADD45g in neonatal CMs. Moreover, GADD45g siRNA reversed the positive effect of LED-Red on the proliferation of neonatal CMs. Taken together, conditioned LED-Red irradiation increased miR-877-3p expression and promoted the proliferation of neonatal CMs by targeting GADD45g. This finding provides a new insight into the role of LED-Red irradiation in neonatal CMs biology and suggests its potential application in myocardial injury repair.


Assuntos
MicroRNAs , Miócitos Cardíacos , Animais , Proliferação de Células/genética , Mamíferos/genética , Mamíferos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Miocárdio/metabolismo
4.
Lasers Med Sci ; 37(2): 789-797, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34581904

RESUMO

Glioma is the most common primary central nervous system tumor; many methods are currently being used to research and treat glioma. In recent years, fluorescent-guided resection (FGR) and photodynamic therapy (PDT) have become hot spots in the treatment of glioma. Based on the existing literatures regarding the FGR enhancing resection rate and regarding efficacy of PDT for the treatment of glioma, this paper made a systematic review of FGR for gross total resection of patients and the PDT for the survival of patients with glioma. Meta-analysis of eligible studies was performed to derive precise estimation of PDT on the prognosis of patients with glioma by searching all related literatures in PubMed, EMBASE, Cochrane, and Web of Science databases, and further to evaluate (GTR) under FGR and the efficacy of PDT therapy, including 1-year and 2-year survival rates, overall survival (OS), and progression-free survival (PFS). According to the inclusion and exclusion criteria, a total of 1294 patients with glioma were included in the final analysis of 31 articles, among which a 73.00% (95% CI, 68.00 ~ 79.00%, P < 0.01) rate of GTR in 27 groups included in 23 articles was reported for those receiving FGR. The OS was 17.78 months (95% CI, 8.89 ~ 26.67, P < 0.01) in 5 articles on PDT-treated patients with glioma, and the mean difference of OS was 6.18 (95% CI, 3.3 ~ 9.06, P < 0.01) between PDT treatment and conventional glioma surgery, showing a statistically significant difference (P < 0.01). The PFS was 10.82 months (95% CI, 7.04 ~ 14.61, P < 0.01) in 5 articles on PDT-treated patients with glioma. A 1-year survival rate of 59.00% (95% CI, 38.00 ~ 77.00%, P < 0.01) in 10 groups included in 8 articles and 2-year survival rate of 25.00% (95% CI, 15.00 ~ 36.00%, P < 0.01) in 7 groups included in 6 articles were reported for those with PDT. FGR and PDT are feasible for treatment of patients with glioma, because FGR can effectively increase the resection rate, at the same time, PDT can prolong the survival time. However, due to the limitation of small sample size in the existing studies, larger samples and randomized controlled clinical trials are needed to analyze the resection under FGR and efficacy of PDT in patients with glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Fotoquimioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Glioma/tratamento farmacológico , Glioma/cirurgia , Humanos
5.
Water Sci Technol ; 84(5): 1190-1205, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34534116

RESUMO

In this study, a new sulfidated nanoscale zero-valent iron (S-nZVI) supported on hydrogel (S-nZVI@H) was successfully synthesized for the removal of chromium (Cr) (VI) from groundwater. The surface morphology, dispersion phenomenon and functional groups of novel S-nZVI@H were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Box-Behnken design (BBD) optimization technology based on response surface methodology (RSM) is applied to demonstrate the influence of the interaction of S-nZVI@H dose, initial Cr(VI) concentration, contact time, and initial pH with the Cr(VI) removal efficiency. The analysis of variance results (F = 118.73, P < 0.0001, R2 = 0.9916) show that the quadratic polynomial model is significant enough to reflect the close relationship between the experimental and predicted values. The predicted optimum removal conditions are: S-nZVI@H dose 9.46 g/L, initial Cr(VI) concentration 30 mg/L, contact time 40.7 min, and initial pH 5.27, and the S-nZVI@H dose is the key factor affecting the removal of Cr(VI). The predicted value (99.76%) of Cr (VI) removal efficiency is in good agreement with the experimental value (97.75%), which verifies the validity of the quadratic polynomial model. This demonstrates that RSM with appropriate BBD can be utilized to optimize the design of experiments for removal of Cr(VI).


Assuntos
Ferro , Poluentes Químicos da Água , Adsorção , Cromo/análise , Hidrogéis , Poluentes Químicos da Água/análise
6.
BMC Musculoskelet Disord ; 21(1): 510, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736621

RESUMO

BACKGROUND: Increased physical activity level is related to lower risk of depressive symptoms, and there is an inverse association between muscle strength and risk of depressive symptoms among the elderly. Although there is evidence of an inverse association between muscle strength and depressive symptoms, the relationship between these variables in a younger population is still unknown. This study aimed to examine the association between handgrip strength, a representative indicator of skeletal muscle strength, and the risk of depressive symptoms among Chinese female college freshmen. METHODS: A cross-sectional study was conducted among 867 participants aged between 16 and 23 years. Handgrip strength was measured with a handheld digital Smedley dynamometer, and handgrip strength relative to body weight (kg/kg) was calculated and was classified into tertiles as follows: low (0.32-0.50), medium (0.51-0.58), and high (0.59-0.94). Depressive symptoms were evaluated using the 20-item Zung self-rating depression scale (SDS), and three cutoff points were used to indicate different depression levels. RESULTS: We found that 10.7% of participants were classified as having severe depressive symptoms using an SDS score of 50 as the cutoff point. After adjusting for potential confounders, the adjusted odds ratios and 95% confidence intervals (CIs) for moderate-to-severe depressive symptoms across tertiles of the relative handgrip strength were 1.00 (reference) for tertile 1, 0.614 (0.353, 1.069) for tertile 2, and 0.537 (0.292, 0.988) for tertile 3 (P for trend = 0.041). The significant associations remained when other cutoff points (SDS scores: 48 or 45) were used. Interactions between handgrip strength and potential confounders for depressive symptoms in the final models were not significant. CONCLUSIONS: Our findings indicate that handgrip strength is inversely and independently related to the risk of depressive symptoms among Chinese female college freshmen. The present findings can help develop an effective intervention strategy against depression. Further intervention studies are needed to explore the mechanisms underlying the effects of handgrip strength on depressive symptoms.


Assuntos
Depressão , Força da Mão , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Força Muscular , Adulto Jovem
7.
J Epidemiol ; 28(9): 397-403, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29681560

RESUMO

BACKGROUND: There is scarce epidemiological evidence regarding the relationships of the consumption of different types of vegetables or fruits with change in skeletal muscle strength. We prospectively examined the relationships among Japanese adults, using handgrip strength to assess skeletal muscle strength. METHODS: A 3-year study was carried out with 259 Japanese adults who were 22-68 years of age. The frequency of consumption of different types of vegetables or fruits were obtained using a validated self-administered dietary history questionnaire. Handgrip strength was measured with a handheld digital Smedley dynamometer. RESULTS: After adjustment for confounding factors, the mean change in handgrip strength in participants stratified according to the level of tomato and tomato product consumption at baseline were -3.2 (95% confidence interval [CI], -4.0 to -2.3) for <1 time/week, -2.7 (95% CI, -3.6 to -1.8) for 1 time/week, -1.6 (95% CI, -2.5 to -0.8) for 2-3 times/week, and -1.7 (95% CI, -2.8 to -0.7) for ≥4 times/week, (P for trend = 0.022). However, the significant relationships of consumption of other types of vegetables and different types of fruits with change in handgrip strength were not observed. CONCLUSION: Higher consumption of tomato and tomato product at baseline was significantly associated with reduced decline in handgrip strength among Japanese adults over a 3-year follow-up period. This study suggests that consumption of tomato and tomato product could be protective against the decline in skeletal muscle strength associated with aging.


Assuntos
Dieta/estatística & dados numéricos , Força da Mão/fisiologia , Solanum lycopersicum , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
J Epidemiol ; 27(1): 42-47, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28135197

RESUMO

BACKGROUND: Unhealthy eating has been found to be associated with the prevalence of depressive symptoms. However, prospective evidence of the combined effects of unhealthy eating and depressive symptoms has not been reported. This study aimed to elucidate the prospective relationship between habitual unhealthy eating habits and depressive symptoms. METHODS: A 2-year prospective cohort study of 376 Japanese adults aged 24-83 years without depressive symptoms at baseline was conducted. Information about participants' eating behaviors was obtained via a self-administered questionnaire, in which skipping breakfast, eating dinner shortly before bedtime, and snacking after dinner were recorded. Depressive symptoms were assessed using the Japanese version of the Zung Self-rating Depression Scale. RESULTS: The 2-year incidence of depressive symptoms was found to be 23.7% (89/376). Covariate-adjusted multivariate Poisson regression analyses showed that habitual snacking after dinner was significantly associated with the incidence of depressive symptoms (relative risk [RR] 1.77; 95% confidence interval [CI], 1.00-3.14, p = 0.049), whereas no relationship was found between skipping breakfast or eating dinner shortly before bedtime and depressive symptoms. On the other hand, there was an interaction effect of snacking after dinner and dinner before bedtime on depressive symptoms (p for the interaction = 0.044). Participants with more than two unhealthy eating behaviors had a higher incidence of depressive symptoms compared to those with fewer than two unhealthy eating behaviors (RR 1.71; 95% CI, 1.06-2.77, p = 0.028). CONCLUSIONS: This prospective study is the first to reveal the combined relationship between unhealthy eating and the incidence of depressive symptoms.


Assuntos
Depressão/epidemiologia , Comportamento Alimentar/psicologia , Comportamentos Relacionados com a Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Lanches/psicologia , Inquéritos e Questionários , Adulto Jovem
9.
Soc Psychiatry Psychiatr Epidemiol ; 52(7): 847-853, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28070597

RESUMO

PURPOSE: Dairy products have been reported to have various beneficial effects on human health. Although some previous studies have shown relationships between dairy consumption and depressive symptoms, the results of these studies were not consistent. This study aimed to investigate the association between frequency of low- and whole-fat dairy consumption, and depressive symptoms. METHODS: This cross-sectional study enrolled 1159 Japanese adults aged 19-83 years. Dietary intake was assessed using a brief self-administered diet history questionnaire. Depressive symptoms were evaluated by a self-rating depression scale (SDS) (the presence of depressive symptoms was defined as an SDS score ≥45 points). Logistic regression models were used to analyze the association between the frequency of low- and whole-fat dairy consumption and depressive symptoms. RESULTS: Higher frequency of low-fat dairy consumption was associated with a lower prevalence of depressive symptoms. In the final adjusted model, the odds ratios and 95% confidence intervals for prevalence of depressive symptoms when no consumption of low-fat dairy was compared to moderate (1-3 times per week) and high (≥4 times/week) frequencies of low-fat dairy consumption were 0.96 (0.71, 1.30) and 0.51 (0.35, 0.77), respectively (p for the trend = 0.004). No relationships were observed between the consumption of whole-fat dairy and depressive symptoms. CONCLUSIONS: The current results indicate that a higher frequency of low-fat dairy consumption may be associated with a lower prevalence of depressive symptoms.


Assuntos
Laticínios/análise , Depressão/epidemiologia , Dieta/efeitos adversos , Gorduras na Dieta/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Inquéritos sobre Dietas , Gorduras na Dieta/análise , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
10.
Front Psychol ; 15: 1363885, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873517

RESUMO

Background: The association between health literacy and healthy dietary behaviors has been explored in the European population. However, there is currently no evidence available specifically pertaining to Chinese college students particularly for interactive health literacy. Aims: The objective of this study was to investigate the association between interactive health literacy (IHL) and dietary behaviors in Chinese college students. Methods: This study included 11,856 Chinese college students (mean age = 18.8 years, SD = 1.2 years). We defined nine healthy dietary behaviors as consumption of water, egg, milk and milk products, vegetables, fruit, red meat, soy and soy products, seafood, and sugar-sweetened beverages. For each food group, participants who met the criterion for being a regular consumer of the item were assigned a score of 1, and otherwise were assigned a score of 0. Thus, the dietary behaviors score ranged from 0 to 9, with higher scores indicating healthier dietary behaviors. We used the revised 28-item Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ) to evaluate IHL; a higher score on this scale indicates a greater health literacy. Multivariate logistic regression was used to analyze the association between IHL level and frequency of different numbers of dietary behaviors. Results: After adjusting for sex, age, annual family income, place of residence, father's education level, and mother's education level, there was a clear and significant positive association between IHL and the likelihood of exhibiting diverse dietary behaviors. The adjusted odds ratio (95% CI) of exhibiting given nine dietary behaviors with reference to tertile 1 according to categories of IHL was as follows: 1.055 (0.694, 1.603) for tertile 2 and 1.849 (1.269, 2.696) for tertile 3 (p for trend = 0.001). Similarly, there are significant positive associations between IHL and the likelihood of exhibiting 2-8 dietary behaviors, except for exhibiting any one dietary behavior. We further found that, in addition to the health awareness factor, there were significant positive associations between physical activity and nutrition factors, and healthier dietary behaviors. Further, there was a significant negative association between interpersonal relationships and dietary behavior. Conclusion: The findings indicate a positive relationship between IHL and dietary behavior, such that the higher the level of IHL among college students, the healthier the dietary behavior they tend to adopt in their daily lives. These findings suggest the importance of developing stages of change-based educational interventions, which could help individuals with limited IHL to not only acquire necessary health-related knowledge but also to strengthen their motivation to engage in healthy dietary behaviors. Future studies should employ longitudinal prospective designs or randomized controlled trials to establish a causal association between IHL and healthy dietary behaviors.

11.
Front Public Health ; 12: 1354231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799683

RESUMO

Introduction: Although previous research has examined the risk factors for drowning behavior among adolescents, it is unclear whether this association is influenced by water safety knowledge. This study aimed to examine whether water safety knowledge is associated with adolescents' drowning risk behaviors and whether drowning risk perceptions and attitudes could have a chain mediating role in the association between water safety knowledge and adolescents' drowning risk behaviors. Methods: This study included 7,485 adolescents from five Chinese provinces and cities. We used the Drowning Risk Behaviors Scales (DRBS) to evaluate the risk of drowning behaviors. The Water Safety Knowledge Scale (WSKS) was used to evaluate the competence level of water safety knowledge. The Drowning Risk Perceptions Scale (DRPS) was used to evaluate the risk level of perceptions, and the Drowning Risk Attitudes Scale (DRAS) was used to evaluate the risk level of attitudes. Results: The results of the mediating effect test showed that water safety knowledge (WSK) affected drowning risk behaviors (DRB) through three indirect paths. Drowning risk perceptions (DRP) and attitudes (DRA) have significantly mediated the association between WSK and DRB. In conclusion, DRP and DRA can act as mediators between WSK and DRB, not only individually, but also as chain mediators, where the direct effect is-0.301, the total indirect effect is-0.214, and the total mediated indirect effect is 41.5%. Discussion: Water safety knowledge negatively predicts adolescents' drowning risk behaviors; water safety knowledge has an inhibitory effect on drowning risk perceptions. Water safety knowledge can directly influence adolescents' drowning risk perceptions and indirectly affect drowning risk behaviors through the mediation of drowning risk perceptions and attitudes comprising three paths: (1) the drowning risk perceptions mediation path, (2) the drowning risk attitudes mediation path, and (3) the drowning risk perceptions and attitudes mediation paths.


Assuntos
Afogamento , Conhecimentos, Atitudes e Prática em Saúde , Assunção de Riscos , Humanos , Afogamento/prevenção & controle , Adolescente , Feminino , Masculino , China , Inquéritos e Questionários , Fatores de Risco , Segurança , Comportamento do Adolescente/psicologia
12.
Psychoneuroendocrinology ; 165: 107046, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38626557

RESUMO

Previous research has shown a decrease in serum testosterone levels in male patients with depression. In recent years, the results of testosterone replacement therapy (TRT) to improve depression have been mixed. Using the classic CUMS model, we induced depressive-like behaviors in rats and observed a decrease in their serum testosterone levels along with an increase in androgen receptor expression in the hippocampus. We then performed castration and sham surgery on male rats and found that testosterone deprivation led to the manifestation of depressive-like behavior that could be ameliorated by TRT. Through a repeated measures experiment consisting of five blocks over a period of 25 days, we discovered that the reduction in depressive-like behavior in testosterone-deprived rats began 22 days after drug administration (0.5 and 0.25 mg/rat). Furthermore, rats in 0.5mgT group showed the most significant improvements. Subsequently, this dose was used in CUMS rats and reduced the occurrence of depressive-like behaviors. Our study has demonstrated the complex interplay between depression and testosterone, as well as the intricate dose-response relationship between TRT and reduction in depression. Our research supports the use of TRT to alleviate depression, but dosage and duration of treatment are critical factors in determining efficacy.


Assuntos
Comportamento Animal , Depressão , Orquiectomia , Testosterona , Animais , Masculino , Testosterona/farmacologia , Testosterona/administração & dosagem , Testosterona/metabolismo , Ratos , Depressão/tratamento farmacológico , Depressão/metabolismo , Comportamento Animal/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Modelos Animais de Doenças , Ratos Sprague-Dawley , Relação Dose-Resposta a Droga , Terapia de Reposição Hormonal/métodos , Receptores Androgênicos/metabolismo , Receptores Androgênicos/efeitos dos fármacos
13.
Eur J Pharmacol ; 963: 176245, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38052413

RESUMO

Mammalian heart is capable to regenerate almost completely early after birth through endogenous cardiomyocyte proliferation. However, this regenerative capacity diminishes gradually with growth and is nearly lost in adulthood. Cannabidiol (CBD) is a major component of cannabis and has various biological activities to regulate oxidative stress, fibrosis, inflammation, and cell death. The present study was conducted to investigate the pharmacological effects of CBD on heart regeneration in post-MI mice. MI models in adult mice were constructed via coronary artery ligation, which were administrated with or without CBD. Our results demonstrate that systemic administration (10 mg/kg) of CBD markedly increased cardiac regenerative ability, reduced infarct size, and restored cardiac function in MI mice. Consistently, in vitro study also showed that CBD was able to promote the proliferation of neonatal cardiomyocytes. Mechanistically, the expression of miR-143-3p related to cardiomyocyte proliferation was significantly down-regulated in CBD-treated cardiomyocytes, while the overexpression of miR-143-3p inhibited cardiomyocyte mitosis and eliminated CBD-induced cardiomyocyte proliferation. Moreover, CBD enhanced the expression of Yap and Ctnnd1, which were demonstrated as the target genes of miR-143-3p. Silencing of Yap and Ctnnd1 hindered the proliferative effects of CBD. We further revealed that inhibition of the cannabinoid receptor 2 impeded the regulatory effect of CBD on miR-143-3p and its downstream target Yap/Ctnnd1, which ultimately eliminated the pro-proliferative effect of CBD on neonatal and adult cardiomyocytes. Taken together, CBD promotes cardiomyocyte proliferation and heart regeneration after MI via miR-143-3p/Yap/Ctnnd1 signaling pathway, which provides a new strategy for cardiac repair in adult myocardium.


Assuntos
Canabidiol , MicroRNAs , Infarto do Miocárdio , Animais , Camundongos , Miócitos Cardíacos , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Infarto do Miocárdio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células , Regeneração/fisiologia , Mamíferos/genética
14.
Cancer Immunol Res ; 12(5): 516-529, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38437646

RESUMO

As understanding of cancer has deepened, increasing attention has been turned to the roles of psychological factors, especially chronic stress-induced depression, in the occurrence and development of tumors. However, whether and how depression affects the progression of gliomas are still unclear. In this study, we have revealed that chronic stress inhibited the recruitment of tumor-associated macrophages (TAM) and other immune cells, especially M1-type TAMs and CD8+ T cells, and decreased the level of proinflammatory cytokines in gliomas, leading to an immunosuppressive microenvironment and glioma progression. Mechanistically, by promoting the secretion of stress hormones, chronic stress inhibited the secretion of the chemokine CCL3 and the recruitment of M1-type TAMs in gliomas. Intratumoral administration of CCL3 reprogrammed the immune microenvironment of gliomas and abolished the progression of gliomas induced by chronic stress. Moreover, levels of CCL3 and M1-type TAMs were decreased in the tumor tissues of glioma patients with depression, and CCL3 administration enhanced the antitumor effect of anti-PD-1 therapy in orthotopic models of gliomas undergoing chronic stress. In conclusion, our study has revealed that chronic stress exacerbates the immunosuppressive microenvironment and progression of gliomas by reducing the secretion of CCL3. CCL3 alone or in combination with an anti-PD-1 may be an effective immunotherapy for the treatment of gliomas with depression. See related Spotlight by Cui and Kang, p. 514.


Assuntos
Quimiocina CCL3 , Progressão da Doença , Glioma , Estresse Psicológico , Microambiente Tumoral , Animais , Humanos , Masculino , Camundongos , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Quimiocina CCL3/metabolismo , Glioma/imunologia , Glioma/metabolismo , Glioma/patologia , Glioma/tratamento farmacológico , Camundongos Endogâmicos C57BL , Estresse Psicológico/imunologia , Estresse Psicológico/complicações , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
15.
Front Immunol ; 14: 1104180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187760

RESUMO

Background: The association between white blood cells (WBCs) and metabolic syndrome (MS) has been consistently reported in previous studies using regional samples. However, it remains unclear whether this relationship has urban-rural differences and is independent of insulin resistance using a large-scale representative sample. Additionally, accurate risk prediction in patients with MS is crucial for developing targeted interventions to enhance the quality of life and prognosis of patients. Aims: The aims of this study were (1) to examine the cross-sectional association between WBCs and MS among the national population and analyze the urban-rural difference and whether insulin resistance plays a moderator effect in this association and (2) to describe the performance to predict MS using machine learning (ML) models. Design: A cross-sectional study was performed using 7,014 data from the China Health and Nutrition Survey (CHNS). Methods: WBCs were analyzed using an automatic hematology analyzer and MS was defined according to the criteria of the American Heart Association scientific statements of 2009. Variables on sociodemographic characteristics (sex, age, and residence), clinical laboratory (BMI and HOMA-IR), and lifestyle characteristics (smoking and drinking status) were used to construct ML models to predict MS [logistic regression (LR) and multilayer perceptron (MLP) neural network]. Results: We found that 21.1% of participants (1,479/7,014) were classified as having MS. In multivariate logistic regression (including insulin resistance), the result revealed a significant positive association between WBCs and MS. The odds ratios (95% CI) for MS with increasing WBC level were 1.00 (reference), 1.65 (1.18, 2.31), and 2.18 (1.36, 3.50) (p for trend: 0.001). For two ML algorithms, two models showed adequate calibration and good discrimination, but the MLP showed better performance (AUC-ROC = 0.862 and 0.867). Conclusion: With the aim of confirming the association between WBCs and MS, this cross-sectional study is the first to show that maintaining normal WBC count levels is helpful to prevent the development of MS, and this association is independent of insulin resistance. The results also showed that the MPL algorithm represented a more prominent predictive performance to predict MS.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Humanos , Estudos Transversais , População do Leste Asiático , Contagem de Leucócitos , Síndrome Metabólica/epidemiologia , Qualidade de Vida , China
16.
Medicine (Baltimore) ; 102(33): e34528, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37603517

RESUMO

Internet addiction (IA) is a prevalent trend among college students, and the relationship between severe IA and poor health status among college students has been well established. However, whether IA is associated with suboptimal health status (SHS) in college students is unclear. This study aimed to investigate the association between IA and SHS risk in Chinese college students. We conducted a cross-sectional study to assess whether IA was related to SHS risk in 2265 college students in Shenyang, China. SHS was assessed using the Suboptimal Health Status Questionnaire with a cutoff score of ≥35 to document SHS. IA was assessed using the validated 20-item Young's Internet Addiction Test with cutoff scores of 31-49 and 50-100 for mile and moderate-to-severe cases, respectively. The prevalence rate of SHS was 54.0%. After adjusting for potential confounding factors, the IA categories were positively related to a higher risk of SHS. The odds ratios (95% confidence intervals) for SHS across IA categories were 1.00, 7.66 (6.00, 9.78), and 27.93 (20.95, 37.24) (P for trend: <.001) after adjusting for multiple confounding factors. This is the first cross-sectional study to demonstrate that IA is independently associated with SHS. This finding suggests that IA is a negative risk factor for SHS.


Assuntos
População do Leste Asiático , Transtorno de Adição à Internet , Humanos , Estudos Transversais , Nível de Saúde , Estudantes
17.
Polymers (Basel) ; 15(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37765618

RESUMO

Nanoscale zero-valent iron (NZVI) is a material that is extensively applied for water pollution treatment, but its poor dispersibility, easy oxidation, and inconvenient collection limit its application. To overcome these drawbacks and limit secondary contamination of nanomaterials, we confine NZVI supported by reduced graphene oxide (rGO) in the scaffold of sodium alginate (SA) gel beads (SA/NZVI-rGO). Scanning electron microscopy showed that the NZVI was uniformly dispersed in the gel beads. Fourier transform infrared spectroscopy demonstrated that the hydrogen bonding and conjugation between SA and rGO allowed the NZVI-rGO to be successfully embedded in SA. Furthermore, the mechanical strength, swelling resistance, and Cr(VI) removal capacity of SA/NZVI-rGO were enhanced by optimizing the ratio of NZVI and rGO. Interestingly, cation exchange may drive Cr(VI) removal above 82% over a wide pH range. In the complex environment of actual Cr(VI) wastewater, Cr(VI) removal efficiency still reached 70.25%. Pseudo-first-order kinetics and Langmuir adsorption isotherm are preferred to explain the removal process. The mechanism of Cr(VI) removal by SA/NZVI-rGO is dominated by reduction and adsorption. The sustainable removal of Cr(VI) by packed columns could be well fitted by the Thomas, Adams-Bohart, and Yoon-Nelson models, and importantly, the gel beads maintained integrity during the prolonged removal. These results will contribute significant insights into the practical application of SA/NZVI-rGO beads for the Cr(VI) removal in aqueous environments.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36767247

RESUMO

Cr(VI) pollution in water bodies is very harmful to human health and the environment. Therefore, it is necessary to remove Cr(VI) from water. In this study, the composite (FP-nZVI) was prepared by loading nano-zero-valent iron (nZVI) onto cellulose filter paper (FP) using a liquid-phase reduction method to improve the dispersibility and oxidation resistance of nZVI. In batch experiments, the effects of iron loading of FP-nZVI, initial concentration of Cr(VI), temperature, and pH on Cr(VI) removal were particularly investigated. The maximum removal rate of 98.6% was achieved at 25 °C, pH = 5, initial concentration of Cr(VI) of 20 mg/L, and FeCl3·6H2O solution concentration of 0.8 mol/L. The removal of Cr(VI) by FP-nZVI conformed to a pseudo-second-order kinetic model and Langmuir isotherm model. The mechanism of Cr(VI) removal was a multi-step removal mechanism, involving adsorption, reduction, and coprecipitation. Column experiments investigated the effect of flow rate (1 mL/min, 3 mL/min, and 5 mL/min) on Cr(VI) removal. We found that increasing flow rate slightly decreased the removal rate of Cr(VI). The transport of Cr(VI) in composite porous media was simulated using HYDRUS-1D, and the results show that the two-site model can well simulate the reactive transport of Cr(VI). This study may provide a useful reference for the remediation of groundwater contaminated with Cr(VI) or other similar heavy metals using FP-nZVI.


Assuntos
Ferro , Poluentes Químicos da Água , Humanos , Poluentes Químicos da Água/análise , Cromo/análise , Água , Adsorção
19.
Mol Med Rep ; 28(4)2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37681444

RESUMO

In recent years, inhibiting tumor cell activity by triggering cell ferroptosis has become a research hotspot. The development of generic targeted nanotherapeutics might bring new ideas for non­invasive applications. Currently, the potential mechanism underlying the universal application of paclitaxel (PTX)­loaded iron oxide nanoparticles (IONP@PTX) to different types of tumors is unclear. The present study aimed to prepare IONP@PTX for targeted cancer therapy and further explore the potential mechanisms underlying the inhibitory effects of this material on the NCI­H446 human small cell lung cancer and brain M059K malignant glioblastoma cell lines. First, a CCK­8 assay was performed to determine cell viability, and then the combination index for evaluating drug combination interaction effect was evaluated. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were monitored using a DCFH­DA fluorescent probe and a C11­BODIPY™ fluorescent probe, respectively. Furthermore, western blotting assay was performed to determine the expression of autophagy­ and iron death­related proteins. The experimental results showed that, compared with either IONP monotherapy, PTX monotherapy, or IONP + PTX, IONP@PTX exerted a synergistic effect on the viability of both cell types, with significantly increased total iron ion concentration, ROS levels and lipid peroxidation levels. IONP@PTX significantly increased the expression of autophagy­related proteins Beclin 1 and histone deacetylase 6 (HDAC6) in both cell lines (P<0.05), increased the expression of light chain 3 (LC3)­II/I in NCI­H446 cells (P<0.05) and decreased that of sequestosome1 (p62) in M059K cells (P<0.05). Moreover, the addition of rapamycin enhanced the IONP@PTX­induced the upregulation of Beclin 1, LC3­II/I and HDAC6 and the downregulation of mTORC1 protein in both cell lines (P<0.05). Moreover, rapamycin enhanced the IONP@PTX­induced downregulation of p62 protein in NCI­H446 cells (P<0.05), suggesting that IONP@PTX induces ferroptosis, most likely through autophagy. Collectively, the present findings show that IONP works synergistically with PTX to induce ferroptosis via the autophagic pathway.


Assuntos
Neoplasias Encefálicas , Ferroptose , Humanos , Proteína Beclina-1 , Corantes Fluorescentes , Espécies Reativas de Oxigênio , Autofagia , Anticorpos , Nanopartículas Magnéticas de Óxido de Ferro
20.
Sci Rep ; 13(1): 17507, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845368

RESUMO

Ischemic stroke stands as a prevalent neurological ailment, where a paucity of methodologies exists for the assessment of functional outcomes post-stroke. Our objective was the development of a WeChat applet for the evaluation of muscle strength and the subsequent evaluation of its validity in ischemic stroke patients experiencing motor dysfunction. The assessment encompassed Lovett and NIHSS, followed by muscle strength values (MSV) and muscle strength ratios (MSR). These metrics were then scrutinized in relation to NIHSS and Lovett, followed by examination of their interrelationships. We enrolled a cohort of 157 patients, with an average age of 65 years, consisting of 96 males and 61 females. Lovett scores in the range of 2-4 and NIHSS scores spanning from 0 to 3 were found to correspond to specific values of MSV and MSR, respectively. Upon conducting correlation analysis, we noted that both MSV and MSR exhibited significant positive correlations with Lovett scores and NIHSS. Remarkably, the correlation of MSR with Lovett scores or NIHSS surpassed that of MSV. The WeChat applet offers a means of digitization and visualization of muscle strength. It correlates well with Lovett score and NIHSS, especially MSR. This bears potential significance in guiding the rehabilitation of stroke patients.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Feminino , Humanos , Idoso , Índice de Gravidade de Doença
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