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1.
FASEB J ; 37(1): e22707, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36520054

RESUMO

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The existence of cancer stem cells (CSC) causes tumor relapses, metastasis, and resistance to conventional therapy. Alternative splicing has been shown to affect physiological and pathological processes. Accumulating evidence has confirmed that targeting alternative splicing could be an effective strategy to treat CRC. Currently, the role of alternative splicing in the regulation of CSC properties in CRC has not been elucidated. Here, we show that RBM17 displays oncogenic roles in CRC cells. RBM17 enhances cell proliferation and reduces chemotherapeutic-induced apoptosis in CRC cells. Besides, RBM17 increases CD133 positive and ALDEFLUOR positive populations and promotes sphere formation in CRC cells. In mechanism studies, we found that FOXM1 is critical for RBM17 enhanced CSC properties. Moreover, FOXM1 alternative splicing is essential for RBM17 enhanced CSC properties in CRC cells. Additionally, RBM17 enhances CSC characteristics by controlling FOXM1 expression to promote Sox2 expression. Furthermore, AKT1 works as an upstream kinase to control RBM17-mediated FOXM1 alternative splicing and enhancement of CSC properties in CRC cells. Our study reveals that AKT1-RBM17-FOXM1-Sox2 axis could be a potential target for modulating alternative splicing to reduce CSC properties in CRC cells.


Assuntos
Neoplasias Colorretais , Humanos , Processamento Alternativo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Processamento de RNA/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-38512474

RESUMO

Excessive screen time and the consumption of sugar-sweetened beverages are found to be independent predictors of depressive symptoms. However, the potential interaction effect of screen time and sugar-sweetened beverages, that is, whether one exposure factor strengthens the association of another with depressive symptoms, remains unclear. A large-scale adolescent health surveillance survey was conducted in 27 schools in eight regions across China. A total of 22,868 students were recruited to complete an eligible questionnaire to provide details of their screen time and sugar-sweetened beverage consumption. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Multiplicative and additive interaction models were performed to estimate the interaction effects of screen time and sugar-sweetened beverages on depressive symptoms, and whether the relationship varied by age group was also examined. The multivariate logistic regression model showed that even if the confounding factors were controlled, screen time and sugar-sweetened beverages were still risk factors for depressive symptoms in adolescents. Interaction models indicated that screen time and sugar-sweetened beverages in combination were related to greater odds of depressive symptoms. Compared with late adolescents, early adolescents had a higher probability of depressive symptoms when exposed to the joint effects. Our study may hopefully deepen the understanding of the association between screen time and sugar-sweetened beverages and depressive symptoms. Future research should further explore how and why screen time and sugar-sweetened beverages affect individuals more profoundly in early adolescence than in late adolescence and how to mitigate this.

3.
Nano Lett ; 23(14): 6610-6618, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37458704

RESUMO

Diabetic ulcers have received much attention in recent years due to their high incidence and mortality, motivating the scientific community to develop various strategies for such chronic disease treatments. However, the therapeutic outcome of these approaches is highly compromised by invasive bacteria and a severe inflammatory microenvironment. To overcome these dilemmas, microenvironment-responsive self-delivery glucose oxidase@manganese sulfide (GOx@MnS) nanoparticles (NPs) are developed by one-step biomineralization. When they encounter the high glucose level in the ulcer site, GOx particles catalyze glucose to decrease the local pH and trigger the steady release of both manganese ions (Mn2+) and hydrogen sulfide (H2S). Mn2+ reacts with hydrogen peroxide to generate hydroxyl radicals for the elimination of bacterial infection; meanwhile, H2S is able to suppress the inflammatory response and accelerate diabetic wound healing through macrophage polarization. The excellent biocompatibility, strong bactericidal activity, and considerable immunomodulatory effect promise GOx@MnS NPs have great therapeutic potential for diabetic wound treatment.


Assuntos
Diabetes Mellitus , Sulfeto de Hidrogênio , Nanopartículas , Humanos , Glucose Oxidase/uso terapêutico , Glucose , Peróxido de Hidrogênio
4.
Pharmacol Res ; 183: 106361, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35882295

RESUMO

There are numerous prescription drugs and non-prescription drugs that cause drug-induced liver injury (DILI), which is the main cause of liver disease in humans around the globe. Its mechanism becomes clearer as the disease is studied further. For an instance, when acetaminophen (APAP) is taken in excess, it produces N-acetyl-p-benzoquinone imine (NAPQI) that binds to biomacromolecules in the liver causing liver injury. Treatment of DILI with traditional Chinese medicine (TCM) has shown to be effective. For example, activation of the Nrf2 signaling pathway as well as regulation of glutathione (GSH) synthesis, coupling, and excretion are the mechanisms by which ginsenoside Rg1 (Rg1) treats APAP-induced acute liver injury. Nevertheless, reducing the toxicity of TCM in treating DILI is still a problem to be overcome at present and in the future. Accumulated evidences show that hydrogel-based nanocomposite may be an excellent carrier for TCM. Therefore, we reviewed TCM with potential anti-DILI, focusing on the signaling pathway of these drugs' anti-DILI effect, as well as the possibility and prospect of treating DILI by TCM based on hydrogel materials in the future. In conclusion, this review provides new insights to further explore TCM in the treatment of DILI.


Assuntos
Produtos Biológicos , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Acetaminofen , Produtos Biológicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Hidrogéis , Medicina Tradicional Chinesa
5.
Acta Pharmacol Sin ; 42(10): 1676-1689, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33514855

RESUMO

Zinc finger E-box-binding homeobox 1 (ZEB1), a functional protein of zinc finger family, was aberrant expressed in many kinds of liver disease including hepatic fibrosis and Hepatitis C virus. Bioinformatics results showed that ZEB1 was abnormally expressed in HCC tissues. However, to date, the potential regulatory role and molecular mechanisms of ZEB1 are still unclear in the occurrence and development of HCC. This study demonstrated that the expression level of ZEB1 was significantly elevated both in liver tissues of HCC patients and cell lines (HepG2 and SMMC-7721 cells). Moreover, ZEB1 could promote the proliferation, migration, and invasion of HCC cells. On the downstream regulation mechanism, ZEB1 could activate the Wnt/ß-catenin signaling pathway by upregulating the protein expression levels of ß-catenin, c-Myc, and cyclin D1. Novel studies showed that miR-708 particularly targeted ZEB1 3'-UTR regions and inhibited the HCC cell proliferation, migration, and invasion. Furthermore, results of nude mice experiments of HCC model indicated that miR-708 could inhibit tumor growth and xenograft metastasis model was established to validate that miR-708 could inhibit HCC cell metastasis through tail-vein injection in vivo. Together, the study suggested that ZEB1 modulated by miR-708 might be a potential therapeutic target for HCC therapy.


Assuntos
Apoptose/fisiologia , Carcinoma Hepatocelular/fisiopatologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Via de Sinalização Wnt/fisiologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Adulto , Idoso , Animais , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica/fisiopatologia
6.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5309-5322, 2020 Nov.
Artigo em Zh | MEDLINE | ID: mdl-33350190

RESUMO

By referring to the standards and procedures of WHQ Handbook for Guideline Development, under the guidance of relevant laws, regulations, and technical documents, in line with the principle of "evidence-based, consensus-based, experience-based", and based on the best available evidences, fully combined with expert experience and patient preferences, we summarized eight clinical questions in this paper: can traditional Chinese medicine(TCM) treatment improve the clinical symptoms and the degree of dyspnea in patients with stable chronic obstructive pulmonary disease(COPD) Can TCM treatment reduce the number of exacerbations in patients with stable COPD? Can TCM treatment improve the exercise tolerance of patients with stable COPD? Can TCM treatment improve the quality of life of patients with stable COPD? Can TCM treatment delay the decline of lung function in patients with stable COPD? Can TCM treatment improve anxiety and depression in patients with stable COPD? Does the point application therapy benefit patients with stable COPD? Can non-pharmacological treatment benefit patients with stable COPD? Based on these eight clinical problems, the cha-racteristics of TCM itself, and actual clinical situation, the recommendations of TCM to treat the stable COPD were formed in this guideline, with intention to provide advice and guidance to clinicians in the use of TCM to treat stable COPD, to relieve symptoms, improve exercise tolerance, improve health status, prevent disease progression, prevent and treat exacerbations, and improve clinical efficacy. Due to the influence of the user's region, nationality, race and other factors, the implementation of this guideline should be based on the actual situations.


Assuntos
Medicina Tradicional Chinesa , Doença Pulmonar Obstrutiva Crônica , Dispneia , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento
7.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5323-5330, 2020 Nov.
Artigo em Zh | MEDLINE | ID: mdl-33350191

RESUMO

As an important auxiliary document in the process of guideline development, the editorial explanation is the extension and complement to the content of the guideline, a basis for fully understanding the technical content of the guideline, an indispensable document for the guideline's traceability. The project team of this guideline, while formulating the Clinical practice guideline for stable chronic obstructive pulmonary disease with traditional Chinese medicine(draft version for comments), also has written the corresponding editorial explanation. In order to enable the relevant medical workers to more accurately understand and apply the guideline, but also to provide readers with a more in-depth understanding of the reasons and processes for the development of the guideline, the paper will give a detailed introduction to the compilation process about the guideline, includes: work overview(project background, task source, drafting and collaboration unit, project team members and their division of labor), main technical content(the basis and principles of guideline development, technical route), main compilation process(the establishment of project team, the formulation of the guideline plan, the project approval and the registration of research programme, the construction of clinical issues and the selection of outcome indicators, evidence search screening and synthesis, evidence evaluation and grading, the formation of recommendations, the writing of exposure draft, external review and self-assessment, etc), expert consensus implementation requirements and measure suggestions(promotion and implementation measures, and post-effect evaluation), other issues need to be explained and so on.


Assuntos
Medicina Tradicional Chinesa , Doença Pulmonar Obstrutiva Crônica , Consenso , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
8.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5331-5343, 2020 Nov.
Artigo em Zh | MEDLINE | ID: mdl-33350192

RESUMO

To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.


Assuntos
Medicina , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Medicamentos de Ervas Chinesas , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Xinafoato de Salmeterol/uso terapêutico
9.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5344-5355, 2020 Nov.
Artigo em Zh | MEDLINE | ID: mdl-33350193

RESUMO

To systematically review the efficacy and safety of Buzhong Yiqi Decoction in the treatment of stable chronic obstructive pulmonary disease(COPD) at the stable stage. Three English databases and four Chinese databases were systematically searched from the database establishment to August 1, 2020. Randomized controlled trials(RCTs) were screened according to the pre-determined inclusion and exclusion criteria, and then the data were extracted. Methodological quality of the included studies was assessed based on Cochrane bias risk tool, and RevMan 5.3 was used for data analysis. A total of 389 articles were retrieved and finally 18 RCTs were included in this study, involving 1 566 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in terms of improving 6-minute walk distance(6 MWD), and delaying the decline of forced expiratory volume in one second(FEV_1) or its % in the expected value as well as the decline in ratio of FEV_1 to forced vital capacity(FVC), Buzhong Yiqi Decoction alone or in combination with conventional Western medicine was superior to conventional therapy Western medicine alone. Subgroup analysis showed that, in terms of reducing traditional Chinese medicine symptom scores, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of reducing the grade of modified medical research council(mMRC), Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of improving 6 MWD, Buzhong Yiqi Decoction combined with conventional treatment or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment alone or Tiotropium Bromide Powder for Inhalation alone. In terms of delaying the decline of FEV_1 or its % in the expected value, Buzhong Yiqi Decoction combined with conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation alone, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. In terms of delaying the decline in FEV_1/FVC, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. Meta-analysis of other outcome measures was not available and no conclusion can be drawn due to the inclusion of only one study. As some studies did not mention the adverse reactions, no safety comments can be made for Buzhong Yiqi Decoction alone or combined with conventional Western medicine. Due to the limitations of the quality and quantity of included studies, the conclusions of this research should be treated with caution. The efficacy of Buzhong Yiqi Decoction for stable COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Volume Expiratório Forçado , Humanos , Medicina Tradicional Chinesa , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio , Capacidade Vital
10.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5356-5361, 2020 Nov.
Artigo em Zh | MEDLINE | ID: mdl-33350194

RESUMO

This article analyze acupoint selection and characteristics of plaster therapy for stable chronic obstructive pulmonary di-sease(COPD) by data mining. The CNKI, VIP, CBM, WanFang, PubMed, EMbase, Cochrane Library were retrieved for collecting clinical studies of plaster therapy for stable COPD. After literature screening, a total of 46 systematic reviews were included. Frequency statistics, cluster analysis, and Apriori correlation analysis were used to analyze the pattern and characteristics of plaster therapy for stable COPD. The result showed that the main acupoints for stable COPD were BL13, Dingchuan, CV22, BL23 and BL20. The acupoints used are mainly concentrated on the chest and back. The most frequently used meridian is the bladder meridian. Analysis of the acupoints yielded 27 correlation rules. And cluster analysis grouped the high frequency acupoints into 5 categories. The results of the study showed that the current choice of acupoints is rather concentrated. "Local acupuncture points" and "matching points with front and back" were the main acupoint selection rules. The choice of acupuncture points reflected the traditional Chinese medicine treatment principle of strengthening healthy Qi to eliminate pathogenic factor, treating both manifestation and root cause of disease, and preventing measure taken after the occurrence of disease.


Assuntos
Terapia por Acupuntura , Meridianos , Doença Pulmonar Obstrutiva Crônica , Pontos de Acupuntura , Mineração de Dados , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
11.
Psychiatry Res ; 337: 115909, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38703563

RESUMO

The correlation between metabolic metrics and mental health remains underexplored, with few in-depth studies examining whether this association exists among college students and whether it might be moderated by socio-ecological risk factors (SERFs) and mediated by resilience. A follow-up study design investigated the association between baseline metabolic metrics, SERFs and resilience and mental health. A multivariable linear regression model using the PROCESS method established the relationship of SERFs, resilience and metabolic metrics with mental health. Participants were 794 adolescents (mean age: 18.64 [±0.90] years). In multivariable linear regression, the high-level SERFs (ß = 0.124), resilience (ß = -0.042), LCI (ß = 0.072), and RFM (ß = 0.145) were associated with higher depression symptoms, while CVH (ß = 0.602), TyG (ß = 0.295), TyG-BMI (ß = 0.004), and RC (ß = -0.041) were not. An association was also observed between SERFs, resilience, RFM and anxiety. Resilience mediated the relationship between metabolic metrics and depression and anxiety, and SERFs moderated this relationship, demonstrating the relationship between resilience, metabolic metrics, SERFs and mental health. By revealing the potential sociological mechanism underlying the relationship between metabolic metrics and adolescents' mental health, this study provides a theoretical basis for further exploration of the biological foundations of mental health.


Assuntos
Ansiedade , Depressão , Saúde Mental , Resiliência Psicológica , Humanos , Feminino , Masculino , Adolescente , Adulto Jovem , Depressão/epidemiologia , Depressão/psicologia , Depressão/metabolismo , Fatores de Risco , Ansiedade/epidemiologia , Ansiedade/psicologia , Ansiedade/metabolismo , Seguimentos , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Adulto
12.
Adv Healthc Mater ; : e2304510, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38532711

RESUMO

Aseptic loosening and bacterial infection pose significant challenges in the clinical application of titanium (Ti) orthopedic implants, which are primarily caused by insufficient osseointegration and bacterial contamination. To address these issues, a responsive coating on Ti surface is constructed, which achieves enhanced osseointegration and infection elimination by on-demand release of therapeutic gas hydrogen sulfide (H2S) and antibiotic. TiO2 nanotubes (TNT) are anodized on the Ti surface to enhance its bioactivity and serve as reservoirs for the antibiotic. An infection microenvironment-responsive macromolecular H2S donor layer is coated on top of TNT to inhibit premature leakage of antibiotic. This layer exhibits a sustained release of low-dosage H2S, which is capable of promoting the osteogenic differentiation and migration of cells. Moreover, the compactness of the macromolecular H2S donor layer could be broken by bacterial invasion, leading to rapid antibiotic release thus preventing infection. In vitro antibacterial experiments validates significant antibacterial activity of the coating against both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Crucially, this coating effectively suppresses implant-associated infection with 98.7% antibacterial efficiency in a rat femoral bone defect model, mitigates inflammation at the defect site and promotes osseointegration of the Ti orthopedic implant.

13.
Psychol Sport Exerc ; 72: 102605, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38346583

RESUMO

BACKGROUND: A growing number of studies have found that physical activity (PA) benefits mental health, and sedentary behavior (SB) increases the risk of psychological symptoms, but it remains unclear whether substituting the duration of different activities may affect the association, and whether sex difference exists among college students. METHODS: A longitudinal survey was conducted in three colleges in Anhui province, China. A total of 8049 participants validly answered the questionnaire, which included demographic variables, PA, SB and negative emotions (depressive, anxiety, and stress symptoms). RESULTS: Substituting 30 min per day of SB with equivalent walking was associated with lower scores of depressive symptoms. Stress symptoms were reduced when SB was substituted by moderate intensity PA (MPA) and walking. Substituting 30 min per day of MPA in place of walking and SB was associated with an amelioration of depressive and stress symptoms in females, and a reallocation of 30 min walking was associated with lower depressive and stress symptom scores when SB was replaced in males. CONCLUSIONS: Replacing SB with walking and MPA ameliorates the depressive and stress symptoms in young adults. The results suggest a reallocation of time from SB or walking to MPA in females while from SB to walking in males may markedly reduce the depressive and stress symptoms in college population.


Assuntos
Comportamento Sedentário , Caracteres Sexuais , Adulto Jovem , Humanos , Masculino , Feminino , Exercício Físico/psicologia , Estudantes , Ansiedade/epidemiologia
14.
Int J Biol Sci ; 20(6): 2219-2235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617542

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Metabolismo dos Lipídeos/genética , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Receptores de Quimiocinas , Inflamação
15.
J Tradit Chin Med ; 43(6): 1068-1071, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37946468

RESUMO

This study aims to provide evidence regarding whether Qingufei paidu decoction (, QFPD) treatment in the acute phase shows long-term benefits for coronavirus disease 2019-associated sequelae. The 10 databases will be retrieved. Every reference list of related trials and gray literature will be searched as well. Study screening, data extraction, and risk of bias evaluation will be performed by two reviewers (CUI Hanjin and FAN Rong). Data analysis will be conducted by using STATA (version 14). Statistical heterogeneity will be explored by a standard χ2 test with a significance level of P < 0.10. Funnel plots, Egger's & Begg's test, and Trim and Fill analysis will be used for publication bias assessment. The results of the present Meta-analysis and systematic review will be disseminated via peer-review journal publication. Ethical approval is not required, as this Meta-analysis will not contain any individual patient data. This systematic review has been registered on PROSPERO (registration number: CRD42021246937) on 15 April 2021.


Assuntos
COVID-19 , Pneumonia , Humanos , Revisões Sistemáticas como Assunto , Metanálise como Assunto
16.
Bioact Mater ; 27: 154-167, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37064802

RESUMO

Due to protection of extracellular polymeric substances, the therapeutic efficiency of conventional antimicrobial agents is often impeded by their poor infiltration and accumulation in biofilm. Herein, one type of surface charge adaptable nitric oxide (NO) nanogenerator was developed for biofilm permeation, retention and eradication. This nanogenerator (PDG@Au-NO/PBAM) is composed of a core-shell structure: thermo-sensitive NO donor conjugated AuNPs on cationic poly(dopamine-co-glucosamine) nanoparticle (PDG@Au-NO) served as core, and anionic phenylboronic acid-acryloylmorpholine (PBAM) copolymer was employed as a shell. The NO nanogenerator featured long circulation and good biocompatibility. Once the nanogenerator reached acidic biofilm, its surface charge would be switched to positive after shell dissociation and cationic core exposure, which was conducive for the nanogenerator to infiltrate and accumulate in the depth of biofilm. In addition, the nanogenerator could sustainably generate NO to disturb the integrity of biofilm at physiological temperature, then generate hyperthermia and explosive NO release upon NIR irradiation to efficiently eradicate drug-resistant bacteria biofilm. Such rational design offers a promising approach for developing nanosystems against biofilm-associated infections.

17.
Bioact Mater ; 19: 198-216, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35510171

RESUMO

Hydrogen sulfide (H2S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H2S are highly associated with its concentrations. At relatively low concentration, H2S shows beneficial functions. However, long-time and high-dose donation of H2S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H2S delivery for precision medicine, H2S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H2S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H2S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H2S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H2S therapies especially imaging-guided H2S theranostics are highlighted. Since H2S donors with stimuli-responsive characters are vital components for establishing intelligent H2S delivery systems, the development of H2S donors is also briefly introduced.

18.
J Affect Disord ; 320: 140-147, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36181912

RESUMO

BACKGROUND: Previous research has found increasing evidence of adverse childhood experiences (ACEs) leading to non-suicidal self-injury (NSSI) and suicidal behaviors. Most studies have focused on a certain type or timing of ACEs or the patterns of multiple types; however, few of them have examined the patterns of ACEs combined types and timing and the gender differences in the association between ACEs and self-harming behaviors. METHODS: A cross-sectional survey was conducted in three Chinese cities from November 2020 to May 2021. We asked 16,853 middle school students to anonymously complete a questionnaire to provide the details of their own ACEs and NSSI or suicidal behaviors. RESULTS: Latent class analysis identified four classes: high ACEs (10 %), high abuse/neglect (20.3 %), moderate ACEs (26.7 %) and low ACEs (43 %). Logistic regression models demonstrated that students in the high ACEs, high abuse/neglect and moderate ACEs subgroups were more likely to engage in NSSI and suicidal behaviors than students with low ACEs. Compared with boys, girls had a higher probability of engaging in NSSI and suicidal behaviors when exposed to the same level of ACEs. CONCLUSION: Co-occurrence of ACEs is associated with high risk of NSSI and suicidal behaviors. Our findings recognized the most dangerous patterns and latent class membership, which supply the evidence for policy makers to adopt preventive measures to protect high-risk individuals. Strategies to relieve the impact of ACEs, especially on girls, need to be considered comprehensively. LIMITATIONS: The study was limited by cross-sectional design, as causality could not be confirmed. In addition, because our survey was retrospective, potential recall bias can not be ignored.


Assuntos
Experiências Adversas da Infância , Comportamento Autodestrutivo , Humanos , Masculino , Feminino , Fatores Sexuais , Cidades , Estudos Transversais , Estudos Retrospectivos , Ideação Suicida , Comportamento Autodestrutivo/epidemiologia , Estudantes , China/epidemiologia , Inquéritos e Questionários , Fatores de Risco
19.
J Control Release ; 352: 586-599, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36328076

RESUMO

Hydrogen sulfide (H2S), known as the third gasotransmitter, exerts various physiological functions including cardiac protection, angiogenesis, anti-inflammatory, and anti-cancer capability. Given its promising therapeutic potential as well as severe perniciousness if improper use, the sustained and tunable H2S delivery systems are highly required for H2S-based gas therapy with enhanced bioactivity and reduced side effects. To this end, a series of stimuli-responsive compounds capable of releasing H2S (termed H2S donors) have been designed over the past two decades to mimic the endogenous generation of H2S and elucidate the biological functions. Further to improve the stability of H2S donors and achieve the targeted delivery, various delivery systems have been constructed. In this review, we focus on the recent advances of an emerging subset, biomolecular-based H2S delivery systems, which combine H2S donors with biomolecular vectors including polysaccharide, peptide, and protein. We demonstrated their basic structures, building strategies, and therapeutic applications respectively to unfold their inherent merits endued by biomolecules including biocompatibility, biodegradability as well as expansibility. The varied development potentials of biomolecular-based H2S delivery systems based on their specific properties are also discussed. At the end, brief future outlooks and upcoming challenges are presented as well.


Assuntos
Gasotransmissores , Sulfeto de Hidrogênio , Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/metabolismo
20.
ACS Macro Lett ; 11(5): 622-629, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35570816

RESUMO

As one of the gasotransmitters, the therapeutic effects of hydrogen sulfide (H2S) were reported widespread in recent years. Considering the short physiological half-life and significant dose-dependent effects of H2S, it is vital to achieve controlled H2S delivery for biomedical applications. Polymeric micelles have been explored to regulate H2S delivery. However, the dilution-induced dissociation of micelles in physiological conditions limits their therapeutic effects. The circulation stability of polymeric micelles could be improved through core-cross-linking, but reduced H2S releasing efficiency is usually unavoidable. To solve these problems, we developed di-para-substituted S-aroylthiooximes (p-diSATOs) as linkers, which integrated cross-linking of micelle core and conjugation of H2S donors through one simple reaction. Compared with SATO-bearing non-cross-linked micelle, the core-cross-linked micelle (CCM) prepared through this method exhibited initial rapid H2S release owing to the electron-withdrawing effect of p-diSATOs, and subsequently, a sustained release could last for a long period of time. Considering the characteristic H2S releasing behavior of CCM, it may accelerate wound healing through initial efficient and subsequent prolonged pro-healing effects. As a proof of concept, we explored the therapeutic potential of CCM using a murine burn wound model, which exhibited pro-healing effect on burn wounds.


Assuntos
Queimaduras , Gasotransmissores , Sulfeto de Hidrogênio , Animais , Sulfeto de Hidrogênio/farmacologia , Camundongos , Micelas , Polímeros
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