RESUMO
While macrophage is one of the major type I interferon (IFN-I) producers in multiple tissues during viral infections, it also serves as an important target cell for many RNA viruses. However, the regulatory mechanism for the IFN-I response of macrophages to respond to a viral challenge is not fully understood. Here we report ADAP, an immune adaptor protein, is indispensable for the induction of the IFN-I response of macrophages to RNA virus infections via an inhibition of the conjugation of ubiquitin-like ISG15 (ISGylation) to RIG-I. Loss of ADAP increases RNA virus replication in macrophages, accompanied with a decrease in LPS-induced IFN-ß and ISG15 mRNA expression and an impairment in the RNA virus-induced phosphorylation of IRF3 and TBK1. Moreover, using Adap-/- mice, we show ADAP deficiency strongly increases the susceptibility of macrophages to RNA-virus infection in vivo. Mechanically, ADAP selectively interacts and functionally cooperates with RIG-I but not MDA5 in the activation of IFN-ß transcription. Loss of ADAP results in an enhancement of ISGylation of RIG-I, whereas overexpression of ADAP exhibits the opposite effect in vitro, indicating ADAP is detrimental to the RNA virus-induced ISGylation of RIG-I. Together, our data demonstrate a novel antagonistic activity of ADAP in the cell-intrinsic control of RIG-I ISGylation, which is indispensable for initiating and sustaining the IFN-I response of macrophages to RNA virus infections and replication.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteína DEAD-box 58 , Interferon Tipo I , Macrófagos , Camundongos Knockout , Infecções por Vírus de RNA , Ubiquitinas , Animais , Macrófagos/virologia , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/metabolismo , Ubiquitinas/metabolismo , Ubiquitinas/genética , Proteína DEAD-box 58/metabolismo , Interferon Tipo I/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Humanos , Receptores Imunológicos/metabolismo , Interferon beta/metabolismo , Vírus de RNA/imunologia , Fator Regulador 3 de Interferon/metabolismoRESUMO
Oxidative stress and abnormal glucose metabolism are the important physiological mechanisms in the occurrence and development of diabetes. Antioxidant peptides have been reported to attenuate diabetes complications by regulating levels of oxidative stress, but few studies have focused on peptides from marine bone collagen. In this study, we prepared the peptides with a molecular weight of less than 1 kD (HNCP) by enzymolysis and ultrafiltration derived from Harpadon nehereus bone collagen. Furthermore, the effects of HNCP on blood glucose, blood lipid, liver structure and function, oxidative stress, and glucose metabolism were studied using HE staining, kit detection, and Western blotting experiment in streptozocin-induced type 1 diabetes mice. After the 240 mg/kg HNCP treatment, the levels of blood glucose, triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in streptozotocin-induced diabetes mice decreased by 32.8%, 42.2%, and 43.2%, respectively, while the levels of serum insulin and hepatic glycogen increased by 142.0% and 96.4%, respectively. The antioxidant enzymes levels and liver function in the diabetic mice were markedly improved after HNCP intervention. In addition, the levels of nuclear factor E2-related factor 2 (Nrf2), glucokinase (GK), and phosphorylation of glycogen synthase kinase-3 (p-GSK3ß) in the liver were markedly up-regulated after HNCP treatment, but the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase1 (PEPCK1) were down-regulated. In conclusion, HNCP could attenuate oxidative stress, reduce blood glucose, and improve glycolipid metabolism in streptozocin-induced type 1 diabetes mice.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Animais , Camundongos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Estreptozocina , Glicemia , Antioxidantes/química , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estresse Oxidativo , Fígado , Glucose/metabolismo , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Peptídeos/metabolismoRESUMO
Muscarinic acetylcholine receptors (MRs) play important roles in the regulation of hepatic fibrosis and the receptor agonists and antagonists can affect hepatocyte proliferation. However, little is known about the impact of M 3R subtypes and associated signaling pathways on liver injury. The aim of this study is to explore the function and mechanism of M 3R in the regulation of liver injury. We evaluate liver injury and detect the changes in related indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), and transforming growth factor-ß1 (TGF-ß1), after administration of an M 3R agonist. Western blot analysis and qRT-PCR show that the transcription factor Sp1 and long noncoding RNA (lncRNA) Gm2199 are also changed significantly. Rescue assay is performed to further confirm that M 3R contributes to the progression of hepatocyte proliferation through regulating Sp1 and Gm2199. The activated M 3R can specifically regulate Gm2199 by inhibiting the expression of Sp1. Meanwhile, Gm2199 directly regulates miR-212, and ERK is a potential target of miR-212. Collectively, these findings define a novel mechanism for activating M 3R to reverse liver injury, which affects hepatocyte proliferation through the Sp1/Gm 2199/miR-212/ERK axis.
Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Cirrose Hepática/genética , Fator de Crescimento Transformador beta1/metabolismo , Proliferação de Células/genética , MicroRNAs/metabolismo , Receptores Muscarínicos , Fator de Transcrição Sp1/genéticaRESUMO
This study shows that there is a huge gap between young females' willingness and practice of accepting voluntary counselling and testing (VCT). Only 2.16% (894/41336) of the participants have had HIV/AIDS tests. The study identified age, education major, confidentiality, attitude, accuracy, self-assessment and expense as major factors associated with young female people's acceptance of VCT in China. Therefore, in order to promote HIV VCT among young females, it is necessary for future programs to be sensitive to the targeted population's needs.
Assuntos
Infecções por HIV , Universidades , China/epidemiologia , Aconselhamento , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , EstudantesRESUMO
Infectious bursal disease virus (IBDV) infection triggers the induction of type I IFN, which is mediated by melanoma differentiation-associated protein 5 recognition of the viral genomic double-stranded RNA (dsRNA). However, the mechanism of IBDV overcoming the type I IFN antiviral response remains poorly characterized. Here, we show that IBDV genomic dsRNA selectively binds to the host cellular RNA binding protein Staufen1 (STAU1) in vitro and in vivo. The viral dsRNA binding region was mapped to the N-terminal moiety of STAU1 (residues 1-468). Down-regulation of STAU1 impaired IBDV replication and enhanced IFN-ß transcription in response to IBDV infection, while having little effect on the viral attachment to the host cells and cellular entry. Conversely, overexpression of STAU1 but not the IBDV dsRNA-binding deficient STAU1 mutant (469-702) led to a suppression of IBDV dsRNA-induced IFN-ß promoter activity. Moreover, we found that the binding of STAU1 to IBDV dsRNA decreased the association of melanoma differentiation-associated protein 5 but not VP3 with the IBDV dsRNA in vitro. Finally, we showed that STAU1 and VP3 suppressed IFN-ß gene transcription in response to IBDV infection in an additive manner. Collectively, these findings provide a novel insight into the evasive strategies used by IBDV to escape the host IFN antiviral response.-Ye, C., Yu, Z., Xiong, Y., Wang, Y., Ruan, Y., Guo, Y., Chen, M., Luan, S., Zhang, E., Liu, H. STAU1 binds to IBDV genomic double-stranded RNA and promotes viral replication via attenuation of MDA5-dependent ß interferon induction.
Assuntos
Infecções por Birnaviridae/virologia , Proteínas do Citoesqueleto/metabolismo , Vírus da Doença Infecciosa da Bursa/genética , Helicase IFIH1 Induzida por Interferon/metabolismo , Interferon beta/metabolismo , RNA de Cadeia Dupla/metabolismo , RNA Viral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Replicação Viral , Animais , Antivirais/metabolismo , Infecções por Birnaviridae/genética , Infecções por Birnaviridae/metabolismo , Galinhas , Proteínas do Citoesqueleto/genética , Genômica , Células HEK293 , Células HeLa , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Helicase IFIH1 Induzida por Interferon/genética , Interferon beta/genética , RNA de Cadeia Dupla/genética , RNA Viral/genética , Proteínas de Ligação a RNA/genéticaRESUMO
While infectious bursal disease virus (IBDV) mainly targets immature B cells and causes T cell infiltration in the bursa of Fabricius (BF) of chickens, the effect of IBDV infection on the properties of T cells and relevant cytokine production in avian gut-associated lymphoid tissues (GALTs) remains unknown. Here, we show that while the CD8+ T cell subset is not affected, IBDV infection decreases the percentage of CD4+ T cells in the cecal tonsil (CT), but not in esophagus tonsil, pylorus tonsil, and Meckel's diverticulum of GALTs, in contrast to BF and spleen, in which the proportion of CD4+ cells increases upon IBDV infection. Further, IBDV infection upregulates IFN-γ, IL-10, and the T cell checkpoint receptor LAG-3 mRNA expression in BF. In contrast, in CTs, IBDV infection significantly increases the production of IFN-ß and CTLA-4 mRNA, while no significant effect is seen in the case of IFN-γ, IL-10 and LAG-3. Together, our data reveal differential modulation of T cell subsets and proinflammatory cytokine production in different lymphoid tissues during the course of IBDV infection.
Assuntos
Subpopulações de Linfócitos B/imunologia , Infecções por Birnaviridae/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Regulação da Expressão Gênica/imunologia , Doenças das Aves Domésticas/imunologia , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Subpopulações de Linfócitos B/virologia , Infecções por Birnaviridae/genética , Infecções por Birnaviridae/patologia , Infecções por Birnaviridae/virologia , Bolsa de Fabricius/imunologia , Bolsa de Fabricius/virologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Galinhas/virologia , Vírus da Doença Infecciosa da Bursa/crescimento & desenvolvimento , Vírus da Doença Infecciosa da Bursa/imunologia , Vírus da Doença Infecciosa da Bursa/patogenicidade , Interferon beta/genética , Interferon beta/imunologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/virologia , Tonsila Palatina/imunologia , Tonsila Palatina/virologia , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/patologia , Doenças das Aves Domésticas/virologia , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
In humans a chromosomal hemideletion of the 16p11.2 region results in variable neurodevelopmental deficits including developmental delay, intellectual disability, and features of autism spectrum disorder (ASD). Serotonin is implicated in ASD but its role remains enigmatic. In this study we sought to determine if and how abnormalities in serotonin neurotransmission could contribute to the behavioral phenotype of the 16p11.2 deletion syndrome in a mouse model (Del mouse). As ASD is frequently associated with altered response to acute stress and stress may exacerbate repetitive behavior in ASD, we studied the Del mouse behavior in the context of an acute stress using the forced swim test, a paradigm well characterized with respect to serotonin. Del mice perseverated with active coping (swimming) in the forced swim test and failed to adopt passive coping strategies with time as did their wild-type littermates. Analysis of monoamine content by HPLC provided evidence for altered endogenous serotonin neurotransmission in Del mice while there was no effect of genotype on any other monoamine. Moreover, we found that Del mice were highly sensitive to the 5-HT2A antagonists M100907, which at a dose of 0.1 mg/kg normalized their level of active coping and restored the gradual shift to passive coping in the forced swim test. Supporting evidence for altered endogenous serotonin signaling was provided by observations of additional ligand effects including altered forebrain Fos expression. Taken together, these observations indicate notable changes in endogenous serotonin signaling in 16p11.2 deletion mice and support the therapeutic utility of 5-HT2A receptor antagonists.
Assuntos
Adaptação Psicológica/fisiologia , Transtorno Autístico/metabolismo , Transtornos Cromossômicos/metabolismo , Deficiência Intelectual/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Serotonina/metabolismo , Estresse Psicológico/metabolismo , Animais , Comportamento Animal/fisiologia , Deleção Cromossômica , Cromossomos Humanos Par 16/metabolismo , Modelos Animais de Doenças , Fluorbenzenos/farmacologia , Masculino , Camundongos , Piperidinas/farmacologia , Receptor 5-HT2A de Serotonina/metabolismoRESUMO
To investigate clothing-induced differences in human thermal response and running performance, eight male athletes participated in a repeated-measure study by wearing three sets of clothing (CloA, CloB, and CloC). CloA and CloB were body-mapping-designed with 11% and 7% increased capacity of heat dissipation respectively than CloC, the commonly used running clothing. The experiments were conducted by using steady-state running followed by an all-out performance running in a controlled hot environment. Participants' thermal responses such as core temperature (Tc), mean skin temperature ([Formula: see text]), heat storage (S), and the performance running time were measured. CloA resulted in shorter performance time than CloC (323.1 ± 10.4 s vs. 353.6 ± 13.2 s, p = 0.01), and induced the lowest [Formula: see text], smallest ΔTc, and smallest S in the resting and running phases. This study indicated that clothing made with different heat dissipation capacities affects athlete thermal responses and running performance in a hot environment. Practitioner Summary: A protocol that simulated the real situation in running competitions was used to investigate the effects of body-mapping-designed clothing on athletes' thermal responses and running performance. The findings confirmed the effects of optimised clothing with body-mapping design and advanced fabrics, and ensured the practical advantage of developed clothing on exercise performance.
Assuntos
Vestuário , Transtornos de Estresse por Calor/prevenção & controle , Corrida/fisiologia , Desempenho Atlético/fisiologia , Regulação da Temperatura Corporal , Teste de Esforço , Temperatura Alta , Humanos , Masculino , Temperatura Cutânea , Adulto JovemRESUMO
BACKGROUND: We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 "doses" (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. METHODS: Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. RESULTS: In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch-induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05). CONCLUSIONS: Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.
Assuntos
Acidose Respiratória/metabolismo , Hipercapnia/metabolismo , NF-kappa B/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Acidose Respiratória/fisiopatologia , Animais , Dióxido de Carbono/metabolismo , Modelos Animais de Doenças , Hipercapnia/fisiopatologia , Molécula 1 de Adesão Intercelular/metabolismo , Troca Gasosa Pulmonar/fisiologia , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Tenofovir and Entecavir are recommended as the first-line medicine of treatment for chronic hepatitis B. The occurrence of hepatocellular carcinoma after the treatment of chronic hepatitis B is a major problem. For the time being it is still unclear whether there remains a difference in risk correlation of hepatocellular carcinoma after the treatment of Tenofovir and Entecavir for chronic hepatitis B. Since previous studies have raised different ideas, this article aims to come to a conclusion targeting such a topic through analyzing the latest data. METHODS: We searched some databases, such as PubMed, Web of Science, and Cochrane Library, for related studies on patients with chronic hepatitis B receiving the treatment of Tenofovir and Entecavir and then developing hepatocellular carcinoma. The search time was set to begin from the establishment time of the above-mentioned databases to May 2022. Two researchers were designated to screen the literature independently according to the inclusion and exclusion criteria set in this study; they then evaluated the quality of the literature included and extracted the data. Revman 5.3 software was used for meta-analysis. RESULTS: After screening the literature, a total of 20 pieces of cohort study literature conformed to the inclusion criteria. Among which were 62,860 cases of patients receiving Entecavir, and 27,544 cases of patients receiving Tenofovir; there were 3669 cases with the occurrence of hepatocellular carcinoma in the Entecavir group and 1089 cases with the occurrence of hepatocellular carcinoma in Tenofovir group. The result of Meta analysis of these 20 pieces of literature shows that compared with the Tenofovir group, the Entecavir group has a lower occurrence rate of hepatocellular carcinoma, and the difference is statistically significant. The results are expressed as odd ratio (OR) and 95% confident interval (95%CI), (OR = 1.66, 95%CI: 1.35-2.05, P < .05). The result of Meta analysis of 10 studies related to Korea shows that the occurrence rate of hepatocellular carcinoma in the Tenofovir group is lower than that of the Entecavir group, and the difference is statistically significant (OR = 1.59, 95%CI: 1.29-1.95, P < .05). The result of meta-analysis of 5 studies related to China shows that the occurrence rate of hepatocellular carcinoma of Tenofovir group is lower than that of Entecavir group, and the difference is statistically significant (OR = 2.35, 95%CI: 1.15-4.81, P < .05). CONCLUSION: The occurrence rate of hepatocellular carcinoma after the treatment of tenofovir for chronic hepatitis B is lower than that of the treatment of entecavir.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Tenofovir/efeitos adversos , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Antivirais/efeitos adversos , Estudos de Coortes , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/diagnóstico , Resultado do TratamentoRESUMO
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that several of the flow cytometric plots featured in Fig. 2A on p. 1050 contained repeating patterns of dots, both vertically and horizontally, in addition to a variety of other apparent anomalies. The authors were asked to provide an explanation to account for the apparent anomalies in this figure, but they did not respond to the request posed by the Editorial Office. Therefore, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 10471053, 2016; DOI: 10.3892/mmr.2015.4629].
RESUMO
Heart failure (HF) is a cardiovascular disease with an extremely high mortality rate. However, Morinda officinalis How (MO) has not been studied for cardiovascular purposes at this time, the aim of this study was to find new mechanism for the MO of treatment of HF through a bioinformatics and experimental validation. The present study also aimed to establish a link between the basic and clinical applications of this medicinal herb. MO compounds and targets were obtained by traditional Chinese medicine systems pharmacology (TCMSP) and Pubchem. Subsequently, HF targets were acquired from DisGeNET and the interactions of all the targets and other human proteins were obtained via String so as to establish a component-target interaction network by Cytoscape 3.7.2. All the targets of clusters were inserted into Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform GO (gene ontology) enrichment analysis. Molecular docking was adopted to predict the targets of MO relevant to the treatment of HF and to further explore the associated pharmacological mechanisms. Subsequently, a series of in vitro experiments, including histopathological staining, immunohistochemical and immunofluorescence analyses were conducted for further verification. Moreover, western blot analysis and in vivo experiments were performed. The results indicated that MO alleviated apoptosis, regulated cholesterol metabolism and transport function, and reduced inflammation, which resulted in the successful treatment of HF. Beta-sitosterol, Asperuloside tetraacetate and americanin A were the key bioactive components of MO. ALB, AKT1, INS, STAT3, IL-6, TNF, CCND1, CTNNB1, CAT, and TP53 were the core potential targets, which were significantly associated with multiple pathways, namely the FoxO signaling pathway, the AMPK signaling pathway, and the HIF-1 signaling pathway. In vivo experiments validated that MO may protect against heart failure or treat this disease by increasing the levels of autophagy via the FoxO3 signaling pathway in rats. The present study suggested that a combination of network pharmacology prediction with experimental validation may offer a useful tool to characterize the molecular mechanism of action of the traditional Chinese medicine (TCM) MO in the treatment of HF.
Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Morinda , Animais , Humanos , Ratos , Doenças Cardiovasculares/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
This study aimed to investigate the association between early sexual initiation and suicide attempts (SAs) among Chinese young people. Our analysis included 9131 college students who had sexual experience from a national sample of 31 provincial administrative regions. Self-reported age at first intercourse was categorized as ≤15, 15-18, and ≥18 years, and the experience of SAs was recorded and analyzed. Compared with females whose sexual debut age was ≥18 years, those ≤15 years (defined as early sexual initiation) had higher odds of SAs in both the forced debut group (odds ratio (OR) 17.04, 95% confidence interval (CI) 4.87-59.66) and the voluntary debut group (OR 37.63, 95% CI 14.96-94.66). Early sexual initiators who lived in rural areas were more inclined to have SAs (female: OR 65.76, 95% CI 19.80-218.42; male: OR 15.39, 95% CI 1.64-144.19). Early sexual initiators who never had parent-child communication about sex were more likely to report having SAs (female: OR 37.81, 95% CI 12.28-116.46). Sexual debut during adolescence, particularly early sexual initiation, was a crucial risk factor for SAs among both sexes. Comprehensive sexuality education and smooth parental communication about sex will provide a supportive environment for young people and hence reduce the potential risks of SAs.
Assuntos
Comportamento Sexual , Tentativa de Suicídio , Adolescente , China/epidemiologia , Coito , Feminino , Humanos , Masculino , Educação SexualRESUMO
Stem cell transplantation technology provides the cell reconstruction of damaged heart a completely new therapy approach. Due to the inappropriate microenvironment such as reactive oxygen radicals caused by ischemic infarct, the survival and retention rates of cell transplantation are not desirable. A thermo sensitive chitosan-vitamin C (CSVC) hydrogel scaffold was developed to reduce oxidative stress injury after myocardial infarction, thereby increasing the cell survival rate of cell transplantation. Vitamin C was conjugated on the chitosan chain by electrostatic adsorption. Compared to chitosan, CSVC complex had a higher solubility and stronger antioxidant property. CSVC hydrogel has suitable gelation time and injectable properties. Scanning electron microscopy showed that chitosan hydrogels had three-dimensional porous structure with irregular pores interconnected throughout the construct. Live/dead and H&E staining results showed that CSVC hydrogel can support the survival and adhesion of cardiomyocytes. Compared with chitosan hydrogel, CSVC hydrogel can clearly improve the survival of cardiomyocytes and reduce the ROS level under H2O2-induced oxidative stress conditions. These results suggest that CSVC hydrogel has the potential to support the survival of cardiomyocytes in tissue engineering.
Assuntos
Quitosana , Hidrogéis , Ácido Ascórbico/farmacologia , Sobrevivência Celular , Quitosana/química , Hidrogéis/química , Hidrogéis/farmacologia , Peróxido de Hidrogênio , Estresse Oxidativo , Engenharia Tecidual/métodosRESUMO
BACKGROUND: Previous studies demonstrate that macrophages synthesis and release catecholamines, which regulate the immune responses in an autocrine manner. These responses are mediated in part by ß-adrenoceptors expressed on macrophages. Some ß-adrenoceptor antagonists are commonly used in clinical conditions. Here we investigated whether the chronic administration of ß-adrenoceptor antagonists upregulate adrenergic system of alveolar macrophage and the potential mechanims. METHODS: Propranolol (30 mg/kg·d) or atenolol (5 mg/kg·d) was administered by gavage to rats for 4 weeks. Then alveolar macrophages were isolated and the expression of ß(1) or ß(2)-adrenoceptor was detected by flow cytometric analysis. Dopamine ß-hydroxylase expression was assessed by Western blot assay and the concentrations of noradrenaline, IL-6, and TNF-α in cell supernatants were measured using ELISA after 2 h or 24 h exposure of alveolar macrophages to 100 ng/ml lipopolysaccharide (LPS). RESULTS: Propranolol increased the mean fluorescence intensity (MFI) of ß(1), ß(2)-adrenoceptor and the frequency of ß(1)-,ß(2)- adrenoceptor positive macrophages. However, only the MFI of ß(1)-adrenoceptor and the frequency of ß(1)-adrenoceptor positive macrophages were increased by atenolol. Furthermore, both propranolol and atenolol promoted LPS-mediated dopamine ß-hydroxylase protein expression and increased noradrenaline production in rat alveolar macrophages. This was accompanied by increased LPS-mediated IL-6 and TNF-α production in cell supernatants of alveolar macrophages. CONCLUSION: These findings demonstrate that propranolol or atenolol upregulates alveolar macrophage adrenergic system, and the response may be ß(1)-adrenergic receptor subtype dependent.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Receptores Adrenérgicos beta 1/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Atenolol/farmacologia , Dopamina beta-Hidroxilase/metabolismo , Corantes Fluorescentes/química , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos Alveolares/metabolismo , Norepinefrina/metabolismo , Propranolol/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 2/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Purpose: Emerging studies indicate that sexual minority youths experience worse health than their heterosexual peers, but few studies have examined the intervening mechanisms linking sexual orientation and health status. This study hypothesizes that interpersonal relationships, moderated by household socioeconomic status (HSES), are important mediators in the association between sexual orientation and health status. Methods: A total of 49,084 youths, consisting of 9499 youths who identified as sexual minority individuals and 39,585 youths who identified as heterosexual, were sampled from a national study on sexual and reproductive health conducted in China. Logistic regression analyses were performed to estimate the association between sexual orientation and self-rated health. Causal mediation and moderated mediation analyses were performed to analyze the mediating and moderating effects of interpersonal relationships and HSES, respectively. Results: Self-rated health was significantly poorer for sexual minority youths compared with heterosexual youths (p < 0.01). From 7.90% to 25.74% of the association between sexual orientation and self-rated health was mediated through poor interpersonal relationships with both parents and peers. A poor relationship with the father accounted for the highest percentage. HSES was found to moderate the mediation effect of interpersonal relationships, with the greatest effect found for sexual minority youths with lower HSES. Conclusion: HSES moderated the indirect effects of interpersonal relationships on the association between sexual orientation and self-rated health. Interventions focused on improving interpersonal relationships for sexual minority youths, especially those with low HSES, merit attention.
Assuntos
Análise de Mediação , Minorias Sexuais e de Gênero , Adolescente , Feminino , Heterossexualidade , Humanos , Masculino , Comportamento Sexual , Classe SocialRESUMO
The functionality and property of pectin are correlated with its structure which is affected by the extraction method used. In this study, three different methods of extracting pectin, the microwave-assisted extraction (MAE), the ultrasonic-assisted extraction (UAE) and the conventional heating extraction (CHE), were used at three different temperatures with both an acid and alkali extraction solution. It was found that temperature mainly influenced pectin yield, while pectin structures and physicochemical properties were affected by the pH condition and extraction technology. The alkali-extraction with MAE and UAE at short time promoted the yield of low-ester pectin. Monosaccharide composition analysis showed a high galacturonic acid (GalA) content in the pectin derived from MAE and UAE. The high viscosity and desirable viscoelastic properties of the acid-MAE pectin were due to its large molecular weight and particle size. The results contribute to our understanding of the association among pectin extraction, structure and properties.
RESUMO
BACKGROUND: College students are at-risk populations of mental health problems and risky sexual behaviors. However, little literature focuses on the association between mental health problems and risky sexual behaviors. Our study examined the association between mental health problems (depressive symptoms, suicide, and mental disorders) and risky sexual behaviors among a large sample of Chinese college students. METHODS: A total of 49,728 Chinese college students (47.5% male) eventually participated in the analysis. A self-administered questionnaire was used to measure mental health, risky sexual behaviors (casual sex, no condom use at last sexual intercourse, group-sex, and a high number of sexual partners), and other sociodemographic characteristics. Logistic regression analysis was used to explore the relationship between mental health and risky sexual behaviors. To ensure the data is representative of the nation's statistics, all analyses were weighed. RESULTS: The prevalence of depressive symptoms, suicide ideation and suicide attempts, and mental disorders was 42.83%, 41.29%, and 7.74%, respectively. 26.13% of participants were sexually active in the previous twelve months. Nearly 35% of sexually active participants were engaged in risky sexual behaviors. Logistic regression results demonstrated that mental health problems were associated with risky sexual behaviors after adjusting confounders. LIMITATIONS: cross-sectional analysis; The self-reported variables may be subject to recall bias and fraud. CONCLUSIONS: There is a relatively high prevalence of mental health problems and risky sexual behaviors amongst Chinese college students. A significant association between mental health problems and risky sexual behaviors was suggested by our study. Our findings support the importance of advocating for mental and reproductive healthcare for college students.
Assuntos
Saúde Mental , Comportamento Sexual , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Assunção de Riscos , Estudantes , Inquéritos e QuestionáriosRESUMO
Overwhelming data indicate that cancer survivors are at higher risk of cardiovascular diseases because chemotherapy induces cardiotoxicity. Mechanistic explanation of this phenomenon is necessary to advise the clinical practice on the prevention of cardiotoxicity in cancer patients. Here we propose that chemotherapy induces cardiotoxicity by inadvertently interrupting the homeostasis of cardiac stem cells and depleting the resident cardiac stem cells pool. As a result, the heart loses the capability of regeneration and repair and demonstrates the cardiotoxicity symptoms. Our hypothesis is supported by several lines of emerging evidence: the high incidence of cardiotoxicity in paediatric cancer patients who still have more cardiac stem cells in the myocardium; the rescue of anthracycline cardiomyopathy by injection of cardiac stem cells; and the adverse cardiotoxicity induced by inhibitors of oncogenic kinases or pathways which target cardiac stem cells besides cancer cells. This may promote our growing appreciation that cardiac stem cells represent new targets of chemotherapy that contribute to cardiotoxicity and open up novel strategies for the preservation or expansion of the cardiac stem cells pool to overcome cardiotoxicity associated with chemotherapy.
Assuntos
Antineoplásicos/efeitos adversos , Cardiopatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Células-Tronco/efeitos dos fármacos , Humanos , Células-Tronco/citologiaRESUMO
Olive oil could attenuate carbon tetrachloride (CCl4) induced liver fibrosis (LF) in mouse model. The present study aimed to evaluate the effects of other common oils on CCl4 induced LF. Healthy male ICR mice were administered with CCl4 intraperitoneally at 2.5 ml/kg twice a week for total 3 weeks. Mice were pre-treated with olive oil, soybean oil, corn oil or lard oil. After treatment, histopathological changes were observed using Masson trichrome staining, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), hydroxyproline (HYP) and triglyceride (TG) were measured by commercial kits. The expression of LF related genes was detected by quantitative real-time PCR. We found that soybean oil or olive oil significantly reduced ALT and AST levels in serum, and MDA, HYP and TG levels in the liver, compared with corn oil or lard oil. Moreover, Masson trichrome staining and real-time PCR showed that the mice treated with CCl4 dissolved in soybean oil or olive oil had less fibrosis and apoptosis in the liver comparted to the mice treated with CCl4 dissolved in corn oil or lard oil. In conclusion, soybean oil but not corn or lard oil exerts protective effects against CCl4 induced LF in mice, possibly due to its antioxidant activity.