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1.
Risk Manag Healthc Policy ; 15: 1395-1405, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911086

RESUMO

Purpose: The present study aimed to investigate nurses' willingness and demand for Internet +home care services in different levels of hospitals in China and analyze the influencing factors. Participants and Methods: From October 1 to December 31, 2021, 5714 nurses from 15 hospitals in five regions of China were recruited in this cross-sectional study using a two-stage random sampling method. A self-designed questionnaire with good reliability and validity was used to measure nurses' willingness and demand for Internet +home care services. χ 2 test, Welch t-test, and multiple linear regression analyses were used to analyze the data. Results: Nurses were highly willing to provide Internet +home care services. Statistical differences were found in the willingness to provide Internet +home care services and the preference for service distance, service platform, and single service fee between nurses in different levels of hospitals (both P<0.05). The willingness to provide "catheter maintenance service" and "rehabilitation nursing service" of nurses in different levels of hospitals were statistically significant (both P<0.05). Nurses' demand for Internet +home care services increased with the level of their hospital. Multiple linear regression showed that professional title, educational level, monthly family income, and mortgage or car loan influence nurses' demand for Internet +home care services. Conclusion: Nurses' willingness and demand for Internet +home care services vary with the level of their hospitals. It is recommended that government and hospitals regulate the service items, the service distance, single service fee, and other contents according to nurses' willingness and demand and establish relevant laws and regulations to ensure the steady and orderly development of the Internet +home care services.

2.
Int J Mol Sci ; 23(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35886932

RESUMO

Studies on ESRRB-regulating porcine-induced pluripotent stem cells (piPSCs) converted to trophoblast-like stem cells (TLSCs) contribute to the understanding of early embryo development. However, the epigenetic modification regulation network during the conversion is poorly understood. Here, the global change in histone H3 Lysine 4, 9, 27, 36 methylation and Lysine 27 acetylation was investigated in piPSCs and TLSCs. We found a high modification profile of H3K36me2 in TLSCs compared to that of piPSCs, whereas the profiles of other modifications remained constant. KDM4C, a H3K36me3/2 demethylase, whose gene body region was combined with ESRRB, was upregulated in TLSCs. Moreover, KDM4 inhibitor supplementation rescued the AP-negative phenotype observed in TLSCs, confirming that KDM4C could regulate the pluripotency of TLSCs. Subsequently, KDM4C replenishment results show the significantly repressed proliferation and AP-positive staining of TLSCs. The expressions of CDX2 and KRT8 were also upregulated after KDM4C overexpression. In summary, these results show that KDM4C replaced the function of ESRRB. These findings reveal the unique and crucial role of KDM4C-mediated epigenetic chromatin modifications in determination of piPSCs' fate and expand the understanding of the connection between piPSCs and TSCs.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Animais , Células-Tronco Pluripotentes Induzidas/metabolismo , Lisina/metabolismo , Metilação , Células-Tronco Pluripotentes/metabolismo , Suínos , Trofoblastos/metabolismo
3.
J Oncol ; 2022: 8704784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847368

RESUMO

An accurate characterization of diseases and compounds is the key to predicting the compound-disease relationship (CDR). However, due to the difficulty of a comprehensive description of CDR, the accuracy of traditional drug development models for large-scale CDR prediction is usually unsatisfactory. In order to solve this problem, we propose a new method that integrates the molecular descriptors of compounds and the symptom descriptors of diseases to build a CDR two-dimensional matrix to predict candidate active compounds. The Matlab software draws grayscale images of CDRs, which are used as a benchmark dataset for training convolutional neural network (CNN) models. The trained model is used to predict candidate antitumor active compounds. Among the AlexNet and GoogLeNet models, we selected the GoogLeNet model for the prediction of active compounds in Chinese medicine, and its Acc, Sen, Pre, F-measure, MCC, and AUC are 0.960, 0.956, 0.965, 0.960, 0.920, and 0.964, respectively. In the prediction results of compounds, 1624 candidate CDRs were found in 124 Chinese medicines. Among them, we obtained 31 features of candidate antitumor active compounds. This method provides new insights for the discovery of candidate active compounds in Chinese medicine.

4.
Risk Manag Healthc Policy ; 15: 1325-1341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35855767

RESUMO

Background: With the aging of China's population, the incidence rate of chronic diseases is rising. At the same time, residents' health awareness is also increasing. Implementing Internet +home care is an inevitable trend in adapting social development. Currently, Internet +home care is in the pilot stage in China, relevant institutional measures are neither standardized nor perfect, and there is no set of quality supervision indicators (QSIs). Purpose: The construction of Internet +home care QSIs in China will provide a theoretical basis for Internet +home care quality supervision. Materials and Methods: The Service-Quality model was used as the theoretical framework, and a literature review, semi-structured interviews, focus group discussions, and Delphi consultations determined the contents of the QSIs and the weight of each indicator. Results: Internet +home care QSIs were constructed and included 5 first-level indicators, 17 secondary indicators, and 69 tertiary indicators. The effective recovery rates of the two rounds of Delphi expert consultation were 100% and 85%, the expert authority coefficients were 0.810 and 0.833, and the Kendall harmony coefficients were 0.189 and 0.125 (P<0.01). The final set of Internet +home care QSIs was as follows: tangibility (4 secondary and 16 tertiary indicators), reliability (4 secondary and 19 tertiary indicators), guarantee (5 secondary and 20 tertiary indicators), responsiveness (2 secondary and 8 tertiary indicators), and empathy (2 secondary and 6 tertiary indicators). Conclusion: The construction of Internet +home care QSIs based on the SERVQUAL model is scientifically valid, and the indicators are reliable. They provide guidance and reference values for the continuous improvement and promotion of Internet +home care. This work also provides a theoretical basis for researching and developing an Internet +home care quality supervision platform.

5.
J Neuroinflammation ; 19(1): 186, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836182

RESUMO

BACKGROUND: Depression is a recurrent and devastating mental disease that is highly prevalent worldwide. Prolonged exposure to stressful events or a stressful environment is detrimental to mental health. In recent years, an inflammatory hypothesis has been implicated in the pathogenesis of stress-induced depression. However, less attention has been given to the initial phases, when a series of stress reactions and immune responses are initiated. Peripheral CD4+ T cells have been reported as the major contributors to the occurrence of mental disorders. Chronic stress exposure-evoked release of cytokines can promote the differentiation of peripheral CD4+ cells into various phenotypes. Among them, Th17 cells have attracted much attention due to their high pathogenic potential in central nervous system (CNS) diseases. Thus, we intended to determine the crucial role of CD4+ Th17 cells in the development of specific subtypes of depression and unravel the underpinnings of their pathogenetic effect. METHODS: In the present research, a daily 6-h restraint stress paradigm was employed in rats for 28 successive days to mimic the repeated mild and predictable, but inevitable environmental stress in our daily lives. Then, depressive-like symptoms, brain-blood barrier (BBB) permeability, neuroinflammation, and the differentiation and functional changes of CD4+ cells were investigated. RESULTS: We noticed that restrained rats showed significant depressive-like symptoms, concomitant BBB disruption and neuroinflammation in the dorsal striatum (DS). We further observed a time-dependent increase in thymus- and spleen-derived naïve CD4+ T cells, as well as the aggregation of inflammatory Th17 cells in the DS during the period of chronic restraint stress (CRS) exposure. Moreover, increased Th17-derived cytokines in the brain can further impair the BBB integrity, thus allowing more immune cells and cytokines to gain easy access to the CNS. Our findings suggested that, through a complex cascade of events, peripheral immune responses were propagated to the CNS, and gradually exacerbated depressive-like symptoms. Furthermore, inhibiting the differentiation and function of CD4+ T cells with SR1001 in the early stages of CRS exposure ameliorated CRS-induced depressive-like behaviour and the inflammatory response. CONCLUSIONS: Our data demonstrated that inflammatory Th17 cells were pivotal in accelerating the onset and exacerbation of depressive symptoms in CRS-exposed rats. This subtype of CD4+ T cells may be a promising therapeutic target for the early treatment of stress-induced depression.


Assuntos
Depressão , Células Th17 , Animais , Encéfalo , Citocinas , Depressão/etiologia , Humanos , Ratos , Restrição Física , Células Th1
6.
Int J Mol Sci ; 23(13)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35806144

RESUMO

Ferroptosis is a relatively novel form of regulated cell death that was discovered in 2012. With the increasing research related to the mechanisms of ferroptosis, previous studies have demonstrated that the inactive of the intracellular antioxidant system and iron overload can result in the accumulation of reactive oxygen species (ROS), which can ultimately cause lipid peroxidation in the various cell types of the body. ROS accumulation can cause sperm damage by attacking the plasma membrane and damaging DNA. Acute ferroptosis causes oxidative damage to sperm DNA and testicular oxidative stress, thereby causing male reproductive dysfunction. This review aims to discuss the metabolic network of ferroptosis, summarize and analyze the relationship between male reproductive diseases caused by iron overload as well as lipid peroxidation, and provide a novel direction for the research and prevention of various male reproductive diseases.


Assuntos
Ferroptose , Sobrecarga de Ferro , Humanos , Ferro/metabolismo , Peroxidação de Lipídeos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Reprodução , Sêmen/metabolismo
7.
Drug Des Devel Ther ; 16: 1621-1645, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669282

RESUMO

Background: Huo Luo Xiao Ling Dan (HLXLD), a famous Traditional Chinese Medicine (TCM) classical formula, possesses anti-atherosclerosis (AS) activity. However, the underlying molecular mechanisms remain obscure. Aim: The network pharmacology approach, molecular docking strategy, and in vitro validation experiment were performed to explore the potential active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. Methods: Several public databases were used to search for active components and targets of HLXLD, as well as AS-related targets. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis. Subsequently, the molecular docking strategy and molecular dynamics simulation were carried out to predict the affinity and stability of active compounds and key targets. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. Results: A total of 108 candidate compounds and 321 predicted target genes were screened. Bioinformatics analysis suggested that quercetin, dihydrotanshinone I, pelargonidin, luteolin, guggulsterone, and ß-sitosterol may be the main ingredients. STAT3, HSP90AA1, TP53, and AKT1 could be the key targets. MAPK signaling pathway might play an important role in HLXLD against AS. Molecular docking and molecular dynamics simulation results suggested that the active compounds bound well and stably to their targets. Cell experiments showed that the intracellular accumulation of lipid and increased secretory of TNF-α, IL-1ß, and MCP-1 in ox-LDL treated RAW264.7 cells, which can be significantly suppressed by pretreating with dihydrotanshinone I. The up-regulation of STAT3, ERK, JNK, and p38 phosphorylation induced by ox-LDL can be inhibited by pretreating with dihydrotanshinone I. Conclusion: Our findings comprehensively demonstrated the active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. These findings would provide a scientific basis for the study of the complex mechanisms underlying disease and drug action.


Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Furanos , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fenantrenos , Quinonas
8.
J Med Microbiol ; 71(5)2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35580023

RESUMO

Introduction. Atherosclerosis is a chronic disorder in which plaque builds up in the arteries and is associated with several cardiovascular and cerebrovascular diseases such as coronary artery disease, cerebral infarction and cerebral haemorrhage. Therefore, there is an urgent need to discover new medications to treat or prevent atherosclerosis.Hypothesis/Gap Statement. The active components of Guanxin Xiaoban capsules may have an effect on the gut microbiome of patients with atherosclerosis and have a role in their therapeutic targets.Aim. The aim of this study was to identify genes and pathways targeted by active ingredients in Guanxin Xiaoban capsules for the treatment of atherosclerosis based on network pharmacology and analysis of changes to the gut microbiome.Methods. Mice were treated with Guanxin Xiaoban capsules. The 16S rDNA genome sequence of all microorganisms from each group of faecal samples was used to evaluate potential structural changes in the gut microbiota after treatment with Guanxin Xiaoban capsules. Western blotting and real-time quantitative PCR were used to detect gene targets in aortic and liver tissues. Haematoxylin and eosin staining was used to observe improvements in mouse arterial plaques.Results. The gut microbiota of atherosclerotic mice is disturbed. After Guanxin Xiaoban treatment, the abundance of bacteria in the mice improved, with an increase in the proportion of Akkermansia and a significant decrease in the proportion of Faecalibaculum. The main ingredients of Guanxin Xiaoban capsules are calycosin, liquiritin, ferulic acid, ammonium glycyrrhizate, aloe emodin, rhein and emodin. The core genes of this network were determined to be glutathione S-transferase mu 1 (GSTM1), vascular endothelial growth factor A (VEGFA) and cyclin-dependent kinase inhibitor 1A (CDKN1A). The compound-target gene network revealed an interaction between multiple components and targets and contributed to a better understanding of the potential therapeutic effects of the capsules on atherosclerosis. In addition, expression of the AGE-receptor for the AGE (RAGE) pathway was significantly inhibited and the mice showed signs of arterial plaque reduction. Guanxin Xiaoban capsules may improve atherosclerosis and reduce the plaque area by inhibiting the AGE-RAGE signalling pathway to delay the development of atherosclerosis. This mechanism appears to involve changes in the gut microbiota. Therefore, Guanxin Xiaoban capsules have potential value as a treatment for atherosclerosis.


Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Placa Aterosclerótica , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/microbiologia , Aterosclerose/patologia , Cápsulas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/microbiologia , Placa Aterosclerótica/patologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
J Orthop Surg Res ; 17(1): 218, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35399100

RESUMO

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease, and chondrocyte extracellular matrix (ECM) degradation is one vital pathological feature of OA. Long noncoding RNA (lncRNA), a new kind of gene regulator, plays an important role in pathogenesis of many diseases like OA. Recent studies have confirmed that lncRNA plasmacytoma variant translocation 1 (PVT1) expression was upregulated in OA patients; however, its effect on ECM degradation remained unknown. METHODS: Cartilage tissue samples were obtained from 6 OA patients admitted in Guangdong Second Traditional Chinese Medicine Hospital. Chondrocytes were isolated and cultured from the collected cartilage tissue. Plasmid construction, RNA interference, cell transfection, fluorescence in situ hybridization (FISH), and pull-down assay were carried out during the research. RESULTS: In this study, PVT1 expression was significantly increased in chondrocytes stimulated by interleukin-1ß (IL-1ß). In addition, inhibition of PVT1 significantly downregulated the increased expressions of ADAM metallopeptidase with thrombospondin type 1 motif-5 (ADAMTS-5) and matrix metalloproteinase-13 (MMP-13) induced by IL-1ß. Further investigation revealed that PVT1 was an endogenous sponge RNA, which directly bound to miR-140 and inhibited miR-140 expression. CONCLUSION: To sum up, this study showed that PVT1 promoted expressions of ADAMTS-5 and MMP-13 as a competing endogenous RNA (ceRNA) of miR-140 in OA, which eventually led to aggravation of ECM degradation, thus providing a new and promising strategy for the treatment of OA.


Assuntos
Condrócitos , Matriz Extracelular , MicroRNAs , Osteoartrite , RNA Longo não Codificante , Proteína ADAMTS5 , Apoptose , Células Cultivadas , Condrócitos/metabolismo , Matriz Extracelular/metabolismo , Humanos , Hibridização in Situ Fluorescente , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , MicroRNAs/metabolismo , Osteoartrite/patologia , RNA Longo não Codificante/metabolismo
10.
Stem Cell Res Ther ; 13(1): 164, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35414044

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSC therapy. This study investigated whether the combination of melatonin and human umbilical cord mesenchymal stem cells (hUC-MSCs) was superior to hUC-MSCs alone in ameliorating high-fat diet and streptozocin (STZ)-induced type II diabetes mellitus (T2DM) in a mouse model. METHODS: Mice were divided into four groups: normal control (NC) group; T2DM group; hUC-MSCs treatment alone (UCMSC) group and pretreatment of hUC-MSCs with melatonin (UCMSC/Mel) group. RESULTS: RNA sequence analysis showed that certain pathways, including the signaling pathway involved in the regulation of cell proliferation signaling pathway, were regulated by melatonin. The blood glucose levels of the mice in the UCMSC and UCMSC/Mel treatment groups were significantly reduced compared with the T2DM group without treatment (P < 0.05). Furthermore, hUC-MSCs enhance the key factor in the activation of the PI3K/Akt pathway in T2DM mouse hepatocytes. CONCLUSION: The pretreatment of hUC-MSCs with melatonin partly boosted cell efficiency and thereby alleviated impaired glycemic control and insulin resistance. This study provides a practical strategy to improve the application of hUC-MSCs in diabetes mellitus and cytotherapy. Overview of the PI3K/AKT signaling pathway. (A) Underlying mechanism of UCMSC/Mel inhibition of hyperglycemia and insulin resistance T2DM mice via regulation of PI3K/AKT pathway. hUC-MSCs stimulates glucose uptake and improves insulin action thus should inhibition the clinical signs of T2DM, through activation of the p-PI3K/Akt signaling pathway and then regulates glucose transport through activating AS160. UCMSC/Mel increases p53-dependent expression of BCL2, and inhibit BAX and Capase3 protein activation. Leading to the decrease in apoptosis. (B) Melatonin modulated PI3K/AKT signaling pathway. Melatonin activated PI3K/AKT response pathway through binding to MT1and MT2 receptor. Leading to the increase in hUC-MSCs proliferation, migration and differentiation. → (Direct stimulatory modification); ┴ ( Direct Inhibitory modification); → ┤ (Multistep inhibitory modification); ↑ (Up regulate); ↓ (Down regulate); PI3K (Phosphoinositide 3-Kinase); AKT ( protein kinase B); PDK1 (Phosphoinositide-dependent protein kinase 1); IR, insulin receptor; GLUT4 ( glucose transporter type 4); ROS (reactive oxygen species); BCL-2 (B-cell lymphoma-2); PDK1 (phosphoinositide-dependent kinase 1) BAX (B-cell lymphoma-2-associated X protein); PCNA (Proliferating cell nuclear antigen); Cell cycle-associated proteins (KI67, cyclin A, cyclin E).


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Melatonina , Transplante de Células-Tronco Mesenquimais , Animais , Diabetes Mellitus Tipo 2/terapia , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositóis/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Cordão Umbilical , Proteína X Associada a bcl-2
11.
Environ Sci Pollut Res Int ; 29(23): 35408-35421, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35048336

RESUMO

For decades, the rapid urbanization and economic development in China inevitably lead to the increase of household energy demand and CO2 emissions. Existing studies regard the household sector as an exogenous sector unrelated to production, ignoring that the wages, goods, and services provided by production sectors will affect the consumption of the household sector. This paper analyzes the impact of the household sector on production sectors and the total CO2 emissions by establishing a semi-closed environmentally extended input-output model in China from 2007 to 2017. Through the calculation of index of the power of dispersion and index of sensitivity of dispersion, the index of sensitivity of dispersion of household is large, and household has push to several sectors' CO2 emissions. Furthermore, we explore the drivers of China's household CO2 emissions using structural decomposition analysis and claim that consumption per capita and urbanization rate are the dominant factors driving household CO2 emissions, while carbon intensity and economic structure are the main factors inhibiting household CO2 emissions. Our research shows a clear picture of sector linkages and driving forces of household CO2 emissions, providing strong evidence for the development of China's household CO2 reduction policies.


Assuntos
Dióxido de Carbono , Desenvolvimento Econômico , Carbono , Dióxido de Carbono/análise , China , Urbanização
12.
Int J Mol Sci ; 23(2)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35055127

RESUMO

Pregnancy loss (PL) is one of the common complications that women can experience during pregnancy, with an occurrence rate of 1 to 5%. The potential causes of pregnancy loss are unclear, with no effective treatment modalities being available. It has been previously reported that the level of miR-125b was significantly increased in placentas of PL patients. However, the role of miR-125b in the development of PL still remains unknown. In the current study, an miR-125b placenta-specific over-expression model was constructed by lentiviral transfecting zona-free mouse embryos followed by embryo transfer. On gestation day 15, it was observed that the placenta was significantly smaller in the miR-125b placenta-specific overexpression group than the control group. Additionally, the abortion rate of the miR-125b placenta-specific overexpression group was markedly higher than in the control group. The blood vessel diameter was larger in the miR-125b-overexpressing specific placenta. In addition, miR-125b-overexpressing HTR8 and JEG3 cell lines were also generated to analyze the migration and invasion ability of trophoblasts. The results showed that miR-125b overexpression significantly suppressed the migration and invasion ability of HTR8 and JEG3 cells. Overall, our results demonstrated that miR-125b can affect embryo implantation through modulating placenta angiogenesis and trophoblast cell invasion capacity that can lead to PL.


Assuntos
Aborto Espontâneo/genética , MicroRNAs/genética , Placenta/química , Regulação para Cima , Animais , Estudos de Casos e Controles , Linhagem Celular , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Especificidade de Órgãos , Gravidez
13.
Theriogenology ; 177: 183-194, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715543

RESUMO

Heat stress is known to negatively impact the reproductive process of livestock, which inevitably leads to a decline in animal fertility. Nuclear factor E2-related factor 2 (Nrf2) is an inducible transcription factor, which is essential for maintaining redox signal transmission against oxidative stress. However, there is no reliable research on the response mechanism of Sertoli Cells (SCs) against heat stress and the activation of Nrf2 when SCs are exposed to heat stress. Here, we used primary mouse SCs and SCs line TM4, along with Nrf2 specific inhibitor to determine the reaction mechanism of SCs to maintain intracellular redox homeostasis and self-survival by activating Nrf2. We found that acute heat stress only affected the vitality of SCs and the expression of functional molecules (tight junction-associated proteins and lactate dehydrogenase A [LDHA]) but did not cause cell apoptosis. When Nrf2 was inhibited, more cell death occurred in TM4 cells post heat stress treatment, along with a greater decrease in cell viability and a significant increase in intracellular ROS levels. Our study clarified for the first time the protective effect of Nrf2 activation on heat stress-induced SCs damage. It explained the possible reasons or mechanisms involved in the survival of SCs, the critical protective cells in the testis, which were not affected by heat stress. This study further improved the response mechanism of SCs in the reproductive injury caused by a high-temperature environment.


Assuntos
Fator 2 Relacionado a NF-E2 , Células de Sertoli , Animais , Apoptose , Resposta ao Choque Térmico , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Células de Sertoli/metabolismo , Testículo/metabolismo
14.
Int J Mol Sci ; 22(23)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34884759

RESUMO

The establishment of porcine pluripotent stem cells (piPSCs) is critical but remains challenging. All piPSCs are extremely sensitive to minor perturbations of culture conditions and signaling network. Inhibitors, such as CHIR99021 and XAV939 targeting the WNT signaling pathway, have been added in a culture medium to modify the cell regulatory network. However, potential side effects of inhibitors could confine the pluripotency and practicability of piPSCs. This study aimed to investigate the roles of AXIN, one component of the WNT pathway in piPSCs. Here, porcine AXIN1 and AXIN2 genes were knocked-down or overexpressed. Digital RNA-seq was performed to explore the mechanism of cell proliferation and apoptosis. We found that (1) overexpression of the porcine AXIN2 gene significantly reduced survival and negatively impacted the pluripotency of piPSCs, and (2) knockdown of AXIN2, a negative effector of the WNT signaling pathway, enhanced the expression of genes involved in cell cycle but reduced the expression of genes related to cell differentiation, death, and apoptosis.


Assuntos
Proteína Axina/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Animais , Apoptose/genética , Apoptose/fisiologia , Proteína Axina/deficiência , Proteína Axina/genética , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Proliferação de Células/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Células Cultivadas , Ciclina D1/genética , Ciclina D1/metabolismo , Técnicas de Silenciamento de Genes , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Modelos Biológicos , Piridinas/farmacologia , Pirimidinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA-Seq , Suínos , Regulação para Cima , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia , beta Catenina/genética , beta Catenina/metabolismo
15.
J Tradit Chin Med ; 41(6): 935-942, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34939390

RESUMO

OBJECTIVE: To evaluate the molecular mechanism underlying the beneficial effect of Bushen Qiangjin capsule (BSQJ), a Traditional Chinese Medicine, on knee osteoarthritis (KOA). METHODS: In the present study, 32 female Sprague-Dawley rats were randomly divided into four groups: control, KOA, high-dose BSQJ (H-BSQJ), and low-dose BSQJ (L-BSQJ). After successfully establishing the KOA model by intra-articular injection of papain, H-BSQJ and L-BSQJ groups were intragastrically administered 0.243 and 0.122 g/kg BSQJ, respectively, daily for 6 weeks. At the end of the experiment, knee articular cartilage tissues of rats were collected for evaluation by hematoxylin and eosin staining, Safranin O-Fast Green staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Serum interleukin-1α and tumor necrosis factor-α levels of rats were detected with an enzyme-linked immunosorbent assay method. Gene expression of Wnt-4, α-catenin, Frizzled-2, glycogen synthase kinase-3ß (GSK-3ß), cysteinyl aspartate-specific proteinases 3 and 9 (caspases 3 and 9), collagen type II alpha 1 (Col2a1), and matrix metalloproteinases 1 and 13 (MMP-1 and MMP-3) of rat knee articular cartilage was quantified by reverse transcription-quantitative polymerase chain reaction analysis. Wnt-4, α-catenin, Frizzled-2, GSK-3ß, cleaved caspase-3, and cleaved caspase-9 protein expression in rat knee articular cartilage was determined by western blot analysis. RESULTS: BSQJ obviously reduced pathological damage and matrix degradation of articular cartilage in KOA rats. Compared with the KOA group, H-BSQJ rats exhibited downregulated mRNA and protein expression of Wnt-4, ß-catenin, Frizzled-2,and caspase-3, as well as upregulated mRNA and protein expression of GSK-3α. In addition, H-BSQJ significantly increased mRNA expression of Col2a1 and decreased mRNA expression of MMP-1 and MMP-13. CONCLUSION: BSQJ exerted a beneficial effect on KOA by a mechanism involving downregulation of the Wnt/α-catenin pathway, which inhibited both cartilage extracellular matrix degradation and chondrocyte apoptosis to ameliorate KOA in rats.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Animais , Cartilagem Articular/metabolismo , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/metabolismo , Papaína/metabolismo , Papaína/farmacologia , Ratos , Ratos Sprague-Dawley , Via de Sinalização Wnt , alfa Catenina/metabolismo
17.
Org Biomol Chem ; 19(44): 9705-9710, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34726225

RESUMO

A practical and efficient methodology for the construction of 3-alkylquinoxalinones through base promoted direct alkylation of quinoxalin-2(1H)-ones with phosphonium ylides as alkylating reagents under metal- and oxidant-free conditions was developed. Various 3-alkylquinoxalin-2(1H)-ones were easily obtained in good to excellent yields. Tentative mechanistic studies suggest that this reaction is likely to involve a nucleophilic addition-elimination process.

18.
Front Cell Dev Biol ; 9: 722365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722505

RESUMO

Abundant evidence proves the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) in the treatment of diabetes mellitus. However, the problems have not been solved that viability of ADMSCs were inconsistent and the cells quickly undergo senescence after in vitro cell culture. In addition, the therapeutic effect of ADMSCs is still not satisfactory. In this study, melatonin (MLT) was added to canine ADMSC culture medium, and the treated cells were used to treat type 2 diabetes mellitus (T2DM). Our research reveals that adding MLT to ADMSC culture medium can promote the viability of ADMSCs. This effect depends on the binding of MLT and MLT receptors, which activates the transforming growth factor ß (TGF-ß) pathway and then changes the cell cycle of ADMSCs and improves the viability of ADMSCs. Since ADMSCs were found to be used to treat T2DM by anti-inflammatory and anti-endoplasmic reticulum (ER) stress capabilities, our data demonstrate that MLT augment several effects of ADMSCs in remission hyperglycemia, insulin resistance, and liver glycogen metabolism in T2DM patients. This suggest that ADMSCs and MLT-ADMSCs is safe and vabulable for pet clinic.

19.
Zool Res ; 42(4): 514-524, 2021 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-34254745

RESUMO

Normal spermatogenic processes require the scrotal temperature to be lower than that of the body as excessive heat affects spermatogenesis in the testes, reduces sperm quality and quantity, and even causes infertility. Endoplasmic reticulum stress (ERS) is a crucial factor in many pathologies. Although several studies have linked ERS to heat stress, researchers have not yet determined which ERS signaling pathways contribute to heat-induced testicular damage. Melatonin activates antioxidant enzymes, scavenges free radicals, and protects the testes from inflammation; however, few studies have reported on the influence of melatonin on heat-induced testicular damage. Using a murine model of testicular hyperthermia, we observed that heat stress causes both ERS and apoptosis in the testes, especially in the spermatocytes. These observations were confirmed using the mouse spermatocyte cell line GC2, where the Atf6 and Perk signaling pathways were activated during heat stress. Knockout of the above genes effectively reduced spermatocyte damage caused by heat stress. Pretreatment with melatonin alleviated heat-induced apoptosis by inhibiting the Atf6 and Perk signaling pathways. This mitigation was dependent on the melatonin receptors. In vivo experiments verified that melatonin treatment relieved heat-induced testicular damage. In conclusion, our results demonstrated that ATF6 and PERK are important mediators for heat-induced apoptosis, which can be prevented by melatonin treatment. Thus, our study highlights melatonin as a potential therapeutic agent in mammals for subfertility/infertility induced by testicular hyperthermia.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Temperatura Alta/efeitos adversos , Melatonina/farmacologia , Espermatócitos/efeitos dos fármacos , Testículo/fisiologia , eIF-2 Quinase/metabolismo , Fator 6 Ativador da Transcrição/genética , Animais , Apoptose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos , eIF-2 Quinase/genética
20.
Biosci Rep ; 41(6)2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34060622

RESUMO

To facilitate temperature adjustments, the testicles are located outside the body cavity. In most mammals, the temperature of the testes is lower than the body temperature to ensure the normal progression of spermatogenesis. Rising temperatures affect spermatogenesis and eventually lead to a decline in male fertility or even infertility. However, the testes are composed of different cell types, including spermatogonial stem cells (SSCs), spermatocytes, spermatozoa, Leydig cells, and Sertoli cells, which have different cellular responses to heat stress. Recent studies have shown that using different drugs can relieve heat stress-induced reproductive damage by regulating different signaling pathways. Here, we review the mechanisms by which heat stress damages different cells in testes and possible treatments.


Assuntos
Fertilidade , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico , Temperatura Alta/efeitos adversos , Infertilidade Masculina/metabolismo , Testículo/metabolismo , Animais , Barreira Hematotesticular/metabolismo , Barreira Hematotesticular/patologia , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/uso terapêutico , Resposta ao Choque Térmico/efeitos dos fármacos , Humanos , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Fatores de Risco , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Transdução de Sinais , Espermatócitos/metabolismo , Espermatócitos/patologia , Espermatogônias/metabolismo , Espermatogônias/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/fisiopatologia
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