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Mesenchymal stem cells (MSCs) are becoming more popular in therapy. Therefore, in-depth studies on mesenchymal stem cells in therapy are urgently needed. However, the difficulty in culturing and propagating MSCs in vitro complicates potential studies on MSCs in a murine model. OP9 cells are a stromal cell line from mouse bone marrow, which have similar characteristics and functions to MSCs and can maintain their original characteristics. Because of these properties, OP9 cells have become a suitable substitute for research on MSCs. Previously, we have found that MSCs can cure inflammatory bowel disease in mice. In this study, we aimed to investigate whether OP9 cells can functionally regulate and alleviate inflammatory diseases. We evaluated the therapeutic effect of OP9 cells in the mouse model of inflammatory bowel disease and found OP9 cells were able to ameliorate inflammatory bowel disease. We explored the existence of NLRP3 inflammasome in OP9 cells, and showed better therapeutic effects when the NLRP3 inflammasome was suppressed. Thus, OP9 cell line is similar to MSCs in characteristic and function, and is an ideal substitute for MSCs research. The preliminary exploration of the inflammasome system in OP9 cells lays a theoretical and methodological foundation for further study of MSCs.
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As a predominant type II protein arginine methyltransferase, PRMT5 plays critical roles in various normal cellular processes by catalyzing the mono- and symmetrical dimethylation of a wide range of histone and nonhistone substrates. Clinical studies have revealed that high expression of PRMT5 is observed in different solid tumors and hematological malignancies and is closely associated with cancer initiation and progression. Accordingly, PRMT5 is becoming a promising anticancer target and has received great attention in both the pharmaceutical industry and the academic community. In this Perspective, we comprehensively summarize recent advances in the development of first-generation PRMT5 enzymatic inhibitors and highlight novel strategies targeting PRMT5 in the past 5 years. We also discuss the challenges and opportunities of PRMT5 inhibition, with the aim of shedding light on future PRMT5 drug discovery.
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Neoplasias , Proteína-Arginina N-Metiltransferasas , Humanos , Proteína-Arginina N-Metiltransferasas/metabolismo , Neoplasias/tratamiento farmacológico , Histonas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , ArgininaRESUMEN
Background: Myelosuppression is a common condition during chemotherapy. Bone-associated mesenchymal stem cells (BA-MSCs) play an essential role in the composition of the hematopoietic microenvironment and support hematopoietic activity. However, chemotherapy-induced damage to BA-MSCs is rarely studied. Recent studies have shown that platelets promote the wound-healing capability of MSCs by mitochondrial transfer. Therefore, this study is aimed at investigating the chemotherapy-induced damage to BA-MSCs and the therapeutic effect of platelet-derived mitochondria. Material/Methods. We established in vivo and in vitro BA-MSC chemotherapy injury models using the chemotherapy agent 5-fluorouracil (5-FU). Changes in the mitochondrial dynamics were detected by transmission electron microscopy, and the expression of mitochondrial fusion and fission genes was analyzed by qRT-PCR. In addition, mitochondrial functions were also explored by flow cytometry and luminometer. Platelet-derived mitochondria were incubated with 5-FU-damaged BA-MSCs to repair the injury, and BA-MSC functional changes were examined to assess the therapy efficacy. The mechanism of treatment was explored by studying the expression of mitochondrial fission and fusion genes and hematopoietic regulatory factor genes in BA-MSCs. Results: Stimulation with 5-FU increased the apoptosis and suppressed cell cycle progression of BA-MSCs both in vivo and in vitro. In addition, 5-FU chemotherapy inhibited the hematopoietic regulatory ability and disrupted the mitochondrial dynamics and functions of BA-MSCs. The mitochondrial membrane potential and ATP content of 5-FU-injured BA-MSCs were decreased. Interestingly, when platelet-derived mitochondria were transferred to BA-MSCs, the 5-FU-induced apoptosis was alleviated, and the hematopoietic regulatory ability of 5-FU-injured BA-MSCs was effectively improved by upregulating the expression of mitochondrial fusion genes and hematopoietic regulatory factor genes. Conclusion: BA-MSCs were severely damaged by 5-FU chemotherapy both in vivo and in vitro. Meanwhile, platelet-derived mitochondria could attenuate the 5-FU-induced injury to BA-MSCs, which provides future research directions for exploring the treatment strategies for chemotherapy-injured BA-MSCs and establishes a research basis for related fields.
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Boron is an essential trace element for animals. Appropriate boron supplementation can produce beneficial effects on the animal body, while a high dose of boron has adverse and even toxic effects. Our aim was to investigate the impact of different doses of boron on the microstructure of duodenum in rats, expression of secretory immunoglobulin A (SIgA) and tight junction protein, cell proliferation and apoptosis. Eighty newly weaned clean Sprague-Dawley (SD) rats were given distilled water supplemented with 0, 10, 20, 40, 80, 160, 320, and 640 mg/L of boron for 60 days. We found that supplementation of 40 and 80 mg/L boron could increase the height of duodenal villi and the crypt depth, the number of intraepithelial lymphocytes (IELs) and goblet cells, the expression of SIgA, Zonula occludens-1 (ZO-1) and occludin, and proliferating cell nuclear antigen (PCNA) in duodenum of rats; decrease expression of Caspase-3 mRNA and the number of Caspase-3-positive cells, but supplementation of 320 and 640 mg/L boron could have the opposite effect in these indexes. The results showed that supplemented with 40 and 80 mg/L of boron could improve the structure and function of duodenum, while supplemented with 320-640 mg/L had a significant inhibitory effect.
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Boro , Proteínas de Uniones Estrechas , Animales , Apoptosis , Boro/farmacología , Proliferación Celular , Duodeno , Inmunidad , Mucosa Intestinal , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Blood from younger individuals has been shown to improve physiological function in recipients in laboratory research, and many proteins from human peripheral blood show antisenescence capabilities. Thus, researchers have questioned whether blood from young donors is superior to blood from older donors. Blood transfusion is a key supportive therapy for trauma patients, and recent studies have reported the influence of blood donor age on recipient patient prognosis. Although some retrospective results found that blood from young donors improves survival, no influence of blood donor age was observed on outcomes in other study groups. The reasons for this discrepancy are complicated, but the fact that data were not obtained from randomized controlled trial (RCT) data should be considered. The current protocol and analysis method provide a feasible RCT design to evaluate the prognosis of severely ill surgery patients who were transfused with blood products from blood donors of different ages. METHODS: The current study is a pragmatic multicenter RCT (open, parallel-group, non-masked, superiority trial). Recruited surgery intensive care unit patients will be randomized into three groups and transfused with blood products from male donors of different ages (< 25, 25-45, and > 45 years). Survival time will be measured within 28 days. The survival characteristics, possible interaction between variables, and potential factors associated with death will be analyzed by Kaplan-Meier analysis, two-way ANOVA, and Cox proportional hazards model, respectively. TRIAL REGISTRATION: ChiCTR: ChiCTR190002. Registered on 22 March 2019. http://www.chictr.org.cn/showproj.aspx?proj=36867 .
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Donantes de Sangre/estadística & datos numéricos , Transfusión Sanguínea , Mortalidad , Análisis de Supervivencia , Factores de Edad , China , Humanos , Unidades de Cuidados Intensivos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Pragmáticos como Asunto , Procedimientos Quirúrgicos OperativosRESUMEN
A cross-sectional study design was applied amongst a random sample (n = 10158) of Chinese adolescents. Self-completed questionnaires, including demographic characteristics, Internet use situation, Youth Internet Addiction Test, Youth Social Support Rating Scale and Zung Self-rating Depression Scale were utilized to examine the study objectives. Among the study population, the prevalence rate of Internet addiction was 10.4%, with 1038 (10.2%) moderately and 21 (0.2%) severely addicted to the Internet. Results from the multivariate logistic regression analyses suggested that a variety of related factors have significant effects on Internet addiction (parental control, per capita annual household income, academic performance, the access to Internet, online activities). The correlation coefficients showed that Internet addiction was negatively correlated with social support and positively associated with depression. Social support had a significant negative predictive effect on Internet addiction. The mediating effect of depression between social support and Internet addiction was remarkable.
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Conducta Adictiva/epidemiología , Internet/estadística & datos numéricos , Apoyo Social , Adolescente , Distribución de Chi-Cuadrado , China/epidemiología , Estudios Transversales , Depresión/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Prevalencia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The present paper innovatively proposed the technology using hyperspectral to detect the body surface tissues that can achieve the systemic analysis of composition and structure by obtaining the multiple spectrum and image information simultaneously. Besides, by the method of data mining, the relationships between diseases and the data including the spectrum, image or synentropy were established. This technology provided more information for the disease detection clinically which can reflect accurately the physiological, biochemical and pathological status and the variation of the body surface tissues, by which both the cost of the equipment and the operation steps can be reduced.