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Photosensitive supercapacitors incorporate light-sensitive materials on capacitive electrodes, enabling solar energy conversion and storage in one device. In this study, heterogeneous structures of rod-shaped ZnO decorated with Ce2S3 nanoparticles on nickel foam (ZnO@Ce2S3/NF) are synthesized using a two-step hydrothermal method as photosensitive supercapacitor electrodes for capacitance enhancement under visible light. The formation of ZnO@Ce2S3 heterogeneous structures is confirmed using various structural characterization techniques. The area-specific capacitance of the ZnO@Ce2S3/NF composite electrode increased from 1738.1 to 1844.0 mF cm-2 after illumination under a current density of 5 mA cm-2, which is 2.4 and 2.8 times higher than that of ZnO and Ce2S3 electrodes under similar conditions, respectively, indicating the remarkable light-induced capacitance enhancement performance. The ZnO@Ce2S3/NF electrode also exhibits a higher photocurrent and photovoltage than the two single electrodes, demonstrating its excellent photosensitivity. The improved capacitance performance and photosensitivity under illumination are attributed to the well-constructed energy-level structure, which stimulates the flow of photogenerated electrons from the outer circuit and the involvement of photogenerated holes in the resulting surface-controlled capacitance. In addition, the assembled ZnO@Ce2S3/NF-based hybrid supercapacitor exhibits a great energy density of 145.0 mWh cm-2 under illumination. This study provides a novel strategy for the development of high-performance solar energy conversion/storage devices.
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BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease. Great progress has been made in the pathogenesis of psoriasis in recent years, but there is no bibliometric study on the pathogenesis of psoriasis. The purpose of this study was to use bibliometrics method to analyze the research overview and hot spots of pathogenesis of psoriasis in recent 10 years, so as to further understand the development trend and frontier of this field. METHODS: The core literatures on the pathogenesis of psoriasis were searched in the Web of Science database, and analyzed by VOSviewer, CiteSpace, and Bibliometrix in terms of the annual publication volume, country, institution, author, journal, keywords, and so on. RESULTS: A total of 3570 literatures were included. China and the United States were the main research countries in this field, and Rockefeller University was the main research institution. Krueger JG, the author, had the highest number of publications and the greatest influence, and Boehncke (2015) was the most cited local literature. J INVEST DERMATOL takes the top spot in terms of the number of Dermatol articles and citation frequency. The main research hotspots in the pathogenesis of psoriasis are as follows: (1) The interaction between innate and adaptive immunity and the related inflammatory loop dominated by Th17 cells and IL-23/IL-17 axis are still the key mechanisms of psoriasis; (2) molecular genetic studies represented by Long Non-Coding RNA (LncRNA); (3) integrated research of multi-omics techniques represented by gut microbiota; and (4) Exploring the comorbidity mechanism of psoriasis represented by Metabolic Syndrome (MetS). CONCLUSION: This study is a summary of the current research status and hot trend of the pathogenesis of psoriasis, which will provide some reference for the scholars studying the pathogenesis of psoriasis.
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Psoriasis , Humanos , Piel , Bibliometría , China , Bases de Datos FactualesRESUMEN
Effective ways to identify and predict men who have sex with men (MSM) at substantial risk for HIV is a global priority. HIV risk assessment tools can improve individual risk awareness and subsequent health-seeking actions. We sought to identify and characterize the performance of HIV infection risk prediction models in MSM through systematic review and meta-analysis. PubMed, Embase, and The Cochrane Library were searched. Eighteen HIV infection risk assessment models with a total of 151,422 participants and 3643 HIV cases were identified, eight of which have been externally validated by at least one study (HIRI-MSM, Menza Score, SDET Score, Li Model, DHRS, Amsterdam Score, SexPro model, and UMRSS). The number of predictor variables in each model ranged from three to 12, age, the number of male sexual partners, unprotected receptive anal intercourse, recreational drug usage (amphetamines, poppers), and sexually transmitted infections were critical scoring variables. All eight externally validated models performed well in terms of discrimination, with the pooled area under the receiver operating characteristic curve (AUC) ranging from 0.62 (95%CI: 0.51 to 0.73, SDET Score) to 0.83 (95%CI: 0.48 to 0.99, Amsterdam Score). Calibration performance was only reported in 10 studies (35.7%, 10/28). The HIV infection risk prediction models showed moderate-to-good discrimination performance. Validation of prediction models across different geographic and ethnic environments is needed to ensure their real-world application.
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Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Masculino , Humanos , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Parejas SexualesRESUMEN
BACKGROUND: Patients with type 2 diabetes Mellitus (T2DM) are more likely to suffer from a higher uric acid level in blood-hyperuricemia (HUA). There are no conclusive studies done to predict HUA among T2DM patients. Therefore, this study aims to explore the risk factors of HUA among T2DM patients and finally suggest a model to help with its prediction. METHOD: In this retrospective research, all the date were collected between March 2017 and October 2019 in the Medical Laboratory Center of the First Affiliated Hospital of Xinjiang Medical University. The information included sociodemographic factors, blood routine index, thyroid function indicators and serum biochemical markers. The least absolute shrinkage and selection operator (LASSO) and multivariate binary logistic regression were performed to screen the risk factors of HUA among T2DM patients in blood tests, and the nomogram was used to perform and visualise the predictive model. The receiver operator characteristic (ROC) curve, internal validation, and clinical decision curve analysis (DCA) were applied to evaluate the prediction performance of the model. RESULTS: We total collected the clinical date of 841 T2DM patients, whose age vary from 19-86. In this study, the overall prevalence of HUA in T2DM patients was 12.6%. According to the result of LASSO-logistic regression analysis, sex, ethnicity, serum albumin (ALB), serum cystatin C (CysC), serum inorganic phosphorus (IPHOS), alkaline phosphatase (ALP), serum bicarbonate (CO2) and high-density lipoprotein (HDLC) were included in the HUA risk prediction model. The nomogram confirmed that the prediction model fits well (χ2 = 5.4952, P = 0.704) and the calibration curve indicates the model had a good calibration. ROC analysis indicates that the predictive model shows the best discrimination ability (AUC = 0.827; 95% CI: 0.78-0.874) whose specificity is 0.885, and sensitivity is 0.602. CONCLUSION: Our study reveals that there were 8 variables that can be considered as independent risk factors for HUA among T2DM patients. In light of our findings, a predictive model was developed and clinical advice was given on its use.
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Diabetes Mellitus Tipo 2 , Hiperuricemia , Humanos , Hiperuricemia/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Estudios Retrospectivos , Factores de Riesgo , China/epidemiologíaRESUMEN
BACKGROUND: Men who have sex with men (MSM) in China hold a low-risk perception of acquiring HIV. This has resulted in an inadequate HIV testing rate. OBJECTIVE: This study aims to investigate whether administering HIV risk self-assessments with tailored feedback on a gay geosocial networking (GSN) app could improve HIV testing rates and reduce sexual risk behaviors in Chinese MSM. METHODS: We recruited MSM from Beijing, China, who used the GSN platform Blued in October 2017 in this 12-month double-blinded randomized controlled trial. From October 2017 to September 2018, eligible participants were randomly assigned to use a self-reported HIV risk assessment tool that provided tailored feedback according to transmission risk (group 1), access to the same HIV risk assessment without feedback (group 2), or government-recommended HIV education materials (control). All interventions were remotely delivered through the mobile phone-based app Blued, and participants were followed up at 1, 3, 6, and 12 months from baseline. The number of HIV tests over the 12-month study was the primary outcome and was assessed using an intention-to-treat analysis with an incident rate ratio (IRR). Unprotected anal intercourse (UAI) over 6 months was assessed by a modified intention-to-treat analysis and was the secondary outcome. All statistical analyses were conducted in SAS 9.3 (SAS Institute, Inc.), and a P value <.05 was considered statistically significant. RESULTS: In total, 9280 MSM were recruited from baseline and were randomly assigned to group 1 (n=3028), group 2 (n=3065), or controls (n=3187). After follow-up, 1034 (34.1%), 993 (32.4%), and 1103 (34.6%) remained in each group, respectively. Over 12 months, group 1 took 391 tests (mean of 2.51 tests per person), group 2 took 352 tests (mean of 2.01 tests per person), and controls took 295 tests (mean of 1.72 tests per person). Group 1 had significantly more HIV testing than the control group (IRR 1.32, 95% CI 1.09-4.58; P=.01), while group 2 did not differ significantly from the controls (IRR 1.06, 95% CI 0.86-1.30; P=.60). The proportion of UAI was not statistically different among different groups, but all 3 groups had UAI, which declined from baseline. CONCLUSIONS: Repeated HIV risk assessments coupled with tailored feedback through GSN apps improved HIV testing. Such interventions should be considered a simple way of improving HIV testing among MSM in China and increasing awareness of HIV status. TRIAL REGISTRATION: ClinicalTrials.gov NCT03320239; https://clinicaltrials.gov/study/NCT03320239.
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Infecciones por VIH , Aplicaciones Móviles , Minorías Sexuales y de Género , Masculino , Humanos , Beijing , Homosexualidad Masculina , Autoevaluación (Psicología) , China , Prueba de VIH , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & controlRESUMEN
BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs, retrospectively registered) have a lot of promise for treating theca interstitial cells(TICs) dysfunction in premature ovarian insufficiency (POI). The mechanisms, however, are still unknown. METHODS: To examine the therapeutic and find the cause, we used both in vivo cisplatin-induced POI rat model and in vitro TICs model. HUCMSCs were injected into the tail veins of POI rats in an in vivo investigation. Then, using ELISA, HE staining, TUNEL apoptosis test kit, immunohistochemistry and western blot, researchers examined hormonal levels, ovarian morphology, TICs apoptosis, NR4A1 and Cyp17a1 in response to cisplatin treatment and hUCMSCs. TICs were obtained from the ovaries of rats and treated with the cisplatin, hUCMSCs supernatant, and the antagonist of NR4A1--DIM-C-pPhOH. ELISA, immunofluorescence, flow cytometry, JC-1 labeling and western blot analysis were used to detect T levels, Cyp17a1, NR4A1, and the anti-apoptotic protein Bcl-2, as well as pro-apoptotic proteins Bax, caspase-9, caspase-3, and cytochrome C(cytc). RESULTS: We discovered that hUCMSCs restored the ovarian function, particularly TICs function based on measures of Cyp17a1 and T expression. NR4A1 was found in ovarian TICs of each group and NR4A1 expression was lower in the POI rats but higher following hUCMSCs therapy. The apoptosis of TICs generated by cisplatin was reduced after treatment with hUCMSCs. In vitro, NR4A1 was expressed in the nucleus of TICs, and NR4A1 as well as phospho-NR4A1 were decreased, following the apoptosis of TICs was emerged after cisplatin treatment. Interestingly, the localization of NR4A1 was translocated from the nucleus to the cytoplasm due to cisplatin. HUCMSCs were able to boost NR4A1 and phospho-NR4A1 expression while TICs' apoptosis and JC-1 polymorimonomor fluorescence ratios reduced. Furthermore, Bcl-2 expression dropped following cisplatin treatment, whereas Bax, cytc, caspase-9, and caspase-3 expression rose; however, hUCMSCs treatment reduced their expression. In addition, DIM-C-pPhOH had no effect on the NR4A1 expression, but it did increase the expression of apoptosis-related factors such as Bax, cytc, caspase-9, and caspase-3, causing the apoptosis of TICs. CONCLUSIONS: These data show that hUCMSCs therapy improves ovarian function in POI rats by inhibiting TICs apoptosis through regulating NR4A1 -mediated mitochondrial mechanisms.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Insuficiencia Ovárica Primaria , Animales , Apoptosis , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Caspasa 9/farmacología , Cisplatino/efectos adversos , Femenino , Humanos , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/terapia , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/farmacología , Ratas , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/farmacologíaRESUMEN
BACKGROUND: As a metastasis-related protein, NEDD9 has been reported in breast cancer (BC) metastasis research. However, there are few studies on the upstream regulators of NEDD9, especially involving the potential role of miRNAs. The purpose of this study was to explain whether miR-107 potentially regulates NEDD9, which may lead to invasion and metastasis of BC. METHODS: MCF-7 and MDA-MB-231 cells were transduced with lentiviruses to construct stably transduced cells with miR-107 overexpression, miR-107 silencing or empty vectors. A luciferase reporter assay was performed to verify the binding of miR-107 and NEDD9. The scratch test and Transwell assay were used to measure cell migration and invasion ability, respectively. For the study of metastasis in vivo, we injected MDA-MB-231 cells into the fat pad of nude mice to develop an orthotopic breast cancer model. RESULTS: We found that NEDD9 expression correlates with the prognosis of BC patients. In BC cell lines, NEDD9 was positively correlated with cell migration ability. Further research revealed that miR-107 inhibited NEDD9 expression by targeting the 3'-untranslated region of NEDD9. Overexpression of miR-107 suppressed the expression of NEDD9, thereby inhibiting the invasion, migration and proliferation of BC cells, but interference with miR-107 promoted the expression of NEDD9 as well as invasion, migration and proliferation. In an in vivo model, overexpression of miR-107 decreased the expression of NEDD9 and inhibited tumour growth, invasion and metastasis; however, these effects were reversed by inhibiting miR-107. CONCLUSIONS: These findings indicated the potential role of miR-107 in regulating NEDD9 in the invasion, migration and proliferation of BC.
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Neoplasias de la Mama , MicroARNs , Regiones no Traducidas 3' , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica/genéticaRESUMEN
BACKGROUND: High-altitude cerebral edema (HACE) is a serious and potentially fatal brain injury that is caused by acute hypobaric hypoxia (HH) exposure. Vasogenic edema is the main pathological factor of this condition. Hypoxia-induced disruptions of tight junctions in the endothelium trigger bloodâbrain barrier (BBB) damage and induce vasogenic edema. Nuclear respiratory factor 1 (NRF1) acts as a major regulator of hypoxia-induced endothelial cell injury, and caveolin-1 (CAV-1) is upregulated as its downstream gene in hypoxic endothelial cells. This study aimed to investigate whether CAV-1 is involved in HACE progression and the underlying mechanism. METHODS: C57BL/6 mice were exposed to HH (7600 m above sea level) for 24 h, and BBB injury was assessed by brain water content, Evans blue staining and FITC-dextran leakage. Immunofluorescence, transmission electron microscope, transendothelial electrical resistance (TEER), transcytosis assays, and western blotting were performed to confirm the role and underlying mechanism of CAV-1 in the disruption of tight junctions and BBB permeability. Mice or bEnd.3 cells were pretreated with MßCD, a specific blocker of CAV-1, and the effect of CAV-1 on claudin-5 internalization under hypoxic conditions was detected by immunofluorescence, western blotting, and TEER. The expression of NRF1 was knocked down, and the regulation of CAV-1 by NRF1 under hypoxic conditions was examined by qPCR, western blotting, and immunofluorescence. RESULTS: The BBB was severely damaged and was accompanied by a significant loss of vascular tight junction proteins in HACE mice. CAV-1 was significantly upregulated in endothelial cells, and claudin-5 explicitly colocalized with CAV-1. During the in vitro experiments, hypoxia increased cell permeability, CAV-1 expression, and claudin-5 internalization and downregulated tight junction proteins. Simultaneously, hypoxia induced the upregulation of CAV-1 by activating NRF1. Blocking CAV-1-mediated intracellular transport improved the integrity of TJs in hypoxic endothelial cells and effectively inhibited the increase in BBB permeability and brain water content in HH animals. CONCLUSIONS: Hypoxia upregulated CAV-1 transcription via the activation of NRF1 in endothelial cells, thus inducing the internalization and autophagic degradation of claudin-5. These effects lead to the destruction of the BBB and trigger HACE. Therefore, CAV-1 may be a potential therapeutic target for HACE. Video abstract.
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Edema Encefálico , Caveolina 1 , Hipoxia , Animales , Ratones , Altitud , Barrera Hematoencefálica , Edema Encefálico/complicaciones , Edema Encefálico/metabolismo , Caveolina 1/metabolismo , Claudina-5/metabolismo , Células Endoteliales/metabolismo , Hipoxia/complicaciones , Hipoxia/metabolismo , Ratones Endogámicos C57BL , Factor Nuclear 1 de Respiración/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Uniones Estrechas/metabolismoRESUMEN
Long chain non-encoding RNA (lncRNA) can affect gene expression through transcription, post transcriptional regulation and epigenetic modification, and it is involved in regulating ovarian physiological function. LncRNA, as a competitive endogenous RNA, can affect the expression of target gene mRNA by competitively binding microRNA (miRNA), which are called lncRNA/miRNA/mRNA regulatory network. It plays an important role in the regulation of ovarian physiological function and the occurrence and development of ovarian reproductive disorders, expecting to become a new target and diagnostic index for the treatment of reproductive disorders.
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MicroARNs , ARN Largo no Codificante , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , ARN MensajeroRESUMEN
It has been reported that ammonia produced by glutaminolysis activates the HIF-1 pathway in several types of cancer cells, but the underlying mechanisms remain unclear. In this study, the effects of ammonia on the activation of HIF-1 pathway and glycolysis in MDA-MB-231 breast cancer cells were investigated and the underlying mechanisms involved were elucidated. The results showed that NH4Cl concentration-dependently increased the protein level of HIF-1α and enhanced the transactivation activity of HIF-1 in MDA-MB-231â¯cells. In addition, NH4Cl increased the expression of GluT1 and LDHA and promoted aerobic glycolysis by activating the HIF-1 pathway. Further study revealed that NH4Cl increased the mitochondrial ROS level and decreased the cellular Fe2+ level in MDA-MB-231â¯cells. Activation of the HIF-1 pathway induced by NH4Cl was inhibited by addition of the antioxidant NAC or the NADPH oxidase (NOX) inhibitor apocynin, indicating the involvement of the NOX-induced ROS generation. When MDA-MB-231â¯cells were treated with NH4Cl, the oxygen consumption of cells increased, followed by the decreased mitochondrial membrane potential and cellular ATP level, indicating the uncoupling of mitochondria. In conclusion, NH4Cl activated the HIF-1 signaling pathway and promoted aerobic glycolysis in MDA-MB-231â¯cells, likely through the promotion of mitochondrial ROS release and mitochondrial uncoupling.
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Amoníaco/farmacología , Neoplasias de la Mama/metabolismo , Glucólisis/efectos de los fármacos , Factor 1 Inducible por Hipoxia/metabolismo , Mitocondrias/metabolismo , Cloruro de Amonio/farmacología , Línea Celular Tumoral , Femenino , Humanos , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
PURPOSE: ß-elemene and cisplatin combined chemotherapy currently is one of the most important settings available for lung cancer therapy in China. However, the clinical outcome is limited by their pharmacokinetic drawbacks. On the other hand, most of nanomedicines have failed in clinical development due to the huge differences between heterogeneous clinical tumor tissues and homogenous cell-derived xenografts. In this work, we fabricated a ß-elemene and cisplatin co-loaded liposomal system to effectively treat lung cancer. METHOD: In vitro cytotoxicity of co-loaded liposomes was studied by MTT, trypan and Hoechst/PI staining, and western blot in A549, A549/DDP, and LCC cells. In vivo antitumor efficacy was evaluated in cell-derived and clinically relevant patient-derived xenografts. RESULTS: Co-loaded liposomes were more cytotoxic to cancer cells, especially than the combination of single-loaded liposomes, benefiting from their simultaneous drug internalization and release. As a result, they exhibited desirable therapeutic outcome in both cell-derived and patient-derived xenografts. CONCLUSION: ß-elemene and cisplatin co-loaded liposomes are a clinically promising candidate for effective lung cancer therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cisplatino/farmacocinética , Liposomas/química , Neoplasias Pulmonares/tratamiento farmacológico , Sesquiterpenos/farmacocinética , Células A549 , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia Celular/efectos de los fármacos , Colesterol/química , Cisplatino/administración & dosificación , Composición de Medicamentos , Liberación de Fármacos , Xenoinjertos , Humanos , Ratones Endogámicos C57BL , Tamaño de la Partícula , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenglicoles/química , Sesquiterpenos/administración & dosificación , Distribución TisularRESUMEN
Previous studies have shown that the ovarian failure in autoimmune-induced premature ovarian failure (POF) mice could be improved by the transplantation of human placenta-derived mesenchymal stem cells (hPMSCs); however, the protective mechanism of hPMSCs transplantation on ovarian dysfunction remains unclear. Ovarian dysfunction is closely related to the apoptosis of granulosa cells (GCs). To determine the effects of hPMSCs transplantation on GCs apoptosis, an autoimmune POF mice model was established with zona pellucida glycoprotein 3 (ZP3) peptide. It is reported that the inositol-requiring enzyme 1α (IRE1α) and its downstream molecules play a central role in the endoplasmic reticulum (ER) stress-induced apoptosis pathway. So the aim of this study is to investigate whether hPMSCs transplantation attenuated GCs apoptosis via inhibiting ER stress IRE1α signaling pathway. The ovarian dysfunction, follicular dysplasia, and GCs apoptosis were observed in the POF mice. And the IRE1α pathway was activated in ovaries of POF mice, as demonstrated by, increased X-box binding protein 1 (XBP1), up-regulated 78 kDa glucose-regulated protein (GRP78) and caspase-12. Following transplantation of hPMSCs, the ovarian structure and function were significantly improved in POF mice. In addition, the GCs apoptosis was obviously attenuated and IRE1α pathway was significantly inhibited. Transplantation of hPMSCs suppressed GCs apoptosis-induced by ER stress IRE1α signaling pathway in POF mice, which might contribute to the hPMSCs transplantation-mediating ovarian function recovery.
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Apoptosis/efectos de los fármacos , Células de la Granulosa/efectos de los fármacos , Células Madre Mesenquimatosas/inmunología , Placenta/citología , Insuficiencia Ovárica Primaria , Animales , Caspasa 12/metabolismo , Modelos Animales de Enfermedad , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Endorribonucleasas/metabolismo , Femenino , Células de la Granulosa/citología , Proteínas de Choque Térmico/metabolismo , Humanos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos BALB C , Ovario/metabolismo , Embarazo , Insuficiencia Ovárica Primaria/metabolismo , Insuficiencia Ovárica Primaria/terapia , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína 1 de Unión a la X-Box/metabolismo , Glicoproteínas de la Zona Pelúcida/metabolismoRESUMEN
The significant positive correlation between ghrelin and iron and hepcidin levels in the plasma of children with iron deficiency anemia prompted us to hypothesize that ghrelin may affect iron metabolism. Here, we investigated the effects of fasting or ghrelin on the expression of hepcidin, ferroportin 1 (Fpn1), transferrin receptor 1 (TfR1), ferritin light chain (Ft-L) proteins, and ghrelin, and also hormone secretagogue receptor 1 alpha (GHSR1α) and ghrelin O-acyltransferase (GOAT) mRNAs in the spleen and/or macrophage. We demonstrated that fasting induces a significant increase in the expression of ghrelin, GHSR1α, GOAT, and hepcidin mRNAs, as well as Ft-L and Fpn1 but not TfR1 proteins in the spleens of mice in vivo. Similar to the effects of fasting on the spleen, ghrelin induced a significant increase in the expression of Ft-L and Fpn1 but not TfR1 proteins in macrophages in vitro. In addition, ghrelin was found to induce a significant enhancement in phosphorylation of ERK as well as translocation of pERK from the cytosol to nuclei. Furthermore, the increased pERK and Fpn1 induced by ghrelin was demonstrated to be preventable by pre-treatment with either GHSR1α antagonist or pERK inhibitor. Our findings support the hypothesis that fasting upregulates Fpn1 expression, probably via a ghrelin/GHSR/MAPK signaling pathway.
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Proteínas de Transporte de Catión/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ayuno/metabolismo , Ghrelina/metabolismo , Macrófagos Peritoneales/enzimología , Receptores de Ghrelina/metabolismo , Transducción de Señal , Bazo/enzimología , Aciltransferasas/genética , Aciltransferasas/metabolismo , Animales , Apoferritinas/genética , Apoferritinas/metabolismo , Proteínas de Transporte de Catión/genética , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Ghrelina/genética , Antagonistas de Hormonas/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Proteínas de la Membrana , Ratones Endogámicos C57BL , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Ghrelina/antagonistas & inhibidores , Receptores de Ghrelina/genética , Bazo/efectos de los fármacos , Regulación hacia ArribaRESUMEN
BACKGROUND/AIMS: The studies in the patients with iron deficiency anemia (IDA) implied the existence of the association of ghrelin with iron or hepcidin levels in the plasma under the pathophysiological conditions. We hypothesized that fasting may be able to affect iron metabolism via ghrelin under the physiological conditions. METHODS: We investigated the effects of fasting on serum ghrelin and iron contents in healthy volunteers (23-31 years) and C57BL/6 male mice (8-week-olds) under the physiological conditions. RESULTS: Fasting induced a significant elevation in both total ghrelin and acylated ghrelin and a reduction in iron levels in the serum of both human and mice. Correlation analysis demonstrated that total ghrelin or acylated ghrelin is negatively correlated with iron in the serum in human and mice. CONCLUSION: Ghrelin has a role to reduce serum iron under the conditions of fasting.
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Ayuno/sangre , Ghrelina/sangre , Hierro/sangre , Acilación , Adulto , Anemia Ferropénica/sangre , Animales , Femenino , Voluntarios Sanos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Adulto JovenRESUMEN
Hypoxia-inducible factor 1α (HIF-1α) is a master regulator of oxygen homeostasis. Under hypoxia, the active HIF1-α subunits are mainly regulated through increased protein stabilization. Little is known concerning HIF-1α transcriptional regulation. Nuclear respiratory factor 1 (NRF-1) is a DNA-binding transcription factor that regulates mitochondrial biogenesis. In this study, we showed that NRF-1was a repressor of HIF-1α. The cellular depletion of NRF-1 by siRNA targeting leads to increased HIF-1αtranscriptional activity. EMSA, ChIP and luciferase activity allowed the identification of two functional NRF-1 binding sites within HIF-1α promoter. This study therefore identifies NRF-1 as a novel regulator of HIF-1α. © 2016 IUBMB Life, 68(9):748-755, 2016.
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Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Mitocondrias/genética , Factor Nuclear 1 de Respiración/genética , Activación Transcripcional/genética , Sitios de Unión/genética , Hipoxia de la Célula/genética , Proteínas de Unión al ADN/genética , Células HEK293 , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Mitocondrias/metabolismo , Factor Nuclear 1 de Respiración/antagonistas & inhibidores , Oxígeno/metabolismo , Regiones Promotoras Genéticas , ARN Interferente Pequeño/genéticaRESUMEN
Transferrin receptor (TfR1) and divalent metal transporter 1 (DMT1) are important proteins for cellular iron uptake, and both are regulated transcriptionally through the binding of hypoxia-inducible factor 1 (HIF-1) to hypoxia-responsive elements (HREs) under hypoxic conditions. These proteins are also regulated post-transcriptionally through the binding of iron regulatory protein 1 (IRP1) to iron-responsive elements (IREs) located in the mRNA untranslated region (UTR) to control cellular iron homeostasis. In iron-deficient cells, IRP1-IRE interactions stabilize TfR1 and DMT1 mRNAs, enhancing iron uptake. However, little is known about the impact of IRP1 on the regulation of cellular iron homeostasis under hypoxia. Thus, to investigate the role of IRP1 in hypoxic condition, overexpression and knockdown assays were performed using HepG2 cells. The overexpression of IRP1 suppressed the hypoxia-induced increase in TfR1 and DMT1 (+IRE) expression and reduced the stability of TfR1 and DMT1 (+IRE) mRNAs under hypoxia, whereas IRP1 knockdown further increased the hypoxia-induced expression of both proteins, preventing the decrease in IRE-dependent luciferase activity induced by hypoxia. Under hypoxic conditions, ferrous iron uptake, the labile iron pool (LIP), and total intracellular iron reduced when IRP1 was overexpressed and further increased when IRP1 was knocked down. IRP1 expression declined and TfR1/DMT1 (+IRE) expression increased with the time of hypoxia prolonged, whereas the binding of IRP1 to the IRE of TfR1/DMT1 mRNA maintained. In summary, IRP1 suppressed TfR1/DMT1 (+IRE) expression, limited the cellular iron content and decreased lactate dehydrogenase (LDH) release induced by hypoxia.
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Antígenos CD/genética , Regulación Neoplásica de la Expresión Génica , Proteína 1 Reguladora de Hierro/metabolismo , Hierro/metabolismo , Receptores de Transferrina/genética , Factores de Transcripción/genética , Antígenos CD/química , Sitios de Unión , Hipoxia de la Célula , Células Hep G2 , Humanos , Hierro/química , Proteína 1 Reguladora de Hierro/genética , L-Lactato Deshidrogenasa/metabolismo , Estabilidad del ARN , ARN Mensajero/metabolismo , Receptores de Transferrina/química , Factores de Transcripción/química , Regiones no TraducidasRESUMEN
Background: In the past few years, a burgeoning interest has emerged in applying gamification to promote desired health behaviors. However, little is known about the effectiveness of such applications in the HIV prevention and care continuum among men who have sex with men (MSM). Objective: This study aims to summarize and evaluate research on the effectiveness of gamification on the HIV prevention and care continuum, including HIV-testing promotion; condomless anal sex (CAS) reduction; and uptake of and adherence to pre-exposure prophylaxis (PrEP), postexposure prophylaxis (PEP), and antiretroviral therapy (ART). Methods: We comprehensively searched PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and the Journal of Medical Internet Research and its sister journals for studies published in English and Chinese from inception to January 2024. Eligible studies were included when they used gamified interventions with an active or inactive control group and assessed at least one of the following outcomes: HIV testing; CAS; and uptake of and adherence to PrEP, PEP, and ART. During the meta-analysis, a random-effects model was applied. Two reviewers independently assessed the quality and risk of bias of each included study. Results: The systematic review identified 26 studies, including 10 randomized controlled trials (RCTs). The results indicated that gamified digital interventions had been applied to various HIV outcomes, such as HIV testing, CAS, PrEP uptake and adherence, PEP uptake, and ART adherence. Most of the studies were conducted in the United States (n=19, 73%). The most frequently used game component was gaining points, followed by challenges. The meta-analysis showed gamification interventions could reduce the number of CAS acts at the 3-month follow-up (n=2 RCTs; incidence rate ratio 0.62, 95% CI 0.44-0.88). The meta-analysis also suggested an effective but nonstatistically significant effect of PrEP adherence at the 3-month follow-up (n=3 RCTs; risk ratio 1.16, 95% CI 0.96-1.38) and 6-month follow-up (n=4 RCTs; risk ratio 1.28, 95% CI 0.89-1.84). Only 1 pilot RCT was designed to evaluate the effectiveness of a gamified app in promoting HIV testing and PrEP uptake. No RCT was conducted to evaluate the effect of the gamified digital intervention on PEP uptake and adherence, and ART initiation among MSM. Conclusions: Our findings suggest the short-term effect of gamified digital interventions on lowering the number of CAS acts in MSM. Further well-powered studies are still needed to evaluate the effect of the gamified digital intervention on HIV testing, PrEP uptake, PEP initiation and adherence, and ART initiation in MSM.
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Infecciones por VIH , Homosexualidad Masculina , Telemedicina , Humanos , Masculino , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Homosexualidad Masculina/estadística & datos numéricos , Homosexualidad Masculina/psicología , Telemedicina/estadística & datos numéricos , Continuidad de la Atención al Paciente/normas , Continuidad de la Atención al Paciente/estadística & datos numéricosRESUMEN
Background: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite. Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue. Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated. Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice.
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The purpose of this study was to examine the dietary views and practices and to identify associated barriers to and facilitators of healthy eating of rural residents emerging from poverty in the context of rapid socio-economic development. A qualitative design with semi-structured interviews was utilized to collect detailed insights into the dietary behaviors of 22 rural residents from 10 villages in Fengshan town, Dafang county, Guizhou province, China. Thematic analysis was applied to interpret the interview data, guided by the socio-ecological model. Four themes were identified: traditional eating patterns, factors influencing food choice, limited knowledge of healthy diet, and lack of nutritional guidance. Barriers to healthy eating included traditional but unhealthy foods, limited nutritional knowledge, inadequate understanding of nutritional requirements, overwhelming nutritional information, and limited professional guidance. Facilitators encompassed healthy traditional eating patterns, household composition, home gardening, preference for traditional bean and soy products, improved food supply and availability owing to poverty alleviation efforts, and being open to receiving professional dietary guidance. As a preliminary investigation into the dietary views and practices of this population, the study highlights a significant gap in the nutritional knowledge and guidance available to rural residents in China, emphasizing the need for comprehensive strategies that address the complex socio-ecological factors influencing dietary behaviors.
RESUMEN
Steamed green tea has a long history and unique aroma, but little is known about its key aroma components. In this study, 173 volatiles in steamed green tea were identified using solvent-assisted flavor evaporation and headspace-solid phase microextraction plus two chromatographic columns of different polarities. Aroma extract dilution analysis revealed 48 highly aroma-active compounds with flavor dilution factors 64-1024. Internal standards were used to calculate odorant active value (OAV), and 11 OAV > 1 key aroma compounds were determined. Omission test identified eight substances, including dimethyl sulfide, (E)-ß-ionone, cis-jasmone, linalool, nonanal, heptanal, isovaleraldehyde and (Z)-3-hexenol, as the key aroma active compounds of steamed green tea. With the increase of withering degree, the content of these substances increased first and then decreased except for heptanal and cis-jasmone. Moreover, the water content of 62 % was suggested to be an appropriate withering degree during the processing of steamed green tea.