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1.
Front Endocrinol (Lausanne) ; 13: 967739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36133311

RESUMO

In recent years, the incidence of infertility has been increasing gradually, while the natural rate of population growth is declining or even at zero growth. China is observed to enter a depth of aging society, leading to more severe infertility. Infertility patients face many predicaments, and many unreasonable behaviors existed in seeking medical diagnosis and treatment, of which the main influencing factor is economic condition. In China, Beijing has taken the lead in providing medical insurance for 16 assisted reproductive technology items. Assuming that all infertile couples with the option of assisted reproduction are treated, there would be a huge market gap. The reimbursement rate can be adjusted based on some factors within the affordable range of the medical insurance fund. Progress on infertility coverage in other countries was also reviewed. This paper cited the data of medical insurance funds in China in the recent 4 years as a reference. Based on the data, it is not currently able to cover all the costs of infertility diagnosis and treatment during the research period, but it is feasible to access selective reimbursement and subsidies for those in particular need as well as to develop some commercial insurances. There is a big gap in the application of assisted reproductive technology between China and developed countries. More comprehensive and constructive policies should be formulated countrywide to standardize the market. Assisted reproduction-related technologies and acceleration of the domestic medical apparatus and instrument replacement should be improved to reduce the cost.


Assuntos
Infertilidade , Seguro , China/epidemiologia , Estudos de Viabilidade , Humanos , Infertilidade/epidemiologia , Infertilidade/terapia , Técnicas de Reprodução Assistida
2.
Ecotoxicol Environ Saf ; 244: 114025, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36049332

RESUMO

Several literatures have examined the risk of chronic respiratory diseases in association with short-term ambient PM2.5 exposure in China. However, little evidence has examined the chronic impacts of PM2.5 exposure on morbidity of chronic respiratory diseases in cohorts from high pollution countries. Our study aims to investigate the associations. Based on a retrospective cohort among adults in northern China, a Cox regression model with time-varying PM2.5 exposure and a concentration-response (C-R) curve model were performed to access the relationships between incidence of chronic respiratory diseases and long-term PM2.5 exposure during a mean follow-up time of 9.8 years. Individual annual average PM2.5 estimates were obtained from a satellite-based model with high resolution. The incident date of a chronic respiratory disease was identified according to self-reported physician diagnosis time and/or intake of medication for treatment. Among 38,047 urban subjects analyzed in all-cause chronic respiratory disease cohort, 482 developed new cases. In CB (38,369), asthma (38,783), and COPD (38,921) cohorts, the onsets were 276, 89, and 14, respectively. After multivariable adjustment, hazard ratio and 95% confidence interval for morbidity of all-cause chronic respiratory disease, CB, asthma, and COPD were 1.15 (1.01, 1.31), 1.20 (1.00, 1.42), 0.76 (0.55, 1.04), and 0.66 (0.29, 1.47) with each 10 µg/m3 increment in PM2.5, respectively. Stronger effect estimates were suggested in alcohol drinkers across stratified analyses. Additionally, the shape of C-R curve showed an increasing linear relationship before 75.00 µg/m3 concentrations of PM2.5 for new-onset all-cause chronic respiratory disease, and leveled off at higher levels. These findings indicated that long-term exposure to high-level PM2.5 increased the risks of incident chronic respiratory diseases in China. Further evidence of C-R curves is warranted to clarify the associations of adverse chronic respiratory outcomes involving air pollution.

3.
J Med Internet Res ; 24(9): e37618, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069842

RESUMO

BACKGROUND: Pressure injury is a common complication after a spinal cord injury. Long-term multidisciplinary follow-up is difficult after such patients have been discharged. Telemedicine promises to provide convenient and effective support for the prevention and treatment of pressure injury, but previous attempts to demonstrate that have produced inconsistent results. OBJECTIVE: The aim of this study is to evaluate the effectiveness of telemedicine in preventing and treating pressure injury among community-dwelling patients with spinal cord injury, and determine which telemedicine form is more effective. METHODS: This systematic review was performed according to the PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Network Meta-Analysis) standards. Ten databases were searched to identify randomized controlled trials and quasi-experimental studies related to the effectiveness of telemedicine intervention in patients with spinal cord injury. Two researchers worked independently and blindly selected studies, extracted data, and assessed the risk of bias. The results were described as relative risk (RR) and weighted mean difference and 95% CI. RESULTS: The 35 studies comprised 25 randomized controlled trials and 10 quasi-experimental studies involving 3131 patients. The results showed that telemedicine can significantly (P<.05) reduce the incidence of pressure injury (RR 0.24, 95% CI 0.14-0.41; P<.05; I2=0%), promote faster healing (RR 0.73, 95% CI 0.62-0.85; P<.05; I2=0%), and yield lower scores on the pressure ulcer scale of healing (weighted mean difference=-1.98, 95% CI -3.51 to -0.46; P<.05; I2=0%). Cumulative ranking estimates showed that combining telemedicine with conventional intervention (93.5%) was the most effective approach. CONCLUSIONS: Telemedicine is a feasible way to prevent pressure injury among patients with spinal cord injuries. It can decrease the incidence and severity of pressure injury and accelerate patients' healing without imposing economic burden. It is best used in tandem with other, more conventional interventions. Due to the limited quality and quantity of included studies, large-scale and well-designed randomized controlled trials are warranted.


Assuntos
Lesão por Pressão , Traumatismos da Medula Espinal , Telemedicina , Humanos , Incidência , Vida Independente , Lesão por Pressão/etiologia , Lesão por Pressão/prevenção & controle , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/terapia
4.
Chem Biol Interact ; 367: 110171, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36108716

RESUMO

Selenium is a trace element that has been shown to inhibit the growth of various cancer cell types. However, its role in cervical cancer and its underlying mechanisms remains largely unknown. Herein, we explored the anti-cervical cancer effect of selenium and its potential mechanisms through xenograft and in vitro experiments. HeLa cell xenografts in female nude mice showed tumor growth retardation, with no obvious liver and kidney toxicity, after being intraperitoneally injected with 3 mg/kg sodium selenite (SS) for 14 days. Compared to the control group, selenium levels in the tumor tissue increased significantly after SS treatment. In vitro experiments, SS inhibited the viability of HeLa and SiHa cells, blocked the cell cycle at the S phase, and enhanced apoptosis. RNA-sequencing, Kyoto encyclopedia of genes and genomes pathway analysis showed that forkhead box protein O (FOXO) was a key regulatory signaling pathway for SS to exhibit anticancer effects. Gene Ontology analysis filtered multiple terms associated with apoptosis, anti-proliferation, and cell cycle arrest. Further research revealed that SS increased intracellular reactive oxygen species (ROS) and impaired mitochondrial function, which activated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) via phosphorylation at Thr172, resulting in activation of FOXO3a and its downstream growth arrest and DNA damage-inducible alpha (GADD45a). In summary, SS exhibited anti-cervical cancer effects, and their mechanisms may be that SS is involved in inducing cell cycle arrest and potentiating cell apoptosis caused by ROS-dependent activation of the AMPK/FOXO3a/GADD45a axis.

5.
Am J Pathol ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36150505

RESUMO

Blastoid/pleomorphic morphology is associated with short survival in mantle cell lymphoma (MCL), but its prognostic value is overridden by proliferation index Ki-67 in multivariate analysis. Here we developed a nuclear segmentation model using deep learning, and nuclei of tumor cells in 103 MCL cases were automatically delineated. Eight nuclear morphometric attributes, including length, width, perimeter, area, length/width ratio, circularity, irregularity, and entropy, were extracted from each nucleus. The mean, variance, skewness, and kurtosis of each attribute were calculated for each case, resulting in 32 morphometric parameters. Compared to classic MCL, 17 morphometric parameters were significantly different in blastoid/pleomorphic MCL. Using univariate analysis, 16 morphometric parameters (including 14 significantly different between classic and blastoid/pleomorphic MCL) were significant prognostic factors. Using multivariate analysis, biologic MCL international prognostic index (bMIPI) risk group (P=0.025), low skewness of nuclear irregularity (P=0.020), and high mean of nuclear irregularity (P=0.047) were independent adverse prognostic factors. Furthermore, a morphometric score calculated from the skewness and mean of nuclear irregularity (P=0.0038) was an independent prognostic factor in addition to bMIPI risk group (P=0.025), and a summed morphometric bMIPI score was useful for risk stratification of MCL patients (P=0.000001). Our results demonstrate for the first time that a nuclear morphometric score is an independent prognostic factor in MCL. It is more robust than blastoid/pleomorphic morphology and can be objectively measured.

6.
Cells ; 11(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36139441

RESUMO

Spermatogonial stem cells (SSCs) are unique adult stem cells capable of self-renewal and differentiation into sperm. Grouper is a protogynous hermaphroditic fish farmed widely in the tropical and subtropical seas. In this study, we established an SSC line derived from adult testis of orange-spotted grouper, Epinephelus coioides. In the presence of basic fibroblast growth factor (bFGF) and leukemia inhibitory factor (LIF), the cells could be maintained with proliferation and self-renewal over 20 months and 120 passages under in vitro culture conditions. The cells exhibited strong alkaline phosphatase activity and the characteristics of SSCs with the expression of germ cell markers, including Vasa, Dazl, and Plzf, as well as the stem cell markers Nanog, Oct4, and Ssea1. Furthermore, the cultured cells could be induced by 11-ketotestosterone treatment to highly express the meiotic markers Rec8, Sycp3, and Dmc1, and produce some spherical cells, and even sperm-like cells with a tail. The findings of this study suggested that the cultured grouper SSC line would serve as an excellent tool to study the molecular mechanisms behind SSCs self-renewal and differentiation, meiosis during spermatogenesis, and sex reversal in hermaphroditic vertebrates. Moreover, this SSC line has great application value in grouper fish aquaculture, such as germ cell transplantation, genetic manipulation, and disease research.

7.
NPJ Digit Med ; 5(1): 145, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109594

RESUMO

The mobile health (mHealth) industry is an enormous global market; however, the dropout or continuance of mHealth is a major challenge that is affecting its positive outcomes. To date, the results of studies on the impact factors have been inconsistent. Consequently, research on the pooled effects of impact factors on the continuance intention of mHealth is limited. Therefore, this study aims to systematically analyze quantitative studies on the continuance intention of mHealth and explore the pooled effect of each direct and indirect impact factor. Until October 2021, eight literature databases were searched. Fifty-eight peer-reviewed studies on the impact factors and effects on continuance intention of mHealth were included. Out of the 19 direct impact factors of continuance intention, 15 are significant, with attitude (ß = 0.450; 95% CI: 0.135, 0.683), satisfaction (ß = 0.406; 95% CI: 0.292, 0.509), health empowerment (ß = 0.359; 95% CI: 0.204, 0.497), perceived usefulness (ß = 0.343; 95% CI: 0.280, 0.403), and perceived quality of health life (ß = 0.315, 95% CI: 0.211, 0.412) having the largest pooled effect coefficients on continuance intention. There is high heterogeneity between the studies; thus, we conducted a subgroup analysis to explore the moderating effect of different characteristics on the impact effects. The geographic region, user type, mHealth type, user age, and publication year significantly moderate influential relationships, such as trust and continuance intention. Thus, mHealth developers should develop personalized continuous use promotion strategies based on user characteristics.

8.
J Colloid Interface Sci ; 629(Pt A): 571-581, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36088702

RESUMO

Novel reusable acid-resistant magnetic polymer nanospheres-immobilized MIL-100 (CoFe2O4@Polymer@MIL-100) catalyst was prepared by a layer-by-layer method to achieve a controllable structure. The obtained core-shell catalyst consisted of modified magnetic nanoparticles as the core, a carboxylic-functionalized polymer as the protective layer, and an MIL-100 shell as the active catalytic layer by chemical bonds on the polymer. The catalysts showed good stability, good magnetic saturation, and acid corrosion resistance. The thickness of the MIL-100 shell could be adjusted by controlling the metal salt concentration and the number of layer-by-layer cycles. Nano-sized MIL-100 showed better mass transfer efficiency and catalytic activity. A conversion of 97.7% after 10 min was observed during acetalization when using CoFe2O4@Polymer@MIL-100 as the catalyst. CoFe2O4@Polymer@MIL-100 could be reused at least five times. The use of a polymer layer on CoFe2O4@Polymer@MIL-100 prevented acidic ligands from corroding the magnetic core. Chemical bonds between MIL-100 and functional magnetic polymer cores improved the catalyst's stability. CoFe2O4@Polymer@MIL-100 exhibited high activity, excellent stability, and easy magnetic separation.

9.
PLoS One ; 17(9): e0268984, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36094942

RESUMO

OBJECTIVE: Low serum adiponectin level can predict hypertension development, and adiponectin gene (ADIPOQ) polymorphisms have been reported to be linked with hypertension risk. Whereas, the interaction between ADIPOQ polymorphisms and environmental factors on the susceptibility of hypertension remained unclear. The purpose of this study was to explore the relationship of ADIPOQ polymorphisms with hypertension risk and their interaction with lipid levels in coal miners. METHODS: A matched case-control study with 296 case-control pairs was performed in a large coal mining group located in North China. The participants were questioned by trained interviewers, and their ADIPOQ genotype and lipid levels were determined. Logistic regression, stratified analysis, and crossover analysis were applied to evaluate the effects of rs2241766, rs1501299, and rs266729 genotypes and gene-lipid interaction on hypertension risk. RESULTS: In this matched case-control study, the genotypes of rs2241766 TG+GG, rs1501299 GT+TT, and rs266729 CG+GG were marginally related to hypertension risk. Individuals with high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) level were susceptible to hypertension (TC: odds ratio [OR] = 1.807, 95% confidence intervals [95%CI] = 1.266-2.581; LDL-C: OR = 1.981, 95%CI = 1.400-2.803; HDL-C: OR = 1.559, 95%CI = 1.093-2.223). Antagonistic interactions were detected between rs2241766 and TC, rs1501299 and TC, rs2241766 and LDL-C, and rs1501299 and HDL-C (rs2241766 and TC: OR = 0.393, 95%CI = 0.191-0.806; rs1501299 and TC: OR = 0.445, 95%CI = 0.216-0.918; rs2241766 and LDL-C: OR = 0.440, 95%CI = 0.221-0.877; rs1501299 and HDL-C: OR = 0.479, 95%CI = 0.237-0.967). Stratified analysis showed that hypertension risk was high for the subjects with rs2241766 TG+GG or rs1501299 GG under the low lipid level but low for those under the high lipid level. In the case group, the TC and LDL-C levels for rs2241766 TG+GG were lower than those for rs2241766 GG, and the TC and HDL-C levels for rs1501299 GT+TT were higher than those for rs1501299 GG. CONCLUSIONS: Although the effects of ADIPOQ polymorphisms alone were not remarkable, an antagonistic interaction was observed between ADIPOQ polymorphisms and lipid levels.


Assuntos
Adiponectina , Hipertensão , Adiponectina/genética , Estudos de Casos e Controles , HDL-Colesterol/genética , LDL-Colesterol/genética , Carvão Mineral , Humanos , Hipertensão/genética , Polimorfismo de Nucleotídeo Único
10.
Colloids Surf B Biointerfaces ; 219: 112799, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36095954

RESUMO

While stem cell transplantation has emerged as a promising approach to improving wound healing outcomes, the application of stem cells to date has been limited by the poor survival and retention of these cells once transplanted. The survival, development, and migratory activity of transplanted cells can be improved through the use of three-dimensional (3D) culture systems. Here, a novel alginate microsphere-collage hydrogel (AMS-Col gel) 3D culture system was developed and found to improve human umbilical cord mesenchymal stem cell (hUCMSC) survival, permitting their sustained release so as to promote wound healing. Through hematoxylin and eosin staining and Masson's trichrome staining, the prepared hUCMSCs-AMS-Col gel was found to exhibit wound healing activity. On day 7 following the hUCMSCs-AMS-Col gel treatment of model wounds, improved collagen fiber deposition and re-epithelialization were evident, with complete epithelial regeneration as of day 14 and near-total wound healing was evident as of day 21. This hUCMSCs-AMS-Col gel was also associated with increased VEGF and FGF2 expression. Together, these data indicate that AMS-Col gels are a promising and novel form of 3D cell culture system capable of improving hUCMSC-mediated wound healing, highlighting the potential clinical utility of this regenerative strategy.

11.
BMC Anesthesiol ; 22(1): 284, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088288

RESUMO

BACKGROUND: Postoperative major adverse cardiovascular events (MACEs) account for more than one-third of perioperative deaths. Geriatric patients are more vulnerable to postoperative MACEs than younger patients. Identifying high-risk patients in advance can help with clinical decision making and improve prognosis. This study aimed to develop a machine learning model for the preoperative prediction of postoperative MACEs in geriatric patients. METHODS: We collected patients' clinical data and laboratory tests prospectively. All patients over 65 years who underwent surgeries in West China Hospital of Sichuan University from June 25, 2019 to June 29, 2020 were included. Models based on extreme gradient boosting (XGB), gradient boosting machine, random forest, support vector machine, and Elastic Net logistic regression were trained. The models' performance was compared according to area under the precision-recall curve (AUPRC), area under the receiver operating characteristic curve (AUROC) and Brier score. To minimize the influence of clinical intervention, we trained the model based on undersampling set. Variables with little contribution were excluded to simplify the model for ensuring the ease of use in clinical settings. RESULTS: We enrolled 5705 geriatric patients into the final dataset. Of those patients, 171 (3.0%) developed postoperative MACEs within 30 days after surgery. The XGB model outperformed other machine learning models with AUPRC of 0.404(95% confidence interval [CI]: 0.219-0.589), AUROC of 0.870(95%CI: 0.786-0.938) and Brier score of 0.024(95% CI: 0.016-0.032). Model trained on undersampling set showed improved performance with AUPRC of 0.511(95% CI: 0.344-0.667, p < 0.001), AUROC of 0.912(95% CI: 0.847-0.962, p < 0.001) and Brier score of 0.020 (95% CI: 0.013-0.028, p < 0.001). After removing variables with little contribution, the undersampling model showed comparable predictive accuracy with AUPRC of 0.507(95% CI: 0.338-0.669, p = 0.36), AUROC of 0.896(95%CI: 0.826-0.953, p < 0.001) and Brier score of 0.020(95% CI: 0.013-0.028, p = 0.20). CONCLUSIONS: In this prospective study, we developed machine learning models for preoperative prediction of postoperative MACEs in geriatric patients. The XGB model showed the best performance. Undersampling method achieved further improvement of model performance. TRIAL REGISTRATION: The protocol of this study was registered at www.chictr.org.cn (15/08/2019, ChiCTR1900025160).


Assuntos
Doenças Cardiovasculares , Aprendizado de Máquina , Idoso , Doenças Cardiovasculares/epidemiologia , Humanos , Modelos Logísticos , Prognóstico , Estudos Prospectivos
12.
Front Aging Neurosci ; 14: 962319, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118683

RESUMO

Objective: Progressive conditions characterized by cognitive decline, including mild cognitive impairment (MCI) and subjective cognitive decline (SCD) are clinical conditions representing a major risk factor to develop dementia, however, the diagnosis of these pre-dementia conditions remains a challenge given the heterogeneity in clinical trajectories. Earlier diagnosis requires data-driven approaches for improved and targeted treatment modalities. Methods: Neuropsychological tests, baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI (rsfMRI), and diffusion weighted scans were obtained from 35 patients with SCD, 19 with MCI, and 36 age-matched healthy controls (HC). A recently developed machine learning technique, Hollow Tree Super (HoTS) was utilized to classify subjects into diagnostic categories based on their FC, and derive network and parcel-based FC features contributing to each model. The same approach was used to identify features associated with performance in a range of neuropsychological tests. We concluded our analysis by looking at changes in PageRank centrality (a measure of node hubness) between the diagnostic groups. Results: Subjects were classified into diagnostic categories with a high area under the receiver operating characteristic curve (AUC-ROC), ranging from 0.73 to 0.84. The language networks were most notably associated with classification. Several central networks and sensory brain regions were predictors of poor performance in neuropsychological tests, suggesting maladaptive compensation. PageRank analysis highlighted that basal and limbic deep brain region, along with the frontal operculum demonstrated a reduction in centrality in both SCD and MCI patients compared to controls. Conclusion: Our methods highlight the potential to explore the underlying neural networks contributing to the cognitive changes and neuroplastic responses in prodromal dementia.

13.
EBioMedicine ; 84: 104267, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36116213

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) exhibits significant familial aggregation; however, its susceptibility genes are largely unknown. Thus, this study aimed to identify germline mutations that might contribute to the risk of familial NPC, and explore their biological functions. METHODS: Whole-exome sequencing was performed in 13 NPC pedigrees with multiple cases. Mutations co-segregated with disease status were further validated in a cohort composed of 563 probands from independent families, 2,953 sporadic cases, and 3,175 healthy controls. Experimental studies were used to explore the functions of susceptibility genes and their disease-related mutations. FINDINGS: The three rare missense mutations in POLN (DNA polymerase nu) gene, P577L, R303Q, and F545C, were associated with familial NPC risk (5/576 [0·87%] in cases vs. 2/3374 [0·059%] in healthy controls with an adjusted OR of 44·84 [95% CI:3·91-514·34, p = 2·25 × 10-3]). POLN was involved in Epstein-Barr virus (EBV) lytic replication in NPC cells in vitro. POLN promoted viral DNA replication, immediate-early and late lytic gene expression, and progeny viral particle production, ultimately affecting the proliferation of host cells. The three mutations were located in two pivotal functional domains and were predicted to alter the protein stability of POLN in silico. Further assays demonstrated that POLN carrying any of the three mutations displayed reduced protein stability and decreased expression levels, thereby impairing its ability to promote complete EBV lytic replication and facilitate cell survival. INTERPRETATION: We identified a susceptibility gene POLN for familial NPC and elucidated its function. FUNDING: This study was funded by the National Key Research and Development Program of China (2021YFC2500400); the National Key Research and Development Program of China (2020YFC1316902); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the National Natural Science Foundation of China (81973131); the National Natural Science Foundation of China (82003520); the National Natural Science Foundation of China (81903395).

14.
Front Endocrinol (Lausanne) ; 13: 893238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147561

RESUMO

Hypothalamus-pituitary-adrenal (HPA) axis plays critical roles in stress responses under challenging conditions such as hypoxia, via regulating gene expression and integrating activities of hypothalamus-pituitary-targets cells. However, the transcriptional regulatory mechanisms and signaling pathways of hypoxic stress in the pituitary remain to be defined. Here, we report that hypoxia induced dynamic changes in the transcription factors, hormones, and their receptors in the adult rat pituitary. Hypoxia-inducible factors (HIFs), oxidative phosphorylation, and cAMP signaling pathways were all differentially enriched in genes induced by hypoxic stress. In the pituitary gene network, hypoxia activated c-Fos and HIFs with specific pituitary transcription factors (Prop1), targeting the promoters of hormones and their receptors. HIF and its related signaling pathways can be a promising biomarker during acute or constant hypoxia. Hypoxia stimulated the transcription of marker genes for microglia, chemokines, and cytokine receptors of the inflammatory response. Corticotropin-releasing hormone receptor 1 (CRHR1) mediated the transcription of Pomc, Sstr2, and Hif2a, and regulated the function of HPA axis. Together with HIF, c-Fos initiated and modulated dynamic changes in the transcription of hormones and their receptors. The receptors were also implicated in the regulation of functions of target cells in the pituitary network under hypoxic stress. CRHR1 played an integrative role in the hypothalamus-pituitary-target axes. This study provides new evidence for CRHR1 involved changes of hormones, receptors, signaling molecules and pathways in the pituitary induced by hypoxia.

15.
Front Mol Biosci ; 9: 843580, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060258

RESUMO

The aim of our study is to reveal the hub genes related to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and their association with immune cell infiltration through bioinformatics analysis combined with experimental validation. In this study, through differential gene expression analysis, 1,516 upregulated and 1,307 downregulated DEG were obtained from dataset GSE136825 of the GEO database. We identified 14 co-expressed modules using weighted gene co-expression network analysis (WGCNA), among which the most significant positive and negative correlations were MEgreen and MEturquoise modules, containing 1,540 and 3,710 genes respectively. After the intersection of the two modules and DEG, two gene sets-DEG-MEgreen and DEG-MEturquoise-were obtained, containing 395 and 1,168 genes respectively. Through GO term analysis, it was found that immune response and signal transduction are the most important biological processes. We found, based on KEGG pathway enrichment analysis, that osteoclast differentiations, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions are the most important in the two gene sets. Through PPI network analysis, we listed the top-ten genes for the concentrated connectivity of the two gene sets. Next, a few genes were verified by qPCR experiments, and FPR2, ITGAM, C3AR1, FCER1G, CYBB in DEG-MEgreen and GNG4, NMUR2, and GNG7 in DEG-MEturquoise were confirmed to be related to the pathogenesis of CRSwNP. NP immune cell infiltration analysis revealed a significant difference in the proportion of immune cells between the NP group and control group. Finally, correlation analysis between target hub genes and immune cells indicated that FPR2 and GNG7 had a positive or negative correlation with some specific immune cells. In summary, the discoveries of these new hub genes and their association with immune cell infiltration are of great significance for uncovering the specific pathogenesis of CRSwNP and searching for disease biomarkers and potential therapeutic targets.

16.
Chem Commun (Camb) ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098079

RESUMO

A novel strategy for the synthesis of 2-arylethenesulfonyl fluorides from nitrones and ethenesulfonyl fluoride (ESF) by the activation of the C-H bond using an inexpensive and readily available Ru-catalyst has been developed. In this process, the directing group can be concomitantly converted to an amide group. Interestingly, changing the substituent of the nitrogen of nitrones from a tert-butyl to a methyl group resulted in the formation of cyclic isoindolinones. Detailed mechanistic studies are also presented.

17.
Front Cell Neurosci ; 16: 971100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072565

RESUMO

This study aimed to explore the mechanism underlying cognitive dysfunction mediated by the lateral hypothalamic area (LHA) in a hypothalamic-hippocampal circuit in rats with lesion-induced hypothalamic obesity (HO). The HO model was established by electrically lesioning the hypothalamic nuclei. The open field (OP) test, Morris water maze (MWM), novel object recognition (NOR), and novel object location memory (NLM) tests were used to evaluate changes in cognition due to alterations in the hypothalamic-hippocampal circuit. Western blotting, immunohistochemical staining, and cholera toxin subunit B conjugated with Alexa Fluor 488 (CTB488) reverse tracer technology were used to determine synaptophysin (SYN), postsynaptic density protein 95 (PSD95), ionized calcium binding adaptor molecule 1 (Iba1), neuronal nuclear protein (NeuN), and Caspase3 expression levels and the hypothalamic-hippocampal circuit. In HO rats, severe obesity was associated with cognitive dysfunction after the lesion of the hypothalamus. Furthermore, neuronal apoptosis and activated microglia in the downstream of the lesion area (the LHA) induced microglial infiltration into the intact hippocampus via the LHA-hippocampal circuit, and the synapses engulfment in the hippocampus may be the underlying mechanism by which the remodeled microglial mediates memory impairments in HO rats. The HO rats exhibited microglial infiltration and synapse loss into the hippocampus from the lesioned LHA via the hypothalamic-hippocampal circuit. The underlying mechanisms of memory function may be related to the circuit.

18.
Immunology ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069580

RESUMO

Endometriosis is a gynaecological condition characterized by the growth of endometrium-like tissues within and outside of the pelvic cavity. Recent studies have demonstrated that aberrant infiltration of M2 macrophages is mainly responsible for the establishment of endometriotic lesions. A growing body of evidence shows that glycolysis and lactate accumulation have great impact on the regulation of immunomicroenvironment. However, the communication signal between glycolysis and macrophages is poorly defined in endometriosis. Hereby, we investigate the correlation between glycolysis and M2 macrophage infiltration in endometriosis. Next, we confirm that lactate is pivotal factor that drives macrophage M2-polarization to promote endoemetriotic stromal cells invasion in vitro and in vivo. In addition, we also identify that the activation of Mettl3 and its target gene Trib1 promote M2 macrophage polarization. Moreover, we also demonstrate that Trib1 induce M2 macrophage polarization via the activation of ERK/ STAT3 signaling pathway. Finally, by injecting 2-DG into endometriosis mice model, we show that the restrain of glycolysis significantly reduces the progression of endometriosis, which provides evidence for lactate as a potential therapeutic strategy for the prevention and treatment of endometriosis.

19.
Sensors (Basel) ; 22(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36146264

RESUMO

Space-time adaptive processing (STAP) is a well-known technique for slow-moving target detection in the clutter spreading environment. For an airborne conformal array radar, conventional STAP methods are unable to provide good performance in suppressing clutter because of the geometry-induced range-dependent clutter, non-uniform spatial steering vector, and polarization sensitivity. In this paper, a knowledge aided STAP method based on sparse learning via iterative minimization (SLIM) combined with Laplace distribution is proposed to improve the STAP performance for a conformal array. The proposed method can avoid selecting the user parameter. the proposed method constructs a dictionary matrix that is composed of the space-time steering vector by using the prior knowledge of the range cell under test (CUT) distributed in clutter ridge. Then, the estimated sparse parameters and noise power can be used to calculate a relatively accurate clutter plus noise covariance matrix (CNCM). This method could achieve superior performance of clutter suppression for a conformal array. Simulation results demonstrate the effectiveness of this method.

20.
Front Neural Circuits ; 16: 955728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105683

RESUMO

Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is an innovative therapy in stroke rehabilitation which has been verified in clinical studies. However, the underlying mechanism of CCNMES are yet to be comprehensively revealed. The main purpose of this study was to apply functional near-infrared spectroscopy (fNIRS) to compare CCNMES-related changes in functional connectivity (FC) within a cortical network after stroke with those induced by neuromuscular electrical stimulation (NMES) when performing wrist extension with hemiplegic upper extremity. Thirty-one stroke patients with right hemisphere lesion were randomly assigned to CCNMES (n = 16) or NMES (n = 15) groups. Patients in both groups received two tasks: 10-min rest and 10-min electrical stimulation task. In each task, the cerebral oxygenation signals in the prefrontal cortex (PFC), bilateral primary motor cortex (M1), and primary sensory cortex (S1) were measured by a 35-channel fNIRS. Compared with NMES, FC between ipsilesional M1 and contralesional M1/S1 were significantly strengthened during CCNMES. Additionally, significantly higher coupling strengths between ipsilesional PFC and contralesional M1/S1 were observed in the CCNMES group. Our findings suggest that CCNMES promotes the regulatory functions of ipsilesional prefrontal and motor areas as well as contralesional sensorimotor areas within the functional network in patients with stroke.


Assuntos
Córtex Motor , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Elétrica , Humanos , Córtex Motor/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral/métodos
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