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2.
Brief Bioinform ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850815

RESUMO

MOTIVATION: The development process of a new drug is time-consuming and costly. Thus, identifying new uses for approved drugs, named drug repositioning, is helpful for speeding up the drug development process and reducing development costs. Existing drug-related disease prediction methods mainly focus on single or multiple drug-disease heterogeneous networks. However, heterogeneous networks, and drug subnets and disease subnet contained in heterogeneous networks cover the common topology information between drug and disease nodes, the specific information between drug nodes and the specific information between disease nodes, respectively. RESULTS: We design a novel model, CTST, to extract and integrate common and specific topologies in multiple heterogeneous networks and subnets. Multiple heterogeneous networks composed of drug and disease nodes are established to integrate multiple kinds of similarities and associations among drug and disease nodes. These heterogeneous networks contain multiple drug subnets and a disease subnet. For multiple heterogeneous networks and subnets, we then define the common and specific representations of drug and disease nodes. The common representations of drug and disease nodes are encoded by a graph convolutional autoencoder with sharing parameters and they integrate the topological relationships of all nodes in heterogeneous networks. The specific representations of nodes are learned by specific graph convolutional autoencoders, respectively, and they fuse the topology and attributes of the nodes in each subnet. We then propose attention mechanisms at common representation level and specific representation level to learn more informative common and specific representations, respectively. Finally, an integration module with representation feature level attention is built to adaptively integrate these two representations for final association prediction. Extensive experimental results confirm the effectiveness of CTST. Comparison with six latest methods and case studies on five drugs further verify CTST has the ability to discover potential candidate diseases.

3.
Gan To Kagaku Ryoho ; 48(11): 1381-1387, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34795131

RESUMO

AIM: We evaluated the safety and potential clinical impact of shortened ramucirumab infusion in Japanese patients from clinical studies. METHODS: Multivariate logistic regression analysis was used to assess any association between infusion rate and increased risk of an immediate infusion-related reaction(IRR). Population pharmacokinetic modeling was used to simulate concentration-time profiles and exposure parameters following a 30- or 60-minute infusion with ramucirumab. RESULTS: From 8 pooled ramucirumab clinical studies, 55 of 559(9.8%)Japanese patients experienced at least one immediate IRR(any grade). When grouped according to infusion rate quartile, the incidence of immediate any-grade IRR was similar across quartiles. Infusion rate was not significantly associated with an increased risk of an immediate IRR; odds ratio per 1 mg/min increase was 0.912, 95% confidence interval 0.724 to 1.149, p=0.436. Patients aged ≥65 years may have a reduced risk of an immediate IRR compared with those aged <65 years, and premedication use was also associated with a reduced risk. Ramucirumab pharmacokinetic profiles were comparable following a 30- or 60-minute infusion. CONCLUSIONS: A shortened infusion duration of ramucirumab is unlikely to affect the efficacy or safety profile in Japanese patients and may be clinically beneficial for patients and health care providers. CLINICAL TRIAL REGISTRATION: RAINBOW-NCT01170663, RAISE- NCT01183780, REACH-NCT01140347, REACH-2-NCT02435433, RAINFALL-NCT02314117, RANGE-NCT02426125, RELAY-NCT02411448, I4T-MC-JVCG-NCT01703091.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Idoso , Ensaios Clínicos como Assunto , Humanos , Japão , Fatores de Tempo
4.
EBioMedicine ; 73: 103669, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34749302

RESUMO

BACKGROUND: Although the association between hypothyroidism and idiopathic pulmonary fibrosis (IPF) is found in observational studies, it remains uncertain whether hypothyroidism causally influences IPF. METHODS: Two-sample Mendelian randomisation (MR) was conducted with hypothyroidism genome-wide association study (GWAS) data in the UK Biobank from 289,307 individuals (18,740 cases and 270,567 controls) and the largest GWAS summary statistics of IPF from 11,259 individuals (2,668 cases and 8,591 controls). Findings were verified using an independent validation dataset, as well as through different MR methods with different model assumptions. A multivariable MR based on Bayesian model averaging was further performed to evaluate whether hypothyroidism, even given several other comorbidities of IPF, remained to be the true causal one of IPF. FINDINGS: A positive causal effect of hypothyroidism on IPF was revealed (MR inverse-variance weighted [MR-IVW], odds ratio [OR]=1.125, 95% confidence interval [CI] 1.028-1.231; P=0.011), which was further verified in an independent validation set (MR-IVW, OR=1.229, 95% CI 1.054-1.432; P=0.008). The results were consistent from a variety of MR methods. Bidirectional analyses also indicated no reverse causation. Multivariable MR analysis showed hypothyroidism had the strongest marginal evidence (marginal inclusion probability=0.397, false discovery rate=0.025) compared with other comorbidities of IPF. INTERPRETATION: Our results illustrate the significant causal effect of hypothyroidism on IPF, which holds even given several other comorbidities of IPF. These findings may have an important insight into pathogenesis and possible future therapies of IPF. FUNDING: National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province and the Young Scholars Program of Shandong University.

5.
BMJ Open ; 11(11): e047564, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824106

RESUMO

INTRODUCTION: A surrogate marker to evaluate artery endothelial response when stimulated by reactive hyperaemia, known as brachial flow-mediated dilation (FMD), has prognostic value in predicting hypertensive organ damage and cardiovascular disease events. However, the degree of correlation between brachial FMD and masked hypertension (MH) outcomes is still unclear. Therefore, the purpose of this study is to pool data regarding FMD with respect to MH. METHODS AND ANALYSIS: Electronic databases MEDLINE, EMBASE, China National Knowledge Infrastructure and Cochrane Library will be searched for the following keywords: endothelial dysfunction, flow-mediated dilation, and masked hypertension, masked uncontrolled hypertension (MUCH) and prehypertension. The following are the eligibility criteria: population-adults (18 years old or older) without hypertension at baseline, with suspected endothelial dysfunction, or from MH/MUCH populations (office blood pressure <140/90 mm Hg and home blood pressure ≥135 mm Hg and/or 85 mm Hg) and from controlled clinical trials, cohort studies, or randomised and controlled trials; exposures-any metrics for FMD; comparisons-participants without MH or MUCH; and outcome-change in FMD between the case group and the control group. Two authors will be engaged in screening and collecting data independently; disagreements will be resolved through discussion. Data extraction will include primary data designated as HR, OR, correlations and regression coefficients. Comprehensive Meta-Analysis V.2.0 will be used to conduct related subgroup and sensitivity analyses and publication bias. ETHICS AND DISSEMINATION: This study does not require ethics approval. It will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020208362.

6.
Am J Cancer Res ; 11(10): 4826-4843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765295

RESUMO

Circulating RNAs (circRNAs) are involved in tumor development and progression by participating in immune regulation. Nevertheless, the circRNAs expression profiles and their roles on the immunomodulatory effects in cutaneous squamous cell carcinoma (cSCC) have rarely been studied. In our study, we identified the differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), mRNAs (DEmRNAs) in cSCC and established the circRNA competing endogenous RNAs (ceRNAs) network. Subsequently, the hub differentially expressed immune-related genes were identified and validated by immunochemistry as well as the GO and KEGG pathway analysis were performed. 54 differentially expressed circRNAs were identified and hub differentially expressed immune-related genes were identified and they were mostly associated with immune response in the progression of cSCC. Our results indicated that the potential immune-related circRNA-miRNA-mRNA network may assist in understanding the molecular mechanisms underlying the carcinogenesis and progression in cSCC. Moreover, the immune-related genes may provide an insight into the pathogenesis, molecular biomarkers, and potential therapeutic targets for cSCC patients.

7.
J Med Chem ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34813314

RESUMO

Targeting poly(ADP-ribose) polymerase1/2 (PARP1/2) is a promising strategy for the treatment of pancreatic cancer with breast cancer susceptibility gene (BRCA) mutation. Inducing the deficiency of homologous recombination (HR) repair is an effective way to broaden the indication of PARP1/2 inhibitor for more patients with pancreatic cancer. Bromodomain-containing protein 4 (BRD4) repression has been reported to elevate HR deficiency. Therefore, we designed, synthetized, and optimized a dual PARP/BRD4 inhibitor III-16, with a completely new structure and high selectivity against PARP1/2 and BRD4. III-16 showed favorable synergistic antitumor efficacy in pancreatic cancer cells and xenografts by arresting cell cycle progression, inhibiting DNA damage repair, and promoting autophagy-associated cell death. Moreover, III-16 reversed Olaparib-induced acceleration of cell cycle progression and recovery of DNA repair. The advantages of III-16 over Olaparib suggest that dual PARP/BRD4 inhibitors are novel and promising agents for the treatment of advanced pancreatic cancer.

8.
Free Radic Biol Med ; 178: 1-6, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34808334

RESUMO

OBJECTIVE: The clinical research on BH4 is limited because of the difficulties on its measurement. In this study, we used our own established LC-MS/MS method to examine the plasma BH4 levels in diabetes to determine whether it could be used as a biomarker for the prediction of kidney injury in those patients. METHODS: Hospitalized diabetes patients in Renmin Hospital of Wuhan University from Jan to Aug 2021 were recruited. To assess the association between plasma BH4 with ACR or eGFR in diabetes, a total of 142 patients with type 2 diabetes (T2DM) were enrolled. They were divided into three groups by albuminuria levels: normoalbuminuria (n = 68), microalbuminuria (n = 48), and macroalbuminuria (n = 26) according to ACR; or into two groups by eGFR: eGFR≥90 or eGFR<90 ml/min for correlation and logistic regression analysis. Plasma BH4 level was measured by LC-MS/MS along with other biochemical indices. RESULTS: Plasma BH4 concentrations were decreased as ACR progressed. BH4 (r = -0.55, P < 0.001) and 2h C-Peptide (CP-2h) (r = -0.248, P = 0.003) levels were negatively correlated with ACR. Moreover, multivariable logistic regression analysis showed BH4 concentrations (B = -0.468, P < 0.001) and CP-2h (B = -0.257, P = 0.028) were independently associated with ACR progression. ROC curve showed that BH4 level has a predictive value on ACR (95%CI 0.686-0.841, sensitivity 69.1%, specificity 73%). Moreover, in diabetes patients with eGFR≥90 ml/min, plasma BH4 level (P = 0.008) is higher than those in diabetes with eGFR<90 ml/min and BH4 was remained independently associated with eGFR after multivariable logistic regression analysis (B = -0.193, P = 0.048). CONCLUSION: Our established LC-MS/MS method could be used on human plasma BH4 measurements and our data suggested that BH4 level can be used as a biomarker for kidney injury in diabetes indicated by its association with ACR progression and early renal function decline.

9.
J BUON ; 26(5): 2003-2009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34761610

RESUMO

PURPOSE: To study the treatment effect of concurrent chemoradiotherapy (CCRT) after surgery and its effect on postoperative swallowing function of patients with locally advanced hypopharyngeal carcinoma. METHODS: The clinical data of 84 patients with advanced hypopharyngeal carcinoma treated in our hospital were retrospectively analyzed. The patients were randomly divided into experimental group and control group, with 42 cases in each group. After both groups of patients were treated with radical neck dissection, the control group received adjuvant radiotherapy while the experimental group received CCRT. RESULTS: The Burke score in the experimental group after treatment was significantly lower than that in the control group (p<0.001). The objective remission rate in the experimental group was significantly higher than that in the control group (p<0.05). The jitter and shimmer in the experimental group after treatment were significantly lower than those in the control group (p<0.05). The quality of life scores of patients in the two groups after treatment were significantly higher than those before treatment (p<0.001), and the quality of life score in the experimental group was significantly higher than that in the control group (p<0.001). And the incidence of gastrointestinal reactions and neutropenia in the experimental group after treatment was significantly lower than that in the control group (p<0.05). The 3-year cumulative survival rate after surgery in the experimental group was significantly higher than in the control group (p<0.05). CONCLUSIONS: CCRT after surgery can effectively improve the swallowing function of patients with locally advanced hypopharyngeal carcinoma, which is worthy of promotion and application.

10.
Child Maltreat ; : 10775595211046550, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730029

RESUMO

A growing body of research has documented that childhood maltreatment is associated with increased risk of child aggression. However, little is known about the mediating and moderating mechanisms underlying the relationships between childhood maltreatment and reactive and proactive functions of aggression. Therefore, the present study examined whether callous-unemotional traits mediated the relationships between childhood maltreatment and two subtypes of aggression and whether these mediating processes were moderated by friendship quality. A cross-sectional study was conducted among 2407 adolescents between 11 and 16 years (M age = 12.75, SD = .58) in Shanxi province, China. Participants filled out questionnaires regarding childhood maltreatment, callous-unemotional traits, aggression, and friendship quality. The results indicated that childhood maltreatment was significantly and positively associated with proactive and reactive aggression, and these relationships were partially mediated by callous-unemotional traits after controlling for demographic variables. Friendship quality moderated the relationship between childhood maltreatment and proactive aggression as well as callous-unemotional traits and proactive aggression. These relationships became weaker for adolescents with high levels of friendship quality. Friendship quality did not moderate the effects of childhood maltreatment and callous-unemotional traits on reactive aggression.

12.
Front Oncol ; 11: 761379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746001

RESUMO

Oral squamous cell carcinoma (OSCC) is a kind of malignant tumors with low survival rate and prone to have early metastasis and recurrence. Cisplatin is an alkylating agent which induces DNA damage through the formation of cisplatin-DNA adducts, leading to cell cycle arrest and apoptosis. In the management of advanced OSCC, cisplatin-based chemotherapy or chemoradiotherapy has been considered as the first-line treatment. Unfortunately, only a portion of OSCC patients can benefit from cisplatin treatment, both inherent resistance and acquired resistance greatly limit the efficacy of cisplatin and even cause treatment failure. Herein, this review outline the underlying mechanisms of cisplatin resistance in OSCC from the aspects of DNA damage and repair, epigenetic regulation, transport processes, programmed cell death and tumor microenvironment. In addition, this review summarizes the strategies applicable to overcome cisplatin resistance, which can provide new ideas to improve the clinical therapeutic outcome of OSCC.

13.
Midwifery ; 103: 103152, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34601233

RESUMO

OBJECTIVE: Pregnant women with recurrent miscarriage have high rates of anxiety and depression. Mindfulness-based interventions have shown benefits in improving mental health in diverse populations; however, few studies have explored their efficacy in pregnant women with recurrent miscarriage, which was investigated in the present study. DESIGN: A nonrandomized controlled study was carried out from August 2019 to November 2020. SETTING: The study was conducted at a regional teaching hospital in Guangzhou, China that provides leading care for recurrent miscarriage. PARTICIPANTS: A total of 158 pregnant women with recurrent miscarriage were recruited and allocated to the intervention group (n = 79) or the control group (n = 79); 131 women completed the study. INTERVENTION: The mindfulness-based intervention consisted of a 1-h education session and daily mindfulness exercises guided by audio recordings during hospitalization. MEASUREMENTS AND FINDINGS: Study outcomes included perceived stress measured with the Perceived Stress Scale; symptoms of anxiety and depression measured with the Self-rating Anxiety Scale and Edinburgh Postnatal Depression Scale, respectively; and positive and negative affect measured with the Positive Affect and Negative Affect Scale - Revised, respectively. Compared to the control group, participants in the intervention group showed significant decreases in perceived stress, depression symptoms, and negative affect and an increase in positive affect after the intervention. Anxiety increased significantly in the control group during the study but remained unchanged in the intervention group. KEY CONCLUSIONS: A mindfulness-based intervention can reduce psychological symptoms and improve mental health in pregnant women with recurrent miscarriage. IMPLICATIONS FOR PRACTICE: A mindfulness-based intervention should be incorporated into routine care to help improve the mental health of pregnant women with recurrent miscarriage.


Assuntos
Aborto Habitual , Atenção Plena , Aborto Habitual/prevenção & controle , Ansiedade/prevenção & controle , China , Depressão/terapia , Feminino , Humanos , Gravidez , Gestantes , Estresse Psicológico/prevenção & controle
14.
Nutrients ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684457

RESUMO

A high maternal triglyceride (mTG) level during early pregnancy is linked to adverse pregnancy outcomes, but the use of specific interventions has been met with limited success. A retrospective cohort study was designed to investigate the impact of gestational weight gain (GWG) on the relationship between high levels of mTG and adverse pregnancy outcomes in normal early pregnancy body mass index (BMI) women. The patients included 39,665 women with normal BMI who had a singleton pregnancy and underwent serum lipids screening during early pregnancy. The main outcomes were adverse pregnancy outcomes, including gestational hypertension, preeclampsia, gestational diabetes, cesarean delivery, preterm birth, and large or small size for gestational age (LGA or SGA) at birth. As a result, the high mTG (≥2.05mM) group had increased risks for gestational hypertension ((Adjusted odds ratio (AOR), 1.80; 95% CI, 1.46 to 2.24)), preeclampsia (1.70; 1.38 to 2.11), gestational diabetes (2.50; 2.26 to 2.76), cesarean delivery (1.22; 1.13 to 1.32), preterm birth (1.42, 1.21 to 1.66), and LGA (1.49, 1.33 to 1.68) compared to the low mTG group, after adjustment for potential confounding factors. Additionally, the risks of any adverse outcome were higher in each GWG subgroup among women with high mTG than those in the low mTG group. High mTG augmented risks of gestational hypertension, preeclampsia, preterm birth, and LGA among women with 50th or greater percentile of GWG. Interestingly, among women who gained less than the 50th percentile of GWG subgroups, there was no relationship between high mTG level and risks for those pregnancy outcomes when compared to low mTG women. Therefore, weight control and staying below 50th centile of the suggested GWG according to gestational age can diminish the increased risks of adverse pregnancy outcomes caused by high mTG during early pregnancy.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação , Resultado da Gravidez , Triglicerídeos/sangue , Adulto , Feminino , Idade Gestacional , Humanos , Gravidez , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco , Adulto Jovem
15.
J Nanobiotechnology ; 19(1): 307, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620160

RESUMO

BACKGROUND: As one of the leading threats for health among women worldwide, breast cancer has high morbidity and mortality. Surgical resection is the major clinical intervention for primary breast tumor, nevertheless high local recurrence risk and breast tissue defect remain two main clinical dilemmas, seriously affecting survival and quality of life of patients. EXPERIMENTAL: We developed a thermoresponsive and injectable hybrid hydrogel platform (IR820/Mgel) by integration of co-loaded porous microspheres (MPs) and IR820 for preventing postoperative recurrence of breast cancer via photothermal therapy and promoting subsequent breast reconstruction. RESULTS: Our results suggested that IR820/Mgel could quickly heated to more than 50.0 â„ƒ under NIR irradiation, enabling killing effect on 4T1 cells in vitro and prevention effect on post-surgical tumor recurrence in vivo. In addition, the hydrogel platform was promising for its minimal invasion and capability of filling irregularly shaped defects after surgery, and the encapsulated MPs could help to increase the strength of gel to realize a long-term in situ function in vivo, and promoted the attachment and anchorage property of normal breast cells and adipose stem cells. CONCLUSIONS: This photothermal hydrogel platform provides a practice paradigm for preventing locally recurrence of breast cancer and a potential option for reconstruction of breast defects.

16.
Front Oncol ; 11: 706415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604044

RESUMO

Background: Gastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown. Methods: CircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK). Results: The level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer. Conclusion: Collectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.

17.
J Gene Med ; : e3391, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34612550

RESUMO

BACKGROUND: Circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) has previously been reported to play a key role in carcinogenesis. Nevertheless, the role of circ-ITCH in nasopharyngeal carcinoma (NPC) remains to be explored. METHODS: Gene expression analysis was performed using a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. The role of circ-ITCH in NPC was explored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, colony formation, transwell invasion, scratch healing and xenograft tumor assays. Furthermore, luciferase reporter assay was carried out to assess the interactions among circ-ITCH, microRNA-214 (miR-214) and phosphatase and tensin homolog (PTEN). RESULTS: The levels of circ-ITCH and PTEN were decreased, whereas the level of miR-214 was increased in NPC tissues collected from 28 subjects compared to normal nasopharynx tissues collected from 15 subjects. Moreover, a negative correlation between circ-ITCH and miR-214 expression and a positive correlation between circ-ITCH and PTEN expression were observed in NPC tissues. Downregulation of circ-ITCH expression was also observed in NPC cell lines. In addition, upregulation of circ-ITCH markedly inhibited NPC cell proliferation, migration and invasion. Furthermore, circ-ITCH was confirmed to exert its function by sponging miR-214. PTEN was found to be a direct target gene of miR-214 and its expression was negatively correlated with miR-214 expression in NPC tissues. Moreover, our results showed that the circ-ITCH/miR-214 axis regulated NPC proliferation, migration and invasion through regulating the expression of PTEN. Upregulation of circ-ITCH or PTEN blocked miR-214-mediated promotion of NPC tumorigenesis in vitro. Additionally, upregulation of circ-ITCH also suppressed NPC tumorigenesis in vivo. CONCLUSIONS: The present study demonstrated that circ-ITCH suppressed NPC tumorigenesis by upregulating PTEN expression through interacting with miR-214, thus proposing a novel mechanism for NPC inhibition.

18.
J Neuroinflammation ; 18(1): 226, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645465

RESUMO

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a severe anoxic brain injury that leads to premature mortality or long-term disabilities in infants. Neuroinflammation is a vital contributor to the pathogenic cascade post-HIE and a mediator to secondary neuronal death. As a plasma membrane G-protein-coupled receptor, GPR39, exhibits anti-inflammatory activity in several diseases. This study aimed to explore the neuroprotective function of GPR39 through inhibition of inflammation post-hypoxic-ischemic (HI) injury and to elaborate the contribution of sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)/nuclear factor, erythroid 2 like 2(Nrf2) in G-protein-coupled receptor 39 (GPR39)-mediated protection. METHODS: A total of 206 10-day-old Sprague Dawley rat pups were subjected to HIE or sham surgery. TC-G 1008 was administered intranasally at 1 h, 25 h, 49 h, and 73 h post-HIE induction. SIRT1 inhibitor EX527, GPR39 CRISPR, and PGC-1α CRISPR were administered to elucidate the underlying mechanisms. Brain infarct area, short-term and long-term neurobehavioral tests, Nissl staining, western blot, and immunofluorescence staining were performed post-HIE. RESULTS: The expression of GPR39 and pathway-related proteins, SIRT1, PGC-1α and Nrf2 were increased in a time-dependent manner, peaking at 24 h or 48-h post-HIE. Intranasal administration of TC-G 1008 reduced the percent infarcted area and improved short-term and long-term neurological deficits. Moreover, TC-G 1008 treatment significantly increased the expression of SIRT1, PGC-1α and Nrf2, but downregulated the expressions of IL-6, IL-1ß, and TNF-α. GPR39 CRISPR EX527 and PGC-1α CRISPR abolished GPR39's neuroprotective effects post-HIE. CONCLUSIONS: TC-G 1008 attenuated neuroinflammation in part via the SIRT1/PGC-1α/Nrf2 pathway in a neonatal rat model of HIE. TC-G 1008 may be a novel therapeutic target for treatment post-neonatal HIE injury.

19.
Front Cardiovasc Med ; 8: 731557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676252

RESUMO

Purpose: We evaluated the long-term effect of a smartphone-facilitated home-based cardiac rehabilitation (HBCR) model in revascularized patients with coronary heart disease (CHD) on major adverse cardiac events (MACE), and secondary outcomes, including safety, quality of life, and physical capacity. Methods: It was a prospective observational cohort study including a total of 335 CHD patients after successful percutaneous coronary intervention (PCI) referred to the CR clinic in China between July 23, 2015 and March 1, 2018. Patients were assigned to two groups: HBCR tailored by monitoring and telecommunication via smartphone app (WeChat) (HBCR group, n = 170) or usual care (control group, n = 165), with follow-up for up to 42 months. Propensity score matching was conducted to match patients in the HBCR group with those in the control group. The patients in the HBCR group received educational materials weekly and individualized exercise prescription monthly, and the control group only received 20-min education at baseline in the CR clinic. The primary outcome was MACE, analyzed by Cox regression models. The changes in the secondary outcomes were analyzed by paired t-test among the matched cohort. Results: One hundred thirty-five HBCR patients were matched with the same number of control patients. Compared to the control group, the HBCR group had a much lower incidence of MACE (1.5 vs. 8.9%, p = 0.002), with adjusted HR = 0.21, 95% CI 0.07-0.85, and also had reduced unscheduled readmission (9.7 vs. 23.0%, p = 0.002), improved exercise capacity [maximal METs (6.2 vs. 5.1, p = 0.002)], higher Seattle Angina Questionnaire score, and better control of risk factors. Conclusions: The Chinese HBCR model using smartphone interaction is a safe and effective approach to decrease cardiovascular risks of patients with CHD and improve patients' wellness. Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR1800015042.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34682486

RESUMO

The main functions of this research are to guide the proportion of urban land that is used and the layout of the facilities on it, help understand the changes to surface runoff that are caused by land being used in urban development, and thus solve surface runoff pollution. Hangzhou City, China has been selected for the experiment, and the way in which its land is utilized as well as the grading of urban construction projects in the demonstration area are specifically analyzed. This study systematically distinguishes the definitions of impervious area based on the Sutherland equation and analyzes the impact of different impervious area subtypes on surface runoff water quality. Then, we compare the impact of impervious area subtypes with the impact of other land-use patterns on surface runoff water quality. This study shows the relationship between different land-use types and runoff water bodies: Land-use index can affect runoff water quality; Greening activities, impervious surface, and the water quality index are negatively correlated; the effective impervious area rate is positively correlated with the water quality index. The paper suggests that increasing the proportion of green spaces and permeable roads in build-up land reduces the effective impervious area (EIA) and thus controls land runoff pollution and improves runoff water quality.


Assuntos
Monitoramento Ambiental , Qualidade da Água , China , Cidades , Chuva , Movimentos da Água
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