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1.
Horm Metab Res ; 54(2): 104-112, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35130571

RESUMO

Some studies have suggested that diabetes may be a risk factor for osteoarthritis. However, whether prediabetes is also associated with osteoarthritis has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoarthritis. This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Ten datasets from six observational studies were included, which involved 41 226 general adults and 10 785 (26.2%) of them were prediabetic. Pooled results showed that prediabetes was not independently associated with osteoarthritis [risk ratio (RR): 1.07, 95% confidence interval (CI): 1.00 to 1.14, p=0.06, I2=0%]. Sensitivity limited to studies with adjustment of age and body mass index showed consistent result (RR: 1.06, 95% CI: 0.99 to 1.14, p=0.09, I2=0%). Results of subgroup analyses showed that prediabetes was not associated with osteoarthritis in cross-sectional or cohort studies, in studies including Asian or non-Asian population, or in studies with different quality scores (p for subgroup difference>0.10). Besides, prediabetes was not associated with osteoarthritis in men or in women, in studies with prediabetes defined as impaired fasting glucose, impaired glucose tolerance, or HbA1c (approximately 39-46 mmol/mol). Moreover, prediabetes was not associated with overall osteoarthritis, and knee or hip osteoarthritis. Current evidence does not support that prediabetes is independently associated with osteoarthritis in adult population.


Assuntos
Intolerância à Glucose , Osteoartrite , Estado Pré-Diabético , Adulto , Glicemia/metabolismo , Estudos Transversais , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Estudos Observacionais como Assunto , Osteoartrite/complicações , Osteoartrite/epidemiologia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/metabolismo , Fatores de Risco
2.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35555604

RESUMO

Pulmonary arterial hypertension (PAH) is a complex and fatal disorder characterized by an unrelenting increase in pulmonary arterial pressure. Excessive proliferation of pulmonary artery smooth muscle cells (PASMC) leads to increased vascular resistance and eventually right ventricular failure and death. Our laboratory has identified a key role for Galectin-3 (GAL-3) in PAH. However, the mechanisms by which GAL-3 alters PASMC behavior remains poorly understood. GAL-3 contains a functional BH1 like domain that has an NWGR sequence with high homology to the anti-apoptotic protein, BCL2, and this domain has previously been shown to be functional in cancer cell lines. Our hypothesis is GAL-3 upregulation plays an important role in driving PASMC proliferation through repression of apoptosis via this NWGR domain. Using adenoviral vector encoding the GAL-3 G182A mutation and isolated GAL-3 PASMCs from a GAL3 KO rat (RPASMC). Our in vitro studies show that overexpression of GAL-3 G182A causes a decrease in viability upon treatment overnight with 0.5% serum containing media(p<.001) compared to normal media (p=.840). When exposed to apoptotic stimuli (TNFα, Cycloheximide) GAL-3 G182A overexpressing GAL-3 KO RPASMCs had significantly (p<.001) decreased vitality. Interestingly however, this domain also seems to regulate non-apoptotic related events such as cell attachment. Our previous work had shown that GAL-3 is readily excreted protein, and co-culture experiments as well as recombinant protein supplementation show that soluble GAL-3 is biologically active and induces SMC growth and proliferation(P<.05). Further experimentation also shows that inhibition of GAL-3 using blocking antibodies prevents SMC proliferation. (p<.05) To test this hypothesis in-vivo we injected GAL-3 KO mice with a liver specific AAV overexpressing GAL-3, or GFP (control) and exposed them to sugen/hypoxia to induce PAH. Surprisingly our initial findings indicate a slight protection with liver GAL-3 overexpression when compared to wt mice.(p<.05) Also very interestingly, while liver overexpression of GAL-3 was very high there was no evidence of GAL3 in the lungs or plasma of GAL3KO mice indicating it may not be secreted from the liver in sufficient amounts unlike what was observed in other cell types. Overall our data suggests that the NWGR domain of GAL-3 is an important regulator of PASMC survivability and the blocking antibody suggests that secreted GAL-3 is capable of regulating SMC proliferation, however it does not appear that hepatocytes secrete sufficient GAL-3 for it to circulate and play a role in the lung vasculature.

3.
Int J Biol Sci ; 18(7): 2949-2961, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541900

RESUMO

Triple-negative breast cancer (TNBC) is a massive threat to women's health due to its high morbidity, malignancy, and the refractory, effective therapeutic option of TNBC is still deficient. The mitochondrial protein showed therapeutic potential on breast cancer, whereas the mechanism and downstream pathway of mitochondrial uncoupling protein 1 (UCP1) was not fully elucidated. We found that UCP1 was negatively regulated to the process of TNBC. Overexpressing UCP1 could inhibit the proliferation and metastasis of TNBC, meanwhile inducing the mitochondrial swelling and activation of mitophagy in vitro. Mitophagy activation was then assessed to elucidate whether it was downstream of UCP1 in TNBC metastasis. GSDME is the core of pyroptosis. We found that GSDME was activated in the TNBC cells when UCP1 levels were high. It regulates TNBC cell proliferation potential instead of the apoptosis process in vitro and in vivo. Our results suggested that UCP1 could inhibit the process of TNBC by activating mitophagy and pyroptosis. Impaired activation of mitophagy weakens the regulation effect of UCP1 on metastasis of TNBC, similar to the impairment of GSDME activation on the proliferation regulation of UCP1 on TNBC. UCP1 might be a novel therapeutic target of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteína Desacopladora 1 , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Mitofagia/genética , Piroptose/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Proteína Desacopladora 1/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-35511849

RESUMO

Gait recognition aims at identifying the pedestrians at a long distance by their biometric gait patterns. It is inherently challenging due to the various covariates and the properties of silhouettes (textureless and colorless), which result in two kinds of pair-wise hard samples: the same pedestrian could have distinct silhouettes (intra-class diversity) and different pedestrians could have similar silhouettes (inter-class similarity). In this work, we propose to solve the hard sample issue with a Memory-augmented Progressive Learning network (GaitMPL), including Dynamic Reweighting Progressive Learning module (DRPL) and Global Structure-Aligned Memory bank (GSAM). Specifically, DRPL reduces the learning difficulty of hard samples by easy-to-hard progressive learning. GSAM further augments DRPL with a structure-aligned memory mechanism, which maintains and models the feature distribution of each ID. Experiments on two commonly used datasets, CASIA-B and OU-MVLP, demonstrate the effectiveness of GaitMPL. On CASIA-B, we achieve the state-of-the-art performance, i.e., 88.0% on the most challenging condition (Clothing) and 93.3% on the average condition, which outperforms the other methods by at least 3.8% and 1.4%, respectively.

5.
Trials ; 23(1): 412, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578345

RESUMO

BACKGROUND: Clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs to be tested, especially in low- and middle-income countries such as China. METHODS: The Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care sites in China. For each city-based stage, sites are randomly assigned to either implementation of the CDSS for hypertension management (which guides doctors' treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided. In a nested trial conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual-antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the changes in blood pressure. DISCUSSION: The LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The nested trial, the LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.

6.
Acta Pharm Sin B ; 12(3): 1514-1522, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35530157

RESUMO

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35534791

RESUMO

OBJECTIVE: Long-term weight loss (LTWL) has been shown to be associated with lower metabolic risk in young adults with overweight/obesity. However, the dose-response association is uncertain. METHODS: In a large-scale nationwide screening project in China, the participants aged 35 to 64 years who recalled overweight/obesity at age 25 years and experienced LTWL or maintained stable weight were included. The dose-response association between LTWL from age 25 to screening (35 to 64 years) and the odds of metabolic syndrome at screening were assessed using multivariable adjusted regression models with restricted cubic splines. RESULTS: A total of 40,150 participants (66.4% women) were included. The increment of LTWL was associated with continuously decreased odds of metabolic syndrome. The odds of metabolic syndrome were 0.64 (0.60 to 0.67), 0.42 (0.40 to 0.45), 0.27 (0.25 to 0.29), and 0.15 (0.13 to 0.17) for those with LTWL of 5% to 9.9%, 10% to 14.9%, 15% to 19.9%, and 20% or greater compared with <5% LTWL, respectively. Moreover, the incremental pattern was observed across all population subgroups. CONCLUSIONS: An incremental association between LTWL from young adulthood and odds of later-life metabolic syndrome was observed. Our findings highlight the effective ways to achieve LTWL to improve lifetime metabolic health for young adults with overweight/obesity.

8.
Front Med (Lausanne) ; 9: 829304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35510250

RESUMO

The vitamin K antagonist is a commonly prescribed effective oral anticoagulant with a narrow therapeutic range, and the dose requirements for different patients varied greatly. In recent years, studies on human intestinal microbiome have provided many valuable insights into disease development and drug reactions. A lot of studies indicated the potential relationship between microbiome and the vitamin K antagonist. Vitamin K is absorbed by the gut, and the intestinal bacteria are a major source of vitamin K in human body. A combined use of the vitamin K antagonist and antibiotics may result in an increase in INR, thus elevating the risk of bleeding, while vitamin K supplementation can improve stability of anticoagulation for oral vitamin K antagonist treatment. Recently, how intestinal bacteria affect the response of the vitamin K antagonist remains unclear. In this review, we reviewed the research, focusing on the physiology of vitamin K in the anticoagulation treatment, and investigated the potential pathways of intestinal bacteria affecting the reaction of the vitamin K antagonist.

9.
Adv Nutr ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524691

RESUMO

Although the association of dietary inflammatory potential, evaluated by the dietary inflammatory index (DII), with all-cause and cause-specific mortality has been reported, evidence remains equivocal, no relevant dose-response meta-analysis having been conducted. To examine the dose-response association of dietary inflammatory potential with risk of all-cause, cancer, and cardiovascular disease (CVD) mortality, PubMed, EMBASE and Web of Science were systematically searched up to 9 August 2021. Cohort studies were included if DII was reported as at least three levels or per incremental increase, and if the associations of DII with all-cause, cancer, and CVD mortality were assessed. Generalized least squares regression was used to estimate study-specific dose-response associations, and the random effect model was used to pool the relative risks (RRs) and 95% confidence intervals (95% CIs) of all cause, cancer, and CVD mortality per 1-unit increase in DII. Restricted cubic splines were used to intuitively display the dose-response association between dietary inflammatory potential and mortality. Among the 1,415 studies retrieved, 15 articles (17 cohort studies involving 397,641 participants) were included in this meta-analysis. With per 1-unit increase in DII, the risks were significantly increased for all-cause mortality (RR: 1.04; 95% CI: 1.03, 1.05, I2 = 51.8%; P-heterogeneity = 0.009), cancer mortality (RR: 1.02; 95% CI: 1.00, 1.04, I2 = 58.6%; P-heterogeneity = 0.013), and CVD mortality (RR: 1.04; 95% CI: 1.02, 1.06, I2 = 85.7%; P-heterogeneity <0.001), respectively. Restricted cubic splines showed significant positive linear associations between DII and the above three outcomes. Our study indicated that pro-inflammatory diets may increase the risk of all-cause, cancer, and CVD mortality in a linear manner.

10.
Ophthalmology ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537532

RESUMO

PURPOSE: To explore whether there is a causal relationship between coffee consumption and primary open-angle glaucoma (POAG). DESIGN: Two-sample Mendelian randomization. PARTICIPANTS: The single-nucleotide polymorphisms (SNPs) associated with coffee consumption (including phenotype 1 and phenotype 2) were selected from a genome-wide association study (GWAS) involving 121,824 individuals of European descent. Coffee intake from MRC-IEU UK Biobank was also used to identify instruments for coffee intake. Summary-level data for POAG were obtained from the largest publicly available meta-analyses involving 16,677 POAG cases and 199,580 controls of European descent. METHODS: Inverse-variance-weighted (IVW) method was the main MR analysis, whereas weighted-median, weighted mode-based estimate (MBE), MR Pleiotropy RESidual Sum and Outlier (PRESSO) test, and MR-Egger regression were used for sensitivity analysis. MAIN OUTCOME MEASURES: Diagnosis of POAG. RESULTS: Three sets of instrumental variables were used to evaluate the causal association between coffee consumption and POAG risk. Results showed that genetically predicted higher coffee consumption phenotype 1 (cups/day) was significantly associated with higher risk of POAG (odds ratio [OR] = 1.241, 95% CI = 1.041-1.480, P = 0.016). Genetically predicted higher coffee consumption phenotype 2 (high vs. no/low) was also significantly associated with higher risk of POAG (OR = 1.155, 95% CI = 1.038-1.284, P=0.008, using the IVW method). Moreover, genetically predicted higher coffee intake from MRC-IEU UK Biobank OpenGWAS was significantly associated with higher risk of POAG (OR = 1.727, 95% CI = 1.230-2.425, P=0.002, using the IVW method). Sensitivity analyses confirmed that the findings were robust to possible pleiotropy. CONCLUSIONS: In conclusion, these findings provide the genetic evidence that higher coffee consumption is associated with a higher risk of POAG. Given that coffee is widely consumed, our findings provide new insights into potential strategies to prevent and manage POAG.

11.
J Environ Manage ; 315: 115164, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500489

RESUMO

The catchment phosphorus buffering capacity (PBF) determines the pressure-state-response relationship between anthropogenic P inputs and aquatic ecosystems at a catchment scale, and is affected by biogeochemical, hydrological, and ecological catchment characteristics. However, the complex relationship between these catchment characteristic factors and their impact pathways on PBF remains ambiguous, leading to large uncertainty in balancing agricultural productivity and water conservation via improving BF through management practices. In this study, the short-term buffering index, calculated from net anthropogenic P input and riverine P exports, was used to quantify the spatiotemporal variations in PBF in source agricultural catchments in the Dongting Lake basin. Partial least squares structural equation modeling was used to investigate the relationship between the PBF and the catchment characteristics. The results indicate that catchment PBF was directly determined by soil properties and hydrological conditions, while landscape patterns significantly mediated the effects of topography on soil and hydrology. Considering the pathway preferences of the model, landscape patterns could be the priority for characterizing and regulating PBF. According to a change-point analysis, the probability of PBF weakening increases dramatically when the proportion of farmland (Farm%) > 24.6%, degree of patch interspersion (Contagion index) < 64.5%, and Perimeter-Area Ratio Distribution (PARA) > 348.7. These findings provide new insights into catchment buffering mechanisms and can be used to promote the simultaneous achievement of agricultural production and environmental conservation goals.

12.
Global Spine J ; : 21925682221097650, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499394

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVES: To develop machine learning (ML) models to predict recurrent lumbar disc herniation (rLDH) following percutaneous endoscopic lumbar discectomy (PELD). METHODS: We retrospectively analyzed 1159 patients who had undergone single-level PELD for lumbar disc herniation (LDH) between July 2014 to December 2019 at our institution. Various preoperative imaging variables and demographic metrics were brought in analysis. Student's t test and Chi-squared test were applied for univariate analysis, which were feature selection for ML models. We established ML models to predict rLDH: Artificial neural networks (ANN), Extreme Gradient Boost classifier (XGBoost), KNeighborsClassifier (KNN), Decision tree classifier (Decision Tree), Random forest classifier (Random Forest), and support vector classifier (SVC). RESULTS: A total 130 patients (11.22%) were diagnosed as rLDH in 1159 patients. Recurrence occurred within 10.25 ± 11.05 months. Body mass index (BMI) (P = .027), facet orientation (FO) (P < .001), herniation type (P = .012), Modic changes (P = .004), and disc calcification (P = .013) are significant factors in univariate analysis (P < .05). Extreme Gradient Boost classifier, Random Forest, ANN showed fine area under the curve, .9315, .9220, and .8814 respectively. CONCLUSION: We developed a deep learning and 2 ensemble models with fine performance in prediction of rLDH following PELD. Predicting re-herniation before surgery has the potential to optimize decision-making and meaningfully decrease the rates of rLDH following PELD. Our ML model identified higher BMI, lower FO, Modic changes, disc calcification in a non-protrusive region, and herniation type (noncontained herniation) as significant features for predicting rLDH.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35488908

RESUMO

PURPOSE: To assess the acquisition rate and agreement of axial length (AL) measurements with the OA-2000, Anterion, and IOLMaster 500 in cataractous patients. METHODS: In total, 298 eyes of 191 cataractous patients were enrolled and scanned with the three devices in random order. The success rate of AL measurements per device was calculated and a chi-square test was utilized to identify the differences in acquisition rate between the three devices. Logistic regression analysis was applied to evaluate the association of different cataract types and severity with the AL measurement acquisition rate. Bland-Altman plots were mapped to appraise the agreement of AL values. RESULTS: AL measurements were successfully achieved in 288 eyes (96.64%) with the OA-2000, in 282 eyes (94.30%) with the Anteiron, and in 246 eyes (82.55%) with the IOLMaster 500. Significant differences in the acquisition rate were found between either of the SS-OCT devices and IOLMaster 500 by chi-square analysis (P < 0.001). No significant difference was noted between OA-2000 and Anterion. Increasing severity of posterior subcapsular cataract was associated with a higher failure rate with the IOLMaster 500. Bland-Altman analysis identified good agreement between the three biometers with narrow 95% limits of agreement. CONCLUSIONS: The OA-2000 and Anterion showed similarly higher acquisition rate of AL measurements than IOLMaster 500 in cataractous patients. Good agreement for AL values was found between the three biometers in cataractous patients.

14.
QJM ; 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380710

RESUMO

BACKGROUND: Patients with kidney disease are at increased risk of adverse mortality events. Numerous studies have demonstrated the positive association of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) with all-cause and cardiovascular (CV) mortality in patients with kidney disease; however, the dose-response meta-analysis have not been reported. We therefore performed this study to evaluate the dose-response associations of hs-cTn with risk of all-cause and CV mortality to improve risk stratification. METHODS: We searched three databases (PubMed, Embase, and Web of Science) to identify relevant prospective cohort studies published up to January 12, 2021. Random-effects models were used to summarize relative risks (RRs) and 95% confidence intervals (CIs) of all-cause and CV mortality. Restricted cubic splines were used to fit the dose-response associations. RESULTS: For each 10 ng/L increase in hs-cTnT and hs-cTnI, the risk increased by 14% (RR = 1.14, 95% CI, 1.10-1.18) and 19% (RR = 1.19, 95% CI, 1.09-1.31) for all-cause mortality, 25% (RR = 1.25, 95% CI, 1.13-1.38) and 19% (RR = 1.19, 95% CI, 1.10-1.29) for CV mortality. A linear trend was found between hs-cTnT and all-cause mortality, whereas a non-linear trend was found in hs-cTnI. Additionally, both hs-cTnT and hs-cTnI were shown to have linear trends with CV mortality. CONCLUSION: Our meta-analysis suggests that hs-cTn had high sensitivity in predicting mortality events. All dose-response trends were rising rather than falling, conferring that any increase in the levels of hs-cTn may possibly predict a death prognosis among CKD patients.

15.
Front Endocrinol (Lausanne) ; 13: 789008, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370945

RESUMO

Background: Androgen excess could profoundly lead to follicular dysplasia or atresia, and finally result in polycystic ovary syndrome (PCOS); however, the exact mechanism remains to be fully elucidated. Methods: PCOS model rats were induced by dehydroepiandrosterone, and their fertility was assessed. The ovarian granulosa cells (GCs) from matured follicles of PCOS model rats were collected and identified by immunofluorescence. The mitochondrial ultrastructure was observed by transmission electron microscope and the mitochondrial function was determined by detecting the adenosine triphosphate (ATP) content and mtDNA copy number. Besides, the expressions of respiratory chain complexes and ATP synthases in relation to mitochondrial function were analyzed. Results: The PCOS model rats were successfully induced, and their reproductive outcomes were obviously adverse. The GCs layer of the ovarian was apparently cut down and the mitochondrial ultrastructure of ovarian GCs was distinctly destroyed. The ATP content and mtDNA copy number of ovarian GCs in PCOS model rats were greatly reduced, and the expressions of NDUFB8 and ATP5j were significantly down-regulated without obvious deletion of mtDNA 4834-bp. Conclusions: Androgen excess could damage mitochondrial ultrastructure and function of GCs in rat ovary by down-regulating expression of NDUFB8 and ATP5j in PCOS.


Assuntos
Síndrome do Ovário Policístico , Androgênios/metabolismo , Animais , Feminino , Células da Granulosa/metabolismo , Mitocôndrias/metabolismo , Folículo Ovariano/metabolismo , Síndrome do Ovário Policístico/metabolismo , Ratos
16.
Plants (Basel) ; 11(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35406941

RESUMO

Cucumbers (Cucumis sativus L.) originated from the South Asian subcontinent, and most of them are fragile to cold stress. In this study, we evaluated the cold tolerance of 115 cucumber accessions and screened out 10 accessions showing high resistance to cold stress. We measured and compared plant hormone contents between cold-tolerant cucumber CT90R and cold-sensitive cucumber CT57S in cold treatment. Most of the detected plant hormones showed significantly higher content in CT90R. To elucidate the role of plant hormones, we compared the leaf- and root-transcriptomes of CT90R with those of CT57S in cold stress treatment. In leaves, there were 1209 differentially expressed genes (DEGs) between CT90R and CT57S, while there were 703 in roots. These DEGs were not evenly distributed across the chromosomes and there were significant enrichments at particular positions, including qLTT6.2, a known QTL controlling cucumber cold tolerance. The GO and KEGG enrichment analysis showed that there was a significant difference in the pathway of plant hormone transductions between CT90R and CT57S in leaves. In short, genes involved in plant hormone transductions showed lower transcription levels in CT90R. In roots, the most significantly different pathway was phenylpropanoid biosynthesis. CT90R seemed to actively accumulate more monolignols by upregulating cinnamyl-alcohol&nbsp;dehydrogenase (CAD) genes. These results above suggest a new perspective on the regulation mechanism of cold tolerance in cucumbers.

17.
Front Immunol ; 13: 818518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422816

RESUMO

Autism spectrum disorder (ASD) is a complex pervasive neurodevelopmental disorder and neuroinflammation may contribute to the pathogenesis of ASD. However, the exact mechanisms of abnormal release of proinflammatory mediators in ASD remain poorly understood. This study reports elevated plasma levels of the proinflammatory chemokine (C-C motif) ligand 5 (CCL5) in children with ASD, suggesting an aberrant inflammatory response appearing in the development of ASD. Mining of the expression data of brain or blood tissue from individuals with ASD reveals that mTOR signaling is aberrantly activated in ASD patients. Our in vitro study shows that suppression of mTOR reduces the gene expression and release of CCL5 from human microglia, supporting that CCL5 expression is regulated by mTOR activity. Furthermore, bacterial lipopolysaccharide (LPS)-induced CCL5 expression can be counteracted by siRNA against NF-κB, suggests a determining role of NF-κB in upregulating CCL5 expression. However, a direct regulatory relationship between the NF-κB element and the mTOR signaling pathway was not observed in rapamycin-treated cells. Our results show that the phosphorylated CREB can be induced to suppress CCL5 expression by outcompeting NF-κB in binding to CREB-binding protein (CREBBP) once the mTOR signaling pathway is inhibited. We propose that the activation of mTOR signaling in ASD may induce the suppression of phosphorylation of CREB, which in turn results in the increased binding of CREBBP to NF-κB, a competitor of phosphorylated CREB to drive expression of CCL5. Our study sheds new light on the inflammatory mechanisms of ASD and paves the way for the development of therapeutic strategy for ASD.


Assuntos
Transtorno do Espectro Autista , NF-kappa B , Transtorno do Espectro Autista/etiologia , Quimiocina CCL5 , Criança , Humanos , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
18.
Molecules ; 27(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35408686

RESUMO

Nanomaterial technology has attracted much attention because of its antibacterial and drug delivery properties, among other applications. Metal-organic frameworks (MOFs) have advantages, such as their pore structure, large specific surface area, open metal sites, and chemical stability, over other nanomaterials, enabling better drug encapsulation and adsorption. In two examples, we used the common pathogenic bacterium Staphylococcus aureus and highly infectious influenza A virus. A novel complex MIL-101(Fe)-T705 was formed by synthesizing MOF material MIL-101(Fe) with the drug favipiravir (T-705), and a hot solvent synthesis method was applied to investigate the in vitro antibacterial and antiviral activities. The results showed that MIL-101(Fe)-T705 combined the advantages of nanomaterials and drugs and could inhibit the growth of Staphylococcus aureus at a concentration of 0.0032 g/mL. Regarding the inhibition of influenza A virus, MIL-101(Fe)-T705 showed good biosafety at 12, 24, 48, and 72 h in addition to a good antiviral effect at concentrations of 0.1, 0.2, 0.4, 0.8, 1.6, and 3 µg/mL, which were higher than MIL-101(Fe) and T-705.


Assuntos
Estruturas Metalorgânicas , Amidas , Antibacterianos , Antivirais/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Pirazinas
19.
Pest Manag Sci ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388600

RESUMO

BACKGROUND: The black carabid beetle Calosoma maximoviczi is a successful predator that serves as both a beneficial insect and a severe threat to economic herbivores. Its hunting technique relies heavily on olfaction, but the underlying mechanism has not been studied. Here, we report the electrophysiological, ecological and molecular traits of bioactive components identified from a comprehensive panel of natural odorants in the beetle-prey-plant system. The aim of this work was to investigate olfactory perceptions and their influence on the behaviours of C. maximoviczi. RESULTS: Among the 200 identified volatiles, 18 were concentrated in beetle and prey samples, and 14 were concentrated in plants. Insect feeding damage to plants led to a shift in the emission fingerprint. Twelve volatiles were selected using successive electrophysiological tests. Field trials showed that significant sex differences existed when trapping with a single chemical or chemical mixture. Expression profiles indicated that sex-biased catches were related to the expression of 15 annotated CmaxOBPs and 40 CmaxORs across 12 chemosensory organs. In silico evaluations were conducted with 16 CmaxORs using modelling and docking. Better recognition was predicted for the pairs CmaxOR5-(Z)-3-hexenyl acetate, CmaxOR6-ß-caryophyllene, CmaxOR18-(E)-ß-ocimene and CmaxOR18-tetradecane, with higher binding affinity and a suitable binding pocket. Lastly, 168Y in CmaxOR6 and 142Y in CmaxOR18 were predicted as key amino acid residues for binding ß-caryophyllene and tetradecane, respectively. CONCLUSION: This work provides an example pipeline for de novo investigation in C. maximoviczi baits and the underlying olfactory perceptions. The results will benefit the future development of trapping-based integrated pest management strategies and the deorphanization of odorant receptors in ground beetles. © 2022 Society of Chemical Industry.

20.
J Invest Surg ; : 1-10, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35414343

RESUMO

BACKGROUND: Which one of the two measures, distal arterial supercharging (DAS) and distal venous superdrainage (DVS), is better to enhance flap survival? No consistent conclusions have been reached. METHODS: All flaps were pedicled on the deep circumflex iliac vessels. Seventy-two healthy male rats were distributed to four groups randomly: DAVS group (distal arteriovenous supercharging group), the thoracodorsal (TD) artery and TD vein were preserved; DAS group (distal arterial supercharging group), the TD vein was ligated; DVS group (distal venous superdrainage group), the TD artery was ligated; control group, the TD artery and TD vein were ligated. Flap survival rate was evaluated on postoperative day 7. Flap angiography was performed to assess vascular changes of the flap. Microvascular density (MVD) was evaluated by hematoxylin and eosin staining, and CD34-positive microvessel density was measured by immunohistochemistry. Vascular endothelial growth factor (VEGF) level was measured by western blot. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated using specialized commercial kits. RESULTS: The mean flap survival rate was increased significantly in DAVS and DAS groups than in DVS and control groups. DAVS and DAS groups had higher flap vascularization, MVD, CD34-positive microvessel density, VEGF expression and SOD level compared to DVS and control groups. DAVS and DAS groups also had lower MDA level relative to DVS and control groups. CONCLUSION: DAS is more conducive to improving the survival rate of the multiterritory perforator flap compared to DVS, mainly by enhancing angiogenesis and preventing ischemia-reperfusion (I/R) injury.

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