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1.
Angiology ; : 33197211004410, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33779311

RESUMO

Previous studies reported that the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT) was a risk factor in cardiovascular disease. Peripheral artery disease (PAD) is an important risk factor for cardiovascular death. However, only a few studies investigated the correlations between the AST/ALT ratio and PAD. We analyzed data from 10 900 patients with hypertension from the Chinese Hypertension Registry Study; 350 patients had PAD (prevalence 3.2%). After adjusting for potential confounders, the AST/ALT ratio was independently and positively associated with risk of PAD (OR: 1.31, 95% CI, 1.13-1.59), and a significant increased risk of PAD for the third AST/ALT ratio tertile (T3) compared with the first tertile (T1; OR: 1.49, 95% CI, 1.09-2.04, P trend = .005) was found. Moreover, when we combined T1 and T2 into one group and used it as a reference group, the risk of PAD increased with the increase in AST/ALT; the risk ratio was 1.52 (95% CI, 1.20-1.95). A higher AST/ALT ratio (≥1.65) was associated with PAD risk in Chinese adults with hypertension. Our results suggest that the AST/ALT ratio may help identify patients at high risk of vascular end points and might be a convenient, economical, and effective tool for evaluating the risk of atherosclerosis.

2.
Development ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741713

RESUMO

Germline sexual fate has long been believed to be determined by the somatic environment, but this idea is challenged by recent studies of foxl3 mutants in medaka. Here we demonstrate that the sexual fate of tilapia germline is determined by the antagonistic interaction of dmrt1 and foxl3, which are transcriptionally repressed in male and female germ cells, respectively. Loss of dmrt1 rescued the germ cell sex reversal in foxl3 Δ7/Δ7 XX fish, and loss of foxl3 partially rescued germ cell sex reversal but not somatic cell fate in dmrt1 Δ5/Δ5 XY fish. Interestingly, germ cells lost sexual plasticity in dmrt1 Δ5/Δ5 XY and foxl3 Δ7/Δ7 XX single mutants, as aromatase inhibitor and estrogen treatment failed to rescue the respective phenotypes. However, recovery of germ cell sexual plasticity was observed in dmrt1/foxl3 double mutants. Importantly, mutation of somatic cell specific foxl2 resulted in testicular development in foxl3 Δ7/Δ7 or dmrt1 Δ5/Δ5 mutants. Our findings demonstrate that sexual plasticity of germ cells relies on the presence of both dmrt1 and foxl3 The existence of dmrt1 and foxl3 allows environmental factors to influence the sex fate decision in vertebrates.

3.
Food Chem ; 352: 129322, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690073

RESUMO

This study explored the effects of brassinolide (BR) soaking, preharvest ultraviolet-B (UV-B) radiation, and their combined treatments on physiological characteristics, chlorophyll fluorescence, and quality of small black bean sprouts during storage. Results indicated that the combined treatments significantly enhanced contents of flavone, free amino acid, and photosynthetic pigment, and activities of phenylalanine ammonia lyase (PAL) and 2-diphenyl-1-picrylhydrazyl(DPPH) radical scavenging in sprouts stored for 5 days compared with BR treatment alone. The combined treatments significantly increased total phenols content and PAL activity, and reduced malonaldehyde content in sprouts compared with UV-B radiation alone. The inhibitory effect of BR or UV-B on fluorescence of photosystem II was weakened by their combined treatments. Comprehensive analysis indicated that the combined treatments could be used to maintain postharvest small black bean sprouts with high levels of nutritional ingredients by probably keeping high photosynthetic capacity, PAL activity, and DPPH radical scavenging rate in sprouts.


Assuntos
Brassinosteroides/farmacologia , Armazenamento de Alimentos , Esteroides Heterocíclicos/farmacologia , Raios Ultravioleta , Vigna/efeitos dos fármacos , Vigna/efeitos da radiação , Flavonas/metabolismo , Malondialdeído/metabolismo , Fenóis/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Vigna/metabolismo
4.
Mol Neurobiol ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675023

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by progressive memory decline and cognitive dysfunctions. Although the causes of AD have not yet been established, many mechanisms have been proposed. Axon-guidance molecules play the roles in the occurrence and development of AD by participating in different mechanisms. Therefore, what roles do axon-guidance molecules play in AD? This study aimed at elucidating how axon-guidance molecules Netrins, Slits, Semaphorins, and Ephrins regulate the levels of Aß, hyperphosphorylation of tau protein, Reelin, and other ways through different signaling pathways, in order to show the roles of axon-guidance molecules in the occurrence and development of AD. And it is hoped that this study can provide a theoretical basis and new perspectives in the search for new therapeutic targets for AD.

5.
Biol Reprod ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33693502

RESUMO

As in other vertebrates, fish reproduction is tightly controlled by gonadotropin signaling. One of the most perplexing aspects of gonadotropin action on germ cell biology is the restricted expression of gonadotropin receptors in somatic cells of the gonads. Therefore, the identification of factors conveying the action of gonadotropins on germ cells is particularly important for understanding the mechanism of reproduction. Insulin-like growth factors (Igfs) are recognized as key factors in regulating reproduction by triggering a series of physiological processes in vertebrates. Recently, a novel member of Igfs called Igf3 has been identified in teleost. Different from the conventional Igf1 and Igf2 that are ubiquitously expressed in a majority of tissues, Igf3 is solely or highly expressed in the fish gonads. The role of Igf3 in mediating the action of gonadotropin through Igf type 1 receptor on several aspects of oogenesis and spermatogenesis have been demonstrated in several fish species. In this review, we will summarize existing data on Igf3. This new information obtained from Igf3 provides insight into elucidating the molecular mechanism of fish reproduction, and also highlights the importance of Igf system in mediating the action of gonadotropin signaling on animal reproduction.

6.
J Nutr ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33693869

RESUMO

BACKGROUND: Risk of chronic kidney disease (CKD) is higher in normal-weight metabolically unhealthy people, especially when combined with hypertension. In this context, whether the visceral adiposity index (VAI), which reflects body fat distribution and metabolism, can be used to identify the risk of CKD among normal-weight hypertensive patients is unclear. OBJECTIVES: This study aimed to evaluate the association between VAI and renal function in normal-weight hypertensive patients. METHODS: In this cross-sectional study, 8591 hypertensive patients with normal BMI from the China H-type Hypertension Registry Study were analyzed. The VAI was calculated with serum triglycerides, serum HDL cholesterol, waist circumference, and BMI. VAI was ln-transformed for analysis on account of the skewed distribution. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL · min-1 · 1.73 m-2. Multivariable linear and multivariable logistic regression analyses were performed to evaluate the association of VAI with eGFR and CKD. RESULTS: The prevalence rate of CKD was 10.1%. Multivariable linear regression analyses showed that an elevated lnVAI reduced eGFR by 2.63 mL · min-1 · 1.73 m-2 (95% CI: -3.54, -1.72 mL · min-1 · 1.73 m-2). Multivariable logistic regression analysis showed that an elevated lnVAI was independently associated with the prevalence of CKD (OR: 1.59; 95% CI: 1.31, 1.93). As possible confounding factors were removed the association became greater. The higher the VAI was, the greater the decrease in eGFR and the higher the risk of CKD. No significant interactions were found in any of the subgroups (age, sex, physical activity, current smoking, current drinking, fasting glucose, LDL cholesterol, blood pressure, and antihypertensive drugs). CONCLUSIONS: VAI, as a simple surrogate measure of visceral fat accumulation, is independently and inversely associated with renal function in normal-weight Chinese hypertensive adults.This trial was registered at chictr.org.cn as ChiCTR1800017274.

7.
Schizophr Res ; 230: 53-60, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33677199

RESUMO

AIM: Schizophrenia and affective disorders all show high heterogeneity in clinical manifestations. A lack of objective biomarkers has long been a challenge in the clinical diagnosis of these diseases. In this study, we aimed to investigate the performance of niacin skin flushing in schizophrenia and affective disorders and determine its clinical potential as an auxiliary diagnostic marker. METHODS: In this case-control study, niacin skin-flushing tests were conducted in 613 patients (including 307 schizophrenia patients, 179 bipolar disorder patients, and 127 unipolar depression patients) and 148 healthy controls (HCs) with a modified method. Differences in niacin skin-flushing responses were compared with adjustment for gender, BMI, age, nicotine dependence, alcohol consumption and educational status. A diagnostic model was established based on a bivariate cut-off. RESULTS: Schizophrenia and affective disorders showed similar performance of niacin bluntness, characterized by attenuated flushing extent and reduced flushing rate. An innovative bivariate cut-off was established according to these two features, by which we could identify -patients with either schizophrenia or affective disorders from HCs with a sensitivity of 55.28%, a specificity of 83.56% and a positive predictive value of 93.66%. CONCLUSIONS: The niacin-induced skin flushing was prevalently blunted in patients with schizophrenia or affective disorders, indicating a promising potential as an auxiliary diagnostic marker in risk prediction and clinical management of these disorders. Additionally, the niacin-blunted subgroup implies a common biological basis in the investigated disorders, which provokes new thoughts in elucidating the pathological mechanisms.

9.
J Psychiatr Res ; 137: 14-21, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33640722

RESUMO

Recent evidence supports an association between lipid metabolism dysfunction and the pathology of schizophrenia which has led to the search for peripheral blood-based biomarkers. The purpose of this study was to investigate the proteins involved in lipid metabolism (especially apolipoprotein) and to explore their potential as biomarkers for schizophrenia. Using multiple reaction monitoring mass spectrometry (MRM-MS), we quantified 22 proteins in serum samples of 109 healthy controls (HCs) and 111 patients with schizophrenia (SCZ), who were divided into discovery and validation sets. We found serum apolipoprotein A4 (ApoA4) to be significantly decreased in SCZ patients compared to HCs (p=1.61E-05). Moreover, the serum ApoA4 level served as an effective diagnostic tool, achieving area under the receiver operating characteristic curves (AUROC) of 0.840 in the discovery set and 0.791 in the validation set. Additionally, apolipoprotein F (ApoF), angiotensinogen (AGT), and alpha1-antichymotrypsin (ACT) levels were significantly higher in patients with schizophrenia than in healthy controls. These proteins combined with ApoA4, provided higher diagnostic accuracy for schizophrenia in the discovery set (AUROC=0.901) and in the validation set (AUROC=0.879). Our results suggest that the serum level of ApoA4 is a novel potential biomarker for schizophrenia. The proteins identified in this study expand the pool of biomarker candidates for schizophrenia and may be linked to the underlying mechanism of the disease.

10.
J Appl Clin Med Phys ; 22(4): 34-43, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33634946

RESUMO

PURPOSE: Radiotherapy plays an important role in the treatment of lung cancer, and both coplanar beam arrangements (CBA) and noncoplanar beam arrangements (NCBA) are adopted in clinic practice. The aim of this study is to answer the question whether NCBA are dosimetrically superior to CBA. METHODS: Search of publications were performed in PubMed, Web of Science, and the Cochran Library till March 2020. The searching terms were as following: ((noncoplanar) or ("non coplanar") or ("4pi") or ("4π")) AND (("lung cancer") or ("lung tumor") or ("lung carcinoma")) AND ((radiotherapy) or ("radiation therapy")). The included studies and extracted data were manually screened. All forest and funnel plots were carried out with RevMan software, and the Egger's regression asymmetry tests were conducted with STATA software. RESULTS: Nine studies were included and evaluated in the meta-analysis and treatment plans were designed with both CBA and NCBA. For the planning target volumes (PTV), D98%, D2%, the conformity index (CI), and the gradient index (GI) had no statistically significant difference. For organs-at-risk (OAR), V20 of the whole lung and the maximum dose of the spinal cord were significantly reduced in NCBA plans compared with CBA ones. But V10, V5, and mean dose of the whole lung, the maximum dose of the heart, and the maximum dose of the esophagus exhibited no significant difference when the two types of beam arrangements were compared. CONCLUSION: After combining multicenter results, NCBA plans have significant advantages in reducing V20 of the whole lung and max dose of spinal cord.

12.
Health Qual Life Outcomes ; 19(1): 45, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546723

RESUMO

OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis to compare differences in health utilities (HUs) assessed by self and proxy respondents in children, as well as to evaluate the effects of health conditions, valuation methods, and proxy types on the differences. METHODS: Eligible studies published in PubMed, Embase, Web of Science, and Cochrane Library up to December 2019 were identified according to PRISMA guidelines. Meta-analyses were performed to calculate the weighted mean differences (WMDs) in HUs between proxy- versus self-reports. Mixed-effects meta-regressions were applied to explore differences in WMDs among each health condition, valuation method and proxy type. RESULTS: A total of 30 studies were finally included, comprising 211 pairs of HUs assessed by 15,294 children and 16,103 proxies. This study identified 34 health conditions, 10 valuation methods, and 3 proxy types. In general, proxy-reported HUs were significantly different from those assessed by children themselves, while the direction and magnitude of these differences were inconsistent regarding health conditions, valuation methods, and proxy types. Meta-regression demonstrated that WMDs were significantly different in patients with ear diseases relative to the general population; in those measured by EQ-5D, Health utility index 2 (HUI2), and Pediatric asthma health outcome measure relative to Visual analogue scale method; while were not significantly different in individuals adopting clinician-proxy and caregiver-proxy relative to parent-proxy. CONCLUSION: Divergence existed in HUs between self and proxy-reports. Our findings highlight the importance of selecting appropriate self and/or proxy-reported HUs in health-related quality of life measurement and economic evaluations.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33569736

RESUMO

BACKGROUND: Several pharmacological agents, such as chloroquine/hydroxychloroquine, have been promoted for COVID-19 treatment or pre-exposure prophylaxis. However, no comprehensive evaluation of the safety of these possible agents is available, and is urgently needed. OBJECTIVE: The purpose of this study was to investigate the risks of cardiac adverse events associated with the possible pharmacotherapies for COVID-19, including certain antimalarial, antiviral, and antibiotic drugs. PATIENTS AND METHODS: We conduced retrospective pharmacovigilance analyses of the US Food and Drug Administration Adverse Event Reporting System database. The reporting odds ratio (ROR), a data mining algorithm commonly used in pharmacovigilance assessment, was generated to quantify the detection signal of adverse events. RESULTS: Among individuals without coronavirus infection from 2015 Q1 to 2020 Q1, increased risks for cardiac disorders were found for antiviral agents such as chloroquine/hydroxychloroquine (ROR: 1.68; 95% confidence interval [CI] 1.66-1.70), lopinavir/ritonavir (ROR: 1.52; 95% CI 1.39-1.66), and antibiotics such as azithromycin (ROR: 1.37; 95% CI 1.30-1.44) and ceftriaxone (ROR: 1.92; 95% CI 1.80-2.05). Increased serious cardiac adverse events, including myocardial infarction, arrhythmia, and cardiac arrest, were also reported for these drugs. Further analyses of individuals with coronavirus infections revealed that 40% of individuals receiving chloroquine/hydroxychloroquine reported serious cardiac adverse events. Two cases resulted in QT prolongations and one case resulted in cardiac arrest. Chloroquine/hydroxychloroquine and azithromycin contributed to all the QT prolongation and cardiac arrest cases. CONCLUSIONS: The current pharmacotherapies for COVID-19 are associated with increased risks of cardiac adverse events. Variations in the cardiac safety profiles of these pharmacotherapies were also observed. Clinicians should closely monitor patients with COVID-19, especially those at high risk, using chloroquine/hydroxychloroquine and azithromycin.

14.
Biomed Res Int ; 2021: 2178143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575322

RESUMO

Background: To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients. Method: We performed a single-center prospective cohort study to analyze changes of NK cells at weeks 12 and 24 from baseline in CHB patients who received PEGylated-interferon- (PEG-IFN-) α-2a versus entecavir. The frequencies of NK, CD56bright, CD56dim, IFNAR2+, NKp46+, NKp46bright, and NKp46dim NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group. Results: In PEG-IFN-α-treated patients, posttreatment CD56bright NK cell frequency increased, but CD56dim NK cell frequency decreased. Additionally, receptor NKp46 and IFNAR2 expression enhanced. In entecavir-treated patients, although NK cell frequency increased, CD56bright and CD56dim NK cell frequencies and IFNAR2 expression did not differ between baseline and posttreatment. In subgroup analyses, posttreatment CD56bright NK cell frequency and IFNAR2 expression significantly increased in PEG-IFN-α responders from baseline, while changes were absent in PEG-IFN-α nonresponders and entecavir treatment responders. Among patients with HBV viremia after entecavir therapy, NK cell frequency significantly increased, whereas NKp46bright and IFNAR2+ NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. Conclusions: In CHB patients, PEG-IFN-α treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.

15.
Anim Biotechnol ; : 1-19, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33635178

RESUMO

The genetic diversity and population structures of five Chongqing local chicken populations were investigated using by 24 microsatellite markers. Results revealed that the mean number of alleles (NA) ranged from 7.08 (Daninghe chicken, DN) to 8.46 (Nanchuan chicken, NC). The highest observed heterozygosity (HO) and expected heterozygosity (HE) were observed in DN (HO = 0.7252; HE = 0.7409) and the lowest HO and HE were observed in XS (Xiushan native chicken [XS], HO = 0.5910 and HE = 0.6697). The inbreeding coefficient (FIS) within population ranged from 0.022 (DN) to 0.119 (XS). Among the 24 microsatellite markers, four loci (MCW0111, MCW0016, ADL0278, and MCW0104) deviated from the Hardy-Weinberg equilibrium in all the studied populations. The results of population polygenetic analysis based on Nei's genetic distance and STRUCTURE software showed that the clustering of the five populations was incomplete consistent with geographical distribution. Moreover, a large number of gene flows were widespread among different populations, suggesting that genetic material exchanges occurred due to human activities and migration which was also verified by PCoA. In summary, this study preliminarily showed that Chongqing local chicken populations had rich genetic diversity and remarkable genetic divergence, but still high risk in conversion. These findings would be useful to the management of conservation strategies and the utilization of local chicken populations in further.

16.
Ann Palliat Med ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33548989

RESUMO

Tumor relapse and pulmonary metastasis, especially unresectable lesions, are the major cause of poor prognosis of patients with osteosarcoma. Anlotinib, a novel small-molecule tyrosine kinase inhibitor (TKI), has been proved to have desirable anti-tumor effects via blocking VEGFR2 and PDGFRß phosphorylation in several tumors, including non-small cell lung cancer and soft tissue sarcoma. In this study, we presented a case of giant delayed pulmonary metastasis of osteosarcoma which was effectively treated by anlotinib. CT scan of this patient showed a giant neoplasm with the size of 1,366 cm3 in the left lung, clinically diagnosed as pulmonary metastasis of osteosarcoma. Due to refusing to chemotherapy and not eligible for surgery of the giant neoplasm, anlotinib was recommended. As a result, the tumor volume decreased more than 82% during 24-week anlotinib administration, from 1,366 to 247 cm3 . Unfortunately, disease progression was observed at 27-week. Although argon-helium cryoablation (AHC) was performed followed by apatinib administration, the patient was dead in 16 weeks after disease progression. The progression-free survival (PFS) and overall survival since anlotinib administration of this patient was 27 weeks and 43 weeks, respectively. The toxicity included hypertension, fatigue and hand-foot skin syndrome in grade1-2, which were controllable and well tolerated. Meanwhile, immunohistochemical staining showed that the expression of VEGFR2 and PDGFRß was decreased significantly and the whole exon sequencing revealed that c-MYC was duplicated, which was potentially associated with anlotinib resistance. Anlotinib had promising anti-tumor efficiency in the treatment of delayed pulmonary metastatic osteosarcoma. However, the potential mechanism of anlotinib resistance and the subsequent therapy after resistance were still challengeable and needed further investigation.

17.
Med Phys ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33550616

RESUMO

PURPOSE: To develop a deep-learning method to predict patient-specific dose volume histograms (DVHs) for radiotherapy planning. METHODS: Patient data included 180 cases with nasopharyngeal cancer, of which 153 cases were used for training and 27 for testing. A network (named 'DVHnet') based on a convolutional neural network (CNN) was designed for directly predicting DVHs of organs at risk (OARs). Two-channel images with contoured structures were generated as the inputs for training the model. A one-dimensional array consisting of 256 continuous volume percentages on a DVH curve for each slice was calculated as the corresponding output. The combined DVH was then calculated. Sixteen OARs were modeled in the study. Prediction accuracy was evaluated against the corresponding DVH curve of ground truth (GT) plans. A global DVH analysis and critical dosimetry metrics for each OAR were calculated for quantitative evaluation. The performance of DVHnet also was evaluated against two baselines: DosemapNet (developed by our research group) and commercial RapidPlan software. RESULTS: The predicted mean differences in average dose of all OARs using DVHnet were 0.30 ± 0.95Gy. And the predicted differences in D2% and D50 can be control within 2.32Gy and 0.69Gy. For most OARs, there were no obvious differences between the dosimetric metrics of the predicted and GT values for both DVHnet and DosemapNet (p≥0.05). Only the predicted D2% of the optic organs for DVHnet, and of brain stem PRV for DosemapNet displayed statistically significant differences. Except for the optic organs, DVHnet performs better than or comparably with RapidPlan. The mean difference in proportion of points of interest were 3.59% ± 7.78%. CONCLUSIONS: A deep-learning network model was developed to automatically extract useful features for accurate prediction of patient-specific DVH curves directly. The performance of DVHnet was comparable to DosemapNet and RapidPlan.

18.
EBioMedicine ; 64: 103239, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33581645

RESUMO

BACKGROUND: Schizophrenia (SZ) is a severe mental disease with highly heterogeneous clinical manifestations and pathological mechanisms. Schizophrenia is linked to abnormalities in cell membrane phospholipids and blunting of the niacin skin flush response, but the associations between these phenotypes and its molecular pathogenesis remain unclear. This study aimed to describe the PLA2/COX pathway, the key link between phospholipids and niacin flush, and to illustrate the pathogenic mechanisms in schizophrenia that mediate the above phenotypes. METHODS: A total of 166 patients with schizophrenia and 54 healthy controls were recruited in this study and assigned to a discovery set and a validation set. We assessed the mRNA levels of 19 genes related to the PLA2/COX cascade in leukocytes by real-time PCR. Plasma IL-6 levels were measured with an ELISA kit. Genetic association analysis was performed on PLA2G4A and PTGS2 to investigate their potential relationship with blunted niacin-skin response in an independent sample set. FINDINGS: Six of the 19 genes in the PLA2/COX pathway exhibited significant differences between schizophrenia and healthy controls. The disturbance of the pathway indicates the activation of arachidonic acid (AA) hydrolysis and metabolization, resulting in the abnormalities of membrane lipid homeostasis and immune function, further increasing the risk of schizophrenia. On the other hand, the active process of AA hydrolysis from cell membrane phospholipids and decreased transcription of CREB1, COX-2 and PTGER4 may explain the reported findings of a blunted niacin response in schizophrenia. The significant genetic associations between PLA2G4A and PTGS2 with the niacin-skin responses further support the inference. INTERPRETATION: These results suggested that the activation of AA hydrolysis and the imbalance in COX-1 and COX-2 expression are involved in the pathogenesis of schizophrenia and blunting of the niacin flush response. FUNDING: This work was supported by the National Key R&D Program of China (2016YFC1306900, 2016YFC1306802); the National Natural Science Foundation of China (81971254, 81771440, 81901354); Interdisciplinary Program of Shanghai Jiao Tong University (ZH2018ZDA40, YG2019GD04, YG2016MS48); Grants of Shanghai Brain-Intelligence Project from STCSM (16JC1420500); Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500); and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01); China Postdoctoral Science Foundation (2018M642029, 2018M630442, 2019M661526, 2020T130407); Natural Science Foundation of Shanghai (20ZR1426700); and Startup Fund for Youngman Research at SJTU (19 × 100040033).

19.
J Investig Med ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558275

RESUMO

This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription-PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3' untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.

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