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1.
Food Chem ; 367: 130697, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365248

RESUMO

Metabolomics is an important branch of systems biology, which can detect changes in the body's metabolism before and after the intervention of functional foods, identify effective metabolites, and predict the interventional effects and the mechanism. This review summarizes the latest research outcomes regarding interventional effects of functional foods on metabolic diseases via metabolomics analysis. Since metabolomics approaches are powerful strategies for revealing the changes in bioactive compounds of functional foods during processing and storage, we also discussed the effects of these parameters on functional food metabolites using metabolomics approaches. To date, a number of endogenous metabolites related to the metabolic diseases after functional foods intervention have been discovered. Unfortunately, the mechanisms of metabolic disease-related molecules are still unclear and require further studies. The combination of metabolomics with other omics technologies could further promote its ability to fully understand the precise biological processes of functional food intervention on metabolic diseases.

2.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4187-4192, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467731

RESUMO

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.


Assuntos
Colite Ulcerativa , Fator 2 Relacionado a NF-E2 , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Sulfato de Dextrana , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais
3.
Exp Cell Res ; 407(2): 112810, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34487733

RESUMO

The miR-10b-5p plays an important role in gastric cancer development but its exact effect on gastric cancer development in vivo has not been fully studied. We showed that miR-10b-5p inhibited the proliferation and migration of gastric cancer cells by down-regulating Tiam1 which was up-regulated in both gastric cancer cells and tissues. Gastric cancer xenograft experiment showed that lenti-miR-10b-5p treatment and agomir-10b-5p injection could significantly retard tumor growth and reduce tumor size and induced apoptosis. Therefore, our results elucidate the tumor suppressor role of miR-10b-5p in gastric cancer in which it acts as a negative regulator of Tiam1 and also provide a molecular mechanism for agomir-10b-5p to treat gastric cancer.

4.
Environ Res ; 204(Pt B): 112041, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34529968

RESUMO

Phthalates, which are widely used in industrial products, can be dermally absorbed into the human body and harm human health. In this study, we measured the levels of phthalates in skin wipes collected from 30 undergraduate volunteers. The body surfaces wiped include the forehead, forearms, hands, back, calves, and insteps. We analyzed the characteristics and possible sources of phthalates on the skin surface and used Monte Carlo simulations to estimate dermal exposure. The mean total dermal exposure was in the range of 0.129-8.25 µg/(kg·day). Seven phthalates were detected, with a detection frequency of 57-100%. Phthalate levels were not significantly different between symmetrical locations, but differed significantly at the same sampling location. The mean dinonyl phthalate (DNP) contribution was the highest on the forehead, back, and forearm. The mean DNP and di (2-n-butoxyethyl) phthalate (DBEP) contributions on hands were the highest and second-highest, respectively. The mean DBEP contribution was the highest on calf and instep. Phthalates level was the maximum on the forehead and instep. Habit and activities can lead to significant differences in phthalate concentrations on the skin surfaces of male and female students. The sum of dermal exposure on the torso, head, and feet perhaps best approximates the total body exposure. To date, information on the dermal exposure and related species of phthalates are limited; therefore, further study is needed.

5.
J Am Heart Assoc ; : e021871, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514840

RESUMO

Background Transcatheter aortic valve replacement with supra-annular transcatheter heart valves has been adopted in patients with degenerated surgical aortic valves. The next generation self-expanding Evolut PRO valve has not been evaluated in patients with surgical valve failure. Methods and Results Patients undergoing transcatheter aortic valve replacement in degenerated surgical aortic valve procedures using the Evolut R or Evolut PRO transcatheter heart valves in the Society of Thoracic Surgeons and American College of Cardiology Transcatheter Valve Therapy Registry between April 2015 and June 2019 were evaluated. Transcatheter valve performance was evaluated by clinical site echocardiography. In-hospital, 30-day, and 1-year clinical outcomes were based on the Society of Thoracic Surgeons-American College of Cardiology-Transcatheter Valve Therapy registry definitions. Transcatheter aortic valve replacement in degenerated surgical aortic valve was performed in 5897 patients (5061 [85.8%] patients received the Evolut R valve and 836 [14.2%] received the Evolut PRO valve). Thirty-day transcatheter heart valves hemodynamic performance was excellent in both groups (mean gradient: Evolut PRO: 13.8±7.5 mm Hg; Evolut R: 14.5±8.1 mm Hg), while paravalvular regurgitation was significantly different between valve types (P=0.02). Clinical events were low at 30 days (Evolut PRO: for the all-cause mortality, 2.8%, any stroke was 1.8%, new pacemaker implantation, 3.0%: Evolut R:all-cause mortality, 2.5%, any stroke was 2.2%, new pacemaker implantation, 5.3%) and 1 year (Evolut PRO: all-cause mortality, 9.2%; any stroke, 3.1%; Evolut R: all-cause mortality, 9.8%; any stroke, 2.9%). Conclusions Transcatheter aortic valve replacement in degenerated surgical aortic valve with self-expandable supra-annular transcatheter heart valves is associated with excellent clinical outcomes and valve hemodynamics. Additional reductions in residual paravalvular regurgitation were obtained with the next generation Evolut PRO.

6.
J Agric Food Chem ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516137

RESUMO

Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects against Xac, Psa, and Xoo. EC50 data exhibited that A8 (19.7 µg/mL) had better antibacterial activity against Xoo than myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the best in vivo antiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 µmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 µmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.

7.
Insect Sci ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516727

RESUMO

Glucose is vital to embryogenesis, as are glucose transporters. Glucose transporter 4 (Glut4) is one of the glucose transporters, which is involved in rapid uptake of glucose by various cells and promotes glucose homeostasis. Although energy metabolism in insect reproduction is well known, the molecular mechanism of Glut4 in insect reproduction is poorly understood. We suspect that Glut4 is involved in maintaining glucose concentrations in the ovaries and affecting vitellogenesis, which is critical for subsequent oocyte maturation and insect fertility. Harmonia axyridis (Pallas) is a model organism for genetic research and a natural enemy of insect pests. We studied the influence of the Glut4 gene on the reproduction and development of H. axyridis using RNA interference technology. Reverse transcription quantitative polymerase chain reaction analysis revealed that HaGlut4 was most highly expressed in adults. Knockdown of the HaGlut4 gene reduced the transcript levels of HaGlut4, and the weight and number of eggs produced decreased significantly. In addition, the transcript levels of vitellogenin receptor and vitellogenin in the fat bodies and the ovaries of h.axyridis decreased after the interference of Glut4, and decreased the triglyceride, fatty acid, total amino acid and ATP content of H. axyridis. This resulted in severe blockage of ovary development and reduction of yolk formation; there was no development of ovarioles in the developing oocytes. These changes indicate that a lack of HaGlut4 can impair ovarian development and oocyte maturation and result in decreased fecundity This article is protected by copyright. All rights reserved.

8.
J Nutr Biochem ; : 108856, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517098

RESUMO

High-fat, high-sugar diet (HFHS) induced leptin resistance and intestinal epithelial dysfunction is implicated in hyperphagia and metabolic disorders. Numerous studies have demonstrated the efficacy of dietary interventions for reducing appetite. This study aims to investigate whether triacylglycerol rich in DHA (DHA-TG) could regulate appetite in mice fed with a HFHS diet and the mechanism by which it achieves that. DHA-TG could reduce food intake and regulate neuropeptides (POMC, AgRP, and NPY) expression in HFHS diet-fed mice. Hypothalamic transcriptome analysis reveals that these effects might be attributed to the role of DHA-TG in modulating hormone secretion and digestive system process. According to ELISA and RT-qPCR analysis, DHA-TG ameliorated leptin secretion and attenuated central leptin resistance induced by HFHS diet feeding. Besides, DHA-TG prevented the damage of intestinal epithelial barrier in nutritive obese mice by improving leptin sensitivity. Based on jejunal transcriptome analysis, DHA-TG also protected intestinal endocrine function, especially the secretion of another anorectic hormone, cholecystokinin (CCK), in HFHS diet-fed mice. Furthermore, DHA-TG was ineffective in repressing appetite and improving gut leakage in leptin-deficient mice (ob/ob mice). In conclusion, DHA-TG has a potential to regulate appetite with the action of leptin and intestinal epithelial functions in HFHS diet-fed mice.

9.
J Investig Med ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518320

RESUMO

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. However, there have been no studies that explored the different time points of ultrasound remission to predict non-progressive structural damage. Given this, the aim of our study is to explore whether early ultrasound remission in patients with rheumatoid arthritis (RA) has predictive value for non-progressive structural damage in the subsequent 12 months. Sixty-one patients with RA were prospectively studied. Synovial hypertrophy, power Doppler (PD) signal, and bone erosions of bilateral wrists, metacarpophalangeal joints I-V, and proximal interphalangeal joints II-III were assessed by ultrasonography at baseline and at 3, 6, and 12 months. Ultrasound remission was defined as no PD signal. Clinical remission was defined as Disease Activity Score in 28 Joints <2.6. Ultrasonography-detected joint damage progression was defined as increase in bone erosion score of ≥1 in the subsequent 12 months. Baseline ultrasonographic factors were not significantly correlated with progressive ultrasonography-detected joint damage in patients with RA at 12 months (all p>0.05). Ultrasound remission at 3 and 6 months was significantly correlated with non-progressive ultrasonography-detected structural damage at 12 months (p=0.006 and p=0.004), with relatively low sensitivity and high specificity. Clinical remission at 3 months was significantly correlated with non-progression of ultrasonography-detected structural damage at 12 months (p=0.029), with relatively low sensitivity and moderate specificity. Ultrasound remission at 3 and 6 months has high specificity in predicting non-progressive structural damage in patients with RA at 12 months; however, the sensitivity is limited.

10.
Environ Res ; 204(Pt A): 111974, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34480945

RESUMO

BACKGROUND: Recent research attention has been paid to anthropogenic heat emissions (AE), temperature increase generated by human activity such as lighting, transportation, manufacturing, construction, and building climate controls. However, there is no epidemiological data available to investigate the association between anthropogenic heat emissions and metabolic syndrome (MetS), a cluster of conditions that increase risk of stroke, heart disease and diabetes. OBJECTIVE: To explore the relationships between AE and MetS in China. METHODS: We recruited 15,477 adults from the 33 Communities Chinese Health Study, a cross-sectional study in northeastern China. We retrieved anthropogenic heat flux by collecting socio-economic and energy consumption data as well as satellite-based nighttime light and Normalized Difference Vegetation Index datasets, including emissions from buildings, transportation, human metabolism, and industries. We also measured MetS components consisting of triglycerides, high density lipoprotein cholesterol, fasting glucose, systolic blood pressure, and diastolic blood pressure, and waist circumference. Restricted cubic spline models were applied to assess the associations between AE and MetS. RESULTS: The median flux of total AE was 30.98 W/m2 and industrial AE was the dominant contributor (87.64%). The adjusted odds ratio and 95% confidence interval (CI) of MetS for the 75th and 95th percentiles of the total AE against the threshold were 1.29 (95% CI: 1.21, 1.38) and 1.65 (95% CI: 1.47, 1.85). Greater AE was associated with higher odds of MetS in a dose-response pattern, and the lowest point of U-shape curve indicated the threshold effect. Participants who are young and middle-aged exhibited stronger associations between AE and MetS. CONCLUSIONS: Our novel findings reveal that AE are positively associated with MetS and that associations are modified by age. Further investigations into the mechanisms of the effects are needed.

11.
J Hazard Mater ; 416: 125867, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492814

RESUMO

Neurodegenerative diseases may be caused by air pollution, such as PM2.5. However, particles still need to be elucidated the mechanism of synergistic neurotoxicity induced by pollutant-loading PM2.5. In this study, we used a reductionist approach to study leading role of lead (Pb) in PM2.5-induced hippocampal neuronal apoptosis and synaptic damage both in vivo and in vitro. Pb in PM2.5 caused neurotoxicity: 1) by increasing ROS levels and thus causing apoptosis in neuronal cells and 2) by decreasing the expression of PSD95 via interfering with the calcium signaling pathway through cAMP/CREB/pCREB/BDNF/PSD95 pathway and reducing the synapse length by 50%. This study clarifies a key factor in PM2.5-induced neurotoxicity and provides the experimental basis for reducing PM2.5-induced neurotoxicity.


Assuntos
Hipocampo , Chumbo , Apoptose , Chumbo/toxicidade , Material Particulado/toxicidade , Sinapses
12.
Artigo em Inglês | MEDLINE | ID: mdl-34480736

RESUMO

INTRODUCTION: At present, some studies have reported that nasal rosacea may be an independent disease, but phenotypic characteristics and risk factors for nasal rosacea remain unknown. This study aimed to clarify the clinical features and explore the risk factors for nasal rosacea. METHODS: A hospital-based retrospective study was conducted, including 1615 rosacea patients and 1501 healthy individuals. The patients were divided into three groups based on the involved areas of the lesions (non-nasal, intermediate and nasal rosacea group). Their demographic data and clinical features were obtained from patients' medical records, and risk factors of nasal rosacea were analyzed. RESULTS: There were 927 (57.4%), 647 (40.1%) and 41 (2.5%) cases in the non-nasal, intermediate and nasal rosacea groups, respectively. Of 41 patients with nasal rosacea, all (100.0%) had fixed erythema and 17 cases (41.5%) had phymatous changes. Compared with control group, male gender (adjusted odds ratio [aOR] = 2.39, 95% confidence interval [CI] = 1.14, 4.99), obesity (aOR = 3.19, 95% CI 1.86, 11.79) and alcohol use (aOR = 1.58, 95% CI 1.22, 5.40) were risk factors for nasal rosacea, but these three factors were not risk factors for non-nasal rosacea and intermediate rosacea groups. Among patients with nasal lesions (compared with patients without nasal phymatous changes), family history of rosacea was a risk factor (aOR = 2.12, 95% CI 1.01, 4.46) for nasal phymatous changes and Fitzpatrick IV skin type was a protective factor (aOR = 0.49, 95% CI 0.28, 0.86). CONCLUSION: Nasal rosacea has relatively specific clinical features and independent risk factors, suggesting that it may be a special type of rosacea.

13.
Chem Commun (Camb) ; 57(71): 8969-8972, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486594

RESUMO

An unprecedented electrochemical heterodifunctionalization of α-CF3 alkenes with benzenesulfonyl hydrazides was accomplished in this work, wherein a ß-sulfonyl and a α-hydroxyl group were simultaneously incorporated across the olefinic double bond in a single operation. Consequently, a series of potentially medicinally valuable and densely functionalized α-trifluoromethyl-ß-sulfonyl tertiary alcohols were assembled under mild conditions. Electrochemically-driven oxidative 1,2-difunctionlization of electron-deficient alkenes well obviates the need for oxidizing reagents, thus rendering this protocol more eco-friendly.

14.
World J Surg Oncol ; 19(1): 283, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34537058

RESUMO

BACKGROUND: To study the clinical value of miR-135 and miR-20a combined with multi-detector computed tomography (MDCT) in the diagnosis of gastric cancer (GC). METHOD: A total of 146 patients with GC admitted to our hospital from January 2017 to June 2019 were selected and enrolled in the GC group. Another 103 patients with gastritis received in the same period were selected for the non-GC group. Besides, 95 healthy subjects who received physical examination in our hospital were selected into the healthy control group. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of serum miR-135 and miR-20a for each group. MDCT was used for detecting the clinical staging map of the enrolled patients. Pearson's correlation analysis was used to analyze the correlation between serum miR-135 and miR-20a in patients with GC. The receiver operating characteristic (ROC) curve was drawn to analyze value of miR-135 and miR-20a in the diagnosis of GC. RESULTS: Compared with non-GC group and healthy control group, the levels of serum miR-135 and miR-20a increased significantly in the GC group, while no significant difference was found between non-GC group and healthy control group (P > 0.05). Analysis of the relationship with clinical characteristics showed that the expression of serum miR-135 and miR-20a in the GC group was significantly correlated with the progression of GC, TNM stage, degrees of differentiation, status of lymph node metastasis, and distant metastasis (P < 0.01). Pearson's correlation analysis results showed positive correlations between miR-135 and miR-20a (r = 0.634, P = 0.000). The ROC analysis results showed that the optimal diagnostic values of miR-135 and miR-20a for GC were 7.56 and 5.82 respectively. The area under the curve (AUC) was 0.873 and 0.793 respectively. The 95% confidence interval (CI) was 0.811-0.935 and 0.697-0.890 respectively. The sensitivity and specificity of miR-135 and miR-20a combined with MDCT in the diagnosis of GC were 90.41% and 93.20% respectively. The sensitivity of combined use was significantly higher than that of single detection (P < 0.01). CONCLUSION: There are high expression levels of serum miR-135 and miR-20a in patients with GC. A combined detection of miR-135 and miR-20a with MDCT can improve the diagnostic sensitivity of GC and improve the accuracy of the final diagnosis. Therefore, multiple combined detection is valuable in the diagnosis of GC.

15.
J Med Chem ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542267

RESUMO

Protein drugs hold great promise as therapeutics for a wide range of diseases. Unfortunately, one of the greatest challenges to be addressed during clinical development of protein therapeutics is their short circulation half-life. Several protein conjugation strategies have been developed for half-life extension. However, these strategies have limitations and there remains room for improvement. Here, we report a novel nature-inspired strategy for enhancing the in vivo half-life of proteins. Our strategy involves conjugating proteins to a hydrophilic small molecule that binds reversibly to the plasma protein, transthyretin. We show here that our strategy is effective in enhancing the pharmacokinetic and pharmacodynamic properties of human interleukin 2 in rats, potentially opening the door for more effective and safer cancer immunotherapies. To our knowledge, this is the first example of successful use of a small-molecule that not only extends the half-life but also maintains the smaller size, binding potency, and hydrophilicity of proteins.

16.
Endocr Connect ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524970

RESUMO

OBJECTIVE: To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy(DN). METHODS: A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least one year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group286.02± 46.66 µmol/L (n=98); Q2 group: 358.23±14.03µmol/L (n=99); Q3 group: 405.50±14.59µmol/L (n=98) and Q4 group: 499.14±56.97µmol/L (n=98).Renal outcome was defined by progression to end stage renal disease (ESRD). Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes. RESULTS: During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%) during follow-up. No significant difference among SUA level the risk of progression of DN (P=0.747) was shown in the Kaplan-Meier survival analysis. In multivariable-adjusted model, HRs for developing ESRD were 1.364(0.621-2.992; p=0.439), 1.518(0.768-3.002; p=0.230) and 1.411(0.706-2.821; p=0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P=0.652). CONCLUSIONS: No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improve ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34533891

RESUMO

OBJECTIVES: To assess the safety profile of redo-TAVR procedures from patients in the transcatheter valve therapy (TVT) Registry. BACKGROUND: The use of transcatheter aortic valves (TAV) to treat previously implanted failing TAVS (TAV-in-TAV) has been an increasingly important topic as indications for TAVR move to younger and lower-risk patients, but data on the safety and efficacy of redo-TAVR is limited. METHODS: Patients undergoing redo-TAVR procedures using the Evolut R, Evolut PRO or Evolut PRO+ valve in the TVT Registry between April 2015 and March 2020 were included. In-hospital, 30-day and 1-year outcomes were analyzed. RESULTS: Redo-TAVR was performed in 292 patients (213 patients received the Evolut R valve and 79 received the Evolut PRO or PRO+ valve). Device success was achieved in 94.5%. In-hospital mortality was 2.1%, stroke occurred in 2.7%, and 77.2% of patients were discharged home. There were no cases of coronary compression/obstruction or myocardial infarction that occurred in index hospitalization. Mean gradient at 30-days was 11.9 ± 6.9 mmHg, and 73.1% had none/trace total aortic regurgitation. CONCLUSIONS: Results from the TVT Registry demonstrate good short-term outcomes after redo-TAVR with the supra-annular, self-expandable Evolut platform. Long-term follow-up is necessary to further expand understanding this complex scenario.

18.
Mol Med Rep ; 24(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34476503

RESUMO

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tuberculosis) infection and has the highest mortality rate of any single infectious disease worldwide. The aim of the present study was to investigate the function of microRNA (miR)­502­3p in M. tuberculosis­infected macrophages. The Gene Expression Omnibus database was used to analyze miR­502­3p expression in patients with TB and healthy individuals. THP­1 and RAW 264.7 cells were transfected with miR­502­3p mimic, miR­502­3p inhibitor, pcDNA3.1­ROCK1 or their negative controls. The expression levels of miR­502­3p and inflammatory cytokines were evaluated using reverse transcription­quantitative PCR. The colony­forming unit assay was performed to assess the survival of M. tuberculosis in macrophages, and Toll­like receptor (TLR)4/NF­κB signaling pathway­associated protein expression levels were detected by western blotting. The nuclear translocation of NF­κB p65 was detected via immunocytochemistry. TargetScan was used to predict the binding sites between miR­502­3p and ROCK1. The interaction between miR­502­3p and Rho­associated coiled­coil­forming protein kinase 1 (ROCK1) was confirmed using a dual­luciferase reporter assay; ROCK1 was demonstrated to be a direct target gene of miR­502­3p. Results from the present study demonstrated that miR­502­3p expression was significantly increased during M. tuberculosis infection in macrophages. Upregulation of miR­502­3p expression levels significantly enhanced the survival of intracellular M. tuberculosis. IL­6, TNF­α, and IL­1ß mRNA expression levels were significantly upregulated during M. tuberculosis infection but were downregulated by miR­502­3p overexpression. Moreover, miR­502­3p mimics transfection significantly downregulated TLR4/NF­κB signaling pathway­associated protein expression and significantly reduced nuclear transcription of NF­κB in M. tuberculosis­infected macrophages. ROCK1 overexpression reversed the miR­502­3p inhibitory effect on cytokine production in M. tuberculosis­infected macrophages. In conclusion, miR­502­3p/ROCK1 may serve an anti­inflammatory role and may improve the survival of M. tuberculosis within macrophages, which may provide a promising therapeutic target for TB.

19.
JMIR Mhealth Uhealth ; 9(9): e29498, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499047

RESUMO

BACKGROUND: Diabetes has placed heavy social and economic burdens on society and families worldwide. Insufficient knowledge and training of frontline medical staff, such as nurses, interns, and residents, may lead to an increase in acute and chronic complications among patients with diabetes. However, interns have insufficient knowledge about diabetes management. The factors that affect interns' current level of diabetes-related knowledge are still unclear. Therefore, understanding the behavioral intentions of interns is essential to supporting the development and promotion of the use of virtual simulation teaching applications. OBJECTIVE: This study aimed to identify the determinants of nursing interns' intentions to use simulation-based education applications. METHODS: From December 1, 2020, to February 28, 2021, the web-based survey tool Sojump (Changsha Xingxin Information Technology Co) was used to survey nursing interns in hospitals across China. Two survey links were sent to 37 partner schools in 23 major cities in China, and they were disseminated through participants' WeChat networks. Multiple regression analysis was used to determine the association between demographic information and basic disease information and the use of the application for treating adult patients. RESULTS: Overall, 883 nursing interns from 23 provinces in China responded to the survey. Among them, the virtual simulation utilization rate was 35.6% (314/883) and the awareness rate was 10.2% (90/883). In addition, among the interns, only 10.2% (90/883) correctly understood the concept of virtual simulation, and most of them (793/883, 89.8%) believed that scenario-simulation training or the use of models for teaching are all the same. Multiple regression analysis showed that the educational level, independent learning ability, and professional identity of the interns were related to use of the application (P<.05). Skills and knowledge that the interns most wanted to acquire included the treatment of hypoglycemia (626/883, 70.9%), functional test simulation (610/883, 69.1%), and blood glucose monitoring technology (485/883, 54.9%). A total of 60.5% (534/883) of the interns wanted to acquire clinical thinking skills, while 16.0% (141/883) wanted to acquire operational skills. Nursing trainees believed that the greatest obstacles to virtual simulation included limited time (280/883, 31.7%), the degree of simulation (129/883, 14.6%), the demand for satisfaction (108/883, 12.2%), and test scores (66/883, 7.5%). CONCLUSIONS: The understanding and usage rate of diabetes virtual simulation teaching applications by Chinese nursing interns is very low. However, they have high requirements regarding this teaching method. Conducting high-quality randomized controlled trials and designing applications that are suitable for the needs of different nurse trainees will increase students' interest in learning and help improve diabetes knowledge among nursing interns.

20.
Proc Natl Acad Sci U S A ; 118(37)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34504019

RESUMO

Endothelial cell (EC) sensing of wall fluid shear stress (FSS) from blood flow governs vessel remodeling to maintain FSS at a specific magnitude or set point in healthy vessels. Low FSS triggers inward remodeling to restore normal FSS but the regulatory mechanisms are unknown. In this paper, we describe the signaling network that governs inward artery remodeling. FSS induces Smad2/3 phosphorylation through the type I transforming growth factor (TGF)-ß family receptor Alk5 and the transmembrane protein Neuropilin-1, which together increase sensitivity to circulating bone morphogenetic protein (BMP)-9. Smad2/3 nuclear translocation and target gene expression but not phosphorylation are maximal at low FSS and suppressed at physiological high shear. Reducing flow by carotid ligation in rodents increases Smad2/3 nuclear localization, while the resultant inward remodeling is blocked by the EC-specific deletion of Alk5. The flow-activated MEKK3/Klf2 pathway mediates the suppression of Smad2/3 nuclear translocation at high FSS, mainly through the cyclin-dependent kinase (CDK)-2-dependent phosphosphorylation of the Smad linker region. Thus, low FSS activates Smad2/3, while higher FSS blocks nuclear translocation to induce inward artery remodeling, specifically at low FSS. These results are likely relevant to inward remodeling in atherosclerotic vessels, in which Smad2/3 is activated through TGF-ß signaling.

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