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1.
J Food Biochem ; : e13987, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730245

RESUMO

The aim of this study was to evaluate the protective effects of Lepidium draba L. extract on cyclophosphamide (CP)-induced oxidative damages to testes in rats using sex hormones, antioxidant properties, inflammatory, and apoptotic pathways. Six groups of male Wistar rats (n = 6/group) received distilled water (NC), CP (100 mg kg-1  day-1 /intraperitoneal), CP with L. draba extract [100 (LDCP 100), 200 (LDCP 200), and 400 (LDCP 400) mg/kg/day/orally] and also only L. draba extract [400 (LD400) mg/kg/day/orally] in 35 days. On day 36 of the study, sperm parameters, serum levels of sex hormones, antioxidant enzyme activity, nitric oxide levels, and inflammatory cytokines and also testicular tissue (ferric reducing antioxidant power and thiobarbituric acid reactive substances levels and expression of ROS-dependent pro/anti-apoptotic pathways) were evaluated. In L. draba-treated groups, especially doses of 200 and 400, in addition to improving sperm parameters and sex hormones (Increased levels of all three hormones luteinizing hormone, follicle-stimulating hormone, and testosterone), serum antioxidant (catalase, superoxide dismutase, and glutathione peroxidase activity increased and nitric oxide levels decreased), and anti-inflammatory properties (levels of IL-6, TNF-α, and IL-1ß decreased and MIF and TGF-ß increased) also showed modification. By strengthening the anti-apoptotic pathway of Keap1/Nrf2/HO1 and inhibiting the apoptotic pathway of Bax/Bcl2/p53/caspase-3, L. draba maintains the structure and function of testicular tissue so that eventually p53-positive testicular cells are reduced and Bcl-2-positive cells increased. L. draba can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti-inflammatory, and antioxidant pathways. PRACTICAL APPLICATIONS: Lepidium draba have considerable antioxidant properties and can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti-inflammatory, and antioxidant pathways. The present results are useful to find a suitable supplement for improving the sexual performance of patients treated with chemotherapy drugs.

2.
Front Behav Neurosci ; 15: 747733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803624

RESUMO

Tai Chi Chuan (TCC) is assumed to exert beneficial effects on functional brain activity and cognitive function in elders. Until now, empirical evidence of TCC induced intra-regional spontaneous neural activity and inhibitory control remains inconclusive. Whether the effect of TCC is better than that of other aerobic exercises is still unknown, and the role of TCC in younger adults is not yet fully understood. Here we used resting-state functional MRI (fMRI) to investigate the effects of 8-week TCC (n = 12) and brisk walking (BW, n = 12) on inhibitory control and fractional amplitude of low-frequency fluctuations (fALFF). The results found that TCC had significant effects on inhibitory control performance and spontaneous neural activity that were associated with significantly increased fALFF in the left medial superior frontal gyrus (Cohen's d = 1.533) and the right fusiform gyrus (Cohen's d = 1.436) and decreased fALFF in the right dorsolateral superior frontal gyrus (Cohen's d = 1.405) and the right paracentral lobule (Cohen's d = 1.132).TCC exhibited stronger effects on spontaneous neural activity than the BW condition, as reflected in significantly increased fALFF in the left medial superior frontal gyrus (Cohen's d = 0.862). There was a significant positive correlation between the increase in fALFF in the left medial superior frontal gyrus and the enhancement in inhibitory control performance. The change in fALFF in the left medial superior frontal gyrus was able to explain the change in inhibitory control performance induced by TCC. In conclusion, our results indicated that 8 weeks of TCC intervention could improve processing efficiency related to inhibitory control and alter spontaneous neural activity in young adults, and TCC had potential advantages over BW intervention for optimizing spontaneous neural activity.

4.
Vet Microbiol ; 263: 109263, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34749283

RESUMO

Transmissible gastroenteritis (TGE) and porcine epidemic diarrhea (PED) are highly transmissible intestinal infections caused by transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), respectively. They are clinically associated with vomiting, diarrhea, and dehydration in piglets. An imbalance in Na+ uptake by intestinal epithelial cells causes TGEV/PEDV-induced diarrhea. However, the mechanism by which TGEV/PEDV-infection in piglets causes Na+ imbalance diarrhea has not been elucidated. In the present study, we demonstrated that specific inhibition of NHE3 activity caused small intestinal bulging, intestinal wall thinning and severe diarrhea in piglets, consistent with the signs of TGEV/PEDV infection. This study further elucidated the role of NHE3 in TGEV/PEDV-induced diarrhea. In this study, small intestinal epithelial cells (IPEC-J2) were used as a model of infection. The results showed that TGEV/PEDV infection reduced NHE3 activity and Na+ uptake in IPEC-J2 cells. Further studies revealed that the use of NHE3-specific inhibitors could reduce the amount of cell membrane NHE3, thereby decreasing Na+ uptake and ultimately leading to diarrhea. Transcriptomic studies performed on obtained jejunal tissues were also consistent with pre-laboratory results. This study will provide a basis for understanding Na+ imbalance diarrhea caused by TGEV/PEDV, as well as for elucidating the diarrheal pathogenesis of other members of α-animal coronaviruses.

5.
Cogn Neurodyn ; 15(6): 1015-1022, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34790268

RESUMO

It is well known that different names of color can lead to distinct attractions to people. To study the neural mechanism underlying this phenomenon, an implicit association test task was designed for color names, in which participants were required to select the possible meanings of a Greek phrase from two color names (in Chinese). The behavioral results showed that the participants were more likely to select novel names for long Greek phrases and dates names for short Greek phrases. The EEG results showed that the mean amplitude of N1 was greater for selections of novel color names than selections of dates names for Greek phrases. Meanwhile, the mean amplitude of N3 for novel color names was more negative than that of dates color names. Significant interaction effect of N3 was also found for the four kinds of selections between Greek phrases and Chinese color names. Moreover, a frontal-positive and occipital-negative distribution for scalp topography of N1 was found, while the scalp topography of N3 was opposite as frontal-negative and occipital-positive distribution, suggesting the importance of visual cortex for perception of the color names and prefrontal cortex for integration and decision of selection. In summary, the results here indicated that colors with novel names could easily attract people's attention than colors with dates names, which might shed light on the usage of color names in real life.

6.
Front Oncol ; 11: 751758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765557

RESUMO

Post-radiation soft tissue sarcomas (PRSTSs) are rare secondary malignancies. In this report, we describe the clinical presentation of a 52-year-old woman who underwent postmastectomy radiation therapy (PMRT) for left-sided breast cancer 2.7 years ago and presented with a left internal mammary mass and left interpectoral nodule on computed tomography. On further evaluation, she was diagnosed with internal mammary rhabdomyosarcoma and interpectoral nodal breast cancer relapse, and was treated with chemotherapy, followed by surgery and endocrine therapy. She developed left pleural metastases and is currently receiving targeted therapy. Internal mammary rhabdomyosarcomas are rare among PRSTSs and pose a diagnostic challenge for patients with breast cancer. Histological evaluation is important for the differential diagnosis of breast cancer relapses with secondary malignancies. The management of post-radiation thoracic rhabdomyosarcomas is challenging, and the prognosis is poor.

7.
BMJ Open ; 11(11): e047774, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772745

RESUMO

AIMS: To develop a nomogram for incident chronic kidney disease (CKD) risk evaluation among community residents with high cardiovascular disease (CVD) risk. METHODS: In this retrospective cohort study, 5730 non-CKD residents with high CVD risk participating the National Basic Public Health Service between January 2015 and December 2020 in Guangzhou were included. Endpoint was incident CKD defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 during the follow-up period. The entire cohorts were randomly (2:1) assigned to a development cohort and a validation cohort. Predictors of incident CKD were selected by multivariable Cox regression and stepwise approach. A nomogram based on these predictors was developed and evaluated with concordance index (C-index) and area under curve (AUC). RESULTS: During the median follow-up period of 4.22 years, the incidence of CKD was 19.09% (n=1094) in the entire cohort, 19.03% (727 patients) in the development cohort and 19.21% (367 patients) in the validation cohort. Age, body mass index, eGFR 60-89 mL/min/1.73 m2, diabetes and hypertension were selected as predictors. The nomogram demonstrated a good discriminative power with C-index of 0.778 and 0.785 in the development and validation cohort. The 3-year, 4-year and 5-year AUCs were 0.817, 0.814 and 0.834 in the development cohort, and 0.830, 0.847 and 0.839 in the validation cohort. CONCLUSION: Our nomogram based on five readily available predictors is a reliable tool to identify high-CVD risk patients at risk of incident CKD. This prediction model may help improving the healthcare strategies in primary care.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34739383

RESUMO

We introduce an innovative solution approach to the challenging dynamic load-shedding problem which directly affects the stability of large power grid. Our proposed deep Q-network for load-shedding (DQN-LS) determines optimal load-shedding strategy to maintain power system stability by taking into account both spatial and temporal information of a dynamically operating power system, using a convolutional long-short-term memory (ConvLSTM) network to automatically capture dynamic features that are translation-invariant in short-term voltage instability, and by introducing a new design of the reward function. The overall goal for the proposed DQN-LS is to provide real-time, fast, and accurate load-shedding decisions to increase the quality and probability of voltage recovery. To demonstrate the efficacy of our proposed approach and its scalability to large-scale, complex dynamic problems, we utilize the China Southern Grid (CSG) to obtain our test results, which clearly show superior voltage recovery performance by employing the proposed DQN-LS under different and uncertain power system fault conditions. What we have developed and demonstrated in this study, in terms of the scale of the problem, the load-shedding performance obtained, and the DQN-LS approach, have not been demonstrated previously.

9.
Chem Commun (Camb) ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755720

RESUMO

We demonstrate a rapid one-step scalable microwave heating-based method to prepare Ti3C2Tx MXenes, which shortens the synthesis time from tens of hours for state-of-the-art approaches to 15 minutes and avoids time-consuming delamination with organic compounds. Noticeably, the microwave-synthesized MXene nanosheets have a tailorable size, a stable colloidal dispersion, high electrical conductivity and superior near-infrared (NIR) photothermal conversion performance.

10.
Front Cardiovasc Med ; 8: 736854, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660739

RESUMO

Background: Several cardiovascular risk factors have been suggested to be associated with anthracycline-induced cardiotoxicity, but their quantitative effects have not reached a consensus. Methods: We searched PubMed, EMBASE, and Cochrane Library databases for manuscripts published from inception to February 2021, which reported the results of cardiotoxicity due to anthracycline chemotherapy without trastuzumab. Cardiotoxicity defined by any reduction of left ventricular eject fraction (LVEF) to below 50% or a >10% reduction from baseline was defined as the primary endpoint. Odd ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model meta-analysis. Results: A total of 7,488 patients receiving anthracycline chemotherapy without trastuzumab were included, who had at least one risk factor at baseline. Hypertension (OR: 1.99; 95% CI: 1.43-2.76), diabetes mellitus (OR: 1.74; 95% CI: 1.11-2.74), and obesity (OR: 1.72; 95% CI: 1.13-2.61) were associated with increased risk of cardiotoxicity. In addition, the relative reduction of global longitudinal strain (GLS) from baseline after anthracycline treatment could significantly improve the detection ability of cardiotoxicity (28.5%, 95% CI: 22.1-35.8% vs. 16.4%, 95% CI: 13.4-19.9%) compared with LVEF. The early detection rate of anthracycline-induced cardiotoxicity (3 months after chemotherapy) by GLS was 30.2% (95% CI: 24.9-36.1%), which is similar with the overall result of GLS. Conclusions: Hypertension, diabetes mellitus, and obesity are associated with increased risk of anthracycline-induced cardiotoxicity, which indicates that corresponding protective strategies should be used during and after anthracycline treatment. The findings of higher detection rate and better early detection ability for cardiotoxicity than LVEF added new proofs for the advantages of GLS in detection of AIC.

11.
Front Bioeng Biotechnol ; 9: 733980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692656

RESUMO

Delayed chest closure (DSC) is widely performed during the treatment of congenital heart diseases. However, the high prevalence of surgical site infection (SSI) in patients undergoing DSC affects prognosis negatively. Herein, we designed a suturable poly (vinyl alcohol)/keratin film loaded with silver nanoparticles (AgNPs) as an alternative material for DSC, which was named PVA/Keratin/AgNPs. The PVA/Keratin/AgNPs films exhibited significantly enhanced mechanical strength after crosslinking by sodium trimetaphosphate (STMP). These films were non-toxic, and cells proliferated with good morphology after 1 week of culture. In addition, PVA/Keratin/AgNPs films provided superior antibacterial ability, as evidenced by the eradication and lower growth rate of Staphylococcus aureus and Escherichia coli. Finally, the PVA/Keratin/AgNPs films were demonstrated to successfully cover the chest cavity temporarily and protect the chest cavity from bacterial infection. These results indicated that the PVA/Keratin/AgNPs films have great prospects to be further exploited for clinical applications in DSC.

12.
Chem Biodivers ; : e2100679, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34651409

RESUMO

Pomelo seeds (PS) are important by-product of pomelo fruits (Citrus grandis Osbeck). The value-added utilization of PS remains highly challenged. This study aimed to investigate the utilization potential of PS as natural antioxidant, antibacterial, herbicidal agents, and their functional components. The ethanolic extract (EE) of PS and its four fractions as PEE (petroleum ether extract), AcOEtE (ethyl acetate extract), BTE (butanol extract), and WE (water extract), were prepared and biologically evaluated. BTE exhibited the best antioxidant activity among all these extracts, in both ABTS (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and FRAP (ferric reducing antioxidant power) assays. AcOEtE was superior to other extracts in herbicidal assay against both Festuca elata Keng (IC50 of 0.48 mg mL-1 ) and Amaranthus retroflexus L. (IC50 of 0.94 mg mL-1 ). Meanwhile, both AcOEtE and BTE demonstrated inhibitory effects against Bacillus subtilis, Escherichia coli, and Xanthomonas citri subsp. citri, with MIC ranging 2.5-5.0 mg mL-1 . Furthermore, the primary chemical components involving naringin, deacetylnomilin, limonin, nomilin, and obacunone, were quantified in all these extracts. PCA (principal component analysis) suggested that naringin might highly contribute to the antioxidant activity of PS, and the herbicidal activity should be ascribed to limonoids. This study successfully identified AcOEtE and BTE as naturally occurring antioxidant, antibacterial, and herbicidal agents, showing application potential in food and cosmetics industries, and organic farming agriculture.

13.
J AOAC Int ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636904

RESUMO

BACKGROUND: The less volatile fraction of perfumes can be easily contaminated by phthalates esters (PAEs) which are endocrine-disrupting chemicals during the production, bottling and transportation processes. It is necessary to establish an innovative and rapid method to determine the trace PAEs in commercial perfumes. OBJECTIVE: Hence, self-built spray-inlet microwave plasma torch ionization coupled with a quadrupole time-of-flight tandem mass spectrometer (QTOF-MS) was developed for direct analysis of PAEs in perfumes with no sample pretreatment. METHODS: Perfumes were sprayed to the MPT's flame directly by sampling pump in 10 µL/min and the ions produced by MPT were introduced into QTOF-MS, the MPT worked at 2450 MHz and 40 W in the 800 ml/min flow rate of argon. RESULTS: For the developed method, excellent linearities were obtained and the correlation coefficient of Di-n-pentyl Phthalate was 0.9799 and the rest were larger than 0.99. The LODs and LOQs were obtained in the ranges of 1.452-18.96 ng/g and 4.839-63.19 ng/g, respectively. The spiked recoveries of PAEs were in the range of 100.1-105.2% with satisfied intra-day RSDs and inter-day RSDs ranging from 1.51-4.34% and 3.45-5.65%, respectively. PAEs in commercial perfumes were successfully detected by spray-inlet MPT-MS2 with low concentrations from 0.036-1.352 µg/g. CONCLUSIONS: The method is a promising tool in field analysis of PAEs in cosmetic solutions where rapid qualitative and quantitative analysis in needed. HIGHLIGHTS: The method was satisfactorily applied to the analysis of commercial perfume samples within 30 s, and earned merits such as simplicity, sensitivity, environmental friendliness and ease operation.

14.
Chemosphere ; 287(Pt 3): 132213, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34560494

RESUMO

The effects of different surfactants (rhamnolipid, trehalolipid and citrate) on phosphorus (P) release and acidogenic fermentation of waste activated sludge (WAS) containing different aluminium phosphate forms (AlPO4, Al(PO3)3) were investigated. Results showed that rhamnolipid was the most effective surfactant to release P from aluminum phosphates (AlPs)-rich sludge. Al(PO3)3 was easier to release P than AlPO4 in WAS due to their different crystal structures. Different surfactants promoted the production of different types of protein. The addition of rhamnolipid was conducive to produce propionate from WAS, while trehalolipid and citrate increased the production of n-butyrate and acetate, respectively. Citrobacter played an important role in producing phosphatase continuously for P release with rhamnolipid addition. Predictive functional profiling indicates that rhamnolipid greatly facilitated adenosine triphosphate (ATP)-binding cassette transporter and quorum sensing. These important discoveries help to enrich P recovery paths from sludge produced with Al-based coagulants in wastewater treatment plants.

15.
Nurs Open ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546665

RESUMO

AIM: This study aims to develop a reliable and validate Chinese version of Oldenburg Burnout Inventory (OLBI). DESIGN: A cross-sectional validation design was adopted in this study. METHODS: After obtaining the copyright by contacting with the author, the original English OLBI was developed to Chinese by forward translation, back-translation, cultural adaptation and a pre-test (20 nurses). The Chinese OLBI and Maslach Burnout Inventory (MBI) were administered to 641 clinical nurses during July and August, 2020. Internal consistency (Cronbach's α coefficient), split reliability (split half coefficient), construct validity (confirmatory factor analysis) and criterion validity (comparison with MBI, using Pearson correlation analysis) were assessed. RESULTS: The Chinese OLBI included 16 items. Exploratory factor analysis extracted two factors with a cumulative contribution of 62.245%. Two-dimensional structure (exhaustion and disengagement) was confirmed. It has good internal consistency (Cronbach's α coefficient values of 0.905, 0.933 and 0.876 for the total questionnaire, exhaustion dimension and disengagement dimension, respectively), split half reliability (split half coefficient = 0.883, p < .01) and criterion validity (r = 0.873, p < .01). Pearson coefficients between 16 items and the scale varied from 0.479-0.765. An acceptable model fit (χ2 /df = 2.49, RMSEA = 0.068, TLI = 0.906, CFI = 0.922, SRMR = 0.061) was achieved.

16.
Front Oncol ; 11: 627016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513654

RESUMO

Background: Mounting randomized clinical trials have proved that immune checkpoint inhibitors (ICIs) achieved better overall survival (OS) and progression-free survival (PFS) than chemotherapy drugs for advanced non-small cell lung cancer (NSCLC) patients. However, some literatures have indicated that different sexes might not have equal immune response. Also, no agreement reached on the issue whether therapeutic benefit of ICIs is related to sex. Objectives: To explore the association between efficacy of ICIs for NSCLC patients and their sexes and summarize overall treatment-related adverse events (TRAEs) in an exploratory manner. Methods: We performed this systematic review and meta-analysis of all potentially relevant studies retrieved from PubMed, EMBASE, and the Cochrane Library until June 2021, for eligible randomized controlled trials (RCTs) comparing immunotherapy with chemotherapy in advanced NSCLC patients. Literature screening, summary data extraction was performed independently and in duplicate. The pooled hazard ratio (HR) and 95% confidence interval (CI) of OS, PFS and TRAEs were calculated, applying STATA software and random-effects models. This study was registered in international prospective register of systematic reviews (PROSPERO), number CRD42020210797. Results: Twenty-one trials involving 12,675 NSCLC patients were included. For patients with advanced NSCLC, ICIs significantly prolonged the OS (males: HR 0.73, 95%CI 0.67-0.79; females: HR 0.73, 95%CI 0.61-0.85) and PFS (males: HR 0.62, 95%CI 0.55-0.70; females: HR 0.68, 95%CI 0.55-0.81) versus chemotherapy. Overall, there was no statistical difference between their sexes (OS: P = 0.97; PFS: P = 0.43), respectively. Owing to insufficient TRAEs data of different sexes, we only found immunotherapy for NSCLC patients had more all-grades (RR 0.88; 95%CI 0.82-0.95) and 3-5 grades (RR 0.60; 95%CI 0.47-0.75) AEs compared with chemotherapy. Conclusion: Our findings indicated that the interaction between immunotherapy efficacy and different sexes was equally evident. Overall, patients with NSCLC could obtain more benefits from ICIs than chemotherapy regimen regardless of their sexes. Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020210797.

17.
Front Cell Dev Biol ; 9: 710112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490258

RESUMO

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease caused by expanded CTG repeats in the 3' untranslated region (3'UTR) of the DMPK gene. The myogenesis process is defective in DM1, which is closely associated with progressive muscle weakness and wasting. Despite many proposed explanations for the myogenesis defects in DM1, the underlying mechanism and the involvement of the extracellular microenvironment remained unknown. Here, we constructed a DM1 myoblast cell model and reproduced the myogenesis defects. By RNA sequencing (RNA-seq), we discovered that periostin (Postn) was the most significantly upregulated gene in DM1 myogenesis compared with normal controls. This difference in Postn was confirmed by real-time quantitative PCR (RT-qPCR) and western blotting. Moreover, Postn was found to be significantly upregulated in skeletal muscle and myoblasts of DM1 patients. Next, we knocked down Postn using a short hairpin RNA (shRNA) in DM1 myoblast cells and found that the myogenesis defects in the DM1 group were successfully rescued, as evidenced by increases in the myotube area, the fusion index, and the expression of myogenesis regulatory genes. Similarly, Postn knockdown in normal myoblast cells enhanced myogenesis. As POSTN is a secreted protein, we treated the DM1 myoblast cells with a POSTN-neutralizing antibody and found that DM1 myogenesis defects were successfully rescued by POSTN neutralization. We also tested the myogenic ability of myoblasts in the skeletal muscle injury mouse model and found that Postn knockdown improved the myogenic ability of DM1 myoblasts. The activity of the TGF-ß/Smad3 pathway was upregulated during DM1 myogenesis but repressed when inhibiting Postn with a Postn shRNA or a POSTN-neutralizing antibody, which suggested that the TGF-ß/Smad3 pathway might mediate the function of Postn in DM1 myogenesis. These results suggest that Postn is a potential therapeutical target for the treatment of myogenesis defects in DM1.

18.
Sci China Life Sci ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34505970

RESUMO

The Hedgehog (Hh) signaling is one of the essential signaling pathways during embryogenesis and in adults. Hh signal transduction relies on primary cilium, a specialized cell surface organelle viewed as the hub of cell signaling. Protein kinase A (PKA) has been recognized as a potent negative regulator of the Hh pathway, raising the question of how such a ubiquitous kinase specifically regulates one signaling pathway. We reviewed recent genetic, molecular and biochemical studies that have advanced our mechanistic understanding of PKA's role in Hh signaling in vertebrates, focusing on the compartmentalized PKA at the centrosome and in the primary cilium. We outlined the recently developed genetic and optical tools that can be harvested to study PKA activities during the course of Hh signal transduction.

19.
Front Pharmacol ; 12: 683296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539392

RESUMO

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014). Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

20.
Virology ; 563: 64-73, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34464882

RESUMO

Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea and vomiting, dehydration, and high mortality in neonatal piglets. Despite extensive research focusing on the pathogenesis of PEDV infection, the molecular pathogenesis of PEDV-induced diarrhea in piglets remains unclear. Na+/H+ exchanger 3 (NHE3), the main exchanger of electroneutral sodium in intestinal epithelial cells, is closely associated with the occurrence of diarrhea. To date, there is no study on whether diarrhea caused by PEDV infection is related to the activity of NHE3. In the present study, it was found that the expression level of cell membrane protein NHE3 significantly decreased after PEDV infection, whereas the total level of protein expression was not significantly changed. The Na+/H+ transport rate and the mRNA abundance of NHE3 decreased; the NHE3 activity decreased gradually with increasing infection time. In vivo, after PEDV infection of newborn piglets, rupture of intestinal villi and interstitial degeneration of intestinal epithelial cells in different intestinal segments were observed by hematoxylin-eosin staining. Immunohistochemical and immunofluorescence methods were used to observe the decreased expression of NHE3 protein on the membrane of intestinal epithelial cells in the jejunum and ileum. Taken together, these data indicate that PEDV infection reduces NHE3 activity in intestinal epithelial cells, hindering Na+ transport and thus causing diarrhea.

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