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1.
Food Chem ; 337: 127978, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920268

RESUMO

Aflatoxin B1 (AFB1) contamination causes huge economic losses. To explore the correlation between catalase (CAT) and AFB1 production during fungal development, we fabricated an electrochemical CAT-activity sensor by measuring residual H2O2 after enzymatic degradation. The sensor made by palladium nanoparticles/carbonized bacterial cellulose nanocomposites exhibits a linear range over 0.5-3.5 U/mL and a detection limit of 0.434 U/mL. Both dry weight and CAT activity of mycelia continuously increase. But, the latter shows a greater increase than the former after three days. Specific CAT activity in crude enzyme extract of A. flavus was quantified. It maintains at ~25.00 U/mg for 3 days and enhances to 28.91 and 45.30 U/mg, respectively, on days 4 and 5. AFB1 production follows the same trend. On days 4 and 5, AFB1 concentration reaches 201.35 and 767.9 ng/mL, respectively. The positive correlation between specific CAT activity and AFB1 production suggests that CAT is involved in AFB1 biosynthesis.

2.
J Ethnopharmacol ; 266: 113453, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039628

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Baizhu Tianma decoction (BBTD) is a classical representative prescription for expelling phlegm, extinguishing wind, strengthening the spleen and dissipating excessive fluid in traditional Chinese medicine (TCM). According to both TCM theory and about 300 years of clinical practice, BBTD is especially suitable for hypertensive patients of abdominal obesity and lacking physical activity. AIM OF THE STUDY: The present study tried to interpret the pharmacology of the ancient formula of BBTD. Herein, we focused on the plasma metabonomics of BBTD and evaluated the effect and targets of BBTD on endothelial protective effect. METHODS: Obesity-related hypertensive mice were induced by high-fat diet for 20 weeks. BBTD (17.8 g/kg) was administered intragastrically for 8 weeks, and telmisartan group (12.5 mg/kg) was used as positive drug. Body weight, blood pressure, triglyceride and cholesterol were recorded to evaluate the efficacy of BBTD in vivo. Lipid deposition in aortic roots was assessed by oil red O staining, while morphology of aortas was observed by HE staining. Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was performed to study the plasma non-targeted metabonomics. According to the data of metabonomics, human aortic endothelial cells (HAECs) were treated by oxidized low-density lipoprotein (ox-LDL, 50 µg/mL) with/without BBTD (2, 1 or 0.5 mg/mL). Apoptosis rate (Annexin V-FITC/PI), migration (Transwell), cytoskeleton (Phalloidin) and density of VE-cadherin (Immunofluorescence staining) were used to investigate the effect of BBTD in vitro. Transcriptome sequencing was performed (2 mg/mL BBTD vs ox-LDL) to screen the possible targets of BBTD in endothelial protection against ox-LDL. RESULTS: BBTD effectively reduced the body weight and total cholesterol, and decreased 12.1 mmHg in SBP and 10.5 mmHg in DBP of obesity-related hypertensive mice (P < 0.05). BBTD attenuated lipid deposition in arterial roots and improved the morphology of aortas in vivo. Plasma metabolite profiles identified 94 differential metabolites and suggested BBTD mainly affected glycerophospholipids and fatty acyls. Bioinformatics analysis indicated sphingolipid metabolism and fluid shear stress and atherosclerosis were main pathways. Therefore, we focused on endothelial protective effect of BBTD against ox-LDL. In vitro, BBTD demonstrated endothelial protective effects, decreasing apoptosis rate, improving cell migration in dose-dependent manner and maintaining cell morphology. Transcriptome sequencing identified 251 downregulated and 603 upregulated mRNAs after 24h-BBTD treatment, which reversed 51.8% change in mRNAs (393 DE mRNAs) induced by ox-LDL. Bioinformatics analysis supported the potential of BBTD in hypertension and suggested that BBTD improved endothelial cells by targeting mainly on p53 and PPAR signaling pathways. CONCLUSIONS: BBTD attenuates obesity-related hypertension by regulating metabolism of glycerophospholipids and endothelial protection.

3.
iScience ; : 101642, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33043282

RESUMO

COVID-19 has broken out since the end of December 2019 and is still spreading rapidly, which has been listed as an international concerning public health emergency. We found the Spike protein of SARS-CoV-2 contains a furin cleavage site, which did not exist in any other betacoronavirus subtype B. Based on a series of analysis, we speculate that the presence of a redundant furin cut site in its Spike protein is responsible for SARS-CoV-2's stronger infectious than other coronaviruses, which leads to higher membrane fusion efficiency. Subsequently, a library of 4,000 compounds including approved drugs and natural products were screened against furin through structure-based virtual screening and then assayed for their inhibitory effects on furin activity. Among them, an anti-parasitic drug, Diminazene, showed the highest inhibition effects on furin with an IC50 of 5.42 ± 0.11 µM, which might be used for the treatment of COVID-19.

4.
Eur J Med Chem ; 209: 112842, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33065375

RESUMO

Ferroptosis is a new type of programmed cell death discovered recently and has been demonstrated to be involved in a number of human diseases such as ischemic stroke. Ferroptosis inhibitors are expected to have potential to treat these diseases. Herein, we report the identification of promethazine derivatives as a new type of ferroptosis inhibitors. Structure-activity relationship (SAR) analyses led to the discovery of the most potent compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (51), which showed an EC50 (half maximal effective concentration) value of 0.0005 µM in the erastin-induced HT1080 cell ferroptosis model. In the MCAO (middle cerebral artery occlusion) ischemic stroke model, 51 presented an excellent therapeutic effect. This compound also displayed favorable pharmacokinetic properties, in particular, a good ability to permeate the blood-brain barrier. Overall, 51 could be a promising lead compound for the treatment of ferroptosis related diseases and deserves further investigations.

5.
J Affect Disord ; 277: 970-976, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065841

RESUMO

BACKGROUND: Depression and anxiety are two common mental disorders in older people. Studies have reported that depression is strongly associate with frailty, but few studies focus on anxiety disorder and comorbid two mental disorders. In this study, we aimed to identify associations between comorbid depressive and anxiety symptoms with frailty in older adults. METHODS: 4,103 community-dwellings adults aged 60 and older from the baseline of the West China Health and Aging Trend (WCHAT) study were included. Frailty was measured by the Fried frailty phenotype criteria. The 15-item Geriatric Depression Scale (GDS-15) and 7-item Generalized Anxiety Disorder Scale (GAD-7) assessed for depressive and anxiety symptoms with a cut-off value of 5. Multinomial logistic regression was used to explore the association between different depressive and anxiety status and frailty. RESULTS: 8.7% of old adults suffered comorbid depressive and anxiety symptoms in the present study. The prevalence of pre-frailty and frailty was 47.0% and 6.7%, respectively. After adjusting for covariates, individuals with comorbid depressive and anxiety symptoms had higher odds of being pre-frail (OR=1.86, 95% CI=1.41, 2.45) and frail (OR=7.03, 95% CI=4.48, 11.05) compared to those without depressive and anxiety symptoms. In the comorbidity group, those with severe comorbid symptoms also had higher prevalence of pre-frailty and frailty. LIMITATIONS: Depressive and anxiety symptom assessments were based on screening tools. CONCLUSIONS: This study suggested comorbid depressive and anxiety symptoms were associated with frailty among Chinese older adults. Further efforts to screen and target depression and anxiety comorbidity may be warranted.

6.
Biol Res ; 53(1): 47, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066819

RESUMO

Nitrogen is the main limiting nutrient after carbon, hydrogen and oxygen for photosynthetic process, phyto-hormonal, proteomic changes and growth-development of plants to complete its lifecycle. Excessive and inefficient use of N fertilizer results in enhanced crop production costs and atmospheric pollution. Atmospheric nitrogen (71%) in the molecular form is not available for the plants. For world's sustainable food production and atmospheric benefits, there is an urgent need to up-grade nitrogen use efficiency in agricultural farming system. The nitrogen use efficiency is the product of nitrogen uptake efficiency and nitrogen utilization efficiency, it varies from 30.2 to 53.2%. Nitrogen losses are too high, due to excess amount, low plant population, poor application methods etc., which can go up to 70% of total available nitrogen. These losses can be minimized up to 15-30% by adopting improved agronomic approaches such as optimal dosage of nitrogen, application of N by using canopy sensors, maintaining plant population, drip fertigation and legume based intercropping. A few transgenic studies have shown improvement in nitrogen uptake and even increase in biomass. Nitrate reductase, nitrite reductase, glutamine synthetase, glutamine oxoglutarate aminotransferase and asparagine synthetase enzyme have a great role in nitrogen metabolism. However, further studies on carbon-nitrogen metabolism and molecular changes at omic levels are required by using "whole genome sequencing technology" to improve nitrogen use efficiency. This review focus on nitrogen use efficiency that is the major concern of modern days to save economic resources without sacrificing farm yield as well as safety of global environment, i.e. greenhouse gas emissions, ammonium volatilization and nitrate leaching.

7.
J Stroke Cerebrovasc Dis ; 29(11): 105205, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066901

RESUMO

BACKGROUND: As access to patient emboli is limited, embolus analogs (EAs) have become critical to the research of large vessel occlusion (LVO) stroke and the development of thrombectomy technology. To date, techniques for fabricating standardized human blood-derived EAs are limited in the variety of compositions, and the mechanical properties relevant to thrombectomy are not quantified. METHODS: EAs were made by mixing human banked red blood cells (RBCs), plasma, and platelet concentrate in 10 different volumetric percentage combinations to mimic the broad range of patient emboli causing LVO strokes. The samples underwent histologic analysis and tensile testing to mimic the pulling action of thrombectomy devices, and were compared to patient emboli. RESULTS: EAs had histologic compositions of 0-96% RBCs, 0.78%-92% fibrin, and 2.1%-22% platelets, which can be correlated with the ingredients using a regression model. At fracture, EAs elongated from 81% to 136%, and the ultimate tensile stress ranged from 16 to 949 kPa. These EAs' histologic compositions and tensile properties showed great similarity to those of emboli retrieved from LVO stroke patients, indicating the validity of such EA fabrication methods. EAs with lower RBC and higher fibrin contents are more extensible and can withstand higher tensile stress. CONCLUSIONS: EAs fabricated and tested using the proposed new methods provide a platform for stroke research and pre-clinical development of thrombectomy devices.

8.
J Voice ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33067118

RESUMO

OBJECTIVE: The study compares the rehabilitation outcome of two voice intervention methods for female elementary school teachers with self-reported voice disorders. METHODS: A total of 34 female teachers from two primary schools volunteered in the study. Participants from one school were assigned to the experimental group (16 teachers), who received the combination of vocal hygiene education and resonant voice therapy. Participants from the other school were assigned to the control group (18 teachers), who received vocal hygiene education only. Pre- and post-treatment data were compared. RESULT: The total score of the Voice Handicap Index (VHI) decreased significantly from 12.19 ± 8.58 to 8.63 ± 7.27 (P < 0.05); the functional score of VHI significantly decreased from 5.38 ± 3.9 to 3.81 ± 3.62 (P < 0.05). No statistical significance was found in physiological and emotional scores of VHI. No statistical significance was found in the control group. In the experimental group, the maximum phonation time was increased from 14.34 ± 6.80s to 17.21 ± 6.06s (P < 0.05), Jitter decreased from 0.45% ± 0.13% to 0.26% ± 0.05% (P < 0.05), and Shimmer decreased from 0.21 ± 0.10. to 0.12 ± 0.03 (P < 0.05). Furthermore, the harmonic to noise ratio increased from 23.06 ± 2.99 to 25.23 ± 1.92 (P < 0.05), Spectrum Convergence Ratio increased from 0.53 ± 0.12 to 0.60 ± 0.11 (P < 0.05), yet no statistical significance was found in Nonlinear Energy Difference Ratio data for the experimental group. No statistical significance was found in the control group. In the auditory perception assessment (GRBAS), the G score decreased from 1.19 ± 0.54 to 0.81 ± 0.40 (P < 0.05), and the R score decreased from 1.19 ± 0.54 to 0.75 ± 0.45 (P < 0.05) in the experimental group. No statistical significance was found in the B, A, and S scores in the experimental group; moreover, none of the GRBAS scores in the control group demonstrated statistical significance. In the voice type component profile (VTC), the proportion of VTC1 of the experimental group increased significantly, while the proportions of VTC3 and VTC4 decreased significantly, indicating the improvement of voice quality was obvious after the intervention. The proportions of VTC of the control group did not demonstrate significant change. CONCLUSION: The results of this study show that a combination of vocal hygiene education and resonant voice therapy can significantly improve the voice function of professional voice users and effectively improve their voice quality. In this study, the professional voice users receiving vocal hygiene education only did not show significant improvement of their voice quality.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1592-1597, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067959

RESUMO

OBJECTIVE: To explore the role of interaction between osteoclast stimulator stromal derived factor 1 alpha (SDF-1α) and osteoblast inhibitor dickkopf-1 (DKK-1) in the development of multiple myeloma (MM) bone disease. METHODS: The serum samples of 51 patients with newly diagnosed MM, 30 age-matched healthy controls, and 35 non-Hodgkin lymphoma patients from June 2011 to May 2014 in Peking Union Medical College Hospital were collected. The serum SDF-1α and DKK-1 were detected by ELISA. Primary myeloma cells and human MM cell line RPMI 8226 were treated with SDF-1α, then DKK-1 mRNA expression was detected by real time PCR. Primary bone marrow stromal cells (BMSCs) were treated with Wnt-3a and/or DKK-1, and the transc-ription level of SDF-1α mRNA was assayed. RESULTS: Serum SDF-1α in MM patients was significantly higher than that in control group (3231.0±1269.5 pg/ml vs 2817.5±419.6 pg/ml)(P=0.036), so was serum DKK-1 (3057.4±1874.7 pg/ml vs 1867.7±1148.4 pg/ml)(P=0.01). There was a positive correlation between serum SDF-1α and DKK-1 in MM patients (r=0.301, P=0.032), but there was no correlation between control group (r=0.15, P=0.428) and non-Hodgkin lymphoma patients (r=0.227, P=0.095). After treated with SDF-1α (20 ng/ml) for 8 and 36 h, the DKK-1 mRNA transcription level in RPMI 8226 increased by 1.92 and 4.19-folds respectively(P=0.365, P=0.099). Moreover, the high transcription level of DKK-1 mRNA was observed in 5 out of 9 MM patients. The detection showed that after treatment with SDF-1α, the transcription level was up-regulated(P=0.043), the Wnt-3a (200 ng/ml) could decrease the expression of SDF-1α mRNA in primary BMSC to 29% of baseline(P=0.028), the adding DKK-1 could reverse the down-regulation effect. CONCLUSION: The serum SDF-1α and DKK-1 level in MM patients is high than normal leve, moreover shows the positive correlation between them. The SDF-1α and DKK-1 can interreact, therefore accerate the formation of MM bone disease.

10.
Lasers Med Sci ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068178

RESUMO

This study was conducted in order to compare the safety and efficacy of LLLT, 5% minoxidil, and combination therapy in the treatment of FPHL. A randomized controlled trial was developed to study the effect of LLLT on FPHL using a device called iHelmet®, which is equipped with 200 5mW laser diode source (650 nm) arrays. Ninety Ludwig's types II-III FPHL patients were randomly divided into 3 groups: LLLT group (A), 5% minoxidil group (B), and combination group(C). Hair density, hair diameter, and scalp oil-secretion were detected to evaluate the treatment effect. Significant improvement of hair density and hair diameter was observed in all stages of FPHL after treatment. Oil-secretion of the three groups was decreased after treatment. The effectiveness of reducing oil-secretion in LLLT group and combination group was higher than minoxidil group (P < 0.05). For improving hair diameter and hair density, combination group was better than LLLT and minoxidil groups. No side effects were reported. Our study illustrated that LLLT is a safe and effective treatment for FPHL. Besides, LLLT can significantly improve its efficacy when used in combination with 5% minoxidil.

11.
Transfusion ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047878

RESUMO

Clinically significant bleeding in patients with hematologic malignancies is a heterogeneous composite outcome currently defined as World Health Organization (WHO) bleeding Grades 2, 3, and 4. However, the clinical significance of some minor bleeds categorized as WHO Grades 1 and 2 remains controversial. We analyzed the number and frequency of individual signs and symptoms of WHO Grades 1 and 2 bleeds and explored their association with more severe incident bleeds graded as WHO Grades 3 and 4. STUDY DESIGN AND METHODS: We aggregated daily bleeding assessment data from three randomized controlled trials conducted in patients with hematologic malignancies that used bleeding as an outcome. Cox proportional hazard regression analysis was used to identify signs and symptoms categorized as WHO Grades 1 and 2 bleeds that were associated with more severe bleeds (Grades 3 and 4). RESULTS: We collected data from 315 patients (n = 5476 daily bleeding assessments; 3383 [61.8%] with a bleed documented). A total of 98.3% (3326/3383) were Grade 1 and 2 bleeds and 1.7% (57/3383) were Grades 3 and 4. Grade 1 and 2 bleeds were composed of 20 different bleeding signs and symptoms. Hematuria (hazard ratio, 16.1; 95% confidence interval, 4.4-59.2; P < .0001) was associated with incident Grade 3 or 4 bleeds. CONCLUSION: In patients with hematologic malignancy, only hematuria (microscopic and/or macroscopic) was associated with more severe incident bleeds. This findings require validation in independent data sets.

12.
Clin Transl Sci ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048433

RESUMO

The aim of this study was to determine the expression of IL-35 and the lymphatic vessel density (LVD) and microvessel density (MVD) in the pathological tissues from patients with non-small cell lung cancer (NSCLC) and to analyze their correlation with other common clinical prognostic factors, as well as patients' overall survival (OS) and progression-free survival (PFS). We analyzed the pathological characteristics of 130 patients with NSCLC and determined the IL-35 expression, MVD, and LVD changes in the pathological tissues by immunohistochemistry. The results showed that IL-35 expression was significantly correlated with tumor differentiation, lymph node metastasis, T staging, LVD, and MVD (P < 0.05) but was not associated with age, sex, smoking, and other factors. Univariate analysis of risk models showed that age, lymph node metastasis, T stage, and high IL-35 expression, LVD, and MVD were significantly associated with NSCLC prognosis (P < 0.05), while gender, smoking, and high differentiation were not correlated with prognosis. Multivariate analysis of the proportional risk model showed that the IL-35 expression, lymph node metastasis, high LVD, and high MVD were significantly correlated with NSCLC prognosis (P < 0.05). In conclusion, IL-35, MVD, and LVD may be independent prognostic markers. In addition, IL-35 might represent a promising clinical drug target for the treatment of NSCLC.

13.
Insect Biochem Mol Biol ; : 103485, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049282

RESUMO

The sensory neuron membrane protein, SNMP1, was initially discovered in moths and is associated with sex pheromone sensitive neurons, suggesting a role in the detection of these semiochemicals. Although DrosophilaSNMP1 has been reported to be involved in detecting of the sex pheromone cis-vaccenyl acetate (cVA), the role of this protein in moths in vivo is still largely unexplored. In this study we developed a SNMP1-/- homozygous mutant line of Helicoverpa armigera using CRISPR/Cas9. Wind-tunnel behavioral experiments showed that HarmSNMP1-/- males could not be attracted by sex pheromones (Z11-16:Ald/Z9-16:Ald = 97/3), while mating behavior obvervations revealed that the SNMP1 mutant males didn't react much to calling females and the rate of copulation was significantly decreased. The electrophysiological results indicated that HarmSNMP1 contributes to the detection of 16-carbon liner sex pheromones, (Z)-11-hexadecenal (Z11-16:Ald), (Z)-9-hexadecenal (Z9-16:Ald), (Z)-11-hexadecanol (Z11-16:OH) and 16-carbon acetate (Z)-11-hexadecenyl acetate (Z11-16:OAc), but is not required for detecting the 14-carbon sex pheromone component (Z)-9-tetradecenal (Z9-14:Ald), an analogue of Z11-16:Ald, which can activate the Z11-16:Ald-responsive neuron. Taken together, our studies indicated that HarmSNMP1 has an important role in the detection of long-chain sex pheromones, but is not essential for detecting shorter chain sex pheromone in vivo.

14.
Toxins (Basel) ; 12(10)2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33049980

RESUMO

Mycotoxigenic fungi and their toxins are a global concern, causing huge economic and health impacts in developing countries such as Ethiopia, where the mycotoxin control system is inadequate. This work aimed to review the occurrences of agriculturally essential fungi such as Aspergillus, Fusarium, and Penicillium and their major mycotoxins in Ethiopian food/feedstuffs. The incidents of crucial toxins, including aflatoxins (B1, B2, G1, G2, M1), fumonisins (B1, B2), zearalenone, deoxynivalenol, and ochratoxin A, were studied. The impacts of chronic aflatoxin exposure on liver cancer risks, synergy with chronic hepatitis B infection, and possible links with Ethiopian childhood malnutrition were thoroughly examined. In addition, health risks of other potential mycotoxin exposure are also discussed, and the impacts of unsafe level of mycotoxin contaminations on economically essential export products and livestock productions were assessed. Feasible mycotoxin mitigation strategies such as biocontrol methods and binding agents (bentonite) were recommended because they are relatively cheap for low-income farmers and widely available in Ethiopia, respectively. Moreover, Ethiopian mycotoxin regulations, storage practice, adulteration practice, mycotoxin tests, and knowledge gaps among value chain actors were highlighted. Finally, sustained public awareness was suggested, along with technical and human capacity developments in the food control sector.

15.
J Mol Diagn ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011442

RESUMO

Numerous studies have identified essential contributions of altered mitochondrial DNA (mtDNA) copy number and mutation in many common disorders including cancer. To date, capture-based next-generation sequencing (NGS) has been widely applied to detect mtDNA mutation, whereas lacks ability in assessing mtDNA copy number. Current strategy for quantifying mtDNA copy number mainly relies on quantitative PCR (qPCR), which is limited in degraded samples. Here, we developed a novel capture-based NGS approach using both mtDNA and nuclear DNA (nDNA) probes to capture target fragments, enabling simultaneous detection of mtDNA mutation and copy number in different sample types. We first evaluated the impacts of selecting reference genes on mtDNA copy number calculation, and finally selected 3 nuclear DNA fragment of 4000bp as internal reference for detection. Then, we verified the effective application of this approach in DNA samples of formalin-fixed, paraffin embedded (FFPE) specimens and body fluids, indicating the widespread applicability. Importantly, our approach exhibited more accurate and stable results in detecting mtDNA copy number compared with qPCR in degraded DNA samples. Moreover, our data indicated this approach had good reproducibility in detecting both mtDNA copy number and mutation among three sample types. Altogether, we have developed a versatile and cost-effective capture-based NGS approach for concurrent detection of mtDNA copy number and mutation, which can find numerous applications in research and diagnosis.

16.
Med Sci Monit ; 26: e925087, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011733

RESUMO

BACKGROUND Diabetic retinopathy (DR) is one of the major causes of vision impairment. Z-ligustilide (3-butylidene-4,5-dihydrophthalide; Z-LIG) is an important volatile oil from the Chinese herb Angelica sinensis (Oliv.) Diels. It has been extensively studied and reportedly has anti-inflammatory, antioxidant, antitumor, analgesic, vasodilatory, and neuroprotective effects. Its effects on DR, however, remain obscure. In this study, we attempted to explore the protective effects of Z-LIG on retinal dysfunction and the potential underlying mechanisms. MATERIAL AND METHODS A diabetic rat model was constructed with streptozotocin injection. Three study groups were constituted: control (CON), diabetic model (DM), and DM+Z-LIG. The DM+Z-LIG group was injected intraperitoneally with 10 mg/kg of Z-LIG. The other groups received the same volume of 3% solution of polysorbate 80. After a 12-week intervention, a series of assessments were performed, including tests for retinal function, morphology, and molecular biology. RESULTS Z-LIG treatment significantly elevated b-wave and OPs2-wave amplitude and thickened the inner layer of the nucleus of the retina, and the outer plexiform and nuclear layers (INL+OPL+ONL). Moreover, the rate of apoptosis and expression of bcl-2- associated X protein (BAX) and cleaved-Caspase-3 were clearly reduced, and the expression of bcl-2 was raised by Z-LIG in retinas of diabetic mice. In addition, the levels of retinal proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha were downregulated by Z-LIG. Furthermore, Z-LIG inhibited expression of vascular endothelial growth factor-alpha (VEGF-alpha) at the mRNA and protein levels. CONCLUSIONS Z-LIG can inhibit inflammatory response and cell apoptosis in retinas of diabetic rats by repressing the VEGF-alpha pathway. Therefore, it may serve as a potential therapeutic agent for DR.

17.
Laryngoscope ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016340

RESUMO

OBJECTIVES/HYPOTHESIS: The individualized risk of airway obstruction after head and neck cancer surgery is unclear, especially oral and oropharyngeal cancer. The study aimed to establish an individualized predictive model for the necessity of temporary tracheotomy in these patients. METHODS: Patients who underwent oral and oropharyngeal cancer surgery from 1999 to 2019 were retrospectively reviewed. A nomogram was developed and validated in patients treated from 1999 to 2009 and 2010 to 2019, respectively. RESULTS: In total, 1551 patients were included. Oropharyngeal cancer, large tumor, midline crossing, preoperative radiation, mandibulectomy, flap reconstruction, and neck dissection were independent risk factors of postoperative airway obstruction in the training group (n = 707). A nomogram incorporating these factors had a C-index of 0.931 and was validated in the testing group (n = 844) (C-index, 0.918). Good calibration curves were observed in both groups. CONCLUSIONS: The nomogram successfully predicted the individual risk of postoperative airway obstruction for patients with oral and oropharyngeal cancer. LEVEL OF EVIDENCE: 4. Laryngoscope, 2020.

18.
Phys Chem Chem Phys ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030470

RESUMO

A systematic understanding of interactions at the nano-bio interface is critical for the development of bio-functional nanomaterials and nano-agents for medical applications, which essentially require high safety, biocompatibility and therapeutic efficiency. As a new member of the two-dimensional material family, α-phase phosphorene carbide (α-PC) has attracted significant research interest in recent years. Benefitting from the unique buckled structure and its rich physical and chemical features, the future applications of α-PC in biological and medical areas are intriguing. Using molecular dynamics simulations (MDs), herein, we theoretically explore the interactions of α-PC nanoribbons with the cell lipid membrane to evaluate the potential biological toxicity to lipids. Our results clearly demonstrate that the α-PC sheet can only penetrate the membrane along its zigzag direction by attracting the lipids to the groove regions. The membrane undergoes slight structural distortion, but quickly recovers after the penetration. Only localized impacts are detected on the membrane after the penetration. In contrast, the intrusion along armchair direction is highly blocked by lipids. Free energy analysis by the umbrella sampling method revealed that the fatty acid tails of lipids prefer to bind along the groove regions of α-PC rather than across the grooves, resulting in a high anisotropic penetration behavior. The overall attraction of α-PC to lipid is weaker than graphene, and the binding lipids cannot be fully extracted from the membrane environment. The self-equilibration of the membrane is fast enough to prevent lipids from escaping, leading to the well-preserved membrane integrity. Our present findings suggest that α-PC might offer new potential as bio-agents with high membrane-penetrating efficiency and lower cytotoxicity. The unique anisotropic behaviors can be further utilized for the design and fabrication of specialized nanomaterials with the capability of efficient and template-directed molecule delivery.

19.
Hum Brain Mapp ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030796

RESUMO

Primary dysmenorrhea (PDM) is cyclic menstrual pain in the absence of pelvic anomalies, and it is thought to be a sex-hormone related disorder. Existing study has focused on the effects of menstrual cramps on brain function and structure, ignoring the psychological changes associated with menstrual pain. Here we examined whether pain empathy in PDM differs from healthy controls (HC) using task-based functional magnetic resonance imaging (fMRI). Fifty-seven PDM women and 53 matched HC were recruited, and data were collected at the luteal and menstruation phases, respectively. During fMRI scans, participants viewed pictures displaying exposure to painful situations and pictures without any pain cues and assessed the level of pain experienced by the person in the picture. Regarding the main effect of the pain pictures, our results showed that compared to viewing neutral pictures, viewing pain pictures caused significantly higher activation in the anterior insula (AI), anterior cingulate cortex, and the left inferior parietal lobule; and only the right AI exhibited a significant interaction effect (group × picture). Post-hoc analyses confirmed that, relative to neutral pictures, the right AI failed to be activated in PDM women viewing painsss pictures. Additionally, there was no significant interaction effect between the luteal and menstruation phases. It suggests that intermittent pain can lead to abnormal empathy in PDM women, which does not vary with the pain or pain-free phase. Our study may deepen the understanding of the relationship between recurrent spontaneous pain and empathy in a clinical disorder characterized by cyclic episodes of pain.

20.
Sci Adv ; 6(41)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33036977

RESUMO

Toxic aggregated amyloid-ß accumulation is a key pathogenic event in Alzheimer's disease (AD), which derives from amyloid precursor protein (APP) through sequential cleavage by BACE1 (ß-site APP cleavage enzyme 1) and γ-secretase. Small interfering RNAs (siRNAs) show great promise for AD therapy by specific silencing of BACE1. However, lack of effective siRNA brain delivery approaches limits this strategy. Here, we developed a glycosylated "triple-interaction" stabilized polymeric siRNA nanomedicine (Gal-NP@siRNA) to target BACE1 in APP/PS1 transgenic AD mouse model. Gal-NP@siRNA exhibits superior blood stability and can efficiently penetrate the blood-brain barrier (BBB) via glycemia-controlled glucose transporter-1 (Glut1)-mediated transport, thereby ensuring that siRNAs decrease BACE1 expression and modify relative pathways. Noticeably, Gal-NP@siBACE1 administration restored the deterioration of cognitive capacity in AD mice without notable side effects. This "Trojan horse" strategy supports the utility of RNA interference therapy in neurodegenerative diseases.

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