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1.
J Fluoresc ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451363

RESUMO

In this study, we successfully synthesized an innovative 1D-Zn(II) coordination polymer, denoted as [Zn(L)(H2O)2]n, employing the Schiff base {4-[(2-hydroxy-3-methoxy-benzylidene)-amino]-benzoic acid} (H2L). The Schiff base was obtained through the reaction of 4-aminobenzoic acid and o-vanillin under slow volatilization conditions. The resulting compound exhibits remarkable green fluorescence emission properties, indicating its potential as a novel fluorescent and sensing material. Hydrogels based on hyaluronic acid (HA) and carboxymethyl chitosan (CMCS), denoted as HA/CMCS hydrogels, were synthesized using a chemical method. Additionally, we utilized bleomycin as a model drug to synthesize a novel bleomycin metal gel and assessed its anti-hemangioma activity. Molecular docking simulations revealed that the Zn complex can form stable bonds with the key target, involving the methoxy and carboxyl groups on the Zn complex.

2.
Front Pharmacol ; 15: 1345522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510646

RESUMO

Cancer cells have adapted to rapid tumor growth and evade immune attack by reprogramming their metabolic pathways. Glutamine is an important nitrogen resource for synthesizing amino acids and nucleotides and an important carbon source in the tricarboxylic acid (TCA) cycle and lipid biosynthesis pathway. In this review, we summarize the significant role of glutamine metabolism in tumor development and highlight the vulnerabilities of targeting glutamine metabolism for effective therapy. In particular, we review the reported drugs targeting glutaminase and glutamine uptake for efficient cancer treatment. Moreover, we discuss the current clinical test about targeting glutamine metabolism and the prospective direction of drug development.

3.
Bioact Mater ; 35: 401-415, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38384987

RESUMO

Peripheral nerve injury (PNI) seriously affects the health and life of patients, and is an urgent clinical problem that needs to be resolved. Nerve implants prepared from various biomaterials have played a positive role in PNI, but the effect should be further improved and thus new biomaterials is urgently needed. Ovalbumin (OVA) contains a variety of bioactive components, low immunogenicity, tolerance, antimicrobial activity, non-toxicity and biodegradability, and has the ability to promote wound healing, cell growth and antimicrobial properties. However, there are few studies on the application of OVA in neural tissue engineering. In this study, OVA implants with different spatial structures (membrane, fiber, and lyophilized scaffolds) were constructed by casting, electrospinning, and freeze-drying methods, respectively. The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity, and can promote vascularization, show good histocompatibility, without excessive inflammatory response and immunogenicity. The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells, while the in vivo results confirmed that OVA implants (the E5/70% and 20 kV 20 µL/min groups) could effectively regulate the growth of blood vessels, reduce the inflammatory response and promote the repair of subcutaneous nerve injury. Further on, the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α (TNF-α), phosphatidylinositide 3-kinases/protein kinase B (PI3K-Akt) signaling pathway, axon guidance, cellular adhesion junctions, and nerve regeneration in Schwann cells. The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.

4.
Int J Biol Macromol ; 253(Pt 4): 127015, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37758111

RESUMO

Peripheral nerve injuries (PNI) currently have limited therapeutic efficacy, and functional scaffolds have been shown to be effective for treating PNI. Ovalbumin (OVA) is widely used as a natural biomaterial for repairing damaged tissues due to its excellent biocompatibility and the presence of various bioactive components. However, there are few reports on the repair of PNI by ovalbumin. In this study, a novel bionic functionalized topological scaffold based on ovalbumin and grafted with tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide was constructed by micro-molding method and surface-biomodification technology. The scaffolds were subjected to a series of evaluations in terms of morphology, mechanics, hydrophilicity, and biocompatibility, and the related molecular mechanisms were further penetrated. The results showed that the scaffolds prepared in this study had aligned ridge/groove structure, good mechanical properties and biocompatibility, and could be used as carriers to slowly release YIGSR, which effectively promoted the proliferation, migration and elongation of Schwann Cells (SCs), and significantly up-regulated the gene expression related to proliferation, apoptosis, migration and axon regeneration. Therefore, the bionic functional topological scaffold has significant application potential for promoting peripheral nerve regeneration and provides a new therapeutic option for repairing PNI.


Assuntos
Axônios , Traumatismos dos Nervos Periféricos , Humanos , Ovalbumina/metabolismo , Regeneração Nervosa/fisiologia , Células de Schwann , Peptídeos/química , Traumatismos dos Nervos Periféricos/terapia , Alicerces Teciduais/química
5.
Food Chem ; 429: 136833, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37454620

RESUMO

Germination is a natural green technology to improve the nutritional and techno-functional quality of plant-based proteins. In this study, the mechanism of improving the functional and antioxidant properties of black and white sesame protein isolates (SPI) through germination process was investigated. Results showed that the surface hydrophobicity and sulfhydryl content increased significantly after germination, which were supported by multispectral analysis suggesting the exposed and unfolded conformational transition of germinated SPI. Moreover, the increased particle size was observed by microscopy analysis and reducing electrophoresis, which indicated that depolymerized protein molecules were rearranged to form protein aggregates during germination. The structural modification induced by germination contributed to the superior solubility (increased to 3.15-fold and 2.36-fold at pH 8 for black and white SPI, respectively), foaming capacity (increased to 3.99-fold and 1.69-fold, respectively), emulsifying ability (increased to 2.84-fold and 2.71-fold, respectively), and diverse chemical antioxidant activities (increased up to 5.60-fold) of SPI in both varieties. This was the first comprehensive study to investigate germination as a promising technology for obtaining high-quality SPI.


Assuntos
Antioxidantes , Sesamum , Proteínas de Soja/química , Sesamum/química , Proteínas de Plantas/genética , Interações Hidrofóbicas e Hidrofílicas
6.
Food Funct ; 14(12): 5716-5727, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37279032

RESUMO

Propionic acid (PA) is a water-soluble substance that has been shown to be beneficial for improving colon-related diseases. However, its appliance as a nutraceutical ingredient is hampered by its volatility, irritating odor, and easy absorption in the stomach and small intestine. A chitosan solution containing propionic acid was dispersed in a palm oil/corn oil mixture with polyglycerol polyricinoleate (PGPR) to form PA-loaded water-in-oil (W/O) emulsions. The stability of the emulsions was improved by the inclusion of both chitosan and palm oil, where the chitosan reduced the emulsion particle size and palm oil increased the viscosity. The thermal volatility and storage stability of the encapsulated propionic acid were significantly improved due to the stability of emulsion structure and hydrogen bonding between chitosan and propionic acid. Around 56% of propionic acid remained within the aqueous phase after the simulated gastrointestinal digestion. Our results indicate that W/O emulsions might be candidates as colon-targeted delivery systems for propionic acid, which could be beneficial for maintaining colon health.


Assuntos
Quitosana , Água , Emulsões/química , Volatilização , Óleo de Palmeira , Água/química , Tamanho da Partícula
7.
Int J Exp Pathol ; 104(5): 258-268, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37381118

RESUMO

Haemangiomas (HAs) are prevalent vascular endothelial cell tumours. With respect to the possible involvement of HIF-1α in HAs, we have explored its role in haemangioma endothelial cell (HemEC) proliferation and apoptosis. shRNA HIF-1α and pcDNA3.1 HIF-α were manipulated into HemECs. HIF-α, VEGF, and VEGFR-2 mRNA and protein levels were assessed by qRT-PCR and Western blotting. Cell proliferation and viability, cell cycle and apoptosis, migration and invasion, and ability to form tubular structures were assessed by colony formation assay, CCK-8, flow cytometry, Transwell assay, and tube formation assay. Cell cycle-related protein levels, and VEGF and VEGFR-2 protein interaction were detected by Western blot and immunoprecipitation assays. An Haemangioma nude mouse model was established by subcutaneous injection of HemECs. Ki67 expression was determined by immunohistochemical staining. HIF-1α silencing suppressed HemEC neoplastic behaviour and promoted apoptosis. HIF-1α facilitated VEGF/VEGFR-2 expression and the VEGF had interacted with VEGFR-2 at protein - protein level. HIF-1α silencing arrested HemECs at G0/G1 phase, diminished Cyclin D1 protein level, and elevated p53 protein level. VEGF overexpression partially abrogated the effects of HIF-1α knockdown on inhibiting HemEC malignant behaviours. Inhibiting HIF-1α in nude mice with HAs repressed tumour growth and Ki67-positive cells. Briefly, HIF-1α regulated HemEC cell cycle through VEGF/VEGFR-2, thus promoting cell proliferation and inhibiting apoptosis.


Assuntos
Células Endoteliais , Hemangioma , Camundongos , Animais , Humanos , Células Endoteliais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/farmacologia , Camundongos Nus , Antígeno Ki-67 , Linhagem Celular Tumoral , Apoptose , Hemangioma/patologia , Proliferação de Células
8.
Ann Vasc Surg ; 88: 257-267, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35817383

RESUMO

BACKGROUND: Diet is fundamental to maintaining and improving human health. There is ample evidence identifying the beneficial and/or harmful effects of diet on noncommunicable diseases such as obesity, diabetes mellitus, and cardiovascular disease. However, the associations of the diet to chronic venous disease has not been fully described. METHODS: Data were collected through a cross-sectional survey conducted on 1,571 community-dwelling adults in 2018. Diet intake frequency was assessed using valid food group consumption frequency questionnaires. Multivariable logistic regression models were used to evaluate the association of diet with chronic venous disease. RESULTS: In total, 857 participants were diagnosed with chronic venous disease. Those who ate soybean products daily and 4-6 days/week had a 51-31% lower risk of chronic venous disease compared with those who only occasionally consumed soybean food, respectively. Participants who consumed eggs and egg products 1-3 days/week versus those who only occasionally ate eggs showed a lower risk of chronic venous disease [odds ratio (OR) 0.542, 95% confidence interval (CI) 0.375-0.782]. Eating fried food 4-6 days each week was associated with an increased risk of chronic venous disease (OR 3.872, 95% CI 1.263-11.599) compared with those who only occasionally ate fried foods. There is a decreasing tendency of the adjusted OR for eating soybean products daily with the severity of disease [chronic venous disease (C0-C2): OR 0.575, 95% CI 0.408-0.812; chronic venous insufficiency (C3-C6): OR 0.222, 95% CI 0.114-0.435]. CONCLUSIONS: A higher frequency in the consumption of soybean products and eggs were associated with a lower risk of chronic venous disease. High level of fried food consumption was positively associated with risk of chronic venous disease. There are certain specific trends in relation to dietary consumption and severity of disease, although these trends were less strong. These associations are largely independent of other dietary and nondietary factors.


Assuntos
Doenças Cardiovasculares , Dieta , Adulto , Humanos , Estudos Transversais , Resultado do Tratamento , Dieta/efeitos adversos , Ovos/efeitos adversos , Doenças Cardiovasculares/etiologia
9.
Food Funct ; 13(22): 11455-11466, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36148831

RESUMO

The development of probiotics encapsulation strategies has always been a hot topic due to the high sensitivity of probiotics to processing, storage and the gastrointestinal environment. In this study, water in oil (W/O) emulsions of single-phase or dual-phase gels were constructed through the water phase, oil phase alone or all gels. And the W/O emulsions were used to encapsulate Bifidobacterium lactis V9. The effects of water, oil and biphasic gels on the physicochemical properties of the emulsion and the probiotic activity were investigated. Water, oil and biphasic gels contribute to the stability of emulsions. Oil-phase gels make the emulsion form a solid-like texture, while water-phase gels have no significant effect on the liquidity of the emulsion. The microscopic image shows that the probiotics were completely encapsulated in the internal aqueous phase due to the excellent water affinity of probiotic powder. In addition, all W/O emulsions retain higher probiotic activity, which is attributed to good physical isolation during the gastric phase, while oil-phase and biphasic gel emulsions have high probiotic activity after intestinal digestion due to reduced lipid digestion by oil-phase gels. A liquid or solid-state encapsulated probiotic emulsion has been developed and can be used as a coating sauce, solid fat, etc., which can provide additional ideas for probiotic encapsulation systems and functional food development.


Assuntos
Probióticos , Água , Emulsões/química , Água/química , Géis/química , Trato Gastrointestinal
10.
BMC Public Health ; 22(1): 1127, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668385

RESUMO

PURPOSE: Despite a maturing literature on the association between subjective wellbeing (SWB) and mental condition, little is known regarding the happiness-physical health relation in China, among middle-aged and elderly women (MAEW) in particular. This study aimed to understand the effect of physical health on the SWB of MAEW in China. METHODS: Data from the 2014 and 2018 China Family Panel Study were used to analyse the SWB of women over the age of 45 years. In addition, descriptive statistics was used to describe the population distribution and panel ordered logit regression for regression analysis. RESULTS: Majority of the respondents reported satisfactory SWB, and the proportion of the respondents who were very happy and happy was more than 68%. In terms of health factors, self-rated health, 2-week morbidity and BMI were significantly related to the SWB of MAEW (all P-values < 0.05). Physical exercise (P-value < 0.01) was positively associated with SWB, whereas smoking status and drinking status were not related to SWB. In addition, demographic indicators, such as registered residence (P-value < 0.01), income (P-value < 0.01) and social status (P-value < 0.01), significantly affected the SWB of MAEW. CONCLUSION: This study showed that MAEW's physical health could affect their SWB. Increased attention should be paid to the physical health of MAEW to improve their SWB. Policy mechanisms could be designed to motivate MAEW to take the initiative to engage in regular physical activity to improve their SWB. In addition, increased attention be paid to groups with low socioeconomic status and high stress, especially those who are employed, to improve residents' happiness.


Assuntos
Felicidade , Renda , Idoso , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade
11.
Thromb Res ; 214: 68-75, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35490647

RESUMO

OBJECTIVES: To identify independent prediction factors for post thrombotic syndrome (PTS) following acute deep vein thrombosis (DVT) and develop a clinical prediction model assessing the risk of PTS in individual patient. METHODS: We prospectively recruited consecutive adult patients with acute DVT who were managed at Shanxi Bethune Hospital, China between June 2014 and December 2016. Investigator assessed PTS using the Villalta scale at 1, 6, 12, 18 and 24 months following diagnosis of DVT. Variable selection was performed by applying the least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation. Based on these data, we established a clinical prediction model for the development of PTS following DVT. The Bootstrap method was used for internal validation. During the process of model development, we re-collected the information of DVT patients from 2016 to 2017 for a temporal validation. The performance of the prediction model included discrimination and calibration, and clinical utility of prediction model was also evaluated using a decision curve analysis. RESULTS: A total of 808 consecutive patients with acute DVT were enrolled in the training and validation datasets, of which 540 patients were included in the training dataset for the development of prediction model and the other 268 patients were in the other dataset for temporal validation. Seventy-six patients in training dataset developed PTS. The prediction factors associated with PTS were ilio-femoral DVT (OR = 4.835, 95% CI: 2.471-9.463), active cancer (OR = 3.006, 95% CI: 1.404-6.435), history of chronic venous insufficiency (OR = 7.464, 95% CI: 3.568-15.616), previous venous thromboembolism (OR = 6.326, 95% CI: 2.872-13.932), and chronic kidney disease (OR = 9.916, 95% CI: 2.238-43.937), duration of compression therapy <6 months (OR = 2.894, 95% CI: 1.595-5.251). The c index of the prediction model was 0.825 (0.774-0.877), and the c index of internal validation and temporal verification were 0.816 and 0.773 (95% CI: 0.699-0.848), indicated that the prediction model had a good discrimination in predicting PTS risk following DVT. All the calibration curve showed the model had a good calibration. The decision curve analysis showed a better net benefit of prediction model predicting PTS risk within threshold probability ranged from 0% to 72% and 86% to 98% in training dataset, and 0% to 58% in the validation datasets. CONCLUSION: Our prediction model can accurately estimate the likelihood of PTS risk and identify high-risk patients who may develop PTS following DVT based on individual characteristics, but further external validation is still required.


Assuntos
Síndrome Pós-Trombótica , Trombose Venosa , Doença Aguda , Adulto , Anticoagulantes/efeitos adversos , Humanos , Modelos Estatísticos , Síndrome Pós-Trombótica/diagnóstico , Prognóstico , Fatores de Risco , Trombose Venosa/complicações , Trombose Venosa/etiologia
12.
Food Chem ; 372: 131225, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34614463

RESUMO

Water-in-oil (W/O) high internal phase emulsions (HIPEs) were prepared using polyglycerol polyricinoleate (PGPR) and polysaccharide blends consisting of konjac glucomannan (KGM) and octenyl succinic anhydride starch (OSA-starch). The formation, stability, and functionality of these emulsions were varied by adjusting the ratio of KGM and OSA-starch. Interfacial tension measurements indicated that the OSA-starch co-adsorbed to the water-oil interface with PGPR, which would have led to the formation of a polysaccharide-layer that helped prevent separation of the HIPEs. The centrifugal stability, rheological and microstructural results indicated that the W/O HIPEs exhibited well pH, ionic and thermal stability. The encapsulation efficiency, stability, and bioaccessibility of the EGCG in the W/O HIPEs were evaluated by using EGCG as a model hydrophilic nutraceutical. This study provides useful insights into the utilization of emulsion technology to reduce the fat content and improve the nutritional profile of foods with oily continuous phases, such as spreads.


Assuntos
Amido , Água , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Reologia
13.
Environ Geochem Health ; 44(3): 817-828, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34075510

RESUMO

As medicinal plants can accumulate harmful metals from the native soil, people's consumption of these materials may cause the human body to accumulate toxic metal elements. This has given rise to people's concerns about the quality and safety of Chinese medicinal materials. This research aims to determine the levels of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb in four medicinal plant species (Aster tataricus L.f., Salvia miltiorrhiza Bge, Radix Aucklandiae, Scutellaria baicalensis Georgi) and their native soil. All samples were collected from Qian'an city, beside Yanshan Mountain Range in Tangshan city, east Hebei Province, north China. The contents of heavy metals we detected in the soil conformed to the current limits. However, the Cd and Hg in the soil had a very high potential ecological risk because of their contents higher than the base level of local soil. The contents of Cu, Cd, Hg and Pb in some medicinal herbs exceeded the standards. The content of Cu in Radix Aucklandiae exceeded the standard by 3 times, and others exceeded the standard by less than one time. The comprehensive health risk assessment of heavy metals with chronic non-carcinogenic effects for human body showed that none of the four medicinal herbs can create a health risk. Thus, there is no strong positive correlation between heavy metal pollution in medicinal herbs and that in the native soil. Further research should be investigated to the connection between the heavy metal levels in the soil and plants, and the comprehensive effects of soil, air and irrigation water on heavy metal pollution of Chinese herbal medicines. We also recommend that Chinese herbal medicines should be cultivated and gathered only from controlled or uncontaminated areas.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Poluição Ambiental , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Medição de Risco , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
14.
Ann Vasc Surg ; 80: 302-312, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34774690

RESUMO

OBJECTIVE: A systematic review and meta-analysis were performed to evaluate the necessity for compression therapy with elastic stockings following endovenous thermal ablation (EVTA) for chronic venous insufficiency. METHODS: MedLine, ScienceDirect and the Cochrane Library were searched for the relevant literature according to the inclusion and exclusion criteria. Two researchers independently extracted data and assessed the quality of the literature. Randomized controlled trials comparing the use of elastic stockings for compression therapy versus no compression therapy following RFA or EVLA for varicose veins were included in this study. The primary outcome of postoperative pain was assessed using the visual analogue pain scale. Secondary outcomes included the bruising score, quality of life, venous clinical severity score, time to return to normal activities, complications, and the rate of saphenous vein occlusion. The mixed effect model or random effect model was used to calculate relative risk (RR), mean difference (MD) or standardized mean difference following the heterogeneity test. Sensitivity analysis was performed for outcomes with high heterogeneity (I2 >50%). Outcomes were described qualitatively for studies that could not be pooled. RESULTS: Six RCTs with 1,045 subjects were included. Overall, postoperative compression therapy significantly reduced the mean pain in the first 10 days post-EVTA (MD = - 4.98,95% CI: -8.71 to -1.24), and the time to return to normal activities (MD = -1.01, 95% CI: -1.97 to -0.06). In terms of the bruising score, the venous clinical severity score, complications (RR = 1.05,95% CI: 0.55-2.00), quality of life at 2 weeks (MD = -0.71,95% CI: -2.09 to 0.67) and 6 months (MD = 0.26,95% CI: -1.22 to 1.74), and the saphenous vein occlusion rate (RR=1.00,95% CI: 0.95-1.04), there were no significant differences between the compression and control groups. CONCLUSION: Our study recommends the routine use of compression therapy with elastic stockings following EVTA of varicose veins to reduce postoperative pain and the time to return to normal activities. However, further multi-center and high-quality randomized clinical trials are needed for the unified treatment for varicose veins, the target population as well as the duration of compression therapy on whether elastic stockings is beneficial following EVTA.


Assuntos
Terapia a Laser , Dor Pós-Operatória/prevenção & controle , Ablação por Radiofrequência , Meias de Compressão , Varizes/cirurgia , Contusões/prevenção & controle , Humanos , Medição da Dor , Qualidade de Vida
15.
ACS Omega ; 6(46): 31321-31329, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34841175

RESUMO

Solubility of hydrogen sulfide (H2S) in 46 single and blended physical absorbents, amines, ionic liquids, and hybrid absorbents of amines + ionic liquids and amines + physical absorbents was successfully predicted based on artificial neural networks (ANNs). Three neural network algorithms of Levenberg-Marquardt (LM), Bayesian regularization (BR), and scaled conjugate gradient (SCG) were applied for architecting the ANN models. The results showed that both the number of hidden neurons and the prediction algorithm affected the prediction of H2S solubility. Based on the mean square error (MSE) and determination coefficient (R 2), the most attractive model was the LM-ANN model with 17 hidden neurons. As a result, very satisfactory prediction performance (for the testing data set) with an MSE of 0.0014 and an R 2 of 0.9817 was obtained from the developed LM-ANN model. Additionally, a parity chart confirmed that the predicted solubility of H2S well aligned with the experimental data. To effectively absorb H2S and maintain high solubility of H2S, the absorbent should be well complied with the operating pressure. For a low-pressure range of less than 100 kPa, amines are very attractive. As the pressure elevated to 100-1000 kPa, amines and hybrid amine + physical absorbents are suggested. Lastly, at a high pressure over 1000 kPa, physical absorbents and ionic liquids are recommended.

16.
Acta Crystallogr F Struct Biol Commun ; 77(Pt 10): 348-355, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605439

RESUMO

Human coronavirus NL63 (HCoV-NL63), which belongs to the genus Alphacoronavirus, mainly infects children and the immunocompromized and is responsible for a series of clinical manifestations, including cough, fever, rhinorrhoea, bronchiolitis and croup. HCoV-NL63, which was first isolated from a seven-month-old child in 2004, has led to infections worldwide and accounts for 10% of all respiratory illnesses caused by etiological agents. However, effective antivirals against HCoV-NL63 infection are currently unavailable. The HCoV-NL63 main protease (Mpro), also called 3C-like protease (3CLpro), plays a vital role in mediating viral replication and transcription by catalyzing the cleavage of replicase polyproteins (pp1a and pp1ab) into functional subunits. Moreover, Mpro is highly conserved among all coronaviruses, thus making it a prominent drug target for antiviral therapy. Here, four crystal structures of HCoV-NL63 Mpro in the apo form at different pH values are reported at resolutions of up to 1.78 Å. Comparison with Mpro from other human betacoronaviruses such as SARS-CoV-2 and SARS-CoV reveals common and distinct structural features in different genera and extends knowledge of the diversity, function and evolution of coronaviruses.


Assuntos
Coronavirus Humano NL63/química , Cristalização/métodos , Cristalografia por Raios X/métodos , Humanos , Concentração de Íons de Hidrogênio , Conformação Proteica
17.
Mol Oncol ; 15(9): 2466-2479, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34058065

RESUMO

Sentinel lymph node (LN) biopsy is currently the standard procedure for clinical LN-negative breast cancer (BC) patients but it is prone to false-negative results and complications. Thus, an accurate noninvasive approach for LN staging is urgently needed in clinical practice. Here, circulating exosomal microRNA (miRNA) expression profiles in peripheral blood from BC patients and age-matched healthy women were obtained and analyzed. We identified an exosomal miRNA, miR-363-5p, that was significantly downregulated in exosomes from plasma of BC patients with LN metastasis which exhibited a consistent decreasing trend in tissue samples from multiple independent datasets. Plasma exosomal miR-363-5p achieved high diagnostic performance in distinguishing LN-positive patients from LN-negative patients. The high miR-363-5p expression level was significantly correlated with improved overall survival. Functional assays demonstrated that exosomal miR-363-5p modulates platelet-derived growth factor (PDGF) signaling activity by targeting PDGFB to inhibit cell proliferation and migration. Our study revealed, for the first time, plasma exosomal miR-363-5p plays a tumor suppressor role in BC and has the potential for noninvasive LN staging and prognosis prediction of BC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação para Baixo , Exossomos/metabolismo , Metástase Linfática/genética , MicroRNAs/sangue , Proteínas Proto-Oncogênicas c-sis/genética , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade
18.
Ann Vasc Surg ; 74: 315-320, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33549775

RESUMO

BACKGROUND: Homocysteine (Hcy) is considered as a modifiable risk factor for vascular disease. This study was aimed to explore the association between serum concentration and the severity of primary chronic venous disease (CVD). METHODS: Clinical data of 582 patients diagnosed with primary CVD were collected and analyzed retrospectively. The Clinical Etiology Anatomy Pathophysiology classification system was used to grade the severity of chronic venous disease. Patients were divided into 2 groups (group A: C1-C3; group B: C4-C6). The association between serum homocysteine levels and the severity of primary chronic venous disease was investigated using rank sum test and logistic regression. RESULTS: The difference between the level of homocysteine in each grade has statistical significance. Group A has higher median Hcy concentrations than Group B (15.40 µmol/L vs. 14.05 µmol/L, P< 0.01). Further binary logistic regression showed no statistical significance among the level of Hcy (11.00-14.75 µmol/L [OR 0.66, 95% CI 0.40-1.11, P= 0.12], 14.75-20.38µmol/L [OR 0.97, 95% CI 0.59-1.69, P = 0.89], ≥20.38 µmol/L [OR 0.67, 95% CI 0.41-1.10, P = 0.11]), but age (OR 1.03, 95% CI 1.01-1.04, P< 0.01) and female (OR 0.41, 95% CI 0.28-0.59, P< 0.01) are associated with more severe stages of CVD. CONCLUSIONS: Higher level of Hcy is associated with more severe stages of CVD, but it not an independent risk factor. However, Advanced age and female are risk factors for CVD development based on logistic regression analysis.


Assuntos
Homocisteína/sangue , Hiper-Homocisteinemia/complicações , Doenças Vasculares/etiologia , Veias , Fatores Etários , Idoso , Biomarcadores/sangue , Doença Crônica , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Regulação para Cima , Doenças Vasculares/sangue , Doenças Vasculares/diagnóstico
19.
Clinics ; 76: e1816, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153936

RESUMO

OBJECTIVE: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features. METHODS: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations. RESULTS: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis. CONCLUSIONS: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.


Assuntos
Humanos , Recém-Nascido , Lactente , Enterocolite Necrosante/diagnóstico por imagem , Doenças do Recém-Nascido , Prognóstico , Curva ROC , Ultrassonografia
20.
Artigo em Inglês | MEDLINE | ID: mdl-30983888

RESUMO

BACKGROUND: Inappropriate admissions cause excessive utilization of health services compared with outpatient services. However, it is still unclear whether inappropriate admissions cause excessive use of health services compared with appropriate admissions. This study aims to clarify the differences in the hospitalization performances between appropriately admitted inpatients and inappropriately admitted inpatients. METHODS: A total of 2575 medical records were obtained after cluster sampling in three counties. Admission appropriateness was assessed by appropriateness evaluation protocol (AEP). The propensity score matching (PSM) was computed to match patients in treatment and control group with similar characteristics, and to examine the differences in the utilization of hospitalization services between the two groups. The samples were matched in two major steps in this study. In the first step, total samples were matched to examine the differences in the utilization of hospital services between the two groups using 15 individual covariates. In the second step, PSM was computed to analyze the differences between the two groups in different disease systems using 14 individual covariates. RESULTS: For the whole sample, the inappropriate group has lower expenditure of hospitalization (EOH) (difference = - 0.12, p = 0.003) and shorter length of stay (LOS) (difference = - 0.73, p = 0.016) than the appropriate group. For number of clinical inspection (NCI), it has no statistically significant difference (difference = - 0.39, p = 0.082) between the two groups. Among different disease systems, no significant differences were observed between the two groups among EOH, LOS and NCI, except that the EOH was lower in the inappropriate group than that in the appropriate group for surgical disease (difference = - 0.169, p = 0.043). CONCLUSION: Inappropriate admissions have generated excessive health service utilization compared with appropriate admissions, especially for internal diseases. The departments in charge of medical services and hospital managers should pay high attention to the health service utilization of the inappropriately admitted inpatients. Relevant medical policies should be designed or optimized to increase the appropriateness in health care service delivery and precision in clinical pathway management.

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