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1.
Ann Transl Med ; 9(20): 1565, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790771

RESUMO

Background: Oral squamous cell carcinoma (OSCC), as the most common oral cancer globally, is very harmful to people's health. Hypoxia is closely related to many cancers. In this study, we have conducted a comprehensive exploration of the impact of hypoxia on OSCC. Methods: First, we calculated the enrichment score (ES) of hypoxia-related genes in the sample based on the enrichment analysis of the single sample Gene Set Enrichment Analysis (ssGSEA) and expressed it as a potential hypoxia index (HPI). We first identified the relationship between HPI and survival time in OSCC tumor samples. Then we assessed the correlation between hypoxia and the degree of infiltration of various immune cells in OSCC tissues, and screened out gene mutations that may be related to HPI in OSCC. Finally, we constructed a prognostic model of hypoxia-related genes. Results: In the immune cell infiltration of OSCC, we found that hypoxia was significantly related to the infiltration of eosinophils, macrophages, neutrophils, T helper cells and Th1 cells. In addition, NSD1 mutations may become a signal to suggest that patients with OSCC have higher HPI. Finally, we constructed a prognostic model of 6 sets of hypoxia-related genes (PGK1, JMJD6, S100A4, SLC2A3, DDIT4 and HK1) in OSCC. Conclusions: Hypoxia is closely related to immune cell infiltration, gene mutation, and prognosis in OSCC patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34847040

RESUMO

With the rapid development of Artificial Intelligence and Internet of Things, an increasing number of computation intensive or delay sensitive biomedical data processing and analysis tasks are produced in vehicles, bringing more and more challenges to the biometric monitoring of drivers. Edge computing is a new paradigm to solve these challenges by offloading tasks from the resource-limited vehicles to Edge Servers in Road Side Units. However, most of the traditional offloading schedules for vehicular networks concentrate on the edge, while some tasks may be too complex for ESs to process. To this end, we consider a collaborative vehicular network in which the cloud, edge and terminal can cooperate with each other to accomplish the tasks. The vehicles can offload the computation intensive tasks to the cloud to save the resource of edge. We further construct the virtual resource pool which can integrate the resource of multiple ESs since some regions may be covered by multiple RSUs. In this paper, we propose a Multi-Scenario offloading schedule for biomedical data processing and analysis in Cloud-Edge-Terminal collaborative vehicular networks called MSCET. The parameters of the proposed MSCET are optimized to maximize the system utility. We also conduct extensive simulations to evaluate MSCET.

3.
Nanoscale ; 13(45): 18996-19003, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34763346

RESUMO

Long-lasting yet visible-light-driven bacterial inhibition is highly desired for environmental protection and public health maintenance. However, conventional semiconductors such as titanium dioxide (TiO2) are impotent for such antibacterial application due to their low utilization rate for visible light. Herein we report the design of a long-lasting yet visible-light-driven antibacterial agent based on marrying luminescent Au nanoclusters (Au NCs for short) to TiO2 (TiO2-NH2@Au NCs). The as-obtained TiO2-NH2@Au NC antibacterial agent not only possesses superior utilization for visible light due to the participation of Au NCs as a good photosensitizer, but also has excellent separation efficacy of photogenerated carriers, thereby efficiently enhancing the generation of reactive oxygen species (ROS) for killing bacteria. Consequently, the TiO2-NH2@Au NCs display excellent antibacterial activity with good durability against both Gram-positive and Gram-negative bacteria such as Staphylococcus aureus (99.37%) and Escherichia coli (99.92%) under visible-light irradiation (λ ≥ 400 nm). This study is interesting because it provides a paradigm change in the design of long-lasting yet visible-light-driven NC-based antibacterial agents for diversified bactericidal applications.


Assuntos
Antibacterianos , Bactérias Gram-Negativas , Antibacterianos/farmacologia , Bactérias Gram-Positivas , Luz , Titânio
4.
Ann Palliat Med ; 10(10): 10756-10767, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763437

RESUMO

BACKGROUND: Myocardial infarction (MI) is one of the most common cardiovascular diseases, inducing severe myocardial injury and leading to high mortality. Bromodomain-containing protein 7 (BRD7), a member of bromodomain-containing protein family, is involved in multiple cellular processes, such as cell cycle, transcriptional regulation, and chromatin remodeling, but the functions of BRD7 in regulating MI-associated myocardial injury are still obscure. In this work, we investigated the effect of BRD7 on MI-induced myocardial injury in vitro and in vivo. METHODS: The MI model was established by ligating the left anterior descending coronary artery (LAD) of rats which were then injected with BRD7 short hairpin RNA (shRNA). The rat H9C2 cardiomyocytes were treated with hypoxia and injected with BRD7 shRNA. The expression of BRD7 in MI rat model, and hypoxia-treated H9C2 cells was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemical staining. The effect of BRD7 was analyzed using western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, echocardiography, and flow cytometry analysis. The expressions of Wnt/ß-catenin signaling relative proteins were determined by western blot. RESULTS: Significantly, BRD7 was highly expressed in MI patients, MI rat models, and hypoxia treated rat H9C2 cardiomyocytes. Echocardiography analysis demonstrated that the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were repressed in the MI rats relative to sham group rats, while the silencing of BRD7 rescued the dysfunction in the model. We also found that BRD7 silencing reduced cardiomyocyte apoptosis in both MI rats and H9C2 cells under the treatment of hypoxia. BRD7 silencing inhibited the activation of Wnt/ß-catenin signaling in H9C2 cells under the treatment of hypoxia. Moreover, Wnt agonist BML294 reversed the anti-apoptosis effect of BRD7 silencing in hypoxia-induced H9C2 cells. CONCLUSIONS: Collectively, we concluded that BRD7 contributed to MI-induced myocardial injury through activating Wnt/ß-catenin signaling. Targeting BRD7 may become a promising therapeutic strategy for the treatment of MI-induced myocardial injury.


Assuntos
MicroRNAs , Infarto do Miocárdio , Animais , Proteínas Cromossômicas não Histona , Humanos , Infarto do Miocárdio/genética , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Função Ventricular Esquerda , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-34815079

RESUMO

A novel perovskite CaLa4Ti4O15:Eu3+ red-emitting phosphor was synthesized via a sol-combustion method, and Gd3+ was further co-doped into structure to improve the luminescence performance. The effects of Eu3+ doping and Gd3+ co-doping concentrations on the microstructure and luminescence properties were investigated. The red emission peaks of as-prepared phosphors originate from the 5D0→7Fj electron transitions of Eu3+ ions. Under 273 nm excitation, the luminescence intensity of Eu3+ was significantly enhanced through the energy transfer between Gd3+ and Eu3+ in CaLa4Ti4O15, and the luminescence intensity was also improved even under the excitation of 394 nm. By combining red-emitting CaLa4Ti4O15:Eu3+, Gd3+ phosphor with commercial blue and green phosphors on n-UV chip (λ = 395 nm), an eye-friendly w-LEDs with appropriate correlated color temperature (4761 K) and high color rendering index (Ra = 93.1) has been realized. The electroluminescence spectrum of the packaged red LED have an excellent match with the PR absorption of plants. In addition, when introducing CaLa4Ti4O15:Eu3+, Gd3+ phosphor into a commercial w-LED with YAG:Ce3+, the adjustable chromaticity parameters like CCT and CRI values can be obtained. These results demonstrated that the as-prepared CaLa4Ti4O15:Eu3+, Gd3+ phosphor is an outstanding candidate as the red component for the application of w-LEDs and plants lighting.

6.
Foods ; 10(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34829061

RESUMO

Soybean whey is a high-yield but low-utilization agricultural by-product in China. In this study, soybean whey was used as a substrate of fermentation by Lacticaseibacillus plantarum 70810 strains. An exopolysaccharide (LPEPS-1) was isolated from soybean whey fermentation by L. plantarum 70810 and purified by ion-exchange chromatography. Its preliminary structural characteristics and antioxidant activity were investigated. Results show that LPEPS-1 was composed of mannose, glucose, and galactose with molar ratios of 1.49:1.67:1.00. The chemical structure of LPEPS-1 consisted of →4)-α-D-Glcp-(1→, →3)-α-D-Galp-(1→ and →2)-α-D-Manp-(1→. Scanning electron microscopy (SEM) revealed that LPEPS-1 had a relatively rough surface. In addition, LPPES-1 exhibited strong scavenging activity against DPPH and superoxide radicals and chelating ability on ferrous ion. This study demonstrated that soybean whey was a feasible fermentation substrate for the production of polysaccharide from L. plantarum 70810 and that the polysaccharide could be used as a promising ingredient for health-beneficial functional foods.

7.
Adv Healthc Mater ; : e2101586, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34601825

RESUMO

Pathological mineralization (PTM) often occurs under inflammation and affects the prognosis of diseases, such as atherosclerosis and cancers. However, how the PTM impacts inflammation has not been well explored. Herein, poly lactic-co-glycolic acid (PLGA)/gelatin/hydroxyapatite (HA) electrospun nanofibers are rationally designed as an ideal PTM microenvironment biomimetic system for unraveling the role of PTM on inflammation. The results demonstrate that the inflammatory response decreases continuously during the process of mineralization. When mature macromineralization forms, the inflammation almost completely disappears. Mechanistically, the PTM formation is mediated by matrix proteins, local high calcium, and cell debris (nuclei), or actively regulated by the lysosomal/plasma membrane components secreted by macrophages. These inflammatory inducible factors (calcium, cell debris, etc.) can be "buried" through PTM process, resulting in reduced immune responses. Overall, the present study demonstrates that PTM is an innate mechanism of inflammation subsidence, providing valuable insight into understanding the action of mineralization on inflammation.

8.
Ann Palliat Med ; 10(9): 9607-9613, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628886

RESUMO

BACKGROUND: Adolescents are a high-risk group for non-suicidal self-injury (NSSI), which seriously affects their physical and mental health. This study aimed to explore the risk factors for depressive adolescents with NSSI. METHODS: A total of 153 adolescents with depression were divided into the NSSI group (n=65) and non-NSSI group (n=88) according to the criteria stipulated by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The Beck scale for suicidal ideation (BSS), adolescent self-rating life events checklist (ASLEC), family adaptability and cohesion evaluation scale II-Chinese version (FACES II-CV), childhood trauma questionnaire short form (CTQ SF), and multidimensional scale of perceived social support (MSPSS) were applied to evaluate suicidal ideation, frequency and intensity of stressful life events, family functions, childhood trauma, and perceived support, respectively. We applied two-dimensional logistic regression to identify risk factors for NSSI. RESULTS: Female gender ratio, suicidal ideation, and attempted suicide were significantly higher in the NSSI group than in the non-NSSI group (all P<0.05). Scores of interpersonal relationships in ASLEC, emotional abuse, and emotional neglect in the CTQ-SF were significantly higher in the NSSI group than those in the non-NSSI group (all P<0.001). The scores of family cohesion (P=0.001) and family adaptability (P=0.01) were significantly lower in the NSSI group than in the non-NSSI group. The MSPSS was used to assess support from the family, and the index was significantly lower in the NSSI group (P<0.001). After adjusting for age and gender, BSS score, interpersonal relationship score, emotional abuse score, and emotional neglect score were identified as independent risk factors for NSSI. CONCLUSIONS: The rate of NSSI in adolescents with depression is high. Higher scores of BSS, interpersonal relationship, emotional abuse, and neglect were independently associated with NSSI.


Assuntos
Depressão , Comportamento Autodestrutivo , Adolescente , Criança , Feminino , Humanos , Fatores de Risco , Ideação Suicida , Tentativa de Suicídio
9.
Sci Rep ; 11(1): 20458, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650063

RESUMO

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

11.
Front Public Health ; 9: 572415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485206

RESUMO

Objective: To understand the impact of COVID-19 epidemic on the mental health status of intensive care unit (ICU) practitioners in China, and to explore the relevant factors that may affect the mental health status of front-line medical workers so as to adopt efficient and comprehensive measures in a timely manner to protect the mental health of medical staff. Methods: The study covered most of the provinces in China, and a questionnaire survey was conducted based on the WeChat platform and the Wenjuanxing online survey tool. With the method of anonymous investigation, we chose ICU practitioners to participate in the investigation from April 5, 2020 to April 7, 2020. The respondents were divided into two groups according to strict criteria of inclusion and exclusion, those who participated in the rescue work of COVID-19 (COVID-19 group) and those who did not (non-COVID-19 group). The SCL-90 self-evaluation scale was used for the evaluation of mental health status of the subjects. Results: A total of 3,851 respondents completed the questionnaire. First, the overall mental health status of the targeted population, compared with the Chinese norm (n = 1,388), was reflected in nine related factor groups of the SCL-90 scale, and significant differences were found in every factor in both men and women, except for the interpersonal sensitivity in men. Second, the overall mental health of the non-COVID-19 group was worse than that of the COVID-19 group by the SCL-90 scale (OR = 1.98, 95% CI, 1.682-2.331). Third, we have revealed several influencing factors for their mental health in the COVID-19 group, current working status (P < 0.001), satisfaction of diet and accommodation (P < 0.05), occupational exposure (P = 0.005), views on the risk of infection (P = 0.034), and support of training (P = 0.01). Conclusion: The mental health status of the ICU practitioners in the COVID-19 group is better than that of the non-COVID-19 group, which could be attributed to a strengthened mentality and awareness of risks related to occupational exposure and enforced education on preventive measures for infectious diseases, before being on duty.


Assuntos
COVID-19 , Epidemias , China/epidemiologia , Feminino , Nível de Saúde , Humanos , Unidades de Terapia Intensiva , Masculino , SARS-CoV-2
12.
Br J Nutr ; : 1-12, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34526168

RESUMO

Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40-69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29-9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.

13.
Environ Sci Technol ; 55(20): 14173-14184, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34590827

RESUMO

Selective inhibition of photosynthesis is a fundamental strategy to solve the global challenge caused by harmful cyanobacterial blooms. However, there is a lack of specificity of the currently used cyanocides, because most of them act on cyanobacteria by generating nontargeted oxidative stress. Here, for the first time, we find that the simplest ß-diketone, acetylacetone, is a promising specific cyanocide, which acts on Microcystis aeruginosa through targeted binding on bound iron species in the photosynthetic electron transport chain, rather than by oxidizing the components of the photosynthetic apparatus. The targeted binding approach outperforms the general oxidation mechanism in terms of specificity and eco-safety. Given the essential role of photosynthesis in both natural and artificial systems, this finding not only provides a unique solution for the selective control of cyanobacteria but also sheds new light on the ways to modulate photosynthesis.


Assuntos
Cianobactérias , Microcystis , Proliferação Nociva de Algas , Ferro , Oxirredução , Fotossíntese
14.
Int J Mol Sci ; 22(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502486

RESUMO

Complement factor B (CFB), a 95-kDa protein, is a crucial catalytic element of the alternative pathway (AP) of complement. After binding of CFB to C3b, activation of the AP depends on the proteolytic cleavage of CFB by factor D to generate the C3 convertase (C3bBb). The C3 convertase contains the catalytic subunit of CFB (Bb), the enzymatic site for the cleavage of a new molecule of C3 into C3b. In addition to its role in activating the AP, CFB has been implicated in pathological ocular neovascularization, a common feature of several blinding eye diseases, however, with somewhat conflicting results. The focus of this study was to investigate the direct impact of CFB on ocular neovascularization in a tightly controlled environment. Using mouse models of laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), our study demonstrated an increase in CFB expression during pathological angiogenesis. Results from several in vitro and ex vivo functionality assays indicated a promoting effect of CFB in angiogenesis. Mechanistically, CFB exerts this pro-angiogenic effect by mediating the vascular endothelial growth factor (VEGF) signaling pathway. In summary, we demonstrate compelling evidence for the role of CFB in driving ocular angiogenesis in a VEGF-dependent manner. This work provides a framework for a more in-depth exploration of CFB-mediated effects in ocular angiogenesis in the future.


Assuntos
Neovascularização de Coroide/metabolismo , Fator B do Complemento/metabolismo , Neovascularização Retiniana/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Neovascularização de Coroide/patologia , Camundongos , Neovascularização Retiniana/patologia
15.
Front Microbiol ; 12: 715450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335553

RESUMO

Hepatitis B virus (HBV) infection is a global public health problem that plagues approximately 240 million people. Chronic hepatitis B (CHB) often leads to liver inflammation and aberrant repair which results in diseases ranging from liver fibrosis, cirrhosis, to hepatocellular carcinoma. Despite its narrow species tropism, researchers have established various in vivo models for HBV or its related viruses which have provided a wealth of knowledge on viral lifecycle, pathogenesis, and immunity. Here we briefly revisit over five decades of endeavor in animal model development for HBV and summarize their advantages and limitations. We also suggest directions for further improvements that are crucial for elucidation of the viral immune-evasion strategies and for development of novel therapeutics for a functional cure.

16.
Int J Biol Macromol ; 188: 833-843, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389385

RESUMO

This study aimed to explore the in vitro simulated digestion and fecal fermentation behaviors of two purified exopolysaccharide fractions (EPS1 and EPS2) from Paecilomyces cicadae TJJ1213 and its effects on human gut microbiota composition. Results showed that EPS1 and EPS2 could not be digested by saliva-gastrointestinal. After fecal fermentation, however, the molecular weight of EPS1 and EPS2 significantly decreased, and the molar ratios of the monosaccharide composition remarkably changed, indicating that EPS1 and EPS2 could be degraded and consumed by human gut microbiota. Notably, EPS1 and EPS2 could significantly modulate the composition, via increasing the relative abundances of Bacteroides and Phascolarctobacterium and decreasing the pathogenic bacteria Escherichia-Shigella, Klebsiella and Fusobacterium. In addition, EPS1 and EPS2 also could promote the production of short-chain fatty acids during fermentation for 24 h. These results suggested that EPS from Paecilomyces cicadae TJJ1213 can be used as a functional food to improve health and prevent diseases by promoting gut health.

17.
BMC Infect Dis ; 21(1): 813, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388976

RESUMO

BACKGROUND: Part of tuberculosis (TB) patients were missed if symptomatic screening was based on the main TB likely symptoms. This study conducted to compare the yield and relative costs of different TB screening algorithms in active case-finding in the whole population in China. METHODS: The study population was screened based on the TB likely symptoms through a face-to-face interview in selected 27 communities from 10 counties of 10 provinces in China. If the individuals had any of the enhanced TB likely symptoms, both chest X-ray and sputum tests were carried out for them furtherly. We used the McNemar test to analyze the difference in TB detection among four algorithms in active case-finding. Of four algorithms, two were from WHO recommendations including 1a/1c, one from China National Tuberculosis Program, and one from this study with the enhanced TB likely symptoms. Furthermore, a two-way ANOVA analysis was performed to analyze the cost difference in the performance of active case-finding adjusted by different demographic and health characteristics among different algorithms. RESULTS: Algorithm with the enhanced TB likely symptoms defined in this study could increase the yield of TB detection in active case-finding, compared with algorithms recommended by WHO (p < 0.01, Kappa 95% CI: 0. 93-0.99) and China NTP (p = 0.03, Kappa 95% CI: 0.96-1.00). There was a significant difference in the total costs among different three algorithms WHO 1c/2/3 (F = 59.13, p < 0.01). No significant difference in the average costs for one active TB case screened and diagnosed through the process among Algorithms 1c/2/3 was evident (F = 2.78, p = 0.07). The average costs for one bacteriological positive case through algorithm WHO 1a was about two times as much as the costs for one active TB case through algorithms WHO 1c/2/3. CONCLUSIONS: Active case-finding based on the enhanced symptom screening is meaningful for TB case-finding and it could identify more active TB cases in time. The findings indicated that this enhanced screening approach cost more compared to algorithms recommend by WHO and China NTP, but the increased yield resulted in comparative costs per patient. And it cost much more that only smear/bacteriological-positive TB cases are screened in active case-finding.


Assuntos
Programas de Rastreamento/economia , Tuberculose/diagnóstico , Tuberculose/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Escarro , Tuberculose/epidemiologia
18.
Food Res Int ; 147: 110515, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399493

RESUMO

Two intracellular polysaccharide fractions (IPS1 and IPS2) were obtained from the mycelium of Paecilomyces cicadae TJJ1213, and the structures were conducted. Results showed that they were homogenous with the average molecular weight of 2.40 × 106 Da and 6.79 × 105 Da. Two fractions were composed of mannose, glucose and galactose with molar ratios of 1.35: 6.93: 1.0 and 2.04: 1.0: 1.87, respectively. The backbone of IPS1 was â†’ 4)-α-D-Glcp (1 â†’ and â†’ 3,4)-α-D-Manp (1 â†’ residues with a side chain consisted of T-α-D-Galp. IPS2 was consisted of â†’ 4)-α-D-Glcp-(1→, →3,4)-α-D-Manp-(1 â†’ and â†’ 2,6)-α-D-Manp-(1 â†’ residues and the branches were also consisted of T-α-D-Galp. In addition, the scanning electron microscope and atomic force microscope images presented different features of IPS1 and IPS2, respectively. Furthermore, two fractions exhibited better immunomodulatory effects. They could markedly promote the proliferation of RAW264.7 cells and enhance phagocytosis, nitric oxide release and cytokines production. These results indicated that IPS1 and IPS2 had potential to enhance immune responses.


Assuntos
Micélio , Polissacarídeos , Animais , Cordyceps , Imunidade , Camundongos , Células RAW 264.7
19.
Mar Drugs ; 19(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34436310

RESUMO

Ocular angiogenic diseases, characterized by abnormal blood vessel formation in the eye, are the leading cause of blindness. Although Anti-VEGF therapy is the first-line treatment in the market, a substantial number of patients are refractory to it or may develop resistance over time. As uncontrolled proliferation of vascular endothelial cells is one of the characteristic features of pathological neovascularization, we aimed to investigate the role of the class I histone deacetylase (HDAC) inhibitor Largazole, a cyclodepsipeptide from a marine cyanobacterium, in ocular angiogenesis. Our study showed that Largazole strongly inhibits retinal vascular endothelial cell viability, proliferation, and the ability to form tube-like structures. Largazole strongly inhibits the vessel outgrowth from choroidal explants in choroid sprouting assay while it does not affect the quiescent choroidal vasculature. Largazole also inhibits vessel outgrowth from metatarsal bones in metatarsal sprouting assay without affecting pericytes coverage. We further demonstrated a cooperative effect between Largazole and an approved anti-VEGF drug, Alflibercept. Mechanistically, Largazole strongly inhibits the expression of VEGFR2 and leads to an increased expression of cell cycle inhibitor, p21. Taken together, our study provides compelling evidence on the anti-angiogenic role of Largazole that exerts its function through mediating different signaling pathways.

20.
Cell Biosci ; 11(1): 162, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419157

RESUMO

BACKGROUND: There are seven human-adaptation lineages of Mycobacterium tuberculosis (Mtb). Tuberculosis (TB) dissemination is strongly influenced by human movements and host genetics. The detailed lineage distribution evolution of Mtb in Zhejiang Province is unknown. We aim to determine how different sub-lineages are transmitted and distributed within China and Zhejiang Province. METHODS: We analysed whole-genome sequencing data for a worldwide collection of 1154 isolates and a provincial collection of 1296 isolates, constructed the best-scoring maximum likelihood phylogenetic tree. Bayesian evolutionary analysis was used to calculate the latest common ancestor of lineages 2 and 4. The antigenic diversity of human T cell epitopes was evaluated by calculating the pairwise dN/dS ratios. RESULTS: Of the Zhejiang isolates, 964 (74.38%) belonged to lineage 2 and 332 (25.62%) belonged to lineage 4. The distributions of the sub-lineages varied across the geographic regions of Zhejiang Province. L2.2 is the most ancient sub-lineage in Zhejiang, first appearing approximately 6897 years ago (95% highest posterior density interval (HDI): 6513-7298). L4.4 is the most modern sub-lineage, first appearing approximately 2217 years ago (95% HDI: 1864-2581). The dN/dS ratios showed that the epitope and non-epitope regions of lineage 2 strains were significantly (P < 0.001) more conserved than those of lineage 4. CONCLUSIONS: An increase in the frequency of lineage 4 may reflect its successful transmission over the last 20 years. The recent common ancestors of the sub-lineages and their transmission routes are relevant to the entry of humans into China and Zhejiang Province. Diversity in T cell epitopes may prevent Mycobacterium tuberculosis from being recognized by the immune system.

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