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1.
Int J Mol Med ; 47(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955502

RESUMO

Generalized pustular psoriasis (GPP) is a rare and severe auto­inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants of IL36RN, CARD14, AP1S3 and MPO genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. These disease­related genes are involved in common inflammatory pathways, in particular in the IL­1/IL­36­chemokines­neutrophil pathogenic axis. At present, no standard therapeutic guidelines have been established for GPP management, and there is a profound need for novel efficacious treatments of GPP. Among them, biological agents antagonizing the IL­36 pathway are promising therapeutics. The aim of the present review is to provide the most recent updates on the genetics, genotype­phenotype correlation and pathological basis of GPP, as well as on biologic treatments available for GPP and relative clinical courses.

2.
Mol Psychiatry ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931731

RESUMO

Glucoregulatory efficiency and ATP production are key regulators for neuronal plasticity and memory formation. Besides its chemotactic and neuroinflammatory functions, the CC chemokine--CCL5 displays neurotrophic activity. We found impaired learning-memory and cognition in CCL5-knockout mice at 4 months of age correlated with reduced hippocampal long-term potentiation and impaired synapse structure. Re-expressing CCL5 in knockout mouse hippocampus restored synaptic protein expression, neuronal connectivity and cognitive function. Using metabolomics coupled with FDG-PET imaging and seahorse analysis, we found that CCL5 participates in hippocampal fructose and mannose degradation, glycolysis, gluconeogenesis as well as glutamate and purine metabolism. CCL5 additionally supports mitochondrial structural integrity, purine synthesis, ATP generation, and subsequent aerobic glucose metabolism. Overexpressing CCL5 in WT mice also enhanced memory-cognition performance as well as hippocampal neuronal activity and connectivity through promotion of de novo purine and glutamate metabolism. Thus, CCL5 actions on glucose aerobic metabolism are critical for mitochondrial function which contribute to hippocampal spine and synapse formation, improving learning and memory.

3.
Methods Mol Biol ; 2281: 67-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33847952

RESUMO

Single-stranded DNA (ssDNA)-binding protein (SSB) is essential for DNA metabolic processes. SSB also binds to many DNA-binding proteins that constitute the SSB interactome. The mechanism through which PriA helicase, an initiator protein in the DNA replication restart process, is stimulated by SSB in Escherichia coli (EcSSB) has been established. However, some Gram-positive bacterial SSBs such as Bacillus subtilis SsbA (a counterpart of EcSSB), Staphylococcus aureus SsbA, SsbB, and SsbC do not activate PriA helicase. Here, we describe some of the methods used in our laboratory to compare SSB-PriA functional and physical interactions in Gram-positive and -negative bacteria.

4.
Oncogene ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846569

RESUMO

The ASPL-TFE3 fusion gene, resulting from t(X;17)(p11.2;q25.3), is one of the most commonly identified fusion genes in Xp11 translocation renal cell carcinoma (tRCC). However, its roles and underlying mechanism in RCC development are not yet clear. Here, we identified ASPL-TFE3 fusion as the most common tRCC subtype in a Chinese population (29/126, 23.03%). This fusion protein translocated into the nucleus and promoted RCC cell proliferation both in vitro and in vivo. Mechanistically, the fusion protein transcriptionally activated the lysosome-autophagy pathway by binding to the promoters of lysosome-related genes. Autophagy, activated by ASPL-TFE3, enabled RCC cells to escape energy stress by promoting the utilization of proteins and lipids. Moreover, we found that the ASPL-TFE3 fusion escaped regulation by the classic mTOR-TFE3 signal and instead activated phospho-mTOR and its downstream targets. Finally, targeting both autophagy and the mTOR axis resulted in a greater antiproliferative effect than single pathway inhibition. In summary, these results confirmed the ASPL-TFE3 fusion as a master regulator of metabolic adaptation mediated by autophagy in tRCC. The simultaneous manipulation of autophagy and the mTOR axis may represent a novel treatment strategy for ASPL-TFE3 fusion RCC.

5.
J Hazard Mater ; 416: 125783, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33839503

RESUMO

In order to investigate the explosion process of calcium carbide (CaC2) dust in the acetylene (C2H2) atmosphere, the explosion characteristics of C2H2 gas and C2H2/CaC2 dust gas-solid two-phase mixture were studied using a 20-L spherical vessel, and the chemical composition of solid residues after explosion were also analyzed. Experimental results showed that the Pex values of C2H2 gas explosion rose first and then remained stable with the increasing stoichiometric ratio values (φ) of C2H2/air, while the (dP/dt)ex values tended to increase at early stage and then decrease, the inflection point of (dP/dt)ex values was φ = 1.78. The explosion severity and risk of C2H2 gas were enhanced by adding CaC2 dust, and the optimum additive concentration of CaC2 dust was 100 g/m3. In the oxygen atmosphere, the C2H2/CaC2 hybrid explosion was divided into two stages when the concentration of CaC2 dust was over 300 g/m3. The explosion risk of the first stage (Stage Ⅰ) was much more serious, while the explosion severity of the second stage (Stage Ⅱ) was much more fierce. The solid residues of hybrid explosion only contained CaO in the oxygen atmosphere, however, Ca(OH)2 and CaO were detected in the solid residues in the air atmosphere, owing to the combustion heat of C2H2 gas in oxygen was higher than that in air. The hydrolysis reaction time of CaC2 particle with large particle size was prolonged, and the diffusion of solid product layer and surface chemical reaction both influenced the hydrolysis process according to the shrinking core model. Based on the explosion and chemical analysis experiments, the explosion mechanism of C2H2/CaC2 dust gas-solid two-phase mixture was analyzed systematically.

6.
Food Funct ; 12(8): 3572-3585, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900346

RESUMO

Type 2 diabetic mellitus (T2DM) is a complicated metabolic disorder that is now considered as a major global public health problem. Fucoidan exhibits diverse biological activities, especially prevention of metabolic diseases. In this regard, we herein aimed to reveal the beneficial effect of Sargassum fusiforme fucoidan (SFF) on high-fat diet (HFD) and streptozotocin (STZ) induced T2DM mice. We noted that on the one hand, SFF significantly decreased fasting blood glucose, diet and water intake, and hyperlipidemia, while on the other hand, it improved glucose tolerance. Furthermore, SFF reduced epididymal fat deposition, attenuated the pathological changes in heart and liver tissues, and decreased oxidative stress in diabetic mice. To explore the underlying mechanisms of these ameliorative effects, the gut microbiota was analyzed. Notably, SFF highly enriched benign microbes including Bacteroides, Faecalibacterium and Blautia, as well as increased levels of (R)-carnitine and choline in the colon of diabetic mice. This may be a potential mechanism for alleviating T2DM, thus implying the benefits of SFF as an adjuvant agent for T2DM treatment. Taken together, this study demonstrated a promising application of fucoidan as one of the adjuvant agents for the management of T2DM in the future.

9.
Biochem Biophys Res Commun ; 556: 106-113, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839405

RESUMO

Among all lung cancer cases, lung adenocarcinoma (LAC) represents nearly 40% and remains the leading cause of cancer deaths worldwide. Although the combination therapy of surgical treatment with radiotherapy, chemotherapy, and immunotherapy, has been used to treat LAC, unfortunately, high recurrence rates and poor survival remain. Therefore, novel prognostic markers and new targets for molecular targeted therapy in LAC is urgently needed. Fork-head box R2 (FOXR2) plays a key role in a wide range of cellular processes, including cellular proliferation, invasion, differentiation, and apoptosis, and it has been reported to be implicated in progression of LAC, thus inhibition of FOXR2 may be a novel targeting therapy for lung cancer. This current study found that E3 ligase PJA1 regulates ubiquitin-mediated degradation of FOXR2 and predicts good outcome of patients with LAC. In addition, it was showed force expression of PJA1 significantly inhibited LAC cells invasion and induced apoptosis in vitro through inactivating Wnt/ß-catenin signaling pathway. In short, our findings reveal that PJA1 could be a potential diagnostic and prognostic biomarkers and the PJA1- FOXR2 axis could be served as a promising target for LAC therapy.

10.
Bioinspir Biomim ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906161

RESUMO

An optical zoom imaging system that can vary the magnification factor without displacing the object and the image plane has been widely used. Nonetheless, conventional optical zoom imaging systems suffer slow response, complicated configuration, vulnerability to misalignment during zoom operation, and are incompatible for miniaturized applications. This review article focuses on state-of-the-art research on novel optical zoom imaging systems that use adaptive liquid lenses. From the aspect of the configuration, according to the amount of the adaptive liquid lenses, we broadly divide the current optical zoom imaging systems using adaptive liquid lenses into two configurations: multiple adaptive liquid lenses, and a single adaptive liquid lens. The principles and configurations of these optical zoom imaging systems are introduced and represented. Three different working principles of the adaptive liquid lens (liquid crystal, polymer elastic membrane, and electrowetting effect) adopted in the optical zoom imaging systems are reviewed. Some representative applications of optical zooming imaging systems using adaptive liquid lenses are introduced. The opportunities and challenges of the optical zoom imaging systems using adaptive liquid lenses are also discussed. This review aims to provide a snapshot of the current state of this research field for attracting more attention to put forward the development of the next-generation optical zoom imaging systems.

11.
Autophagy ; : 1-18, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33749503

RESUMO

Basal macroautophagy/autophagy has recently been found in anucleate platelets. Platelet autophagy is involved in platelet activation and thrombus formation. However, the mechanism underlying autophagy in anucleate platelets require further clarification. Our data revealed that LC3-II formation and SQSTM1/p62 degradation were noted in H2O2-activated human platelets, which could be blocked by 3-methyladenine and bafilomycin A1, indicating that platelet activation may cause platelet autophagy. AMPK phosphorylation and MTOR dephosphorylation were also detected, and block of AMPK activity by the AMPK inhibitor dorsomorphin reversed SQSTM1 degradation and LC3-II formation. Moreover, autophagosome formation was observed through transmission electron microscopy and deconvolution microscopy. These findings suggest that platelet autophagy was induced partly through the AMPK-MTOR pathway. In addition, increased LC3-II expression occurred only in H2O2-treated Atg5f/f platelets, but not in H2O2-treated atg5-/- platelets, suggesting that platelet autophagy occurs during platelet activation. atg5-/- platelets also exhibited a lower aggregation in response to agonists, and platelet-specific atg5-/- mice exhibited delayed thrombus formation in mesenteric microvessles and decreased mortality rate due to pulmonary thrombosis. Notably, metabolic analysis revealed that sphingolipid metabolism is involved in platelet activation, as evidenced by observed several altered metabolites, which could be reversed by dorsomorphin. Therefore, platelet autophagy and platelet activation are positively correlated, partly through the interconnected network of sphingolipid metabolism. In conclusion, this study for the first time demonstrated that AMPK-MTOR signaling could regulate platelet autophagy. A novel linkage between AMPK-MTOR and sphingolipid metabolism in anucleate platelet autophagy was also identified: platelet autophagy and platelet activation are positively correlated.Abbreviations: 3-MA: 3-methyladenine; A.C.D.: citric acid/sod. citrate/glucose; ADP: adenosine diphosphate; AKT: AKT serine/threonine kinase; AMPK: AMP-activated protein kinase; ANOVA: analysis of variance; ATG: autophagy-related; B4GALT/LacCS: beta-1,4-galactosyltransferase; Baf-A1: bafilomycin A1; BECN1: beclin 1; BHT: butylate hydrooxytoluene; BSA: bovine serum albumin; DAG: diacylglycerol; ECL: enhanced chemiluminescence; EDTA: ethylenediamine tetraacetic acid; ELISA: enzyme-linked immunosorbent assay; GALC/GCDase: galactosylceramidase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/GluSDase: glucosylceramidase beta; GPI: glycosylphosphatidylinositol; H2O2: hydrogen peroxide; HMDB: human metabolome database; HRP: horseradish peroxidase; IF: immunofluorescence; IgG: immunoglobulin G; KEGG: Kyoto Encyclopedia of Genes and Genomes; LAMP1: lysosomal associated membrane protein 1; LC-MS/MS: liquid chromatography-tandem mass spectrometry; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MPV: mean platelet volume; MTOR: mechanistic target of rapamycin kinase; ox-LDL: oxidized low-density lipoprotein; pAb: polyclonal antibody; PC: phosphatidylcholine; PCR: polymerase chain reaction; PI3K: phosphoinositide 3-kinase; PLS-DA: partial least-squares discriminant analysis; PRP: platelet-rich plasma; Q-TOF: quadrupole-time of flight; RBC: red blood cell; ROS: reactive oxygen species; RPS6KB/p70S6K: ribosomal protein S6 kinase B; SDS: sodium dodecyl sulfate; S.E.M.: standard error of the mean; SEM: scanning electron microscopy; SGMS: sphingomyelin synthase; SM: sphingomyelin; SMPD/SMase: sphingomyelin phosphodiesterase; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; UGT8/CGT: UDP glycosyltransferase 8; UGCG/GCS: UDP-glucose ceramide glucosyltransferase; ULK1: unc-51 like autophagy activating kinase 1; UPLC: ultra-performance liquid chromatography; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PtdIns3P: phosphatidylinositol-3-phosphate; WBC: white blood cell; WT: wild type.

12.
Biochem Biophys Res Commun ; 551: 33-37, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33714757

RESUMO

Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway of pyrimidine nucleotides and considered an attractive target for potential antimalarial, anticancer, and antipathogen chemotherapy. Whether the FDA-approved clinical drug 5-fluorouracil (5-FU) that is used to target the enzyme thymidylate synthase for anticancer therapy can also bind to DHOase remains unknown. Here, we report the crystal structures of DHOase from Saccharomyces cerevisiae (ScDHOase) complexed with malate, 5-FU, and 5-aminouracil (5-AU). ScDHOase shares structural similarity with Escherichia coli DHOase. We also characterized the binding of 5-FU and 5-AU to ScDHOase by using the fluorescence quenching method. These complexed structures revealed that residues Arg18, Asn43, Thr106, and Ala275 of ScDHOase were involved in the 5-FU (PDB entry 6L0B) and 5-AU binding (PDB entry 6L0F). Overall, these results provide structural insights that may facilitate the development of new inhibitors targeting DHOase and constitute the 5-FU and 5-AU interactomes for further clinical chemotherapies.

14.
Appl Opt ; 60(6): 1535-1543, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33690486

RESUMO

To achieve non-uniform imaging with a large field of view and high efficiency as well as to obtain an adjustable fovea with super-resolution, we proposed a curved retina-like camera array imaging system (CRCS), which is built by an eight-camera array distributed non-uniformly on a curved surface and a camera coaxial with Risley prisms located in the center. By the non-uniform imaging, the field of view of the developed prototype is 150∘×40∘ with a reduction of data redundancy by 87.62%. Besides, the experimental results show that CRCS can obtain clear and sharp images of farther targets of interest around the fovea field of view with a constant focal length.

15.
Medicina (Kaunas) ; 57(2)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671309

RESUMO

Background and Objectives: The programs of enhanced recovery after surgery are the new revolution in surgical departments; however, features of this concept have not been systematically explored. Therefore, the purpose of this study was to explore Enhanced recovery after surgery (ERAS)-related research using bibliometric analysis. Materials and Methods: The search strategy of ERAS programs was conducted in the Web of Science database. Bibliometric analysis was further performed by Excel and Bibliometrix software. The relationship between citation counts and Mendeley readers was assessed by linear regression analysis. Results: 8539 studies from 1994-2019 were included in the present research, with reporting studies originating from 91 countries using 18 languages. The United States (US) published the greatest number of articles. International cooperation was discovered in 82 countries, with the most cooperative country being the United Kingdom. Henrik Kehlet was found to have published the highest number of studies. The journal Anesthesia and Analgesia had the largest number of articles. Linear regression analysis presented a strong positive correlation between citations and Mendeley readers. Most research was related to gastrointestinal surgery in this field. Conclusion: This bibliometric analysis shows the current status of ERAS programs from multiple perspectives, and it provides reference and guidance to scholars for further research.

16.
Cell Host Microbe ; 29(4): 503-507, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33676588

RESUMO

Since the outbreak of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, the viral genome has acquired numerous mutations with the potential to increase transmission. One year after its emergence, we now further analyze emergent SARS-CoV-2 genome sequences in an effort to understand the evolution of this virus.


Assuntos
/virologia , Evolução Molecular , Genoma Viral , Mutação , /genética , /imunologia , Humanos
17.
Microorganisms ; 9(2)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668643

RESUMO

Bacillus amyloliquefaciens TL promotes broiler chicken performance by improving nutrient absorption and utilization and reducing intestinal inflammation. In this study, RNA-sequencing (RNA-seq)-based transcriptomes of ileal tissues collected from probiotic-fed and control broiler chickens were analyzed to elucidate the effects of the probiotic B. amyloliquefaciens TL, as a feed additive, on the gut immune function. In total, 475 genes were significantly differentially expressed between the ileum of probiotic-fed and control birds. The expression of genes encoding pyruvate kinase, prothymosin-α, and heat stress proteins was high in the ileum of probiotic-fed birds (FPKM > 500), but not in the control group. The gene ontology functional enrichment and pathway enrichment analyses revealed that the uniquely expressed genes in the control group were mostly involved in immune responses, whereas those in the probiotic group were involved in fibroblast growth factor receptor signaling pathways and positive regulation of cell proliferation. Bacillus amyloliquefaciens TL downregulated the expression of certain proinflammatory factors and affected the cytokine-cytokine receptor interaction pathway. Furthermore, B. amyloliquefaciens TL in broiler diets altered the expression of genes involved in immune functions in the ileum. Thus, it might contribute to improved broiler growth by regulating the immune system and reducing intestinal damage in broilers.

18.
Catheter Cardiovasc Interv ; 97 Suppl 2: 1072-1079, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33764682

RESUMO

OBJECTIVES: To investigate a strategy for ultra-low volume contrast percutaneous coronary intervention (PCI) with the aims of preserving renal function and observing the 90-day clinical endpoint in patients with non-ST-elevated myocardial infarction (non-STEMI) and chronic kidney disease (CKD). BACKGROUND: The feasibility, safety, and clinical utility of PCI with ultra-low radio-contrast medium in patients with non-STEMI and CKD are unknown. METHODS: A total of 29 patients with non-STEMI and CKD (estimated glomerular filtration rate [eGFR] of ≤60 ml/min/1.73 m2 ) were included. Ultra-low volume contrast PCI was performed after minimal contrast coronary angiography using zero contrast optical coherence tomography (OCT) guidance. Pre- and post-PCI angiographic measurements were performed using quantitative flow ratio (QFR) for pre-perfusion assessment and verifying improvement. RESULTS: The median creatinine level was 2.1 (inter-quartile range 1.8-3.3), and mean eGFR was 48 ± 8 ml/min/1.73 m2 pre-PCI. During the PCI procedure, OCT revealed 15 (52%) cases of abnormalities post-dilation. There was no significant change in the creatinine level and eGFR in the short- or long-term, and no major adverse events were observed. CONCLUSION: In non-STEMI patients with high-risk CKD who require revascularization, QFR and no contrast OCT-guided ultra-low contrast PCI may be performed safely without major adverse events.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33669713

RESUMO

During the COVID-19 pandemic, older adults appear to be more susceptible to the coronavirus disease. Although the health stakes are higher for older adults, individuals of all ages should adopt preventive measures to contain the human-to-human transmission of the virus. This study conducted a national online survey of 1843 adults at the early stage of the COVID-19 pandemic in the U.S. to examine age disparities in preventive behaviors against the virus. The results show that older generations, motivated by a higher perceived severity of the disease, were more likely to take the precautionary actions recommended by the U.S. Centers for Disease Control and Prevention (CDC) than younger generations. This thus suggests that persuasive health messages addressing the severity of COVID-19 might reduce the generational gap and promote preventive behaviors among young people, to protect themselves and the elderly.


Assuntos
Fatores Etários , Comportamentos Relacionados com a Saúde , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Inquéritos e Questionários , Adulto Jovem
20.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760134

RESUMO

Islet transplantation (IT) is considered the most effective endocrine replacement therapy for diabetes mellitus (DM). Studies have demonstrated that IT can repair testicular structural injury caused by inflammatory and oxidative stress in a diabetic rat model. However, highly effective exogenous antioxidant and anti-inflammatory drugs can achieve this effect. Testicular interstitial fibrosis caused by long-term hyperglycemia is however difficult to reverse or recover. Thus far, there are no effective drugs that prevent or relieve testicular interstitial fibrosis. Therefore, it is necessary to explore the potential benefit of IT on testicular interstitial fibrosis induced by DM and its underlying molecular mechanisms. In the present study, Wistar rats were used to establish a DM model by intraperitoneal injection of streptozotocin. The diabetic models then underwent IT or received insulin treatment after 12 weeks. IT was more effective than insulin treatment in ameliorating diabetic-induced testicular interstitial fibrosis, Leydig cells apoptosis, testosterone deficiency and poor sperm motility. IT and insulin treatment both significantly inhibited the upregulation of TGF-ß1 and phosphorylated Smad2 in DM, with IT being more effective than insulin. The present study's findings proved that IT effectively protects diabetic-induced testicular interstitial fibrosis probably by inhibiting the TGF-ß1/Smad2 signaling pathway, which offers hope in male patients with DM complicating with testicular interstitial fibrosis.


Assuntos
Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/genética , Fibrose/terapia , Proteína Smad2/genética , Fator de Crescimento Transformador beta1/genética , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Fibrose/etiologia , Fibrose/genética , Fibrose/patologia , Humanos , Insulina/genética , Transplante das Ilhotas Pancreáticas , Células Intersticiais do Testículo/patologia , Células Intersticiais do Testículo/transplante , Masculino , Ratos , Ratos Wistar , Testículo/patologia , Testículo/cirurgia , Testículo/transplante
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