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1.
Int Immunopharmacol ; 129: 111618, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38354508

RESUMO

BACKGROUND: Acute hepatitis is a progressive inflammatory disorder that can lead to liver failure. Endothelial permeability is the vital pathophysiological change involved in infiltrating inflammatory factors. DDX24 has been implicated in immune signaling. However, the precise role of DDX24 in immune-mediated hepatitis remains unclear. Here, we investigate the phenotype of endothelium-targeted Ddx24 conditional knockout mice with Concanavalin A (ConA)-induced hepatitis. METHODS: Mice with homozygous endothelium-targeted Ddx24 conditional knockout (Ddx24flox/flox; Cdh5-Cre+) were established using the CRISPR/Cas9 mediated Cre-loxP system. We investigated the biological functions of endothelial cells derived from transgenic mice and explored the effects of Ddx24 in mice with ConA-induced hepatitis in vivo. The mass spectrometry was performed to identify the differentially expressed proteins in liver tissues of transgenic mice. RESULT: We successfully established mice with endothelium-targeted Ddx24 conditional knockout. The results showed migration and tube formation potentials of murine aortic endothelial cells with DDX24 silencing were significantly promoted. No differences were observed between Ddx24flox/flox; Cdh5-Cre+ and control regarding body weight and length, pathological tissue change and embryogenesis. We demonstrated Ddx24flox/flox; Cdh5-Cre+ exhibited exacerbation of ConA-induced hepatitis by up-regulating TNF-α and IFN-γ. Furthermore, endothelium-targeted Ddx24 conditional knockout caused vascular hyper-permeability in ConA-injected mice by down-regulating vascular integrity-associated proteins. Mechanistically, we identified Ddx24 might regulate immune-mediated hepatitis by inflammation-related permeable barrier pathways. CONCLUSION: These findings prove that endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice because of vascular hyper-permeability. The findings indicate a crucial role of DDX24 in regulating immune-mediated hepatitis, suggesting DDX24 as a potential therapeutic target in the disorder.


Assuntos
Células Endoteliais , Hepatite , Animais , Camundongos , Concanavalina A/toxicidade , Células Endoteliais/metabolismo , Endotélio/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos
2.
Bioorg Chem ; 144: 107134, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237389

RESUMO

Two series of 2,4-diarylaminopyrimidine derivatives containing sulfonamide moiety were designed and synthesized for screening as inhibitors of focal adhesion kinase (FAK). Most compounds significantly inhibited the enzymatic activities of FAK, and the best compound was 7b (IC50 = 0.27 nM). A majority of aminoethyl sulfonamide derivatives could effectively inhibit the proliferation of human cancer cell lines (HCT116, A549, MDA-MB-231 and Hela) expressing high levels of FAK. Particularly, compounds 7b, 7c, and 7o exhibited more significant efficacy against all of four cancer cell lines within concentrations of 1.5 µM. Furthermore, these three compounds displayed higher selectivity of cancer cells over normal cells (SI value > 14), compared to the positive control TAE226 (SI value = 1.63). Interestingly, introduction of dithiocarbamate moiety to the aminoethyl sulfonamide derivatives can indeed improve the antiproliferative activities against A549 cells. Especially, compound 8d demonstrated most significant cytotoxicity activity against A549 cells with an IC50 value of 0.08 µM, which is 20-fold superior to parent compound 7k. Additionally, compound 7b, which display the best anti-FAK potency, can inhibit the clone formation and migration of HCT-116 cells, and cause cell cycle arrest at G2/M phase, inducing apoptosis by promoting ROS production. Overall, these results suggest that 7b is a valuable FAK inhibitor that deserves further optimization to improve its druggability.


Assuntos
Antineoplásicos , Humanos , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Proteína-Tirosina Quinases de Adesão Focal , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Relação Estrutura-Atividade , Sulfonamidas/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia
3.
J Vasc Surg Venous Lymphat Disord ; 12(1): 101662, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37572775

RESUMO

OBJECTIVE: Endovenous microwave ablation (EMA) is a recently developed thermal ablation technique used in the treatment of lower limb varicose veins. However, its efficacy and safety have been largely understudied. In the present study, we sought to explore the clinical results of EMA and radiofrequency ablation (RFA) in treating lower limb varicose veins. METHODS: Patients who underwent EMA (n = 65) or RFA (n = 46) at our institute from September 2018 to September 2020 were included in this retrospective investigation. The clinical results and complications were evaluated at 1, 3, 6, and 12 months after the procedure. The effects on disease severity and quality of life were evaluated using the venous clinical severity score and chronic venous insufficiency questionnaire (CIVIQ). RESULTS: The technical success rate was 100% for both experimental groups. Although the operative time between the two groups was comparable, the EMA technique was associated with lower direct costs (P < .001), although also with prolonged hospitalization (P < .001). We found that the use of EMA correlated with more pain at 48 hours postoperatively. Except for the visual analog scale scores, no statistically significant variations were observed in the occurrence of postoperative complications within the first 48 hours postoperatively between the EMA and RFA groups, including paresthesia, ecchymosis, induration, and phlebitis (P > .05). At 4 weeks postoperatively, significantly less pigmentation was observed in the RFA group than in the EMA group (13.04% vs 32.31%; P = .020). However, the pigmentation had resolved in all patients by 12 months postoperatively. The two groups had a reduction in the venous clinical severity scores and an increase in the CIVIQ scores after the procedure. However, the CIVIQ scores within the RFA group had increased more than had those within the EMA group (P < .05). No significant differences were found in recurrence between the two groups (EMA group, 1.54%; RFA group, 2.17%; P = .804). CONCLUSIONS: Both ablation techniques are safe and effective. RFA is associated with relatively higher treatment costs but shorter hospitalization and better quality of life improvement.


Assuntos
Ablação por Cateter , Terapia a Laser , Ablação por Radiofrequência , Varizes , Insuficiência Venosa , Humanos , Varizes/diagnóstico por imagem , Varizes/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Micro-Ondas/efeitos adversos , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/cirurgia , Ablação por Radiofrequência/efeitos adversos , Veia Safena/cirurgia , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Terapia a Laser/métodos
4.
Biol Res ; 56(1): 60, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978575

RESUMO

BACKGROUND: The decline in the quantity and quality of mitochondria are closely associated with infertility, particularly in advanced maternal age. Transferring autologous mitochondria into the oocytes of infertile females represents an innovative and viable strategy for treating infertility, with no concerns regarding ethical considerations. As the donor cells of mitochondria, stem cells have biological advantages but research and evidence in this area are quite scarce. METHODS: To screen out suitable human autologous ooplasmic mitochondrial donor cells, we performed comprehensive assessment of mitochondrial physiology, function and metabolic capacity on a varity of autologous adipose, marrow, and urine-derived mesenchymal stromal cells (ADSC, BMSC and USC) and ovarian germline granulosa cells (GC). Further, to explore the biosafety, effect and mechanism of stem cell-derived mitochondria transfer on human early embryo development, randomized in-vitro basic studies were performed in both of the young and aged oocytes from infertile females. RESULTS: Compared with other types of mesenchymal stromal cells, USC demonstrated a non-fused spherical mitochondrial morphology and low oxidative stress status which resembled the oocyte stage. Moreover, USC mitochondrial content, activity and function were all higher than other cell types and less affected by age, and it also exhibited a biphasic metabolic pattern similar to the pre-implantation stage of embryonic development. After the biosafety identification of the USC mitochondrial genome, early embryos after USC mitochondrial transfer showed improvements in mitochondrial content, activity, and cytoplasmic Ca2+ levels. Further, aging embryos also showed improvements in embryonic morphological indicators, euploidy rates, and oxidative stress status. CONCLUSION: Autologous non-invasively derived USC mitochondria transfer may be an effective strategy to improve embryonic development and metabolism, especially in infertile females with advanced age or repeated pregnancy failure. It provides evidence and possibility for the autologous treatment of infertile females without invasive and ethical concerns.


Assuntos
Infertilidade Feminina , Oócitos , Feminino , Humanos , Gravidez , Envelhecimento , Infertilidade Feminina/metabolismo , Infertilidade Feminina/terapia , Mitocôndrias , Oócitos/metabolismo , Células-Tronco
5.
Surg Innov ; 30(4): 445-454, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37026616

RESUMO

BACKGROUND: This study aims to investigate the value of the AngioJet thrombectomy system with adjunct of catheter-directed thrombolysis (CDT) in treating lower extremity deep venous thrombosis (LEDVT). METHODS: 48 patients who were clinically confirmed LEDVT and treated by percutaneous mechanical thrombectomy (PMT) combined with CDT, were included in this retrospective study (AJ-CDT, n = 33; Suction-CDT, n = 15). Baseline characteristics, clinical outcomes and surveillance data were reviewed and analyzed. RESULTS: The overall clot reduction rate of AJ-CDT group was significantly higher than that of Suction-CDT group (77.86% vs 64.47%, P = .027). The CDT therapeutic time (5.75 ± 3.04 vs 7.67 ± 2.82 days, P = .045) and urokinase dosage (3.63 ± 2.16 vs 5.76 ± 2.12 million IU, P = .003) were lower in AJ-CDT group, respectively. There was statistical significance in the transient hemoglobinuria between 2 groups (72.73% vs 6.67%, P < .001). At postoperative 48 hours, the serum creatinine (Scr) value was higher in AJ-CDT group compared to Suction-CDT group statistically (78.56 ± 32.16 vs 60.21 ± 15.72 µmol/l, P = .049). However, the incidence of acute kidney injury (AKI) and uric acid (UA) concentration at postoperative 48 hours between these 2 groups were no statistical difference. There was no statistical significance in the Villalta score and post-thrombosis syndrome (PTS) incidence during postoperative follow-up. CONCLUSIONS: AngioJet thrombectomy system is more effective for the treatment of LEDVT by providing a higher clot reduction rate with shorter thrombolytic time and lower thrombolytic drug dosage. However, the device-related potential risk of renal function injury should be taken appropriate precautions.


Assuntos
Terapia Trombolítica , Trombose Venosa , Humanos , Terapia Trombolítica/efeitos adversos , Estudos Retrospectivos , Sucção , Resultado do Tratamento , Trombectomia/efeitos adversos , Trombose Venosa/tratamento farmacológico , Trombose Venosa/cirurgia , Fibrinolíticos/uso terapêutico , Fibrinolíticos/efeitos adversos , Cateteres , Extremidade Inferior
7.
Talanta ; 253: 123956, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36167012

RESUMO

In view of the biological significance and micro-heterogeneity of protein glycosylation for human health, specific enrichment of N-glycosylated proteins/peptides from complex biological samples is a prerequisite for the discovery of disease biomarkers and clinical diagnosis. In this work, we propose a "grafting-from" N-glycoprotein enriching method based on the in-situ growth of thermoresponsive polymer brushes from the N-glycosylated site of proteins. The initiator was first attached to the pre-oxidized glycan moieties by hydrazide chemistry, from which the thermoresponsive polymers can be grown to form giant protein-polymer conjugates (PPC). The thermosensitive PPC can be precipitated and separated by raising the temperature to above its lower critical solubility temperature (LCST). Mass spectrometry verified 210 N-glycopeptides corresponding to 136 N-glycoproteins in the rabbit serum. These results demonstrate the capability of the tandem thermoprecipitation strategy to enrich and separate N-glycoprotein/glycopeptide. Due to its simplicity and efficiency specifically, this method holds the potential for identifying biomarkers from biological samples in N-glycoproteome analysis.


Assuntos
Glicopeptídeos , Polímeros , Humanos , Animais , Coelhos , Glicoproteínas
8.
Front Microbiol ; 13: 959433, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118230

RESUMO

The high morbidity of patients with coronavirus disease 2019 (COVID-19) brings on a panic around the world. COVID-19 is associated with sex bias, immune system, and preexisting chronic diseases. We analyzed the gene expression in patients with COVID-19 and in their microbiota in order to identify potential biomarkers to aid in disease management. A total of 129 RNA samples from nasopharyngeal, oropharyngeal, and anal swabs were collected and sequenced in a high-throughput manner. Several microbial strains differed in abundance between patients with mild or severe COVID-19. Microbial genera were more abundant in oropharyngeal swabs than in nasopharyngeal or anal swabs. Oropharyngeal swabs allowed more sensitive detection of the causative SARS-CoV-2. Microbial and human transcriptomes in swabs from patients with mild disease showed enrichment of genes involved in amino acid metabolism, or protein modification via small protein removal, and antibacterial defense responses, respectively, whereas swabs from patients with severe disease showed enrichment of genes involved in drug metabolism, or negative regulation of apoptosis execution, spermatogenesis, and immune system, respectively. Microbial abundance and diversity did not differ significantly between males and females. The expression of several host genes on the X chromosome correlated negatively with disease severity. In this way, our analyses identify host genes whose differential expression could aid in the diagnosis of COVID-19 and prediction of its severity via non-invasive assay.

9.
Ann Vasc Surg ; 84: 286-297, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35247533

RESUMO

BACKGROUND: We aimed to compare the clinical outcomes of pre-emptive angioplasty versus post-thrombotic percutaneous endovascular restoration of dysfunctional arteriovenous fistula (AVF). METHODS: This retrospective study reviewed the data from 80 patients who underwent 114 endovascular interventions for a malfunctioning AVF from July 2016 to August 2019. Stenotic AVFs were treated with pre-emptive angioplasty. Thrombosed AVFs were treated with percutaneous pharmacomechanical fibrinolysis with urokinase used only during the operation or continuously infused. The differences in patency rates were evaluated using the Kaplan-Meier method. In addition, univariate and multivariate regression Cox models were used to determine influential factors on the postintervention primary patency. RESULTS: Post-thrombotic interventions and pre-emptive angioplasty yielded statistically similar rates in clinical success (100 vs. 100%), anatomic success (94 vs. 89%; P = 0.52), complication (4 vs. 11%; P = 0.29), as well as postintervention primary, assisted primary and secondary patency (P = 0.80; 0.57; 0.57). The use of pre-emptive angioplasty was associated with reduced total cost (¥25,108 vs. ¥30,833, P < 0.001). The patients who used urokinase only during the operation prolonged both the primary and assisted primary patency (P = 0.02; 0.002), while those with continuous infusion of urokinase had worst patency rates and high costs (¥39,275 vs. ¥25,108 vs. ¥27,140, P < 0.001). Compared with the other locations, dysfunction in the anastomotic or juxta-anastomotic segment (HR = 0.41, P = 0.001) was associated with prolonged postintervention primary patency. CONCLUSIONS: No clinical outcome differences were found between the post-thrombotic percutaneous endovascular interventions and pre-emptive angioplasty. However, pre-emptive angioplasty decreased access expenditure.


Assuntos
Angioplastia com Balão , Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Trombose , Angioplastia/efeitos adversos , Angioplastia/métodos , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/métodos , Fístula Arteriovenosa/etiologia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/métodos , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/terapia , Humanos , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Trombose/etiologia , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversos , Grau de Desobstrução Vascular
10.
IEEE J Biomed Health Inform ; 26(6): 2648-2659, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34928809

RESUMO

Hard sample selection can effectively improve model convergence by extracting the most representative samples from a training set. However, due to the large capacity of medical images, existing sampling strategies suffer from insufficient exploitation for hard samples or high time cost for sample selection when adopted by 3D patch-based models in the field of multi-organ segmentation. In this paper, we present a novel and effective online hard patch mining (OHPM) algorithm. In our method, an average shape model that can be mapped with all training images is constructed to guide the exploration of hard patches and aggregate feedback from predicted patches. The process of hard mining is formalized as a multi-armed bandit problem and solved with bandit algorithms. With the shape model, OHPM requires negligible time consumption and can intuitively locate difficult anatomical areas during training. The employment of bandit algorithms ensures online and sufficient hard mining. We integrate OHPM with advanced segmentation networks and evaluate them on two datasets containing different anatomical structures. Comparative experiments with other sampling strategies demonstrate the superiority of OHPM in boosting segmentation performance and improving model convergence. The results in each dataset with each network suggest that OHPM significantly outperforms other sampling strategies by nearly 2% average Dice score.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos
11.
Sheng Wu Gong Cheng Xue Bao ; 37(11): 4075-4082, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34841807

RESUMO

The rapid screening of tumor markers is a challenging task for early diagnosis of cancer. This study aims to use highly sensitive chemiluminescent protein microarray technology to efficiently screen a variety of low abundance tumor related markers. A new material, termed integrated polydimethylsiloxane modified silica gel (iPDMS), was obtained by adding a surface polymerization initiator with olefin end to the conventional polydimethylsiloxane, and fixing into the three-dimensional structure of polydimethylsiloxane by thermal crosslinking through silicon hydrogen bonding. In order to make the iPDMS material resistant to non-specific protein adsorption, a poly(OEGMA) polymer brush was synthesized by surface-initiated atom transfer radical polymerization at the active initiation site. Finally, 20 tumor-related antigens were printed into the specific areas of the microarray by high-throughput spray printing technology, and assembled into 48-well detection microtiterplates of the iPDMS microarray. It was found the VEGFR and VEGF121 autoantibodies that obtained from 8 common tumors (breast cancer, lung cancer, colon cancer, gastric cancer, liver cancer, leukemia, lymphoma and ovarian cancer) can be used as potential tumor markers. The chemiluminescence labeled iPDMS protein microarray can be used for the screening of tumor autoantibodies at early stage.


Assuntos
Autoanticorpos , Análise Serial de Proteínas , Adsorção , Dimetilpolisiloxanos , Sílica Gel , Propriedades de Superfície
12.
Biomacromolecules ; 22(10): 4237-4243, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474556

RESUMO

Formation of protein-polymer conjugates (PPCs) is critical for many studies in chemical biology, biomedicine, and enzymatic catalysis. Polymers with coordinated physicochemical properties confer synergistic functions to PPCs that overcome the inherent limitation of proteins. However, application of PPCs has been synthetically restricted by the limited modification sites and polymer grafting method. Here, we present a versatile strategy for site-selective PPC synthesis. The initiator was specifically tethered to the preoxidized glycan moieties through oxime chemistry. Polymer brushes were grown in situ from the glycan by atom-transfer radical polymerization to generate well-controlled PPCs. Notably, the modification is site-specific, multivalent, and alterable depending on protein glycosylation. Additionally, we demonstrated that the cytocompatible method enabled the growth of polymer chains from the surface of living yeast cells. These results verified a facile technology for surface modification of biomacromolecules by desired polymers for various biomedical applications.


Assuntos
Polímeros , Polissacarídeos , Glicoproteínas , Polimerização , Propriedades de Superfície
13.
Sheng Wu Gong Cheng Xue Bao ; 37(4): 1360-1367, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33973448

RESUMO

Imported malaria has become a major risk factor for malaria prevention and control in China. How to screen malaria quickly for people entering China is an urgent problem to be solved. Protein microarrays are widely used in high-throughput screening and diagnosis. In this study, surface plasmon resonance (SPR) technique for malaria detection was established by using the specific adsorption surface treated by polyethylene glycol polymer, and the malaria specific antigen HRP2 was used as capture probe. The optimal concentration of antigen, sensitivity and specificity of detection, as well as anti-interference ability of the chip were analyzed. The SPR protein chip was applied to detect specific antibodies of malignant malaria in serum with the advantage of label-free, instant and fast. Compared with fluorescence quantitative PCR, there were no significant difference in sensitivity and specificity between the two methods. This study lays a foundation for further development of protein microarray for malaria typing identification, and it is conducive to the rapid screening of malaria for people entering.


Assuntos
Malária , Ressonância de Plasmônio de Superfície , Anticorpos , China , Humanos , Malária/diagnóstico , Análise Serial de Proteínas
15.
JMIR Public Health Surveill ; 7(2): e24204, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591286

RESUMO

BACKGROUND: Obtaining comprehensive epidemic information for specific global infectious diseases is crucial to travel health. However, different infectious disease information websites may have different purposes, which may lead to misunderstanding by travelers and travel health staff when making accurate epidemic control and management decisions. OBJECTIVE: The objective of this study was to develop a Global Infectious Diseases Epidemic Information Monitoring System (GIDEIMS) in order to provide comprehensive and timely global epidemic information. METHODS: Distributed web crawler and cloud agent acceleration technologies were used to automatically collect epidemic information about more than 200 infectious diseases from 26 established epidemic websites and Baidu News. Natural language processing and in-depth learning technologies have been utilized to intelligently process epidemic information collected in 28 languages. Currently, the GIDEIMS presents world epidemic information using a geographical map, including date, disease name, reported cases in different countries, and the epidemic situation in China. In order to make a practical assessment of the GIDEIMS, we compared infectious disease data collected from the GIDEIMS and other websites on July 16, 2019. RESULTS: Compared with the Global Incident Map and Outbreak News Today, the GIDEIMS provided more comprehensive information on human infectious diseases. The GIDEIMS is currently used in the Health Quarantine Department of Shenzhen Customs District (Shenzhen, China) and was recommended to the Health Quarantine Administrative Department of the General Administration of Customs (China) and travel health-related departments. CONCLUSIONS: The GIDEIMS is one of the most intelligent tools that contributes to safeguarding the health of travelers, controlling infectious disease epidemics, and effectively managing public health in China.


Assuntos
Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis/epidemiologia , Epidemias/prevenção & controle , Monitoramento Epidemiológico , Saúde Global/estatística & dados numéricos , Sistemas de Informação , Doença Relacionada a Viagens , China/epidemiologia , Humanos
16.
Bioorg Chem ; 108: 104653, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33517002

RESUMO

Pyruvate kinase M2 isoform (PKM2) plays a key role in cancer progression through both metabolic and non-metabolic functions, thus it is recognized as a potential target for cancer diagnosis and treatment. In this study, we discovered a sulfonamide-dithiocarbamate compound 8a as a novel PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8a analogs were designed and synthesized for screening as potent PKM2 activators. Among them, compound 8b (AC50 = 0.136 µM) and 8k (AC50 = 0.056 µM) showed higher PKM2 activation activities than positive control NZT (AC50 = 0.228 µM), and they (IC50 < 1 µM) exhibited more significant anti-proliferative activities against human tumor cell lines than NZT (IC50 > 10 µM). Especially, compound 8k inhibited the proliferation of multiple cancer cells, but showed little toxicity on normal cells. In addition, we found that compound 8k inhibit the colony formation of MCF7 cells. Western blot analysis demonstrated that 8k could reduce PKM2 nuclear localization and block the downstream signaling pathway of PKM2, resulting in suppression of tumor cell proliferation. Overall, compound 8k may be a promising candidate for further mechanistic investigation of PKM2 and cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Membrana/antagonistas & inibidores , Piperazina/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proteínas de Transporte/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Proteínas de Membrana/metabolismo , Estrutura Molecular , Piperazina/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Hormônios Tireóideos/metabolismo
17.
Fish Shellfish Immunol ; 110: 75-85, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33444736

RESUMO

As a lower vertebrate, the immune defense mechanism of fish mainly depends on the innate immune system. Nucleotide-binding oligomerization domain-like receptors (NLRs) are an important class of pattern recognition receptors in the innate immune system. In this study, NOD1 gene was cloned and characterized in Nile tilapia (Oreochromis niloticus). The ORF of Nile tilapia NOD1 gene was 2826 bp long and encoded 941 amino acid residues with a structure of CARD-NACHT-LRRs that was similar to the other counterparts in mammals and fishes. Phylogenetic and synteny analysis showed that NOD1 was conserved among different fishes and existed at least in the early stage of fish evolution. Expression pattern revealed that NOD1 mRNA was constitutively expressed in the tested tissues, while had high expression level in main immune organs and mucosal immune tissues (liver, head kidney, spleen, blood, gill, and intestine). Following Streptococcus agalactiae challenge, Nile tilapia NOD1 mRNA expression levels were altered in immune organs (liver, head kidney, spleen, blood), and the expression pattern was similar in liver, spleen and blood. Furthermore, the ligand recognition and signaling pathway of Nile tilapia NOD1 were also analyzed, it showed that NOD1 could recognize Tri-DAP intracellularly and activated NF-κB signaling pathway. In summary, our results indicated that the Nile tilapia NOD1 may play an important role in innate immune system and provided a basis for the functional study of NOD1 in teleost.


Assuntos
Ciclídeos/genética , Ciclídeos/imunologia , Regulação da Expressão Gênica , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/imunologia , Animais , Ácido Diaminopimélico , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia
18.
Wei Sheng Yan Jiu ; 49(4): 613-616, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32928357

RESUMO

OBJECTIVE: To investigate the dietary exposure level of advanced glycation end products(AGEs) in the diet of Shenzhen residents. METHODS: 3 markets, 6 supermarkets and 10 chain catering units in Shenzhen were selected as sampling points. 196 food samples were collected in 11 categories in batches from December 2016 to October 2017. The AGEs content database was obtained by detecting carboxy methyl lysine by ELISA competition method. Combined with the food consumption data of Shenzhen residents in the 2011 survey of dietary and nutritional status of Shenzhen residents, through Monte Carlo simulation, the probability distribution of AGEs dietary exposure was calculated by using the Latin hypercube method from the AGEs content data and consumption data, and the result were expressed by the exposure corresponding to different percentiles(P50 and P95). RESULTS: In Shenzhen, 50% of the population had a dietary exposure of more than 37. 2 mg/d per person, while 5% of the population had a dietary exposure of more than 65. 9 mg/d per person. The first three factors that had a great impact on the dietary exposure of AGEs were the AGEs content of cereal and its products, the AGEs content of meat and its products, and the consumption of cereal and its products. The top three sources of AGEs exposure for both P50 and P95 were cereal and its products and its products taste, meat and its products. CONCLUSION: 5% of Shenzhen residents had a high intake of AGEs, which mainly came from cereals and their products, condiments, meat and their products.


Assuntos
Dieta , Carne , Exposição Dietética , Grão Comestível , Estado Nutricional
19.
Plants (Basel) ; 9(3)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244958

RESUMO

Environmental factors that drive carbon storage are often used as an explanation for alpine treeline formation. However, different tree species respond differently to environmental changes, which challenges our understanding of treeline formation and shifts. Therefore, we selected Picea jezoensis and Betula ermanii, the two treeline species naturally occurring in Changbai Mountain in China, and measured the concentration of non-structural carbohydrates (NSC), soluble sugars and starch in one-year-old leaves, shoots, stems and fine roots at different elevations. We found that compared with P. jezoensis, the NSC and soluble sugars concentrations of leaves and shoots of B. ermanii were higher than those of P. jezoensis, while the starch concentration of all the tissues were lower. Moreover, the concentration of NSC, soluble sugars and starch in the leaves of B. ermanii decreased with elevation. In addition, the starch concentration of B. ermanii shoots, stems and fine roots remained at a high level regardless of whether the soluble sugars concentration decreased. Whereas the concentrations of soluble sugars and starch in one-year-old leaves, shoots and stems of P. jezoensis responded similarly changes with elevation. These findings demonstrate that compared with P. jezoensis, B. ermanii has a higher soluble sugars/starch ratio, and its shoots, stems and fine roots actively store NSC to adapt to the harsh environment, which is one of the reasons that B. ermanii can be distributed at higher altitudes.

20.
J Healthc Eng ; 2020: 6053065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184979

RESUMO

Objectives: We have developed a pulsed xenon ultraviolet light-based real-time air disinfection system with rapid and effective disinfection by using high-intensity pulse germicidal UV. Disinfection of the ambulance's environment is critical in the prevention of infectious cross contamination. Methods: In this study, a pulsed xenon ultraviolet light-based air disinfection system was established for real-time air disinfection in ambulances. In this system, a pulsed xenon ultraviolet (PX-UV) was used to generate broad-spectrum (200-320 nm), high-intensity ultraviolet light to deactivate and kill bacteria and viruses. The results showed that the use of PX-UV could be effective in reducing E. coli, Staphylococcus albus, and environmental pathogens level in ambulances (≥90% reduction in 30 mins). Results: This device was relatively simple and easy to use and does not leave chemical residues or risk exposing patients and workers to toxic chemicals. Conclusions: This appears to be a practical alternative technology to achieve automated air disinfection in ambulances.


Assuntos
Ambulâncias , Anestésicos Inalatórios , Desinfecção/instrumentação , Raios Ultravioleta , Xenônio
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