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1.
Cereb Cortex ; 33(8): 4293-4304, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36030380

RESUMO

Neocortical vasoactive intestinal polypeptide-expressing (VIP+) interneurons display highly diverse morpho-electrophysiological and molecular properties. To begin to understand the function of VIP+ interneurons in cortical circuits, they must be clearly and comprehensively classified into distinct subpopulations based on specific molecular markers. Here, we utilized patch-clamp RT-PCR (Patch-PCR) to simultaneously obtain the morpho-electric properties and mRNA profiles of 155 VIP+ interneurons in layers 2 and 3 (L2/3) of the mouse somatosensory cortex. Using an unsupervised clustering method, we identified 3 electrophysiological types (E-types) and 2 morphological types (M-types) of VIP+ interneurons. Joint clustering based on the combined electrophysiological and morphological features resulted in 3 morpho-electric types (ME-types). More importantly, we found these 3 ME-types expressed distinct marker genes: ~94% of Sncg+ cells were ME-type 1, 100% of Mybpc1+ cells were ME-type 2, and ~78% of Parm1+ were ME-type 3. By clarifying the properties of subpopulations of cortical L2/3 VIP+ interneurons, this study establishes a basis for future investigations aiming to elucidate their physiological roles.


Assuntos
Córtex Somatossensorial , Peptídeo Intestinal Vasoativo , Animais , Camundongos , Fenômenos Eletrofisiológicos , Interneurônios/fisiologia , Córtex Somatossensorial/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Proteínas de Neoplasias/metabolismo , gama-Sinucleína/metabolismo , Proteína de Ligação a Androgênios/metabolismo
2.
Curr Microbiol ; 81(9): 292, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090417

RESUMO

The taxonomic relationship between Streptomyces violarus and Streptomyces violaceus was reevaluated using a polyphasic taxonomic approach in this work. Phylogenetic analysis based on 16S rRNA gene sequences indicated that Streptomyces violarus JCM 4534 T was closely related to Streptomyces arenae ISP 5293 T. However, phylogenetic analysis based on five house-keeping gene (atpD, gyrB, recA, rpoB and trpB) showed that the evolutionary neighbor of Streptomyces violarus JCM 4534 T was Streptomyces violaceus CGMCC 4.1456 T, suggesting that there was a close genetic relationship between these two strains. The average nucleotide identity and digital DNA-DNA hybridization values between them were 97.0 and 72.9%, respectively, greater than the 96.7 and 70% cut-off points recommended for delineating a Streptomyces species. This result indicated that they belonged to the same genomic species which was also verified by a comprehensive comparison of phenotypic and chemotaxonomic characteristics between Streptomyces violarus JCM 4534 T and Streptomyces violaceus CGMCC 4.1456 T. According to all these data and the rule of priority in nomenclature, it is proposed the Streptomyces violarus (Artamonova and Krassilnikov 1960) Pridham 1970 is a later heterotypic synonym of Streptomyces violaceus (Rossi Doria 1891) Waksman 1953. In addition, based on dDDH, Streptomyces violaceus and Streptomyces violarus are simultaneously designated as two different subspecies, i.e., Streptomyces violaceus subsp. violaceus and Streptomyces violaceus subsp. violarus.


Assuntos
DNA Bacteriano , Filogenia , RNA Ribossômico 16S , Streptomyces , Streptomyces/genética , Streptomyces/classificação , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Hibridização de Ácido Nucleico , Proteínas de Bactérias/genética
3.
J Transl Med ; 21(1): 656, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740194

RESUMO

BACKGROUND: The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Recent studies have suggested that CTNNB1 hyperactivation is closely related to the occurrence and development of bladder cancer (BCa). As a member of the deubiquitinating enzyme (DUB) family, ubiquitin C-terminal hydrolase L3 (UCHL3) is abnormally expressed in various cancers. In this study, we discovered that UCHL3 is a novel oncogene in bladder cancer, suggesting it is a promising target against bladder cancer. METHODS: We utilized CRISPR‒Cas9 technology to construct cell lines with UCHL3 stably overexpressed or knocked out. The successful overexpression or knockout of UCHL3 was determined using Western blotting. Then, we performed CCK-8, colony formation, soft agar and Transwell migration assays to determine the impact of the UCHL3 gene on cell phenotype. RNA-seq was performed with UCHL3-depleted T24 cells (established via CRISPR-Cas9-mediated genomic editing). We analyzed differences in WNT pathway gene expression in wild-type and UCHL3-deficient T24 cell lines using a heatmap and by gene set enrichment analysis (GSEA). Then, we validated the effect of UCHL3 on the Wnt pathway using a dual fluorescence reporter. We then analyzed the underlying mechanisms involved using Western blots, co-IP, and immunofluorescence results. We also conducted nude mouse tumor formation experiments. Moreover, conditional UCHL3-knockout mice and bladder cancer model mice were established for research. RESULTS: We found that the overexpression of UCHL3 boosted bladder cancer cell proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed tumor tumorigenesis in vitro and in vivo. UCHL3 was highly associated with the Wnt signaling pathway and triggered the activation of the Wnt signaling pathway, which showed that its functions depend on its deubiquitination activity. Notably, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer cells and associated with indicators of advanced clinicopathology. CONCLUSION: In summary, we found that UCHL3 is amplified in bladder cancer and functions as a tumor promoter that enhances proliferation and migration of tumor cells in vitro and bladder tumorigenesis and progression in vivo. Furthermore, we revealed that UCHL3 stabilizes CTNNB1 expression, resulting in the activation of the oncogenic Wnt signaling pathway. Therefore, our findings strongly suggest that UCHL3 is a promising therapeutic target for bladder cancer.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Camundongos , Animais , Neoplasias da Bexiga Urinária/genética , Transformação Celular Neoplásica , Carcinogênese , Enzimas Desubiquitinantes
4.
Neurol Neurochir Pol ; 55(6): 582-591, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34783353

RESUMO

INTRODUCTION: Different categories of hospitals in China have varying levels of patient education. Stroke recognition and emergency medical services (EMS) usage in patients appears to be closely associated with patient education in hospital. This study aimed to explore the effect of hospital classification in China on a patient's ability to recognise stroke symptoms and the likelihood of using the EMS. MATERIAL AND METHODS: A cross-sectional, community-based study was conducted from January to May 2017, and 1,426 residents who had previously been hospitalised were analysed. The patients involved in the study were from 69 administrative areas in China. Multivariable logistic regression models were developed separately for primary, secondary, and tertiary hospitals to identify the associations between hospital grades and patient stroke recognition or the prospects of them using the EMS. RESULTS: Among the 1,426 patients studied, 725 had been admitted to tertiary hospitals, 448 to secondary hospitals, and 253 to primary hospitals. According to univariate analysis, tertiary hospital patients were more likely to use the EMS than patients in primary and secondary hospitals. The difference therein was still significant after full adjustment. CONCLUSIONS: Patients in tertiary hospitals were significantly more likely to use the EMS promptly compared to patients in primary or secondary hospitals. Therefore, patient education on timely EMS usage at stroke onset should be enhanced in primary and secondary hospitals in China.


Assuntos
Serviços Médicos de Emergência , Acidente Vascular Cerebral , Estudos Transversais , Serviço Hospitalar de Emergência , Hospitais , Humanos , Intenção , Acidente Vascular Cerebral/terapia
5.
J Cell Physiol ; 235(2): 1120-1128, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31294463

RESUMO

The long noncoding RNA MEG3 is a significant tumor-suppressive gene in various tumors. But its biological role in bladder cancer remains uninvestigated. Herein, the biological mechanism of MEG3 in bladder cancer pathogenesis was explored. First, the expression of MEG3 in bladder cancer cells was examined, and we found that it was significantly reduced. In addition, in bladder cancer cells, we observed htat miR-494 was increased. Then, MEG3 was overexpressed in UMUC3 and SW780 cells and it could negatively modulate miR-494 expression. Bladder cancer cell proliferation was repressed, cell apoptosis was triggered and meanwhile, the cell cycle was remarkably arrested by the overexpression of MEG3. Moreover, the increase of MEG3 suppressed bladder cancer cell migration and invasion capacity. MEG3 can sponge miR-494 and the binding sites between them were confirmed by carrying out a series of functional assays. Furthermore, PTEN was speculated as a putative target of miR-494. Meanwhile, we found that miR-494 inhibitors induced PTEN. Finally, in vivo assays were conducted to prove that MEG3 can restrain bladder tumor growth by modulating miR-494 and PTEN. In conclusion, it was suggested MEG3 can interact with miR-494 to regulate PTEN in bladder cancer development.


Assuntos
MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Animais , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Experimentais , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/genética , Regulação para Cima
6.
Crit Care ; 24(1): 554, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917257

RESUMO

BACKGROUND: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. METHODS: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. RESULTS: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. CONCLUSIONS: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.


Assuntos
Estado Terminal/terapia , Oxigenação por Membrana Extracorpórea/normas , Mortalidade Hospitalar/tendências , Resultado do Tratamento , Adolescente , Adulto , Idoso , Pequim/epidemiologia , Criança , Estado Terminal/epidemiologia , Estado Terminal/mortalidade , Estudos Transversais , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Molecules ; 26(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374387

RESUMO

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, µM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 µM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , SARS-CoV-2/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Triterpenos/farmacologia , Proteínas Virais/metabolismo , Células HEK293 , Humanos , Ligação Proteica
8.
J Cell Physiol ; 234(10): 18423-18431, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30980388

RESUMO

Cancer stem cells (CSCs) have been recognized as the significant cause of tumor recurrence. Long noncoding RNAs (lncRNAs) are involved in various cancers, including human laryngeal cancer. So far the correlation between lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) and CSC-like properties in human laryngeal cancer remains barely known. In our current study, two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R) with different radio sensitivities were cultured. Interestingly, CSC-like phenotypes were much more enriched in Hep-2R cells. We found that DGCR5 was upregulated and microRNA-506 (miR-506) was downregulated in Hep-2R cells. In addition, silence of DGCR5 could inhibit the stemness and enhance the radiosensitivity of Hep-2R cells. Meanwhile, overexpression of miR-506 also suppressed the CSC-like traits and the radiosensitivity was increased significantly. In addition, miR-506 was predicted as target of DGCR5 and the correlation between them was validated in our study. Finally, we observed that Wnt pathway exerted a significant role in human laryngeal CSCs and DGCR5 inhibition could repress Wnt signaling activity by sponging miR-506. In vivo assays were performed and we found that DCGR5 depressed stemness of human laryngeal cancer cells through modulating miR-506 and Wnt signaling pathway. Taken these together, we reported that DGCR5 induced CSC-like properties by sponging miR-506 through activating Wnt in human laryngeal carcinoma cells.


Assuntos
Neoplasias Laríngeas/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , RNA Longo não Codificante/metabolismo , Tolerância a Radiação/genética , Via de Sinalização Wnt , Animais , Sequência de Bases , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Laríngeas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Neoplasias de Células Escamosas/genética , Neoplasias de Células Escamosas/patologia , Células-Tronco Neoplásicas/patologia , Fenótipo , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genética
9.
J Cell Physiol ; 234(8): 12918-12925, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30549038

RESUMO

Long noncoding RNAs (lncRNAs) exert critical roles in the development of various cancers, including human laryngeal cancer. Radioresistance contributes to the predominant causes of laryngeal cancer recurrence after radiotherapy. The aim of our study was to investigate the association of dysregulated lncRNA and radiation resistance in human larynx squamous carcinoma. Here, we investigated the biological roles of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in radioresistance of human laryngeal cancer. Two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R), with different radiosensitivities in vitro were used in the present study. We observed that DGCR5 was significantly upregulated in Hep-2R cells. Inhibition of DGCR5 by LV-shDGCR5 transfection restrained Hep-2R cell proliferation and sensitized cells to radiation. Reversely, overexpression of DGCR5 exhibited an opposite phenomenon in vitro. In addition, microRNA (miR)-195 was predicted as a direct downstream target of DGCR5. Dual-luciferase reporter and RNA immunoprecipitation assays verified the direct interaction between them. Meanwhile, miR-195 was observed to be reduced in Hep-2R cells and miR-195 mimics repressed Hep-2 cell growth. Moreover, radiosensitivity of Hep-2R cells was greatly enhanced by overexpression of miR-195, which could be reversed by upregulation of DGCR5. Finally, in vivo experiments were used to validate that knockdown of DGCR5 suppressed laryngeal carcinoma via targeting miR-195. In conclusion, we indicated that DGCR5 could contribute to the radioresistance of human laryngeal carcinoma cells via sponging miR-195.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Laríngeas/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , RNA Longo não Codificante/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Laríngeas/metabolismo , Tolerância a Radiação/genética , Regulação para Cima
10.
Chin Med Sci J ; 34(3): 157-167, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601298

RESUMO

Objective Urine is a promising biomarker source for clinical proteomics studies. Regional physiological differences are common in multi-center clinical studies. In this study, we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China. Methods In this study, morning urine samples were collected from healthy urban residents in three regions of China (Haikou, Xi'an and Xining) and urinary proteins were preserved using a membrane-based method (Urimem). The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions. Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database, and pathway enrichment of the differential urinary proteins was analyzed using KEGG. Results We identified 1898 proteins from Urimem samples using label-free proteome quantification, of which 56 urine proteins were differentially expressed among the three regions (P < 0.05). Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than inter-sex differences. After gender stratification, 16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples. Among these differential proteins, several proteins have been previously reported as urinary disease biomarkers. Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection. Regional differences are a confounding factor influencing the urine proteome and should be considered in future multi-center biomarker studies.


Assuntos
Proteoma/metabolismo , Urina , Adulto , Povo Asiático , Biomarcadores/urina , China , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , Espectrometria de Massas em Tandem
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 615-621, 2019 Oct 30.
Artigo em Zh | MEDLINE | ID: mdl-31699191

RESUMO

Objective To validate the Union Physio-Psycho-Social Assessment Questionnaire(UPPSAQ-70)and test its validity and reliability.Methods From April,2013 to July,2018,patients were asked to finish the computer evaluation of UPPSAQ-70 and Symptom Checklist 90(SCL-90)in Peking Union Medical College Hospital(PUMCH).Confirmatory factor analysis(CFA)was conducted on the SPSS 17.0,and the number of fixed factors was 8 factors and 3 factors.Amos 23.0 was used to verify the original 8-factor model,8-factor revision model,3-factor model,3-factor revision model,and single-factor model.Each factor of SCL-90 was used as the calibration standard to calculate the correlation coefficient between factors.The retest reliability was tested by the outpatients in PUMCH in July,2018.Results Exploratory factor analysis indicated that the 8-factor revised model included:depression,anxiety and fatigue,sleep,physical discomfort,sexual function,happiness and satisfaction,hypochondria,and social anxiety.The 3 factors revised model included that:psychological,physiological and social dimension.Confirmatory factor analysis indicated that the 8-factor modified model was superior to the 3-factor model and the single-factor model: χ 2=10 410.4,df=1862,RMSEA=0.07,CFI=0.753,and NFI=0.715.With SCL-90 as the standard criteria,except the low correlation coefficient between emotional scale and depression(r=0.600)and anxiety(r=0.520),the correlation coefficients of other symptoms were below 0.5.The chronbach's α between each factor and total score of UPPSAQ-70 was between 0.823 and 0.904,and the Chronbach's α coefficient of the whole scale was between 0.954 and 0.956 after each item was deleted.The retest reliability of the scale of 32 participants Chronbach's α was 0.847.Each item of the scale measured between one week was significantly correlated(P<0.05). Conclusion UPPSAQ-70 is a good scale for evaluating overall health status and is especially feasible in general hospitals.


Assuntos
Testes Psicológicos/normas , Psicometria , Inquéritos e Questionários , Análise Fatorial , Humanos , Reprodutibilidade dos Testes
12.
Cancer Immunol Immunother ; 67(5): 797-803, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29478100

RESUMO

A subset of bladder patients does not respond to BCG treatment effectively and the underlying reason behind this observation is currently unclear. CD4+ T cells are composed of various subsets that each expresses a distinctive set of cytokines and can potently shift the immune response toward various directions. In this study, we examined the CD4+ T-cell cytokine response in bladder cancer patients toward BCG stimulation. We found that bladder cancer patients presented a variety of responses toward BCG, with no uniform characteristics. Those patients with high IFN-γ and IL-21 expression in CD4+ T cells presented significantly better prognosis than patients with low cytokine secretion in CD4+ T cells. Tumor-infiltrating CD4+ T cells were significantly less potent in expressing IFN-γ, IL-4, and IL-17, and more potent in expressing IL-10 than circulating CD4+ T cells. In addition, we found no difference in CD80, CD86, or MHC II expression by macrophages from patients with different IFN-γ and IL-21 levels. However, the secretion of IL-12, a Th1-skewing cytokine, was released at significantly higher level by macrophages from patients with high IFN-γ or high IL-21 secretion. We also identified that modulating monocytes/macrophages by GM-CSF-mediated polarization resulted in significantly elevated expression of IFN-γ and IL-21 from CD4+ T cells. Overall, these results suggested that the specific types of responses mounted by CD4+ T cells were critical to the final outcome of bladder cancer patients and can be influenced by monocyte/macrophage polarization.


Assuntos
Vacina BCG/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Interferon gama/imunologia , Interleucinas/imunologia , Macrófagos/imunologia , Neoplasias da Bexiga Urinária/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Células Cultivadas , Humanos , Interferon gama/metabolismo , Interleucinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Prognóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
13.
Exp Cell Res ; 352(1): 123-129, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28163057

RESUMO

Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)-1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1ß and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1ß and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway.


Assuntos
Células Epiteliais/patologia , Fibrose/prevenção & controle , Hipóxia/complicações , Inflamação/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Nefropatias/prevenção & controle , Lipopolissacarídeos/efeitos adversos , Proteínas do Tecido Nervoso/metabolismo , Anti-Inflamatórios/farmacologia , Apoptose , Western Blotting , Proliferação de Células , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Humanos , Hipóxia/fisiopatologia , Técnicas In Vitro , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Biomed Environ Sci ; 31(4): 261-271, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29773089

RESUMO

OBJECTIVE: To investigate the prevalence and possible factors influencing metabolic syndrome in people from Guizhou Province and to explore the predictive value of the fat-to-muscle ratio in diagnosing metabolic syndrome. METHODS: A multistage stratified sampling method was used in this cross-sectional study of 20-80 years old Han and Bouyei populations from Guizhou Province, southwestern China, from October-December 2012. The study included 4,553 cases of metabolic syndrome, that was defined according to 2005 International Diabetes Federation criteria. The receiver operating characteristic curve was used for determining the sensitivity, specificity, and predictive ability of the fat-to-muscle ratio for the diagnosis of metabolic syndrome. RESULTS: The age-standardized prevalence of metabolic syndrome was 11.38% (men: 9.76%; women: 12.72%) for Han and 4.78% (men: 4.43%; women: 5.30%) for Bouyei populations. In Guizhou Province, the cut-off value for the men fat-to-muscle ratio was 0.34, the area under the curve was 0.95, and the sensitivity and specificity were 0.94 and 0.85, respectively. The cut-off value for the women fat-to-muscle ratio was 0.55, the area under the curve was 0.91, and the sensitivity and specificity were 0.93 and 0.79, respectively. CONCLUSION: The fat-to-muscle ratio is highly predictive of metabolic syndrome in Guizhou Province, and a useful reference indicator.


Assuntos
Tecido Adiposo/fisiologia , Povo Asiático , Composição Corporal/genética , Composição Corporal/fisiologia , Síndrome Metabólica/genética , Músculo Esquelético/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Predisposição Genética para Doença , Humanos , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem
15.
Ren Fail ; 39(1): 423-431, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28335679

RESUMO

Puerarin (PR) is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been widely used in traditional Chinese herbal medicine for the treatment of various diseases. Oxidative stress and epithelial cell apoptosis play important roles in the renal fibrotic process. The present study aimed to determine whether or not PR inhibits renal fibrosis by reducing oxidative stress induced-epithelial cell apoptosis. In vivo, unilateral ureteral obstruction (UUO) induced renal fibrosis, and epithelial cell apoptosis. A total of 24 mice were randomly assigned to four experimental groups: sham, UUO alone, UUO +50 mg/kg PR, and UUO +100 mg/kg PR. In vitro, 200 µM hydrogen peroxide (H2O2) induced epithelial cell apoptosis. The experiments were dived into four groups: control, H2O2 alone, H2O2+50 µM PR, and H2O2+100 µM PR. Tubular injury was measured in the renal cortex of the mice through periodic acid-Schiff (PAS) staining, and the extracellular matrix (ECM) was measured through Sirius red (SR), immunohistochemistry (IHC) staining, and Western blot. Renal epithelial cell apoptosis was measured through terminal deoxynucleotidyl transferase-mediated dUTP Nick-End labeling (TUNEL), flow cytometry (FCM), and Hoechst assays. The protein expression of NOX4, caspase3, ERK, P38, and JNK was assessed through Western blot. PAS staining showed that PR decreased renal tubular injury in UUO mice. SR and IHC staining demonstrated that PR decreased the accumulation of ECM. PR treatment significantly inhibited epithelial cell apoptosis according to the results of TUNEL, FCM, Hoechst, and Western blot. Furthermore, NOX4 increased in UUO mice and decreased with PR treatment. H2O2-derived oxidative stress activated epithelial apoptosis and mitogen-activated protein kinases (MAPK), and PR treatment significantly reversed it. These results suggest that PR treatment ameliorates renal fibrosis by inhibiting oxidative stress induced-epithelial cell apoptosis through MAPK signaling.


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Epiteliais/efeitos dos fármacos , Isoflavonas/farmacologia , Rim/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Células Epiteliais/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose , Citometria de Fluxo , Peróxido de Hidrogênio , Marcação In Situ das Extremidades Cortadas , Isoflavonas/administração & dosagem , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Rim/citologia , Rim/patologia , Túbulos Renais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Estresse Oxidativo , Pueraria/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Tumour Biol ; 37(2): 2095-103, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26346167

RESUMO

Prostate cancer is one of the biggest health problems for the aging male. To the present, the roles of dysregulated microRNAs in prostate cancer are still unclear. Here, we evaluated the anti-proliferative role of miR-378 in prostate cancer. And, we found that the expression of miR-378 was significantly downregulated in clinical prostate cancer tissues. In vitro assay suggested that overexpression of miR-378-suppressed prostate cancer cell migration and invasion promoted cell apoptosis. Furthermore, we identified and validated MAPK1 as a direct target of miR-378. Ectopic expression of MAPK1 rescues miR-378-suppressed cell migration and invasion. In vivo assay demonstrated that the stably miR-378-overexpressed prostate cancer cells displayed a significantly reduction in tumor growth. Taken together, our data suggested that miR-378 may act as a potential therapeutic target against human prostate cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/biossíntese , Neoplasias da Próstata/patologia , Adulto , Idoso , Animais , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/genética , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase em Tempo Real
17.
Biomed Environ Sci ; 27(5): 325-34, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24827713

RESUMO

OBJECTIVE: To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China. METHODS: A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria. RESULTS: The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions. CONCLUSION: Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.


Assuntos
Síndrome Metabólica/epidemiologia , Circunferência da Cintura , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(4): 986-9, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25007614

RESUMO

Nano-silver colloid was synthesized by using microwave method on the mixtures of sodium citrate solution and silver nitrate solution. The method has advantages of fast heating speed, uniform temperature distribution and easily controlled reaction conditions. The sizes and size distributions of the silver particles were characterized by means of quasi-elastic laser scattering (QLS). The average particles size was (53.27 +/- 2.65) nm and the size of the particles was mainly distributed around 56 nm. Surface-enhanced Raman spectra of the degradation products from goat horn were obtained with silver colloid as active substrate. It was observed that the Raman signal of SERS was enhanced significantly compared with that of regular Raman spectrum, especially at the Raman bands of 659, 830, 850, 929, 999, 1 028, 1 280, 1 439 and 1 599 cm(-1) which reflect the biochemical components in degradation products. The characteristic Raman bands of degradation products from goat horn were preliminary assigned. The assignments showed that the main constituents of the degradation products from goat horn were amino acids and polypeptides. It was for the first time that Surface-enhanced Raman spectroscopy was used to detect trace degradation products from the horns. Raman signal enhancement can be obtained with high sensitivity for the trace concentrations as low as ppm level. It is concluded that surface-enhanced Raman spectroscopy can provide a fast, direct and precise detecting method for the detection of trace degradation solution from horns.


Assuntos
Cabras , Cornos/química , Análise Espectral Raman , Animais , Coloides , Nanopartículas Metálicas , Micro-Ondas , Tamanho da Partícula , Prata
19.
Appl Immunohistochem Mol Morphol ; 32(1): 24-31, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37859432

RESUMO

Recently, the US Food and Drug Administration (FDA) approved the Ventana MMR RxDx Panel as the first immunohistochemical companion diagnostic test for identification of tumors with mismatch repair (MMR) status. The aim of this study was to investigate the accuracy of this test in comparison with polymerase chain reaction (PCR)-based microsatellite instability (MSI) analysis. We assessed the MMR/MSI concordance rate in 140 cases of endometrioid carcinoma. MMR status was evaluated by immunohistochemistry (MMR-IHC), and MSI status was evaluated by PCR-based analysis (MSI-PCR). Potential molecular mechanisms responsible for MSH6 staining variations were also analyzed. Immunohistochemistry showed that 34 tumors (24.3%) were MMRd; these included 26 with combined MLH1/PMS2 loss, 2 with combined MSH2/MSH6 loss, and 6 with isolated MSH6 loss. Heterogeneous MSH6 loss was found in 10 tumors and was recognized only in tumors with combined MLH1/PMS2 loss. Eight of 10 tumors with heterogeneous MSH6 loss harbored MSH6 C8 tract instability, suggesting a secondary somatic event after MLH1/PMS2 loss. MSI-PCR revealed that 102 tumors were MSS, 4 were MSI-low, and 34 were MSI-high. Consequently, MMR-IHC and MSI-PCR showed perfect concordance (kappa=0.080, P <0.0001). However, 10 of the 34 MSI-high tumors, including the 6 tumors with isolated MSH6 loss, showed only minimal microsatellite shift by MSI-PCR, which may have been erroneously interpreted as MSS or MSI-low. On the basis of these findings, we consider that the FDA-approved immunohistochemical panel can detect MMR variations consistently and is more accurate than MSI-PCR for determining the applicability of immune checkpoint inhibitors for treatment of endometrioid carcinomas.


Assuntos
Carcinoma Endometrioide , Neoplasias Colorretais , Estados Unidos , Feminino , Humanos , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento , United States Food and Drug Administration , Instabilidade de Microssatélites , Reparo de Erro de Pareamento de DNA , Fenótipo , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Neoplasias Colorretais/patologia
20.
Ergonomics ; 56(8): 1225-31, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23789793

RESUMO

Accurate evaluation of emergencies is a critical concern in long-duration space flights. Accordingly, we studied the effect of 45 days of - 6° head-down bed rest - a model that simulates the conditions in microgravity environments - on the evaluation of orally reported emergencies. Sixteen male participants listened to corresponding emergency scenarios and assessed the severity of these situations eight times before, during and after bed rest. The results revealed a ' recency effect': compared with emergency descriptions in the order of serious to mild, those framed in the reverse order were judged to be more serious. However, the severity ratings did not vary with time spent in the simulated microgravity environment. These findings are similar to those observed in a regular environment on Earth, indicating that the design principles of information presentation for situations on Earth may also be extended to designs intended for outer space. PRACTITIONER SUMMARY: A recency effect was found in the evaluation of orally reported emergencies under simulated microgravity conditions. The design principles of information presentation for situations on Earth may also be extended to designs intended for outer space.


Assuntos
Comunicação , Emergências/psicologia , Julgamento , Simulação de Ausência de Peso/psicologia , Adulto , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Masculino , Tempo de Reação , Fatores de Tempo , Adulto Jovem
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