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1.
Medicina (Kaunas) ; 60(5)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38792963

RESUMEN

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein-protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Renales , Conexina 43 , Neoplasias Renales , Humanos , Conexina 43/análisis , Conexina 43/metabolismo , Neoplasias Renales/genética , Biomarcadores de Tumor/análisis , Pronóstico , beta Catenina , Línea Celular Tumoral , Masculino , Femenino
2.
Small ; 19(3): e2205489, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319477

RESUMEN

Current diabetic wound treatments remain unsatisfactory due to the lack of a comprehensive strategy that can integrate strong applicability (tissue adhesiveness, shape adaptability, fast self-healability, and facile dressing change) with the initiation and smooth connection of the cascade wound healing processes. Herein, benefiting from the multifaceted bonding ability of tannic acid to metal ions and various polymers, a family of tannin-europium coordination complex crosslinked citrate-based mussel-inspired bioadhesives (TE-CMBAs) are specially developed for diabetic wound healing. TE-CMBAs can gel instantly (< 60 s), possess favorable shape-adaptability, considerable mechanical strengths, high elasticity, considerable wet tissue adhesiveness (≈40 kPa), favorable photothermal antimicrobial activity, excellent anti-oxidant activity, biocompatibility, and angiogenetic property. The reversible hydrogen bond crosslinking and sensitive metal-phenolic coordination also confers TE-CMBAs with self-healability, pH-responsive europium ion and TA releasing properties and on-demand removability upon mixing with borax solution, enabling convenient painless dressing change and the smooth connection of inflammatory microenvironment modulation, angiogenesis promotion, and effective extracellular matrix production leveraging the acidic pH condition of diabetic wounds. This adhesive dressing provides a comprehensive regenerative strategy for diabetic wound management and can be extended to other complicated tissue healing scenarios.


Asunto(s)
Adhesivos , Diabetes Mellitus , Humanos , Adhesivos/química , Europio , Cicatrización de Heridas , Vendajes , Concentración de Iones de Hidrógeno , Hidrogeles/química , Antibacterianos/química
3.
Future Oncol ; 19(2): 147-158, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36779488

RESUMEN

Aim: To assess the efficacy and safety of combination of PD-1 inhibitors, recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer (NSCLC). Methods: A total of 100 patients with advanced NSCLC were retrospectively reviewed and analyzed (58 in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy; 42 in the group receiving Rh-endostatin and chemotherapy). The primary end point was progression-free survival. Results: Patients in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy had significantly improved progression-free survival (10.2 vs 6.5 months; p < 0.001) and objective response rate (67.2 vs 42.9%; p = 0.015), with acceptable toxicity. Conclusion: Our study showed the superiority of combination therapy of PD-1 inhibitors and Rh-endostatin as first-line treatment for advanced NSCLC.


This study retrospectively analyzed the effectiveness and safety of PD-1 inhibitors combined with recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer. Among them, 58 patients received a PD-1 inhibitor combined with Rh-endostatin and chemotherapy (treatment group), and 42 patients received Rh-endostatin combined with chemotherapy (control group). Patients in the treatment group had a significantly improved objective response rate (67.2 vs 42.9%; p = 0.015) and prolonged survival without their disease getting worse (10.2 vs 6.5 months; p < 0.001). No significant differences were found in the adverse events between the two groups.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Endostatinas , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
4.
BMC Nephrol ; 24(1): 37, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36792978

RESUMEN

BACKGROUND: Cardiac valvular calcification (CVC) is prevalent in haemodialysis (HD) patients. Its association with mortality in Chinese incident haemodialysis (IHD) patients remains unknown. METHODS: A total of 224 IHD patients who had just begun HD therapy at Zhongshan Hospital, Fudan University, were enrolled and divided into two groups according to the detection of cardiac valvular calcification (CVC) by echocardiography. The patients were followed for a median of 4 years for all-cause mortality and cardiovascular mortality. RESULTS: During follow-up, 56 (25.0%) patients died, including 29 (51.8%) of cardiovascular disease. The adjusted HR related to all-cause mortality was 2.14 (95% CI, 1.05-4.39) for patients with cardiac valvular calcification. However, CVC was not an independent risk factor for cardiovascular mortality in patients who had just begun HD therapy. CONCLUSION: CVC at baseline is an independent risk factor for all-cause mortality in HD patients and makes an independent contribution to the prediction of all-cause mortality. These findings support the use of echocardiography at the beginning of HD.


Asunto(s)
Calcinosis , Enfermedades de las Válvulas Cardíacas , Humanos , Estudios de Seguimiento , Pueblos del Este de Asia , Calcinosis/complicaciones , Enfermedades de las Válvulas Cardíacas/complicaciones , Diálisis Renal
5.
Psychopathology ; 56(3): 194-205, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35901786

RESUMEN

INTRODUCTION: Research has shown that people with mental illnesses (PMI) are found to show poorer lifestyle than the general population. Yet, the effect of their psychiatric symptoms in the association between gender difference, health-promoting behaviors, and quality of life have received little attention. The present study examined the association between symptom severity, health-promoting behaviors, and quality of life among PMI in Hong Kong. Gender difference on the association between these variables was also examined. METHOD: A cross-sectional survey was conducted among 591 individuals with DSM-IV-TR Axis 1 diagnosis recruited from the community. RESULTS: Results from MANOVA showed that PMI with more severe psychiatric symptoms engaged in a significantly lower level of health-promoting behaviors and reported a lower level of quality of life. Results from structural equation modeling showed that health-promoting behaviors mediated the association between psychiatric symptoms and quality of life. Multigroup analyses showed that the association between psychiatric symptoms and health-promoting behaviors was stronger among female participants, while the association between health-promoting behaviors and quality of life was stronger among male participants. DISCUSSION/CONCLUSION: Despite clear evidence suggesting symptom severity to be negatively correlated with quality of life, the underlying mechanism has been less clear. There is a need to promote health-promoting behaviors in order to improve the quality of life of PMI. Gender-specific interventions are warranted.


Asunto(s)
Trastornos Mentales , Calidad de Vida , Humanos , Masculino , Femenino , Calidad de Vida/psicología , Estudios Transversales , Promoción de la Salud/métodos , Pueblos del Este de Asia , Trastornos Mentales/psicología
6.
Int J Mol Sci ; 24(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37175710

RESUMEN

Despite the huge human and economic costs of invasive insects, which are the main group of invasive species, their environmental impacts through various mechanisms remain inadequately explained in databases and much of the invasion biology literature. High-throughput sequencing technology, especially whole-genome sequencing, has been used as a powerful method to study the mechanisms through which insects achieve invasion. In this study, we reviewed whole-genome sequencing-based advances in revealing several important invasion mechanisms of invasive insects, including (1) the rapid genetic variation and evolution of invasive populations, (2) invasion history and dispersal paths, (3) rapid adaptation to different host plant ranges, (4) strong environmental adaptation, (5) the development of insecticide resistance, and (6) the synergistic damage caused by invasive insects and endosymbiotic bacteria. We also discussed prevention and control technologies based on whole-genome sequencing and their prospects.


Asunto(s)
Genómica , Insectos , Animales , Humanos , Insectos/genética , Adaptación Fisiológica/genética , Aclimatación , Ambiente
7.
BMC Cancer ; 22(1): 1295, 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36503478

RESUMEN

PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with cytotoxic chemotherapy are highly effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study is to evaluate the efficacy and safety of this combination in advanced NSCLC patients with an EGFR/TP53 co-mutation. METHODS: Ninety-five advanced NSCLC patients with an EGFR/TP53 co-mutation were enrolled in this study. Treatments with either EGFR-TKI monotherapy (T group, n = 61) or EGFR-TKI combined with chemotherapy (TC group, n = 34) were evaluated in relation to objective response rate (ORR), disease control rate (DCR), median time to progression (TTP), and median overall survival (OS). RESULTS: There were no statistically significant differences in DCR between the treatment groups. The ORR was significantly improved in the TC group versus the T group (55.9% vs. 34.4%, P = 0.042). A higher median TTP was noted in TC group compared with T group (16.1 vs. 11.1 months, P = 0.002). Patients without brain metastases in TC group had a longer median OS than in T group (48.4 vs. 28.8 months, P = 0.003). However, there was a non-significant trend towards longer OS in TC group in the entire cohort (36.9 vs. 28.2 months, P = 0.078). Cox multivariate regression analysis showed that clinical stage, brain metastases, EGFR21 L858R mutation, and T790M status at first progression were independent risk factors for OS. However, the incidence of grade 3 or higher adverse events were higher in the TC group than in the T group (32.4% vs. 13.1%, P = 0.025). CONCLUSION: Our study indicates that EGFR-TKIs combined with chemotherapy could significantly improve the ORR and TTP of advanced NSCLC patients with an EGFR/TP53 co-mutation. Combination therapy may be a promising treatment for advanced NSCLC patients with an EGFR/TP53 co-mutation without brain metastases.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Mutación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/efectos adversos , Proteína p53 Supresora de Tumor/genética
8.
Microb Cell Fact ; 21(1): 186, 2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36085205

RESUMEN

BACKGROUND: Amyrin is an important triterpenoid and precursor to a wide range of cosmetic, pharmaceutical and nutraceutical products. In this study, we metabolically engineered the oleaginous yeast, Yarrowia lipolytica to produce α- and ß-amyrin on simple sugar and waste cooking oil. RESULTS: We first validated the in vivo enzymatic activity of a multi-functional amyrin synthase (CrMAS) from Catharanthus roseus, by expressing its codon-optimized gene in Y. lipolytica and assayed for amyrins. To increase yield, prevailing genes in the mevalonate pathway, namely HMG1, ERG20, ERG9 and ERG1, were overexpressed singly and in combination to direct flux towards amyrin biosynthesis. By means of a semi-rational protein engineering approach, we augmented the catalytic activity of CrMAS and attained ~ 10-folds higher production level on glucose. When applied together, protein engineering with enhanced precursor supplies resulted in more than 20-folds increase in total amyrins. We also investigated the effects of different fermentation conditions in flask cultures, including temperature, volumetric oxygen mass transfer coefficient and carbon source types. The optimized fermentation condition attained titers of at least 100 mg/L α-amyrin and 20 mg/L ß-amyrin. CONCLUSIONS: The design workflow demonstrated herein is simple and remarkably effective in amplifying triterpenoid biosynthesis in the yeast Y. lipolytica.


Asunto(s)
Yarrowia , Fermentación , Ingeniería Metabólica , Ácido Mevalónico , Ingeniería de Proteínas , Yarrowia/genética
9.
Environ Res ; 214(Pt 4): 113970, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35987371

RESUMEN

Photoassisted persulfate activation (PPA) is highly efficient oxidation process, but the eligible catalysts are scarce. Herein, a visible-light-responsive Ag6Si2O7 was anchored on Cu(II)-exchanged attapulgite (Cu-Pal) via a facile precipitation-deposition method to construct a novel PDS activator. The synthesized catalyst was systemically analyzed by a series of characterization techniques. The results revealed that Ag6Si2O7 nanoparticles were evenly dispersed on Cu-Pal to form heterojunction. 16%-Ag6Si2O7/Cu-Pal, an optimal catalyst exhibited excellent catalytic performance and stability in the visible-light-assisted PDS activation for AR18 degradation. The influences of reaction parameters on this process were investigated. Under the optimal conditions ([catalyst] = 1.0 g L-1, [PDS] = 3.9 mM, pHi = 5.1), 50 mg L-1 of AR18 was completely degraded within 30 min. More importantly, quenching experiments and EPR tests revealed that besides the common SO4•- and •OH, 1O2 and O2•- were generated as main reactive oxygen species in the PPA by 16%-Ag6Si2O7/Cu-Pal. Moreover, it was found that surface hydroxyl groups of the catalyst and copper species incorporated in Pal could significantly influence PDS activation and ROS generation. Based on these results, together with PDS decomposition, fluorescent probe analysis, and XPS analysis of the used catalyst, the possible mechanisms of the PPA by 16%-Ag6Si2O7/Cu-Pal were proposed. Finally, the versatility and practicability of the established PPA process were verified by degrading other organic contaminants and testing effects of the coexisting anions and water matrices on AR18 degradation. This study may provide new insights for designing and developing the efficient heterogeneous catalysis for wastewater treatment via persulfate-based AOP.


Asunto(s)
Contaminantes Ambientales , Purificación del Agua , Catálisis , Compuestos de Magnesio , Compuestos de Silicona
10.
Sensors (Basel) ; 22(16)2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-36015747

RESUMEN

Federated learning (FL) and split learning (SL) are two emerging collaborative learning methods that may greatly facilitate ubiquitous intelligence in the Internet of Things (IoT). Federated learning enables machine learning (ML) models locally trained using private data to be aggregated into a global model. Split learning allows different portions of an ML model to be collaboratively trained on different workers in a learning framework. Federated learning and split learning, each have unique advantages and respective limitations, may complement each other toward ubiquitous intelligence in IoT. Therefore, the combination of federated learning and split learning recently became an active research area attracting extensive interest. In this article, we review the latest developments in federated learning and split learning and present a survey on the state-of-the-art technologies for combining these two learning methods in an edge computing-based IoT environment. We also identify some open problems and discuss possible directions for future research in this area with the hope of arousing the research community's interest in this emerging field.


Asunto(s)
Internet de las Cosas , Humanos , Inteligencia , Aprendizaje Automático
11.
J Orthop Sci ; 27(2): 420-428, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33775509

RESUMEN

BACKGROUND: Primary knee osteoarthritis remains a difficult-to-control degenerative disease. With the rise in average life expectancy and the incidence of obesity, osteoarthritis has brought an increasing economic and physical burden on people. This article summarizes the latest understanding of platelet-rich plasma in the treatment of knee osteoarthritis, and reviews the economic issues of PRP. METHODS: The literatures in Pubmed, Embase, Cochrane library, Web-science and other databases were searched, and literature inclusion and exclusion criteria were formulated. According to the Cochrane systematic reviewer's manual, the included literatures were grouped, and qualitative descriptions and quantitative meta-analysis were performed. Continuous statistical methods were used to compare the effects and adverse effects of PRP before and after treatment, as well as between PRP and other conservative treatments. RESULTS: A total of 12 randomized controlled trials were included in this study. A total of 959 KOA patients (1070 knees) were enrolled and followed for 3-12 months. PRP total knee scores were significantly better than baseline at 1, 2, 3, 6 and 12 months after treatment (1 month: SMD = 0.60, P < 0.01; 2 months: SMD = 0.98, P < 0.01; 3 months: SMD = 1.16, P < 0.01; 6 months: SMD = 1.49, P < 0.01; 12 months: SMD = 1.47, P < 0.01). In terms of adverse reactions, PRP did not increase the risk of adverse events compared with HA (OR = 0.96, P = 0.85). CONCLUSIONS: Compared with many other treatment methods, intra-articular injection of PRP has been proven to be safe and effective to improve the quality of life of patients with KOA.


Asunto(s)
Osteoartritis de la Rodilla , Plasma Rico en Plaquetas , Humanos , Ácido Hialurónico/efectos adversos , Inyecciones Intraarticulares , Osteoartritis de la Rodilla/terapia , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
12.
J Cell Mol Med ; 25(2): 1012-1023, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33332718

RESUMEN

Podocyte injury is associated with albuminuria and the progression of diabetic nephropathy (DN). NADPH oxidase 4 (NOX4) is the main source of reactive oxygen species (ROS) in the kidney and NOX4 is up-regulated in podocytes in response to high glucose. In the present study, the effects of Salvianolate on DN and its underlying mechanisms were investigated in diabetic db/db mice and human podocytes. We confirmed that the Salvianolate administration exhibited similar beneficial effects as the NOX1/NOX4 inhibitor GKT137831 treated diabetic mice, as reflected by attenuated albuminuria, reduced podocyte loss and mesangial matrix accumulation. We further observed that Salvianolate attenuated the increase of Nox4 protein, NOX4-based NADPH oxidase activity and restored podocyte loss in the diabetic kidney. In human podocytes, NOX4 was predominantly localized to mitochondria and Sal B treatment blocked HG-induced mitochondrial NOX4 derived superoxide generation and thereby ameliorating podocyte apoptosis, which can be abrogated by AMPK knockdown. Therefore, our results suggest that Sal B possesses the reno-protective capabilities in part through AMPK-mediated control of NOX4 expression. Taken together, our results identify that Salvianolate could prevent glucose-induced oxidative podocyte injury through modulation of NOX4 activity in DN and have a novel therapeutic potential for DN.


Asunto(s)
Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/patología , NADPH Oxidasa 4/metabolismo , Estrés Oxidativo , Extractos Vegetales/farmacología , Podocitos/patología , Adenilato Quinasa/metabolismo , Animales , Apoptosis/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Glucosa/toxicidad , Humanos , Masculino , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Podocitos/efectos de los fármacos , Podocitos/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos
13.
Biochem Biophys Res Commun ; 559: 48-55, 2021 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-33932899

RESUMEN

Podocyte injury is associated with albuminuria and the progression of diabetic nephropathy (DN). MiR-34a, a p53-regulated miRNA, directly targets SIRT1 and contributed to DN progression. MiR-34a represses SIRT1 to activate p53 and establish a positive feedback loop. However, whether p53/miR-34a/SIRT1 signaling is activated in podocytes and contributes to DN pathogenesis remains elusive. In this study, we observed that serum miR-34a level was positively correlated with podocyte injury in DN patients. The expression of acetylated p53 and miR-34a was upregulated, SIRT1was downregulated in glomeruli from patients with DN and STZ induced diabetic mice, as well as in human podocytes treated with advanced glycation end (AGE). MiR-34a antagonism in vitro and vivo in STZ induced diabetic mice developed alleviated glomerulus injury as reflected by attenuated albuminuria, reduced podocyte loss and restored autophagic flux. In human podocyte, inhibition of AGE formation by pyridoxamine prevented miR-34a dependent repression of SIRT1, p53 acetylation and activate podocyte autophagy in a dose-dependent manner. MiR-34a overexpression increases acetylation of p53 by translational repression of SIRT1. SIRT1 overexpression also impacts AGE induced apoptosis through deacetylating p53, whereas silencing of SIRT1 by EX527 attenuated the cytoprotective functions of miR-34a knockdown. Moreover, blockade of p53 acetylation significantly rescued miR-34a-induced apoptosis through SIRT1 restoration. Collectively, we demonstrate that by activation of p53, AGE induced the transcription of miR-34a, miR-34a in turn repressed SIRT1 to activate p53, resulting in a positive-feedback loop and contributing to podocyte injury. Targeting modulation of p53/miR-34a/SIRT1 feedback by miR-34a knockdown or overexpression of SIRT1 could rescue podocyte injury during DN.


Asunto(s)
Nefropatías Diabéticas/genética , MicroARNs/genética , Podocitos/patología , Sirtuina 1/genética , Proteína p53 Supresora de Tumor/genética , Acetilación , Animales , Línea Celular , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Regulación de la Expresión Génica , Productos Finales de Glicación Avanzada/genética , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Podocitos/metabolismo , Sirtuina 1/metabolismo , Proteína p53 Supresora de Tumor/metabolismo
14.
Int J Neurosci ; 131(10): 975-983, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32378973

RESUMEN

BACKGROUND: Glioblastoma (GBM) is the most common aggressive primary cancer occurring in the brain tissue. GBM accounts 16% of primary brain tumors and half of gliomas. Additionally, the incidence of GBM is increases with aging, and reaches the peak at the age of 75 to 84 years. The survival of patients with GBM remains at a low level, only less than 5% patients diagnosed with GBM survive for 5 years. Temozolomide (TMZ) is a DNA alkylating agent and is currently a first line chemotherapeutic treatment for GBM. TMZ combined with radiation therapy has been shown to prolong the overall survival (OS) to 14.6 months compared with 12.1 months for radiation therapy alone. NF-E2-related factor 2 (Nrf2) is a transcription factor that contains seven functional domains. The binding of Keap1 to Nrf2 is a central regulator of the cellular defense mechanism against environmental stresses. METHODS: First, Nrf2 overexpression and inhibition models were constructed in U251 cells using transfection. The percentage of viable cells was detected using the MTT assay. Then, the expression of the HO-1 regulator was detected using qPCR, and the concentrations of oxidative stress related factors were detected using ELISAs. The levels of proteins related to oxidative stress and the Ras/Raf/MEK signaling pathway was detected using western blotting analysis. RESULTS: We initially established Nrf2 inhibition and activation cell models in U251 cells and found that the inhibition of Nrf2 expression decreased the mRNA and protein levels of the anti-oxidative enzymes, as well as the secretion of these enzymes into the cellular microenvironment. These effects might be mediated by the inhibition of Ras/Raf/MEK signaling pathway, leading to the inhibition of cellular proliferation. CONCLUSIONS: Inhibition of Nrf2 expression might enhance the effect of TMZ on the treatment of GBM and might be a new therapeutic strategy.


Asunto(s)
Antineoplásicos Alquilantes/farmacología , Glioma/tratamiento farmacológico , Quinasas Quinasa Quinasa PAM/efectos de los fármacos , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Temozolomida/farmacología , Quinasas raf/efectos de los fármacos , Proteínas ras/efectos de los fármacos , Humanos , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Quinasas raf/antagonistas & inhibidores , Proteínas ras/antagonistas & inhibidores
15.
J Cell Mol Med ; 23(5): 3429-3440, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30793492

RESUMEN

Acidic microenvironment is commonly observed in ischaemic tissue. In the kidney, extracellular pH dropped from 7.4 to 6.5 within 10 minutes initiation of ischaemia. Acid-sensing ion channels (ASICs) can be activated by pH drops from 7.4 to 7.0 or lower and permeates to Ca2+ entrance. Thus, activation of ASIC1a can mediate the intracellular Ca2+ accumulation and play crucial roles in apoptosis of cells. However, the role of ASICs in renal ischaemic injury is unclear. The aim of the present study was to test the hypothesis that ischaemia increases renal epithelia cell apoptosis through ASIC1a-mediated calcium entry. The results show that ASIC1a distributed in the proximal tubule with higher level in the renal tubule ischaemic injury both in vivo and in vitro. In vivo, Injection of ASIC1a inhibitor PcTx-1 previous to ischaemia/reperfusion (I/R) operation attenuated renal ischaemic injury. In vitro, HK-2 cells were pre-treated with PcTx-1 before hypoxia, the intracellular concentration of Ca2+ , mitochondrial transmembrane potential (∆ψm) and apoptosis was measured. Blocking ASIC1a attenuated I/R induced Ca2+ overflow, loss of ∆ψm and apoptosis in HK-2 cells. The results revealed that ASIC1a localized in the proximal tubular and contributed to I/R induced kidney injury. Consequently, targeting the ASIC1a may prove to be a novel strategy for AKI patients.


Asunto(s)
Canales Iónicos Sensibles al Ácido/metabolismo , Apoptosis , Células Epiteliales/patología , Riñón/lesiones , Daño por Reperfusión/complicaciones , Animales , Calcio/metabolismo , Caspasa 3/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Humanos , Espacio Intracelular/metabolismo , Túbulos Renales/efectos de los fármacos , Túbulos Renales/lesiones , Túbulos Renales/patología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos C57BL , Modelos Biológicos , Péptidos/farmacología , Daño por Reperfusión/patología , Venenos de Araña/farmacología
16.
Phys Chem Chem Phys ; 21(38): 21381-21388, 2019 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-31531469

RESUMEN

In multiferroics, electromagnons have been recognized as a noticeable topic due to their indispensable role in magnetoelectric, magnetodielectric, and magnetocapacitance effects. Here, the electromagnons of Bi1-xNdxFeO3 (x = 0-0.2) nanoparticles are studied via terahertz time-domain spectroscopy, and the impacts of doping concentrations on electromagnons have been discussed. We found that the electromagnons in Bi1-xNdxFeO3 nanoparticles are associated with their phase transition. The total coupling weight of electromagnons is gradually increased in polar R3c structures and then reduces in the antipolar Pbam phase, and the weight in the antipolar phase is less than that of the pure R3c phase. Interestingly, a colossal electromagnon is observed at polar-antipolar and antiferromagnetic-ferromagnetic phase boundaries. Our work offers an avenue for designing and choosing materials with better magnetodielectric and magnetocapacitance properties.

17.
Cell Physiol Biochem ; 46(5): 1807-1820, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29705777

RESUMEN

BACKGROUND/AIMS: Even though delayed ischemic preconditioning (DIPC) has been reported to produce renal protection, the underlying mechanism remains poorly understood. We reported that a 15-minute renal ischemic preconditioning (IPC) 4 days before subsequent ischemia-reperfusion attenuated renal injury Kidney dendritic cells (DCs) are abundant in the renal tubulointerstitium and, depending on their status, can induce immune activation or tolerance. The aim of the present study was to investigate the role of DCs in IPC of the kidney. METHODS: Mouse kidneys were challenged by transient brief episodes of sublethal ischemia followed by subsequent prolonged ischemia. DC abundance and maturation in the spleen and kidney were measured by flow cytometry and immunohistochemical staining. To confirm the function of mature DCs in the renoprotective effect of IPC on renal ischemia-reperfusion injury the A2 adenosine receptor (A2AR) antagonist SCH58261 was administered to stimulate DC maturation prior to assessment of renal functional and histological injury and the inflammatory reaction. RESULTS: Compared with sham-operated animals, preconditioned mice had a reduced injury with less CD11c+ cells, lower levels of the pro-inflammatory cytokine IL-17 and reduced expression of the mature DC marker CCR7. Preconditioned mice also produced more of the anti-inflammatory cytokine IL-10. Both renal cells and splenocytes from these mice had more DCs (CD45+/CD11c+/F4/80-), but fewer of these DCs were mature (CD45+/CD11c+/ F4/80-/MHC-II+/CD80+) compared with those from sham-treated animals, suggesting that the immunomodulatory effect of renal ischemic preconditioning is both local and systemic. Additionally, injection of the A2AR antagonist SCH58261 reversed IPC-induced inhibition of DC maturation and mitigated the protective effect of preconditioning, suggesting that DC maturation contributes to immune cell-mediated ischemic preconditioning. CONCLUSION: Our results show that DIPC of the kidney provides local and systemic immunosuppression by inhibiting DC maturation and hence mediates a renal protective effect.


Asunto(s)
Lesión Renal Aguda/terapia , Células Dendríticas/patología , Precondicionamiento Isquémico/métodos , Riñón/patología , Daño por Reperfusión/terapia , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/patología , Animales , Células Dendríticas/inmunología , Terapia de Inmunosupresión/métodos , Interleucina-17/análisis , Interleucina-17/inmunología , Riñón/inmunología , Masculino , Ratones Endogámicos C57BL , Daño por Reperfusión/inmunología , Daño por Reperfusión/patología
18.
Opt Express ; 24(11): 12301-9, 2016 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-27410145

RESUMEN

We establish a one-to-one mapping between the local phase slip and the spatial position near the focus by scanning a thin jet along the propagation direction of laser beams. The measurement shows that the optimal phase of terahertz can be utilized to characterize in situ the spatially dependent relative phase of the two-color field. We also investigate the role of the Gouy phase shift on terahertz generation from two-color laser-induced plasma. The result is of critical importance for phase-dependent applications of two-color laser-field, including high-order harmonic and terahertz generation.

19.
J Formos Med Assoc ; 115(1): 31-7, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25659662

RESUMEN

BACKGROUND/PURPOSE: Inflammation plays an important role in promoting ovarian tumorigenesis and cancer progression. However, the relationship between polymorphisms in inflammatory response genes and risk of ovarian cancer remains poorly understood. In this study, we investigated the association of PPARG Pro12Ala, IL6-174G/C, E-selectin S128R, NFKB1-94 ins/del, NFKBIA-826C/T, and ICAM-1 K469E polymorphisms with ovarian cancer risk in a Chinese population. METHODS: Genotyping of the polymorphisms was performed on 687 cases and 687 controls employing the PCR-RFLP technique, and the logistic regression model was used to measure the risk association. RESULTS: A significantly increased risk association was observed for the heterozygous genotypes of PPARG [odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.01-2.29] and E-selectin (OR = 1.77, 95% CI = 1.07-2.93) polymorphisms, as well as the homozygous ins/ins genotype of NFKB1 polymorphism (OR = 1.39, 95% CI = 1.00-1.92). By contrast, ICAM-1 KE genotype was associated with a decreased ovarian cancer risk (OR = 0.77, 95% CI = 0.60-0.98). In addition, the NFKB1 del/del + NFKBIA TT combination was also found to be associated with a decreased ovarian cancer risk, with OR = 0.12 (95% CI = 0.01-0.95). The associations of the NFKB1 and ICAM-1 polymorphisms replicated the findings of previous reports, assuring the reliability of the results obtained. CONCLUSION: NFKB1 and ICAM-1 polymorphisms could serve as useful ovarian cancer risk prediction biomarkers for the Chinese population, while the utility of PPARG and E-selectin polymorphisms as biomarkers requires further confirmation in independent ovarian cancer cohorts.


Asunto(s)
Biomarcadores , Neoplasias Ováricas/genética , Polimorfismo de Nucleótido Simple , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Selectina E/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteínas I-kappa B/genética , Molécula 1 de Adhesión Intercelular/genética , Interleucina-6/genética , Modelos Logísticos , Masculino , Persona de Mediana Edad , Inhibidor NF-kappaB alfa , Subunidad p50 de NF-kappa B/genética , PPAR gamma/genética , Reproducibilidad de los Resultados
20.
Phys Rev Lett ; 115(12): 123002, 2015 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-26430992

RESUMEN

We report the synchronized measurements of terahertz wave generation and high-harmonic generation from aligned nitrogen molecules in dual-color laser fields. Both yields are found to be alignment dependent, showing the importance of molecular structures in the generation processes. By calibrating the angular ionization rates with the terahertz yields, we present a new way of retrieving the angular differential photoionization cross section (PICS) from the harmonic signals which avoids specific model calculations or separate measurements of the alignment-dependent ionization rates. The measured PICS is found to be consistent with theoretical predications, although some discrepancies exist. This all-optical method provides a new alternative for investigating molecular structures.

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