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1.
Artigo em Inglês | MEDLINE | ID: mdl-38085929

RESUMO

BACKGROUND: Previous observational studies have been controversial regarding the association of leukocyte telomere length (LTL) with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: First, we conducted an observational study utilizing UK Biobank data. The correlation between LTL and the risk of PCa and BPH was evaluated via multivariate-adjusted logistic regression. Then, we conducted a 2-sample Mendelian randomization to examine causal links between LTL (472 174 individuals) and PCa as well as BPH. To verify the reliability of the primary analysis, we conducted a second analysis and sensitivity analyses. RESULTS: In the UK Biobank study, individuals in the longer quartiles of LTL were observed to have a higher risk of PCa (1.155-fold to 1.349-fold, all p < .001) and BPH (1.119-fold to 1.212-fold, all p < .001) compared to those in the lowest quartile in multivariate-adjusted logistic regression. We observed that genetically predicted longer LTL resulted in a 1.427-fold risk of PCa (odds ratio [OR] = 1.427, 95% confidence interval [CI] = 1.197-1.702, p < .001) and 1.539-fold risk of BPH (OR = 1.539, 95% CI = 1.387-1.707, p < .001) in the primary analysis. In the second analysis, the results also indicated that longer LTL increased the genetic liability to both PCa (OR = 1.338, 95% CI = 1.189-1.507, p < .001) and BPH (OR = 1.006, 95% CI = 1.003-1.008, p < .001). Sensitivity analyses also supported the reliability of the results. CONCLUSIONS: Our study provides convincing evidence supporting that longer LTL increases the risk of PCa and BPH in European individuals. Large-scale studies are needed to elucidate the potential mechanisms of LTL in PCa and BPH occurrence.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , Hiperplasia Prostática/genética , Análise da Randomização Mendeliana , Bancos de Espécimes Biológicos , Reprodutibilidade dos Testes , Biobanco do Reino Unido , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Leucócitos , Telômero , Estudo de Associação Genômica Ampla
2.
Transl Androl Urol ; 12(7): 1137-1154, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37554528

RESUMO

Background: Previous studies have shown that education level is associated with the prognosis of cadaveric kidney transplant recipients. However, it is unclear whether education affects the prognosis of living kidney transplant (LDKT) recipients. In addition, it remains to be determined whether the uneven distribution of educational levels consistently affects the prognosis of LDKT recipients across ethnic groups (White, Black, Hispanic and Asian). Methods: After establishing inclusion and exclusion criteria, we conducted a retrospective study of LDKT recipients who received their first single LDKT between 2005 and 2020. The LDKT recipients were divided into lower- and higher-education groups according to categorize the educational level of recipients, and transplant outcomes, including graft survival, patient survival, and death-censored graft survival (DCGS), were analyzed and compared. Results: Graft survival, DCGS and patient mortality were significantly better in the higher-education group compared with those in the lower-education group (P<0.001), with the risk of graft failure, death censored graft failure (DCGF) and patient mortality increasing by 11%, 15% and 7% in the lower-education group, respectively. Furthermore, compared with the higher-education group, the risk of graft failure in Black recipients increased by 18% [adjusted hazard ratio (aHR), 1.18; 95% confidence interval (CI): 1.07 to 1.30], and the risk of patient mortality among White recipients decreased by 7% (aHR, 0.93; 95% CI: 0.87 to 0.99). However, there were no significant differences in graft failure and patient mortality among Hispanic and Asian recipients, respectively. Conclusions: This study revealed that LDKT recipients with a higher education level had better transplant outcomes. However, these transplant outcome differences were mainly found in White and Black recipients. These data confirm the significant effect of different levels of education on the prognosis of LDKT recipients.

3.
Prostate ; 83(14): 1358-1364, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37455410

RESUMO

BACKGROUND: Previous observational studies have indicated that metabolic abnormalities are associated with benign prostatic hyperplasia (BPH). The limitations of the research methodology of observational studies do not allow causal inference to be drawn; however, Mendelian randomization (MR) can clarify this. METHODS: Using summary-level data from genome-wide association studies, we conducted a two-sample MR study to examine the causality of the metabolic syndrome (MetS) and its components on BPH (26,358 BPH cases and 110,070 controls). The random-effects inverse-variance weighted was employed as the primary method for MR analyses. RESULTS: We observed that genetically predicted waist circumference (WC) (odds ratio [OR] = 1.236, 95% confidence interval [CI]: 1.034-1.478, p = 0.020) and diastolic blood pressure (DBP) (OR = 1.011, 95% CI: 1.002-1.020, p = 0.020) were significantly positively associated with BPH risk. We did not identify a causal effect of MetS (OR = 0.975, 95% CI: 0.922-1.031, p = 0.375), systolic blood pressure (OR = 1.004, 95% CI: 0.999-1.008, p = 0.115), triglycerides (OR = 1.016, 95% CI: 0.932-1.109, p = 0.712), high-density lipoprotein (OR = 1.005, 95% CI: 0.930-1.086, p = 0.907), and fasting blood glucose (OR = 1.037, 95% CI: 0.874-1.322, p = 0.678) on BPH. In the multivariable MR analysis, we observed that the risk effect of DBP (OR = 1.013, 95% CI: 1.000-1.026, p = 0.047) on BPH persisted after conditioning with WC (OR = 1.132, 95% CI: 0.946-1.356, p = 0.177). CONCLUSIONS: Our study provides genetic evidence supporting the causal effect of DBP on BPH, although the effect of WC needs to be further validated.


Assuntos
Síndrome Metabólica , Hiperplasia Prostática , Masculino , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único
4.
Front Surg ; 10: 1045363, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36793312

RESUMO

Background: Racial/ethnic disparity in waiting-list mortality among candidates listed for kidney transplantation (KT) in the United States remains unclear. We aimed to assess racial/ethnic disparity in waiting-list prognosis among patients listed for KT in the United States in the current era. Methods: We compared waiting-list and early posttransplant in-hospital mortality or primary nonfunction (PNF) among adult (age ≥18 years) white, black, Hispanic, and Asian patients listed for only KT in the United States between July 1, 2004 and March 31, 2020. Results: Of the 516,451 participants, 45.6%, 29.8%, 17.5%, and 7.1% were white, black, Hispanic, and Asian, respectively. Mortality on the 3-year waiting list (including patients who were removed for deterioration) was 23.2%, 16.6%, 16.2%, and 13.8% in white, black, Hispanic, and Asian patients, respectively. The cumulative incidence of posttransplant in-hospital death or PNF after KT was 3.3%, 2.5%, 2.4%, and 2.2% in black, white, Hispanic, and Asian patients,respectively. White candidates had the highest mortality risk on the waiting list or of becoming too sick for a transplant, while black (adjusted hazard ratio, [95% confidence interval, CI], 0.67 [0.66-0.68]), Hispanic (0.59 [0.58-0.60]), and Asian (0.54 [0.52-0.55]) candidates had a lower risk. Black KT recipients (odds ratio, [95% CI] 1.29 [1.21-1.38]) had a higher risk of PNF or death before discharge than white patients. After controlling confounders, black recipients (0.99 [0.92-1.07]) had a similar higher risk of posttransplant in-hospital mortality or PNF as white patients than Hispanic and Asian counterparts. Conclusions: Despite having a better socioeconomic status and being allocated better kidneys, white patients had the worst prognosis during the waiting periods. Black recipients and white recipients have higher posttransplant in-hospital mortality or PNF.

5.
Front Oncol ; 12: 1017498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505816

RESUMO

Purpose: Posttransplant skin cancer is the most common malignancy after patients have undergone renal transplantation. Through comprehensive observation with a large sample size nationwide, understanding the risk factors and outcome of posttransplant skin cancer will help to develop appropriate patient surveillance and disease prevention strategies. Materials and methods: This retrospective population-based cohort study was based on Organ Procurement and Transplantation Network data released in March 2021. Characteristics and outcomes, including patient survival and graft survival of recipients, were compared. Risk factors for posttransplant skin cancer, cancer onset momentum, and mortality were determined. Results: A total of 199,564 renal transplant recipients were included. After renal transplantation, 7,334 (3.68%), 6,093 (3.05%), and 936 (0.47%) were diagnosed with squamous cell carcinoma, basal cell carcinoma, and melanoma, respectively. Skin cancer was the major cause of death (squamous cell carcinoma: 23.8%, basal cell carcinoma: 18%, and melanoma: 41.6%). Five-year survival rates ranked from best to worst were as follows: basal cell carcinoma (96.7 [95% confidence interval: 96.3-97.2]%), squamous cell carcinoma (94.1 [93.5-94.6]%), melanoma (89.7 [87.7-91.6]%), and cancer-free (87.4 [87.2-87.5]%) (p < 0.001 for all except melanoma vs. cancer-free, p = 0.534). Regarding graft survival, death-censored graft survival, posttransplant skin cancer, and melanoma were significantly better than the cancer-free group (p < 0.001). Independent risk factors for developing posttransplant skin cancer included older age, male sex, Caucasian race, pretransplant malignancy, polycystic kidney disease-induced end-stage renal disease (ESRD), retransplantation, private health insurance, T-cell depletion induction, and tacrolimus/mycophenolic acid use. Caucasian race and pretransplant malignancy were independent risk factors for posttransplant skin cancer onset momentum. Male sex, Caucasian race, pretransplant malignancy, hypertension- or diabetes-induced ESRD, retransplantation, diabetes history, deceased donor, cyclosporin, and mTOR inhibitor use were independent risk factors for posttransplant skin cancer mortality. Conclusion: Although posttransplant skin cancer is a major cause of recipient death, information regarding its impact on patient and graft survival is limited. Given the differences regarding risk factors for posttransplant skin cancer incidence, onset momentum, and mortality, personalized approaches to screening may be appropriate to address the complex issues encountered by kidney transplant recipients.

6.
Front Oncol ; 12: 955771, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249010

RESUMO

Purpose: The incidence of end-stage renal disease (ESRD) caused by renal cell carcinoma (RCC) is increasing with the high prevalence of RCC as well as those with treatment-related renal function impairment. Worries about tumor recurrence after transplant-related immunosuppression hinder the recommendation of kidney transplantation for RCC-induced ESRD patients. However, no direct analysis has been performed to identify whether kidney transplantation can offer better survival than maintaining dialysis. Materials and methods: This retrospective population-based cohort study was based on Organ Procurement and Transplantation Network data released in March 2021. Characteristics and outcomes were compared, including the patient and graft survival of candidates and recipients with RCC-induced ESRD etiology as well as other primary diseases. Results: Patients with RCC-induced ESRD were older; more likely to be male, White, and obese; and more likely to have a history of diabetes and dialysis. They also had higher creatinine levels, more delayed graft function, more primary non-function, and higher Kidney Donor Profile Index score donors, compared with the glomerulonephritis (GN) group. While waiting, RCC candidates suffered the worst outcomes of all groups, a 44% (adjusted hazard ratio [aHR], 1.44 [1.27-1.62]) higher risk of removal than GN patients. After transplantation, RCC recipients demonstrated comparable patient survival and better graft survival (p=0.21 and p=0.13, respectively). Compared with still-waiting RCC patients, the RCC recipients who received kidney transplants had significantly better outcomes (13.6 [9.3-17.8] vs. 61 [52-68.4] %), decreasing the death or deteriorating risk by 84% (aHR, 0.16 [0.13-0.20]). Conclusions: Patients with RCC-induced ESRD can dramatically benefit from kidney transplantation. Hence, these patients should not be limited to transplantation by strict strategies or a delayed waiting time out of their malignancy history.

7.
Front Surg ; 9: 1050416, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36700016

RESUMO

Background: Race is a prognostic indicator in kidney transplant (KT). However, the effect of donor-recipient race-matching on survival after KT remains unclear. Methods: Using the United Network for Organ Sharing (UNOS) database, a retrospective study was conducted on 244,037 adults who received first-time, kidney-alone transplantation between 2000 and 2019. All patients were categorized into two groups according to donor-recipient race-matching, and the living and deceased donor KT (LDKT and DDKT) were analyzed in subgroups. Results: Of the 244,037 patients, 149,600 (61%) were race-matched, including 107,351 (87%) Caucasian, 20,741 (31%) African Americans, 17,927 (47%) Hispanics, and 3,581 (25%) Asians. Compared with race-unmatching, race-matching showed a reduced risk of overall mortality and graft loss (unadjusted hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.84-0.87; and unadjusted HR 0.79, 95% CI: 0.78-0.80, respectively). After propensity score-matching, donor-recipient race-matching was associated with a decreased risk of overall graft loss (P < 0.001) but not mortality. In subgroup analysis, race-matching was associated with higher crude mortality (HR 1.12, 95% CI: 1.06-1.20 in LDKT and HR 1.11, 95% CI: 1.09-1.14 in DDKT). However, race-matching was associated with a decreased risk of graft loss in DDKT (unadjusted HR 0.97, 95% CI: 0.96-0.99), but not in LDKT. After propensity score-matching, race-matching had better outcomes for LDKT (patient survival, P = 0.047; graft survival, P < 0.001; and death-censored graft survival, P < 0.001) and DDKT (death-censored graft survival, P = 0.018). Nonetheless, race-matching was associated with an increased adjusted mortality rate in the DDKT group (P < 0.001). Conclusion: Race-matching provided modest survival advantages after KT but was not enough to influence organ offers. Cofounding factors at baseline led to a contorted crude conclusion in subgroups, which was reversed again to normal trends in the combined analysis due to Simpson's paradox caused by the LDKT/DDKT ratio.

8.
Front Surg ; 9: 1063649, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36704512

RESUMO

Objective: To investigate the association between age, metabolic syndrome (MetS) and improvement in nocturia in patients with benign prostate hyperplasia (BPH) receiving holmium laser enucleation of the prostate (HoLEP). Methods: The retrospective study was conducted on patients treated for BPH using HoLEP between January 2021 and May 2022. Lower urinary tract symptoms (LUTS) were measured before surgery and at 3 months postoperatively using the International Prostate Symptom Score (IPSS). The criteria of the Adult Treatment Panel III (ATP III) were adopted to diagnose the MetS. Unsatisfactory improvement in nocturia was defined as <50% reduction in nocturia from baseline on the IPSS. Results: One hundred and seventy-five patients were eventually enrolled, with a median age of 69 years (IQR: 63/73). Unsatisfactory improvement in nocturia was reported in 95 patients (54%) after HoLEP. These patients were older (73; IQR: 67/79 vs. 66; IQR: 60/71, P < 0.001) and more likely to present with higher postoperative total (6; IQR: 4/9 vs. 3; IQR:2/5, P < 0.001), voiding (1; IQR: 0/3 vs. 1; IQR: 0/2, P = 0.017), and storage (4; IQR: 3/6 vs. 2; IQR: 1/4, P < 0.001) IPSS when compared to patients with satisfactory improvement in nocturia. Overall, 63 of 175 (36%) patients were diagnosed with MetS and of these, 44 (70%) reported unsatisfactory improvement in nocturia (P = 0.002) after HoLEP. Multivariate analysis revealed that age (OR = 1.117, 95% CI: 1.068-1.169, P < 0.001) and MetS (OR = 3.613, 95% CI: 1.727-7.562, P = 0.001) were independent risk factors for unsatisfactory improvement in nocturia after HoLEP. Conclusion: Our findings suggest that increased age and MetS were associated with unsatisfactory improvement in nocturia in patients with BPH after HoLEP. Lifestyle management, including weight loss, may be of great importance in the improvement of nocturia.

9.
Mol Med Rep ; 24(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34590150

RESUMO

Forkhead box (FOX) proteins are multifaceted transcription factors that have been shown to be involved in cell cycle progression, proliferation and metastasis. FOXP4, a member of the FOX family, has been implicated in diverse biological processes in tumor initiation and progression. However, the molecular mechanisms of FOXP4 in laryngeal squamous cell carcinoma (LSCC) remain unknown. In the present study, differentially expressed transcripts in transforming growth factor­ß­treated TU177 cells were screened using microarrays and it was found that FOXP4 was significantly upregulated. The high expression of FOXP4 was detected in LSCC tissues and cells, and predicted poor prognosis. The role of FOXP4 in laryngeal cancer cell proliferation, migration and invasion was determined by gain­ and loss­of­function assays. Besides, FOXP4 was demonstrated to participate in the epithelial­mesenchymal transition process at the mRNA and protein levels. Mechanically, FOXP4 directly bound to the promoter of lymphoid enhancer­binding factor 1 and activated Wnt signaling pathway, which was confirmed via chromatin immunoprecipitation and luciferase reporter assays. Consequently, these findings provided novel mechanisms of FOXP4 in LSCC progression, which may be considered as potential therapeutic and prognostic targets for LSCC.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias de Cabeça e Pescoço/genética , Humanos , Análise em Microsséries , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Via de Sinalização Wnt
10.
Medicine (Baltimore) ; 99(29): e21229, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702895

RESUMO

To design and develop artificial intelligence (AI) hydrocephalus (HYC) imaging diagnostic model using a transfer learning algorithm and evaluate its application in the diagnosis of HYC by non-contrast material-enhanced head computed tomographic (CT) images.A training and validation dataset of non-contrast material-enhanced head CT examinations that comprised of 1000 patients with HYC and 1000 normal people with no HYC accumulating to 28,500 images. Images were pre-processed, and the feature variables were labeled. The feature variables were extracted by the neural network for transfer learning. AI algorithm performance was tested on a separate dataset containing 250 examinations of HYC and 250 of normal. Resident, attending and consultant in the department of radiology were also tested with the test sets, their results were compared with the AI model.Final model performance for HYC showed 93.6% sensitivity (95% confidence interval: 77%, 97%) and 94.4% specificity (95% confidence interval: 79%, 98%), with area under the characteristic curve of 0.93. Accuracy rate of model, resident, attending, and consultant were 94.0%, 93.4%, 95.6%, and 97.0%.AI can effectively identify the characteristics of HYC from CT images of the brain and automatically analyze the images. In the future, AI can provide auxiliary diagnosis of image results and reduce the burden on junior doctors.


Assuntos
Hidrocefalia/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Inteligência Artificial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Eur J Pharmacol ; 863: 172701, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31568784

RESUMO

Myocardial ischemia/reperfusion (IR) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a ß-galactoside-binding lectin, acts as a biomarker in heart disease. However, it remains unclear whether manipulating galectin-3 affects the susceptibility of the heart to IR injury. In this study, RNA sequencing (RNA-seq) analysis identified that Lgals3 (galecin-3) plays an indispensable role in IR-induced cardiac damage. Immunostaining and immunoblot assays confirmed that the expression of galectin-3 was markedly increased in myocardial IR injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental IR injury was significantly attenuated by galectin-3 inhibitors including pectin (1%, i.p.) from citrus and binding peptide G3-C12 (5.0 mg/kg, i.p.). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed IR-mediated cardiomyocyte apoptosis. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) levels were well-preserved and IR-induced changes of mitochondrial cyto c, cytosol cyto c, caspase-9, caspase-3, Bcl-2 and Bax in the galectin-3 inhibitor-treated groups were observed. Our findings indicate that the pathological upregulation of galectin-3 contributes to IR-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential.


Assuntos
Cardiotônicos/farmacologia , Galectina 3/antagonistas & inibidores , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Coração/efeitos dos fármacos , Coração/fisiopatologia , Homeostase/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Infarto do Miocárdio/complicações , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Pectinas/farmacologia , Pectinas/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Regulação para Cima/efeitos dos fármacos
12.
J Clin Neurosci ; 64: 141-144, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31000330

RESUMO

The ventriculoperitoneal (VP) shunt is a gold standard procedure to treat hydrocephalus. However, shunt malfunction is the common complications after surgery. In this study, we utilize phase-contrast cine magnetic resonance imaging (PC cine MRI) to improve the diagnosis of VP shunt malfunction. In in vitro and in vivo experiment results demonstrate the cerebrospinal fluid (CSF) flow velocities in the shunt tube are significantly decreased in the shunt malfunction group, which indicated PC cine MRI could evaluate the CSF flow dynamics of VP shunt effectively. This method is noninvasive and simple, also can improve the diagnosis of shunt malfunction.


Assuntos
Falha de Equipamento , Imagem Cinética por Ressonância Magnética/métodos , Neuroimagem/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Derivação Ventriculoperitoneal/efeitos adversos , Feminino , Humanos , Hidrocefalia/cirurgia , Masculino
13.
Toxicol Appl Pharmacol ; 369: 60-72, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30831131

RESUMO

Hypoxic pulmonary vasoconstriction (HPV) can be modulated by Rho/Rho kinase signaling, which can alter HPV vascular function via regulating myosin light chain phosphorylation, in a manner generally believed to be Ca2+-independent. We hypothesized that the RhoA/ROCK signaling pathway also can regulate HPV vascular function via a Ca2+-dependent mechanism, signaling through the functional transient receptor potential canonical (TRPC) channels. In this study, male BALB/c mice were exposed to normoxic or 10% oxygen (hypoxic) conditions for six weeks, after which systolic pressure and right ventricular hypertrophy were assessed. Transient intracellular calcium was monitored using a fluorescence imaging system. Muscle tension was measured with a contractile force recording system, and protein expression was assessed by immunoblotting. We found that the expressions of RhoA and ROCK were increased in mouse pulmonary arteries (PAs) under conditions of chronic hypoxia. Inhibition of the RhoA/ROCK signaling pathway prevented the development of hypoxic pulmonary hypertension (HPH), as evidenced by significantly reduced PA remodeling and pulmonary vasoconstriction. Immunoblotting results revealed that inhibition of the RhoA/ROCK signaling pathway significantly decreased the expression of HIF-1α. Knockdown of HIF-1α down-regulated the expression and function of the TRPC1 and TRPC6 channels in PASMCs under conditions of hypoxia. Contraction of the PAs and a Ca2+ influx into PASMCs through either receptor- or store-operated Ca2+ channels were also increased after hypoxia. However, RhoA/ROCK inhibitors markedly attenuated these changes. These results indicate that inhibition of the RhoA/ROCK signaling pathway ameliorates HPH via HIF-1α-dependent functional TRPCs.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Amidas/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Arterial/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Hipertensão Arterial Pulmonar/prevenção & controle , Piridinas/farmacologia , Canais de Cátion TRPC/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Sinalização do Cálcio , Linhagem Celular , Modelos Animais de Doenças , Hipóxia/complicações , Hipóxia/enzimologia , Hipóxia/fisiopatologia , Masculino , Camundongos Endogâmicos BALB C , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/enzimologia , Hipertensão Arterial Pulmonar/enzimologia , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/enzimologia , Artéria Pulmonar/fisiopatologia , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6/genética , Canal de Cátion TRPC6/metabolismo , Vasoconstrição/efeitos dos fármacos , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/genética
14.
Toxicol Appl Pharmacol ; 368: 26-36, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30776389

RESUMO

Cardiac dysfunction is a vital complication during endotoxemia (ETM). Accumulating evidence suggests that enhanced glycolytic metabolism promotes inflammatory and myocardial diseases. In this study, we performed deep mRNA sequencing analysis on the hearts of control and lipopolysaccharide (LPS)-challenged mice (40 mg/kg, i.p.) and identified that the glycolytic enzyme, 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase 3 (PFKFB3) might play an indispensable role in ETM-induced cardiac damage. Quantitative real-time PCR validated the transcriptional upregulation of PFKFB3 in the myocardium of LPS-challenged mice and immunoblotting and immunostaining assays confirmed that LPS stimulation markedly increased the expression of PFKFB3 at the protein level both in vivo and in vitro. The potent antagonist 3-(3pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was used to block PFKFB3 activity in vivo (50 mg/kg, i.p.) and in vitro (10 µM). Echocardiographic analysis and TUNEL staining showed that 3PO significantly alleviated LPS-induced cardiac dysfunction and apoptotic injury in vivo. 3PO also suppressed the LPS-induced secretion of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and lactate in the serum, in addition to lactate in the myocardium. PFKFB3 inhibition also diminished the nuclear translocation and phosphorylation of transcription factor nuclear factor-κB (NF-κB) in both adult cardiomyocytes and HL-1 cells. Furthermore, immunoblotting analysis showed that 3PO inhibited LPS-induced apoptotic induction in cardiomyocytes. Taken together, these findings demonstrate that PFKFB3 participates in LPS-induced cardiac dysfunction via mediating inflammatory and apoptotic signaling pathway.


Assuntos
Apoptose , Endotoxemia/enzimologia , Cardiopatias/enzimologia , Mediadores da Inflamação/metabolismo , Miócitos Cardíacos/enzimologia , Fosfofrutoquinase-2/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Endotoxemia/patologia , Endotoxemia/prevenção & controle , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Cardiopatias/prevenção & controle , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Fosfofrutoquinase-2/antagonistas & inibidores , Fosfofrutoquinase-2/genética , Piridinas/farmacologia , Transdução de Sinais
15.
World Neurosurg ; 103: 355-359, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28433841

RESUMO

OBJECTIVE: To provide a simple and reliable method for the diagnosis of ventriculoperitoneal shunt malfunction. METHODS: A total of 14 participants were enrolled in this study, consisting of 7 patients with suspected shunt malfunction and 7 control cases with apparent normal drainage. In all cases, 0.1 mL of 5% glucose solution was injected into the reservoir and 0.1 mL of cerebrospinal fluid was withdrawn from the reservoir 20 minutes later to measure glucose concentration. RESULTS: The glucose concentration in cerebrospinal fluid of the shunt malfunction group was greater than that of the control group (P < 0.05). CONCLUSIONS: The proposed method is reliable, safe, and relatively simple for the diagnosis of ventriculoperitoneal shunt malfunction and provides a reference for treatment.


Assuntos
Falha de Equipamento , Derivação Ventriculoperitoneal/instrumentação , Adulto , Estudos de Casos e Controles , Líquido Cefalorraquidiano , Diagnóstico Precoce , Desenho de Equipamento , Feminino , Glucose/análise , Voluntários Saudáveis , Humanos , Hidrocefalia/cirurgia , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto Jovem
16.
Sensors (Basel) ; 15(9): 23745-62, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26393596

RESUMO

Temperature distribution is a critical indicator of the health condition for Liquefied Petroleum Gas (LPG) storage tanks. In this paper, we present a large-scale wireless temperature monitoring system to evaluate the safety of LPG storage tanks. The system includes wireless sensors networks, high temperature fiber-optic sensors, and monitoring software. Finally, a case study on real-world LPG storage tanks proves the feasibility of the system. The unique features of wireless transmission, automatic data acquisition and management, local and remote access make the developed system a good alternative for temperature monitoring of LPG storage tanks in practical applications.

17.
Sensors (Basel) ; 14(5): 8829-50, 2014 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-24854060

RESUMO

Pavements always play a predominant role in transportation. Health monitoring of pavements is becoming more and more significant, as frequently suffering from cracks, rutting, and slippage renders them prematurely out of service. Effective and reliable sensing elements are thus in high demand to make prognosis on the mechanical properties and occurrence of damage to pavements. Therefore, in this paper, various types of functionality enhancement of industrialized optical fiber sensors for pavement monitoring are developed, with the corresponding operational principles clarified in theory and the performance double checked by basic experiments. Furthermore, a self-healing optical fiber sensing network system is adopted to accomplish full-scale monitoring of pavements. The application of optical fiber sensors assembly and self-healing network system in pavement has been carried out to validate the feasibility. It has been proved that the research in this article provides a valuable method and meaningful guidance for the integrity monitoring of civil structures, especially pavements.

18.
Acta Neurochir (Wien) ; 154(6): 1081-6; discussion 1086, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22466153

RESUMO

BACKGROUND: Studies have demonstrated that brain oedema formation following spontaneous intracerebral haemorrhage is associated with substances derived from blood clots or blood components. However, these studies did not completely reveal the role of blood components in brain oedema formation following traumatic intracerebral haemorrhage (TICH). Here, we explore the role of erythrocytes in brain oedema development by studying the effect of erythrocytes on brain water content (BWC) and expression of haem oxygenase-1 (HO-1) in rats with TICH. METHODS: A total of 120 Sprague-Dawley rats were randomly divided into four experimental treatment groups: traumatic brain injury (TBI), TBI plus whole blood (WB), TBI plus lysed red blood cells (RBCs; LRBC) and TBI plus packed RBCs (PRBC). Following TBI, which was established by applying a free-falling device, WB, LRBC or PRBC were infused with stereotactic guidance into the injured cortex to produce a model of TICH. All rats were killed at 1, 3 or 5 days after TBI or TICH. BWC was measured, and immunohistochemistry for HO-1 was performed. RESULTS: In the WB, PRBC and TBI groups, BWC at 3 days post-TBI or post-TICH was the greatest. However, BWC in the LRBC group at 1 day was markedly higher than that at 3 and 5 days. Comparisons among the four groups showed that BWC in the LRBC group was the highest at 1 day, and the highest at 3 days in the WB and PRBC groups; there was no significant difference at 5 days. Positive expression of HO-1 in the WB, PRBC and LRBC groups coincided with changes in BWC. CONCLUSIONS: Our results indicate that erythrocytes play an important role in delayed brain oedema formation (3 days post-injury) following TICH, but have no significant influence on brain oedema at early stages (1 day post-injury), and that the mechanisms of delayed brain oedema involve RBC breakdown products.


Assuntos
Água Corporal/fisiologia , Edema Encefálico/sangue , Artérias Cerebrais/fisiopatologia , Hemorragia Cerebral Traumática/sangue , Eritrócitos/fisiologia , Heme Oxigenase-1/biossíntese , Animais , Edema Encefálico/etiologia , Artérias Cerebrais/lesões , Hemorragia Cerebral Traumática/complicações , Modelos Animais de Doenças , Feminino , Heme Oxigenase-1/sangue , Heme Oxigenase-1/genética , Masculino , Ratos , Ratos Sprague-Dawley
19.
Huan Jing Ke Xue ; 33(1): 260-5, 2012 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-22452220

RESUMO

The contents of heavy metals (As, Cd, Cu, Zn, Ni and Pb) in soils from Xiangjiang River Basin, Hunan Province, China, were analyzed by toxicity characteristic leaching procedure (TCLP) and Nemrow method. Results showed that the total contents of As, Cd, Cu, Zn, Ni and Pb were 4.25-549.67, 0.13-76.84, 11.49-281.69, 7.75-7234.81, 5.50-56.65 and 8.60-2084.81 mg x kg(-1), respectively, and the available contents of As, Cd, Cu, Zn, Ni and Pb extracted by TCLP were 0.02-10.97, 0.06-28.41, 0.04-72.29, 0.59-1 152.32, 0.07-10. 65 and 0.17-1 165.58 mg x kg(-1). The contents of available heavy metals extracted by TCLP correlated with total contents of heavy metals. Moreover, the pollution index Nemrow method showed that 72 samples at safety level, alert level, light pollution level, medium pollution level and heavy pollution level ratios were 60.52%, 11.33%, 5.65%, 4.22% and 18.38% separately, illustrating that pollution of heavy metals in soil samples of Xiangjiang River Basin is serious.


Assuntos
Metais Pesados/análise , Poluentes do Solo/análise , Solo/análise , Cádmio/análise , China , Cobre/análise , Monitoramento Ambiental , Chumbo/análise , Medição de Risco , Rios
20.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 8): o2119, 2010 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-21588409

RESUMO

The title compound, C(16)H(12)Br(2)F(2)S(2) [systematic name: 1(2),1(5)-dibromo-5(2),5(5)-difluoro-2,7-dithia-1,5(1,4)-dibenzenaocta-phane], has two approximately parallel benzene rings with a dihedral angle of 1.53 (15)° between them and with a centroid-centroid distance of 3.3066 (18) Å. In the crystal structure, mol-ecules are stacked along the a axis through an inter-molecular π-π inter-action with a centroid-centroid distance of 3.7803 (18) Å. Mol-ecules are also connected by a C-H⋯S inter-action, forming a chain along the b axis.

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