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1.
Int J Mol Med ; 45(3): 715-730, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922237

RESUMO

Age­related hearing loss, also termed central presbycusis, is a progressive neurodegenerative disease; it is a devastating disorder that severely affects the quality of life of elderly individuals. Substantial evidence has indicated that oxidative stress and associated protein folding dysfunction have a marked influence on neurodegenerative diseases. In this study, we aimed to cells to investigate whether metformin protects against age­related pathologies and to elucidate the underlying mechanisms; specifically, we focused on the role of unfolded protein response (UPR) via the AMPK/ERK1/2 signaling pathways. For this purpose, the biguanide compound, metformin, a medication widely used in the treatment of type 2 diabetes, was administered to rats in a model of mimetic aging. In addition, senescent PC12 were treated with metformin. Although it has been well established that UPR signaling is activated in response to cellular stress and is associated with the pathogenesis of neuronal deterioration, the detailed functions of the UPR in the auditory cortex remain unclear. We found that metformin treatment markedly affected the UPR and the AMPK/ERK1/2 signaling pathway, and maintained the auditory brainstem response (ABR) threshold during the aging process. The results indicated that the regulation of the UPR and AMPK/ERK1/2 signaling pathway by metformin significantly attenuated hearing loss, cell apoptosis and age­related neurodegeneration. Reversing these harmful effects through the use of metformin suggests its involvement in restoring the antioxidant status and protein homeostasis related to the underlying pathology of presbycusis. The findings of this study may provide a better approach for the treatment of age­related neurodegeneration diseases.

2.
Int J Clin Oncol ; 25(2): 338-346, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31720994

RESUMO

OBJECTIVE: PBRM1, located on 3p21, functions as a tumor suppressor and somatic mutation of PBRM1 is frequent in clear cell renal cell carcinoma (ccRCC). This study aims to determine the influence of PBRM1 expression on the prognosis of patients with mRCC receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We identified 116 mRCC patients who were administered sunitinib or sorafenib as first-line therapy, between January 2006 and December 2016 at our institution. PBRM1 expression was assessed by immunohistochemistry. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS), log-rank test was used to compare the survival outcomes between patients with low and high PBRM1 expression levels, and the Cox proportional hazard regression model was used to estimate the prognostic value. Prognostic accuracy was determined using Harrell concordance index, and nomograms were built to evaluate the prognosis of mRCC. RESULTS: Patients with low PBRM1 expression had significantly shorter median PFS (9 vs 26 months, P < 0.001) and OS (21 vs 44 months, P < 0.001) than those with high expression. Multivariate analysis showed that PBRM1 expression was an independent predictor of PFS (HR 1.975, P = 0.013) and OS (HR 2.282, P = 0.007). The model built by the addition of PBRM1 improved the C-index of PFS and OS to 0.72 and 0.82, respectively. CONCLUSIONS: The expression of PBRM1 could be a significant prognostic factor for mRCC patients treated with targeted therapy, and it increases the prognostic accuracy of the established prognostic model.

3.
Obes Surg ; 30(1): 327-335, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31602628

RESUMO

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) could affect immunological activity after surgery. We examined the role of RYGB on the NOD-like receptor pyrin domain containing-6 (NLRP6) in the intestine after surgery in rat models. METHODS: Expression of intestinal NLRP6 in the lean, obesity, RYGB, and sham-pair fed (PF) groups was analyzed by quantitative RT-PCR, Western blotting, and immunohistochemistry. Gut microbiota abundance was determined by 16S rRNA sequencing. Cohousing experiments were conducted to analyze the effects of gut microbiota. Inflammatory cell infiltration and gut permeability were further validated. RESULTS: Obese rats had decreased intestinal NLRP6 levels, which could be restored by RYGB but not by calorie restriction. This regulation was dependent on the gut microbiota-related metabolites, taurine, and histamine. After RYGB, there were increased levels of taurine, which could positively affect NLRP6 expression. The pair-fed groups showed increased histamine, which had the opposite effects on NLRP6. Obese rats had greater intestinal permeability along with increased CD8+ T cell infiltration. However, RYGB but not calorie restriction could restore these changes in a manner, dependent on gut NLRP6 expression. CONCLUSIONS: In rat models, RYGB could efficiently restore abnormal gut permeability and reduce inflammation in the intestine, depending on reactivation of NLRP6.

4.
Curr Eye Res ; 45(1): 64-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31294618

RESUMO

Purpose: Adeno-associated virus vector (AAV) is the most accepted gene delivery vector for retinal gene therapy. Müller cells play an important role in maintaining homeostasis and neuronal structural integrity, stability and it has been found to be involved in many retinopathies. The aim of this study is to identify a rAAV2/6 mutant which has increased tropism for Müller cell of the mouse retina.Materials and Methods: Using amino acid mutagenesis, we created a rAAV2/6 capsid mutant, rAAV2/6-S663L. In vivo imaging and retinal flat mount were employed to analyze the gene expression of rAAV2/6-S663L and wt rAAV2/6 in mouse retinal tissue. Retinal tissue cryosection, immunohistochemistry (IHC), Müller cell-specific promoter-controlled gene expression, and double AAV fluorescent protein co-expression were performed to determine the targeting of rAAV2/6-S663L for mouse retinal Müller cells.Results: In vivo imaging, retinal flat mount and retinal tissue cryosection results showed that rAAV2/6-S663L and wt rAAV2/6 have different specific tropisms in mouse retina and rAAV2/6-S663L is more preferentially targeting Müller cells. Müller cell-specific promoter-controlled gene expression experiments and IHC test confirmed that rAAV2/6-S663L has a higher tendency to infect Müller cells than wt rAAV2/6. Co-infection of the mouse retina with one rAAV2/6-S663L expressing EGFP under the control of GFAP promoter and the other one expressing mCherry under the control of CMV promoter revealed co-expression of the two fluorescent proteins in Müller cells.Conclusions: The results confirmed that rAAV2/6-S663L has a higher tropism for Müller cells than wt rAAV2/6. Our findings could add a new useful tool for retinal disease gene therapy.

5.
World J Clin Cases ; 7(20): 3217-3225, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31667172

RESUMO

BACKGROUND: Colorectal cancer is a common malignant tumor of the digestive tract. The relationship between sentinel polyps (rectal polyps with proximal colon cancer) and proximal colon cancer has received extensive attention in recent years. However, there is still no clear conclusion regarding the relationship. AIM: To investigate the clinical characteristics of sentinel polyps and their correlation with proximal colon cancer. METHODS: A retrospective analysis of 2587 patients with rectal polyps from January 2006 to December 2017 was performed. According to whether or not proximal colon cancer was diagnosed, the patients were divided into either a sentinel polyp group (192 patients) or a pure rectal polyp group (2395 patients). The endoscopic features, clinicopathological features, therapeutic effects, and short-term prognosis were analyzed and compared between the two groups. RESULTS: The mean age of patients in the sentinel polyp group was generally higher than that of the pure rectal polyp group, and the positivity rates of anemia, stool occult blood, and tumor markers of the sentinel polyp group were also significantly higher than those in the rectal polyp group (χ 2 = 90.56, P < 0.01; χ 2 = 70.30, P < 0.01; χ 2 = 92.80, P < 0.01). The majority of the patients in the sentinel polyp group had multiple polyps, large polyps, adenomatous polyps, or sessile polyps (χ 2 = 195.96, P < 0.01; χ 2 = 460.46, P < 0.01; χ 2 = 94.69, P < 0.01; χ 2 = 48.01, P < 0.01). Most of the proximal colon cancers were Duke's A and B stages in the sentinel polyp group. In the pure rectal polyp group, 2203 patients underwent endoscopic treatment, and all of the patients were cured and discharged. In the sentinel polyp group, 65 patients underwent radical operation, and 61 patients received endoscopic submucosal dissection or endoscopic mucosal resection. Additionally, 21 patients were lost to follow-up after 6-12 mo, and the loss rate was 10.94%. A total of 63.16% of patients experienced remission without tumor recurrence or metastasis, 33.33% of patients experienced tumors regression or improved symptoms, and the other 3.51% of the patients died. CONCLUSION: If there are multiple, sessile, and adenomatous rectal polyps with a maximum diameter > 1 cm, the possibility of the carcinogenesis of the polyps or of the proximal colon should be monitored closely. These patients should be followed in the short-term and should undergo a whole-colon examination.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31731510

RESUMO

Outsourcing the hazardous materials (HazMat) transportation is an effective way for manufacturing enterprises to avoid risks and accidents as well as to retain sustainable development in economic growth and social inclusion while not bringing negative impacts on the public and the environment. It is imperative to develop viable and effective approaches to selecting the most appropriate HazMat transportation alternatives. This paper aims at proposing an integrated multi-criteria group decision making approach that combines proportional hesitant fuzzy linguistic term set (PHFLTS) and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) to address the problem of HazMat transportation alternative evaluation and selection. PHFLTSs are adopted to represent the congregated individual evaluations in a bid to avoid information loss and increase the reliability of results. Two weight assignment models are then proposed to determine the comprehensive weights of experts and criteria. Furthermore, several novel manipulations of PHFLTS are also defined to enrich its applicability. The TOPSIS method is subsequently extended to the context of PHFLTSs to rank alternatives and choose the best one. Eventually, the feasibility and validity of the proposed approach are verified by a practical case study of a HazMat transportation alternative evaluation and selection decision and further comparison analyses.

7.
J Ovarian Res ; 12(1): 94, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615559

RESUMO

PURPOSE: The polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder, clinically characterized by oligo-ovulation/chronic anovulation, menstrual irregularities, hyperandrogenism (such as hirsutism, acne), hyperinsulinemia, and obesity. Prostatic-specific antigen (PSA) has been identified as a potential new marker in PCOS women. Although the precise role of PSA in PCOS patients still remains undetermined, PSA might serve as a useful clinical marker and might even represent a new diagnostic criterion of hyperandrogenemia in females of PCOS. METHODS: A meta-analysis was performed in the study to identify the association between the polycystic ovary syndrome and prostatic-specific antigen. To identify eligible original articles, we searched a range of computerized databases, including Medline via PubMed, EMBASE, CNKI and Web of Science with a systematic searching strategy. The characteristics of each study and standard mean differences (SMD) with corresponding confidence intervals (CIs) were calculated and subgroup analysis was performed to analyze heterogeneity. RESULTS: A total of 532 patients from seven articles were included in the meta-analysis. We identified a significant relationship between polycystic ovary syndrome and prostatic-specific antigen, with a pooled SMD of 0.81 (95% CI: 0.58 to 1.04; P < 0.01). The pooled data were calculated with the random-effects model as a moderate significant heterogeneity was found among the studies. CONCLUSIONS: The meta-analysis suggested that there was a significant association between the polycystic ovary syndrome and prostatic-specific antigen and we should not ignore the role of PSA in the PCOS patients in clinical.

8.
Int J Ophthalmol ; 12(8): 1351-1355, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456929

RESUMO

The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome (AIDS) patients with cytomegalovirus retinitis (CMVR) was investigated. A total of 32 eyes in 23 AIDS patients diagnosed as CMVR from 2017 to 2018 were included in the retrospective study. All patients underwent induction therapy by using intravenous drip of the anti-cytomegalovirus (CMV) agent ganciclovir (5 mg/kg q12h) combined with intravitreal ganciclovir injection (3 mg/time, 2 times/wk). The visual acuity, fundus photographs, lesion location, and number of intravitreal injections were observed preoperatively and postoperatively. Totally 14 eyes were cured during induction therapy. The number of injections [4.13 (2 to 6)] in CMVR patients with peripherally fundus lesions were significantly lower than those with central lesions [4.89 (2 to 6)]. The individualized therapy of intravitreal ganciclovir injections for AIDS patients with CMVR can effectively reduce the numbers of intravitreal injections.

9.
Medicine (Baltimore) ; 98(26): e16073, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261518

RESUMO

The present study aims to measure the retinal thickness of the macular region of AIDS patients with normal ocular fundus, HIV-related microvascular retinopathy patients and cytomegalovirus retinitis (CMVR) patients by optical coherence tomography, and generalize the characteristics of retinal thickness of these 3 groups of patients.In this retrospective case series, the study object comprised of 111 AIDS patients who received diagnosis and treatment in the Ophthalmology Department of Beijing Youan Hospital. There are 33 patients in the AIDS normal ocular fundus group, 47 patients in the HIV-related microvascular retinopathy group, and 31 patients in the CMVR group. The retinal thickness of the macular region of these above patients was measured. The main indicators were retinal thickness of 9 macular partitions, best corrected visual acuity, CD4+ T lymphocyte count, and the start of highly active antiretroviral therapy.In the CMVR group, except for the nasal-outer and temporal-outer sectors, the thickness of the affected eye of the rest of the regions was greater than that of healthy eye (P < .05). Furthermore, there was a difference in thickness of the superior-outer and inferior-outer sectors between the AIDS normal ocular fundus group and HIV-related microvascular retinopathy group. The difference in thickness of the superior-inner sector between patients in the AIDS normal ocular fundus group and CMVR group was not statistically significant, while the difference in thickness of the rest of the regions was statistically significant. The difference in thickness of various regions between patients in the HIV-related microvascular retinopathy group and CMVR group was statistically significant.The retinal thickness of patients in the CMVR group generally increased, the retinal thickness of superior-outer and inferior-outer sections of patients in the HIV-related microvascular retinopathy group increased, when compared to the AIDS normal ocular fundus group. These optical coherence tomography (OCT) examination results present its own characteristics in different eye diseases in AIDS patients, and different stages of eye disease.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Síndrome de Imunodeficiência Adquirida/diagnóstico por imagem , Macula Lutea/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Doenças Vasculares/diagnóstico por imagem , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/patologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/patologia , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Fundo de Olho , Humanos , Macula Lutea/patologia , Masculino , Microvasos , Pessoa de Meia-Idade , Tamanho do Órgão , Doenças Retinianas/complicações , Doenças Retinianas/patologia , Vasos Retinianos , Estudos Retrospectivos , Tomografia de Coerência Óptica , Doenças Vasculares/complicações , Doenças Vasculares/patologia , Acuidade Visual , Adulto Jovem
10.
Front Microbiol ; 10: 1322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249564

RESUMO

The identification of recent HIV-1 infection is clinically important for the effective treatment and prevention of transmission. However, the window period for seroconversion with respect to various HIV-1 antibodies is not well characterized. In addition, the routine HIV testing algorithms are not particularly appropriate for the identification of recent HIV-1 infection. In this study, we enrolled individuals who showed seroconversion from negative Western blot (WB) or indeterminate WB results and analyzed the window periods for appearance of HIV-1 antibodies. A total of 10,934 individuals with suspected HIV infection were tested by Wuhan CDC between 2012 and 2017; of these, 40 individuals with initial negative WB and 102 individuals with initial indeterminate WB who showed positive WB results within 100 days were included in the analysis. The mean time for seroconversion was 43.90 (95% confidence interval [CI]: 37.30-50.50) days and 42.15 (95% CI: 37.99-46.30) days, respectively. The time duration for p31 seroconversion among people with negative WB and indeterminate WB was 58.11 (95% CI, 44.30-71.92) days and 51.91 (95% CI, 44.55-59.28) days, respectively, both of which were significantly longer (p = 0.0169) than those in people without p31 seroconversion. A similar difference was observed with respect to p66 seroconversion, with a window time of 53.53 (95% CI, 43.54-63.52) days and 47.87 (95% CI, 43.16-52.57) days among people with negative WB and indeterminate WB, respectively. These data suggest that HIV-1 antibody p66, like p31, may serve as a potential serological marker for distinguishing Fiebig stage V and stage VI at day 70 post-infection.

11.
J Med Ultrason (2001) ; 46(4): 459-466, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31102067

RESUMO

PURPOSE: To evaluate the value and diagnostic performance of virtual touch tissue imaging quantification (VTIQ) and to determine the optimum cut-off value for differential diagnosis between benign and malignant breast lesions. METHODS: Conventional ultrasonography (US) and VTIQ were performed in 454 patients with 466 breast lesions with a Siemens Acuson S3000 ultrasound machine. All lesions were assessed by an ultrasound Breast Imaging Reporting and Data System (BI-RADS) and confirmed by histopathology. The maximum, mean, and minimum shear wave velocity (SWV) values were quantitatively measured in m/s within the regions of interest (ROIs) and ranged from 0.5 to 10 m/s. The sensitivity, specificity, accuracy, and area under the receiver operating curve (AUC) of the VTIQ, BI-RADS, and combined data were compared. RESULTS: Among the 466 breast lesions, 266 were benign and 200 were malignant. All of the SWV values of the malignant lesions were significantly greater than those of the benign ones (P < 0.05). The optimal cut-off values for SWVmax, SWVmin, SWVmean, and SWVmax/SWVmin obtained from ROC analysis were 5.37 m/s, 3.08 m/s, 4.04 m/s, and 1.83, respectively. Logistic regression analysis revealed that BI-RADS was an independent risk factor for the differential diagnosis of breast lesions, whereas SWV values were not independent risk factors. CONCLUSIONS: VTIQ is useful in the differential diagnosis between benign and malignant breast lesions. The combination of VTIQ and ultrasonic BI-RADS can improve the diagnostic performance.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Ultrassonografia Mamária/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Adulto Jovem
12.
Cardiovasc Diabetol ; 18(1): 48, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987625

RESUMO

OBJECTIVE: The importance of triglycerides (TG) level as a risk factor for cardiovascular diseases (CVD) has been extensively investigated in the general population; however, their relationship in patients with type 2 diabetes mellitus (T2DM) is uncertain. We aimed to assess the association of TG with CVD in T2DM individuals. RESEARCH DESIGN AND METHODS: We searched bibliographic databases for studies published until June 2018, reporting on the relationship between TG and CVD in T2DM people. A random-effects model with inverse variance weighting was used to compute pooled estimates of the most fully adjusted risk ratios (RR) and corresponding 95% confidence intervals (CI) according to TG categories, unit TG, and logarithm (log) of TG for CVD. RESULTS: A total of 31 studies were included, involving 132,044 T2DM patients with 10,733 incident cardiovascular events. The pooled RR (95% CI) of CVD for an increase in baseline TG, log TG by 1-mmol/l and categorized in the highest vs. the lowest TG in T2DM were 1.06 (1.02, 1.09), 1.30 (1.18, 1.42) and 1.30 (1.16, 1.46), corresponding to a CVD risk increase of 6%, 30% and 30%, respectively. The pooled RR (95% CI) of CVD for per 1-mmol/L TG increment in eight studies and TG categories in three studies were 1.03 (0.98, 1.08) and 1.39 (0.92, 2.1) in T2DM patients adjusted for other lipids parameter, respectively. CONCLUSIONS: In T2DM patients, an elevated triglyceride level cannot serve as an independent marker for an increased risk of cardiovascular events, but still, the higher serum TG levels tend to be associated with increased risks of CVD.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Triglicerídeos/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Humanos , Prognóstico , Medição de Risco , Fatores de Risco , Regulação para Cima
13.
Acta Pharm Sin B ; 9(2): 324-334, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30972280

RESUMO

Histone lysine-specific demethylase 1 (LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) of clear cell renal cell carcinomas (ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage (P=0.006), especially tumor stage (P=0.017) and lymph node metastasis (P=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (P<0.001) and recurrence-free survival (P<0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC in vitro and in vivo. Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the CDKN1A gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in ccRCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.

14.
Biosci Rep ; 39(2)2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30626727

RESUMO

Aminoglycoside antibiotics-induced hearing loss is a common sensorineural impairment. Spiral ganglion neurons (SGNs) are first-order neurons of the auditory pathway and are critical for the maintenance of normal hearing. In the present study, we investigated the time-course of morphological changes and the degeneration process of spiral ganglion cells (SGCs) following chronic kanamycin-induced deafness and determined whether the endoplasmic reticulum (ER) stress was involved in the degeneration of SGNs. We detected density changes in SGCs and the expressions of Bip, inositol requirement 1 (IRE1)α, activating transcription factor-6α, p-PERK, p-eIF2α, CHOP, and caspase-12 at each time point after kanamycin treatment. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was also performed. The number of SGC deletions reached ∼50% at the 70th day after kanamycin administration and the ER of most SGCs were dilated. The expression of p-PERK, p-eIF2α, p-IRE1α, Bip, caspase-12, and Chop was significantly unregulated after kanamycin treatment. The number of SGCs that were positive for both TUNEL and caspase-12 increased from day 7 to 28. Taken together, these data demonstrate that ER stress was involved in kanamycin-induced apoptosis of SGNs. Kanamycin-induced SGN apoptosis is mediated, at least in part, by ER stress-induced upregulation of CHOP and caspase-12.


Assuntos
Surdez/patologia , Estresse do Retículo Endoplasmático , Canamicina/efeitos adversos , Neurônios/patologia , Gânglio Espiral da Cóclea/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 12/metabolismo , Surdez/induzido quimicamente , Surdez/fisiopatologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Proteínas de Choque Térmico/metabolismo , Masculino , Complexos Multienzimáticos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Sprague-Dawley , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/metabolismo , Gânglio Espiral da Cóclea/ultraestrutura , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo
15.
Clin Hemorheol Microcirc ; 71(1): 17-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30010112

RESUMO

OBJECTIVE: To compare the enhancement pattern of hepatic angiomyolipoma (HAML) on contrast enhanced ultrasound (CEUS) and magnetic resonance (MR). METHODS: The data of seven patients (females; age 28-52 years; mean, 42 years) with histologically proven HAMLs were retrospectively reviewed. All patients underwent CEUS and MR examination. The images were analyzed by two experienced doctors who blinded to the clinical and pathological information of cases. RESULTS: The mean diameter of the nodule was 5.7 cm (range: 3.2-10 cm). Histopathologic results revealed 4 nodules to be myomatous type and 3 nodules to be mixed type. All nodules showed hyperenhanced during arterial phase on both CEUS and MRI. During portal and delayed phase, washout was more showed on MRI (5/7, 71.4%) than on CEUS (2/7, 28.6%). CONCLUSIONS: There is discrepancy of enhancement pattern between CEUS and MRI. The quick wash-in and sustained hyperenhancement on CEUS may be helpful for the diagnosis of HAML.


Assuntos
Angiomiolipoma/diagnóstico por imagem , Meios de Contraste/uso terapêutico , Imagem por Ressonância Magnética/métodos , Ultrassonografia/métodos , Adulto , Angiomiolipoma/patologia , Meios de Contraste/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Med Ultrason ; 20(4): 420-426, 2018 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-30534647

RESUMO

The aim of this study is to evaluate if contrast enhanced ultrasound (CEUS) can improve the differential diagnostic performance of gallbladder (GB) lesions. MATERIALS AND METHODS: Forty-nine patients (18 men, 31 women; mean age, 54.8±14.4 years, range age, 22-78 years) with GB lesions (mass-forming and wall-thickened types) were enrolled in this study. All patients underwent conventional ultrasonography (US) and CEUS examination. The imaging characteristics of GB lesions were analyzed to compare the diagnostic performance of US and CEUS. The final diagnosis was obtained by histopathology. RESULTS: There were significant differences between benign and malignant GB lesions with regards to size, shape, vascularity, the integrity and margin of GB wall and time to iso-enhancement on CEUS (p<0.05). However, no significant difference was found concerning the enhancement patterns between the two groups (p>0.05). Logistic regression analysis showed that the boundary between liver and GB wall (p=0.017) and vascularity on color Doppler flow imaging (p=0.013) were two independent predictors of malignancy. The diagnostic accuracy of US could be improved in combination with CEUS (65.3% vs 83.7%). The diagnostic accuracy of the GB wall thickening type was higher than the mass forming type. CONCLUSION: CEUS could improve the diagnostic performance of GB lesions, especially for wall-thickened type lesions.


Assuntos
Meios de Contraste , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Aumento da Imagem/métodos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Vesícula Biliar/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Ultrassonografia/métodos , Adulto Jovem
17.
Mol Cancer ; 17(1): 157, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30419914

RESUMO

PURPOSE: Although microRNAs (miRNAs) were revealed as crucial modulators in tumor metastasis and target therapy, our understanding of their roles in metastatic renal cell carcinoma (mRCC) and Sunitinib treatment was limited. Here we sought to identify human miRNAs that acted as key regulators in renal cancer metastasis and Sunitinib treatment. EXPERIMENTAL DESIGN: We focused on 2 published microarray data to select out our anchored miRNA and then explored the roles of miR-452-5p both in vitro and in vivo, which was downregulated after Sunitinib treatment while upregulated in metastasis renal cell carcinoma (RCC) tissues. RESULTS: Here, we discovered that treating with Sunitinib, the targeted receptor tyrosine kinase inhibitor (TKI), inhibited renal cancer cell migration and invasion via attenuating the expression of miR-452-5p. The novel identified miR-452-5p was upregulated and associated with poor prognosis in RCC. Preclinical studies using multiple RCC cells and xenografts model illustrated that miR-452-5p could promote RCC cell migration and invasion in vitro and in vivo. Mechanistically, P65 could directly bind to the miR-452-5p promoter and thus transcriptionally induce miR-452-5p expression, which led to post-transcriptionally abrogate SMAD4 expression, thus inhibition of its downstream gene SMAD7. CONCLUSION: Our study presented a road map for targeting this newly identified miR-452-5p and its SMAD4/SMAD7 signals pathway, which imparted a new potential therapeutic strategy for mRCC treatment.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , MicroRNAs/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Smad4/metabolismo , Proteína Smad7/metabolismo , Sunitinibe/farmacologia , Regiões 3' não Traduzidas , Animais , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Camundongos , Modelos Biológicos , Metástase Neoplásica , Fenótipo , Prognóstico , Regiões Promotoras Genéticas , Ligação Proteica , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Int J Mol Med ; 42(6): 3371-3385, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272261

RESUMO

Central presbycusis is the most common sensory disorder in the elderly population, however, the underlying molecular mechanism remains unclear. NF­E2­related factor 2 (Nrf2) is a key transcription factor in the cellular response to oxidative stress, however, the role of Nrf2 in central presbycusis remains to be elucidated. The aim of the present study was to investigate the pathogenesis of central presbycusis using a mimetic aging model induced by D­galactose (D­gal) in vivo and in vitro. The degeneration of the cell was determined with transmission electron microscopy, terminal deoxynucleotidyl transferase­mediated deoxyuridine 5'­triphosphate nick­end labeling staining, and senescence­associated ß­galactosidase staining. The expression of protein was detected by western blotting and immunofluorescence. The quantification of the mitochondrial DNA (mtDNA) 4,834­base pair (bp) deletion and mRNA was detected by TaqMan quantitative polymerase chain reaction (qPCR) and reverse transcription­qPCR respectively. Cell apoptosis and intracellular ROS in vitro were determined with flow cytometry. The levels of nuclear Nrf2, and the mRNA levels of Nrf2­regulated antioxidant genes, were downregulated in the auditory cortex of aging rats, which was accompanied by an increase in 8­hydroxy­2'­deoxyguanosine formation, an accumulation of mtDNA 4,834­bp deletion, and neuron degeneration. In addition, oltipraz, a typical Nrf2 activator, was found to protect cells against D­gal­induced mtDNA damage and mitochondrial dysfunction by activating Nrf2 target genes in vitro. It was also observed that activating Nrf2 with oltipraz inhibited cell apoptosis and delayed senescence. Taken together, the data of the present study suggested that the age­associated decline in Nrf2 signaling activity and the associated mtDNA damage in the auditory cortex may be implicated in the degeneration of the auditory cortex. Therefore, the restoration of Nrf2 signaling activity may represent a potential therapeutic strategy for central presbycusis.


Assuntos
Córtex Auditivo/metabolismo , DNA Mitocondrial/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Presbiacusia/metabolismo , Envelhecimento/genética , Envelhecimento/fisiologia , Animais , Apoptose/genética , Apoptose/fisiologia , Dano ao DNA/genética , Dano ao DNA/fisiologia , DNA Mitocondrial/genética , Marcação In Situ das Extremidades Cortadas , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Células PC12 , Presbiacusia/genética , Ratos
19.
Lab Chip ; 18(22): 3507-3515, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30351335

RESUMO

Respiratory viruses are major threats causing development of acute respiratory tract infections, which are common causes of illness and death throughout the world. Here, an integrated microsystem based on real-time colorimetry was developed for diagnosing multiple respiratory viruses. The microsystem employed magnetic beads for nucleic acid extraction and an eight-channel microfluidic array chip integrated with a loop-mediated isothermal amplification system for point-of-care screening of respiratory viruses. The overall detection process (including sample collection, nucleic acid extraction, sample loading, real-time detection, and signal output) could be completed within 1 h. Our results show that the developed method could specifically recognize influenza A virus subtypes (H1N1, H3N2, H5N1, and H7N9), influenza B virus, and human adenoviruses. The results obtained with 109 clinical samples indicate that the developed method has high specificity (100%, confidence interval 94.9-100.0) and sensitivity (96%, confidence interval 78.1-99.9). The integration of magnetic bead-based pre-treatment techniques and microfluidic isothermal amplification provides an effective solution for rapidly detecting etiological agents of respiratory diseases. The strategy of using a closed chip system and real-time colorimetry reduced aerosol contamination and ensured the accuracy of the results. The developed method provides an effective alternative for rapid point-of-care screening for viruses that cause respiratory disease syndromes and further aids in accurate and timely detection to control and prevent the spread of respiratory diseases caused by such pathogens.


Assuntos
Adenoviridae/isolamento & purificação , Colorimetria/instrumentação , Dispositivos Lab-On-A-Chip , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Orthomyxoviridae/isolamento & purificação , Adenoviridae/genética , Humanos , Nanopartículas de Magnetita/química , Orthomyxoviridae/genética , Fatores de Tempo
20.
Urol Int ; 101(4): 391-399, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30184524

RESUMO

OBJECTIVES: The purpose of this work was to investigate the effect of sorafenib or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell carcinoma (RCC) with tumor thrombus. METHODS: A total of 92 RCC patients with tumor thrombus were included in this 2-center retrospective research from January 2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant therapy in 9 patients and 14 patients, respectively, and 69 patients constituted non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used to compare the survival outcomes of patients with or without neoadjuvant therapy. RESULTS: The overall median RFS and OS time for all 92 patients were 28 months (95% CI 17-39 months) and 42 months (95% CI 30-54 months). Patients with neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p = 0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant therapy. CONCLUSIONS: Neoadjuvant therapy of sorafenib or sunitinib might not improve survival outcomes for high risk RCC patients with tumor thrombus. Thus, neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Terapia Neoadjuvante , Sorafenibe/uso terapêutico , Sunitinibe/uso terapêutico , Adulto , Idoso , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombose/complicações , Trombose/tratamento farmacológico , Resultado do Tratamento
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