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1.
World J Mens Health ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38606869

RESUMO

Autophagy is a conservative lysosome-dependent material catabolic pathway, and exists in all eukaryotic cells. Autophagy controls cell quality and survival by eliminating intracellular dysfunction substances, and plays an important role in various pathophysiology processes. Erectile dysfunction (ED) is a common male disease. It is resulted from a variety of causes and pathologies, such as diabetes, hypertension, hyperlipidemia, aging, spinal cord injury, or cavernous nerve injury caused by radical prostatectomy, and others. In the past decade, autophagy has begun to be investigated in ED. Subsequently, an increasing number of studies have revealed the regulation of autophagy contributes to the recovery of ED, and which is mainly involved in improving endothelial function, smooth muscle cell apoptosis, penile fibrosis, and corpus cavernosum nerve injury. Therefore, in this review, we aim to summarize the possible role of autophagy in ED from a cellular perspective, and we look forward to providing a new idea for the pathogenesis investigation and clinical treatment of ED in the future.

3.
Molecules ; 29(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38257228

RESUMO

The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2-5) named albaphenol A-E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7-16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1-16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC50 45.5 and 61.0 µM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC50 2.5-32.8 µM) than the positive control galantamine (IC50 35.3 µM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 µM. The structure-activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor-enzyme complex.


Assuntos
Acetilcolinesterase , Benzofuranos , Butirilcolinesterase , Simulação de Acoplamento Molecular , Benzofuranos/farmacologia , Córtex Cerebral
4.
J Adv Res ; 58: 149-161, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37236543

RESUMO

INTRODUCTION: The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification and intervention of patients with ED. The present study aimed to clarify the causal association between 42 predominant risk factors and ED. METHODS: Univariate Mendelian Randomization (MR), multivariate MR, and mediation MR analyses were used to investigate the causal association between 42 modifiable risk factors and ED. Combined results were pooled from two independent ED genome-wide association studies to verify the findings. RESULTS: Genetically predicted body mass index (BMI), waist circumference, trunk fat mass, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, insomnia, snoring, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder were found to increase the risk of ED (all P < 0.05). Additionally, genetic liability to higher body fat percentage and alcohol consumption were suggestively associated with an increased risk of ED (P < 0.05 and adjusted P > 0.05). Genetic predisposition to higher sex hormone-binding globulin (SHBG) levels could decrease the risk of ED (P < 0.05). No significant association was detected between lipid levels and ED. Multivariate MR identified type 2 diabetes, basal metabolic rate, cigarette consumption, hypertension, and coronary heart disease as risk factors for ED. The combined results confirmed that waist circumference, whole body fat mass, poor overall health rating, type 2 diabetes, basal metabolic rate, adiponectin, cigarette consumption, snoring, hypertension, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, and major depressive disorder could increase the risk of ED (all P < 0.05), while higher SHBG decreased the risk of ED (P = 0.004). There were suggestive significances of BMI, insomnia, and stroke on ED (P < 0.05 and adjusted P > 0.05). CONCLUSION: This comprehensive MR study supported the causal role of obesity, type 2 diabetes, basal metabolic rate, poor self-health rating, cigarette and alcohol consumption, insomnia and snoring, depression, hypertension, stroke, ischemic stroke, coronary heart disease, myocardial infarction, heart failure, SHBG, and adiponectin in the onset and development of ED.


Assuntos
Doença das Coronárias , Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Disfunção Erétil , Insuficiência Cardíaca , Hipertensão , AVC Isquêmico , Infarto do Miocárdio , Distúrbios do Início e da Manutenção do Sono , Acidente Vascular Cerebral , Masculino , Humanos , Adiponectina , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Ronco , Fatores de Risco
5.
Aging (Albany NY) ; 15(7): 2667-2688, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37036471

RESUMO

BACKGROUND: Immunogenic cell death (ICD) is a form of regulated cell death (RCD) which could drive the activation of the innate and adaptive immune responses. In this work, we aimed to develop an ICD-related signature to facilitate the assessment of prognosis and immunotherapy response for melanoma patients. METHODS: A set of machine learning methods, including consensus clustering, non-negative matrix factorization (NMF) method and least absolute shrinkage and selection operator (LASSO) logistic regression model, and bioinformatics analytic tools were integrated to construct an ICD-related risk score (ICDscore). CIBERSORT and ESTIMATE algorithm were used to evaluate the infiltration of immune cells. The 'pRRophetic' package in R and 6 cohorts of melanoma patients receiving immunotherapy were used for therapy sensitivity analyses. The predictive performance between ICDscore with other mRNA signatures were also compared. RESULTS: The ICDscore could predict prognosis and immunotherapy response in multiple cohorts, and displayed superior performance than other forms of cell death-related signatures or 52 published signatures. The melanoma patients with low ICDscore were marked with high infiltration of immune cells, high expression of immune checkpoint inhibitor-related genes, and increased tumor mutation burden. CONCLUSIONS: In conclusion, we constructed a stable and robust ICD-related signature for evaluating the prognosis and benefits of immunotherapy, and it could serve as a promising tool to guide decision-making and surveillance for individual melanoma patients.


Assuntos
Morte Celular Imunogênica , Melanoma , Humanos , Melanoma/terapia , Prognóstico , Imunoterapia , Aprendizado de Máquina , Microambiente Tumoral
6.
Aging Male ; 26(1): 2195932, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37038659

RESUMO

BACKGROUND: This study aimed to investigate the association between different metabolic syndrome-body mass index (MetS-BMI) phenotypes and the risk of kidney stones. MATERIALS AND METHODS: Participants aged 20-80 years from six consecutive cycles of the NHANES 2007-2018 were included in this study. According to their MetS status and BMI, the included participants were allocated into six mutually exclusive groups: metabolically healthy normal weight (MHN)/overweight (MHOW)/obesity (MHO) and metabolically unhealthy normal weight (MUN)/overweight (MUOW)/obesity (MUO). To explore the association between MetS-BMI phenotypes and the risk of kidney stones, binary logistic regression was used to determine the odds ratios (ORs). RESULTS: A total of 13,589 participants were included. It was revealed that all the phenotypes with obesity displayed higher risks of kidney stones (OR = 1.38, p < 0.01 for MHO & OR = 1.80, p < 0.001 for MUO, in the fully adjusted model). The risk increased significantly when metabolic dysfunction coexisted with overweight and obesity (OR = 1.39, p < 0.05 for MUOW & OR = 1.80, p < 0.001 for MUO, in the fully adjusted model). Of note, the ORs for the MUO and MUOW groups were higher than those for the MHO and MHOW groups, respectively. CONCLUSIONS: Obesity and unhealthy metabolic status can jointly increase the risk of kidney stones. Assessing the metabolic status of all individuals may be beneficial for preventing kidney stones.


Assuntos
Cálculos Renais , Síndrome Metabólica , Obesidade , Humanos , Índice de Massa Corporal , Estudos Transversais , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Síndrome Metabólica/epidemiologia , Inquéritos Nutricionais , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Fatores de Risco , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Feminino
7.
Int J Impot Res ; 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36813836

RESUMO

Vitamin D3 is an important element in improving erectile function. However, the mechanisms of vitamin D3 remain unknown. Thus, we explored the effect of vitamin D3 on erectile function recovery after nerve injury in a rat model and investigated its possible molecular mechanisms. Eighteen male Sprague-Dawley rats were used in this study. The rats were randomly divided into three groups: the control, bilateral cavernous nerve crush (BCNC), and BCNC + vitamin D3 groups. BCNC model was established in rats by surgery. The intracavernosal pressure and the ratio of intracavernosal pressure to mean arterial pressure were utilized to evaluate erectile function. Masson trichrome staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and western blot analysis were performed on penile tissues to elucidate the molecular mechanism. The results indicated that vitamin D3 alleviated hypoxia and suppressed the fibrosis signalling pathway by upregulating the expression of eNOS (p = 0.001), nNOS (p = 0.018) and α-SMA (p = 0.025) and downregulating the expression of HIF-1α (p = 0.048) and TGF-ß1 (p = 0.034) in BCNC rats. Vitamin D3 promoted erectile function restoration by enhancing the autophagy process through decreases in the p-mTOR/mTOR ratio (p = 0.02) and p62 (p = 0.001) expression and increases in Beclin1 expression (p = 0.001) and the LC3B/LC3A ratio (p = 0.041). Vitamin D3 application improved erectile function rehabilitation by suppressing the apoptotic process through decreases in the expression of Bax (p = 0.002) and caspase-3 (p = 0.046) and an increase in the expression of Bcl2 (p = 0.004). Therefore, We concluded that vitamin D3 improved the erectile function recovery in BCNC rats by alleviating hypoxia and fibrosis, enhancing autophagy and inhibiting apoptosis in the corpus cavernosum.

8.
Int J Impot Res ; 35(2): 95-102, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35027721

RESUMO

Despite the high prevalence of erectile dysfunction, patients are reluctant to seek medical advice, which leads to low diagnostic rates in clinical practice. Artificial intelligence has been widely applied in the diagnosis of many diseases and may alleviate the situation. However, the applications of artificial intelligence in erectile dysfunction have not been reviewed to date. Therefore, the assistance from artificial intelligence needs to be summarized. In this review, 418 publications before January 10, 2021, regarding artificial intelligence applications in diagnosing and predicting erectile dysfunction, were retrieved from five databases, including PubMed, EMBASE, the Cochrane Library, and two Chinese databases (WANFANG and CNKI). In addition, the reference lists of the included studies or relevant reviews were checked to avoid bias. Finally, 30 articles were reviewed to summarize the current status, merits, and limitations of applying artificial intelligence in diagnosing and predicting erectile dysfunction. The results showed that artificial intelligence contributed to developing novel diagnostic questionnaires, equipment, expert systems, classifiers by images and predictive models. However, most of the included studies were not subjected to external validations, resulting in doubt on the generalizability. In the future, more rigorously designed studies with high-quality datasets for erectile dysfunction are required.


Assuntos
Inteligência Artificial , Disfunção Erétil , Masculino , Humanos , Disfunção Erétil/diagnóstico , Inquéritos e Questionários
9.
Asian J Androl ; 25(3): 421-425, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35946227

RESUMO

Sleep has attracted extensive attention due to its significance in health. However, its association with erectile dysfunction (ED) is insufficiently investigated. To investigate the potential causal links between sleep traits (insomnia, sleep duration, and chronotype) and ED, this study was performed. The single-nucleotide polymorphisms (SNPs) associated with insomnia, sleep duration, and chronotype were retrieved from previous genome-wide association studies (GWAS). A conventional two-sample Mendelian randomization (MR) was used to estimate the causal links between sleep traits and ED. The summary statistics of ED were from individuals of European ancestry (6175 cases vs 217 630 controls). As shown by the random effect inverse-variance-weighting (IVW) estimator, genetically predicted insomnia was causally associated with a 1.15-fold risk of ED (95% confidence interval: 1.07-1.23, P < 0.001). Sleep duration and morningness were not causally associated with ED, as indicated by the IVW (all P > 0.05). These findings were consistent with the results of sensitivity analyses. Based on genetic data, this study provides causal evidence that genetically predicted insomnia increases the risk of ED, whereas sleep duration and chronotype do not.


Assuntos
Disfunção Erétil , Distúrbios do Início e da Manutenção do Sono , Masculino , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/genética , Estudo de Associação Genômica Ampla , Disfunção Erétil/epidemiologia , Disfunção Erétil/genética , Sono/genética , Fenótipo , Polimorfismo de Nucleotídeo Único
10.
Front Pharmacol ; 13: 973394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278151

RESUMO

Background: Peyronie's disease (PD) is a progressive fibrotic disorder of the penis that is adverse to men's health. Currently, effective and reliable non-surgical options for PD are limited. Since the Food and Drug Administration (FDA) approved it in 2013, intralesional injection of collagenase Clostridium histolyticum (CCH) became the only licensed treatment for PD. This meta-analysis aims to evaluate the clinical efficacy and safety of CCH in treating PD, predominantly based on post-FDA studies. Methods: The primary outcome was clinical efficacy evaluated by the percentages of improvement in penile curvature (PC) and Peyronie's disease symptom bother score (PD bother score). The secondary outcome was the safety assessed by treatment-related adverse events (TRAEs). Heterogeneity was assessed by Cochran's Q and I 2 tests. Sensitivity and subgroup analyses were performed to explore the source of heterogeneity. Funnel plots and Egger's test were used to evaluate the publication bias. Results: A total of 11 studies with 1,480 intentions to treat (ITT) population were included. The pooled effect of the improvement of PC was 35% (95% CI: 0.33-0.38), and the pooled improvement of the PD bother score was 41% (95% CI: 0.37-0.45). No heterogeneity was found at the pooled improvement of PC (p = 0.845, I 2 = 0.00%). Meanwhile, some heterogeneity existed in the pooled improvement of the PD bother score (p = 0.069, I 2 = 43.4%). The pooled effect of TRAEs was 93% (95% CI 0.88-0.97) with significant heterogeneity (p < 0.000, I 2 = 92.3%). Conclusion: The intralesional injection of CCH could significantly improve the penile deformity of PD patients. Meanwhile, CCH appears to ameliorate the PD bother score to some extent and has acceptable clinical safety. Future studies are required to clarify the long-term outcomes of CCH injection in the treatment of PD.

11.
Front Endocrinol (Lausanne) ; 13: 896369, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692403

RESUMO

Background: The association between snoring and erectile dysfunction (ED) is inconsistent in multiple observational studies. To clarify the causal association of snoring on ED, we performed this two-sample Mendelian randomization study. Materials and Methods: The single nucleotide polymorphisms (SNPs) associated with snoring were retrieved from the UK biobank cohort with 314,449 participants (117,812 cases and 196,637 controls). The summary statistics of ED were obtained from the European ancestry with 223,805 subjects (6,175 cases and 217,630 controls). Single-variable Mendelian randomization (MR) and multivariable MR were used to assess the causal relationship between snoring and ED. Results: Snoring increases the risk of ED (Odds ratio [OR] = 3.45, 95% confidence interval [CI] = 1.68 - 7.09, P < 0.001) in the inverse variance weighting estimator. In sensitivity analyses, the ORs for the weighted median, MR robust adjusted profile score, and MR Pleiotropy Residual Sum and Outlier approach, MR-Egger, and maximum likelihood method are 5.70 (95% CI = 1.19 - 27.21, P < 0.05), 3.14 (95% CI = 1.01 - 9.72, P < 0.05), 3.11 (95% CI = 1.63 - 5.91, P < 0.01), 1.23 (95% CI = 0.01 - 679.73, P > 0.05), and 3.59 (95% CI = 1.07 - 12.00, P < 0.05), respectively. No heterogeneity and pleiotropy are observed (P for MR-Egger intercept = 0.748; P for global test = 0.997; P for Cochran's Q statistics > 0.05). After adjusting for total cholesterol, triglyceride, low-density lipoprotein, and cigarette consumption, the ORs for ED are 5.75 (95% CI = 1.80 - 18.34, P < 0.01), 4.16 (95% CI = 1.10 - 15.81, P < 0.05), 5.50 (95% CI = 1.62 - 18.69, P < 0.01), and 2.74 (95% CI = 1.06 - 7.10, P < 0.05), respectively. Conclusion: This study provides genetic evidence supporting the causal role of snoring in ED.


Assuntos
Disfunção Erétil , Análise da Randomização Mendeliana , Causalidade , Disfunção Erétil/complicações , Disfunção Erétil/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Ronco/complicações , Ronco/genética
12.
Front Psychiatry ; 13: 766639, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693968

RESUMO

Erectile dysfunction (ED) is a disease with a wide scope of etiologies. Obstructive sleep apnea (OSA) is considered one of the risk factors for ED and is less studied. A growing lot of evidence show an association between OSA and ED. This study provides an updated review of the relationship between ED and OSA and the possible physiological mechanisms of ED in patients with OSA based on the current evidence. In clinical interviews, patients with ED may benefit from a sleep evaluation. However, further clinical investigations and more basic research are needed to illustrate the relationship between ED and OSA.

13.
Aging Male ; 25(1): 159-166, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35635060

RESUMO

BACKGROUND: The prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) remains high in men. However, whether reduced sleep duration enhances the risk of LUTS/BPH remains unknown. MATERIALS AND METHODS: The 2015 China Health and Retirement Longitudinal Study was used in this study. Binary logistic regression was adopted to test the relationship between sleep duration and LUTS/BPH. Restricted cubic spline (RCS) regression was used to examine the non-linear association. In sensitivity analyses, propensity scores matching was performed to verify the robustness of the results. RESULTS: In this study, 8,920 males aged 40 years above were enrolled. In the fully adjusted logistic model, across the quartiles of sleep duration, the odds ratios of LUTS/BPH were 1.00 (reference), 0.94 (95% CI 0.77-1.15), 0.74 (95% CI 0.58-0.94), 0.54 (0.37-0.75), respectively. The results of RCS indicated a non-linear inverted U-shaped association between sleep duration and LUTS/BPH (p for non-linearity <0.05). In the subgroup analyses, no significant effects of settlements, alcohol and cigarette consumption, depression, and hypertension on the association between sleep duration and prevalent LUTS/BPH were observed (p for interaction >0.05). CONCLUSION: Reduced sleep duration is significantly associated with the increases of the LUTS/BPH risk in Chinese middle-aged and elderly males.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Idoso , Estudos Transversais , Humanos , Estudos Longitudinais , Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Sono
14.
Front Nutr ; 9: 843534, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495913

RESUMO

Background: The causal relationship between homocysteine (Hcy) levels and chronic kidney disease (CKD) remains unclear. This study was performed to estimate the potential causal effects of Hcy on the estimated glomerular filtration rate (eGFR) and CKD. Materials and Methods: The single nucleotide polymorphisms (SNPs) associated with one standard deviation (SD) Hcy increase were identified using the genome-wide association study (GWAS). The summary statistics of the eGFR and CKD were from the CKDGen project in the European ancestry and the Population Architecture using Genomics and Epidemiology (PAGE) project in the non-European ancestry. Two-sample Mendelian randomization (MR) analyses were used in this study to verify the causal effects among Hcy, eGFR, and CKD. Results: The results showed that 1-SD Hcy increase was causally associated with eGFR decline in the CKDGen project (ß = -0.027 log ml.min-1/1.73 m2, p < 0.01 for the overall cohort; ß = -0.028 log ml.min-1/1.73 m2, p < 0.01 after excluding the patients with diabetes). In addition, 1-SD Hcy increase was associated with a 1.32-fold risk of CKD in the PAGE project (95% CI = 1.06-1.64, p < 0.05). The association was directionally similar in the CKDGen project [odds ratio (OR) = 1.08, 95% CI = 0.97-1.44, p = 0.098]. The pooled OR of CKD was 1.24 (95% CI = 1.07-1.44, p < 0.05) per 1-SD Hcy increase. Conclusion: Using genetic data, Hcy increase is causally associated with renal function injury and further CKD.

15.
Int J Biol Sci ; 18(3): 1107-1119, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173542

RESUMO

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood.


Assuntos
Células Epiteliais Alveolares , Surfactantes Pulmonares , Animais , Autofagia/genética , Corpos Lamelares , Lisossomos/metabolismo , Camundongos , Surfactantes Pulmonares/metabolismo , Tensoativos/metabolismo
16.
J Transl Med ; 20(1): 47, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090513

RESUMO

Cumulative evidence indicates that the abnormal regulation of the NEDD4 family of E3-ubiquitin ligases participates in the tumorigenesis and development of cancer. However, their role in lung adenocarcinoma (LUAD) remains unclear. This study comprehensively analyzed the NEDD4 family in LUAD data sets from public databases and found only NEDD4L was associated with the overall survival of LUAD patients. Gene set enrichment analysis (GSEA) indicated that NEDD4L might be involved in the regulation of mTORC1 pathway. Both cytological and clinical assays showed that NEDD4L inhibited the activity of the mTOR signaling pathway. In vivo and in vitro experiments showed that NEDD4L could significantly inhibit the proliferation of LUAD cells. In addition, this study also found that the expression of NEDD4L was regulated by EGFR signaling. These findings firstly revealed that NEDD4L mediates an interplay between EGFR and mTOR pathways in LUAD, and suggest that NEDD4L held great potential as a novel biomarker and therapeutic target for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Proliferação de Células/genética , Regulação para Baixo/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Ubiquitina-Proteína Ligases Nedd4 , Transdução de Sinais
17.
Andrology ; 10(1): 143-153, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333872

RESUMO

BACKGROUND: Intracavernous pressure measurement following cavernous nerve electrostimulation has been extensively adopted for the evaluation of erectile function in animals. However, the effect of measurement time and acidosis during anesthesia is still lacking. OBJECTIVE: To explore the effect of measurement time and acidosis during anesthesia. MATERIALS AND METHODS: Fifty-six male Sprague-Dawley rats were used and anesthetized by a spontaneous inhalation of isoflurane. In the first step, rats were randomly divided into four groups: a control group and three time-delayed measurement groups (intracavernous pressure measurement beginning at 15, 30, and 45 min after cavernous nerve exposure). In the second step, rats were randomly divided into three groups: a control group and two time-delayed measurement groups. Two intravenous fluid support strategies were used in time-delayed measurement groups: a normal saline solution and an isotonic Na2 CO3 solution. RESULTS: Isoflurane-anesthetized rats developed systemic acidosis that worsens with time during intracavernous pressure measurement, which results in a significant decrease in the maximum intracavernous pressure value, intracavernous pressure/mean arterial pressure ratio, and total intracavernous pressure measured. The Na2 CO3 infusion could effectively correct acidosis. The decrease in intracavernous pressure was related to the reduced nitric oxide synthase activity, decreased cyclic guanosine monophosphate concentration, and reactive oxygen species activation in rat penis under acidosis conditions. DISCUSSION AND CONCLUSION: Prolonged isoflurane anesthesia-induced acidosis markedly depresses the erectile response to cavernous nerve electrostimulation in rats. In this situation, it is recommended to supplement with a Na2 CO3 infusion to maintain a normal acid-base balance.


Assuntos
Acidose/fisiopatologia , Anestésicos Inalatórios/farmacologia , Pressão Arterial/efeitos dos fármacos , Isoflurano/farmacologia , Pênis/irrigação sanguínea , Acidose/induzido quimicamente , Anestésicos Inalatórios/efeitos adversos , Animais , Modelos Animais de Doenças , Estimulação Elétrica , Disfunção Erétil , Isoflurano/efeitos adversos , Masculino , Ereção Peniana/efeitos dos fármacos , Pênis/inervação , Ratos , Ratos Sprague-Dawley
18.
Food Funct ; 13(2): 501-513, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34928288

RESUMO

Aging is frequently accompanied by various types of physiological deterioration, which increases the risk of human pathologies. Global public health efforts to increase human lifespan have increasingly focused on lowering the risk of aging-related diseases, such as diabetes, neurodegenerative diseases, cardiovascular disease, and cancers. Dietary intervention is a promising approach to maintaining human health during aging. Lactoferrin (LF) is known for its physiologically pleiotropic properties. Anti-aging interventions of LF have proven to be safe and effective for various pharmacological activities, such as anti-oxidation, anti-cellular senescence, anti-inflammation, and anti-carcinogenic. Moreover, LF has a pivotal role in modulating the major signaling pathways that influence the longevity of organisms. Thus, LF is expected to be able to attenuate the process of aging and greatly ameliorate its effects.


Assuntos
Lactoferrina , Substâncias Protetoras , Envelhecimento/efeitos dos fármacos , Animais , Anti-Inflamatórios , Humanos , Lactoferrina/química , Lactoferrina/farmacologia , Camundongos , Modelos Biológicos , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia
19.
Front Chem ; 10: 1063284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618870

RESUMO

Two undescribed butenolide derivatives, asperteretal J (1) and K (2), together with 13 known ones (3-15) were isolated from an endophytic fungus Aspergillus terreus SGP-1, the fermentation product of which exhibited selective inhibitory activity toward butyrylcholinesterase. The structures of the new compounds were elucidated based on HRMS and NMR data, and the absolute configurations were determined by specific optical rotation comparison. All compounds were evaluated for cholinesterase inhibitory effects with galantamine as a positive control. Compounds 4-8 selectively inhibited butyrylcholinesterase with IC50 values of 18.4-45.8 µM in a competitive manner, with Ki values of 12.3-38.2 µM. The structure-activity relationship was discussed. Molecular docking and dynamic simulation of the inhibitor-enzyme complex were performed to better understand the interactions.

20.
Aging Male ; 24(1): 148-159, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34751610

RESUMO

BACKGROUND: Currently, China has an increasingly aging population. However, the prevalence of metabolic syndrome (MetS) in this high-risk population for metabolic diseases remains unknown. This study investigates the age- and gender-specific prevalence and associated factors of MetS in the middle-aged and elderly Chinese population. METHODS: Data were collected and subjected to descriptive statistics. Further, univariate logistic regression was used to evaluate the relevant factors, and then multivariate logistic regression was selected to construct the final model. RESULTS: A total of 10,834 participants were included in the present study. The overall prevalence of MetS is 32.97% as defined by International Diabetes Federation (IDF) and 29.75% under National Cholesterol Education Program-The Adult Treatment Panel III (NCEP-ATP III) criteria. With aging, the prevalence of MetS descends in males while ascends in females. In the >70 years old group, the prevalence of MetS is three times higher in females than that in males (50.43% versus 16.03%). Across all age groups and sexes, the prevalence of MetS in urban areas is significantly higher than in rural areas. Besides, regardless of gender, the prevalence of MetS is the highest for those living in the north region (28.41% for males and 51.74% for females) and the lowest for those living in the southwest region (13.91% for males and 31.58% for females). Finally, an afternoon nap has been identified as a positively associated factor, while blood urea nitrogen (BUN) has been identified as a negatively associated factor (p < 0.05). CONCLUSION: The prevalence of MetS varies in different age groups, sexes, living areas, and regions. An afternoon nap is positively associated with the prevalence of MetS, while BUN is negatively associated with MetS.


Assuntos
Síndrome Metabólica , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
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