Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
1.
Int J Mol Sci ; 25(10)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38791274

RESUMEN

Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFß1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune-inflammatory processes and the tissue remodeling caused by aging.


Asunto(s)
Envejecimiento , Restricción Calórica , Inflamación , Proteína con Dominio Pirina 3 de la Familia NLR , Próstata , Ratas Sprague-Dawley , Animales , Masculino , Restricción Calórica/métodos , Ratas , Próstata/metabolismo , Próstata/patología , Envejecimiento/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamación/metabolismo , Inflamación/patología , Factor de Crecimiento Transformador beta1/metabolismo , Inflamasomas/metabolismo , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Estrés Oxidativo , Fibrosis , Superóxido Dismutasa-1/metabolismo
2.
Stud Health Technol Inform ; 314: 58-62, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38785004

RESUMEN

Stroke remains a significant global health burden, with substantial costs and morbidity associated with its occurrence. To address this challenge, STROKE 5.0 proposes a comprehensive approach to stroke care management, integrating advanced digital technologies and clinical expertise. This paper presents the rationale, design, and potential impact of the STROKE 5.0 platform, which aims to optimize stroke care delivery from pre-hospital assessment through acute hospitalization. The platform facilitates early symptom recognition, efficient emergency response, and streamlined hospital management through intelligent decision support systems. By leveraging predictive analytics and personalized care pathways, STROKE 5.0 seeks to enhance clinical outcomes while providing a platform capable of optimizing the efficiency of service delivery. This innovative model represents a proactive shift towards evidence-based, patient-centered stroke care, with implications for healthcare quality improvement and resource allocation in the digital health domain.


Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Prestación Integrada de Atención de Salud
3.
Life (Basel) ; 14(4)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38672713

RESUMEN

Partial nephrectomy (PN) is the primary surgical method for renal tumor treatment, typically involving clamping the renal artery during tumor removal, leading to warm ischemia and potential renal function impairment. Off-clamp approaches have been explored to mitigate organ damage, yet few results have emerged about the possible effects on hemoglobin loss. Most evidence comes from retrospective studies using propensity score matching, known to be sensitive to PS model misspecification. The energy balancing weights (EBW) method offers an alternative method to address bias by focusing on balancing all the characteristics of covariate distribution. We aimed to compare on- vs. off-clamp techniques in PN using EB-weighted retrospective patient data. Out of 333 consecutive PNs (275/58 on/off-clamp ratio), the EBW method achieved balanced variables, notably tumor anatomy and staging. No significant differences were observed in the operative endpoints between on- and off-clamp techniques, although off-clamp PNs showed slight reductions in hemoglobin loss and renal function decline, albeit with slightly higher perioperative blood loss. Our findings support previous evidence, indicating comparable surgical outcomes between standard and off-clamp procedures, with the EBW method proving effective in balancing baseline variables in observational studies comparing interventions.

4.
Nutrients ; 16(5)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38474715

RESUMEN

Gut dysbiosis refers to an imbalance in gut microbiota composition and function. Opuntia ficus-indica extract has been shown to modulate gut microbiota by improving SCFA production in vivo and gastrointestinal discomfort (GD) in humans. The aim of this study was to demonstrate the efficacy of OdiliaTM on gastrointestinal health by changing the microbial diversity of species involved in inflammation, immunity, oxidation, and the brain-gut-muscle axis. A randomized, double-blind clinical trial was conducted in 80 adults with gut dysbiosis. The intervention consisted of a 300 mg daily intake of OdiliaTM (n = 40) or maltodextrin as a placebo (n = 40), administered for 8 weeks. Intervention effect was evaluated using 16S metagenomics and GIQLI/GSAS scores at baseline, at 4 and 8 weeks. Eight weeks of OdiliaTM supplementation positively modulates gut microbiota composition with a significant reduction in the Firmicutes to Bacteroidetes ratio (p = 0.0012). Relative abundances of beneficial bacteria (Bacteroides and Clostridium_XIVa) were significantly increased (p < 0.001), in contrast to a significant reduction in pro-inflammatory bacteria (p < 0.001). Accordingly, GIQLI and GSAS scores revealed successful improvement in GD. OdiliaTM may represent an effective and well-tolerated treatment in subjects with gut dysbiosis.


Asunto(s)
Opuntia , Prebióticos , Adulto , Humanos , Disbiosis/microbiología , Heces/microbiología , Bacterias , Método Doble Ciego
5.
Int J Mol Sci ; 24(4)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36835594

RESUMEN

Nod-like receptor protein 3 (NLRP3) is a multi-protein complex belonging to the innate immune system, whose activation by danger stimuli promotes inflammatory cell death. Evidence supports the crucial role of NLRP3 inflammasome activation in the transition of acute kidney injury to Chronic Kidney Disease (CKD), by promoting both inflammation and fibrotic processes. Variants of NLRP3 pathway-related genes, such as NLRP3 itself and CARD8, have been associated with susceptibility to different autoimmune and inflammatory diseases. In this study, we investigated for the first time the association of functional variants of NLRP3 pathway-related genes (NLRP3-rs10754558, CARD8-rs2043211), with a susceptibility to CKD. A cohort of kidney transplant recipients, dialysis and CKD stage 3-5 patients (303 cases) and a cohort of elderly controls (85 subjects) were genotyped for the variants of interest and compared by using logistic regression analyses. Our analysis showed a significantly higher G allele frequency of the NLRP3 variant (67.3%) and T allele of the CARD8 variant (70.8%) among cases, compared with the control sample (35.9 and 31.2%, respectively). Logistic regressions showed significant associations (p < 0.001) between NLRP3 and CARD8 variants and cases. Our results suggest that the NLRP3 rs10754558 and CARD8 rs2043211 variants could be associated with a susceptibility to CKD.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD , Proteína con Dominio Pirina 3 de la Familia NLR , Insuficiencia Renal Crónica , Anciano , Humanos , Proteínas Adaptadoras de Señalización CARD/genética , Predisposición Genética a la Enfermedad , Genotipo , Inflamasomas/genética , Proteínas de Neoplasias/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Polimorfismo de Nucleótido Simple , Diálisis Renal , Insuficiencia Renal Crónica/genética
6.
Life (Basel) ; 14(1)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38255667

RESUMEN

Cancer has been described as a risk factor for greater susceptibility to SARS-CoV-2 infection and severe COVID-19, mainly for patients with metastatic disease. Conversely, to that reported for most solid and hematological malignancies, the few available clinical studies reported that the infection did not increase the risk of death in renal cancer patients. The expression on proximal tubular renal cells of the key players in cellular viral uptake, ACE2, TMPRSS2, and NRP1, seems to be the mechanism for the direct kidney injury seen in patients with COVID-19. Interestingly, data from The Cancer Genome Atlas and experimental analyses on various renal cancer cell lines demonstrated that the above-reported receptors/cofactors are maintained by renal cancer cells. However, whether SARS-CoV-2 infection directly kills renal cancer cells or generates enhanced immunogenicity is a question worth investigating. In addition, some researchers have further addressed the topic by studying the expression and prognostic significance of gene signatures related to SARS-CoV-2 infection in renal cancer patients. The emerging data highlights the importance of better understanding the existence of a link between renal cancer and COVID-19 since it could lead to the identification of new prognostic factors and the development of new therapeutic targets in the management of renal cancer patients.

7.
Artículo en Inglés | MEDLINE | ID: mdl-36177957

RESUMEN

The nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) inflammasome, a multiprotein complex belonging to the innate immune system, plays a key role in the chronic inflammatory response, through the production of proinflammatory cytokines, IL-1ß and IL-18, which can elicit their effects through receptor activation, both locally and systemically. Furthermore, it has been demonstrated the interaction of NLRP3 inflammasome components with redox signaling, endoplasmic reticulum stress, and mitochondrial function. A growing literature reported the involvement of NLRP3 platform dysregulation in the pathophysiology of different chronic diseases so it has been proposed that the inhibition of NLRP3 inflammasome could represent a new potential therapeutic target in the management of autoimmune and chronic inflammatory diseases, including cancer. In addition, it has been demonstrated that Sars-CoV2 preferentially activates NLRP3 inflammasome, strongly contributing to the hyperinflammatory state responsible for COVID-19. Recently, in vitro and animal models of both infectious and non-infectious male genital tract diseases affecting fertility, demonstrated the activation of the innate immune system, leading to increased levels of pro-inflammatory cytokines, as well as apoptosis and pyroptosis and that it was likely mediated by activation of the NLRP3 inflammasome. The objective of this review was to analyze the evidence on the role and the mechanisms by which NLRP3-inflammasome pathway activation may exert detrimental effects on the male reproductive system. Furthermore, although the literature data are still discordant, this review also highlighted the possible connection between SARS-CoV-2 infection/NLRP3 activation/oxidative stress and male infertility.

8.
Exp Dermatol ; 31(2): 143-153, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34331820

RESUMEN

The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study, we explored whether the activation of the autophagic pathway through the low-affinity receptor for nerve growth factor, p75NTR , may have a pivotal role in the anti-cancer effect exerted by Rapamycin in S. Our Kimmunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. In vitro experiments on KS cell lines showed that Rapamycin exposure reduced cell viability by increasing the autophagic process, in the absence of apoptosis, through the transcriptional activation of p75NTR via EGR1. Interestingly, p75NTR gene silencing prevented the increase of the autophagic process and the reduction of cell viability. Moreover, p75NTR activation promoted the upregulation of phosphatase and tensin homolog (PTEN), a tumour suppressor that modulates the PI3K/Akt/mTOR pathway. In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi's sarcoma, autophagy triggered by Rapamycin through p75NTR represented a major mechanism by which mTOR inhibitors may induce tumour regression. Additionally, it suggested that p75NTR protein analysis could be proposed as a new potential biomarker to predict response to Rapamycin in kidney transplant recipients affected by Kaposi's sarcoma.


Asunto(s)
Sarcoma de Kaposi , Sirolimus , Apoptosis , Autofagia , Humanos , Fosfatidilinositol 3-Quinasas , Sarcoma de Kaposi/patología , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo
9.
Brain Sci ; 11(6)2021 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-34204352

RESUMEN

We propose a new set of clinical variables for a more accurate early prediction of safe decannulation in patients with severe acquired brain injury (ABI), during a post-acute rehabilitation course. Starting from the already validated DecaPreT scale, we tested the accuracy of new logistic regression models where the coefficients of the original predictors were reestimated. Patients with tracheostomy were retrospectively selected from the database of the neurorehabilitation unit at the S. Anna Institute of Crotone, Italy. New potential predictors of decannulation were screened from variables collected on admission during clinical examination, including (a) age at injury, (b) coma recovery scale-revised (CRS-r) scores, and c) length of ICU period. Of 273 patients with ABI (mean age 53.01 years; 34% female; median DecaPreT = 0.61), 61.5% were safely decannulated before discharge. In the validation phase, the linear logistic prediction model, created with the new multivariable predictors, obtained an area under the receiver operating characteristics curve of 0.901. Our model improves the reliability of simple clinical variables detected at the admission of the post-acute phase in predicting decannulation of ABI patients, thus helping clinicians to plan better rehabilitation.

10.
Life (Basel) ; 11(7)2021 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-34209730

RESUMEN

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.

11.
Minerva Endocrinol (Torino) ; 46(3): 309-316, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33855388

RESUMEN

BACKGROUND: The activation of NLRP3 inflammasome machinery has a central role in obesity-induced inflammation. Genetic studies well support the involvement of functional variants of NLRP3 and its negative regulator, CARD8, in the pathogenesis of complex diseases with an inflammatory background. We have investigated the influence of NLRP3 (rs4612666; rs10754558) and CARD8 (rs204321) genetic variants in both the inflammatory status of visceral adipose tissue (VAT) from patients with severe obesity and in the systemic oxidative stress before and after sleeve-gastrectomy (SLG). METHODS: Twenty-three consecutive severe obese patients candidate to SLG were enrolled in the study. Visceral adipose tissue (VAT) biopsies, obtained during SLG, were used to evaluate the expression of NLRP3, IL-1ß, IL-6, and MCP-1 by real-time RT-PCR. DNA was extracted from peripheral blood lymphocytes and genotyped by RFLP analysis. Before and 3 months after SLG, all patients underwent the assessment of oxidative stress, biochemical parameters, and body composition as measured by bioelectrical impedance analysis (BIA). RESULTS: Increased expression of NLRP3, IL-6, IL-1ß, and MCP-1 mRNA was observed in VAT of rs4612666 C variant carriers, in which higher oxidative stress was also detected as compared to non-carrier individuals. In all patients, oxidative stress, biochemical and BIA parameters improved after SLG, regardless of genotype. No significant correlations were found with the other genetic variants. CONCLUSIONS: Our results suggest that the NLRP3 rs4612666 C variant may promote a worse pro-inflammatory milieu and higher oxidative stress, thus leading patients to a more severe obesity phenotype. A larger study is needed to confirm this assumption and to investigate the impact of the NLRP3 rs4612666 C variant on severe obesity.


Asunto(s)
Grasa Intraabdominal , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas Adaptadoras de Señalización CARD/metabolismo , Humanos , Inflamasomas/genética , Grasa Intraabdominal/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteínas de Neoplasias/metabolismo , Obesidad/genética , Estrés Oxidativo/genética
12.
Front Hum Neurosci ; 14: 570544, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33192402

RESUMEN

In this study, we sought to assess the predictors of outcome in patients with disorders of consciousness (DOC) after severe traumatic brain injury (TBI) during neurorehabilitation stay. In total, 96 patients with DOC (vegetative state, minimally conscious state, or emergence from minimally conscious state) were enrolled (69 males; mean age 43.6 ± 20.8 years) and the improvement of the degree of disability, as assessed by the Disability Rating Scale, was considered the main outcome measure. To define the best predictor, a series of demographical and clinical factors were modeled using a twofold approach: (1) logistic regression to evaluate a possible causal effect among variables; and (2) machine learning algorithms (ML), to define the best predictive model. Univariate analysis demonstrated that disability in DOC patients statistically decreased at the discharge with respect to admission. Genitourinary was the most frequent medical complication (MC) emerging during the neurorehabilitation period. The logistic model revealed that the total amount of MCs is a risk factor for lack of functional improvement. ML discloses that the most important prognostic factors are the respiratory and hepatic complications together with the presence of the upper gastrointestinal comorbidities. Our study provides new evidence on the most adverse short-term factors predicting a functional recovery in DOC patients after severe TBI. The occurrence of medical complications during neurorehabilitation stay should be considered to avoid poor outcomes.

14.
J Clin Med ; 9(6)2020 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-32630390

RESUMEN

Patients with kidney transplantation often have a worse quality of life than the general population. One of the reasons for this, in male patients, is the high prevalence of erectile dysfunction. This is mainly due to the presence of comorbidities, surgery for kidney transplantation, adverse drug effects, psychological changes related to chronic disease, as well as hyperprolactinemia and hypogonadism. Whenever these endocrine dysfunctions occur after kidney transplantation, they must be corrected with appropriate treatment, i.e., testosterone replacement therapy. Administration of the phosphodiesterase-5 inhibitor (PDE5i) sildenafil at the recommended posology does not significantly alter the pharmacokinetics of the calcineurin inhibitors cyclosporin A or tacrolimus and does not impair kidney allograft function. Tacrolimus increases the peak concentration and prolongs the half-life of PDE5i in kidney transplant patients and, therefore, daily administration cannot be recommended due to the significant drop in blood pressure. Intracavernous injection or topical application of alprostadil can be a second-line option for the treatment of erectile dysfunction after kidney transplantation, which does not alter cyclosporine concentrations and does not deteriorate kidney function. Finally, penile prostheses can be successfully implanted following pelvic organ transplantation after eliminating the risk of infection associated with surgery.

15.
Int J Food Sci Nutr ; 71(5): 581-592, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31690142

RESUMEN

In this cross-sectional web-survey, carried out in 340 employees (24-67 years) among university staff of Southern Italy, we assessed the adherence to the Mediterranean Diet (MD). Using an online questionnaire based on validated 14-point MD Adherence Screener (MEDAS), the mean of the score was 7.34 (±1.9) for total population independently of sex. In population divided by the cut-off age of 45 years, MD adherence resulted significantly lower in younger respect to older group (p = .003). In multiple regression analyses we observed the direct association between MEDAS score and older age group also after adjustments. Importantly, in all sample the percentage of adherers to recommendations for fruits, nuts and fish resulted outside dietary guidelines. The present findings underscore the need to develop healthy education programmes aimed to improve the consumption of several components of the MD, particularly among young adults, in order to prevent the early onset of chronic non-transmittable diseases.


Asunto(s)
Dieta Mediterránea , Conducta Alimentaria , Conductas Relacionadas con la Salud , Universidades , Adulto , Factores de Edad , Anciano , Estudios Transversales , Encuestas sobre Dietas , Femenino , Humanos , Internet , Italia/epidemiología , Masculino , Persona de Mediana Edad , Política Nutricional , Adulto Joven
16.
J Clin Med ; 8(9)2019 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-31500383

RESUMEN

Recent epidemiological studies suggest an increase of sexual and reproductive chronic diseases caused by problematic behaviours acquired during peri-pubertal age. The aims of our study were: (i) to investigate awareness of sexual transmitted infections (STIs) among adolescents; (ii) to describe the close relationship between possibly incorrect lifestyles during adolescence and reproductive and sexual disturbances during adulthood. The "Amico-Andrologo" survey is a permanent nationwide surveillance program supported by the Italian Ministry of Health. We administered a validated structured interview to investigate the lifestyle of adolescents and their knowledge of STIs. We selected a cohort of 360 male high-school students aged ≥18 years old. In this cohort, 150 (41.5%) were smokers while 59 (19.7%) smoked more than 10 cigarettes/day; 25 (9.3%) declared a consumption ≥6 drinks/weekend; and 65 (19.7%) were habitual cannabis consumers (at least twice/week). Among the sample of students selected, the main sources of sexual disease information were the internet and friends. The perceived level of knowledge on STIs was the same between students that used contraceptive methods and students that did not. The present results demonstrate that adolescents in Calabria do not receive appropriate information about risky health behaviours. Therefore, there is a necessity for specific educational programs to increase awareness of dangerous behaviours during the transitional age that is relevant for a safe sexual and reproductive adult life.

17.
BMC Neurol ; 19(1): 68, 2019 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-30999877

RESUMEN

BACKGROUND: To evaluate the utility of the revised coma remission scale (CRS-r), together with other clinical variables, in predicting emergence from disorders of consciousness (DoC) during intensive rehabilitation care. METHODS: Data were retrospectively extracted from the medical records of patients enrolled in a specialized intensive rehabilitation unit. 123 patients in a vegetative state (VS) and 57 in a minimally conscious state (MCS) were included and followed for a period of 8 weeks. Demographical and clinical factors were used as outcome measures. Univariate and multivariate Cox regression models were employed for examining potential predictors for clinical outcome along the time. RESULTS: VS and MCS groups were matched for demographical and clinical variables (i.e., age, aetiology, tracheostomy and route of feeding). Within 2 months after admission in intensive neurorehabilitation unit, 3.9% were dead, 35.5% had a full recovery of consciousness and 66.7% remained in VS or MCS. Multivariate analysis demonstrated that the best predictor of functional improvement was the CRS-r scores. In particular, patients with values greater than 12 at admission were those with a favourable likelihood of emergence from DoC. CONCLUSIONS: Our study highlights the role of the CRS-r scores for predicting a short-term favorable outcome.


Asunto(s)
Trastornos de la Conciencia , Recuperación de la Función , Índice de Severidad de la Enfermedad , Adulto , Anciano , Coma , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
18.
Nutr Cancer ; 71(2): 320-333, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30661406

RESUMEN

Most of the common drugs used to treat the cervical cancer, which main etiological factor is the HPV infection, cause side effects and intrinsic/acquired resistance to chemotherapy. In this study we investigated whether an olive leaf extract (OLE), rich in polyphenols, was able to exert anti-tumor effects in human cervical cancer cells (HeLa). MTT assay results showed a reduction of HeLa cells viability OLE-induced, concomitantly with a gene and protein down-regulation of Cyclin-D1 and an up-regulation of p21, triggering intrinsic apoptosis. OLE reduced NFkB nuclear translocation, which constitutive activation, stimulated by HPV-oncoproteins, promotes cancer progression and functional studies revealed that OLE activated p21Cip/WAF1 in a transcriptional-dependent-manner, by reducing the nuclear recruitment of NFkB on its responsive elements. Furthermore, OLE treatment counteracted epithelial-to-mesenchymal-transition and inhibited anchorage-dependent and -independent cell growth EGF-induced. Finally, MTT assay results revealed that OLE plus Cisplatin strengthened the reduction of cells viability Cisplatin-induced, as OLE inhibited NFkB, AkT and MAPK pathways, all involved in Cisplatin chemoresistance. In conclusion, we demonstrated that in HeLa cells OLE exerts pro-apoptotic effects, elucidating the molecular mechanism and that OLE could mitigate Cisplatin chemoresistance. Further studies are needed to explore the potential coadiuvant use of OLE for cervical cancer treatment.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Olea/química , Extractos Vegetales/farmacología , Polifenoles/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Quinasas p21 Activadas/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Células HeLa , Humanos , Regulación hacia Arriba/efectos de los fármacos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología
19.
Transpl Infect Dis ; 21(1): e13027, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30431214

RESUMEN

INTRODUCTION: Cytomegalovirus (CMV) infection represents a common cause of morbidity and mortality in kidney transplant recipients (KTR). The NF-kB signaling pathway is highly involved in the pathogenesis of CMV infection. The -94ins/delATTG functional polymorphism in the promoter of NFKB1 has been associated with low intracellular levels of the protein and high incidence of inflammatory and autoimmune disease. In this study, we evaluated the association of this NFKB1 polymorphism with the risk of CMV infection. METHODS: CMV infection was defined as virus isolation or detection of viral antigens or nucleic acid in any body fluid or tissue specimen. Using Cox regression and survival analysis, we analyzed the association between the polymorphism and CMV infection as well as recurrence in the first 12 months after transplantation. RESULTS: We analyzed the -94ins/delATTG NFKB1 polymorphism of 189 KTRs. The 65% of CMV infections occurred in ins/ins group. Survival free from CMV infection was 54.7% for ins/ins group and 79.4% for deletion carriers one year after transplantation (P < 0.0001). At multivariate regression, deletion carriers showed a lower risk of CMV infection and recurrence with respect to ins/ins KTRs (HR = 0.224 P = 0.0002; HR = 0.307, P = 0.012, respectively). CONCLUSIONS: In conclusion, pretransplantation screening for NFKB1 -94ins/delATTG polymorphism may predict CMV infection and improve the management of patients at higher risk of infection in the post-transplant period.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Trasplante de Riñón/efectos adversos , Subunidad p50 de NF-kappa B/genética , Complicaciones Posoperatorias/diagnóstico , Regiones Promotoras Genéticas/genética , Adulto , Biomarcadores/análisis , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Humanos , Mutación INDEL , Incidencia , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/genética , Complicaciones Posoperatorias/virología , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/métodos , Pronóstico
20.
J Nephrol ; 31(5): 775-783, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30019104

RESUMEN

BACKGROUND: Clinical studies have demonstrated that, after renal transplantation (TX), testosterone deficiency (TD) at the time of the procedure is independently associated with lower survival of the patient and graft. However, data between TD and the functional CAG polymorphism of the androgen receptor promoter (AR) are discordant. We investigated the prevalence of TD and its association with body composition, biochemical parameters, the Aging Males' Symptoms rating scale (AMS) domains and AR polymorphism. METHODS: In 112 TX patients, we assessed the AMS, biochemical/hormonal (FSH/LH/TT) anthropometric/bioimpedance analysis parameters, and AR CAG polymorphism of AR by gene sequencing. RESULTS: Median values of total testosterone (TT) were 340 ng/dl and 52% of TX patients were affected by TD. Significant correlations between TT and FSH and FSH and LH (p = 0.005, p < 0.0001, respectively) were found. TD patients had lower estimated glomerular filtration rate (eGFR) and hemoglobin (Hb) (p = 0.034, p = 0.022 respectively) and showed higher values of C-reactive protein (p = 0.023) and fat tissue index/adipose tissue mass (p = 0.034 and p = 0.021, respectively), and lower values of serum albumin (p = 0.003) and high-density lipoprotein-cholesterol (p = 0.038) levels. Significant differences were found in the number of patients on mammalian target of rapamycin inhibitors immunosuppressant therapy (p = 0.045). Logistic regression analysis did not show any correlation between age, AMS scores, TT or CAG repeat length, gonadotropins, time of the transplant, and dialysis. CONCLUSIONS: Our results suggest that in TX recipients an appropriate sexual hormonal evaluation should be performed, as we found a high prevalence of TD. However, further studies are needed to clarify the association between TD and patient and graft survival.


Asunto(s)
Composición Corporal , Hipogonadismo/sangre , Trasplante de Riñón , Insuficiencia Renal Crónica/cirugía , Testosterona/deficiencia , Receptores de Trasplantes , Adulto , Anciano , Biomarcadores/sangre , Hormona Folículo Estimulante/sangre , Humanos , Hipogonadismo/epidemiología , Hipogonadismo/genética , Hipogonadismo/fisiopatología , Italia/epidemiología , Trasplante de Riñón/efectos adversos , Hormona Luteinizante/sangre , Persona de Mediana Edad , Polimorfismo Genético , Prevalencia , Receptores Androgénicos/genética , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Testosterona/sangre , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...