Search results for "Tea"

Identification of noncovalent proteasome inhibitors with high selectivity for chymotrypsin-like activity by a multistep structure-based virtual scree…

2016

Noncovalent proteasome inhibitors introduce an alternative mechanism of inhibition to that of covalent inhibitors, e.g. carfilzomib, used in cancer therapy. A multistep hierarchical structure-based virtual screening (SBVS) of the 65,375 NCI lead-like compound library led to the identification of two compounds (9 and 28) which noncovalently inhibited the chymotrypsin-like (ChT-L) activity (Ki = 2.18 and 2.12 μM, respectively) with little or no effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and post-glutamyl peptide hydrolase (PGPH) activities. A subsequent hierarchical similarity search over the full NCI database with the most active tripeptide-based inh…

BRCA1/2 molecular assay for ovarian cancer patients: A survey through Italian departments of oncology and molecular and genomic diagnostic laboratori…

2019

In Italy, 5200 new ovarian cancers were diagnosed in 2018, highlighting an increasing need to test women for BRCA1/2. The number of labs offering this test is continuously increasing. The aim of this study was to show the results coming from the intersociety survey coordinated by four different Clinical and Laboratory Italian Scientific Societies (AIOM, SIAPEC-IAP, SIBIOC, and SIGU). A multidisciplinary team belonging to the four scientific societies drew up two different questionnaires: One was targeted toward all Italian Departments of Medical Oncology, and the second toward laboratories of clinical molecular biology. This survey was implemented from September 2017 to March 2018. Seventy-…

New Insights into the Occurrence of Matrix Metalloproteases -2 and -9 in a Cohort of Breast Cancer Patients and Proteomic Correlations

2018

Matrix metalloproteases (MMPS) are a family of well-known enzymes which operate prevalently in the extracellular domain, where they fulfil the function of remodeling the extracellular matrix. Within the about 26 family members, encoded by 24 genes in humans, MMP-2 and MMP-9, have been regarded as the primary responsibility for the basement membrane and pericellular ECM rearrangement. In cases of infiltrating carcinomas, which arise from the epithelial tissues of a gland or of an internal organ, a marked alteration of the expression and the activity levels of both MMPs is known to occur. Present investigation represents the continuation and upgrading of our previous studies, now focusing on …

2017

Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of …

A "systems medicine" approach to the study of non-alcoholic fatty liver disease

2016

a b s t r a c t The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diag- nosis criteria, and new endpoints of clinical trials).…

Two-year-old girl with tuberous xanthomas.

2018

A 2-year-old girl was referred for evaluation because she had two nodular lesions located on both heels, and another elongated lesion in the intergluteal cleft. On physical examination, two yellow to orange well-defined nodules, suggestive of xanthomas, were bilaterally located on the Achilles tendon areas (figure 1A). Moreover, another yellowish, slightly raised lesion with band-like morphology was seen in the intergluteal cleft (figure 1B). There were no other anomalies on physical examination. Figure 1 (A) Tuberous xanthoma located on the left heel. (B) Planar xanthoma located in the intergluteal cleft. (C) Peripheral blood smear examination showing numerous red cells and two macrothromb…

Guidelines are silver, but a multidisciplinary team discussion may be golden?

2018

Autoimmune polyglandular diseases.

2019

Autoimmune polyglandular diseases (APD) are defined as the presence of two autoimmune -induced endocrine failures. With respect to the significant morbidity and potential mortality of APD, the diagnostic objective is to detect APD at an early stage, with the advantage of less frequent complications, effective therapy and better prognosis. This requires that patients at risk be regularly screened for subclinical endocrinopathies prior to clinical manifestation. Regarding the time interval between manifestation of first and further endocrinopathies, regular and long-term follow-up is warranted. Quality of life and psychosocial status are poor in APD patients and involved relatives. Familial c…

Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.

2019

Abstract Objectives In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mg·h/L at steady-state in at least 80% of neonates. Results A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if &lt…

Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease

2017

BACKGROUND AND AIMS: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model.METHODS: Rats were fed a high-fat, high-cholesterol (HFHC) diet for four weeks resulting in moderately severe NASH. Animals were treated with intravenous NPC2 or placebo twice weekly for either the last two weeks or the entire four weeks. End-points were liver/body- and spleen/body…