263 research outputs found
An update on vitamin d metabolism
Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver hydroxylase CYP2R1, the specificity of 1α-hydroxylase in different tissues and cell types and the genomic, non-genomic and epigenomic effects of vitamin D receptor, which will be addressed in the present review. Moreover, in the last decades, several extraskeletal effects which can be attributed to vitamin D have been shown. These beneficial effects will be here summarized, focusing on the immune system and cardiovascular system
Transthyretin stabilization: An emerging strategy for the treatment of alzheimerâs disease?
Transthyretin (TTR), previously named prealbumin is a plasma protein secreted mainly by the liver and choroid plexus (CP) that is a carrier for thyroid hormones (THs) and retinol (vitamin A). The structure of TTR, with four monomers rich in ÎČ-chains in a globular tetrameric protein, accounts for the predisposition of the protein to aggregate in fibrils, leading to a rare and severe disease, namely transthyretin amyloidosis (ATTR). Much effort has been made and still is required to find new therapeutic compounds that can stabilize TTR (âkinetic stabilizationâ) and prevent the amyloid genetic process. Moreover, TTR is an interesting therapeutic target for neurodegenerative diseases due to its recognized neuroprotective properties in the cognitive impairment context and interestingly in Alzheimerâs disease (AD). Much evidence has been collected regarding the neuroprotective effects in AD, including through in vitro and in vivo studies as well as a wide range of clinical series. Despite this supported hypothesis of neuroprotection for TTR, the mechanisms are still not completely clear. The aim of this review is to highlight the most relevant findings on the neuroprotective role of TTR, and to summarize the recent progress on the development of TTR tetramer stabilizers
Normocalcemic primary hyperparathyroidism: a survey in a small village of Southern Italy
We investigated the prevalence of normocalcemic primary hyperparathyroidism (NPHPT) in the adult population living in a village in Southern Italy. All residents in 2010 (n=2045) were invited by calls and 1046 individuals accepted to participate. Medical history, calcium intake, calcium, albumin, creatinine, parathyroid hormone (PTH) and 25OHD were evaluated. NPHPT was defined by normal albumin-adjusted serum calcium, elevated plasma PTH, and exclusion of common causes of secondary hyperparathyroidism (SHPT) (serum 25OHD <30âng/ml, estimated glomerular filtration rate (eGFR) <60âml/min per 1.73âm(2) and thiazide diuretics use), overt gastrointestinal and metabolic bone diseases. Complete data were available for 685 of 1046 subjects. Twenty subjects did not meet the inclusion criteria and 341 could not be evaluated because of thawing of plasma samples. Classical PHPT was diagnosed in four women (0.58%). For diagnosing NPHPT the upper normal limit of PTH was established in the sample of the population (n=100) who had 25OHD â„30âng/ml and eGFR â„60âml/min per 1.73âm(2) and was set at the mean+3s.d. Three males (0.44%) met the diagnostic criteria of NPHPT. These subjects were younger and with lower BMI than those with classical PHPT. Our data suggest, in line with previous studies, that NPHPT might be a distinct clinical entity, being either an early phenotype of asymptomatic PHPT or a distinct variant of it. However, we cannot exclude that NPHPT might also represent an early phase of non-classical SHPT, since other variables, in addition to those currently taken into account for the diagnosis of NPHPT, might cumulate in a normocalcemic subject to increase PTH secretion
NLRP3 Inflammasome From Bench to Bedside: New Perspectives for Triple Negative Breast Cancer
The tumor microenvironment (TME) is crucial in cancer onset, progression and response to treatment. It is characterized by an intricate interaction of immune cells and cytokines involved in tumor development. Among these, inflammasomes are oligomeric molecular platforms and play a key role in inflammatory response and immunity. Inflammasome activation is initiated upon triggering of pattern recognition receptors (Toll-like receptors, NOD-like receptors, and Absent in melanoma like receptors), on the surface of immune cells with the recruitment of caspase-1 by an adaptor apoptosis-associated speck-like protein. This structure leads to the activation of the pro-inflammatory cytokines interleukin (IL)-1ÎČ and IL-18 and participates in different biological processes exerting its effects. To date, the NodâLike Receptor Protein 3 (NLRP3) inflammasome has been well studied and its involvement has been established in different cancer diseases. In this review, we discuss the structure, biology and mechanisms of inflammasomes with a special focus on the specific role of NLRP3 in breast cancer (BC) and in the sub-group of triple negative BC. The NLRP3 inflammasome and its down-stream pathways could be considered novel potential tumor biomarkers and could open new frontiers in BC treatment
Salivary cortisol and α-amylase: subclinical indicators of stress as cardiometabolic risk
Currently, the potential for cardiovascular (CV) stress-induced risk is primarily based on the theoretical (obvious) side effects of stress on the CV system. Salivary cortisol and α-amylase, produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, are still not included in the routine evaluation of CV risk and require additional and definitive validation. Therefore, this article overviews studies published between 2010 and 2015, in which salivary cortisol and α-amylase were measured as stress biomarkers to examine their associations with CV/CMR (cardiometabolic risk) clinical and subclinical indicators. A comprehensive search of PubMed, Web of Science and Scopus electronic databases was performed, and 54 key articles related to the use of salivary cortisol and α-amylase as subclinical indicators of stress and CV/CMR factors, including studies that emphasized methodological biases that could influence the accuracy of study outcomes, were ultimately identified. Overall, the biological impact of stress measured by salivary cortisol and α-amylase was associated with CV/CMR factors. Results supported the use of salivary cortisol and α-amylase as potential diagnostic tools for detecting stress-induced cardiac diseases and especially to describe the mechanisms by which stress potentially contributes to the pathogenesis and outcomes of CV diseases
Promoter methylation and downregulated expression of the TBX15 gene in ovarian carcinoma.
TBX15 is a gene involved in the development of mesodermal derivatives. As the ovaries and the female reproductive system are of mesodermal origin, the aim of the present study was to determine the methylation status of the TBX15 gene promoter and the expression levels of TBX15 in ovarian carcinoma, which is the most lethal and aggressive type of gynecological tumor, in order to determine the role of TBX15 in the pathogenesis of ovarian carcinoma. This alteration could be used to predict tumor development, progression, recurrence and therapeutic effects. The study was conducted on 80 epithelial ovarian carcinoma and 17 control cases (normal ovarian and tubal tissues). TBX15 promoter methylation was first determined by pyrosequencing following bisulfite modification, then by cloning and sequencing, in order to obtain information about the epigenetic haplotype. Immunohistochemical analysis was performed to evaluate the correlation between the methylation and protein expression levels. Data revealed a statistically significant increase of the TBX15 promoter region methylation in 82% of the tumor samples and in various histological subtypes. Immunohistochemistry showed an inverse correlation between methylation levels and the expression of the TBX15 protein. Furthermore, numerous tumor samples displayed varying degrees of intratumor heterogeneity. Thus, the present study determined that ovarian carcinoma typically expresses low levels of TBX15 protein, predominantly due to an epigenetic mechanism. This may have a role in the pathogenesis of ovarian carcinoma independent of the histological subtype
In Situ Hexavalent Chromium Reduction by Injection of Organic Substrates in the Aquifer
Among the innovative technologies for in situ remediation of hexavalent
chromium in groundwater, bio-induced reduction is under investigation. In this process
the reduction of Cr(VI) is stimulated by a strongly reducing environment, created by the
injection of organic substrates that are rapidly degraded by autochthonous heterotrophic
microorganisms. Tests were performed at the laboratory scale to investigate the
behavior of two different organic substrates from food industry (permeate from cheese
whey ultrafiltration and a waste from the brewing process), in terms of dissolved Cr(VI)
abatement and kinetics, also as a function of the initial Cr(VI) concentration (5000 or
10000 ÎŒg/L). The tests showed that, under proper conditions, very low Cr(VI)
concentrations (1.3 ïg/L) and removal efficiency up to about 100% can be obtained after
36 d incubation
Prevention and Control of COVID-19 in Italian Prisons: Stringent Measures and Unintended Consequences
Psychopathological symptoms of patients with heroin addiction entering opioid agonist or therapeutic community treatment.
The relationship between substance use disorders and psychiatric pathology is still an open question. The main aim of the present study was to verify whether the five psychopathological dimensions identified through the SCL-90 tool in a previous study carried out on patients with heroin addiction entering an outpatient opioid agonist treatment (OAT) were also observable in those entering a residential treatment community (TC). Further aims were to look at differences in the psychopathological profiles of patients entering a TC versus an OAT treatment and at the correlation between gender and the observed psychopathology.A confirmatory factor analysis was performed on the results of SCL-90 filled by 1,195 patients with heroin dependence entering TC treatment. It replicates the extraction method previously used on 1,055 OAT patients with heroin addiction by using a principal component factor analysis (PCA). The association between the kind of treatment received (TC or OAT), gender, and the psychopathological dimensions was assessed through logistic regression and general linear model (GLM) analysis.The PCA carried out on the SCL-90 results of patients entering a TC yielded a five-factor solution, confirming the same dimensions observed in patients entering an OAT: 'worthlessness and being trapped', 'somatization', 'sensitivity-psychoticism', 'panic anxiety', and 'violence-suicide'. The logistic regression analysis showed a statistically significant association between 'somatization' and 'violence-suicide' severity score and OAT. GLM analysis showed that psychopathological factorial scores for 'worthlessness-being trapped', 'somatic symptoms', and 'panic anxiety' dimensions were more severe in OAT vs TC male patients and in TC vs OAT female ones. 'Violence suicide' followed the same severity pattern for males, but did not differ in TC vs OAT females, while 'sensitivity-psychoticism' did not differ in OAT vs TC patients. The five dimensions did not differ in OAT males vs females.Our research appears to confirm the existence of a specific aggregation of psychological/psychiatric features within the category of individuals with heroin addiction. It also shows a correlation between the dominant psychopathological subgroup and the assignment to TC versus OAT. Further research is needed to clarify the differences between the five psychopathological subgroups and their determinants
Extended Adjuvant Endocrine Treatment in Luminal Breast Cancers in the Era of Genomic Tests
In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice
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