A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, since there is no effective therapy ...for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of anti-inflammatory mediators, cell membrane fluidity, intracellular signaling, and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represents a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.
MEMS (Micro Electro-Mechanical Systems) sensors enable a vast range of applications: among others, the use of MEMS accelerometers for seismology related applications has been emerging considerably in ...the last decade. In this paper, we provide a comprehensive review of the capacitive MEMS accelerometers: from the physical functioning principles, to the details of the technical precautions, and to the manufacturing procedures. We introduce the applications within seismology and earth sciences related disciplines, namely: earthquake observation and seismological studies, seismic surveying and imaging, structural health monitoring of buildings. Moreover, we describe how the use of the miniaturized technologies is revolutionizing these fields and we present some cutting edge applications that, in the very last years, are taking advantage from the use of MEMS sensors, such as rotational seismology and gravity measurements. In a ten-year outlook, the capability of MEMS sensors will certainly improve through the optimization of existing technologies, the development of new materials, and the implementation of innovative production processes. In particular, the next generation of MEMS seismometers could be capable of reaching a noise floor under the lower seismic noise (few tenths of ng/ Hz ) and expanding the bandwidth towards lower frequencies (∼0.01 Hz).
Progressive familial intrahepatic cholestasis (PFIC) includes autosomal recessive cholestatic rare diseases of childhood.
To update the panel of single genes mutations involved in familial ...cholestasis.
PubMed search for “familial intrahepatic cholestasis” alone as well as in combination with other key words was performed considering primarily original studies and meta-analyses.
PFIC1 involves ATP8B1 gene encoding for aminophospholipid flippase FIC1. PFIC2 includes ABCB11 gene, encoding for protein functioning as bile salt export pump. PFIC3 is due to mutations of ABCB4 gene responsible for the synthesis of class III multidrug resistance P-glycoprotein flippase. PFIC4 and PFIC5 involve tight junction protein-2 gene and NR1H4 gene encoding for farnesoid X receptor. Benign Intrahepatic Cholestasis, Intrahepatic Cholestasis of Pregnancy and Low-phospholipid-associated cholelithiasis involve the same genes and are characterized by intermittent attacks of cholestasis, no progression to cirrhosis, reversible pregnancy-specific cholestasis and cholelithiasis in young people. Blood and liver tissue levels of bile-excreted drugs can be influenced by the presence of mutations in PFIC genes, causing drug-induced cholestasis. Mutations in PFIC genes might increase the risk of liver cancer.
There is a high proportion of unexplained cholestasis potentially caused by specific genetic pathophysiologic pathways. The use of next generation sequencing and whole-exome sequencing could improve the diagnostic process in this setting.
Abstract Sarcopenia, occurring as a primary consequence of aging, is a progressive generalized decline of skeletal muscle mass, strength and function. The pathophysiology of sarcopenia is complex and ...multifactorial. One major cause of muscle mass and strength loss with aging appears to be the alteration in hormonal networks involved in the inflammatory processes, muscle regeneration and protein synthesis. This review describes the recent findings concerning the role of the aging on the endocrine system in the development of sarcopenia. We also report the benefits and safety of hormone replacement therapy in elderly subjects and discuss future perspectives in the therapy and prevention of skeletal muscle aging.
Human aging is currently defined as a physiological decline of biological functions in the body with a continual adaptation to internal and external damaging. The endocrine system plays a major role ...in orchestrating cellular interactions, metabolism, growth, and aging. Several
studies from worms to mice showed that downregulated activity of the GH/IGF-1/insulin pathway could be beneficial for the extension of human life span, whereas results are contradictory in humans. In the present review, we discuss the potential role of the IGF-1 system in modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better physiologic reserve capacity, a shift of cellular metabolism from cell proliferation to repair activities and a decrease in accumulation of senescent cells. Therefore, understanding of the link between IGF-1/insulin system and longevity may have future clinical applications in promoting healthy aging and in Rehabilitation Medicine.
Abstract
SMYD3 is a methylase previously linked to cancer cell invasion and migration. Here we show that SMYD3 favors TGFβ-induced epithelial–mesenchymal transition (EMT) in mammary epithelial cells, ...promoting mesenchymal and EMT transcription factors expression. SMYD3 directly interacts with SMAD3 but it is unnecessary for SMAD2/3 phosphorylation and nuclear translocation. Conversely, SMYD3 is indispensable for SMAD3 direct association to EMT genes regulatory regions. Accordingly, SMYD3 knockdown or its pharmacological blockade with the BCI121 inhibitor dramatically reduce TGFβ-induced SMAD3 association to the chromatin. Remarkably, BCI121 treatment attenuates mesenchymal genes transcription in the mesenchymal-like MDA-MB-231 cell line and reduces their invasive ability in vivo, in a zebrafish xenograft model. In addition, clinical datasets analysis revealed that higher SMYD3 levels are linked to a less favorable prognosis in claudin-low breast cancers and to a reduced metastasis free survival in breast cancer patients. Overall, our data point at SMYD3 as a pivotal SMAD3 cofactor that promotes TGFβ-dependent mesenchymal gene expression and cell migration in breast cancer, and support SMYD3 as a promising pharmacological target for anti-cancer therapy.
Two linear proline-rich peptides (
-
), bearing an N-terminal pyroglutamate, were isolated from the marine bacterium
sp. V1, associated with the marine sponge
, collected in the volcanic CO
vents in ...Ischia Island (South Italy). Peptide production was triggered at low temperature following the one strain many compounds (OSMAC) method. Both peptides were detected together with other peptides (
-
) via an integrated, untargeted MS/MS-based molecular networking and cheminformatic approach. The planar structure of the peptides was determined by extensive 1D and 2D NMR and HR-MS analysis, and the stereochemistry of the aminoacyl residues was inferred by Marfey's analysis. Peptides
-
are likely to arise from
V1 tailor-made proteolysis of tryptone. Peptides
and
were shown to display antioxidant properties in the ferric-reducing antioxidant power (FRAP) assay.
Abstract The sustainability of healthcare systems is threatened by the increasing (absolute and relative) number of older persons referring to clinical services. Such global phenomenon is questioning ...the traditional paradigms of medicine, pushing towards the need of new criteria at the basis of clinical decision algorithms. In this context, frailty has been advocated as a geriatric condition potentially capable of overcoming the weakness of chronological age in the identification of individuals requiring adapted care due to their increased vulnerability to stressors. Interestingly, frailty poses itself beyond the concept of nosological conditions due to the difficulties at correctly framing traditional diseases in the complex and heterogeneous scenario of elders. Thus, frailty may play a key role in public health policies for promoting integrated care towards biologically aged individuals, currently presenting multiple unmet clinical needs. At the same time, the term frailty has also been frequently used in the literature for framing a physical condition of risk for (mainly functional) negative endpoints. The combination of such physical impairment with an organ-specific phenotype (e.g., the age-related skeletal muscle decline or sarcopenia) may determine the assumptions for the development of a clinical condition to be used as potential target for ad hoc interventions against physical disability. In the present article, we present the background of frailty and sarcopenia, and discuss their potentialities for reshaping current clinical and research practice in order to promote holistic approach to older patients, solicit personalization of care, and develop new targets for innovative interventions.
The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a central hub for the regulation of cell proliferation, apoptosis, cell cycle, metabolism, and ...angiogenesis. Several studies have recently suggested that the PI3K/Akt/mTOR signaling pathway is implicated in the pathogenesis and progression of neuroendocrine tumors. Medullary thyroid cancer (MTC) is a neuroendocrine tumor developing from the C cells of the thyroid. Mutations in the RET proto-oncogene are involved in the pathogenesis of several forms of MTC. The deregulation of the PI3K/Akt/mTOR pathway seems to contribute to the tumorigenic activity of RET proto-oncogene mutations. Targeting this pathway through specific inhibitors at simple or multiple sites may represent an attractive potential therapeutic approach for patients with advanced MTCs. The aim of this review is to examine the role of the PI3K/Akt/mTOR pathway in the development and progression of MTC and the new therapeutic options that target this signaling pathway.
Summary
The discovery of biomarkers able to predict biological age of individuals is a crucial goal in aging research. Recently, researchers' attention has turn toward epigenetic markers of aging. ...Using the Illumina Infinium HumanMethylation450 BeadChip on whole blood DNA from a small cohort of 64 subjects of different ages, we identified 3 regions, the CpG islands of ELOVL2, FHL2, and PENK genes, whose methylation level strongly correlates with age. These results were confirmed by the Sequenom's EpiTYPER assay on a larger cohort of 501 subjects from 9 to 99 years, including 7 cord blood samples. Among the 3 genes, ELOVL2 shows a progressive increase in methylation that begins since the very first stage of life (Spearman's correlation coefficient = 0.92) and appears to be a very promising biomarker of aging.
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