Inositol is a physiological compound belonging to the sugar family. The two inositol stereoisomers, myo-inositol and D-chiroinositol are the two main stereisomers present in our body. Myo-inositol is ...the precursor of inositol triphosphate, a second messenger regulating many hormones such as TSH, FSH and insulin. D-chiroinositol is synthetized by an insulin dependent epimerase that converts myo-inositol into D-chiro-inositol. Polycistic Ovary Syndrome (PCOS) is a metabolic and hormonal disorder and a common cause of infertility. Insulin resistance and the consequent hyperinsulinaemia contribute to hyperandrogenism development, typical marker of PCOS. In these patients myo and/or D-chiro-inositol administration improves insulin sensivity while only myo-inositol is a quality marker for oocytes evaluation. Myo-inositol produces second messengers for FSH and glucose uptake, while D-chiroinositol provides second messengers promoting glucose uptake and glycogen synthesis. The physiological ratio of these two isomers is 40:1 (MI/DCI) and seems to be an optimal approach for the treatment of PCOS disorders.
Alpha-lipoic acid (ALA) plays a key role in many physiological processes, exerting anti-inflammatory, immunomodulatory, antioxidant, detoxifying, and insulin sensitizing activities. Since ALA ...improves insulin resistance (IR), it has been suggested that ALA could be beneficial it in the treatment of PCOS. The natural polyol myo-Inositol (myo-Ins) and its isomers (D-Chiro-Inositol, D-Chiro-Ins) has proven to improve PCOS features and clinical outcome, according to a compelling body of available studies. Few studies have proposed to strengthen the inositol effect by associating ALA. ALA does not seem to influence significantly reproductive hormones, while its beneficial effects are presumably restricted to the metabolic features of insulin resistant PCOS women. Therefore, ALA usefulness in improving inositol activity still awaits convincingly confirmation. Experimental studies as well as proper randomized clinical trials, should be specifically tailored to assess this hypothesis. In absence of reliable evidence, ALA should not be recommended in the routinary clinical management of PCOS, even if associated to myo-Ins.
We have designed a set of experiments to test the role of borosilicate reactor on the yielding of the Miller-Urey type of experiment. Two experiments were performed in borosilicate flasks, two in a ...Teflon flask and the third couple in a Teflon flask with pieces of borosilicate submerged in the water. The experiments were performed in CH
, N
, and NH
atmosphere either buffered at pH 8.7 with NH
Cl or unbuffered solutions at pH ca. 11, at room temperature. The Gas Chromatography-Mass Spectroscopy results show important differences in the yields, the number of products, and molecular weight. In particular, a dipeptide, multi-carbon dicarboxylic acids, PAHs, and a complete panel of biological nucleobases form more efficiently or exclusively in the borosilicate vessel. Our results offer a better explanation of the famous Miller's experiment showing the efficiency of borosilicate in a triphasic system including water and the reduced Miller-Urey atmosphere.
The outbreak of Sars-CoV-2 (COVID-19) poses serious challenges to people's health worldwide. The management of the disease is mostly supportive, and respiratory failure from acute respiratory ...distress syndrome is the leading cause of death in a significant proportion of affected patients. Preliminary data point out that dramatic increase in IL-6 and subsequent cytokine release syndrome may account for the development of fatal interstitial pneumonia. Inhibition of IL-6 by blocking its specific receptor with monoclonal antibodies has been advocated as a promising attempt. Here we assess the potential utility of myo-Inositol, a polyol already in use for treating the newborn Respiratory Distress Syndrome, in downregulating the inflammatory response upon Sars-CoV-2 infection. Myo-Inositol proved to reduce IL-6 levels in a number of conditions and to mitigate the inflammatory cascade, while being devoid of any significant side effects. It is tempting to speculate that inositol could be beneficial in managing the most dreadful effects of Sars-CoV-2 infection.
Abstract Cancer is a highly complex disease due to the disruption of tissue architecture. Thus, tissues, and not individual cells, are the proper level of observation for the study of carcinogenesis. ...This paradigm shift from a reductionist approach to a systems biology approach is long overdue. Indeed, cell phenotypes are emergent modes arising through collective non-linear interactions among different cellular and microenvironmental components, generally described by “phase space diagrams”, where stable states (attractors) are embedded into a landscape model. Within this framework, cell states and cell transitions are generally conceived as mainly specified by gene-regulatory networks. However, the system's dynamics is not reducible to the integrated functioning of the genome–proteome network alone; the epithelia–stroma interacting system must be taken into consideration in order to give a more comprehensive picture. Given that cell shape represents the spatial geometric configuration acquired as a result of the integrated set of cellular and environmental cues, we posit that fractal-shape parameters represent “omics” descriptors of the epithelium–stroma system. Within this framework, function appears to follow form, and not the other way around.
This work describes the possibility to combine multicomponent chemistry and multienzymes cascade transformations in a unique reactive framework to yield highly functionalized 1,4-benzoxazines under ...favorable heterogeneous conditions. The synthetic scheme involved the generation in situ of electrophilic reactive quinone intermediates of tyrosol esters catalyzed by lipase M and tyrosinase followed by nucleophilic 1,6-Michael addition of selected α-amino acid methyl esters, and successive intramolecular lactonization and aromatization processes. The immobilization of the multienzymes cascade on electroactive lignin nanoparticles improved the sustainability and recyclability of the overall system.
The inhibition of the metastatic capability of cancer cells is a pivotal aim of current anticancer strategies. We investigated herein the anti-migrating and anti-invasive properties of Zebrafish ...embryo extracts (SL) - an integrative formula comprising morphogenetic factors extracted from zebrafish embryos - alone or in association with 5-Fluoro-Uracil (5-FU), when added to metastatic breast cancer cells (MDA-MB-231) and in normal epithelial breast cells (MCF10A) committed toward an inflammatory phenotype upon TGF-β1 stimulation.
Invasiveness, migrating capability, cytoskeleton architecture and related molecular factors involved in the epithelial-mesenchymal transition were studied after treatment with 5-FU, with and without SL.
Remarkably, in both circumstances, embryo extracts amplify the migratory inhibition triggered by the anticancer drug 5-Fu. The fact that such an effect is noticed in normal as well as in cancerous cells suggests that the critical target of embryo extracts is specifically represented by the migrating/invasive phenotype. However, while 5-FU was unable in antagonizing the invasiveness of cancerous cells, the association with SL can significantly impair the invasive capability of tumor cells. These findings are noticeably associated with the reversion of the EMT phenotype in SL-treated cells, as documented by the contemporary downregulation of TCTP and some EMT-related molecular effectors, like α-SMA and Vimentin.
Embryo fish extracts significantly counteract the migrating and invasive phenotype of cancerous and inflammatory breast cells treated with the chemotherapeutic drug 5-FU. The availability of a compound able to amplify 5-Fu activity while significantly hampering the invasive phenotype of breast cancer should provide invaluable benefits, namely if we consider that this compound is substantially deprived of side-effects.
Monitoring hepatitis C virus (HCV) infection among injecting drug users (IDUs) in the community is complicated by difficulties in obtaining biological specimens and biases in recruitment and ...follow‐up. This study examined the utility of dried blood spot (DBS) specimens from IDUs recruited using respondent‐driven sampling (RDS). Active IDUs underwent a computer‐assisted interview and provided a DBS sample, tested for HCV antibody (anti‐HCV) and HCV‐RNA. HCV incidence was estimated from the proportion of anti‐HCV‐negative subjects found HCV‐RNA‐positive and estimates of the duration of this state. Results were adjusted according to RDS derived sample weights. HCV‐RNA testing was performed on 288 DBS samples; 173 were anti‐HCV‐positive (54% weighted), of which 70 (42%, 95%CI 34–50% weighted) were RNA‐negative indicating cleared infection. Among the 115 anti‐HCV‐negatives, 14 were RNA‐positive suggesting an incidence of 38–47 per 100pyrs. Incident infections were younger than anti‐HCV‐negative and prevalent infections: 25 vs. 29 and 34, respectively. Incidence was highest among individuals with poor needle exchange coverage. One hundred and fourteen were genotyped (60 1a, 46 3a): a cluster of 14 had homology of >98.5% including 10 incident infections. Public health surveillance of HCV among IDUs could be enhanced through the collection of DBS samples with appropriate recruitment approaches. DBS allow differentiation between individuals with cleared infections, ongoing infection and those recently infected. They also enable virus characterization at genotype and nucleotide level. This would allow surveillance to inform development of harm reduction interventions, and the international evidence base for these.
Seedlings of clover (Triflorium hybridum) were colonized by Bacillus thuringiensis when spores and seeds were co-inoculated into soil. Both a strain isolated in the vegetative form from the ...phylloplane of clover, 2810-S-4, and a laboratory strain, HD-1, were able to colonize clover to a density of about 1000 CFU/g leaf when seeds were sown in sterile soil and to a density of about 300 CFU/g leaf in nonsterile soil. A strain lacking the characteristic insecticidal crystal proteins produced a similar level of colonization over a 5-week period as the wild type strain, indicating that crystal production was not a mitigating factor during colonization. A small plasmid, pBC16, was transferred between strains of B. thuringiensis when donor and recipient strains were sprayed in vegetative form onto leaves of clover and pak choi (Brassica campestris var. chinensis). The rate of transfer was about 0.1 transconjugants/recipient and was dependent on the plant species. The levels of B. thuringiensis that naturally colonized leaves of pak choi produced negligible levels of mortality in third instar larvae of Pieris brassicae feeding on the plants. Considerable multiplication occurred in the excreted frass but not in the guts of living insects. Spores in the frass could be a source of recolonization from the soil and be transferred to other plants. These findings illustrate a possible cycle, not dependent on insect pathology, by which B. thuringiensis diversifies and maintains itself in nature.
Cell shape is mainly determined by biophysical constraints, interacting according to non-linear dynamics upon the basic units provided by the genome. In turn, the specific configuration a cell ...acquires plays a fundamental, permissive role in modulating gene expression and many other complex biological functions. Cell shape is tightly connected to cell activity and can be considered the most critical determinant of cell function. As a consequence, measurable parameters describing shape could be considered as 'omics' descriptors of the specific level of observation represented by the cell-stroma system. Such an approach promises to formalize some of the underlying basic mechanisms and, ultimately, provide a holistic understanding of the biological processes.
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