SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance

Tissue transglutaminase in celiac disease: role of autoantibodies.

In celiac disease (CD), gluten, the disease-inducing toxic component in wheat, induces the secretion of IgA-class autoantibodies which target tissue transglutaminase (tTG). These autoantibodies are produced in the small-intestinal mucosa, and, during gluten consumption, they can also be detected in patients' serum but disappear slowly from the circulation on a gluten-free diet. Interestingly, after adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. The finding of IgA deposits on extracellular tTG in the liver, kidney, lymph nodes and muscles of patients with CD indicates that tTG is accessible to the gut-derived autoantibodies. Although the specific autoantibody response directed against tTG is very characteristic in celiac patients, their role in the immunopathology of the celiac mucosal lesion is a matter of debate. Here we report a brief summary of anti-tTG antibody effects demonstrating that these antibodies are functional and not mere bystanders in the disease pathogenesis. In fact, they inhibit intestinal epithelial cell differentiation, induce intestinal epithelial cell proliferation, increase epithelial permeability and activate monocytes and disturb angiogenesis

Assessment of the conformational features of Vasoactive Intestinal Peptide in solution by limited proteolysis experiments

The structural features of vasoactive intestinal peptide (VIP) and of its Gln16-diaminopropane derivative (VIP-DAP) in solution were investigated by limited proteolysis experiments with trypsin and thermolysin. The proteolysis of the native peptide by both proteinases takes place near the residues in positions 12 and 21/22, suggesting that these amino acids are embedded in segments more flexible than the rest of the molecule. VIP-DAP appears to be more resistant to the proteolytic attack of trypsin, indicating that the derivatization in position 16 is able to stabilize the structure of the peptide. Moreover, the analysis of the mass spectra of the proteolytic mixtures supports the evidence that the derivatization is also able to protect Met17 against oxidation. From these data it can be concluded that VIP in solution under physiological conditions is characterized by the presence of segments with secondary structure, linked together by ‘‘hinge’’ regions that confer flexibility to the peptide, whereas VIP-DAP is embedded in a more rigid conformation, more suitable to receptor interaction

Different effect of a period of caloric restriction following treatment with a normal lipid or hyperlipidic diet in the experimental animal model: focus on mitochondrial dynamics proteins in the liver.

Introduction: An excess of the daily caloric intake facilitates accumulations of fat that leads to the development of obesity. Caloric restriction is the strategy used to restore body composition to optimal levels. Likewise, a period of hypo-nutrition following a balanced diet promotes nutritional deficiencies. Both conditions above described induce changes in the cellular metabolism to which the mitochondria actively participate. These organelles are very dynamic and undergo against continuous fusion and fission processes in correlation with their functionality. Objectives: In this study were monitored the effects of a caloric restriction period, following treatments with normal or hyperlipidic diet, on mitochondrial dynamics in rat liver. Therefore, 4 experimental groups were constituted: N (control diet); HFD high fat diet); Nr (N + restriction); HFDr (HFD + restriction). Attention was focused on the main mitochondrial dynamics’ proteins, monitored by western blot: MFN2 (Mitofusin 2) and OPA1 (Optic atrophy type 1) as fusion markers; DRP1 (Dynamin-related protein 1) as a fission marker. Results: The data show reduction of MFN2 and increase of DRP1 in the Nr group compared to N with variation of the high and low isoforms of OPA1, suggesting increase of the mitochondrial fission. In contrast, both MFN2 and DRP1 increase in the HFDr group compared to HFD. In this case, the data seem to suggest a beneficial effect of the restriction with a probable induction of the mitochondrial biogenesis. This mechanism, in fact, could make more the utilization of lipids mobilized by deposits in consequence to caloric restriction. Conclusions: In conclusion, we can assume that a reduced caloric intake generates reorganization of the mitochondrial liver network by acting differently on the basis of the nutritional conditions prior to the hypocaloric regimen

pH-sensitive polymersomes: controlling swelling via copolymer structure and chemical composition

pH-sensitive vesicles used as drug delivery systems (DDSs) are generally composed of protonable copolymers. The disaggregation of these nanoparticles (NPs) during drug release implies the dispersion of positively charged cytotoxic polyelectrolytes in the human body. To alleviate such issue, we synthesised A(BC)n amphiphilic block copolymers with linear (n = 1) and branched (n = 2) architectures to obtain pH-sensitive vesicles capable of releasing drugs in acidic conditions via controlled swelling instead of disaggregation. We obtained this feature by fine-tuning the relative amount of pH-sensitive and hydrophobic monomers. We studied pH-driven swelling by measuring NPs size in neutral and acidic conditions, the latter typical of tumours or inflamed tissues (pH 3c6) and lysosomes (pH 3c4.5). Dynamic light scattering (DLS) and zeta potential data provided useful indications about the influence of architecture and chemical composition on NPs swelling, stability and polycation release. Results demonstrated that vesicles made of linear copolymers with 3c22\u201328% in mol of protonable monomers in the \u2018BC\u2019 block swelled more than other species following a pH change from pH 7.4 to pH 4.5. We finally evaluated the cytotoxicity of vesicles composed of linear species, and paclitaxel (PTX) release from the latter in both cancer and normal cells. \ua9 2017 Informa UK Limited, trading as Taylor & Francis Group

1,1,1-trichloro-2,2-bis (p-chlorophenyl)-ethane (DDT) and 1,1-Dichloro-2,2-bis (p, p’-chlorophenyl) ethylene (DDE) as endocrine disruptors in human and wildlife: A possible implication of mitochondria

1,1,1-trichloro-2,2-bis (p-chlorophenyl)-ethane (DDT) and its main metabolite 1,1-Dichloro-2,2-bis (p, p’-chlorophenyl) ethylene (DDE) act as endocrine disruptors in humans and wildlife. Immunomodulatory functions have also been attributed to both xenobiotics. DDT was banned in the 1970s due to its toxicity, but it is still produced and used for indoor residual spraying with disease vector control purposes. Due to their persistence and lipophilic properties, DDT and DDE can bioaccumulate through the food chain, being stored in organisms' adipose depots. Their endocrine disruptor function is mediated by agonist or antagonist interaction with nuclear receptors. Present review aimed to provide an overview of how DDT and DDE exposure impacts reproductive and immune systems with estrogen-disrupting action in humans and wildlife. Studies showing DDT and DDE impact on mitochondrial function and apoptosis pathway will also be reviewed, suggesting the hypothesis of direct action on mitochondrial steroid receptors