Copper(II) Coordination Abilities of the Tau Protein’s NTerminus Peptide Fragments: A Combined Potentiometric, Spectroscopic and Mass Spectrometric Study

Copper(II) and nickel(II) complexes of the N-terminal peptide fragments of tau protein have been studied by potentiometric and various spectroscopic techniques (UV-vis, CD, ESR and ESI-MS). The octapeptide Tau(9-16) (Ac-EVMEDHAG-NH2) contains H14 residue of the native protein, while Tau(26-33) (Ac-QGGYTMHQ-NH2) and its mutants Ac-KGGYTMHK-NH2 and Ac-KGGATMHK-NH2 include H32. To compare the binding ability of H14 and H32 in a single molecule the decapeptide Ac-EDHAGTMHQD-NH2 has also been synthesized and studied. Histidyl residues are the primary metal binding sites for both metal ions, but in the case of Tau(9-16) the side chain carboxylate functions can enhance the stability of the M-Nim coordinated complexes. Deprotonation and metal ion coordination of amide groups occur around the physiological pH range for copper(II) and in slightly alkaline samples for nickel(II). The formation of the amide coordinated species with (Nim,N–,N–,N–) binding mode changes the metal ion preference and the complexes formed with the peptides containing H32 residue predominate over those of H14 in alkaline samples

Effects of the drying method for flowers of Cynara cardunculus var. Altilis on milk coagulating properties

In the production of some traditional cheeses from vegetable rennet, raw extracts of Cynara cardunculus flowers are used as the coagulant. During the preparation of this rennet, there are many factors that can influence its coagulation activity. We studied the flowers of Cynara cardunculus var. altilis to evaluate the effects of some of these factors: ripening stage of the flower at harvest, type of drying, part of the flower subjected to drying, toasting of the pistils, and maceration time of the pistils. The results show that it is possible to improve the coagulation activity of the traditional preparation of Cynara cardunculus flowers through some practices such as the rapid drying of the flowers/pistils at a controlled temperature, the toasting treatment of the pistils carried out after the slow drying of the flowers, and the extension of the extraction time to 24 h

Longitudinal virological and immunological profile in a case of human monkeypox infection

In a male with severe proctitis, monkeypox virus DNA was detected in skin lesions, blood, nasopharynx, and rectum, underlying the generalized viral spreading. Rectal involvement was still found when skin lesions disappeared. At the early-stage, increase of cytotoxic and activated T-cells, while reduction of CD56dimCD57+NK cells compared to recovery time-point was observed

Anti-inflammatory Effect of Curcumin, Homotaurine, and Vitamin D3 on Human Vitreous in Patients with Diabetic Retinopathy

Purpose: To determine the levels of pro-inflammatory cytokines and soluble mediators (TNF-α, IL6, IL2, and PDGF-AB) in 28 vitreous biopsies taken from patients with proliferative diabetic retinopathy (PDR) and treated with increasing doses of curcumin (0. 5 and 1 μM), with or without homotaurine (100 μM) and vitamin D3 (50 nM). Materials and Methods: ELISA tests were performed on the supernatants from 28 vitreous biopsies that were incubated with bioactive molecules at 37◦C for 20h. The concentration of the soluble mediators was calculated from a calibration curve and expressed in pg/mL. Shapiro-Wilk test was used to verify the normality of distribution of the residuals. Continuous variables among groups were compared using the General Linear Model (GLM). Homoscedasticity was verified using Levene and Brown-Forsythe tests. Post-hoc analysis was also performed with the Tukey test. A p ≤ 0.05 was considered statistically significant. Results: The post-hoc analysis revealed statistically detectable changes in the concentrations of TNF-α, IL2, and PDGF-AB in response to the treatment with curcumin, homotaurine, and vitamin D3. Specifically, the p-values for between group comparisons are as follows: TNF-α: (untreated vs. curcumin 0.5μM + homotaurine 100μM + vitamin D3 50nM) p = 0.008, (curcumin 0.5μM vs. curcumin 0.5μM + homotaurine 100μM + vitamin D3 50nM) p = 0.0004, (curcumin 0.5μM vs. curcumin 1μM + homotaurine 100μM + vitamin D3 50nM) p = 0.02, (curcumin 1μM vs. curcumin 0.5μM + homotaurine 100μM + vitamin D3 50nM) p = 0.025, and (homotaurine 100 μM + vitamin D3 50 nM vs. curcumin 0.5 μM + homotaurine 100μM + vitamin D3 50nM) p = 0.009; IL2: (untreated vs. curcumin 0.5μM + homotaurine 100μM + vitamin D3 50nM) p = 0.0023, and (curcumin 0.5μM vs. curcumin 0.5 μM+ homotaurine 100 μM + vitamin D3 50 nM) p = 0.0028; PDGF-AB: (untreated vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.04, (untreated vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.0006, (curcumin 0.5μM vs. curcumin 1μM + homotaurine 100μM + vitamin D3 50nM) p=0.006, and (homotaurine 100μM + vitamin D3 50nM vs. curcumin 1μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.022. IL6 levels were not significantly affected by any treatment. Conclusions: Pro-inflammatory cytokines are associated with inflammation and angiogenesis, although there is a discrete variability in the doses of the mediators investigated among the different vitreous samples. Curcumin, homotaurine, and vitamin D3 individually have a slightly appreciable anti-inflammatory effect. However, when used in combination, these substances are able to modify the average levels of the soluble mediators of inflammation and retinal damage. Multi-target treatment may provide a therapeutic strategy for diabetic retinopathy in the future

Blue rubber bleb nevus syndrome and pulmonary hypertension: An unusual association

INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital systemic angiodysplasia with multiple vascular malformations in the skin, gastrointestinal tract and, less often, in other internal organs and the brain. CASE REPORT: A 36-year-old man with past history of BRBNS was admitted to our hospital for progressive dyspnea and fatigue. Primary pulmonary hypertension (PPH) was diagnosed. He then developed acute abdominal pain and dyspnea, dying in a few hours due to sudden cardiac arrest. Postmortem examination demonstrated angiomatous lesions located in the skin, small bowel, heart, lungs, liver and thyroid. The lesions were slightly raised, soft and compressible and microscopically consisted of dilated vascular channels lined by a flattened endothelium. The vascular wall was formed by several layers of smooth muscle cells, intermixed with abundant aggregates of elastic lamellae and thin collagen fibers. Luminal thrombi were a frequent finding. In the small bowel, we identified the presence of an abnormally large artery directly opening into a thin-walled venous channel. The most striking finding in the lungs was the presence of thrombi of varying age in the lumen of segmental and elastic arteries, as well as muscular arteries and arterioles. Severe medial hypertrophy of muscular arteries and muscolarization of arterioles were also present. Intimal proliferative lesions and plexiform lesions were never observed. CONCLUSION: The pulmonary findings are consistent with recurrent thromboembolic events from shunts in the visceral lesions. To our knowledge, this is the first report of BRBNS with visceral arterovenous (AV) fistulae complicated by thromboembolic pulmonary hypertension (PH)

Insufficienza renale acuta in paziente con carcinoma epatocellulare sottoposto a chemioembolizzazione transarteriosa

Transarterial chemoembolization (TACE) is included among the wide therapeutic tools for the treatment of hepatocellular carcinoma (HCC), tumour with high frequency and malignancy. The approach is invasive and, beyond the discomfort for the patient, it is charged by a number of side effects and complications. In this study we report the case of renal acute failure of hypovolemic origin, as a consequence of a TACE in a patient suffering from HCC, occurred after one week of intervention. The different possible mechanisms involved in the pathogenesis of this complication are discussed

C. spinosa L. subsp. rupestris Phytochemical Profile and Effect on Oxidative Stress in Normal and Cancer Cells

Spices, widely used to improve the sensory characteristics of food, contain several bioactive compounds as well, including polyphenols, carotenoids, and glucosynolates. Acting through multiple pathways, these bioactive molecules affect a wide variety of cellular processes involved in molecular mechanisms important in the onset and progress of human diseases. Capparis spinosa L. is an aromatic plant characteristic of the Mediterranean diet. Previous studies have reported that different parts (aerial parts, roots, and seeds) of C. spinosa exert various pharmacological activities. Flower buds of C. spinosa contain several bioactive compounds, including polyphenols and glucosinolates. Two different subspecies of C. spinosa L., namely, C. spinosa L. subsp. spinosa, and C. spinosa L. subsp. rupestris, have been reported. Few studies have been carried out in C. spinosa L. subsp. rupestris. The aim of our study was to investigate the phytochemical profile of floral buds of the less investigated species C. spinosa subsp. rupestris. Moreover, we investigated the effect of the extract from buds of C. spinosa subsp. rupestris (CSE) on cell proliferation, intracellular ROS levels, and expression of the antioxidant and anti-apoptotic enzyme paraoxonase-2 (PON2) in normal and cancer cells. T24 cells and Caco-2 cells were selected as models of advanced-stage human bladder cancer and human colorectal adenocarcinoma, respectively. The immortalized human urothelial cell line (UROtsa) and human dermal fibroblast (HuDe) were chosen as normal cell models. Through an untargeted metabolomic approach based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS), our results demonstrate that C. spinosa subsp. rupestris flower buds contain polyphenols and glucosinolates able to exert a higher cytotoxic effect and higher intracellular reactive oxygen species (ROS) production in cancer cells compared to normal cells. Moreover, upregulation of the expression of the enzyme PON2 was observed in cancer cells. In conclusion, our data demonstrate that normal and cancer cells are differentially sensitive to CSE, which has different effects on PON2 gene expression as well. The overexpression of PON2 in T24 cells treated with CSE could represent a mechanism by which tumor cells protect themselves from the apoptotic process induced by glucosinolates and polyphenols