This study aimed to compare phenotypic and genetic characteristics of Lactobacillus rhamnosus strains isolated at the end of the ripening of Parmigiano Reggiano cheese and to investigate an important prerequisite of probiotic interest, such as the capability to survive at low pH and in presence of bile salts. The use of API 50 CH, RAPD-PCR analysis and species-specific PCR allowed to ascertain the identity of 63 L. rhamnosus strains. Three L. rhamnosus strains isolated from Parmigiano Reggiano cheese, L. rhamnosus ATCC 7469T and the commercial strain L. GG were assayed to estimate the resistance to various stress factors reproducing in vitro some conditions of the gastro-intestinal environment such as low pH and different amounts of bile salts and acids. The behaviour of almost all the tested strains isolated from Parmigiano Reggiano cheese resulted analogous to that showed by L. GG.

No abstract

Recent cardiology research studies have reported the role, function, and structure of the mitochondrial permeability transition pore (mPTP) and have shown that its opening plays a key role in the progression of myocardial cell death secondary to reperfusion. In this manuscript, we validated a new pharmacological approach as an adjunct to reperfusion in myocardial infarction (MI) treatment and describe the discovery, optimization, and structure-activity relationship (SAR) studies of the first small-molecule mPTP opening inhibitors based on a 1,3,8-triazaspiro[4.5]decane scaffold that targets the c subunit of the F/F-ATP synthase complex. We identified three potential compounds with good mPTP inhibitory activity and beneficial effects in a model of MI, including a decreased apoptotic rate in the whole heart and overall improvement of cardiac function upon administration during reperfusion. The selected compounds did not show off-target effects at the cellular and mitochondrial levels. Moreover, the compounds preserved the mitochondrial ATP content despite interacting with the ATP synthase complex.

Double glycosylation of cysteine-containing peptides has been carried out by a one-pot two-step sequence comprising selective S-propargylation followed by photoinduced (lambda (max) 365 nm) free-radical hydrothiolation with glycosyl thiols. Conditions were established for the sequential introduction of two different thiol residues such as a glycosyl and a biotinyl derivative.

Beta-secretase (BACE1) is a key enzyme in the formation of amyloid-β; its activity/ concentration is increased in brain and cerebrospinal fluid of patients with late-onset Alzheimer's disease (LOAD). Since BACE1 was found also in blood, we evaluated its potential as peripheral biomarker. To this aim, serum BACE1 activity was assessed in 115 subjects with LOAD and 151 controls. We found that BACE1 changed across groups (p < 0.001) with a 25% increase in LOAD versus controls. High levels of BACE1 (IV quartile) were independently associated with the diagnosis of LOAD (OR 2.8; 1.4-5.7). Diagnostic accuracy was 76% for LOAD. Our data suggest that increased BACE1 activity in serum may represent a potential biomarker for LOAD. Additional studies are needed to confirm the usefulness of BACE1, alone or in combination with other markers, in discriminating patients and predicting LOAD onset and progression.

No abstract

Protein misfolding and amyloid formation are associated with various human diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Type-2 Diabetes mellitus (T2DM). No disease-modifying therapeutics are available for them. Despite the lack of sequence homology between the corresponding proteins, aromatic residues are recognized as common key motifs in the formation and stabilization of amyloid structures via π−π stacking. Thus, targeting aromatic recognition interfaces could be a useful approach for inhibiting amyloid formation as well as disrupting the preformed amyloid fibrils. Combining experimental and computational approaches, we demonstrated the anti-amyloidogenic effect of naphthoquinone-tryptophan-based hybrid molecules toward PHF6 (τ-derived aggregative peptide), Amyloid β (Aβ42), and human islet amyloid polypeptide (hIAPP) implicated in AD and T2DM, respectively. These hybrid molecules significantly inhibited the aggregation and disrupted their preformed fibrillar aggregates in vitro, in a dose-dependent manner as evident from Thioflavin T/S binding assay, CD spectroscopy, and electron microscopy. Dye leakage assay from LUVs and cell-based experiments indicated that the hybrid molecules inhibit membrane disruption and cytotoxicity induced by these amyloids. Furthermore, in silico studies provided probable mechanistic insights into the interaction of these molecules with the amyloidogenic proteins in their monomeric or aggregated forms, including the role of hydrophobic interaction, hydrogen bond formation, and packing during inhibition of aggregation and fibril disassembly. Our findings may help in designing novel therapeutics toward AD, T2DM, and other proteinopathies based on the naphthoquinone derived hybrid molecules.

Abstract:The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N 1 -(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC 50 values in the low micromolar range.