Quercetin, a well-known flavonoid with significant medicinal potential, was derivatized at the C8 position with a tetrahydroisoquinoline (THIQ) moiety, and physicochemical and pharmacological properties, inhibition potential, antioxidant activity, and cytotoxicity of new compounds were evaluated. Physicochemical and pharmacological properties, including lipophilicity, membrane permeability, and P-glycoprotein substrate affinity, were assessed theoretically using the SwissADME software. The metal-chelating ability of the new compounds was evaluated on metal ions Fe, Zn, and Cu, whose homeostasis disruption is linked to the development of Alzheimer's disease.
View Article and Find Full Text PDFThis study, conducted at two university-based infectious disease clinics, included 216 patients with chronic hepatitis C. The primary objective was to assess the positive and negative predictive values, sensitivity, and specificity of achieving a sustained virological response (SVR) at 4 weeks compared to 12 weeks post-therapy. The results demonstrated a maximum sensitivity of 100% for achieving SVR at 12 weeks after reaching SVR at 4 weeks for all analyzed genotypes, except for genotype 1b treated with EBR/GZR therapy, where the specificity was 75%.
View Article and Find Full Text PDFWe have synthesized 22 C-1 functionalized--aryl-1,2,3,4-tetrahydroisoquinoline derivatives showing biological activities towards cholinergic enzymes. Synthesis was performed using visible-light-promoted photo-redox chemistry, starting from a common intermediate, and the application of this synthetic methodology drastically simplified synthetic routes and purification of desired compounds. All synthesized derivates were divided into four groups based on the substituents in the C-1 position, and their inhibition potencies towards two cholinergic enzymes, acetyl- and butyrylcholinesterase were evaluated.
View Article and Find Full Text PDFHepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) accounting for around one-third of all HCC cases. Prolonged inflammation in chronic hepatitis C (CHC), maintained through a variety of pro- and anti-inflammatory mediators, is one of the aspects of carcinogenesis, followed by mitochondrial dysfunction and oxidative stress. Immune response dysfunction including the innate and adaptive immunity also plays a role in the development, as well as in the recurrence of HCC after treatment.
View Article and Find Full Text PDFIntroduction: We aimed to describe neurological manifestations and functional outcome at discharge in patients with West Nile neuroinvasive disease.
Methods: This retrospective study enrolled inpatients treated in the University Clinic for Infectious and Tropical Diseases in Belgrade, Serbia, from 1 June until 31 October 2022. Functional outcome at discharge was assessed using modified Rankin scale.
Introduction: Coronavirus disease of 2019 (COVID-19) is a global health problem. The impact of chronic liver diseases on the course and outcome of COVID-19 is still the subject of research. The aim of this study was to show the characteristics of COVID-19 patients with chronic liver diseases, and to establish the risk factors for unfavourable outcome.
View Article and Find Full Text PDFVisible light promoted photoredox catalyzed formation of α-amino radicals from cyclic tertiary amine compounds and their subsequent addition to Michael acceptors performed in flow conditions allowed access to a wide range of functionalized N-aryl-substituted tetrahydroisoquinolines (THIQs) and N-aryl-substituted tetrahydro-β-carbolines (THBCs). Visible light in conjunction with Ru(bpy)Cl photocatalyst allowed the formation and high reactivities of α-amino radicals in flow conditions at room temperature. These reactions gave valuable products with high efficiencies; some previously unavailable reaction pathways photo or thermal reaction conditions; i.
View Article and Find Full Text PDFA merger of organocatalysis and visible light photoredox catalysis performed in flow allowed access to a wide range of functionalized N-aryl-substituted tetrahydroisoquinolines (THIQs) in a formal C-H oxidation/Mannich reaction. Strecker type functionalization and copper-catalyzed alkynylation of several N-aryl-substituted THIQs were also successfully performed in flow, giving valuable products with high efficiencies. The use of custom-made porous polymeric type microreactors proved to be crucial regarding the C-H oxidation step and overall reaction performance.
View Article and Find Full Text PDFTrachoma is a devastating neglected tropical disease caused by Chlamydia trachomatis and the leading global cause of infectious blindness. Although antibiotic treatment against trachoma is efficient (SAFE strategy), additional affordable therapeutic strategies are of high interest. Water-filtered infrared A and visible light (wIRA/VIS) irradiation has proven to reduce chlamydial infectivity in vitro and ex vivo.
View Article and Find Full Text PDFOcular chlamydial infections with the ocular serovars A, B, Ba, and C of represent the world's leading cause of infectious blindness. Carrageenans are naturally occurring, sulfated polysaccharides generally considered safe for food and topical applications. Carrageenans can inhibit infection caused by a variety of viruses and bacteria.
View Article and Find Full Text PDFOligoclonal combinations of several monoclonal antibodies (MAbs) are being considered for the treatment of various infectious pathologies. These combinations are less sensitive to antigen structural changes than individual MAbs; at the same time, their characteristics can be more efficiently controlled than those of polyclonal antibodies. The main goal of this study was to evaluate the binding characteristics of six biclonal equimolar preparations (BEP) of tetanus toxin (TeNT)-specific MAbs and to investigate how the MAb combination influences the BEPs' protective capacity.
View Article and Find Full Text PDFFollowing infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model.
View Article and Find Full Text PDFWe demonstrated that a recombinant banana lectin (rBanLec), which structural characteristics and physiological impacts highly resemble those reported for its natural counterparts, binds murine peritoneal macrophages and specifically modulates their functional characteristics. By using rBanLec in concentrations ranging from 1 μg to 10 μg to stimulate resident (RMs) and thioglycollate-elicited (TGMs) peritoneal macrophages from BALB/c and C57BL/6 mice, we have shown that effects of rBanLec stimulation depend on its concentration but also on the functional status of macrophages and their genetic background. rBanLec, in a positive dose-dependent manner, promotes the proliferation of TGMs from both BALB/c and C57BL/6 mice, while its mitogenic influence on RMs is significantly lower (BALB/c mice) or not detectable (C57BL/6 mice).
View Article and Find Full Text PDFAntibodies capable to neutralize tetanus toxin (TeNT) are key factors in protection against tetanus disease. Although antibody-based therapeutics for treatment of tetanus exist on the market its production is tedious. Hence, the tetanus-specific antibodies preparation that could be easily produced in large scale in vitro would be beneficial.
View Article and Find Full Text PDF