A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki-Miyaura Coupling.

A ligand-free approach for the Suzuki-Miyaura cross coupling reaction using Natural Deep Eutectic Solvents (NaDES) towards coumarin analogs is described. A model reaction between the synthetically prepared 3-(4-acetyloxy-phenyl)-6-bromo-4-methyl-coumarin () and phenylboronic acid was performed in five different NaDES as well as in pure glycerol, using two inorganic bases and palladium catalysts. The reaction proceeded smoothly in Choline Chloride/Glycerol (ChCl/Gly) and Betaine/Glycerol (Bet/Gly) NaDES at 90 °C in 24 h, affording the desired product in high yields up to 95%.

The Metabolic and Antioxidant Activity Profiles of Aged Greek Grape Marc Spirits.

In the last decade, "expressions" of grape marc spirits aged in wooden barrels of characteristic amber color and complex sensory attributes have been introduced. Yet studies on constituents migrating from the barrel to the beverage are scarce, and their metabolic profile remains unexplored. Furthermore, the literature on the assessment of their antioxidant activity is limited.

Circulatory Metabolite Ratios as Indicators of Lifestyle Risk Factors Based on a Greek NAFLD Case-Control Study.

An ensemble of confounding factors, such as an unhealthy diet, obesity, physical inactivity, and smoking, have been linked to a lifestyle that increases one's susceptibility to chronic diseases and early mortality. The circulatory metabolome may provide a rational means of pinpointing the advent of metabolite variations that reflect an adherence to a lifestyle and are associated with the occurrence of chronic diseases. Data related to four major modifiable lifestyle factors, including adherence to the Mediterranean diet (estimated on MedDietScore), body mass index (BMI), smoking, and physical activity level (PAL), were used to create the lifestyle risk score (LS).

A Computational Approach for the Discovery of Novel DNA Methyltransferase Inhibitors.

Nowadays, the explosion of knowledge in the field of epigenetics has revealed new pathways toward the treatment of multifactorial diseases, rendering the key players of the epigenetic machinery the focus of today's pharmaceutical landscape. Among epigenetic enzymes, DNA methyltransferases (DNMTs) are first studied as inhibition targets for cancer treatment. The increasing clinical interest in DNMTs has led to advanced experimental and computational strategies in the search for novel DNMT inhibitors.

Association of endometriosis with Sjögren's syndrome: Genetic insights (Review).

Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition.

Serum metabolomic profiling unveils distinct sex-related metabolic patterns in NAFLD.

Objective: Obesity poses an increased risk for the onset of Nonalcoholic fatty liver disease (NAFLD). The influence of other factors, such as sex in the incidence and severity of this liver disease has not yet been fully elucidated. Thus, we aimed to identify the NAFLD serum metabolic signatures associated with sex in normal, overweight and obese patients and to associate the metabolite fluctuations across the increasing liver steatosis stages.

A quest for the stereo-electronic requirements for selective agonism for the neurotrophin receptors TrkA and TrkB in 17-spirocyclic-dehydroepiandrosterone derivatives.

Introduction: The neurotrophin system plays a pivotal role in the development, morphology, and survival of the nervous system, and its dysregulation has been manifested in numerous neurodegenerative and neuroinflammatory diseases. Neurotrophins NGF and BDNF are major growth factors that prevent neuronal death and synaptic loss through binding with high affinity to their specific tropomyosin-related kinase receptors namely, TrkA and TrkB, respectively. The poor pharmacokinetic properties prohibit the use of neurotrophins as therapeutic agents.

Design and Synthesis of Novel 2-Acetamido, 6-Carboxamide Substituted Benzothiazoles as Potential BRAFV600E Inhibitors - In vitro Evaluation of their Antiproliferative Activity.

The oncogenic BRAFV600E kinase leads to abnormal activation of the MAPK signaling pathway and thus, uncontrolled cellular proliferation and cancer development. Based on our previous virtual screening studies which issued 2-acetamido-1,3 benzothiazole-6-carboxamide scaffold as active pharmacophore displaying selectivity against the mutated BRAF, eleven new substituted benzothiazole derivatives were designed and synthesized by coupling of 2-acetamidobenzo[d]thiazole-6-carboxylic acid with the appropriate amines in an effort to provide even more efficient inhibitors and tackle drug resistance often developed during cancer treatment. All derived compounds bore the benzothiazole scaffold substituted at position-2 by an acetamido moiety and at position-6 by a carboxamide functionality, the NH moiety of which was further linked through an alkylene linker to a sulfonamido (or amino) aryl (or alkyl) functionality or a phenylene linker to a sulfonamido aromatic (or non-aromatic) terminal pharmacophore in the order -C H -NHSO -R or reversely -C H -SO N(H)-R.

Correction: Boulaka et al. Genoprotective Properties and Metabolites of β-Glucan-Rich Edible Mushrooms Following Their In Vitro Fermentation by Human Faecal Microbiota. 2020, , 3554.

The authors wish to add the following information to the Authors and Affiliation section of our paper published in [...

Genetic factors involved in the co‑occurrence of endometriosis with ankylosing spondylitis (Review).

Previous research has revealed an association between endometriosis and various autoimmune diseases, while recent data suggest, for the first time, an association between endometriosis and the risk of developing ankylosing spondylitis (AS). AS, the prototype of spondyloarthritides diseases, is a systemic, chronic, immune‑mediated inflammatory arthritis, which primarily affects the spine and sacroiliac joints, as well as the axial skeleton with or without extraspinal manifestations. AS is of polygenic inheritance and numerous immunologically relevant genes contribute to its development.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis.

Association of endometriosis with cardiovascular disease: Genetic aspects (Review).

Cardiovascular disease (CVD) comprises a broad spectrum of pathological conditions that affect the heart or blood vessels, including sequelae that arise from damaged vasculature in other organs of the body, such as the brain, kidneys or eyes. Atherosclerosis is a chronic inflammatory disease of the arterial intima and is the primary cause of coronary artery disease, peripheral vascular disease, heart attack, stroke and renal pathology. It represents a leading cause of mortality worldwide and the loss of human productivity that is marked by an altered immune response.

In Vitro Fermentation of Mushrooms by Human Fecal Microbiota: Metataxonomic Analysis and Metabolomic Profiling of Fermentation Products.

Edible mushrooms contain biologically active compounds with antioxidant, antimicrobial, immunomodulatory and anticancer properties. The link between their anticancer and immunomodulatory properties with their possible prebiotic activity on gut micro-organisms has been the subject of intense research over the last decade. Lyophilized Pleurotus eryngii (PE) mushrooms, selected due to their strong lactogenic effect and anti-genotoxic, immunomodulatory properties, underwent in vitro static batch fermentation for 24 h by fecal microbiota from eight elderly apparently healthy volunteers (>65 years old).

Functional significance of the rare rs35667974 gene polymorphism, associated with multiple autoimmune diseases, using a structural biological approach.

Autoimmune diseases, which affect approximately 5% of human population, are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Recent genome wide association studies (GWAS) have successfully identified novel autoimmune disease-associated loci, with many of them shared by multiple disease-associated pathways but much of the genetics and pathophysiological mechanisms remain still obscure. Considering that most of the potential causal variants are still unknown, many studies showed that the missense variant rs35667974 at interferon-induced with helicase C domain 1 () gene is protective for type 1 diabetes (T1D), psoriasis (PS) and psoriatic arthritis (PsA).

Novel purine analogues regulate IL-1β release via inhibition of JAK activity in human aortic smooth muscle cells.

Purine analogues bearing a nitrate ester motif were previously discovered as cardioprotective and anti-inflammatory agents, but the anti-inflammatory mechanism remains to be established. We therefore investigated the anti-inflammatory effect of two purine analogues, MK118 bearing a nitrate ester moiety and the methyl-substituted analogue MK196 in Aortic Smooth Muscle Cells (AoSMCs), with emphasis on IL-1β release. The AoSMCs were stimulated with LPS with or without purine analogue, followed by ELISA, Olink proteomics, Western blot and real time PCR of NLRP3 inflammasome components.