Computational approaches to shed light on molecular mechanisms in biological processes

Computational approaches based on Molecular Dynamics simulations, Quantum Mechanical methods and 3D Quantitative Structure-Activity Relationships were employed by computational chemistry groups at the University of Milano-Bicocca to study biological processes at the molecular level. The paper reports the methodologies adopted and the results obtained on Aryl hydrocarbon Receptor and homologous PAS proteins mechanisms, the properties of prion protein peptides, the reaction pathway of hydrogenase and peroxidase enzymes and the defibrillogenic activity of tetracyclines. © Springer-Verlag 2007

Discovery of a AHR pelargonidin agonist that counter-regulates Ace2 expression and attenuates ACE2-SARS-CoV-2 interaction

The severe acute respiratory syndrome (SARS)-CoV-2 is the pathogenetic agent of Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE)2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV-2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of Ace2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin activates the Aryl hydrocarbon Receptor (AHR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent TNBS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of Ace2 mRNA expression. Colon levels of Ace2 mRNA were directly correlated with Tnf-α mRNA levels. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV-2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV-2 Spike protein to ACE2 and reduces the SARS-CoV-2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner

Structural and Functional Loss in Restored Wetland Ecosystems

In restored wetland ecosystems with apparently natural hydrology and biological structure, biogeochemical function may remain degraded, even a century after restoration efforts

Camouflaging vitiligo using a spray tan

Vitiligo is a depigmenting skin disorder that can cause significant patient distress. Treatment of vitiligo is challenging and should address patient's concern for cosmetic treatment. Herein, we report the case of a 60-year-old patient who achieved temporary improvement in pigmentation using a spray tan. Camouflaging vitiligo using a spray-tan is a reasonable, safe, and effective mechanism for management of vitiligo

Mirtazapine for the Treatment of Chronic Pruritus

Background: Chronic pruritus is a debilitating condition associated with a wide range of dermatologic, systemic and psychogenic etiologies. In patients with chronic pruritus that is refractory to conventional therapy, symptoms can significantly decrease quality of life by contributing to anxiety, sleep disturbances, and in many cases depression. Recent studies have demonstrated the effectiveness of mirtazapine in relieving chronic itch that is refractory to standard first-line therapies. Methods: We searched PubMed for English-language articles containing the words (“pruritus” or “itch”) AND “antidepressant” and then conducted a systematic review of the current literature to summarize the efficacy of mirtazapine in treating chronic itch. Results: All studies reported a reduction in itch intensity following the administration of mirtazapine. Conclusion: Collectively, these studies suggest the potential for mirtazapine to relieve chronic itch attributed to dermatological causes and malignancies. As, such mirtazapine may be an option for patients with chronic pruritus that is refractory to typical first-line treatments

Intramolecular Horner-Wadsworth-Emmons olefination route to annulated carbohydrates

Depending on the length of the C-alkyl chain, vicinal beta-ketophosphonates of pyranosulosides afforded, under mild basic conditions, cyclopentenone- or cyclohexenone-annulated sugars

Stereochemistry of Sphinxolides and Reidispongiolides. Asymmetric Synthesis of C17-C22 fragment of reidispongiolide A

Five fragments, 2a-4b, embedding all the stereogenic centers of reidispongiolide A (1), have been prepared by a controlled ozonolysis of the natural compound. The absolute stereochemistry of the asymmetric centers of fragment 3, corresponding to the C17-C22 portion of reidispongiolide A, was determined by enantioselective synthesis and application of the advanced Mosher method