Performance of Italian zeolitic tuffs and pozzolana in 2-chlorophenol removal from contaminated groundwater. Lab-scale experience

The physical and chemical properties of zeolites and the availability of localized deposits of naturally occurring zeolitized tuffs and pozzolana, make them desirable for and applicable to the remediation of contaminated groundwater. This paper documents the results of a laboratory study to test the capacity of native Italian zeolites to remove 2-chlorophenol (2-CP) from water. Italian zeolitic tuff and pozzolana were characterized in terms of their chemical and structural properties and of their adsorption capacities. Moreover, the experimental activity investigated their adsorption behaviour: time and pH dependence of the adsorption process was evaluated. The results of the time-dependence adsorption study under a constantly stirred condition showed that the adsorption increases with a longer contact time for all samples; the highest adsorption occurred at pH=8 divided by 8.5. Due to the good removal efficiencies obtained, a column test simulating the condition of an in situ permeable reactive barrier was carried out, in order to estimate the removal kinetics and the long-term behaviour. The removal efficiencies reached values higher than 90%, even if some long-term performance worsening occurred, due to the progressive exhaustion of the adsorption sites. These experiments demonstrate the capacity of naturally occurring zeolites to remove 2-CP from water and the opportunity to make economic use of these native deposits for in situ groundwater remediation

Computational tools for the study of the structure-property relationship and design of new biologically active compounds

The aim of this PhD course was to explore a broad overview on the topic of the Structure-Property Relationship (SPR) with a strong emphasis on the pratical aspects. Data in chemical research, and in particular in drug discovery, is varied and oftentimes very complex. In drug discovery one has to make sense of different type of data such as structural, biological, physico-chemical, pharmacological, toxicological and so on, which, ultimately have to be associated to a single molecular structure. In order to sort out these data and extract appropriate information, a number of tools have been devised on computers and workstations in the form of different programs; the reader will find that many of these tools and methods have been used during this PhD course. More in details in Chapter 1 the homology modeling of the adenosine receptors was explored and accompanied to the pharmacophoric analysis and synthesis of new compounds. In Chapter 2 the analysis of the MMP-inhibitor interaction led us to implement the Amber Forcefield, and the following docking analysis allowed the design of new selective inhibitors. The modeling of the activate form of the cannabinoid receptors (Chapter 3) corresponded to an attempt for going away from the homology modeling procedures; together with the goal of obtaining a quantitative model from an automated docking study. In Chapter 4 the study of ligand-estrogen receptor interaction was developed exploring the free energy calculation, while finally in the last Chapter the angiotensin receptor AT1 construction led us to propose a new binding orientation for the non-peptide antagonists, using the 3D-QSAR approach as validation and predictive method

Investigating the Efficacy of DNA Damage with Bleach in Forensic Laboratories and at Crime Scenes

Household/commercial bleach (6% NaOCl, sodium hypochlorite) degrades DNA through oxidative damage, production of chlorinated base products, and cleavage of DNA strands (breaking it into smaller and smaller fragments). The presence of these lesions significantly impacts the ability to generate a full genetic profile from an evidentiary sample. In fact, knowledge of the damaging effect of bleach on DNA is the basis for its use in forensic laboratories to clean workbenches and prevent cross-contamination of samples between cases. Additionally, bleach is used intentionally by criminals to clean up crime scenes and destroy DNA evidence. A previous study demonstrated that bleach has a decreased effect on native DNA that is still encompassed within a body fluid (compared to naked DNA that has already been extracted) (Ambers et al. 2014). This research project expanded on the previous study, with an increased sample size and expanded data set. Numerous variables were tested, including dried blood, wet (uncoagulated) blood, native DNA, naked DNA, dried semen, wet (liquid) semen, and varying concentrations of bleach. DNA in whole human blood or semen (native conformation) and extracted (naked) DNA were immersed in two different concentrations of bleach for a 1-hour exposure period. Solid-phase DNA extraction and human-DNA-specific quantification revealed that sufficient quantities of DNA were recovered for STR typing, for both native and naked DNA templates and after exposure to both bleach concentrations (with higher DNA recovery from native samples vs. naked templates)

Interaction of anticancer reduced Schiff base coumarin derivatives with human serum albumin investigated by fluorescence quenching and molecular modeling

The specific binding of five reduced Schiff base derived 7-amino-coumarin compounds with antitumor activity to human serum albumin, the principal binding protein of blood, was studied by fluorescence spectroscopy. Their conditional binding constants were computed and the reversible binding at the Sudlow’s site I was found to be strong (KD ~ 0.03-2.09 M). Based on the data albumin can provide a depot for the compounds and is responsible for their biodistribution and transport processes. The experimental data is complemented by protein– ligand docking calculations for two representatives which support the observations. The proton dissociation constants of the compounds were also determined by UV-Vis spectrophotometric and fluorometric titrations to obtain the actual charges and distribution of the species in the various protonation states at physiological pH

Erectile dysfunction and its management in patients with diabetes mellitus

Diabetes can be described as a syndrome of multiple closely related conditions induced by a chronic state of hyperglycaemia resulting from defective insulin secretion, insulin action or both. Chronic complications associated with diabetes (including neuropathy, vascular disease, nephropathy and retinopathy) are common, and of these, erectile dysfunction (ED) deserves special attention. ED and its correlation with cardiovascular disease require careful evaluation and appropriate treatment. PDE5 inhibitors (PDE5is) are an important tool for the treatment of ED, with new drugs coming onto the market since the late 90s. This review offers an overview of PDE5is and their use in treating ED in diabetes. We underline the differences between different types of PDE5i, focusing on available doses, duration of action, T ½, side effects and selectivity profiles in relation to patients with diabetes. We also discuss the link between diabetes and ED in presence of various associated cofactors (obesity, hypertension and its pharmacological treatments, atherosclerosis, hyperhomocysteinaemia, neuropathy, nephropathy, hypogonadism and depression). Finally a number of past and ongoing clinical trials on the use of PDE5is in patients with diabetes are presented to offer an overview of the appropriate treatment of ED in this condition

Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions

α/β-Hydrolase Domain (ABHD) Inhibitors as New Potential Therapeutic Options against Lipid-Related Diseases

Much of the experimental evidence in the literature has linked altered lipid metabolism to severe diseases such as cancer, obesity, cardiovascular pathologies, diabetes, and neurodegenerative diseases. Therefore, targeting key effectors of the dysregulated lipid metabolism may represent an effective strategy to counteract these pathological conditions. In this context, α/β-hydrolase domain (ABHD) enzymes represent an important and diversified family of proteins, which are involved in the complex environment of lipid signaling, metabolism, and regulation. Moreover, some members of the ABHD family play an important role in the endocannabinoid system, being designated to terminate the signaling of the key endocannabinoid regulator 2-arachidonoylglycerol. This Perspective summarizes the research progress in the development of ABHD inhibitors and modulators: design strategies, structure-activity relationships, action mechanisms, and biological studies of the main ABHD ligands will be highlighted

Produzione di vettori energetici per via fermentativa da rifiuti organici

Il continuo sviluppo del trasporto pone ai Paesi europei la difficile sfida di conciliare le accresciute esigenze di mobilità con quelle di tutela dell’ambiente e della salute dei cittadini. Il trasporto, soprattutto quello su strada, è tradizionalmente un’importante fonte di produzione di ossidi di carbonio (CO e CO2), di azoto (NOx), di zolfo (SOx), di idrocarburi incombusti e di particolato solido. Tale settore rappresenta, dunque, una delle priorità su cui intervenire immediatamente, dato che da esso proviene circa un quarto delle emissioni totali di gas serra e che una mobilità sostenibile è indispensabile anche su scala globale. Pertanto, nel corso degli ultimi anni si stanno avviando attività sperimentali e di ricerca finalizzate alla produzione di biofuel a partire dalla valorizzazione di scarti provenienti dall’industria agroalimentare, del legno e dal settore dei rifiuti urbani. In quest’ottica, i rifiuti lignocellulosici ed in particolare quelli organici di origine urbana rappresentano una materia prima ampiamente disponibile e reperibile sul territorio e al tempo stesso una valida risorsa ambientale, giacché possiedono un potenziale energetico che può essere recuperato e riutilizzato tramite le attuali tecnologie a disposizione. In questo quadro si inserisce il presente Progetto di Ricerca di durata triennale, sviluppato nell’ambito del Dottorato di Ricerca in Ingegneria Ambientale di SAPIENZA, Università di Roma. L’obiettivo è stato quello di valutare le rese produttive in termini di idrogeno e metano da scarti organici di origine diversa, mediante il processo di digestione anaerobica, evidenziando le differenze e le criticità emerse nella valutazione delle rese di processo legate alla natura stessa dei substrati impiegati e alle specifiche condizioni operative richieste per l’applicazione del processo. Le matrici utilizzate nella sperimentazione sono state le seguenti: rifiuti organici da raccolta differenziata costituiti da diverse tipologie di scarti umidi (FW); frazione organica selezionata meccanicamente rifiuto urbano indifferenziato (OF); scarti di origine domestica prelevati da una mensa universitaria (M). L’attività è stata interamente svolta nel laboratorio di Ingegneria Sanitaria-Ambientale, presso il Dipartimento di Ingegneria Civile, Edile e Ambientale, di SAPIENZA, Università di Roma. L’iter procedurale della sperimentazione, seguito ad una fase di approfondita ricerca bibliografica, ha previsto la realizzazione delle seguenti fasi principali di cui sono riportati sinteticamente i risultati più importanti

Three-dimensional interactions analysis of the anticancer target c-src kinase with its inhibitors

Src family kinases (SFKs) constitute the biggest family of non-receptor tyrosine kinases considered as therapeutic targets for cancer therapy. An aberrant expression and/or activation of the proto-oncogene c-Src kinase, which is the oldest and most studied member of the family, has long been demonstrated to play a major role in the development, growth, progression and metastasis of numerous human cancers, including colon, breast, gastric, pancreatic, lung and brain carcinomas. For these reasons, the pharmacological inhibition of c-Src activity represents an effective anticancer strategy and a few compounds targeting c-Src, together with other kinases, have been approved as drugs for cancer therapy, while others are currently undergoing preclinical studies. Nevertheless, the development of potent and selective inhibitors of c-Src aimed at properly exploiting this biological target for the treatment of cancer still represents a growing field of study. In this review, the co-crystal structures of c-Src kinase in complex with inhibitors discovered in the past two decades have been described, highlighting the key ligand–protein interactions necessary to obtain high potency and the features to be exploited for addressing selectivity and drug resistance issues, thus providing useful information for the design of new and potent c-Src kinase inhibitors

Mangosteen Extract Shows a Potent Insulin Sensitizing Effect in Obese Female Patients: A Prospective Randomized Controlled Pilot Study.

There is a widely acknowledged association between insulin resistance and obesity/type 2 diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits—known for their antioxidant properties—have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety and efficacy of treatment with mangosteen extract on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. Twenty-two patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (homeostatic model assessment-insulin resistance, HOMA-IR −53.22% vs. −15.23%, p = 0.004), and no side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible supplementary role of mangosteen extracts in the treatment of obesity, insulin resistance, and inflammation