38 research outputs found
Understanding potentials and restrictions of solvent-free enzymatic polycondensation of itaconic acid: an experimental and computational analysis
6siItaconic acid is a chemically versatile unsaturated diacid that can be produced by fermentation and potentially it can replace petrol based monomers such as maleic and fumaric acids in the production of curable polyesters or new biocompatible functionalized materials. Unfortunately, due to the presence of the unsaturated C=C bond, polycondensation of itaconic acid is hampered by cross reactivity and isomerization. Therefore, enzymatic polycondensations would respond to the need of mild and selective synthetic routes for the production of novel bio-based polymers. The present work analyses the feasibility of enzymatic polycondensation of diethyl itaconate and, for the first time, provides comprehensive solutions embracing both the formulation of the biocatalyst, the reaction conditions and the choice of the co-monomers. Computational docking was used to disclose the structural factors responsible for the low reactivity of dimethyl itaconate and to identify possible solutions. Surprisingly, experimental and computational analysis revealed that 1,4-butanediol is an unsuitable co-monomer for the polycondensation of dimethyl itaconate whereas the cyclic and rigid 1,4-cyclohexanedimethanol promotes the elongation of the oligomers.partially_openembargoed_20160430Corici, Livia; Pellis, Alessandro; Ferrario, Valerio; Ebert, Cynthia; Cantone, Sara; Gardossi, LuciaCorici, Livia; Pellis, Alessandro; Ferrario, Valerio; Ebert, Cynthia; Cantone, Sara; Gardossi, Luci
Gut microbiota: a new path to treat obesity
Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss
On the staking of miniaturized air-breathing microbial fuel cells
This work focuses on the scale-up of the MFCs by miniaturization and multiplication strategy. Performances of five stacks containing 1, 2, 5, 8 and 16 MFCs were compared. Each stack was evaluated under individual, parallel and series electrical connection as well as for cascade or individual hydraulic connection. Cascade feeding mode with a tank per stack favours the COD removal when the number of MFCs in the stack increases. However, despite operating without COD limitations, the energy production was disadvantaged. By changing the feeding system of a tank per stack into an individual tank per MFC, the performance of the whole stack enhances considerably. Stacking in series can increase the voltage 6 times while stacking in parallel can increase the current output about 4 times. For example, 8 MFCs can achieve 2.03âŻV connected in series and 6.98âŻmA connected in parallel. In addition, the power can be increased up to about 10 times leading to a power range high enough for real life applications
Assessing the extent and timing of chemosensory impairments during COVID-19 pandemic
Chemosensory impairments have been established as a specific indicator of COVID-19. They affect most patients and may persist long past the resolution of respiratory symptoms, representing an unprecedented medical challenge. Since the SARS-CoV-2 pandemic started, we now know much more about smell, taste, and chemesthesis loss associated with COVID-19. However, the temporal dynamics and characteristics of recovery are still unknown. Here, capitalizing on data from the Global Consortium for Chemosensory Research (GCCR) crowdsourced survey, we assessed chemosensory abilities after the resolution of respiratory symptoms in participants diagnosed with COVID-19 during the first wave of the pandemic in Italy. This analysis led to the identification of two patterns of chemosensory recovery, partial and substantial, which were found to be associated with differential age, degrees of chemosensory loss, and regional patterns. Uncovering the self-reported phenomenology of recovery from smell, taste, and chemesthetic disorders is the first, yet essential step, to provide healthcare professionals with the tools to take purposeful and targeted action to address chemosensory disorders and their severe discomfort
Assessing the extent and timing of chemosensory impairments during COVID-19 pandemic
Chemosensory impairments have been established as a specific indicator of COVID-19. They affect most patients and may persist long past the resolution of respiratory symptoms, representing an unprecedented medical challenge. Since the SARS-CoV-2 pandemic started, we now know much more about smell, taste, and chemesthesis loss associated with COVID-19. However, the temporal dynamics and characteristics of recovery are still unknown. Here, capitalizing on data from the Global Consortium for Chemosensory Research (GCCR) crowdsourced survey, we assessed chemosensory abilities after the resolution of respiratory symptoms in participants diagnosed with COVID-19 during the first wave of the pandemic in Italy. This analysis led to the identification of two patterns of chemosensory recovery, partial and substantial, which were found to be associated with differential age, degrees of chemosensory loss, and regional patterns. Uncovering the self-reported phenomenology of recovery from smell, taste, and chemesthetic disorders is the first, yet essential step, to provide healthcare professionals with the tools to take purposeful and targeted action to address chemosensory disorders and their severe discomfort
Evolving biocatalysis to meet bioeconomy challenges and opportunities
4siThe unique selectivity of enzymes, along with their remarkable catalytic activity, constitute powerful tools for transforming renewable feedstock and also for adding value to an array of building blocks and monomers produced by the emerging bio-based chemistry sector. Although some relevant biotransformations run at the ton scale demonstrate the success of biocatalysis in industry, there is still a huge untapped potential of catalytic activities available for targeted valorization of new raw materials, such as waste streams and CO2. For decades, the needs of the pharmaceutical and fine chemistry sectors have driven scientific research in the field of biocatalysis. Nowadays, such consolidated advances have the potential to translate into effective innovation for the benefit of bio-based chemistry. However, the new scenario of bioeconomy requires a stringent integration between scientific advances and economics, and environmental as well as technological constraints. Computational methods and tools for effective big-data analysis are expected to boost the use of enzymes for the transformation of a new array of renewable feedstock and, ultimately, to enlarge the scope of biocatalysis.partially_openopenPellis, Alessandro; Cantone, Sara; Ebert, Cynthia; Gardossi, LuciaPellis, Alessandro; Cantone, Sara; Ebert, Cynthia; Gardossi, Luci
Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited.
Methods
This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (nâ=â648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12âmonths of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint.
Results
We observed a significant decrease in NPS from a median value of 6 (IQR 5â6) at baseline to 1.0 (IQR 0.0â2.0) at 12âmonths (pâ<â.001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49â70) at baseline to 11 (IQR 6â21; pâ<â.001) at 12âmonths. Sniffin' Sticks scores showed a significant increase over 12âmonths (pâ<â.001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12âmonths based on EPOS 2020 criteria.
Conclusions
Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell
Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms
In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings â€2 indicate high odds of symptomatic COVID-19 (4<10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable
A new conception of polymeric supports for the solid phase peptide synthesis: rigidity and porosity as determinant factors for the success in industrial applications
2006/2007In questo studio di tesi sono stati sviluppati ed ottimizzati nuovi supporti rigidi per la sintesi in fase
solida in collaborazione con lâazienda Resindion srl. (Mitsubishi Chemical Corporation).
Tali supporti, denominati Synbeads, sono stati poi caratterizzati dal punto di vista chimico e fisico
ed applicati alla sintesi peptidica in fase solida.
La parte iniziale dello studio si Ăš concentrata sulla messa a punto del processo di polimerizzazione
in modo da ottenere dei polimeri Synbeads caratterizzati da un grado di porositĂ ottimale e da una
omogenea distribuzione del diametro particellare.
Questi due parametri infatti influiscono notevolmente sullâapplicabilitĂ dei polimeri per sintesi su
fase solida:
- il grado di porositĂ , nei polimeri rigidi e che quindi non rigonfiano in solvente, deve
garantire un buon trasferimento di massa dei reagenti e nello stesso tempo assicurare una
buona resistenza dei polimeri stessi allo stress meccanico
- la distribuzione particellare deve essere compresa in un ben definito range di diametro, in
modo da permettere lâutilizzo dei Synbeads anche in sistemi automatizzati, senza che vi
siano presente né particelle fini che potrebbero intasare i filtri, né particelle di dimensioni
troppo grandi che potrebbero rendere difficoltoso il trasferimento delle stesse nei sistemi
automatici.
La successiva fase di ottimizzazione dei Synbeads si Ăš concentrata su altri due parametri molto
importanti, ossia la lunghezza dello spaziatore tra la matrice polimerica e il gruppo funzionale e la
densitĂ di gruppi funzionali presenti sui polimeri:
- una distanza ottimale del gruppo funzionale dalla matrice del polimero ne garantisce la
completa accessibilitĂ chimica, evitando problematiche legate allâingombro sterico
- la densitĂ di gruppi funzionali deve assicurare sia una buona capacitĂ di carico (mmoli di
gruppi funzionali per gdry di polimero) sia una completa accessibilitĂ chimica di tutti i gruppi
funzionali presenti sul polimero.
In seguito a questo studio di ottimizzazione sono stati preparati i Synbeads con gruppo funzionale
amminico (Synbeads A310).
Partendo quindi dalle caratteristiche chimico-fisiche ottimizzate per la produzione dei Synbeads
A310, sono stai messi a punto dei protocolli per la preparazione e la caratterizzazione dei altri
Synbeads recanti gruppi funzionali diversi, ossia clorometilenici, bromometilenic, carbossilici ed
idrossilici.
Successivamente, i Synbeads A310 sono stati funzionalizzati con diversi linker che ne permettano
applicazioni diverse nella sintesi in fase solida.
Infatti, i Synbeads recanti i linker sono stati utilizzati per la preparazione da diversi
Fmoc-AA-Wang-Synbeads e per la sintesi di un pentapeptide. Questo pentapeptide costituisce la
sequenza dei primi cinque aminoacidi del FuzeonÂź, un peptide che presenta attivitĂ inibitoria nei
confronti dellâHIV.
Lâapplicazione dei Synbeads Ăš stata studiata anche per quanto riguarda il loro possibile utilizzo
nella sintesi peptidica automatizzata con lâimpiego di microonde, in particolare nel sistema Liberty
CEMÂź. Grazie alle caratteristiche chimico-fisiche dei Synbeads e alla messa a punto di protocolli
sintetici adatti a questi polimeri rigidi, si Ăš potuto ottenere il prodotto desiderato con buone rese e un
elevato grado di purezza.
Nella parte finale di questo studio di tesi Ăš stata indagata la distribuzione dei gruppi funzionali
allâinterno della matrice dei Synbeads.
Combinando la tecnica ATR-FT IR con luce convenzionale e con luce di sincrotrone Ăš possibile
seguire la diffusione dei reagenti allâinterno della matrice polimerica e verificare lâomogeneitĂ della
matrice stessa.
Dopo aver messo a punto questa metodologia analitica, che permette unâindagine approfondita di
ciĂČ che avviene allâinterno della matrice dei polimeri rigidi non trasparenti, un altro approccio
analitico Ăš stato sviluppato. Al fine di poter verificare in modo piĂč rapido lâomogeneitĂ della
matrice polimerica, sezioni di Synbeads funzionalizzati con diverse concentrazioni di fluoresceina
sono stati analizzati, permettendo in tal modo di verificare anche la distribuzione dei gruppi
funzionali.
Questo studio di dottorato quindi ha permesso di ottenere una nuova classe di polimeri rigidi per la
sintesi su fase solida, i Synbeads, che hanno dimostrato di permettere lâottenimento di ottimi
risultati sia nella sintesi classica che in quella assistita da microonde.
Nuovi approcci analitici sono stati studiati e applicati per verificare lâomogeneitĂ della matrice
polimerica e seguire i fenomeni di diffusione allâinterno della matrice stessa.
In tal modo, i Synbeads presentano un ottimo potenziale per unâapplicazione su larga scala in
processi industriali.XX Ciclo197