101,944 research outputs found
Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn's disease
No full textIn Crohn's disease (CD), the tissue-damaging inflammation is sustained by defects of counter-regulatory mechanisms, which normally inhibit immune-inflammatory signals and promote repair of mucosal injury. In particular, in inflamed gut of CD patients there are elevated levels of Smad7, an intracellular protein that inhibits the function of transforming growth factor (TGF)-β1. Knockdown of Smad7 with a specific antisense oligonucleotide, named mongersen, restores TGF-β1 activity thus leading to suppression of inflammatory pathways and resolution of colitis in mice. Consistently, oral administration of mongersen to patients with active CD induces clinical remission. In this article, we review the available data supporting the pathogenic role of Smad7 in CD and discuss the results of recent phase I and II trials assessing the efficacy and safety of mongersen in CD patients
Tofacitinib for the treatment of ulcerative colitis
No full textABSTRACT: Introduction: Management of patients with active ulcerative colitis (UC), one of the most frequent inflammatory bowel diseases in human beings, is mainly based on the use of mesalamine and corticosteroids. Since in the long-term, these two drugs may be ineffective in nearly one third of the patients, immunosuppressants and/or biologics are needed to control disease activity. Areas covered: The marked activation of JAK/STAT molecules in inflamed mucosa of UC patients and the demonstration that UC-associated mucosal injury is driven by soluble factors that signal through JAK/STAT pathways led to investigation of JAK inhibitors for the treatment of active UC. Tofacitinib, an oral inhibitor of the cytokine-driven JAK-STAT signalling cascade, has recently been proposed for the treatment of moderate-to-severe UC. Phase 2 study showed the efficacy of tofacitinib to induce clinical and endoscopic improvement/remission and the safety profile of the drug. Herein the authors review this compound. Expert opinion: The results obtained from clinical trials with tofacitinib suggest that this drug could be a new treatment option for patients with moderate to severe UC. However, further experimentation is needed to assess the efficacy of this drug in selected subgroups of patients as well as to maintain remission and to determine the long-term safety profile of the drug
Effects of local and systemic immune challenges on the expression of selected salivary genes in the malaria mosquito anopheles coluzzii
No full textSalivary glands play a crucial tripartite role in mosquito physiology. First, they secrete factors that greatly facilitate both sugar and blood meal acquisition. Second, the transmission of pathogens (parasites, bacteria and viruses) to the vertebrate host requires both the recognition and invasion of the salivary glands. Third, they produce immune factors that both protect the organ from invading pathogens and are also able to exert their activity in the crop and the midgut when saliva is re-ingested during feeding. Studies on mosquito sialomes have revealed the presence of several female and/or male salivary gland-specific or enriched genes whose function is completely unknown so far. We focused our attention on these orphan genes, and we selected, according to sequence and structural features, a shortlist of 11 candidates with potential antimicrobial properties. Afterwards, using qPCR, we investigated their expression profile at 5 and 24 h after an infectious sugar meal (local challenge) or thoracic microinjection (systemic challenge) of Gram-negative (Escherichia coli, EC) or Gram-positive (Staphylococcus aureus, SA) bacteria. We observed a general increase in the transcript abundance of our salivary candidates between 5 and 24 h after local challenge. Moreover, transcriptional modulation was determined by the nature of the stimulus, with salivary gland-enriched genes (especially hyp15 upon SA stimulus) upregulated shortly after the local challenge and later after the systemic challenge. Overall, this work provides one of the first contributions to the understanding of the immune role of mosquito salivary glands. Further characterization of salivary candidates whose expression is modulated by immune challenge may help in the identification of possible novel antimicrobial peptides
Oligonucleotide-Based Therapies for Inflammatory Bowel Disease
No full textthe growing understanding of the immunopathogenesis of inflammatory bowel diseases (IBDs) has contributed to the identification of new targets whose expression/activity can be modulated for therapeutic purposes. several approaches have been employed to develop selective pharmaceutical compounds; among these, antisense oligonucleotides (ASOs) or synthetic oligonucleotides represent a valid option for inhibiting or enhancing, respectively, the expression/function of molecules that have been implicated in the control of IBD-related inflammation. In this context, data have been accumulated for the following compounds: alicaforsen, an ASO targeting intercellular adhesion molecule-1, a transmembrane glycoprotein that regulates rolling and adhesion of leukocytes to inflamed intestine; DIMS0150 and BL-7040, two oligonucleotides that enhance toll-like receptor-9 activity; mongersen, an ASO that inhibits smad7, thereby restoring transforming growth factor-beta 1/Smad-associated signaling; STNM01, a double-stranded RNA oligonucleotide silencing carbohydrate sulfotransferase, an enzyme involved in fibrogenic processes, and hgd40, a specific DNAzyme inhibiting expression of the transcription factor GATA3. In this article, we review the rationale and the available data relative to the use of these agents in IBD. although pre-clinical and phase II trials in IBD support the use of oligonucleotide-based therapies for treating the pathogenic process occurring in the gut of patients with these disorders, further work is needed to establish whether and which patients can benefit from specific ASOs and identify biomarkers that could help optimize treatment
Atti di concorrenza sleale, Commento sub art. 2598
No full textThe provision of the article in question responds to a general principle of market governance - of a public nature - and, at the same time, identifies a series of rules - of a private nature - sufficient to regulate the business activity in its development. The provisions of the law manage the phase of the competitive dynamic which concerns the confrontation between companies perceived in its function of external appreciability
Sanzioni [Commento sub art. 2599]
No full textThe exercise of the injunction is unrelated to the recurrence of the subjective assumptions of willful misconduct or negligence (art. 2598) as the potential damage alone is necessary and sufficient, i.e. the potential attitude of the defendant's conduct to damage the company of the promoter of the action
Commento sub art. 2599, Codice Civile Ipertestuale Commentato
No full textThe exercise of the injunction is unrelated to the recurrence of the subjective assumptions of willful misconduct or negligence (art. 2598) as the potential damage alone is necessary and sufficient, i.e. the potential attitude of the defendant's conduct to damage the company of the promoter of the action
Atti di concorrenza sleale, Commento sub art. 2598 , Codice Civile Ipertestuale Commentato
No full textThe provision of the article in question responds to a general principle of market governance - of a public nature - and, at the same time, identifies a series of rules - of a private nature - sufficient to regulate the business activity in its development. The provisions of the law manage the phase of the competitive dynamic which concerns the confrontation between companies perceived in its function of external appreciability
Azione delle associazioni professionali, Commento sub art. 2601 c.c., Codice Civile Ipertestuale Commentato
No full textThe legitimacy of professional associations results as legitimacy to act iure proprio for the protection of category interests. On the basis of the abrogation of the corporate law, it is believed that the legitimacy of the entity integrates a case of procedural substitution. Professional associations would exceptionally be entitled to act in their own name, but in any case always to protect the interests of the associated entrepreneurs harmed by the unlawful act
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