27 research outputs found

    Optical gain in laser diodes with null reflectivity

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    Optical gain measurement is extended to chips designed for external cavity lasers, where facet reflectivity is intentionally kept null, which prevents from any application of the Hakki-Paoli method. The new method is first shown to be consistent with the standard methods, by applying it to a chip with Fabry-Perot resonances and comparing the results of the new and the Hakki-Paoli method. The validated new method is then applied to the non-reflecting cavity of a tunable laser diode based on external cavity

    Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology

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    The scientific community, recently, has focused notable attention on the chemopreventive and therapeutic effects of dietary polyphenols for human health. Emerging evidence demonstrates that polyphenols, flavonoids and vitamins counteract and neutralize genetic and environmental stressors, particularly oxidative stress and inflammatory process closely connected to cancer initiation, promotion and progression. Interestingly, polyphenols can exert antioxidant or pro-oxidant cytotoxic effects depending on their endogenous concentration. Notably, polyphenols at high dose act as pro-oxidants in a wide type of cancer cells by inhibiting Nrf2 pathway and the expression of antioxidant vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), GPx, heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system which play an essential role in the metabolism of reactive oxygen species (ROS), detoxification of xenobiotics and inhibition of cancer progression, by inducing apoptosis and cell cycle arrest according to the hormesis approach. Importantly, mutagenesis of Nrf2 pathway can exacerbate its “dark side” role, representing a crucial event in the initiation stage of carcinogenesis. Herein, we review the hormetic effects of polyphenols and nanoincapsulated-polyphenols in chemoprevention and treatment of brain tumors via activation or inhibition of Nrf2/vitagenes to suppress carcinogenesis in the early stages, and thus inhibit its progression. Lastly, we discuss innovative preclinical approaches through mini-brain tumor organoids to study human carcinogenesis, from basic cancer research to clinical practice, as promising tools to recapitulate the arrangement of structural neuronal tissues and biological functions of the human brain, as well as test drug toxicity and drive personalized and precision medicine in brain cancer

    Crystallization-Induced Dynamic Resolution toward the Synthesis of (<i>S</i>)‑7-Amino‑5<i>H</i>,7<i>H</i>‑dibenzo[<i>b</i>,<i>d</i>]‑azepin-6-one: An Important Scaffold for γ‑Secretase Inhibitors

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    An enantioselective synthesis of (<i>S</i>)-7-amino-5<i>H</i>,7<i>H</i>-dibenzo­[<i>b</i>,<i>d</i>]­azepin-6-one (<i>S</i>-<b>1</b>) is described. The key step in the sequence involved crystallization-induced dynamic resolution (CIDR) of compound <b>7</b> using Boc-d-phenylalanine as a chiral resolving agent and 3,5-dichlorosalicylaldehyde as a racemization catalyst to afford <i>S</i>-<b>1</b> in 81% overall yield with 98.5% enantiomeric excess

    A systematic review of salvage therapies in refractory metastatic colorectal cancer

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    Purpose: Established that the only approved agents in previously treated metastatic colorectal cancer (CRC) are trifluoridine/tipiracil and regorafenib, we conducted a systematic review of all the published phase 2-3 trials, with the scope to evaluate the benefit of any later-line regimens in refractory metastatic CRC. Methods: Phase 2-3 studies that enrolled patients with stage IV disease receiving salvage therapies for refractory CRC were identified using electronic databases (Pubmed, EMBASE, and Cochrane Library). Clinical outcomes were pooled using a point estimates for the weighted values of median overall survival (OS), progression-free survival (PFS), response rate (ORR), stable disease rate (SD), and 6-month and 1-year OS. Results: Overall, 7556 patients were included from 67 studies (n = 70 arms). Overall, the pooled ORR and SD were 15.4% (95% CI 13-18%) and 36.9% (95% CI 33.5-40.6%). Median PFS, 6-month and 1-year OS, and median OS were 3.2 (95% CI 2.9-3.3) months, 65.4% (95% CI 61.9-68.8%), 36% (95% CI 32.3-39.9%) and 8.8 (95% CI 8.3-9.2) months. Overall survival was different in the monochemotherapy, polychemotherapy, chemotherapy + targeted therapy, and targeted therapy alone arms (7.6, 9.5, 10.3, and 7.9 months, respectively, P for difference = 0.01). Median PFS were respectively 2.3, 3.9, 3.8, and 2.6, respectively (P for difference &lt; 0.01). Conclusions: Overall, combination therapy (polychemotherapy with or without targeted agents) is associated with a higher control of disease and better outcome than approved agents. Treatment, if possible, should be personalized according to the patients' conditions, physician preference and molecular profile of disease

    Emergency surgical treatment of colonic acute diverticulitis: a multicenter observational study on behalf of the Italian society of colorectal surgery (SICCR) Lombardy committee

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    Colonic diverticulitis can be treated conservatively, but some cases require surgery. Patients can undergo Hartmann’s procedure (H) or resection with primary anastomosis (RA), with or without diverting stoma. This multicenter observational retrospective study aims to evaluate the adherence to current guidelines by assessing the rate of RA and H in Lombardy, Italy, and to analyze differences in patients’ features. This study included data collected from nine surgical units performing emergency surgery in Lombardy, in 2019 and 2021. Data for each year were retrospectively collected through a survey among Italian Society of Colorectal Surgery (SICCR) Lombardy members. Additional data were about: Hinchey’s classification, laparoscopic (VLS) or converted procedures, procedures with more than two operators, procedures in which the first operator was older than 40&nbsp;years, night or weekend procedures, older-than-80 patients, COVID-19 positivity (just 2021). The total number of operations performed was 254, 115 RA and 130 H (45.3% and 51.2%, diff. 12%, p = 0.73), and 9 (3.5%) other procedures. RAs were more frequent for Hinchey 1 and 2 patients, whereas Hs were more frequent for Hinchey 3 and 4. RAs without ileostomy were significantly less than Hs (66 vs. 130, p = 0.04). Laparoscopy was more used for RA compared to H (57 vs. 21, p = 0.03), whereas no difference was found between RA and H with respect to conversion rate, the presence of more than two operators in the team, the presence of a first operator older than 40&nbsp;years, night or weekend operations, and for older-than-80 patients. This study confirms the adherence to current guidelines for the treatment of acute colonic diverticulitis in Lombardy, Italy. It can be considered as a preliminary survey with interesting results that may open the way to a further prospective observational study to clarify some aspects in the management of this disease
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