has been used as a medicinal herb for the treatment of hepatic diseases and alcohol intoxication. AIM OF THE STUDY: The genotoxic effect and the antigenotoxic potential of ethanolic extract of H. dulcis leaves and its methanolic fraction were evaluated against ethanol-induced damages in SH-SY5Y cells. MATERIALS AND METHODS: The phytochemical analysis and antioxidant activity of H. dulcis extracts were also assessed. In d3 vitamin , a systems biology analysis was performed to investigate the molecular pathway of action of the H. dulcis leaves compounds. RESULTS: The ethanolic extract and its methanolic fraction presented genotoxicity through comet assay at 5 and 25 mg/mL. On the other hand, both extracts showed protective action against ethanol at all concentrations. Additionally, an NBT superoxide anion formation when SH-SY5Y cells were challenged with ethanol. HPLC analysis indicated the presence of quercitrin, isoquercitrin, and rutin. Further, system biology assays indicated a molecular action pathway, where the compounds from the leaves of H. dulcis, in addition to performing free radical scavenging activity, activate PP2A, and may inhibit the apoptosis pathway activated by ethanol-induced oxidative stress. CONCLUSIONS: This work is important to indicate potential antigenotoxic and antioxidant properties of H. dulcis leaves, and its use can be investigated against DNA damage induced by ethanol. 2288, 92010-000, Canoas, RS, Brazil. Electronic address: Av. Farroupilha, 8001, 92425-900, Canoas, RS, Brazil. competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. calcifediol in symptomatic COVID-19 outpatients. OBJECTIVES: This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID- METHODS: COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS: In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 983; 95% confidence interval [CI], 695-390; P = 922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 5 versus 5 d; HR, 372; 95% CI, 945-991; P = 0962; Wilcoxon P = 0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION: ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study. with buy vitamin d3 and elucidating the molecular signalling pathways Photodynamic therapy (PDT) is a promising non-invasive treatment modality for cancer and can be potentiated by combination with chemotherapy. Here, we combined PDT of novel porphyrin-based photosensitizers with low dose doxorubicin (Dox) to get maximum outcome. Dox potentiated and showed synergism with PDT under in vitro conditions on CTWT cells. The current colon cancer treatment strategies assure partial or even complete tumour regression but loco-regional relapse or distant metastasis is the major cause of death despite combination therapy. The spared cells after the treatment contribute to relapse and it is important to study their behaviour in host environment. Hence, we developed relapse models for PDT, Dox and combination treatments by transplanting respectively treated equal number of live cells to mice (n = 5) for tumour formation. Most of the treated cells lost tumour forming ability, but some treatment resistant cells developed tumours in few mice. These tumours served as relapse models and Western blot analysis of tumour samples provided clinically relevant information to delineate resistance strategies of individual as well as combination therapies at molecular level. Our results showed that low dose Dox helped in increasing the tumour inhibiting effect of PDT in combination therapy, but still there are indeed possibilities of relapse at later stages due to chemoresistance and immune suppression that may occur post-treatment. We observed that the combination therapy may also lead to the development of multidrug resistant (MDR) phenotype during relapse.
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