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Insights into Off-Label therapeutic strategies against mild and severe COVID-19 infection

Tue, 20 Jul 2021 00:00:00 GMT

Title: Insights into Off-Label therapeutic strategies against mild and severe COVID-19 infection Authors: Arshad, Bushra; Iqbal, Tahira; Bhatti, Khalid Pervez; Ahmed, Sheraz; Zaman, Wajid; Fazal Ullah; Nazeer, Amna; Saqib, Saddam Abstract: Currently, prevention and control of the coronavirus disease pneumonia epidemic situation are grim globally. To cope with total sheer carriers and patients of COVID-19 requires intensive medical support and adjunctive therapies to overcome the disease. The epidemic can be controlled with the help of both, disease suppression via community health measures and adjunctive therapies for patients suffering from infection. Till date, we do not have any proper antiCOVID-19 therapy. In order to achieve the overall realization of this pandemic, there is a need to identify treatments depending upon their direct or indirect targets; like inhibition of polyprotein synthesis, transmembrane serine protease, inhibition of viral entry and endocytosis. This could be possible by turning the focus in the direction towards the development of numerous tentative drugs, particularly in the severe to badly ill. Though, majority of these off-label adjunctive medicines are being inspected in a lot of clinical trials at different stages, scientific organizations have endeavored to elucidate the situation where these adjunctive drugs might be practiced as off-label, open- label or compassionate. Our review compiles the adjunctive therapies adopted in COVID-19 infected patients according to clinical severity in conjugation with practicing recommendations from existing guidance rules issued by global professional bodies in healthcare.

Clinical outcomes of using second – versus first-Generation EGFR-tkis for the First-Line treatment of advanced NSCLC patients with EGFR mutations: A meta-analysis

Tue, 20 Jul 2021 00:00:00 GMT

Title: Clinical outcomes of using second – versus first-Generation EGFR-tkis for the First-Line treatment of advanced NSCLC patients with EGFR mutations: A meta-analysis Authors: Hou, Bing; Lu, Xiao; Gao, Dong-Cai; Liu, Quan-Xing; Zhou, Dong; Zheng, Hong; Dai, Ji-Gang Abstract: First-generation EGFR-TKIs (gefitinib/erlotinib) and second-generation EGFR-TKI (afatinib) have become the current first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC), however, the effects of using second-generation EGFR-TKIs compared to those of using first-generation EGFR-TKIs as a first-line treatment for NSCLC patients with EGFR mutations remain unknown. We conducted this meta-analysis based on 4 retrospective and 2 randomized controlled studies published between 2016 and 2018. We surveyed the effectiveness of afatinib/dacomitinib and gefitinib/erlotinib as first-line treatments for stage III-IV EGFR-mutated NSCLC patients. The combined hazard ratio (HR) for the progression free survival (PFS) of second-generation EGFR-TKI group versus that first-generation drug group was 0.64 [95% confidence interval (95% CI) 0.55–0.74; P<0.001], demonstrating a superior PFS in the second-generation group. This outcome coincided with the subgroup analyses comparing the PFS of patients with EGFR exon 19 deletion (HR = 0.68 [95% CI 0.55–0.83; P = 0.0002]) or L858R mutation (HR = 0.64 [95% CI 0.51– 0.81; p=0.0002]). Meanwhile, second-generation drugs could to significantly improve the time to progression (TTFs) compared to first-generation drugs (HR = 0.81 [95% CI 0.67–0.89; P = 0.03]). Afatinib and dacomitinib may be the superior first-line treatment for advanced NSCLC patients with EGFR mutations

Atractylenolide II induces cell cycle arrest and apoptosis in breast cancer cells through ER pathway

Tue, 20 Jul 2021 00:00:00 GMT

Title: Atractylenolide II induces cell cycle arrest and apoptosis in breast cancer cells through ER pathway Authors: Dou, Shaohua; Yang, Chao; Zou, Danfeng; Da, Wa; Masood, Muqaddas; Adlat, Salah; Baima, Yang-Jin; Nasser, MI; Li, Bin; Jiang, Nan Abstract: In this research, atractylenolide II (ATR II) on apoptosis, cell cycle cells via ER pathway in breast cancer (MDA-MB-231 and MCF-7) cells are assessed. The effect of ATR II on cell proliferation was detected by MTT assay. Additional flow cytometry, luciferase, the western blot were performed to detect the signaling pathway cytotoxicity of ATR II. We have also carried out autodock measurements to validate our results. Our findings showed ATR II could inhibit breast cancer cell growth by apoptosis mainly through G2/M-phase cell cycle arrest. Besides, the cytotoxicity of ATTR II on breast cancer was also correlated by the regulation of endrogen receptors and promising an anti-inflammatory activity via inhibiting NF-KB signaling pathways. Taking together, ATR II could be a potential anticancer drug for breast cancer.

Anti-inflammatory and anti-nociceptive activities of polyphenols from Feijoa fruit and leaves

Tue, 20 Jul 2021 00:00:00 GMT

Title: Anti-inflammatory and anti-nociceptive activities of polyphenols from Feijoa fruit and leaves Authors: Mahmoudi, Mitra; Seif, Sadaf; Khan, Barkat Ali; Alshahrani, Sultan M; Arimi, Amirali; Allami, Alireza; Alqahtani, Saad S.; Ebrahimzadeh, Mohammad Ali Abstract: Many pharmacological activities have been reported from plants polyphenols. The aim of this study was to investigate anti inflammatory and antinociceptive activities of polyphenols from Feijoa sellowiana fruit and leaves. For the anti-inflammatory activity evaluation, inhibition of carrageenan induced edema was used. While for the evaluation of antinociceptive activity of the extract, writhing and hot plate tests in mice were used. Impairment in mouse coordination was evaluated by rota-rode test. Carrageenan induced edema was significantly inhibited by the extract at 50-400 mg kg-1 doses, when comparison was made with control group. The extract of leaf at the dose of 50 mg kg-1 i.p. the activity was equipotent with diclofenac (p>0.05). Extract reduced the writhing count in 50-400 mg kg-1 of doses. Fruit extract showed higher activity than diclofenac (p<0.001) at 400 mg kg-1 doses. In all tested doses, the extract significantly augmented the pain threshold in hot plate thermal test. No locomotor impairment in mice was induced by the extract at any tested doses. Extract was safe and didnot demonstrate any noxiousness up to 1 g kg-1.This study indicates the potential therapeutic use of Feijoa as a potent anti-inflammatory and antinociceptive agent.