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Lung carcinoma is the leading cause of cancer-related mortalities worldwide, and present therapeutical interventions are not successful enough to treat this disease in many cases. Recent years have witnessed a surge in exploring natural compounds for their antiproliferative efficacy to expedite the characterization of novel anticancer chemotherapeutics. Swertia chirayita is a valued medicinal herb and possess intrinsic pharmaceutical potential. However, elucidation of its anticancer effects at molecular levels remains unclear and needs to be investigated. We assessed the anticancer and apoptotic efficacy of S . chirayita ethanolic extract ( Sw -EtOH) on non-small cell lung cancer (NSCLC) A549 cells during this exploratory study. The results elucidated that S. chirayita extract induced toxic effects within lung cancer cells by ~1 fold during cytotoxicity and LDH release assay at a 400 μg/ml concentration. Sw -EtOH extract elevates the level of ROS, resulting in the disruption of Δψm and release of cytosolic cytochrome c by 3.15 fold. Activation of caspases-3, -8 & -9 also escalated by ~1 fold, which further catalyze the augmentation of PARP cleavage (~3 folds), resulting in a four-fold increase in Sw -EtOH induced apoptosis. The gene expression analysis further demonstrated that Sw -EtOH extracts inhibited JAK1/STAT3 signaling pathway by down-regulating the levels of JAK1 and STAT3 to nearly half a fold. Treatment of Sw -EtOH modulates the expression level of various STAT3 associated proteins, including Bcl-XL, Bcl-2, Mcl-1, Bax, p53, Fas, Fas-L, cyclinD1, c-myc, IL-6, p21 and p27 in NSCLC cells. Thus, our study provided a strong impetus that Sw -EtOH holds the translational potential of being further evaluated as efficient cancer therapeutics and a preventive agent for the management of NSCLC.

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The present paper focuses on the modeling of the COVID-19 infection with the use of hospitalization, isolation and quarantine. Initially, we construct the model by spliting the entire population into different groups. We then rigorously analyze the model by presenting the necessary basic mathematical features including the feasible region and positivity of the problem solution. Further, we evaluate the model possible equilibria. The theoretical expression of the most important mathematical quantity of major public health interest called the basic reproduction number is presented. We are taking into account to study the disease free equilibrium by studying its local and global asymptotical analysis. We considering the cases of the COVID-19 infection of Pakistan population and find the parameters using the estimation with the help of nonlinear least square and have . Further, to determine the influence of the model parameters on disease dynamics we perform the sensitivity analysis. Simulations of the model are presented using estimated parameters and the impact of various non-pharmaceutical interventions on disease dynamics is shown with the help of graphical results. The graphical interpretation justify that the effective utilization of keeping the social-distancing, making the quarantine of people (or contact-tracing policy) and to make hospitalization of confirmed infected people that dramatically reduces the number of infected individuals (enhancing the quarantine or contact-tracing by 50% from its baseline reduces 84% in the predicted number of confirmed infected cases). Moreover, it is observed that without quarantine and hospitalization the scenario of the disease in Pakistan is very worse and the infected cases are raising rapidly. Therefore, the present study suggests that still, a proper and effective application of these non-pharmaceutical interventions are necessary to curtail or minimize the COVID-19 infection in Pakistan.

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