ABSTRACT
India has the highest burden of both tuberculosis (TB) and multidrug-resistant TB (MDR-TB) based on the WHO Global TB Report 2019. Although the available data suggest that the total TB incidence has declined, the absolute number of new cases is still increasing. The number of reported TB cases in India in 2018 was 2.2 million, which was 1.5 million in 2009. About 47% increment in TB case notification in India within a decade shows a persistent public health problem. India contributes about 22% of the World's TB burden. Indian National Strategic Plan 2017-2025, sets out the government plans to eliminate TB by 2025. However, the milestone seems unrealistic to achieve the TB eradication goal by 2025. We developed a five-dimensional mathematical model to understand the TB dynamics in India and investigate the possibility of the earliest TB eradication time frame. The model stratifies the entire TB class into three different classes as drug-sensitive (DS), MDR, and isolated classes. The effective reproduction number, equilibrium points, and stability analysis of the model were carried out. This model predicts the total estimated cases of DS-TB and MDR-TB from 2018 to 2035 through numerical simulation and suggests that TB may be eliminated by 2035 in India if the treatment success rate could be achieved to 95%, by contact tracing and isolating at least 50% of MDR-TB.
ABSTRACT
This paper deals with mathematical modelling and analysis of a SEIQR model to study the dynamics of COVID-19 considering delay in conversion of exposed population to the infected population. The model is analysed for local and global stability using Lyapunov method of stability followed by Hopf bifurcation analysis. Basic reproduction number is determined, and it is observed that local and global stability conditions are dependent on the number of secondary infections due to exposed as well as infected population. Our study reveals that asymptomatic cases due to exposed population play a vital role in increasing the COVID-19 infection among the population.
ABSTRACT
This research paper aims at studying the impact of lockdown on the dynamics of novel Corona Virus Disease (COVID-19) emerged in Wuhan city of China in December 2019. Perceiving the pandemic situation throughout the world, Government of India restricted international passenger traffic through land check post (Liang, 2020) and imposed complete lockdown in the country on 24 March 2020. To study the impact of lockdown on disease dynamics we consider a three-dimensional mathematical model using nonlinear ordinary differential equations. The proposed model has been studied using stability theory of nonlinear ordinary differential equations. Basic reproduction ratio is computed and significant parameters responsible to keep basic reproduction ratio less than one are identified. The study reveals that disease vanishes from the system only if complete lockdown is imposed otherwise disease will always persist in the population. However, disease can be kept under control by implementing contact tracing and quarantine measures as well along with lockdown if lockdown is imposed partially.
ABSTRACT
AIMS: To potentiate the well-documented tumor protecting ability of paullones, literatures demand for rational modifications in paullone ring structure and exploration of a precise mechanism underlying their antitumor effects. Thus, recently we synthesized novel paullone-like scaffold, 5H-benzo [2, 3][1,4]oxazepino[5,6-b]indoles, where compounds 13a and 14a attenuated the growth of liver cancer specific Hep-G2 cells in vitro and formed stable binding complex with IL-6. Henceforth, we hypothesized that this action is probably due to the blockade of IL-6 mediated JAK2/STAT3 signaling cascade. MAIN METHODS: A preclinical study was conducted using NDEA-induced HCC rat model by oral administration of FOIs at 10â¯mg/kg dose for 15â¯days. The molecular insights were confirmed through ELISA, qRT-PCR, western blot analyses. The study was further confirmed by data-based mathematical modeling using the quantitative data obtained from western blot analysis. 1H NMR based metabolomics study was also performed to unveil metabolite discriminations among various studied groups. KEY FINDINGS: We identified that the HCC condition was produced due to the IL-6 induced activation of JAK2 and STAT3 which, in turn, was due to enhanced phosphorylation of JAK2 and STAT3. The treatment with FOIs led to the significant blockade of the IL-6 mediated JAK2/STAT3 signaling pathway. Besides, FOIs showed their potential ability in restoring perturbed metabolites linked to HCC. In particular, the anticancer efficacy of compound 13a was comparable or somewhat better than marketed chemotherapeutics, 5-flurouracil. SIGNIFICANCE: These findings altogether opened up possibilities of developing fused oxazepino-indoles (FOIs) as new candidate molecule for plausible alternative of paullones to treat liver cancer.