Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers.

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Agglomeration economies are the external benefits earned from clustering of industries and people in cities. The study assumes unbridled clustering of population in emerging urban agglomerations turning economies into diseconomies. This study empirically investigates the heterogeneous socioeconomic impacts of agglomeration economies in selected cities of Punjab, Pakistan, from 1998 to 2018, using the Pooled Mean Group and the Mean Group techniques of Panel ARDL. Agglomeration economies are determined by population density, number of registered factories, employment size, and housing, in the cities of Punjab. The study designed four indices for socioeconomic conditions using principal component analysis. These include: educationindex, healthcare-index, water & sanitation-index, and economic conditions-index. Research findings reveal pressures of high population density, unemployment, and costly housing on educational & healthcare facilities, poor sanitation & waste management, in cities of Punjab, Pakistan. The study suggests that policy makers and urban planners to develop short term and long term policies and development plans for villages and secondary cities to uplift wellbeing of the local population. Nonetheless, cities need to decentralize for sustainable development and management.