7,742 research outputs found

    Investigating the impact of lung cancer cell-of-origin on tumour metabolic phenotype and heterogeneity

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    Non-small-cell lung cancer has been described as highly heterogenous which results in different metabolic phenotypes. There are multiple factors which contribute to this heterogeneity, one of which is the tumour cell-of-origin. In the lung, there are five cell types reported to be cells-of-origin: alveolar epithelial type 2, club, basal, neuroendocrine and bronchioalveolar stem cells. This project focuses on the interaction between the cell-of-origin and the metabolic phenotype of lung cancer, and we aim to assess the contribution of the cell-of-origin to lung cancer metabolic resultant phenotype and heterogeneity. To accomplish this, we have established two complementary model systems, one in vitro and one in vivo. In our in vitro model, we isolated specific lung cell types, including AT2 cells, basal cells, and club cells, utilising their unique cell surface markers. By introducing oncogenic KRAS mutations and deleting the P53 gene, we are creating lineage-restricted organoids. These organoids will serve as valuable tools for characterizing the metabolic aspects of tumours arising from different cell-of-origin backgrounds within an in vitro setting. In our in vivo model, we induced NSCLC tumours in mice with genetic modifications using viral vectors, namely Ad5-mSPC-Cre, Ad5-CC10-Cre, and Ad5- bk5-Cre. These vectors are selectively expressed in AT2, club, and basal cells, respectively. To ensure the validity of our comparisons, we have carefully monitored tumour growth dynamics and burden in these mouse models. Our comprehensive analysis has revealed three distinct transcriptomic subtypes (S1, S2, and Acetate) within these NSCLC tumours. Notably, S1 and Acetate subtypes are enriched in tumours originating from specific cell types. Positron emission tomography (PET) imaging has unveiled metabolic variations, with S1 tumours displaying heightened [18F]FDG uptake and the Acetate subtype exhibiting increased [11C]acetate uptake. Furthermore, our multi-omics approach, encompassing transcriptomics, proteomics, and metabolomics, has exposed disparities in critical metabolic pathways, such as glycolysis, hypoxia response, and apoptosis. In summary, our research provides a comprehensive examination of the metabolic heterogeneity of NSCLC based on the cell-of-origin independently of genomic alterations

    The uncharted territory of host-pathogen interaction in tuberculosis

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    Mycobacterium tuberculosis (M.tb) effectively manipulates the host processes to establish the deadly respiratory disease, Tuberculosis (TB). M.tb has developed key mechanisms to disrupt the host cell health to combat immune responses and replicate efficaciously. M.tb antigens such as ESAT-6, 19kDa lipoprotein, Hip1, and Hsp70 destroy the integrity of cell organelles (Mitochondria, Endoplasmic Reticulum, Nucleus, Phagosomes) or delay innate/adaptive cell responses. This is followed by the induction of cellular stress responses in the host. Such cells can either undergo various cell death processes such as apoptosis or necrosis, or mount effective immune responses to clear the invading pathogen. Further, to combat the infection progression, the host secretes extracellular vesicles such as exosomes to initiate immune signaling. The exosomes can contain M.tb as well as host cell-derived peptides that can act as a double-edged sword in the immune signaling event. The host-symbiont microbiota produces various metabolites that are beneficial for maintaining healthy tissue microenvironment. In juxtaposition to the above-mentioned mechanisms, M.tb dysregulates the gut and respiratory microbiome to support its replication and dissemination process. The above-mentioned interconnected host cellular processes of Immunometabolism, Cellular stress, Host Microbiome, and Extracellular vesicles are less explored in the realm of exploration of novel Host-directed therapies for TB. Therefore, this review highlights the intertwined host cellular processes to control M.tb survival and showcases the important factors that can be targeted for designing efficacious therapy

    Beta-glucans to enhance adoptive therapy of anti-cancer T cells

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    Bioactives and their roles in bone metabolism of osteoarthritis: evidence and mechanisms on gut-bone axis

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    Bioactives significantly modify and maintain human health. Available data suggest that Bioactives might play a beneficial role in chronic inflammatory diseases. Although promised, defining their mechanisms and opting to weigh their benefits and limitations is imperative. Detailed mechanisms by which critical Bioactives, including probiotics and prebiotics such as dietary lipids (DHA, EPA, alpha LA), vitamin D, polysaccharides (fructooligosaccharide), polyphenols (curcumin, resveratrol, and capsaicin) potentially modulate inflammation and bone metabolism is limited. Certain dietary bioactive significantly impact the gut microbiota, immune system, and pain response via the gut-immune-bone axis. This narrative review highlights a recent update on mechanistic evidence that bioactive is demonstrated demonstrated to reduce osteoarthritis pathophysiology

    Combined Nutrition and Exercise Interventions in Community Groups

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    Diet and physical activity are two key modifiable lifestyle factors that influence health across the lifespan (prevention and management of chronic diseases and reduction of the risk of premature death through several biological mechanisms). Community-based interventions contribute to public health, as they have the potential to reach high population-level impact, through the focus on groups that share a common culture or identity in their natural living environment. While the health benefits of a balanced diet and regular physical activity are commonly studied separately, interventions that combine these two lifestyle factors have the potential to induce greater benefits in community groups rather than strategies focusing only on one or the other. Thus, this Special Issue entitled “Combined Nutrition and Exercise Interventions in Community Groups” is comprised of manuscripts that highlight this combined approach (balanced diet and regular physical activity) in community settings. The contributors to this Special Issue are well-recognized professionals in complementary fields such as education, public health, nutrition, and exercise. This Special Issue highlights the latest research regarding combined nutrition and exercise interventions among different community groups and includes research articles developed through five continents (Africa, Asia, America, Europe and Oceania), as well as reviews and systematic reviews
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