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Background Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism. We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects. Methods PBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (β-oxidation) or pyruvate (direct Krebs’ cycle substrate) was measured using the XFp Extracellular Flux Analyzer. Plasma levels of inflammatory cytokines IFN-γ, IL-17, TNF-α, IL-5, IL-9 and IFN-α were measured using flow cytometry. RAW264.7 cells were exposed to cigarette smoke condensate (CSC) for 1 h and its effect on cell viability, cellular metabolism and phagocytosis ability were also studied. Patient’s data was analyzed using the Mann Whitney U test, whereas Student’s t test was performed to analyze the in-vitro data. Results PBMCs from COPD subjects showed a significant decrease in extracellular acidification rate (ECAR) while utilizing glucose as compared to HNS (151.9 Vs 215%). Mitochondrial oxygen consumption rate (OCR) on palmitate or pyruvate was also found to be significantly lower in COPD subjects as compared to HS and a strong positive correlation between palmitate OCR in PBMCs and FEV 1 (r = 0.74, p < 0.05) and FVC (r = 0.79, p < 0.05) values in HS was observed. The metabolic shift towards fatty acid metabolism in healthy smokers promoted an inflammatory cytokine response with a greater increase in the levels of IL-5, IL-9 and IFN-α as compared to IFN-γ, IL-17 and TNF-α. In-vitro experiments with RAW 264.7 cells showed similar metabolic alterations and a reduced ability to phagocytose Streptococcus pneumonia and Haemophilus influenza after cigarette smoke exposure in the presence of glucose or palmitate. Conclusions These findings indicate a metabolic basis for the inflammatory response in COPD and could suggest a new therapeutic target for controlling the immune response and delaying the onset of disease. Trial registration This observational study was retrospectively registered in the Clinical Trails Registry – India (ICMR – NIMS) on 19th January 2018 with the registration number CTRI/2018/01/011441 . Electronic supplementary material The online version of this article (10.1186/s12931-019-1139-2) contains supplementary material, which is available to authorized users.

A novel treatment strategy by co-targeting c-Myc and tumor stroma was explored in vemurafenib-resistant melanoma. BRD4 proteolysis targeting chimera (ARV-825) and nintedanib co-loaded PEGylated nanoliposomes (ARNIPL) were developed to incorporate a synergistic cytotoxic ratio. Both the molecules have extremely poor aqueous solubility. A modified hydration method with citric acid was used to improve the loading of both the molecules in liposomes. ARNIPL with mean particle size 111.1 ± 6.55 nm exhibited more than 90% encapsulation efficiency for both the drugs and was found to be physically stable for a month at 4 °C. Both the molecules and ARNIPL showed significantly higher cytotoxicity, apoptosis and down-regulation of target proteins BRD4 and c-Myc in vemurafenib-resistant cell line (A375R). Vasculogenic mimicry and clonogenic potential of A375R were significantly inhibited by ARNIPL. Tumor growth inhibition in 3D spheroids with reduction of TGF-β1 was observed with ARNIPL treatment. Therefore, ARNIPL could be a promising therapeutic approach for the treatment of vemurafenib-resistant melanoma.

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In an attempt to find a potential cure for cancer, scientists have been probing the efficacy of the food we eat and its bioactive components. Over the decades, there has been an exponentially increasing trend of research correlating food and cancer. This review explains the molecular mechanisms by which bioactive food components exhibit anticancer effects in several cancer models. These bioactive compounds are mainly plant based or microbiome based. While plants remain the primary source of these phytochemicals, little is known about probiotics, i.e., microbiome sources, and their relationships with cancer. Thus, the molecular mechanisms underlying the anticancer effect of probiotics are discussed in this review. The principal mode of cell death for most food bioactives is found to be apoptosis. Principal oncogenic signaling axes such as Akt/PI3K, JAK/STAT, and NF-κB seem to be modulated due to these bioactives along with certain novel targets that provide a platform for further oncogenic research. It has been observed that probiotics have an immunomodulatory effect leading to their chemopreventive actions. Various foods exhibit better efficacy as complete extracts than their individual phytochemicals, indicating an orchestrated effect of the food components. Combining bioactive agents with available chemotherapies helps synergize the anticancer action of both to overcome drug resistance. Novel techniques to deliver bioactive agents enhance their therapeutic response. Such combinations and novel approaches are also discussed in this review. Notably, most of the food components that have been studied for cancer have shown their efficacy in vivo. This bolsters the claims of these studies and, thus, provides us with hope of discovering anticancer agents in the food that we eat.