The activation of immune cells in response to stimuli present in their microenvironment is regulated by their metabolic profile. Unlike the signal transduction events, which overlap to a huge degree in diverse cellular processes, the metabolome of a cell reflects a more precise picture of cell physiology and function. Different factors governing the cellular metabolome include receptor signaling, macro and micronutrients, normoxic and hypoxic conditions, energy needs, and biomass demand. Macrophages have enormous plasticity and can perform diverse functions depending upon their phenotypic state. This review presents recent updates on the cellular metabolome and molecular patterns associated with M1 and M2 macrophages, also termed “classically activated macrophages” and “alternatively activated macrophages,” respectively. M1 macrophages are proinflammatory in nature and predominantly Th1‐specific immune responses induce their polarization. On the contrary, M2 macrophages are anti‐inflammatory in nature and primarily participate in Th2‐specific responses. Interestingly, the same macrophage cell can adapt to the M1 or M2 phenotype depending upon the clues from its microenvironment. We elaborate on the various tissue niche‐specific factors, which govern macrophage metabolism and heterogeneity. Furthermore, the current review provides an in‐depth account of deregulated macrophage metabolism associated with pathological disorders such as cancer, obesity, and atherosclerosis. We further highlight significant differences in various metabolic pathways governing the cellular bioenergetics and their impact on macrophage effector functions and associated disorders.
Sestrin2 expression was found to be significantly reduced in p53 mutated SGC cases and in cases with strong p53 nuclear immunopositivity, suggesting that loss of sestrin2 may be of biological significance in the development of SGC and as a key downstream component of p53 tumour suppression network in eyelid SGC.
The DNA topoisomerase (topo) II of chloroquine-sensitive and chloroquine-resistant strains of the rodent malaria parasite P. berghei were utilized as a target for testing of antimalarial compounds. Compounds belonging to the bischalcone and chalcone series significantly inhibited enzyme activity and percentage parasitaemia of chloroquine-sensitive and chloroquine-resistant strains of P. berghei. Compounds 1a, 1b, 2a, 2b, and 2c showed 100% inhibition while compounds 2h and 2i showed 60% and 63% inhibition of topoisomerase II activity of the chloroquinesensitive strain, respectively. Compounds 2a, 2b, and 2d significantly inhibited the topo II activity of chloroquine-resistant strain. Compounds 2g and 2e specifically inhibited the topo II activity of the chloroquine-resistant strain of P. berghei with no effect on the chloroquine-sensitive strain. The in vitro topo II inhibition by chalcone and bischalcone analogs can be correlated with their in vivo antimalarial activity, as compounds 2c and 2h inhibited both in vitro activity of topo II and in vivo parasitaemia of the chloroquine-sensitive strain of P. berghei. In the chloroquine-resistant strain, compounds 2c, 2e, 2g, and 2i inhibited activity against both in vitro topo II and parasitaemia in vivo. The significant inhibition of topo II in the chloroquine-resistant strain by some of the analogs suggests the utilization of these structures for the synthesis of compounds active against chloroquine-resistant malarial parasites.
Oxidative stress is a phenomenon that occurs in the body when there is an imbalance between the production of oxygen reactive species (free radical) and antioxidant molecules. Rusting of iron takes place on continuous expo- sure to oxygen. Likewise, the accumulation of free radicals in the body results in oxidative stress which results in tissue damage and thus leads to various diseases. Rasayana Chikitsa helps in the attainment of good quality of rasa. Guduchi [Tinospora cordifolia (Willd) Miers. F. & Thomas] is a marvellous drug having Rasayana property belonging to the Menispermaceae family enriched with antioxidant molecules. It has the power to detoxify, reju- venate and boost the immune system. ‘Guduchi’ the word itself conveys the meaning ‘which protects the body from diseases.Tinospora cordifolia is well known for its properties such as antioxidant, anti-hyperglycemic, anti-hyperlipidemic, hepato-protective, cardio-protective, neuroprotective, osteo-protective, radio-protective, anti-anxiety, adaptogenic agent, analgesic, anti-inflammatory, antipyretic, thrombolytic agent, anti-diarrheal, anti-ulcer, anti-microbial and anti-cancer agent. An attempt has been made to review the role of Guduchi in the pre- vention of oxidative stress based on the different studies carried out regarding the antioxidant activity of Guduchi. Studies proved that the Phenolic content of Guduchi is meant for its antioxidant activity. Based on Ayurvedic the- ories, Guduchi acts at the level of Agni and helps in the formation of the fine quality of rasa. Also, prevent the accumulation of a toxic substance called Ama that which is considered as the root cause of disease.
Keywords: Guduchi, free radical, Oxidative stress, Antioxidant activity
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