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: The transcriptional factor PPAR-γ belongs to the nuclear receptor family, which has become a potential therapeutic target for several neurodegenerative diseases and metabolic disorders. Interestingly, PPAR-γ has been reported to have beneficial effects in various chronic neurological conditions via upregulation of its transcriptional co-activator PGC-1α and followed by regulation of multiple molecular events. Although several factors contribute to the progression of neurodegeneration, the dysfunction of PGC-1α expression is primarily interlinked with the pathogenesis of major neurodegenerative diseases. This review gives an insight that ligand-dependent activation of PPAR-γ by glitazones could initiate the structural conformational changes of the secondary proteins, thus recruiting the PGC-1α to form a regulatory stable complex which hampers the various molecular pathways contributing to neurodegeneration. The promising outcomes of the preliminary in silico studies included in this review support that PPAR-γ dependent activation of central PGC-1α signaling by novel glitazones is an encouraging strategy to enhance the oxy-radicals detoxifying system, anti-inflammatory responses, and mitochondrial biogenesis required for neuroprotection in various neurodegenerative conditions.

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Colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. The present study has been carried out to see the frequency of lost MMR protein expression and its histopathological characteristics in unselected colorectal cancer patients from north India. 103 consecutive patients of colorectal cancer who underwent surgery between 2014-2018 in a tertiary care teaching hospital in North India were included in the study. The study was approved by the Institute’s Ethical Committee. MMR protein status was determined by Immunohistochemistry (IHC) to examine the expression of MLH1, PMS2, MSH2 and MSH6 on paraffin-embedded tissues. Patients with MLH1deficient protein were further followed by BRAF V600E testing. The histopathological features were correlated with MMR protein expression. IHC results revealed a loss of different MMR protein expression in 33 (32%) patients. the most frequent loss was lost MSH2 12(36.4%) followed by MLH1 10(30.3%), PMS2 8(24.2%) and MSH6 3(9.1%); Out of 10 MLH1 deficient cases, 6 (60%) were BRAF V600E mutant and 4 (40%) were BRAF-wild-type. We have found significance with medullary histological phenotype, poor histological grade and TILS. In our study, the frequency of MMR protein loss was found in 32% of patients of CRC. The loss was significantly associated with medullary phenotype, degree of differentiation and presence of tumor infiltrating lymphocytes (TILS).

Multiple sclerosis (MS) is a neurological condition with a complicated autoimmune component that mainly affects women in their forties and fifties. The disorder appears in several forms, ranging from episodic somatosensory impairment to progressive and irreversible central nervous system (CNS) injury. The fundamental cause of this disorder is lack of serotonin (5HT), a neurotransmitter with numerous immune effects. Decreased 5-HT levels or synthesis have also been related to increased proinflammatory cytokines in the CNS. Among several other proinflammatory cytokines, two prototypic pro-inflammatory cytokines, interleukin-1 (IL-1β) and tumor necrosis factor (TNF-α) have been identified as primary effectors of neuroinflammation's functional effects on neurodegeneration.TNF-α is a pleiotropic cytokine that regulates homeostasis, immunity, and inflammation and IL-1β is also a cytokine with neuroimmunological and neurophysiological functions. MS patients are usually on drugs that change the serotonergic system, because of increased clinical comorbidities and proven serotonin deficits. Several studies have shown that higher 5-HT levels have anti-inflammatory and immune-modulating properties, which could help to delay the progression of the disease.