Statins are known to modulate cell surface cholesterol (CSC) and AMP-activated protein kinase (AMPK) in non-neural cells; however no study demonstrates whether CSC and AMPK may regulate simvastatin induced neuritogenesis (SIN). We found that simvastatin (SIM) maintains CSC as shown by Fillipin III staining, Flotillin-2 protein expression / localization and phosphorylation of various receptor tyrosine kinases (RTKs) in the plasma membrane. Modulation of CSC revealed that SIN is critically dependent on this CSC. Simultaneously, phospho array for mitogen activated protein kinases (MAPKs) revealed PI3K / Akt as intracellular pathway which modulates lipid pathway by inhibiting AMPK activation. Though, SIM led to a transient increase in AMPK phosphorylation followed by a sudden decline; the effect was independent of PI3K. Strikingly, AMPK phosphorylation was regulated by protein phosphatase 2A (PP2A) activity which was enhanced upon SIM treatment as evidenced by increase in threonine phosphorylation. Moreover, it was observed that addition of AMP analogue and PP2A inhibitor inhibited SIN. Bio-composition of neurites shows that lipids form a major part of neurites and AMPK is known to regulate lipid metabolism majorly through acetyl CoA carboxylase (ACC). AMPK activity is negative regulator of ACC activity and we found that phosphorylation of ACC started to decrease after 6 hrs which becomes more pronounced at 12 hrs. Addition of ACC inhibitor showed that SIN is dependent on ACC activity. Simultaneously, addition of Fatty acid synthase (FAS) inhibitor confirmed that endogenous lipid pathway is important for SIN. We further investigated SREBP-1 pathway activation which controls ACC and FAS at transcriptional level. However, SIM did not affect SREBP-1 processing and transcription of its target genes likes ACC1 and FAS. In conclusion, this study highlights a distinct role of CSC and ACC in SIN which might have implication in process of neuronal differentiation induced by other agents.

Nonsteroid anti-inflammatory drugs (NSAIDs) represent standard therapy for the alleviation of pain and inflammation. At present various classes of compounds have been reported as selective inhibitors of cyclooxygenase-2 (COX-2). However, they are associated with adverse side effects. To address these issues, we report here a new class of compounds that exhibit potent analgesic and anti-inflammatory response. Substituted bromo-benzothiophene carboxamides (4-11) were examined for their analgesic and anti-inflammatory properties. Our findings demonstrate that newly synthesized bromobenzothiophene carboxamide derivatives 4, 6, and 8 attenuate nociception and inflammation at lower concentration than classical NSAIDs, such as ibuprofen. These compounds act by selectively inhibiting COX-2 and by disrupting the prostaglandin-E2-dependent positive feedback of COX-2 regulation, which was further substantiated by reduction in the levels of cytokines, chemokines, neutrophil accumulation, synthesis of prostaglandin-E2, expression of COX-2, and neutrophil activation at lower concentration than the classic NSAID ibuprofen. Toxicological study reveals that these compounds are well tolerated and metabolized to avoid any toxicity. Thus, these molecules represent a new class of analgesic and anti-inflammatory agents.

A signicant proportion of patients who recovered from SARCoV-2 infection develop chronic symptoms lasting weeks or months, referred as Long COVID. Though the exact etiology of Long COVID is unknown; however, one of major symptom experienced by these patients is chronic fatigue syndrome which is associated with several mitochondrial disorders or viral diseases. In this review, a systematic approach has been performed to explain Long COVID as possible outcome of mitochondrial dysfunction. The review highlights what is known in literature about the dysfunctional pathways which can develop in mitochondria and their relationship to viruses and associated mitochondrial disorders. It also identies potential areas which require urgent, further research in order to help clinical management and interventional studies for better long-term outcomes.

Background: Hypotension is one of the major adverse effects seen in patients undergoing spinal anaesthesia and is reported to be seen in more than 30 percent of the cases of patients receiving spinal anaesthesia. It has been highlighted in various studies that the use of atropine and ephedrine in the improvement of hemodynamic parameter when used preoperatively in spinal aesthesia. Hence; we carried this study to evaluate and compare the heart rate and mean arterial pressure after spinal anaesthesia with prophylactic use of atropine, ephedrine and placebo in elderly patients. Materials & Methods:The present study was conducted among 120 patients who underwent surgical procedures under spinal anaesthesia. Patients were randomly divided into three study groups; Group 1 (40 patients): who received normal saline, Group 2 (40 patients) who received 0.6 mg of atropine and Group 3 (40 patients) who received 12 mg of ephedrine. Study drugs were administered to the patients one minute after the spinal anaesthesia. Recording of the various parameters such as amount of vasopressor needed (phenlyephrine), after 15 minutes of spinal anaesthesia, sensory level reached presence of intra-operative angina and intra/postoperative confusion and other side effects till six hours post-surgically was done. All the results were analyzed by SPSS software. Results: MAP at the baseline time in the three study groups was found to be 98.5, 91.5 and 93.7 respectively. 14 patients in

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