Browsing by Author "Yadav, Sushil"

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Evaluation of Anti-depressant and Analgesic- Like Activity of Ondansetron in Rodents Model of Co-morbid Pain and Depression
(IJPER, 2015-02) Mahesh, R.; Yadav, Sushil
Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report the comorbidity of pain and depression-like behavior. The antidepressant and analgesic like activity of Ondansetron (OND, 0.25-2mg/kg) were investigated in animal models of acute depression (forced swim test ) and pain ( tail flick test) , existence of co-morbidity of pain and depression was simulated in surgical models in rats like olfactory bulbectomy (OBX) model of chronic depression and chronic constrictive injury (CCI) of chronic pain conditions. Acute administration of OND (0.5-2mg/kg i.p) significantly reduced the duration of immobility in mice in FST and increased the time latency in tail flick test. Behavioural anomalies shown by OBX rats in open field test was significantly reversed by OND (1-2 mg/kg p.o) but OBX rats failed to show the any kind of nociception. Further OND successfully reversed pain in CCI rats. In addition to reversal of pain, OND (1-2mg/kg p.o) significantly reduced the hyperactivity exhibited by CCI rats in open field test suggesting the effect of OND in co-morbid pain and depression. OND exhibited significant antidepressant and analgesic like effect as indicated by its ability to reduce swim stress induced immobility and reduction in writhing. The present study showed that OND has equal efficacy in comorbid pain and depression-like behavioural mediated through serotonergic system.
Evaluation of Anti-depressant and Analgesic- Like Activity of Ondansetron in Rodents Model of Co-morbid Pain and Depression
(IJPER, 2015-02) Mahesh, R.; Yadav, Sushil
Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report the comorbidity of pain and depression-like behavior. The antidepressant and analgesic like activity of Ondansetron (OND, 0.25-2mg/kg) were investigated in animal models of acute depression (forced swim test ) and pain ( tail flick test) , existence of co-morbidity of pain and depression was simulated in surgical models in rats like olfactory bulbectomy (OBX) model of chronic depression and chronic constrictive injury (CCI) of chronic pain conditions. Acute administration of OND (0.5-2mg/kg i.p) significantly reduced the duration of immobility in mice in FST and increased the time latency in tail flick test. Behavioural anomalies shown by OBX rats in open field test was significantly reversed by OND (1-2 mg/kg p.o) but OBX rats failed to show the any kind of nociception. Further OND successfully reversed pain in CCI rats. In addition to reversal of pain, OND (1-2mg/kg p.o) significantly reduced the hyperactivity exhibited by CCI rats in open field test suggesting the effect of OND in co-morbid pain and depression. OND exhibited significant antidepressant and analgesic like effect as indicated by its ability to reduce swim stress induced immobility and reduction in writhing. The present study showed that OND has equal efficacy in comorbid pain and depression-like behavioural mediated through serotonergic system.
Lipopolymeric nanoplex-mediated CRISPR/Cas9 delivery for VEGF-A knockdown in psoriatic angiogenesis
(ACS, 2025-10) Yadav, Sushil; Mittal, Anupama; Chitkara, Deepak
Psoriasis is a chronic, incurable inflammatory skin disease characterized by immune cell infiltration, aberrant keratinocyte differentiation, and enhanced angiogenesis. Overexpression of the vascular endothelial growth factor-A (VEGF-A) gene promotes angiogenesis and is essential for endothelial cell migration, adhesion, and proliferation. Therefore, downregulating VEGF-A represents a promising therapeutic strategy for angiogenesis-related disorders. We investigated the application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) ribonucleoprotein complexes (sgRNA/eGFP-Cas9 RNPs) targeting VEGF-A in psoriasis. To enable efficient delivery in vitro and in vivo, we developed lipopolymeric nanoplexes (NPXs) encapsulating sgRNA/eGFP-Cas9 RNPs. These NPXs exhibited a particle size of 142.2 nm (polydispersity index: 0.144), a zeta potential of +4.27 mV, and achieved >70% transfection efficiency in HaCaT (human immortalized keratinocyte) cells. Ex vivo skin permeation studies demonstrated 66% of permeation after 24 h. The optimized NPX formulation was incorporated into a Carbopol-based gel, which displayed non-Newtonian, shear-thinning behavior with variable thixotropy and achieved 48% of skin permeation after 24 h. In vivo efficacy assessment in an imiquimod-induced psoriasis model in Swiss albino mice showed significantly improved Psoriasis Area and Severity Index (PASI) scores, reduced epidermal damage, and suppressed keratinocyte proliferation compared to naked RNPs and blank gel controls. Gene editing analysis revealed an indel frequency of 40.7% by T7 endonuclease I assay and 14% by Sanger sequencing. Enhanced cellular uptake, efficient skin permeation and retention, and improved therapeutic efficacy collectively highlight the potential of NPX-mediated CRISPR/Cas9 delivery as a noninvasive strategy for psoriasis treatment.