Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade

Introduction: Heme oxygenase (HO), a major cytoprotective enzyme, attenuates oxidative stress and obesity. The canonical Wnt signaling cascade plays a pivotal role in the regulation of adipogenesis. The present study examined the interplay between HO-1and the Wnt canonical pathway in the modulation of adipogenesis in mesenchymal stem cell (MSC)-derived adipocytes. Methods: To verify the role of HO-1 in generating small healthy adipocytes, cobalt protoporphyrin (CoPP), inducer of HO-1, was used during adipocyte differentiation. Lipid accumulation was measured by Oil red O staining and lipid droplet size was measured by BODIPY staining. Results: During adipogenesis in vitro, differentiating pre-adipocytes display transient increases in the expression of genes involved in canonical Wnt signaling cascade. Increased levels of HO-1 expression and HO activity resulted in elevated levels of b-catenin, pGSK3b, Wnt10b, Pref-1, and shh along with increased levels of adiponectin (P \u3c 0.05). In addition, induction of HO-1 resulted in a reduction in C/EBPa, PPARg, Peg-1/Mest, aP2, CD36 expression and lipid accumulation (P \u3c 0.05). Suppression of HO-1 gene by siRNA decreased Wnt10b, pGSK3b and b-catenin expression, and increased lipid accumulation. The canonical Wnt responsive genes, IL-8 and SFRP1, were upregulated by CoPP and their expression was decreased by the concurrent administration of tin mesoporphyrin (SnMP), an inhibitor of HO activity. Furthermore, knockdown of Wnt10b gene expression by using siRNA showed increased lipid accumulation, and this effect was not decreased by concurrent treatment with CoPP. Also our results show that blocking the Wnt 10b antagonist, Dickkopf 1 (Dkk-1), by siRNA decreased lipid accumulation and this effect was further enhanced by concurrent administration of CoPP. Conclusions: This is the first study to demonstrate that HO-1 acts upstream of canonical Wnt signaling cascade and decreases lipogenesis and adipocyte differentiation suggesting that the HO-1 mediated increase in Wnt10b can modulate the adipocyte phenotype by regulating the transcriptional factors that play a role in adipogenesis. This is evidenced by a decrease in lipid accumulation and inflammatory cytokine levels, increased adiponectin levels and elevation of the expression of genes of the canonical Wnt signaling cascade

Platelet Augmentation Potential of Polyherbal Formulation in Cyclophosphamide-Induced Thrombocytopenia in Wistar Rats

Introduction: Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood. Several medicinal plants possess curative and protective effect against thrombocytopenia associated with diseases or drugs.Aim: In the present study, we have investigated the platelet augmentation activity of polyherbal formulation (VITA PLAT Capsule) in cyclophosphamide-induced thrombocytopenic rat model. Materials and methods: Twenty-four albino Wistar rats were divided into four groups. Thrombocytopenia was induced in the rats by administering cyclophosphamide (25 mg/kg, i.p.) for three days to all the groups except normal controls. The test groups were given orally a polyherbal formulation suspended in normal saline for 14 days. Blood was withdrawn from the retro-orbital plexus of the rats on days 1, 7, and 14 of study to determine platelet counts in all groups. Clotting time and bleeding time were determined on the last day of study. Data were collected and analyzed using GraphPad Prism 8. Results: The results showed that the polyherbal formulation treatment could significantly ameliorate platelet count in thrombocyto-penic rats in the initial as well as in the later phase. The total WBC count was also improved during later phase in test groups. However, there is no significant difference between clotting time and bleeding time in all groups. Conclusions: Our study suggests a potential role of this formulation in the augmentation of platelet counts in various thrombocyto-penic disorders including a role in ameliorating the haemorrhagic complications of dengue fever

Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade

INTRODUCTION: Heme oxygenase (HO), a major cytoprotective enzyme, attenuates oxidative stress and obesity. The canonical Wnt signaling cascade plays a pivotal role in the regulation of adipogenesis. The present study examined the interplay between HO-1and the Wnt canonical pathway in the modulation of adipogenesis in mesenchymal stem cell (MSC)-derived adipocytes. METHODS: To verify the role of HO-1 in generating small healthy adipocytes, cobalt protoporphyrin (CoPP), inducer of HO-1, was used during adipocyte differentiation. Lipid accumulation was measured by Oil red O staining and lipid droplet size was measured by BODIPY staining. RESULTS: During adipogenesis in vitro, differentiating pre-adipocytes display transient increases in the expression of genes involved in canonical Wnt signaling cascade. Increased levels of HO-1 expression and HO activity resulted in elevated levels of β-catenin, pGSK3β, Wnt10b, Pref-1, and shh along with increased levels of adiponectin (P < 0.05). In addition, induction of HO-1 resulted in a reduction in C/EBPα, PPARγ, Peg-1/Mest, aP2, CD36 expression and lipid accumulation (P < 0.05). Suppression of HO-1 gene by siRNA decreased Wnt10b, pGSK3β and β-catenin expression, and increased lipid accumulation. The canonical Wnt responsive genes, IL-8 and SFRP1, were upregulated by CoPP and their expression was decreased by the concurrent administration of tin mesoporphyrin (SnMP), an inhibitor of HO activity. Furthermore, knockdown of Wnt10b gene expression by using siRNA showed increased lipid accumulation, and this effect was not decreased by concurrent treatment with CoPP. Also our results show that blocking the Wnt 10b antagonist, Dickkopf 1 (Dkk-1), by siRNA decreased lipid accumulation and this effect was further enhanced by concurrent administration of CoPP. CONCLUSIONS: This is the first study to demonstrate that HO-1 acts upstream of canonical Wnt signaling cascade and decreases lipogenesis and adipocyte differentiation suggesting that the HO-1 mediated increase in Wnt10b can modulate the adipocyte phenotype by regulating the transcriptional factors that play a role in adipogenesis. This is evidenced by a decrease in lipid accumulation and inflammatory cytokine levels, increased adiponectin levels and elevation of the expression of genes of the canonical Wnt signaling cascade

Quality of life with ribociclib versus abemaciclib as first-line treatment of HR+/HER2− advanced breast cancer: a matching-adjusted indirect comparison

BackgroundA cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + endocrine therapy is recommended as first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Quality of life (QoL) is an important endpoint that affects treatment decisions. Understanding the relevance of CDK4/6i treatment on QoL is gaining importance given use in earlier treatment lines for ABC and an emerging role in treating early breast cancer in which QoL may be more impactful. In the absence of head-to-head trial data, a matching-adjusted indirect comparison (MAIC) permits comparative efficacy between trials.ObjectiveIn this analysis, patient-reported QoL for MONALEESA-2 [ribociclib + aromatase inhibitor (AI)] and MONARCH 3 (abemaciclib + AI) was compared using MAIC with a focus on individual domains.DesignAn anchored MAIC of QoL comparing ribociclib + AI versus abemaciclib + AI was performed using data from the European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ)-C30 and BR-23 questionnaires.MethodsIndividual patient data from MONALEESA-2 and published aggregated data from MONARCH 3 were included in this analysis. Time to sustained deterioration (TTSD) was calculated as the time from randomization to a ⩾10-point deterioration with no later improvement above this threshold.ResultsPatients from the ribociclib (n = 205) and placebo (n = 149) arms of MONALEESA-2 were matched with patients from the abemaciclib (n = 328) and placebo (n = 165) arms of MONARCH 3. After weighting, baseline patient characteristics were well balanced. TTSD significantly favored ribociclib versus abemaciclib in appetite loss [hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.27-0.81], diarrhea (HR, 0.42; 95% CI, 0.23-0.79), fatigue (HR, 0.63; 95% CI, 0.41-0.96), and arm symptoms (HR, 0.49; 95% CI, 0.30-0.79). TTSD did not significantly favor abemaciclib compared with ribociclib in any functional or symptom scale of the QLQ-C30 or BR-23 questionnaires.ConclusionsThis MAIC indicates that ribociclib + AI is associated with better symptom-related QoL than abemaciclib + AI for postmenopausal patients with HR+/HER2- ABC treated in the first-line setting.Trial registrationNCT01958021 (MONALEESA-2) and NCT02246621 (MONARCH 3)

Abstracts of Scientifica 2022

This book contains the abstracts of the papers presented at Scientifica 2022, Organized by the Sancheti Institute College of Physiotherapy, Pune, Maharashtra, India, held on 12–13 March 2022. This conference helps bring researchers together across the globe on one platform to help benefit the young researchers. There were six invited talks from different fields of Physiotherapy and seven panel discussions including over thirty speakers across the globe which made the conference interesting due to the diversity of topics covered during the conference. Conference Title:  Scientifica 2022Conference Date: 12–13 March 2022Conference Location: Sancheti Institute College of PhysiotherapyConference Organizer: Sancheti Institute College of Physiotherapy, Pune, Maharashtra, Indi

3rd National Conference on Image Processing, Computing, Communication, Networking and Data Analytics

This volume contains contributed articles presented in the conference NCICCNDA 2018, organized by the Department of Computer Science and Engineering, GSSS Institute of Engineering and Technology for Women, Mysore, Karnataka (India) on 28th April 2018