Studies on the activities of antioxidant enzymes under induced drought stress in in vivo and in vitro plants of Macrotyloma uniflorum (Lam.) Verdc.

Activities of glutathione reductase, guaiacol peroxidase, catalase and contents of ascorbic acid, Hydrogen peroxide were analysed in in vitro and in vivo plants of Macrotyloma uniflorum under Polyethylene glycol (PEG) induced drought condition. Water stress was induced in in vitro plants by supplementing the regeneration medium with PEG (Mol. Wt. 6000) at the concentrations ranging from 5 to 25% while in in vivo plants by watering PEG solution with the same concentrations. The activities of glutathione reductase and guaiacol peroxidase were increased under induced drought stress condition in both treated samples. On contrary, catalase activities were decreased. The contents of ascorbic acid and hydrogen peroxide were enhanced correspondingly as the concentration of the PEG increased from 5 to 25%. The role of antioxidant enzymes under water stress condition is discussed. Further, the feasibility of mining the novel genes of drought resistance from the in vitro plants of Macrotyloma uniflorum is highlighted

ASSOCIATION OF SERUM URIC ACID AND LIPID PROFILE IN TYPE 2 DIABETIC PATIENTS WITH AND WITHOUT DIABETIC RETINOPATHY

Objectives: Diabetic retinopathy (DR) is one of the microvascular complications in type 2 diabetes (T2D).  Elevated serum uric acid (SUA) has been shown to play a significant role in diabetic neuropathy and nephropathy but there is little information on retinopathy. Therefore, the present study was aimed to investigate the SUA and lipid profile in T2D patients with and without DR and the association between SUA and severity of DR.Methods: The study was conducted in the ophthalmology OPD at Sri Lakshmi Narayana Institute of Medical Sciences. The presence of T2D was confirmed by investigating fasting blood glucose level (normal limit < 110 mg/dl) in all the individuals. DR was examined by detailed dilated fundoscopic examination. Based on the fundus examination, patients were divided in to diabetes with signs of DR and those without signs of DR. Age and sex matched healthy were taken as controls. Fasting blood sugar, SUA and lipid profile were investigated for these groups. Results: The study found elevated SUA and abnormal lipid profile in DR group when compared to non-DR and control groups. We also found the significant association between SUA and severity of DR particularly in males.Conclusion: We found a significant association between SUA and severity of DR in T2D patients. Further studies with large sample size are needed to establish the role of elevated SUA and the mechanism involved in the pathogenesis of retinopathy in diabetic patients. Regular measurements of SUA level could be advised to the diabetic patients for the early management

Preclinical assessment of ulixertinib, a novel ERK1/2 inhibitor

Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. In xenograft studies it inhibited tumor growth in BRAF-mutant melanoma and colorectal xenografts as well as KRAS-mutant colorectal and pancreatic models. Ulixertinib is currently in Phase I clinical development for the treatment of advance solid tumors. The objective of the study is to assess the metabolic stability (in various pre-clinical and human liver microsomes/hepatocytes), permeability, protein binding, CYP inhibition, CYP induction and CYP phenotyping of ulixertinib. We have also studied the oral and intravenous pharmacokinetics of ulixertinib in mice, rats and dogs. Ulixertinib was found to be moderately to highly stable in various liver microsomes/hepatocytes tested. It is a medium permeable (2.67 x 10-6 cm /sec) drug and a substrate for efflux (efflux ratio: 3.02) in Caco-2 model. Ulixertinib was highly bound to plasma proteins. CYPs involved in its limited metabolism and it is CYP inhibition IC50 ranged between 10-20 μM. Post oral administration ulixertinib exhibited early Tmax (0.50-0.75 h) in mice and rats indicating absorption was rapid, however in dogs Tmax attained at 2 h. The half-life (t½) of ulixertinib by intravenous and oral routes ranged between 1.0-2.5 h across the species. Clearance and volume of distribution by intravenous route for ulixertinib were found to be 6.24 mL/min/kg and 0.56 L/kg; 1.67 mL/min/kg and 0.36 L/kg and 15.5 mL/min/kg and 1.61 L/kg in mice, rats and dogs, respectively. Absolute oral bioavailability in mice and rats was > 92 %, however in dogs it was 34 %

Preclinical assessment of ulixertinib, a novel ERK1/2 inhibitor

Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. In xenograft studies it inhibited tumor growth in BRAF-mutant melanoma and colorectal xenografts as well as KRAS-mutant colorectal and pancreatic models. Ulixertinib is currently in Phase I clinical development for the treatment of advance solid tumors. The objective of the study is to assess the metabolic stability (in various pre-clinical and human liver microsomes/hepatocytes), permeability, protein binding, CYP inhibition, CYP induction and CYP phenotyping of ulixertinib. We have also studied the oral and intravenous pharmacokinetics of ulixertinib in mice, rats and dogs. Ulixertinib was found to be moderately to highly stable in various liver microsomes/hepatocytes tested. It is a medium permeable (2.67 x 10-6 cm /sec) drug and a substrate for efflux (efflux ratio: 3.02) in Caco-2 model. Ulixertinib was highly bound to plasma proteins. CYPs involved in its limited metabolism and it is CYP inhibition IC50 ranged between 10-20 µM. Post oral administration ulixertinib exhibited early Tmax (0.50-0.75 h) in mice and rats indicating absorption was rapid, however in dogs Tmax attained at 2 h. The half-life (t½) of ulixertinib by intravenous and oral routes ranged between 1.0-2.5 h across the species. Clearance and volume of distribution by intravenous route for ulixertinib were found to be 6.24 mL/min/kg and 0.56 L/kg; 1.67 mL/min/kg and 0.36 L/kg and 15.5 mL/min/kg and 1.61 L/kg in mice, rats and dogs, respectively. Absolute oral bioavailability in mice and rats was > 92 %, however in dogs it was 34 %

Magnetic nanoparticles are highly toxic to chloroquine-resistant Plasmodium falciparum, dengue virus (DEN-2), and their mosquito vectors

SURESH KUMAR SUBBIAH (A04156) / / / Kadarkarai Murugan,Jiang Wei,Mohamad Saleh Alsalhi,Marcello Nicoletti,Manickam Paulpandi,Christina Mary Samidoss,Devakumar Dinesh,Balamurugan Chandramohan,Chellasamy Paneerselvam,Jayapal Subramaniam,Chithravel Vadiva

Regeneration of multiple shoots from the callus cultures of Macrotyloma uniflorum (Lam.) Verdc

An effective protocol for the regeneration of multiple shoots from the callus, derived from shoot tip and cotyledonary node, was developed for the first time for Macrotyloma uniflorum (Lam.) Verdc. Shoot apices and cotyledonary nodes from 9-d-old aseptically grown seedlings were inoculated onto MS, L 2 and MMS media supplemented with various growth regulators. Proliferation of about 17 shoots was obtained on AS supplemented MS medium after 16 d of culture, while about 14 and 20 shoots regenerated from the callus on MMS1+NAA (1.86 μM)+BAP(0.45 μM) and L2+IBA (0.45 μM)+BAP (0.11 μM), respectively after 30 d of culture. Regenerated shoots were rooted on MS+IAA (0.11 μM)+Kn (0.21 μ) with upto 6 roots per shoot. Rooted shoots were sequentially acclimatized by transferring them to sterile distilled water and tap water before planting in various pot mixtures. A maximum of 60 survival rate was noticed on a mixture of soil:sand:manure (1:1:1)

Regeneration of multiple shoots from the callus cultures of <i style="">Macrotyloma uniflorum </i>(Lam.) Verdc.

101-105An effective protocol for the regeneration of multiple shoots from the callus, derived from shoot tip and cotyledonary node, was developed for the first time for Macrotyloma uniflorum (Lam.) Verdc. Shoot apices and cotyledonary nodes from 9-d-old aseptically grown seedlings were inoculated onto MS, L2 and MMS media supplemented with various growth regulators. Proliferation of about 17 shoots was obtained on AS supplemented MS medium after 16 d of culture, while about 14 and 20 shoots regenerated from the callus on MMS1+NAA (1.86 μM)+BAP (0.45 μM) and L2+IBA (0.45 μM)+BAP (0.11 μM), respectively after 30 d of culture. Regenerated shoots were rooted on MS+IAA (0.11 µM)+Kn (0.21 µM) with upto 6 roots per shoot. Rooted shoots were sequentially acclimatized by transferring them to sterile distilled water and tap water before planting in various pot mixtures. A maximum of 60% survival rate was noticed on a mixture of soil:sand:manure (1:1:1)

Nanofabrication of Graphene Quantum Dots with High Toxicity Against Malaria Mosquitoes, Plasmodium falciparum and MCF-7 Cancer Cells: Impact on Predation of Non-target Tadpoles, Odonate Nymphs and Mosquito Fishes

Recently, it has been highlighted an overlooked connection between the biting activity of Anopheles mosquitoes and the spread of cancer. The excellent physico-chemical properties of graphene quantum dots (GQDs) make them a suitable candidate for biomedical applications. We focused on the toxicity of GQDs against Plasmodium falciparum and its vector Anopheles stephensi, and their impact on predation of non-target mosquito predators. Biophysical methods, including UV–vis, photoluminescence, FTIR and Raman spectroscopy, XRD analysis and TEM, confirmed the effective GQD nanosynthesis. LC50 against A. stephensi ranged from 0.157 (larva I) to 6.323 ppm (pupa). The antiplasmodial activity of GQDs was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of P. falciparum. IC50 were 82.43 (CQ-s) and 85.17 μg/ml (CQ-r). In vivo experiments conducted on Plasmodium berghei infecting albino mice showed moderate activity of GQDs if compared to chloroquine. Concerning non-target effects, the predation efficiency of Gambusia affinis, Anax immaculifrons and Hoplobatrachus tigerinus post-treatment with GQDs was enhanced. Lastly, GQDs were toxic against MCF-7 breast cancer cell lines with an IC50 = 24.81 μg/ml, triggering apoptosis in treated cells. Overall, we highlighted the multipurpose potential of GQDs for the development of newer drugs in the fight against Anopheles vectors, Plasmodium parasites and breast cancer cells

Nanofabrication of Graphene Quantum Dots with High Toxicity Against Malaria Mosquitoes, Plasmodium falciparum and MCF-7 Cancer Cells: Impact on Predation of Non-target Tadpoles, Odonate Nymphs and Mosquito Fishes

Recently, it has been highlighted an overlooked connection between the biting activity of Anopheles mosquitoes and the spread of cancer. The excellent physico-chemical properties of graphene quantum dots (GQDs) make them a suitable candidate for biomedical applications. We focused on the toxicity of GQDs against Plasmodium falciparum and its vector Anopheles stephensi, and their impact on predation of non-target mosquito predators. Biophysical methods, including UV–vis, photoluminescence, FTIR and Raman spectroscopy, XRD analysis and TEM, confirmed the effective GQD nanosynthesis. LC50 against A. stephensi ranged from 0.157 (larva I) to 6.323 ppm (pupa). The antiplasmodial activity of GQDs was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of P. falciparum. IC50 were 82.43 (CQ-s) and 85.17 μg/ml (CQ-r). In vivo experiments conducted on Plasmodium berghei infecting albino mice showed moderate activity of GQDs if compared to chloroquine. Concerning non-target effects, the predation efficiency of Gambusia affinis, Anax immaculifrons and Hoplobatrachus tigerinus post-treatment with GQDs was enhanced. Lastly, GQDs were toxic against MCF-7 breast cancer cell lines with an IC50 = 24.81 μg/ml, triggering apoptosis in treated cells. Overall, we highlighted the multipurpose potential of GQDs for the development of newer drugs in the fight against Anopheles vectors, Plasmodium parasites and breast cancer cells