Photoperiod manipulation improves growth performance, haematological indices and economic returns of Indian butter catfish, Ompok bimaculatus (Bloch, 1794).

Photoperiod manipulation is emerging as an effective approach for regulating physiological functions in fish. This study aimed to assess the impact of photoperiod on the growth performance, haematological responses, and economic returns of the endangered and highly valued Indian butter catfish, Ompok bimaculatus. Fish with an average body weight of 28.60 ± 4.78 g were randomly placed in six FRP tanks, each measuring 120 × 45 × 60 cm3. Each tank contained 20 fish exposed to a light intensity of 1500 lx under different photoperiods [24:0 light: dark (L: D), 15 L: 9D, 12 L: 12D, 9 L: 15D, 0 L: 24D and a natural photoperiod (control)], and fed at a daily rate of 2% of their body weight twice daily for 60 days. The fish in the 15 L: 9D photoperiod exhibited the highest final weight (g), percentage weight gain, specific growth rate (SGR) and survival rate, while the lowest was displayed in 24 L: 0D photoperiod group. The feed conversion ratio (FCR) was at its lowest in the catfish subjected to the 15 L: 9D photoperiod. Regarding haematological parameters, the 15 L: 9D photoperiod group showed higher total erythrocyte count, total leukocyte count, haemoglobin levels, and haematocrit values compared to the other groups. Conversely, the 0 L: 24D group, which experienced prolonged darkness, exhibited the lowest values in these parameters. Moreover, the 24 L: 0D, 9 L: 15D, and 0 L: 24D groups displayed a lower mean corpuscular volume (MCV) but higher mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) when compared to the control group. The economic analysis revealed that O. bimaculatus reared in a moderate photoperiod (15 L: 9D) displayed better growth, feed utilization, and overall health. This finding suggests that adopting a 15 L: 9D photoperiod can lead to enhanced production and improved economic returns for farmers culturing this high-value catfish in the future.

Preconditioning with INC280 and LDK378 drugs sensitizes MGMT-unmethylated glioblastoma to temozolomide: Pre-clinical assessment.

Temozolomide (TMZ) therapy is the standard of care for patients with glioblastoma (GBM). Clinical studies have shown that elevated levels of DNA repair protein O (6)-methylguanine-DNA methyltransferase (MGMT) or deficiency/defect of DNA mismatch repair (MMR) genes is associated with TMZ resistance in some, but not all, GBM tumors. Another reason for GBM treatment failure is signal redundancy due to coactivation of several functionally linked receptor tyrosine kinases (RTKs), including anaplastic lymphoma kinase (ALK) and c-Met (hepatocyte growth factor receptor). As such, these tyrosine kinases serve as potential targets for GBM therapy. Thus, we tested two novel drugs: INC280 (Capmatinib: a highly selective c-Met receptor tyrosine kinase-RTK inhibitor) and LDK378 (Ceritinib: a highly selective anaplastic lymphoma kinase-ALK inhibitor), aiming to overcome TMZ resistance in MGMT-unmethylated GBM cells in in vitro cell culture models. Treatments were examined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, caspase-3 assay and western blot analysis. Results obtained from our experiments demonstrated that preconditioning with INC280 and LDK378 drugs exhibit increased MMR protein expression, specifically MMR protein MLH1 (MutL Homolog 1) and MSH6 (MutS Homolog 6) and sensitized TMZ in MGMT-unmethylated GBM cells via suppression of ALK and c-Met expression. INC280 and LDK378 plus TMZ also induced apoptosis by modulating downstream signaling of PI3K/AKT/STAT3. Taken together, this data indicates that co-inhibition of ALK and c-MET can enhance growth inhibitory effects in MGMT-unmethylated cells and enhance TMZ sensitivity in-vitro, suggesting c-Met inhibitors combined with ALK-targeting provide a therapeutic benefit in MGMT-unmethylated GBM patients.

Albumin-Assisted Method Allows Assessment of Release of Hydrophobic Drugs From Nanocarriers.

Polymeric nanoparticles have been extensively studied as drug delivery vehicles both in vitro and in vivo for the last two decades. In vitro methods to assess drug release profiles usually utilize degradation of nanoparticles in aqueous medium, followed by the measurement of the concentration of the released drug. This method, however, is difficult to use for drugs that are poorly water soluble. In this study, a protocol for measuring drug release kinetic using albumin solution as the medium is described. Albumin is a major blood transport protein, which mediates transport of many lipid soluble compounds including fatty acids, hormones, and bilirubin. The use of a dialysis-based system utilizing albumin dialysate solution allows hydrophobic drug release from a diverse set of drug delivery modalities is demonstrated. The method using liposomes and PLGA nanoparticles as drug carriers, and two model hydrophobic drugs, 17ß-estradiol, and dexamethasone is validated.