No abstract

Ischemic stroke is a devastating CNS insult with few clinical cures. Poor understanding of underlying mechanistic network is the primary limitation to develop novel curative therapies. Extracellular accumulation of granzyme B subsequent ischemia promotes neurodegeneration. Inhibition of granzyme B can be one of the potent strategies to mitigate neuronal damage. In present study, we investigated the effect of murine Serpina3n and human (homolog) SERPINA3 against cerebral ischemia through granzyme B inactivation. Recombinant Serpina3n/SERPINA3 were expressed by transfected 293 T cells, and eluted proteins were examined for postischemic influence both in vitro and in vivo. During in vitro test, Serpina3n was found effective enough to inhibit granzyme B, while SERPINA3 was ineffectual to counter cytotoxic protease. Treatment of hypoxic culture with recombinant Serpina3n/SERPINA3 significantly increased cell viability in dosage-dependent manner, recorded maximum at the highest concentration (4 mM). Infarct volume analysis confirmed that 50 mg/kg dosage of exogenous Serpina3n was adequate to reduce disease severity, while SERPINA3 lacked behind in analeptic effect. Immunohistochemical test, western blot analysis, and protease activity assay’s results illustrated successful diffusion of applied protein to the ischemic lesion and reactivity with the target protease. Taken together, our findings demonstrate therapeutic potential of Serpina3n by interfering granzyme B-mediated neuronal death subsequent cerebral ischemia.

Cancer is counted as a second leading cause of death among nontransmissible diseases. Identification of novel anticancer drugs is therefore necessary for the effective treatment of cancer. Conventional drug discovery is time consuming and expensive process. Unlike conventional drug discovery, drug repositioning offers a novel strategy for urgent drug discovery since it is a cost-effective and faster process. Bazedoxifene (BZA) is a synthetic selective estrogen receptor modulator, approved by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women. BZA is now being studied for its anticancer activity in various cancers including breast cancer, liver cancer, pancreatic cancer, colon cancer, head and neck cancer, medulloblastoma, brain cancer, and gastrointestinal cancer. Studies have reported that BZA is effective in reducing cancer progression through multiple mechanisms. BZA could effectively inhibit STAT3, PI3K/AKT, and MAPK signaling pathways and induce apoptosis. In addition to its anticancer activity as monotherapy, BZA has been shown to enhance the chemotherapeutic efficacy of clinical drugs such as paclitaxel, cisplatin, palbociclib, and oxaliplatin in multiple neoplasms. This review mainly focused on the anticancer activity, cellular targets, and anticancer mechanism of BZA, which may help the further design and conduct of research and repositioning it for oncological clinic trials.

No abstract

We have evaluated the effects of different fish feeds on the body composition, growth, and enzyme activities of Labeo rohita (Rohu). In total, 240 fishes between the average weights of 24.77±2.15g were studied. The treatments were applied in a completely randomized design, with 4 treatments of 60 fishes each. Treatments consisted of four different fish feeds [Oryza (T1), AMG (T2), Aqua (T3), and Supreme (T4)]. Body composition, growth performance, and enzyme activities were evaluated. There was a significant variation in performance of fishes fed with different type of feed; as fishes having Oryza feed showed the highest weight gain, specific growth rate (SGR), and best feed conversion ratio (FCR) as compared to other groups that were considered to be significant (P ≤ 0.05). High net weight gain was obtained in T4 when compared with T2 and T3. FCR value of T4 was less than T1 but higher than T2, T3 and T2, which showed the lowest values. The specific growth rate was recorded as average in T4, but T2 led a high SGR than T3. Similarly, crude protein level and digestive enzymes activity was recorded significantly highest in fed with Oryza (T1) as compared to AMG (T2), Aqua (T3), and Supreme (T4). Water quality parameters were recorded significant in all treatments except pH and DO of treatment (T1), significantly different from other treatments. It was concluded that Rohu (Labeo rohita) could show a promising growth rate and protease enzyme activity when fed with the Oryza feed of 25% protein.