Disease modeling has become challenging in the context of amyotrophic lateral sclerosis (ALS), as obtaining viable spinal motor neurons from postmortem patient tissue is an unlikely possibility. Limitations in the animal models due to their phylogenetic distance from human species hamper the success of translating possible findings into therapeutic options. Accordingly, there is a need for developing humanized models as a lead towards identifying successful therapeutic possibilities. In this study, human embryonic stem cells-BJNHem20-were differentiated into motor neurons expressing HB9, Islet1, and choline acetyl transferase using retinoic acid and purmorphamine. These motor neurons discharged spontaneous action potentials with two different frequencies (< 5 and > 5 Hz), and majority of them were principal neurons firing with < 5 Hz. Exposure to cerebrospinal fluid from ALS patients for 48 h induced several degenerative changes in the motor neurons as follows: cytoplasmic changes such as beading of neurites and vacuolation; morphological alterations, viz., dilation and vacuolation of mitochondria, curled and closed Golgi architecture, dilated endoplasmic reticulum, and chromatin condensation in the nucleus; lowered activity of different mitochondrial complex enzymes; reduced expression of brain-derived neurotrophic factor; up-regulated neurofilament phosphorylation and hyperexcitability represented by increased number of spikes. All these changes along with the enhanced expression of pro-apoptotic proteins-Bax and caspase 9-culminated in the death of motor neurons.

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Wnt/β-Catenin signaling pathway plays a major role in embryonic development and tumorogenesis on several human cancers. In colorectal cancer, the frequent mutations of Adenomatous polyposis coli (APC), β-Catenin and Glycogen synthase kinase 3β (GSK-3β) leads to accumulate the unphosphorylated β-catenin in cytoplasm. Further, its translocate into the nucleus, where it interacted with T-cell factor/ Lymphocyte enhancer factor (TCF/LEF) family of transcription factors to activate inappropriate expression of downstream targets. Therefore, Wnt/β-Catenin signaling proteins are mainly focused as potential therapeutic targets on colorectal cancer. In recent investigations, the antitumorogenic and chemopreventive property of phytochemicals extracted from the flowers of Butea monosperma (Bm) has been elucidated by using transgenic and rodent animal models. In the present study, the eight major compounds of n-butanol fractions of Bm flowers were docked against Wnt/β-Catenin signaling proteins by using AutoDock tool v 4.2 and ADT v1.5.4. The incurred active compounds of butrin and isobutrin showed a good binding interaction with Wnt/β-Catenin proteins. Hence, this finding suggesting that butrin and isobutrin would be considered as a potent antitumorogenic drug to target Wnt/β-Catenin associated cancers.

Synthesis and Antimicrobial Activity Studies of Certain Pyrimidinyl OxadiazoloAzetidinones. -The antibacterial screening reveals that compounds (VIIIb), (VIIId) and (VIIIe) show good activities against M.lutues and P.aeruginosa. Compounds (VIIIb), (VIIId) show significant activities against A.niger, and compounds (VIIIa), (VIIId) and (VIIIe) show good activities against C.albicans. -(GEORGE*, S.; SABITHA, R.; GOVINDHAMMAL, V.; RAVI, T. K.; Indian J. Chem., Sect. B: Org.

Pet ether and acetone extracts of the plant Aristolochia Bracteata were prepared using Soxlet extraction. phytochemical analysis of Aristolochia Bracteata showed the presence of alkaloids, carbohydrates, flavones, triterpenoids and phytosterols in the crude extracts. In the present study, Pet.ether and acetone extracts of Aristolochia Bracteata was investigated for their anti pyretic activity. Injection of 20 ml/kg (s.c) of 20% aqueous suspension of Brewer's yeast suspension produced pyrexia in rats. Extracts at 250 mg/kg exhibited significant anti pyretic activity. Aspirin (300mg/kg) was included as standard. Pet. Ether extracts was found to be more effective than acetone extract.