Type 3 Diabetes (T3D) is a neuroendocrine disorder that represents the progression of Type 2 Diabetes Mellitus (T2DM) to Alzheimer’s disease (AD). T3D contributes in the increase of the total load of Alzheimer’s patients worldwide. The protein network based strategies were used for the analysis of protein interactions and hypothesis was derived describing the possible routes of communications among proteins. The hypothesis provides the insight on the probable mechanism of the disease progression for T3D. The current study also suggests that insulin degrading enzyme (IDE) could be the major player which holds the capacity to shift T2DM to T3D by altering metabolic pathways like regulation of beta-cell development, negative regulation of PI3K/AKT pathways and amyloid beta degradation.

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COVID-19, emerged at the end of 2019 have dramatically threatened the health, economy, and social mobility of people around the world and till date no medication is available for its treatment. An amazing herb, Nigella sativa , having antiviral, antihypertensive, anti- diarrhoeal, analgesics, and anti-bacterial properties, needs to be explored for its efficacy against SARS-CoV-2, the causative agent of COVID-19. In-silico studies were carried out to understand the role of its bioactive constituents in COVID-19 treatment and prevention. Firstly, the disease network was prepared by using ACE2 (Angiotensin-II receptor), as it is the entry site for virus. It was used to decipher the mechanism of SARS-COV-2 infection in humans. Second, the target receptors for N. sativa were predicted and protein interaction studies were conducted. Further, docking studies were also performed to analyse it for treatment purpose as well. This study concludes that pathways undertaken by N. sativa bioactive constituents were similar to the pathways followed in SARS-COV-2 pathology, like renin-angiotensin system, kidney functions, regulation of blood circulation, blood vessel diameter , etc . Also, in docking studies, the constituents of N. sativa , α-hederin, Thymohydroquinone and Thymoquinone were observed to be efficiently binding to ACE2. Also, the bioactive phytoconstituents are involved in molecular pathways like HIF1, VEGF, IL-17, AGE-RAGE, chemokine and calcium signaling pathways which can be majorly helpful in combating hypoxia and inflammation caused due to compromised immune system and oxidative stress. Therefore, N. sativa standardized extract having the above phytoconstituents could be useful in COVID-19 and hence opens a new treatment line.

Zebrafish (ZF) is an incredible animal for the study of neurological disorders. Its behaviour is like higher vertebrate animals, which makes it gainful and robust. Understanding the psychological and biological implications of housing settings for ZFs is very crucial in improving the replicability and dependability of ZF behavioural research. Individual housing triggers depression-like symptoms that suggest that housing conditions have negative effects on ZF and can result in the data discrepancy. Based on various behavioural analyses, we have evaluated that the ZFs kept in isolation and the ZFs kept in herd conditions exhibit different behavioural patterns. Interestingly, normal isolated subjects exhibit similar behavioural patterns as Alzheimer disease (AD)-induced subjects; hence, this can have serious implications on any study concerning behaviour of ZFs. Therefore, we have reported a new behavioural test named "Alarm Test", which effectively discriminates normal isolated subjects from AD subjects. Alarm Test is observed to be better than other tests used for studying fear and anxiety in ZFs as it uses the indigenous compound released by ZFs during fear and makes use of the same for analysis. This can reduce the involvement of chemicals during behavioural analysis as well as sacrifice of ZFs for collection of alarm substance.

Hepatocellular carcinoma (HCC) is one of the major health problems with increasing incidence worldwide. We report the elevation in transthyretin (TTR) expression following HCC induction using diethylnitrosamine (DEN) and 2-aminoacetylfluorine (2-AAF) in male Wistar rats. The increase in its expression took place at very early stage and remained elevated throughout HCC progression. The analysis of TTR gene in HCC bearing rats revealed four novel mutations that alter three amino acids at positions 61, 100, and 115. While these mutations do not directly affect the binding of TTR to thyroxine (T 4 ), the mutation in amino acid 115 interferes with TTR tetramer formation that leads to its accumulation. Further, the mutated TTR is unable to cleave C-terminal of apolipoprotein A1 (APOA1) that results in abnormal lipid metabolism. This has correlation with development of liver cirrhosis and HCC. Furthermore, the mutated TTR seems to have potential as biomarker for early detection of HCC. K E Y W O R D S2-aminoacetylfluorine, apolipoprotein A1, diethylnitrosamine, expression, mutations, tetramer formation

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Aim:: Poor nutritional effect of junk food induces injurious adversities to the liver and brain but still most of the developing nations survives on these diets to compensate for fast-paced lifestyle. Aim of the study is to infer the proteinconnections behind liver-brain axis and identify the role of these proteins in causing neurodegenerative disorders. Background: : Chronic consumption of fructose and fat rich food works as a toxin in body and have the ability to cause negative metabolic shift. Recently a study was published in Annals of Internal Medicine (2019) citing the loss of vision and hearing in a 14-year-old boy whose diet was strictly restricted to fries and junk-food for almost a decade. This puts the entire body on insulin resistance and related co-morbidities and causes simultaneous damaging effects in liver as well brain. This work provides insights into liver-brain axis and explains how liver is involved in brain related disorders. Objective: : In this study transcriptomic data relating to chronic eating of junk-food was analyzed and simultaneous damage that happens in liver and brain was assessed at molecular level. Method:: Transcriptomic study was taken from GEO database and analysed to find out the genes dysregulated in both liver and brain during this metabolic stress. Cytoscapev3.7 was used to decipher the signalling between liver and brain. This connection between both was called as Liver-Brain axis. Results : The results obtained from our study indicates the role of TUBB5-HYOU1-SDF2L1-DECR1-CDH1-EGFR-SKP2- SOD1-IRAK1-FOXO1 gene signature towards the decline of concurrent liver and brain health. Dysregulated levels of these genes are linked to molecular processes like cellular senescence, hypoxia, glutathione synthesis, amino acid modification, increased nitrogen content, synthesis of BCAAs, cholesterol biosynthesis, steroid hormone signalling and VEGF pathway. Conclusion: We strongly advocate that prolonged consumption of junk food is a major culprit in brain related disorders like Alzheimer’s disease and propose that receptors for brain diseases lie outside the brain and aiming them for drug discovery and design may be beneficial in future clinical studies. This study also discusses the connection between NAFLD (nonalcoholic fatty liver disease) and sAD (sporadic Alzheimer’s disease) owing to liver-brain axis.

Background: Lung cancer is the most common cancer with a high mortality rate. The diagnosis only at advanced stages and lack of effective treatment are the main factors responsible for high mortality. Tobacco smoke is the major responsible factor for inflammation and tumor development in lungs. Objective: The present study was carried out to identify differentially expressed proteins and elucidate their role in carcinogenesis. Methods: The lung cancer was developed in Wistar rats by using NNK as carcinogen and cancer development was confirmed by histopathological examination. The 2D SDS PAGE was used to analyse total proteins and find out differentially expressed proteins in NNK treated lung tissue vis-a-vis control tissue. The findings of proteomic analysis were further validated by quantification of corresponding transcripts using Real Time PCR. Finally, Cytoscape was used to find out protein-protein interaction. Results: The histopathological examinations showed neoplasia at 9th month after NNK treatment. The proteomic analysis revealed several differentially expressed proteins, four of which were selected for further studies. (TOM34, AL1A1, PADI2 and KLRBA) that were up regulated in NNK treated lung tissue. The real time analysis showed over expression of the genes coding for the selected proteins. Thus, the proteomic and transcriptomic data corroborate each other. Further, these proteins showed interaction with the members of NF-κB family and STAT3. Conclusion: We conclude that these proteins play a substantial role in the induction of lung cancer through NF-κB and STAT3 pathway. Therefore, these may have the potential to be used as therapeutic targets and for early detection of lung cancer.