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   Table of Contents - Current issue
Coverpage
January 2019
Volume 6 | Issue 1
Page Nos. 1-36

Online since Wednesday, April 24, 2019

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REVIEW ARTICLE  

Klotho: An emerging factor in neurodegenerative diseases p. 1
Gauri V Pathare, Kavita K Shalia
DOI:10.4103/BMRJ.BMRJ_3_19  
Soluble Klotho protein is present in blood, urine, and cerebrospinal fluid and works as a humoral factor exerting different biological effects. Several animal studies have demonstrated the association of age-related neurodegeneration with Klotho deficiency. Lower Klotho levels have been reported in patients suffering from cognitive impairment, dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and other neurodegenerative diseases. Due to its antiaging properties, Klotho is the obvious choice to be studied as a protective/therapeutic agent in neurobiology. In this review, we have attempted to shed light on the different neurodegenerative diseases affected by deficiency of Klotho and its neuroprotective role against pathogenicity of the disease.
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ORIGINAL ARTICLES Top

Nitrate stress-induced bioactive sulfated polysaccharides from Chlamydomonas reinhardtii p. 7
Jyoti Vishwakarma, Vaishnavi Parmar, Sirisha L Vavilala
DOI:10.4103/BMRJ.BMRJ_8_19  
Sulfated polysaccharides (SPs) are anionic carbohydrate polymers synthesized as extracellular or cell wall components by most of the algae and have potent bioactive properties. In the current study, Chlamydomonas reinhardtii (Cr) cells were attributed to sodium nitrate stress in concentrations such as 5 mM, 10 mM, 20 mM, 30 mM, and a control to determine the productivity and bioactivity of SPs. SPs are extracted by hot water method using 80% ethanol. The percentage yield of SPs increased with an increase in concentration of sodium nitrate as compared to control. Biochemical analysis of the extract showed an increase in carbohydrate content (22%–95%), uronic acid content (23%–60%), and sulfate content from control to 30 mM NaNO3-treated extracts. The amount of reducing and nonreducing sugars was found to be 6.16% and 89.06%, respectively, while the protein content is ~16%. The antioxidant potential of SPs showed increased antioxidant activity with an increase in concentration of NaNO3 stress. The analysis resulted in maximum chelating activity of 83.73% assayed in concentration range of 1–8 μg/ml, total antioxidant activity of 70.36% in concentration 0.05–2μg/ml, and hydroxyl radical scavenging activity of 79.52% in concentration 250–1000 μg/ml; reducing potential was observed with the highest absorbance of 0.87; the 2,2-diphenyl-1-picrylhydrazyl scavenging activity showed the highest activity of 63.61%, while the superoxide scavenging activity was 92% at 0.1–1 μg/ml. Furthermore, Cr-SPs inhibited the growth of Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacterial growth as indicated by clear zones that increased in size with an increasing concentration of NaNO3. These results provide opportunities to develop Cr-SPs as natural antioxidant and antibacterial agents.
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Molecular docking study for evaluation of neuroprotective potential of sericin against cerebral stroke and exploring its biomaterial properties p. 17
Khushboo Maurya, Anand Kumar Pandey
DOI:10.4103/BMRJ.BMRJ_5_19  
Background: Cerebral stroke, the third leading cause of death worldwide results from the improper blood supply to the brain due to occlusions in the brain arteries. This leads to production of free radicals contributed by cyclo-oxygenases (COX), acid sensing ion channels (ASIC) and matrix metalloproteinases (MMPs) causing adverse conditions of inflammation, oxidative stress, and acidosis leading to neuronal death thereby proving these enzymes as potent targets. Sericin, a 38 amino acid long protein found in silk fiber is known for its anti-inflammatory and anti-oxidant property. Aim and Objectives: Inhibition of the above-mentioned targets by silk protein sericin to reduce the pathological features by structural interactions as well as reducing inflammation and oxidative stress due to the natural properties of compound. Methodology: In the present study we studied structural inhibition of effective targets by sericin through molecular docking analysis. Also, the semi crystalline nature of sericin was deduced through in silico XRD spectral analysis. Result: Structural inhibition through molecular docking analysis proved highly efficient inhibition. Also, the in silico XRD spectral analysis proved sericin to be a potential biomaterial for scaffold development. Conclusion: Sericin can not only act as an effective drug against cerebral ischemia but can also be used to develop scaffold to repair damaged brain.
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Transforming growth factor beta receptor 2 single-nucleotide polymorphism association with oral cancer and In silico identification of small drug-like molecules as inhibitors to transforming growth factor Beta-2 receptor p. 25
Shaleen Multani, Hetal Damani Shah, Dhananjaya Saranath
DOI:10.4103/BMRJ.BMRJ_1_19  
Objective: Oral cancer, in India, constitutes 26% of global oral cancer burden. The major risk factors include tobacco, areca nut, alcohol, and human papillomavirus 16/18; however, only 5%–10% of the high-risk individuals develop oral cancer, indicating the role of genomic variants in susceptibility to oral cancer. Conventional treatment options in oral cancer have resulted in relatively poor prognosis and an unmet need of treatment. In silico analysis, therefore, was performed to identify small drug-like molecules as potential inhibitors of transforming growth factor beta-2 receptor (TGFβRII). Materials and Methods: Seven single-nucleotide polymorphisms (SNPs) were analyzed in 500 histopathologically confirmed oral cancer samples and 500 long-term tobacco users (LTTUs) as controls using allelic discrimination real-time polymerase chain reaction or high-resolution melting analysis. The differential frequencies in oral cancer and LTTUs were calculated using SPSS software (version 19), and odds ratio (OR) to indicate risk to oral cancer using Hutchon.net. structure-based virtual screening of drug-like molecules was performed to identify lead inhibitor molecules to TGFβRII using Schrödinger Suite 2015-4. Results: Heterozygous GC genotype of TGFBR2 rs9843143 demonstrated increased risk ([P = 0.011; OR 1.61 [1.25–2.1]) while CC genotype showed decreased risk (P = 0.005; OR 0.61 [0.44–0.83]) to oral cancer. Increased/decreased risk to oral cancer was not observed for the other SNPs. In silico analysis identified six molecules as inhibitors of TGFβRII kinase domain from 17,723 conformers from Maybridge HitFinder library and 2685 conformers from MEGx AnalytiCon natural product library. Conclusion: SNP rs9843143 (TGFBR2) demonstrated a significant association (P < 0.05) with oral cancer and six potential inhibitors of TGFβRII kinase were identified using in silico analysis.
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CASE REPORT Top

Metastatic hepatocellular carcinoma manifesting as primary esophageal carcinoma: A rare case report p. 34
K Jayaprakash Shetty, HL Kishan Prasad, Shubha Bhat, Michelle Mathias, Vijith Shetty
DOI:10.4103/BMRJ.BMRJ_2_18  
Hepatocellular carcinoma (HCC) metastasizing to the esophagus and mimicking as a primary tumor of the esophagus is extremely rare, being present in <0.4% in some autopsy series. This report describes a case of 70-year-old male with metastatic HCC to esophagogastric junction causing diagnostic dilemma. An endoscopic examination revealed an ulcerative lesion in the lower end of the esophagus. The biopsy specimen obtained from a tumor revealed the pseudoglandular arrangement of tumor cells. Ultrasound abdomen showed liver nodule with biopsy confirming as HCC. Immunohistochemistry (IHC) of the esophageal mass showed positivity for Hep par 1, Glypican-3, Arginase, CA 19-9, CK 19, CDX2, pCEA, SATB2, and Ki-67 having 70% positivity confirming the HCC. Among these IHC panels, all are specific markers of HCC, but CDX2 and SATB2 were aberrantly expressed in our case. He was started on six cycles of chemotherapy (apristar 125 mg, epirubicin 40 mg, oxaliplatin 100 mg, and capecitabine 500 mg). After 8 months of follow-up, he was symptomatically improved. However, later, the patient was lost to follow-up. The accurate pretreatment staging and then providing stage-appropriate treatment is crucial in optimizing esophageal and hepatocellular cancer outcomes. Cases of premortem-diagnosed esophageal metastasis from HCC are extremely rare. Our case was ideal for IHC, which plays an important role in arriving at proper cases. Furthermore, it confirmed and highlighted the rare manifestations of hepatocellular carcinoma.
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