Biomedical and Biotechnology Research

Understanding the genetics of gastric and esophageal cancer using Drosophila melanogaster as a model organism Preeti Thiyagarajan, Venkatachalam Deepa Parvathi Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):269-273 Drosophila melanogaster, a vicious model, has helped in significant discoveries about several conserved mechanisms. The insect intestine had remained unexplored until the identification of adult somatic stem cells which triggered the invention of genetic amenability of this insect organ in powerful and artistic ways. A variety of mechanisms within the fruit flies' intestine are conserved in human gastrointestinal systems and will, therefore, become relevant within the context of human pathologies such as gastrointestinal cancers and obesity. In line with current guidelines, maintaining a high degree of suspicion of hereditary etiology (genetic involvement) helps in disease diagnosis. In this review, genetics of two crucial cancers are discussed. Mutation or transcriptional silencing of the cadherin-1 (CDH1) gene and tumor protein p53 gene is related to familial diffuse gastric cancer (GC) and esophageal adenocarcinoma, respectively. Testing for CDH1 mutations in patients with familial clustering of hereditary diffuse GC has proven consistent. Further studies on the expression and also the alteration within the proteins within the E-CDH pathways and Hippo pathway may function as biomarkers for early detection. Dysregulation of various mechanisms ends up in invasion, proliferation, and metastases. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been.

General awareness on hantavirus infection: A brief review Rashed Noor Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):274-279 Hantavirus is a negative, stranded RNA virus, largely known to be transmitted to humans, especially working in forestry from the rodents. The human-to-human transmission of this virus is still in obscure; however, upon transmission of this virus from the rodent fluids, its fatality is noticed mainly through the hyperinflammatory syndrome and the cardiopulmonary syndrome. Several reports revealed an alternation of the immune response including the natural killer cells, CD8+ T cells, neutrophils, and several cytokines during the viral pathogenesis. Unlike the other emerging viruses including the currently ongoing novel coronavirus (COVID-19) pandemic, the global mortality rate due to hantavirus infection is so far very low, which, in turn, made the general people all around the world know a very little about this virus. Besides, no effective antiviral therapy including vaccines has yet been developed to combat the viral infection. Lots of comprehensive reports elaborately discussed this virus pointing toward its dreadfulness. The current review discussed the fatal effects of the hantavirus infection in a relatively simplistic way, which can be easily understood by the general community who are still unaware of the risks posed by this relatively uncommon virus.

Genetic makeup and associated virulence posed by the enteropathogenic Escherichia coli and the Enterotoxigenic Escherichia coli pathotypes Syeda Muntaka Maniha, Rashed Noor Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):280-284 The enteropathogenic Escherichia coli (EPEC) is known to trigger diarrhea in infants, whereas the enterotoxigenic E. coli (ETEC) accounts for the children's diarrhea and the travelers' diarrhea. Transmission of the pathogenic bacteria usually occurs in a fecal–oral route usually originating from the poultry items. Thus, the study relating these E. coli pathotypes to the required virulence factors would be of great interest for the welfare of mass public health. Although the reports on the food-oriented pathogenic E. coli so far are actually uncountable, the present review especially concentrated on the genetics of virulence factors required for the pathogenesis by EPEC and ETEC based on the information given by the previous literature. The review focused on the expressional regulation of the components required for the EPEC pathophysiological impact on humans. The necessary studies correlating the genome with the expression of the virulence factors have been well discussed.

Does epstein–barr virus participate in the development of breast cancer? A brief and critical review with molecular evidences Muhammad Usman, Yasir Hameed, Mukhtiar Ahmad Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):285-292 The oncogenic potential of Epstein–Barr virus (EBV) has been well studied in human breast cancer (BC) so far but still controversies surround its role. In the present study, we aimed to perform a comprehensive and critical review of the results and methodologies used by the previous studies to identify the association between EBV markers with human breast. We also proposed a criterion based on the Bradford hill postulates of causation and EBV prevalence to evaluate the results of previous studies for proving EBV etiological role in breast cancer. A PubMed search engine-based strategy was implemented to retrieve all the relevant studies. In total, 50 original studies were retrieved. Out of which 20 were case–control studies while others were not. The positivity ratios of EBV detection in breast cancer samples varied study wise. Few studies did not identify the EBV markers in breast cancer while others identified it with different detection positivity ratios varying from 2.9% to 75.8%. Similarly, the EBV detection positivity ratios in normal and benign samples also varied between 0%–35% and 0%–75.8%, respectively. In total, 18 out of 20 case–control studies, the positivity ratios of EBV detection were higher or equal in breast samples as compared to controls, while two case–control studies also report the opposite results. However, the odds ratios and confidence intervals were not reported. The results failed to prove EBV as a potential biomarker of breast cancer but rather suggested its role as a cause-effect or at least co-participant.

The role of estrogen in breast cancer Roaa Khadem, Fatimah Chassab Mahdi, Karrar AI-Mosawi, Ali Abdul Hussein S. AL-Janabi Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):293-296 Estrogen has a significant effect on the development of breast cancer. Its activities in the human body are mainly performed by binding to cellular estrogen receptor (ER). Breast cancer in relate to the presence of ER can be divided into ER-positive and ER-negative breast cancer. The role of estrogen and its receptors in the development of breast cancer will be discussed in this review.

Influence of De novo mutation in autism Ann Mary Alappat Sanjeev, Bharathi Kathirvel, Kaviya Mohandass, Vijaya Anand Arumugam Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):297-301 Autism and autism spectrum disorders (ASD) affects the areas of social awareness and interaction, verbal and nonverbal communication, and behaviors and interests, which are grouped among neurobehavioral disorders. One in 68 children is affected with ASD according to the estimate from the Center for Disease Control and Prevention's autism and developmental disabilities monitoring network and an increasing prevalence observed worldwide. A characteristic heterogeneity in ASD determined genetic variability as a major contributor. Whole-exome sequencing of ASD individuals revealed that discrete de novo mutation (single-nucleotide variation or small indels) also contribute to the overall genetic risk of ASD apart from rare genetic variation affecting single nucleotides of protein-coding DNA or rare genomic copy number variants as assessed through other high-throughput genomic methods. These genes are involved in synaptic transmission and regulated during brain development by acting upstream or downstream of Wingless- related integration site (WNT), bone morphogenetic proteins/transforming growth factor-β, sonic hedgehog, fibroblast growth factor, and retinoic acid signaling pathways. The current review focuses on genes involved in synaptic function, undergoing de novo mutation leading to ASD condition.

FNCas9 editor-linked uniform detection assay: An innovative COVID-19 sleuth Tarun Kumar Suvvari, MD Nawaz, Mani Kruthika Mantha Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):302-304 Relying on traditional diagnostic approaches like quantitative polymerase chain reaction is not appropriate for both time and cost in sudden outbreaks and pandemics such as COVID-19. In such cases, diagnostic approaches through rapid sequencing of pathogenic DNA and RNA are important for accelerated clinical prognosis. FNCas9 Editor-Linked Uniform Detection Assay (FELUDA) is one such diagnostic approach toward the pathogenic genome, developed by CSIR-IGIB. FELUDA is a paper strip diagnostic test like pregnancy, based on clustered regularly interspaced short palindromic repeats/Cas technology of gene editing. FELUDA showed 96% sensitivity and 98% specificity across all range of viral loads in clinical samples. Due to its low cost, it can drastically reduce the Indian budget toward the rapid testing and COVID-19 diagnostic kits.

Phytochemical and antioxidant assessments of Dioscorea bulbifera stem tuber Othuke Bensandy Odeghe, Elias Adikwu, Chioma Cynthia Ojiego Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):305-311 Background: Dioscorea bulbifera (D. bulbifera) is used in traditional medicine for the treatment of many disease conditions. However, there is a paucity of information on the antioxidant potential of its stem tuber. Methods: The antioxidant activity of the methanolic extract of D. bulbifera stem tuber was evaluated by measuring its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anion radical (O2-) and nitric oxide (NO) radical. It was also analyzed for bioactive secondary metabolites using standard qualitative and quantitative spectrophotometric methods. Results: The extract showed total phenolic content (0.243 ± 0.052 mg) gallic acid equivalent compared to tannins content (0.259 ± 0.034 mg). Low flavonoid contents (0.060 ± 0.025 mg) quercetin equivalent (QE) and high flavonol contents (1.399 ± 0.075 mg) QE were found in the extract. The extract showed a potent concentration-dependent DPPH radical inhibitory potential with maximal inhibition activity (69.39 ± 1.62%) at 5000 μg/mL compared to ascorbic acid with maximal inhibition activity (88.9 ± 2.67%) at the same concentration. The extract produced maximal O2- anion inhibitory activity (52.86 ± 0.68%) at 2500 μg/mL compared to quercetin with maximal inhibitory activity (68.23 ± 0.41%) at the same concentration. The extract exhibited NO activity in a dose-depend fashion when compared to α-tocopherol. Conclusion: These results showed that D. bulbifera stem tuber extract contains bioactive secondary metabolites with potent-free radical scavenging activity, which could be extracted and standardized for use as food, medicine, and in industries.

Detailed analyses about predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in invasive lobular breast cancer Esra Arslan, Tamer Aksoy Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):312-317 Backgrounds: Management of invasive lobular breast cancer (ILC) is limited with only using standard uptake value (SUV) max of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. We aimed detailed predictive, prognostic and clinical value of parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) with survival data. Methods: Forty-nine ILC was included in this study. SUVmax, MTV, and TLG documented in molecular and histopathological subtypes. SUVmax, MTV, and TLG compared with nodal involvement, distant metastasis, estrogen receptor (ER), progesterone receptors (PR) and HER status, Ki-67 and survival data. Results: 61.2% luminal A, 36.7% luminal B and 2.0% TN. 53.1% classic and 46.9% pleomorphic. 93.9% ER + and 81.6% had e-cadherin loss. Mean SUVmax was 8.32 ± 4.73. No statistically significant relationship found between classical and pleomorphic with SUVmax (P = 0.616). FDG uptake found significantly higher with tumor >2 cm (P = 0.039). Luminal B SUVmax significantly higher than luminal A (P = 0.013). PR-, Ki-67 high expression, axillary involvement and luminal B significantly reduced survival time (P = 0.034, 0.019, 0.032, and 0.005, respectively). Statistically significant correlation found between high MTV and TLG, tumor diameter (TD) (P = 0.001 and 0.000, respectively). Conclusions: Loss e-cadherin and pleomorphic types did not affect the prognosis. ILC shows low FDG sensitivity compared other breast cancer types, it found to be significantly associated with prognostic factors; TD, molecular subtype, Ki-67 and metastasis. Although volumetric parameters did not add extrapredictive value to FDG involvement pattern, it was found that method remains in diagnosis, staging, and treatment follow-up of ILC.

Synthesis, characterization, and In vitro antibacterial activity and molecular docking studies of N4, N4'-dibutyl-3,3'-dinitro-[1,1'-Biphenyl]-4,4'-diamine K Muddukrishnaiah, V Vijayakumar, B Samuel Thavamani, VP Shilpa, N Radhakrishnan, Heba S Abbas Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):318-322 Background: Resistant growth is recognized as a significant public health hazard to human health worldwide among the most critical bacterial diseases. The evolving multidrug-resistant species are now commonly found in community settings, not just in the hospital area, which means that antibiotic bacteria reservoirs are beyond the hospital. Aim: In this study, we synthesized novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and evaluation of its antimicrobial activity against clinical bacteria. Methods: Single-step synthesis of novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and well characterized using spectroscopic methods, namely FT-IR, NMR, mass spectrometry, and CHNS. Besides, prepared compound molecular docking investigations, molecular physicochemical, absorption, distribution, metabolism, and excretion (ADME) analysis were also carried out. Results and Discussion: Novel Synthesized N4, N4'-dibutyl-3,3'-diaminobenzidine (DAB) was conducted for antibacterial activity against clinical Klebsiella spp. and Staphylococcus aureus and Pseudomonas spp. by the disc-diffusion method and followed by serial dilution method. N4, N4'-dibutyl-3,3'-DAB showed bacteriostatic action of 500 μg/ml, 1000 μg/ml for Klebsiella spp. and Staphylococcus aureus. The molecular physicochemical investigation exhibited that 1 violation and ADME analysis presented a low gastro intestinal effect. Docking investigations disclosed the capability of synthesized molecule potential to dock with beta-lactamase protein through patch dock methodology. Conclusion: N4, N4'-dibutyl-3,3'-DAB is the novel compound that was found to be attractive for the “drug hunters” as a potential agent for the management of infectious diseases against the human pathogens Klebsiella spp. and Staphylococcus aureus.

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