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The Impact of Fatty Acid Compounds in a Sacha Inchi Oil Supplement on Rats

Dietary oils are important sources of macronutrients and micronutrients, which can affect health. Sacha inchi oil (SIO), a type of edible oil extracted from Plukenetia volubilis, a plant native to tropical regions, is reported to be rich in omega-3 fatty acids. Previous studies have shown that omega-3 fatty acids are essential, offering numerous health benefits, including improvements in metabolic syndrome, cardiovascular disease, and gut microbiota. Typically, omega-3 sources are animal-based, especially fish oil and cod liver oil. SIO presents an interesting plant-based source of essential fatty acids. However, the compounds and effects of SIO on health and safety are not yet clear. In this study, the effects of SIO were studied both in vitro and in vivo. In vitro, we investigated the chemical compounds by evaluating the fatty acid and antioxidant content. In the in vivo study, the oil supplements were administered orally to male Sprague-Dawley rats continuously for 12 weeks. The effects were also evaluated through measurements of the body composition, fatty acid profile, liver enzymes, and morphology and lipid content of organs; the histology of the organs was assessed using H&E and Oil Red O staining. SIO has a high content of omega-3 fatty acids and significant antioxidant capacity. The rats treated with SIO for 12 weeks showed no increased risk of fatty liver or toxicity in any organs. These results indicate that SIO has high levels of alpha-linolenic acid (omega-3) fatty acids and antioxidant compounds, without altering body composition or serum parameters. Furthermore, SIO did not result in any adverse effects in the rats. These results confirm that SIO is a safe and effective source of omega-3, offering benefits for health.

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A Computational Approach to Comparative Analysis of Aflatoxin B1-Specific Aptamers for Detection: Insights into Molecular Interactions and Binding Affinities

Aflatoxins (AFs) are the carcinogenic secondary metabolites produced by fungi such as Aspergillus flavus, A. parasiticus, and A. nomius. These fungi are widespread and have severely contaminated food/feed supplies. The major health consequences of consuming AF-contaminated food/feed are Hepatocellular carcinoma and its associated complications. Therefore, detecting and quantifying AFs in foods and feeds is critical to achieve food safety. Among the available methods, aptamer-based techniques are receiving more attention considering their specificity, sensitivity, low cost, and ease of production and handling. Though AFB1-specific aptamers have been well studied, ligand–aptamer molecular interactions are not clear. In the present study, the three-dimensional structures of available AFB1-specific DNA aptamers were predicted using RNA-based web servers with an automated machine translation principle and some manual changes in the script file. Molecular docking was performed between selected DNA aptamers and AFB1. Molecular docking results revealed that the AFB1 was located inside the pocket area of the predicted tertiary structures and formed electrostatic interactions with the nucleotides of aptamers. The binding affinities of all aptamers were between -7.3 and -11.7 kcal/mol. This study adds to our understanding of how AFB1 interacts with all available aptamers. The developed workflow enables the generation and examination of additional appealing ligand–aptamer complexes to detect AF and other mycotoxins.

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Lung Cancer Biomarker Identification from Differential Expression Analysis Using RNA-Seq Data for Multitargeted Drug Designing

Lung cancer poses a significant global health challenge, causing most cancer deaths. It therefore necessitates a detailed exploration into its molecular intricacies in search of potential treatment targets. The strategy is to delay disease progression and to practice early intervention to reduce the number of patients that ultimately develop lung cancer. Therefore, promising novel biomarkers for early diagnosis are urgently required. We performed an RNA sequencing analysis of lung cancer, using the SRA database (SRR119055), with 60 samples, including 30 control and 30 tumorous samples. A DEG analysis of tumorous and healthy subjects was performed using Bioconductor in R with its other packages to transform and normalize all transcriptomic data. We identified important genes from the lung cancer samples which include five upregulated genes, namely, COL11A1, CTPS1, SULF1, SPP1, and DIO2, and five downregulated genes, which are EN1, ARRDC3-AS1, VEGFD, TMEM100, and PSEN1, from the network and their associated genes. We also identified two hub genes, PRKACB and TAOK1, responsible for cell proliferation, differentiation, apoptosis, and cytoskeletal dynamics. Furthermore, we repurposed the FDA-approved drugs as multitargeted inhibitors against all upregulated genes to inhibit the function of most genes, followed by DFT and MD simulation to validate their effectiveness in lung cancer.

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Molecular structure considerations for the possibility of
sequence-dependent DNA resonances
, , , ,

For years, the mechanisms of non-chemical and non-contact communication between cells and organisms have not been studied to the same extent as those associated with the chemical mediators. The novel molecular structure considerations for the possibility of DNA sequence-dependent electromagnetic resonances (DNASDEMRs) are proposed. It is hypothesized that the resonant vibrations naturally occur in the clouds of delocalized electrons and protons in a stack of DNA bases and that some DNA sequence repeats, abundant in the genome, serve as universal resonators, which bidirectionally connect the chromatin structure. The existence of a DNA resonance code is proposed as an algorithm for the transformation of the genomic sequence into the organism’s structure, and an initial model of sequence-specific electromagnetic resonances in DNA was proposed to explain some reported observations. The DNA interaction with a weak electromagnetic field due to DNASDEMR can play a role in non-contact communication between cells as well as in the development of certain non-communicable diseases (NCDs). Our additions to the original concept of DNA resonance give extra reasons to link the organism-level consideration to the molecular consideration through the idea of field coordination and adjustment. This allows us to explain the soft coordination of all molecular events in the body through non-contact communication. Solving this issue will bring medical technologies to a fundamentally new level.

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Integrated Bioinformatics Analysis for Identifying Hub Genes and Therapeutic Targets in Recurrent Breast cancer Liver metastasis

Introduction: Breast cancer during advancement to the metastatic stage involves the liver, thereby diminishing the survival rate among 50% of cases. Currently, there are few therapeutic protocols for breast cancer liver metastasis (BCLM) available, thereby necessitating a deeper understanding of the molecular patterns governing this molecular mechanism. Therefore, in the present study, by analyzing the differentially expressed genes (DEGs) between primary breast tumors and BCLM lesions, we aim to shed light on the diversities of this process.

Methods: In this study, we investigated breast cancer liver metastasis relapse by employing a comprehensive approach that integrates data filtering, Gene Ontology and KEGG Pathway Analysis, Overall Survival analysis, identification of the alterations in the DEGs, visualization of the protein–protein interaction network, Signor 2.0, identification of positively correlated genes, screening results of the function of hub genes, immune cell infiltration analysis, copy number variant analysis, gene-to-mRNA interactions, transcription factor analysis, and identification of potential treatment targets.

Results: Our results showed two genes, PCK1 and LPL, were differentially expressed between primary breast tumors and BCLM lesions. PCK1 is a regulator of gluconeogenesis, and LPL, involved in lipid metabolism, impacts cancer cell energetics and biosynthetic capabilities. Elevated PCK1 levels show a correlation with a poorer prognosis, indicating an aggressive phenotype. The transcription factors (AR, PPARA, RXRA, RXRB, and RXRG) regulating both genes offer insights into energy homeostasis, metabolism, and cell growth. Immune infiltration analysis suggests their collective role in modulating the tumor microenvironment, influencing immunosurveillance and evasion.

Conclusion: This study’s integrative approach unveils metabolic reprogramming, suggesting altered PCK1 and LPL expression are key in breast cancer metastasis recurrence.

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Potential role of the Gut Metabolite, Trimethylamine N-oxide as a folding inhibitor of Carbonic Anhydrase: A new insight for its involvement in Dementia

Introduction: Trimethylamine N-Oxide (TMAO) is an important metabolite, which is synthesized from the dietary precursors’ choline, betaine, and carnitine in various organisms. In humans, TMAO is synthesized by the metabolism of these dietary precursors by the action of enzymes produced by gut microbiota, and its high levels are abundantly found in serum and cerebrospinal fluid (CSF). Although TMAO is a stress protectant, especially in urea-rich organisms, it is an atherogenic agent in humans and is associated with various diseases. Specifically, there has been a strong correlation between serum TMAO levels and the development of Dementia. We have investigated the effect of TMAO on Carbonic anhydrase (CA) as after repeated failure of drugs that target Aβ in clinical trials, CA is considered to be an alternative target.

Methods: In the present study, we have investigated the effect of TMAO on the structural and functional integrity of CA using various biophysical and biochemical approaches. Cellular approches are also used to confirm the effect.

Results: Our result indicates that TMAO acts as a ligand of CA that is specifically targeted to its folding intermediate, Uf. We discovered that TMAO inhibits the folding of CA by disrupting the Uf state and eventually impairing the cis/trans isomerization. Furthermore, TMAO is capable of inducing cell cycle arrest and eventually increasing ROS levels.

Conclusion: This study highlights a novel molecular insight into the involvement of TMAO in AD dementia and other proteopathy-associated diseases.

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Fabrication of rice starch matrix loaded with Aegle marmelos (L.) fruit extract to produce chromogenic food packages with enhanced shelf life and spoilage detection

Introduction: Changes in consumer preferences and the demand for safe and high-quality food products have led to innovative developments like intelligent packaging systems (IPs) or smart/active packages that directly communicate with consumers, providing information about the quality of packed food through visual change and aiding in the enhancement of freshness. Biopolymers play an important role in mitigating fossil fuel-based environmental concerns and reducing carbon footprint.

Methods: Thin biocomposites made of a rice starch matrix loaded with Aegle marmelos (L.) fruit extract were synthesised using the solvent casting method for the detection of freshness in dairy and seafood products through spoilage-induced pH modification. Additionally, their antimicrobial and antioxidant properties were also explored for shelf life enhancement. Material characterisation was investigated through UTM, FTIR and SEM.

Results: The results show that A. marmelos extract showed colour changes detectable both under UV and with the naked eye following pH fluctuations occurring during the spoilage of milk and prawns placed on the prepared thin sheet. SEM analysis revealed how the starch molecule absorbed the plant extract into its matrix structure, producing a neat, thin film. FTIR was also used to confirm how the plant material interacts with the starch used. UTM studies indicated that the Young’s modulus of the starch film decreased, thereby contributing to better mechanical strength.

Conclusion: This investigation produced insights into a novel, completely biodegradable, flavonoid-based pH biosensor that can successfully be used in food packages for freshness detection.

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Plumbagin Alleviates Intracerebroventricular-Quinolinic Acid Induced Depression-Like Behaviour and Memory Deficits in Wistar Rats.

Plumbagin, a hydroxy-1,4-naphthoquinone, has anti-inflammatory and antioxidant properties that provide neuroprotection. The current investigation intended to determine the impact of plumbagin on behavioural and cognitive impairments in male Wistar rats caused by intrahippocampal quinolinic acid (QA) administration utilizing stereotaxic apparatus, and additionally to elucidate the underlying mechanisms. QA i.c.v. (300nM/4μl in Normal saline) was injected into the hippocampus. When QA was administered, subjects showed signs of depression (forced swim test, tail suspension test), anxiety (open field test, elevated plus maze), and anhedonia (sucrose preference test). Additionally, in the hippocampal region of QA-treated rats compared to normal control, oxido-nitrosative stress (increased nitrite content, lipid peroxidation, with reduction of GSH), inflammation (increased IL-1β), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were noted. Ten and twenty mg/kg of plumbagin; Rats given QA for 21 days showed a significant improvement in their behavioural and memory deficits when treated with plumbagin (10 and 20 mg/kg; p.o.). In addition, the hippocampal MDA and nitrite levels were lowered and the GSH level was raised following plumbagin administration. Moreover, plumbagin therapy was reported to improve mitochondrial impairment and QA-induced cholinergic dysfunction (AChE). To sum up, our findings indicated that plumbagin has the potential to function as a neuroprotective medication that could be an effective means to treat chronic neurobehavioral abnormalities caused due to neurodegeneration.

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Exploring carbendazim–aptamer interactions via in silico modeling and molecular dynamics simulations

Carbendazim (CBZ), a systemic fungicide, has been found in a variety of food and feed products, agricultural soil, and water bodies, raising concerns about its possible environmental and organismal effects. While aptamers have been identified as a viable detection approach, the fundamental mechanics of ligand binding in this context have not been thoroughly investigated. In this study, CBZ-specific aptamers (CZ1, CZ2, CZ5, CZ6, CZ12, and CZ13) with known sequences were used to evaluate the binding interactions of CBZ and the aptamer. The analysis entails an all-atom molecular dynamics (MD) simulation in an aqueous environment after ensemble molecular docking. Because this aptamer lacked 3D structural information, it was rebuilt using an in-house workflow. Multiple CBZ molecules were found in a putative binding area of the anticipated 3D aptamer structure. The aptamer-CBZ complex was subjected to a 100 ns MD simulation, which allowed for the investigation of component interactions. The internal loop of the aptamer was found to include CBZ-specific bases. A prominent interaction between the aptamer and CBZ for all the studied aptamers (CZ1, CZ2, CZ5, CZ6, CZ12, and CZ13) involved H-bonds, and a hydrophobic interaction between T-shaped Pi-Pi and Pi-alkyl was observed throughout the MDS. The binding energies (BE, kJ/mol) recorded for the aptamer-CBZ complexes CZ1, CZ2, CZ5, CZ6, CZ12, and CZ13 were -136.66± 2.27, -93.81±1.92, -67.53±4.25, -86.16±1.75, -52.29±3.86, and -90.03±1.96 respectively. This study advances our understanding of ligand--aptamer interactions. The established workflow makes it easier to create and explore new fascinating ligand--aptamer complexes.

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Untargeted Proteomics approach to study Congenital Hearing Loss cases

Introduction: Congenital Hearing Loss (CHL) is considered the most prevalent chronic condition among children. Biomarker studies of CHL are the need of the hour for the early diagnosis of the disease. Among the biomarkers of hearing loss, extracellular biomarkers of ear disorders are considered potential diagnostic tools. Protein biomarkers are considered crucial in early-stage diagnosis of CHL cases. Methods: A total of 72 samples were collected and grouped into an Experimental (n=36) and Control (n=36) group. This study was approved by the Institutional Ethics Committee of Karnataka Institute of Medical Sciences, Hubballi, India. After obtaining informed consent from the participants, 05mL blood samples were collected and serum samples were separated by centrifugation at 4000rpm for 05 mins and stored at -80oC until further analysis. Pooled samples were processed for reduction, alkylation, and trypsin digestion before undergoing Liquid Chromatography Mass Spectrometry–Quadrupole Time of Flight (LCMS Q-TOF) analysis. Mascot search analysis was performed to identify peptide sequences and STRING software was used for network analysis of selected proteins. Results: Significant proteins were identified among the study subjects. These comprised Guanine nucleotide protein, Glutamate receptor ionotopic protein, Complement C3, Putative transmembrane protein, Zinc finger protein, Alpha 2 glycoprotein, E3 ubiquitin protein, Cadherin, Alpha Tectorin, Myosin, etc. All these proteins are associated with Congenital Hearing Loss and are involved in the mechano-transduction of soundwaves inside the cochlea. Conclusion: In this study, proteins associated with CHL have been identified among human subjects. The validation of these protein markers in serum samples using ELISA test will confirm the findings. Our panel of protein biomarkers may help in studying the underlying causes of the disease, which may direct us to its early diagnosis.

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