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Canavan disease is caused by mutations in the ASPA gene, leading to diminished catalytic activity of aspartoacylase in the brain. Clinical missense mutations are found throughout the enzyme structure, with many of these mutated enzymes having not only decreased activity but also compromised stability. High-throughput screening of a small molecule library has identified several compounds that significantly increase the thermal stability of the E285A mutant enzyme, the most predominant clinical mutation in Canavan disease, while having a negligible effect on the native enzyme. Based on the initial successes, some structural analogs of these initial hits were selected for further examination. Glutathione, NAAG and patulin were each confirmed to be competitive inhibitors, indicating the binding of these compounds at the dimer interface or near the active site of the E285A enzyme. The experimental results were theoretically examined with the help of the docking analysis method. The structure activity-guided optimization of these compounds can potentially lead to potential pharmacological chaperones that could alleviate the detrimental effect of ASPA mutations in Canavan patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plants are crucial medicinal resources, with 80 % of people relying on them for primary healthcare. The search for natural antiviral compounds is increasing, especially in semi-arid ecosystems where abiotic stress promotes the production of beneficial secondary metabolites. This review highlights semi-arid plants with the potential as functional foods to combat viral diseases and other illnesses. Literature was searched in databases like ScienceDirect to gather information on novel compounds from stress-tolerant semi-arid plant species. These compounds have potential uses in treating viral infections and other health issues such as diabetes and high blood pressure. The review screened 61 semi-arid plants known for their antiviral metabolites. Eight plants were identified with novel antiviral compounds. Key metabolites include agathisflavone, pectic arabinogalactan, azadirachtin, aloin, aloe-emodin, aloesaponarin I, allicin, terpenoids, chlorogenic acids, curcumin, chromones, β-sitosterol, lupeol, oleuropein, carissol, β-amyrin, and ∆-9-tetrahydrocannabinol. Stress-tolerant semi-arid plants are significant sources of metabolites for treating infectious diseases and boosting immune systems. Further research on these metabolites in animal models is needed to verify their efficacy for treating human diseases during endemic and pandemic outbreaks, such as COVID-19., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Calcium is a fundamental and integrative element and helps to ensure optimal health by regulating various physiological and pathological processes. While there is substantiated evidence confirming the beneficial effects of calcium in the treatment, management, and prevention of various health conditions, including cancer, conflicting studies are imperative to acknowledge the potential negative role of calcium supplementation. The studies on calcium supplementation showed that a specific dose can help in the maintenance of good human health, and in the control of different types of diseases, including cancer. Calcium alone and when combined with vitamin D, emerges as a promising therapeutic option for efficiently managing cancer growth, when used with chemotherapy. Combination therapy is considered a more effective approach for treating advanced types of colorectal cancer. Nevertheless, several challenges drastically influence the treatment of cancer, such as individual discrepancy, drug resistance, and stage of cancer, among others. Henceforth, novel preventive, reliable therapeutic modalities are essential to control and reduce the incidence and mortality of colorectal cancer (CRC). The calcium-sensing receptor (CaSR) plays a pivotal role in calcium homeostasis, metabolism, and regulation of oncogenesis. Numerous studies have underscored the potential of CaSR, a G protein-coupled receptor, as a potential biomarker and target for colorectal cancer prevention and treatment. The multifaceted involvement of CaSR in anti-inflammatory and anti-carcinogenic processes paves the way for its utilization in the diagnosis and management of colorectal cancer. The current review highlights the important role of supplemental calcium in overall health and disease, along with the exploration of intricate mechanisms of CaSR pathways in the management and prevention of colorectal cancer.

Alzheimer's disease (AD) is a neurodegenerative pathologic entity characterized by the abnormal presence of tau and macromolecular Aβ deposition that leads to the degeneration or death of neurons. In addition to that, glucose-6-phosphate dehydrogenase (G6PD) has a multifaceted role in the process of AD development, where it can be used as both a marker and a target. G6PD activity is dysregulated due to its contribution to oxidative stress, neuroinflammation, and neuronal death. In this context, the current review presents a vivid depiction of recent findings on the relationship between AD progression and changes in the expression or activity of G6PD. The efficacy of the proposed G6PD-based therapeutics has been demonstrated in multiple studies using AD mouse models as representative animal model systems for cognitive decline and neurodegeneration associated with this disease. Innovative therapeutic insights are made for the boosting of G6PD activity via novel innovative nanotechnology and microfluidics tools in drug administration technology. Such approaches provide innovative methods of surpassing the blood-brain barrier, targeting step-by-step specific neural pathways, and overcoming biochemical disturbances that accompany AD. Using different nanoparticles loaded with G6DP to target specific organs, e.g., G6DP-loaded liposomes, enhances BBB penetration and brain distribution of G6DP. Many nanoparticles, which are used for different purposes, are briefly discussed in the paper. Such methods to mimic BBB on organs on-chip offer precise disease modeling and drug testing using microfluidic chips, requiring lower sample amounts and producing faster findings compared to conventional techniques. There are other contributions to microfluid in AD that are discussed briefly. However, there are some limitations accompanying microfluidics that need to be worked on to be used for AD. This study aims to bridge the gap in understanding AD with the synergistic use of promising technologies; microfluid and nanotechnology for future advancements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phospholipases such as phospholipase-A, phospholipase-B, phospholipase-C and phospholipase-D are important functional enzymes of the cell membrane responsible for a variety of functions such as signal transduction, production of lipid mediators, metabolite digestion and playing a pathological role in central nervous system diseases. Phospholipases have shown an association with Alzheimer's disease and these enzymes have found a correlation with several metabolic pathways that can lead to the activation of inflammatory signals via astrocytes and microglial cells. We also highlighted unhealthy practices like smoking and consuming processed foods, rich in nitroso compounds and phosphatidic acid, which contribute to neuronal damage in AD through phospholipases. A few therapeutic approaches such as the use of inhibitors of phospholipase-D,phospholipase A2 as well as autophagy-mediated inhibition have been discussed to control the onset of AD. This paper serves as a crosstalk between phospholipases and their role in neurodegenerative pathways as well as their influence on other biomolecules of lipid membranes, which are acquired through unhealthy diets and possible methods to treat these anomalies occurring due to their metabolic disorder involving phospholipases acting as major signaling molecules.

Osmolytes are small organic molecules that are known to stabilize proteins and other biological macromolecules under various stressful conditions. They belong to various categories such as amino acids, methylamines, and polyols. These substances are commonly known as 'compatible solutes' because they do not disrupt cellular processes and help regulate the osmotic balance within cells. In the case of ribonuclease A (RNase A), which is prone to aggregation, the presence of osmolytes can help to maintain its structural stability and prevent unwanted interactions leading to protein aggregation. In this study, we investigated the interaction between RNase A and several osmolytes using molecular docking and molecular dynamics (MD) simulations. We performed molecular docking to predict the binding mode and binding affinity of each osmolyte with RNase A. MD simulations were then carried out to investigate the dynamics and stability of the RNase A-osmolyte complexes. Our results show that two osmolytes, glucosylglycerol and sucrose have favorable binding affinities with RNase A. The possible role of these osmolytes in stabilizing the RNase A and prevention of aggregation is also explored. By providing computational insights into the interaction between RNase A and osmolytes, the study offers valuable information that could aid in comprehending the mechanisms by which osmolytes protect proteins and help in designing therapeutics for protein-related disorders based on osmolytes. These findings may have significant implications for the development of novel strategies aimed at preventing protein misfolding and aggregation in diverse disease conditions.Communicated by Ramaswamy H. Sarma.

Osmolytes are small organic compounds accumulated at higher concentrations in the cell under various stress conditions like high temperature, high salt, high pressure, etc. Osmolytes mainly include four major classes of compounds including sugars, polyols, methylamines, and amino acids and their derivatives. In addition to their ability to maintain protein stability and folding, these osmolytes, also termed as chemical chaperones, can prevent protein misfolding and aggregation. Although being efficient protein folders and stabilizers, these osmolytes exhibit certain unavoidable limitations such as nearly molar concentrations of osmolytes being required for their effect, which is quite difficult to achieve inside a cell or in the extracellular matrix due to nonspecificity and limited permeability of the blood-brain barrier system and reduced bioavailability. These limitations can be overcome to a certain extent by using smart delivery platforms for the targeted delivery of osmolytes to the site of action. In this context, osmolyte-functionalized nanoparticles, termed nano-osmolytes, enhance the protein stabilization and chaperone efficiency of osmolytes up to 10 5 times in certain cases. For example, sugars, polyols, and amino acid functionalized based nano-osmolytes have shown tremendous potential in preventing protein aggregation. The enhanced potential of nano-osmolytes can be attributed to their high specificity at low concentrations, high tunability, amphiphilicity, multivalent complex formation, and efficient drug delivery system. Keeping in view the promising potential of nano-osmolytes conjugation in tailoring the osmolyte-protein interactions, as compared to their molecular forms, the present review summarizes the recent advancements of the nano-osmolytes that enhance the protein stability/folding efficiency and ability to act as artificial chaperones with increased potential to prevent protein misfolding disorders. Some of the potential nano-osmolyte aggregation inhibitors have been highlighted for large-scale screening with future applications in aggregation disorders. The synthesis of nano-osmolytes by numerous approaches and future perspectives are also highlighted., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Inflammatory biomarkers have been very useful in detecting and monitoring inflammatory processes along with providing helpful information to select appropriate therapeutic strategies. C-reactive protein (CRP) is a nonspecific, but quite useful medical acute inflammatory biomarker and is associated with persistent chronic inflammatory processes. Several studies suggest that different levels of CRP are correlated with neurological disorders such as Alzheimer's disease (AD). However, dynamics of CRP levels have also been observed in virus/bacterial-related infections leading to inflammatory responses and this triggers mTOR-mediated pathways for neurodegeneration diseases. The biophysical structural transition from CRP to monomeric CRP (mCRP) and the significance of the ratio of CRP levels on the onset of symptoms associated with inflammatory response have been discussed. In addition, mTOR inhibitors act as immunomodulators by downregulating the expression of viral infection and can be explored as a potential therapy for neurological diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nickel hydroxide nanoparticles (NHNPs) are extremely important semiconducting materials for applications in energy storage and energy harvesting devices. This study uses a novel variation in molarity of the sodium hydroxide (NaOH) precipitator solution to enhance the direct optical band gap in the NHNPs chemically synthesized by using nickel nitrate hexahydrate (Ni(NO 3 ) 2 ·6H 2 O) as the precursor. The simple, energy benign chemical precipitation route involved the usage of 1 M (Ni(NO 3 ) 2 ·6H 2 O) solutions as the precursor and 0.4 M, 0.6 M, and 0.8 M NaOH solutions as the precipitator solutions. The simple variation in precipitator molarity induces an increase in pH from about 6.9 to 7.5 of the reactant solution. As the molarity of the precursor solution does not change, the change in pH of the reactant solution is equivalent to the change in the pH of the precipitator solution. The NHNPs characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), Fourier-transform infrared (FTIR) and ultraviolet-visible (UV-vis) techniques confirm a reduction of the nanocrystallite size from about 6.8 to 4.5 nm with a concomitant enhancement in the direct optical band gap energy from about 2.64 to 2.74 eV. The possible mechanisms that could be operative behind obtaining microstructurally tuned (MT)-NHNPs and band gap engineering (BGE) of the MT-NHNPs are discussed from both theoretical and physical process perspectives. Further, the implications of these novel results for possible future applications are briefly touched upon. The reported results might be useful to assess the material as an active electrode to improve the performance of batteries., (© 2022 John Wiley & Sons Ltd.)

Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chlorpyrifos (CPF) is an extensively used organophosphate pesticide for crop protection. However, there are concerns about it contaminating the environment and human health, with estimated three lakh deaths annually. The molecular modeling protocol was assisted in redesigning thirteen well-known CPF linkers and inserting them at five selectable CPF (R1-R5) positions of CPF to get 258 CPF derivatives. CPF and its derivatives were optimized using LigPrep and docked to a grid centralized on Trp214 using extra precision glide docking. The Binding free energy of complexes was calculated using molecular mechanics/generalized born surface area (MM-GBSA). CPF and CPFD-225 have glide scores of - 3.08 and - 6.152 kcal/mol, respectively, with human serum albumin and ΔG bind for CPF (- 33.041817 kcal/mol) (- 52.825 kcal/mol) for CPF-D225. The top ten CPF derivatives showed at least ninefold better binding free energy than the CPF proposed for polyclonal antibody production. Subsequently, molecular docking studies revealed that CPF and its derivatives could bind to human serum albumin (HSA). Furthermore, using the Desmond package, a 100-ns molecular dynamics (MD) simulation was performed on the potential binding site. The final systems of CPF-HSA and CPF-222D complexes consist of 76,014 and 76,026 atoms, respectively. The physical stability of both the systems (CPF-HSA and CPF-222D) was analyzed by considering the overall potential energy, RMSF, RMSD, Hydrophobic interactions, and water-mediated patterns, which showed total energy of - 141,610 kcal/mol and - 140,150 kcal/mol, respectively., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03344-7., Competing Interests: Conflict of interestThe authors declare that no competing interests exist., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Since its inception, food additive has been an integral part of the food processing industry with various commercial roles. Besides its advantages, various studies have already highlighted its long-term adverse effects on human health. However, in terms of protein structures and functions, the innate mechanism that triggers these effects has not been elucidated in previously reported studies. Our work takes an in silico approach to delve into structural implications resulting from these additives with three well studied metabolic proteins-lysozyme, bovine serum albumin (BSA) and ribonuclease A. Three classes of food additives- synthetic color, preservatives, and phosphate-containing, are taken here to understand their effects on the aforementioned metabolic proteins. Conventional molecular docking and dynamics (MD) studies reveal that these additives induce significant structural perturbations. Among them, carmoisine brings about the most secondary structural changes for lysozyme and ribonuclease A, whereas sodium tripolyphosphate affects BSA the most. To restore the secondary structural loss, we further examine the roles of osmolytes through cross-docking and higher timescale MD simulations. These studies unravel that application of osmolytes like raffinose and trehalose triggers structural restoration for BSA, lysozyme and ribonuclease A, and highlight their roles as co-formulants to alleviate the adverse effects of food additives., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Osmolytes are naturally occurring small molecular weight organic molecules, which are accumulated in large amounts in all life forms to maintain the stability of cellular proteins and hence preserve their functions during adverse environmental conditions. Trimethylamine N-oxide (TMAO) and N,N,N-trimethylglycine (betaine) are methylamine osmolytes that have been extensively studied for their diverse roles in humans and have demonstrated opposing relations with human health. These osmolytes are obtained from food and synthesized endogenously using dietary constituents like choline and carnitine. Especially, gut microbiota plays a vital role in TMAO synthesis and contributes significantly to plasma TMAO levels. The elevated plasma TMAO has been reported to be correlated with the pathogenesis of numerous human diseases, including cardiovascular disease, heart failure, kidney diseases, metabolic syndrome, etc.; Hence, TMAO has been recognized as a novel biomarker for the detection/prediction of several human diseases. In contrast, betaine acts as a methyl donor in one-carbon metabolism, maintains cellular S-adenosylmethionine levels, and protects the cells from the harmful effects of increased plasma homocysteine. Betaine also demonstrates antioxidant and anti-inflammatory activities and has a promising therapeutic value in several human diseases, including homocystinuria and fatty liver disease. The present review examines the multifarious functions of TMAO and betaine with possible molecular mechanisms towards a better understanding of their emerging and diverging functions with probable implications in the prevention, diagnosis, and treatment of human diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ilyas, Wijayasinghe, Khan, El Samaloty, Adnan, Dar, Poddar, Singh, Sharma and Khan.)

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [ Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera , which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Singh, Jayant, Singh, Bhutani, Poddar, Chaudhary, Khan, Adnan, Siddiqui, Hassan, Khan, Lai and Khan.)

Microbial desalination cells (MDC) are evaluated as an environmentally friendly approach for purifying saline water by using power generated by the decomposition of organic materials in the wastewater. The present study is to evaluate the ferrocyanide-redox and biocathode approach in treating simulated saline water and subsequently recovering bio-electricity using actual domestic reverse osmosis reject water. For the desalination of simulated saline water and domestic reverse osmosis reject water, a three-chamber microbial desalination cell with graphite electrodes and anion and cation exchange membranes was constructed. When treating simulated saline water, the biocathode technique achieved a 5% improvement in salt removal and a 4.9% increase in current and power density when compared to the ferrocyanide-redox approach. When biocathode MDC was used to treat domestic reverse osmosis reject water, a maximum current and power density of 3.81 μA/cm 2 and 0.337 μW/cm 2 , respectively, were recorded, as well as COD removal of 83.9% at the desalination chamber and ions reduction for Na, K, and Ca of up to 79%, 76.5%, and 72%, respectively, in a batch operation for 31 days with a stable pH (≈ 7). Thus, the study revealed a microbial desalination cell capable of recovering bioenergy and reducing salt from domestic reverse osmosis reject water with a consistent pH range., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2022.)

Background: The world has been battling several vector-borne diseases since time immemorial. Socio-economic marginality, precipitation variations and human behavioral attributes play a major role in the proliferation of these diseases. Lockdown and social distancing have affected social behavioral aspects of human life and somehow impact on the spread of vector borne diseases. This article sheds light into the relationship between COVID-19 lockdown and global dengue burden with special focus on India. It also focuses on the interconnection of the COVID-19 pandemic (waves 1 and 2) and the alteration of human behavioral patterns in dengue cases., Methods: We performed a systematic search using various resources from different platforms and websites, such as Medline; Pubmed; PAHO; WHO; CDC; ECDC; Epidemiology Unit Ministry of Health (Sri Lanka Government); NASA; NVBDCP from 2015 until 2021. We have included many factors, such as different geographical conditions (tropical climate, semitropic and arid conditions); GDP rate (developed nations, developing nations, and underdeveloped nations). We also categorized our data in order to conform to COVID-19 duration from 2019 to 2021. Data was extracted for the complete duration of 10 years (2012 to 2021) from various countries with different geographical region (arid region, semitropic/semiarid region and tropical region)., Results: There was a noticeable reduction in dengue cases in underdeveloped (70-85%), developing (50-90%), and developed nations (75%) in the years 2019 and 2021. The dengue cases drastically reduced by 55-65% with the advent of COVID-19 s wave in the year 2021 across the globe., Conclusions: At present, we can conclude that COVID-19 and dengue show an inverse relationship. These preliminary, data-based observations should guide clinical practice until more data are made public and basis for further medical research., (© 2022. The Author(s).)

The coronavirus pandemic hit the world lately and caused acute respiratory syndrome in humans. The causative agent of the disease was soon identified by scientists as SARS-CoV-2 and later called a novel coronavirus by the general public. Due to the severity and rapid spread of the disease, WHO classifies the COVID-19 pandemic as the 6th public health emergency even after taking efforts like worldwide quarantine and restrictions. Since only symptomatic treatment is available, the best way to control the spread of the virus is by taking preventive measures. Various types of antigen/antibody detection kits and diagnostic methods are available for the diagnosis of COVID-19 patients. In recent years, various phytochemicals and repurposing drugs showing a broad range of anti-viral activities with different modes of actions have been identified. Repurposing drugs such as arbidol, hydroxychloroquine, chloroquine, lopinavir, favipiravir, remdesivir, hexamethylene amiloride, dexamethasone, tocilizumab, interferon-β, and neutralizing antibodies exhibit in vitro anti-coronaviral properties by inhibiting multiple processes in the virus life cycle. Various research groups are involved in drug trials and vaccine development. Plant-based antiviral compounds such as baicalin, calanolides, curcumin, oxymatrine, matrine, and resveratrol exhibit different modes of action against a wide range of positive/negative sense-RNA/DNA virus, and future researches need to be conducted to ascertain their role and use in managing SARS-CoV-2. Thus this article is an attempt to review the current understanding of COVID- 19 acute respiratory disease and summarize its clinical features with their prospective control and various aspects of the therapeutic approach., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

There has been substantial progress in artificial intelligence (AI) algorithms and their medical sciences applications in the last two decades. AI-assisted programs have already been established for remote health monitoring using sensors and smartphones. A variety of AI-based prediction models are available for gastrointestinal, inflammatory, non-malignant diseases, and bowel bleeding using wireless capsule endoscopy, hepatitis-associated fibrosis using electronic medical records, and pancreatic carcinoma utilizing endoscopic ultrasounds. AI-based models may be of immense help for healthcare professionals in the identification, analysis, and decision support using endoscopic images to establish prognosis and risk assessment of patients' treatment employing multiple factors. Enough randomized clinical trials are warranted to establish the efficacy of AI-algorithms assisted and non-AI-based treatments before approval of such techniques from medical regulatory authorities. In this article, available AI approaches and AI-based prediction models for detecting gastrointestinal, hepatic, and pancreatic diseases are reviewed. The limitations of AI techniques in such diseases' prognosis, risk assessment, and decision support are discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Various microbial strains and techniques are being used to improve power production in microbial fuel cells. Cow dung is a peculiar source of anaerobic and micro-aerophilic organisms that were employed in this study to isolate exo-electrogenic microorganisms. To validate their exo-electrogenic nature, all eight visually distinct bacterial single-cell colonies were tested using the ferrocyanide reduction assay, which resulted in the selection of one bacterial strain AD1-ELB with the ability to reduce ferrocyanide for further biochemical, physiological and electrochemical characterization. The selected strain AD1-ELB was identified as Bacillus velezensis by 16 s rRNA gene sequencing. When used in a single-chambered MFC, the isolated AD1-ELB strain produced a maximum open-circuit voltage of 455 mV with a maximum current density of 51.78 µA/cm 2 and maximum power density of 4.33 µW/cm 2 on the 16th day. Bacillus velezensis AD1-ELB strain was treated with low-frequency ultrasound (40 kHz) for 1, 2, 3, 4, and 5 min to assess the effect of ultrasonic pre-treatment on an isolated pure culture-based microbial fuel cell. A 3-min exposure to low-frequency ultrasonic therapy resulted in an increase in maximum power of 4.33 µW/cm 2 with a current density of 51.78 µA/cm 2 in the MFC, which decreases significantly after 4 and 5 min. Thus, the overall power density achieved was 1.89 times greater than in MFCs with untreated strain. These findings support the use of low-frequency ultrasonic stimulation to improve the performance of microbial fuel cell devices and are restricted to the pure, single-cell strain AD1-ELB, with the potential for variation if some other isolated strain is utilized, hence requiring further study to determine its relative variations., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2021.)

Epigenetics in the current times has become a gateway to acquire answers to questions that were left unanswered by classical and modern genetics, be it resolving the complex mystery behind neurodegenerative disorders or understanding the complexity behind life-threatening cancers. It has presented to the world an entirely new dimension and has added a dynamic angle to an otherwise static field of genetics. Alzheimer's disease is one of the most prevalent neurodegenerative disorders is largely found to be a result of alterations in epigenetic pathways. These changes majorly comprise an imbalance in DNA methylation levels and altered acetylation and methylation of histones. They are often seen to cross-link with metabolic regulatory pathways such as that of mTOR, contributing significantly to the pathophysiology of AD. This review focusses on the study of the interplay of the mTOR regulatory pathway with that of epigenetic machinery that may elevate the rate of early diagnosis and prove to be a gateway to the development of an efficient and novel therapeutic strategy for the treatment of Alzheimer's disease at an early stage., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Medicinal or herbal plants are widely used for their many favourable properties and are generally safe without any side effects. Saponins are sugar conjugated natural compounds which possess a multitude of biological activities such as medicinal properties, antimicrobial activity, antiviral activity, etc. Saponin production is a part of the normal growth and development process in a lot of plants and plant extracts such as liquorice and ginseng which are exploited as potential drug sources. Herbal compounds have shown a great potential against a wide variety of infectious agents, including viruses such as the SARS-CoV; these are all-natural products and do not show any adverse side effects. This article reviews the various aspects of saponin biosynthesis and extraction, the need for their integration into more mainstream medicinal therapies and how they could be potentially useful in treating viral diseases such as COVID-19, HIV, HSV, rotavirus etc. The literature presents a close review on the saponin efficacy in targeting mentioned viral diseases that occupy a high mortality rate worldwide. This manuscript indicates the role of saponins as a source of dynamic plant based anti-viral remedies and their various methods for extraction from different sources., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Today, the world is suffering from the pandemic of a novel coronavirus disease (COVID-19), a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the third fatal coronavirus outbreak that has already occurred in the 21st century. Even six months after its emergence, hundreds of thousands of people are still being infected with SARS-CoV-2, and thousands of lives are lost every day across the world. No effective therapy has been approved to date for the treatment of this disease, suggesting the need to broaden the scope in the search for effective treatments. Throughout history, folk medicine has been successfully used to treat various ailments in humans, and Traditional Chinese Medicine has been instrumental in the containment of a number of viral diseases. Owing to their high chemical diversity and safety profiles, natural products offer great promises as potentially effective antiviral drugs. In recent years, a large number of anti-coronaviral phytochemicals with different mechanisms of action have been identified. Among them, tetra-O-galloyl-β-D-glucose, caffeic acid, and saikosaponin B2 block viral entry. A number of flavonoids inhibit viral proteases. Silvestrol inhibits protein synthesis. Myricetin and scutellarein inhibit viral replication. Emodin, luteolin, and quercetin demonstrate anti-coronaviral activity by inhibiting multiple processes in the virus life cycle. In this review, we critically evaluate the findings of the natural product-based anticoronaviral research that has been published during the last two decades, and attempt to provide a comprehensive description about their utility as potential broad-spectrum anti-coronaviral drugs, examining leads that may guide/facilitate anti-SARS-CoV-2 drug development studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's Disease (AD), characterized by abnormally phosphorylated tau, Paired Helical Filaments (PHFs), Neurofibrillary Tangles (NFTs), deregulated mammalian Target Of Rapamycin (mTOR), and Aβ deposits, is a multifactorial disease with sleep disorders being one of the causative agents. Therefore, we have reviewed the literature and have tried to decode the existence of positive feedback, reciprocal and a bidirectional relationship allying between sleep disturbances and AD. Much light has been thrown on the role of tau pathology and amyloid pathology in sleep pathology and its association with AD pathology. We have also discussed the role of melatonin in regulating sleep disorders and AD. The neuroprotective effect of melatonin via inhibiting tau hyperphosphorylation and Aβ deposition has also been discussed. Moreover, astrocytes involvement in aggravating AD has also been highlighted in this review. Several therapeutic approaches aimed at improving both sleep disorders and AD have been duly discussed such as administration of antidepressants and antihistamines, immunotherapy, metal chelators, melatonin supplementation, light therapy and physical activity. Despite consistent efforts, the complete etiology concerning sleep disorder and AD is still unclear. Therefore, further research is needed to unravel the mechanism involved and also to develop strategies that may help in obstructing AD in its preclinical stage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cyclooxygenases (COX) are enzymes catalyzing arachidonic acid into prostanoids. COX exists in three isoforms: COX-1, 2, and 3. COX-1 and COX-2 have been widely studied in order to explore and understand their involvement in Alzheimer's disease (AD), a progressive neuroinflammatory dementia. COX-2 was traditionally viewed to be expressed only under pathological conditions and to have detrimental effects in AD pathophysiology and neurodegeneration. However, an increasing number of reports point to much more complex roles of COX-2 in AD. Mammalian/mechanistic target of rapamycin (mTOR) has been considered as a hub which integrates multiple signaling cascades, some of which are also involved in AD progression. COX-2 and mTOR are both involved in environmental sensing, growth, and metabolic processes of the cell. They are also known to act in cooperation in many different cancers and thus, their role together in normal cellular functions as well as AD has been explored in this review. Some of the therapeutic approaches targeting COX-2 and mTOR in AD and cancer are also discussed., (Copyright © 2020 Tyagi, Kamal and Poddar.)

This study involves a detailed investigation about the effect of three elicitors, such as chitosan, jasmonic acid and salicylic acid (SA) on withaferin A and withanolide A contents of Withania somnifera (L.) Dunal (Poshita variety). Moreover, the different environmental regimes were also studied to assess and optimise the accumulation of withaferin A and Withanolide A contents. In an open environment, the total withaferin A content was found to be increased 6.3 and 5.8 times when sprayed with chitosan, 10 ppm and 50 ppm, respectively, as compared to control. Similarly, the total withanolide A content was found to be increased 4.5 and 3.6 times when sprayed with jasmonic acid (400 ppm and 200 ppm, respectively) with respect to control. In a controlled condition, the total withaferin A content was found to be increased 6 and 4.5 times when sprayed with jasmonic acid (400 ppm and 200 ppm, respectively) as compared to control. On the other hand, the total withanolide A content was found to be enhanced by 7 and 4.3 times when sprayed with jasmonic acid (400 ppm) and SA (1 ppm), respectively, as compared to control. Therefore, this study was focussed on the optimisation of enhanced accumulation of withaferin A and withanolide A contents in the aerial parts of the plant in open and controlled environment by foliar application of elicitors in minimal concentrations., (© King Abdulaziz City for Science and Technology 2020.)

Alzheimer's disease, categorized by the piling of amyloid-β (Aβ), hyperphosphorylated tau, PHFs, NFTs and mTOR hyperactivity, is a neurodegenerative disorder, affecting people across the globe. Osmolytes are known for osmoprotectants and play a pivotal role in protein folding, function and protein stability, thus, preventing proteins aggregation, and counteracting effects of denaturing solutes on proteins. Osmolytes (viz., sorbitol, inositol, and betaine) perform a pivotal function of maintaining homeostasis during hyperosmotic stress. The selective advantage of utilising osmolytes over inorganic ions by cells is in maintaining cell volume without compromising cell function, which is important for organs such as the brain. Osmolytes have been documented not only as neuroprotectors but they also seem to act as neurodegenerators. Betaine, sucrose and trehalose supplementation has been seen to induce autophagy thereby inhibiting the accumulation of Aβ. In contrast, sucrose has also been associated with mTOR hyperactivity, a hallmark of AD pathology. The neuroprotective action of taurine is revealed when taurine supplementation is seen to inhibit neural damage, apoptosis and oxidative damage. Inositol stereoisomers (viz., scyllo-inositol and myo-inositol) have also been seen to inhibit Aβ production and plaque formation in the brain, inhibiting AD pathogenesis. However, TMAO affects the aging process adversely by deregulating the mTOR signalling pathway and then kindling cognitive dysfunction via degradation of chemical synapses and synaptic plasticity. Thus, it can be concluded that osmolytes may act as a probable therapeutic approach for neurodevelopmental disorders. Here, we have reviewed and focussed upon the impact of osmolytes on mTOR signalling pathway and thereby its role in AD pathogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The hyperphosphorylation of tau protein and the overexpression of mTOR are considered to be the driving force behind Aβ plaques and Neurofibrillay Tangles (NFT's), hallmarks of Alzheimer's disease (AD). It is now evident that miscellaneous diseases such as Diabetes, Autoimmune diseases, Cancer, etc. are correlated with AD. Therefore, we reviewed the literature on the causes of AD and investigated the association of tau and mTOR with other diseases. We have discussed the role of insulin deficiency in diabetes, activated microglial cells, and dysfunction of blood-brain barrier (BBB) in Autoimmune diseases, Presenilin 1 in skin cancer, increased reactive species in mitochondrial dysfunction and deregulated Cyclins/CDKs in promoting AD pathogenesis. We have also discussed the possible therapeutics for AD such as GSK3 inactivation therapy, Rechaperoning therapy, Immunotherapy, Hormonal therapy, Metal chelators, Cell cycle therapy, γ-secretase modulators, and Cholinesterase and BACE 1-inhibitors which are thought to serve a major role in combating pathological changes coupled with AD. Recent research about the relationship between mTOR and aging and hepatic Aβ degradation offers possible targets to effectively target AD. Future prospects of AD aims at developing novel drugs and modulators that can potentially improve cell to cell signaling, prevent Aβ plaques formation, promote better release of neurotransmitters and prevent hyperphosphorylation of tau.

Canavan disease is a fatal neurological disorder caused by defects in the gene that produces the enzyme aspartoacylase. Enzyme replacement therapy can potentially be used to overcome these defects if a stable enzyme form that can gain access to the appropriate neural cells can be produced. Achieving the proper cellular targeting requires a modified form of aspartoacylase that can traverse the blood-brain barrier. A PEGylated form of aspartoacylase that shows dramatic enhancement in brain tissue access and distribution has been produced. While the mechanism of transport has not yet been established, this modified enzyme is significantly less immunogenic than unmodified aspartoacylase. These improved properties set the stage for more extensive enzyme replacement trials as a possible treatment strategy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We directly measure the dynamics of the HIV trans-activation response (TAR)-DNA hairpin with multiple loops using single-molecule Förster resonance energy transfer (smFRET) methods. Multiple FRET states are identified that correspond to intermediate melting states of the hairpin. The stability of each intermediate state is calculated from the smFRET data. The results indicate that hairpin unfolding obeys a "fraying and peeling" mechanism, and evidence for the collapse of the ends of the hairpin during folding is observed. These results suggest a possible biological function for hairpin loops serving as additional fraying centers to increase unfolding rates in otherwise stable systems. The experimental and analytical approaches developed in this article provide useful tools for studying the mechanism of multistate DNA hairpin dynamics and of other general systems with multiple parallel pathways of chemical reactions.

Osmolytes are naturally occurring small molecules accumulated intracellularly to protect organisms from various denaturing stresses. Similar to the two faces of a coin, several of these osmolytes are stabilizing and destabilizing proteins depending on the concentrations and/or solvent conditions. For example, the well known stabilizing osmolyte, trehalose destabilizes some proteins at high concentration and/or high pH. In spite of the fact that destabilizing aspects of osmolytes can modulate many cellular processes including regulation of protein homeostasis (proteostasis), protein-protein interaction, and protein-DNA interaction, researchers have mostly focused on the stabilizing aspects of osmolytes. Thus, it is important to look into both aspects of osmolytes to determine their precise role under physiological conditions. In this article, we have discussed both stabilizing and destabilizing/denaturant aspects of osmolytes to uncover both sides of the coin., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Experimental results of RNase-A stabilization by sugar osmolytes show that the change in the Gibbs free energy (ΔGD) associated with the equilibrium, N (native) state ↔ D (denatured) state of the protein in the presence of equimolar mixture of monosaccharides is larger than that of the corresponding oligosaccharides at a given temperature and pH. However, at the molar scale, ΔGD obtained in the presence of an oligosaccharide is much higher as compared with ΔGD obtained using individual monosaccharide. We used scaled particle theory (SPT) to explain these experimental observations. The effective length, called Tolman's length that describes the curvature correlations to a surface area or surface tension and in turn contributes to the change in free energy, is discussed. Tolman's length is higher for corresponding monomer mixture than the oligosaccharide molecules. Based on SPT analysis, a geometrical model is proposed for clustering of monosaccharides in the mixture due to high particle density. The cluster is presumed to have weak interaction among them due to larger hydrodynamic radius than that of the bonded molecules of oligosaccharides.

We report the effects of stabilizing osmolytes (low molecular mass organic compounds that raise the midpoint of thermal denaturation) on the stability and function of RNase-A under physiological conditions (pH 6.0 and 25 degrees C). Measurements of Gibbs free energy change at 25 degrees C (DeltaG(D) degrees ) and kinetic parameters, Michaelis constant (K(m)) and catalytic constant (k(cat)) of the enzyme mediated hydrolysis of cytidine monophosphate, enabled us to classify stabilizing osmolytes into three different classes based on their effects on kinetic parameters and protein stability. (a) Polyhydric alcohols and amino acids and their derivatives do not have significant effects on DeltaG(D) degrees and functional activity (K(m) and k(cat)). (b) Methylamines increase DeltaG(D) degrees and k(cat), but decrease K(m). (c) Sugars increase DeltaG(D) degrees , but decrease both K(m) and k(cat). These findings suggest that, among the stabilizing osmolytes, (a) polyols, amino acids and amino acid derivatives are compatible solutes in terms of both stability and function, (b) methylamines are the best refolders (stabilizers), and (c) sugar osmolytes stabilize the protein, but they apparently do not yield functionally active folded molecules.

Thermal denaturation curves of ribonuclease-A were measured by monitoring changes in the far-UV circular dichroism (CD) spectra in the presence of different concentrations of six sugars (glucose, fructose, galactose, sucrose, raffinose and stachyose) and mixture of monosaccharide constituents of each oligosaccharide at various pH values in the range of 6.0-2.0. These measurements gave values of T(m) (midpoint of denaturation), DeltaH(m) (enthalpy change at T(m)), DeltaC(p) (constant-pressure heat capacity change) under a given solvent condition. Using these values of DeltaH(m), T(m) and DeltaC(p) in appropriate thermodynamic relations, thermodynamic parameters at 25 degrees C, namely, DeltaG(D)(o) (Gibbs energy change), DeltaH(D)(o) (enthalpy change), and DeltaS(D)(o) (entropy change) were determined at a given pH and concentration of each sugar (including its mixture of monosaccharide constituents). Our main conclusions are: (i) each sugar stabilizes the protein in terms of T(m) and DeltaG(D)(o), and this stabilization is under enthalpic control, (ii) the protein stabilization by the oligosaccharide is significantly less than that by the equimolar concentration of the constituent monosaccharides, and (iii) the stabilization by monosaccharides in a mixture is fully additive. Furthermore, measurements of the far- and near-UV CD spectra suggested that secondary and tertiary structures of protein in their native and denatured states are not perturbed on the addition of sugars.

Presence of adrenocorticotropic hormone (ACTH) was investigated in tissues from 150 cases of primary breast cancer. ACTH peptides were detected in 16.7% cases and ACTH expression was higher in post-menopausal cancers. A significant association was noticed between the presence of ACTH and the positive estrogen receptor (ER) status of tumors. The study indicated a probable role of these ectopic ACTH peptides in steroid hormone related pathology of breast cancer.