Graph theoretical descriptors differentiate d-Mannose isomers in the principal component proposed feature space: A computational approach.

The intricate nature of carbohydrates, particularly monosaccharides, stems from the existence of several chiral centers within their tertiary structures. Predicting and characterizing the molecular geometries and electrostatic landscapes of these substances is difficult due to their complex electrical properties. Moreover, these structures can display a substantial degree of conformational flexibility due to the presence of many rotatable bonds. Moreover, identifying and distinguishing between D and L enantiomers of monosaccharides presents a significant analytical obstacle since there is a need for empirically measurable properties that can distinguish them. This work uses Principal Component Analysis (PCA) to explore the chemical information included in 3D descriptors in order to comprehend the conformational space of d-Mannose stereoisomers. The isomers may be discriminated by utilizing 3D matrix-based indices, geometrical descriptors, and RDF descriptors. The isomers can be distinguished by descriptors, such as the Harary-like index from the reciprocal squared geometrical matrix (H_RG), Harary-like index from Coulomb matrix (H_Coulomb), Wiener-like index from Coulomb matrix (Wi_Coulomb), Wiener-like index from geometrical matrix (Wi_G), Graph energy from Coulomb matrix (SpAbs_Coulomb), Spectral absolute deviation from Coulomb matrix (SpAD_Coulomb), and Spectral positive sum from Coulomb matrix (SpPos_Coulomb). Among these descriptors, the first two, H_RG and H_Coulomb, perform the best in differentiation among the 3D-Matrix-Based Descriptors (3D-MBD) class. The results obtained from this study provide a significant chemical insight into the structural characteristics of the compounds inside the graph theoretical framework. These findings are likely to serve as the basis for developing new methods for analytical experiments.

The artificial neural network selects saccharides from natural sources a promise for potential FimH inhibitor to prevent UTI infections.

The major challenge in the development of affordable medicines from natural sources is the unavailability of logical protocols to explain their mechanism of action in biological targets. FimH (Type 1 fimbrin with D-mannose specific adhesion property), a lectin on E. coli cell surface is a promising target to combat the urinary tract infection (UTI). The present study aimed at predicting the inhibitory capacity of saccharides on FimH. As mannosides are considered FimH inhibitors, the readily accessible saccharides from the PubChem collection were utilized. The artificial neural networks (ANN)-based machine learning algorithm Self-organizing map (SOM) has been successfully employed in predicting active molecules as they could discover relationships through self-organization for the ligand-based virtual screening. Docking was used for the structure-based virtual screening and molecular dynamic simulation for validation. The result revealed that the predicted molecules malonyl hexose and mannosyl glucosyl glycerate exhibit exactly similar binding interactions and better docking scores as that of the reference bioassay active, heptyl mannose. The pharmacokinetic profile matches that of the selected bioflavonoids (quercetin malonyl hexose, kaempferol malonyl hexose) and has better values than the control drug bioflavonoid, monoxerutin. Thus, these two molecules can effectively inhibit type 1 fimbrial adhesin, as antibiotics against E. coli and can be explored as a prophylactic against UTIs. Moreover, this investigation can pave the way to the exploration of the potential benefits of plant-based treatments. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00212-5.

Mannose: a potential saccharide candidate in disease management.

There are a plethora of antibiotic resistance cases and humans are marching towards another big survival test of evolution along with drastic climate change and infectious diseases. Ever since the first antibiotic [penicillin], and the myriad of vaccines, we were privileged to escape many infectious disease threats. The survival technique of pathogens seems rapidly changing and sometimes mimicking our own systems in such a perfect manner that we are left unarmed against them. Apart from searching for natural alternatives, repurposing existing drugs more effectively is becoming a familiar approach to new therapeutic opportunities. The ingenious use of revolutionary artificial intelligence-enabled drug discovery techniques is coping with the speed of such alterations. D-Mannose is a great hope as a nutraceutical in drug discovery, against CDG, diabetes, obesity, lung disease, and autoimmune diseases and recent findings of anti-tumor activity make it interesting along with its role in drug delivery enhancing techniques. A very unique work done in the present investigation is the collection of data from the ChEMBL database and presenting the targetable proteins on pathogens as well as on humans. It shows Mannose has 50 targets and the majority of them are on human beings. The structure and conformation of certain monosaccharides have a decisive role in receptor pathogen interactions and here we attempt to review the multifaceted roles of Mannose sugar, its targets associated with different diseases, as a natural molecule having many success stories as a drug and future hope for disease management.

Artificial Neural Network-Based Study Predicts GS-441524 as a Potential Inhibitor of SARS-CoV-2 Activator Protein Furin: a Polypharmacology Approach.

Furin, a pro-protein convertase, plays a significant role as a biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS-CoV-2, furin has become the center of attraction for researchers as the spike protein contains a polybasic furin cleavage site. In the present work, we have searched for novel inhibitors against this interesting human target from FDA-approved antiviral. To enhance the selection of new inhibitors, we employed Kohonen's artificial neural network-based self-organizing maps for ligand-based virtual screening. Promising results were obtained which can help in drug repurposing and network pharmacology studies can address the errors generated due to promiscuity/polypharmacology. We found 15 existing FDA antiviral drugs having the potential to inhibit furin. Among these, six compounds have targets on important human proteins (LDLR, FCGR1A, PCK1, TLR7, DNA, and PNP). The role of these 15 drugs inhibiting furin can be established by studying further on patients infected with number of viruses including SARS-CoV-2. Here we propose two promising candidate FDA drugs GS-441524 and Grazoprevir (MK-5172) for repurposing as inhibitors of furin. The best results were observed with GS-441524.

Unravelling Vitamin B12 as a potential inhibitor against SARS-CoV-2: A computational approach.

The new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is the etiological agent of Coronavirus disease 2019 (COVID-19), which becomes an eventual pandemic outbreak. Lack of proper therapeutic management has accelerated the researchers to repurpose existing drugs with known preclinical and toxicity profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. Vitamins are necessary nutrients for cell growth, function, and development. Furthermore, they play an important role in pathogen defence via cell-mediated responses and boost immunity. Using a computational approach, we intend to identify the probable inhibitory effect of all vitamins on the drug targets of COVID-19. The computational analysis demonstrated that vitamin B12 resulted in depicting suitable significant binding with furin, RNA dependent RNA polymerase (RdRp), Main proteases (Mpro), ORF3a and ORF7a and Vitamin D3 with spike protein and vitamin B9 with non structural protein 3 (NSP3). A detailed examination of vitamins suggests that vitamin B12 may be the component that reduces virulence by blocking furin which is responsible for entry of virus in the host cell. Details from the Molecular Dynamics (MD) simulation study aided in determining vitamin B12 as a possible furin inhibitor.

Modulation of physiological oxidative stress and antioxidant status by abiotic factors especially salinity in aquatic organisms.

Exposure to a variety of environmental factors such as temperature, pH, oxygen and salinity may influence the oxidative status in aquatic organisms. The present review article focuses on the modulation of oxidative stress with reference to the generation of reactive oxygen species (ROS) in aquatic animals from different phyla. The focus of the review article is to explore the plausible mechanisms of physiological changes occurring in aquatic animals due to altered salinity in terms of oxidative stress. Apart from the seasonal variations in salinity, global warming and anthropogenic activities have also been found to influence oxidative health status of aquatic organisms. These effects are discussed with an objective to develop precautionary measures to protect the diversity of aquatic species with sustainable conservation. Comparative analyses among different aquatic species suggest that salinity alone or in combination with other abiotic factors are intricately associated with modulation in oxidative stress in a species-specific manner in aquatic animals. Osmoregulation under salinity stress in relation to energy demand and supply are also discussed. The literature survey of >50 years (1960-2020) indicates that oxidative stress status and comparative analysis of redox modulation have evolved from the analysis of various biotic and/or abiotic factors to the study of cellular signalling pathways in these aquatic organisms.

Interfacial magnetism and exchange coupling in BiFeO3-CuO nanocomposite.

Ferromagnetic BiFeO3 nanocrystals of average size 9 nm were used to form a composite with antiferromagnetic CuO nanosheets, with the composition (x)BiFeO3/(100-x)CuO, x = 0, 20, 40, 50, 60, 80 and 100. The dispersion of BiFeO3 nanocrystals into the CuO matrix was confirmed by x-ray diffraction and transmission electron microscopy. The ferromagnetic ordering as observed in pure BiFeO3 occurs mainly due to the reduction in the particle size as compared to the wavelength (62 nm) of the spiral modulated spin structure of the bulk BiFeO3. Surface spin disorder of BiFeO3 nanocrystals gives rise to an exponential behavior of magnetization with temperature. Strong magnetic exchange coupling between the BiFeO3 nanocrystal and the CuO matrix induces an interfacial superparamagnetic phase with a blocking temperature of about 80 K. Zero field and field cooled magnetizations are analyzed by a ferromagnetic core and disordered spin shell model. The temperature dependence of the calculated saturation magnetization exhibits three magnetic contributions in three temperature regimes. The BiFeO3/CuO nanocomposites reveal an exchange bias effect below 170 K. The maximum exchange bias field HEB is 1841 Oe for x = 50 at 5 K under field cooling of 50 kOe. The exchange bias coupling results in an increase of coercivity of 1934 Oe at 5 K. Blocked spins within an interfacial region give rise to a remarkable exchange bias effect in the nanocomposite due to strong magnetic exchange coupling between the BiFeO3 nanocrystals and the CuO nanosheets.

Effect of oleic acid ligand on photophysical, photoconductive and magnetic properties of monodisperse SnO2 quantum dots.

Oleic acid capped monodisperse SnO(2) quantum dots (QDs) of size 2.7 nm were synthesized by thermal decomposition and oxidation of Sn(II)(oleate) complex in high boiling nonpolar solvent octadecene using oleic acid as a capping agent and N-methylmorpholine N-oxide as an oxidizing agent. FTIR, DSC and TGA were employed to understand the growth of the oleic acid capped SnO(2) QDs through the decomposition of metal fatty acid complex. The surface defect-related luminescence properties of the QDs were demonstrated using steady-state and time-resolved spectroscopy. The oleic acid capping on the QD surface modifies the electronic structure of SnO(2) and generates blue emission. Moreover the surface capping on the QDs diminishes the photocatalytic activity of bare SnO(2) QDs due to absence of surface oxygen and adsorbed hydroxyl group on the surface of the capped QDs. The capping by the long chain ligand oleic acid makes the SnO(2) QDs less conducting. Ligand exchange of the long chain oleic acid (2.5 nm) by the short chain n-butylamine (0.6 nm) increases the current density of SnO(2) around 43 times due to the reduction of the interparticle distance. Ferromagnetic behaviour of oleic acid capped QDs may be ascribed to the defects in the host due to the alteration of the electronic structure owing to the capping.

Vibrational spectroscopy and ionic conductivity of polyethylene oxide-NaClO4-CuO nanocomposite.

Structure, morphology and thermal properties of polyethylene oxide (PEO) with sodium perchlorate (NaClO(4)) as electrolytic salt have been investigated by incorporating cupric monoxide (CuO) nanoparticles. Monoclinic CuO affects melting and glass transition temperatures of PEO-NaClO(4). Crystallinity and free ion concentration change with the variation of CuO concentration. The maximum ionic conductivity is observed for 10 wt.% CuO. Ionic conductivity follows Arrhenius type behavior as a function of temperature.

Template-free synthesis of mesoporous CuO dandelion structures for optoelectronic applications.

A simple template-free hydrothermal route was used for the synthesis of novel mesoporous CuO dandelion structures formed by self-organized CuO nanorods. A very high surface area approximately 325 m(2)/g and remarkably enhanced photoconductivity under white light irradiation of the CuO dandelions were observed compared to the nanocrystals. The extremely high photoconductivity is attributed to the presence of oxygen related hole-trap states at the large surface area of the dandelions. The fast response (tau = 24 s) of the photocurrent holds promise for the fast photo-sensing device applications.

Supplementation of curcumin and vitamin E enhances oxidative stress, but restores hepatic histoarchitecture in hypothyroid rats.

AIMS: In the present study, the effects of vitamin E and curcumin on hepatic dysfunction, mitochondrial oxygen consumption as well as hyperlipidemia in hypothyroid rats are reported. MAIN METHODS: Adult male rats were rendered hypothyroid by administration of 0.05% 6-n-propyl-2-thiouracil (PTU) in their drinking water, while vitamin E (200 mg/kg body weight) and curcumin (30 mg/kg body weight) were supplemented orally for 30 days. KEY FINDINGS: Hypothyroidism-induced elevation in serum aspartate aminotransferase activity was found to decline in vitamin E and curcumin treated rats. Nevertheless, distorted histoarchitecture revealed in hypothyroid rat liver was alleviated to normal by vitamin E and curcumin treatment. Regulation of hypothyroidism induced decrease in complexes I and II mediated mitochondrial respiration by vitamin E and curcumin was found to be different. Administration of curcumin to hypothyroid rats alleviates the decreased state 4 respiration and increased respiratory control ratio (RCR) level in complex I mediated mitochondrial oxygen consumption, whereas complex II mediated respiration was not influenced by exogenous antioxidants. Although, increase in serum concentration of total cholesterol was not modified by exogenous antioxidants, increased level of non-high-density lipoprotein cholesterol (non-HDL-C) in serum of hypothyroid rats was further enhanced by vitamin E and curcumin. Moreover, a significant elevation in mitochondrial lipid peroxidation and protein carbonylation was noticed in hypothyroid groups treated with vitamin E and curcumin. SIGNIFICANCE: The present study suggests that supplementation of curcumin and vitamin E enhances oxidative stress parameters and hyperlipidemia; nevertheless, it protects hypothyroid-induced altered rectal temperature, serum transaminase activity and hepatic histoarchitecture.

Thyroid hormone influences antioxidant defense system in adult rat brain.

The objective of the current study was to find out whether thyroid hormone influences antioxidant defense parameters of rat brain. Several oxidative stress and antioxidant defense parameters of mitochondrial (MF) and post-mitochondrial (PMF) fractions of cerebral cortex (CC) of adult rats were compared among euthyroid (control), hypothyroid [6-n-propylthiouracil (PTU)-challenged], and hyperthyroid (T3-treatment to PTU-challenged rats) states. Oxidative stress parameters, such as thiobarbituric acid-reactive substances (TBA-RS) and protein carbonyl content (PC), in MF declined following PTU challenge in comparison to euthyroid rats. On the other hand, when PTU-challenged rats were treated with T3, a significant increase in the level of oxidative stress parameters in MF was recorded. Hydrogen peroxide content of MF as well as PMF of CC was elevated by PTU-challenge and brought to normal level by subsequent treatment of T3. Although mitochondrial glutathione (reduced or oxidized) status did not change following PTU challenge, a significant reduction in oxidized glutathione (GSSG) level was noticed in PMF following the treatment. T3 administration to PTU-challenged rats had no effect on mitochondrial glutathione status. Total and CN-resistant superoxide dismutase (SOD) activities in MF of CC augmented following PTU challenge. CN-resistant SOD activity did not change when PTU-challenged rats were treated with T3. Although CN-sensitive SOD activity of PMF remained unaltered in response to PTU challenge, its activity increased when PTU-challenged rats were treated with T3. Catalase activity in PMF of CC of PTU-challenged rats increased, whereas the activity was decreased when hypothyroid rats were treated with T3. Similarly, total and Se-dependent glutathione peroxidase (GPx) activities of MF increased following PTU challenge and reduced following administration of T3. Se-independent GPx activity of MF and PMF and glutathione reductase activity of PMF decreased following PTU challenge and did not change further when rats were treated with T3. On the other hand, glutathione S-transferase activity of MF and PMF of CC did not change following PTU challenge but decreased below detectable level following T3 treatment. Results of the current investigation suggest that antioxidant defense parameters of adult rat brain are considerably influenced by thyroid states of the body.