Cow milk oligosaccharides (CMOs) have garnered significant attention due to their association with enhanced infant immune system development, defence against pathogens, and anti-inflammatory properties. Understanding their structural variations is crucial for unlocking their diverse biological functions. This paper explores the structural diversity of CMOs isolated from different cow breeds and their potential health implications. Recent research has elucidated various CMO structures, revealing a rich landscape of oligosaccharides with unique arrangements and potential bioactivities. Compounds such as Aurose, Tarose, Osose, and Tosose, identified in cow colostrum from the Jarsi breed, provide insights into early milk production. Similarly, discoveries like Asose, Urose, Ausose, and Tausose in black cow milk highlight the diversity within specific cow varieties. Further investigations into oligosaccharides from Lal Muha cow milk, including Rusose, Usose, Taurose, and Uruose, and from Chauri cow milk, such as Bosose, Unninose, Nakose, and Nienose, underscore the complex interplay between cow genetics and milk composition. Findings from black cow milk, including Indicose, Indose, Indinose, Bosnose, and Dicusose, emphasise the potential bioactivity of oligosaccharides. Recent work on Tharparkar Cow milk oligosaccharides like Tharoside, Parkoside, Karoside, and Arkaroside showcases ongoing efforts to explore carbohydrate complexity across different cow breeds. These discoveries open avenues for further research into the structural variations of CMOs and how they affect human health.

Protein is an important biomolecule that needs to maintain 3D (three-dimensional) dynamic structure in respective physiological conditions in order for homeostasis to be maintained in an organism. This 3D structure is majorly governed by non-covalent interactions. These interactions are highly subjected to changes in the local physicochemical environments of proteins. Any changes in the environment perturb the protein 3D conformation, leading to partial unfolding, consequently rendering the protein non-functional. In recent years, various domains of biological sciences have increasingly embraced nanoparticles, primarily driven by its diverse array of physicochemical properties and applications. Protein adsorption onto nanoparticle surfaces affects the interaction that governs a 3D structure, resulting in conformational rearrangement and altered functional efficacy. The induced changes are very important to explaining the proper functioning of proteins in the presence of nanoparticles, regardless of whether if it is being used as a platform for various biological applications. In this line, lysozyme, a well-studied globular protein model, interacts with the ZnONP interface and its effect on the protein conformational rearrangement in different pH conditions using various biophysical techniques is explored. Lysozymes exhibit different conformations at varying pH levels, affecting their interaction with ZnONP. This protein conformation significantly influences the nature of interactions and ultimately impacts its thermodynamic attributes with ZnONP. Once the lysozyme interacts with the ZnONP interface, it sequesters the protein monomeric population into predominantly two populations, where the stable bulk monomeric population remains in equilibrium with relatively less thermodynamically stable monomeric lysozymes present in corona of the protein--ZnONP complex. However, changes in the conformation do not affect the secondary structure or the functional efficacy of the protein, thereby leaving the protein functional and adequately preserving its efficacy.

ABSTRACT:

Graphitic carbon nitride (g-C₃N₄) and zinc oxide (ZnO) are two promising materials that have been extensively studied for their potential applications in photocatalytic and biomedical fields including biosensors, bioimaging, photodynamic therapy, drug delivery, chemotherapy, and the antimicrobial segment because of its biocompatible nature.For biogenic synthesis of ZnO will be carried out using aqueous leaf extract of Rosa indicia. The synthesis of g-C₃N₄/ZnO nanocomposites will be achieve through hydrothermal synthesis, to produce materials with enhanced photocatalytic and biomedical properties due to development of heterojunction. Synthesized g-C₃N₄/ZnO hybrid nanostructure may have band gap around 2.85eV to 3.01eV. The photocatalytic activity of the composites is evaluated through the degradation of organic pollutants under simulated solar irradiation, demonstrating their potential for environmental remediation. In biomedical applications, the g-C₃N₄/ZnO nanocomposites exhibit biocompatibility and are explored for use in drug delivery systems, tissue engineering, and antimicrobial coatings. The incorporation of g-C₃N₄/ZnO nanocomposites into biomaterials enhances their mechanical, thermal, and electrical properties, making them suitable for various biomedical applications. Techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV-Vis spectroscopy are employed to analyze the crystal structure, surface morphology, particle size, chemical composition, and optical properties of the composites. The comprehensive characterization of these materials is crucial for their successful development and utilization in various technological domains.

Vanda roxburghii (VR), a native medicinal plant in Bangladesh belonging to the Orchidaceae family, has been previously reported to be effective against Alzheimer’s disease (AD). This study aimed to investigate the potential mechanism of the phytoconstituents of VR against AD using network pharmacology and molecular docking analysis. The phytoconstituents of VR were listed from several databases and their blood–brain barrier (BBB) permeability was predicted using SwissADME. Targets of the BBB permeable actives were predicted using SwissTargetPrediction and Similarity Ensemble Approach databases. The putative genes responsible for AD were obtained from GeneCards and DisGenet databases. The common targets for both VR and AD were scrutinized for how the protein–protein interaction (PPI) network was constructed using STRING and how the core protein targets were identified using Cytoscape. Gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the target genes using DAVID. Finally, the binding interactions between the phytochemicals and targets of AD were validated by molecular docking using PyRx.

In total, 4 phytochemicals with 328 exclusive target genes were predicted to cross the BBB. Moreover, 1046 exclusive disease targets for AD were identified and 103 shared targets of VR and AD were acquired. From the PPI network, 5 targets with higher possibilities of therapeutic activity rates of VR on AD were obtained. Furthermore, 428 biological processes, 82 cellular components, and 98 molecular functions were enriched with GO functions, and 144 KEGG pathways (including Alzheimer’s disease, apoptosis, and endocrine resistance pathways) were found enriched for VR associated with anti-AD activities and were analyzed. Molecular docking analysis further verified the definite binding capacity of the four actives with the five target proteins (APP, JUN, ESR1, MAPK1, and MAPK3) involved in the significant KEGG pathways and GO functions. Our findings provide directions for further research on the phytochemicals of VR.

Immobilized microalgae (MA) are widely used for the production of biomass and high value-added metabolites, the biocapture of nutrients and heavy metals, and for the destruction of organic pollutants in wastewater. The use of chitosan (CH) as a carrier for MA cultivation has many advantages, including its availability, non-toxicity, biodegradability, biocompatibility and high sorption capacity. However, for successful CH application, it is crucial to increase the cost-effectiveness of microalgae–chitosan systems as compared to traditional technologies. One of the prospective approaches is the synthesis of composites on the basis of chitosan and natural polysaccharide-containing wastes (PCWs) like apple pomace (AP) and mycelium (M), which are the main by-products in the apple juice processing industry and in mushroom farming.

A CH solution and an AP or MM suspension in 2% (w/w) acetic acid were mixed in a 1:3, 1:1, or 3:1 ratio, cross-linked with glutaraldehyde, and freeze-dried to prepare porous and solid composite sponges. The chlorophyte strain Lobosphaera IPPAS C-2047 served as the object in the present work. To reveal the effect of CH/PCW ratio on MA attachment and biocompatibility, we followed the kinetics of MA immobilization. The proportion of unattached cells was deduced from measurements of chlorophyll content in Lobosphaera cell suspensions after their incubation with the composites. Immobilization efficiency was defined as percentage of attached cells calculated relative to the control.

After 24 h incubation, the immobilization efficiency of composites with 25% AP and 25%, 50% M was 25–35% higher as compared to additive-free CH, while composites with 75% of AP and M showed the lowest immobilization efficiency.

We concluded that AP and M additives have prospective features for CH-based composite production in terms of their low cost and sustainability. oreover, their addition resulted in the enhancement of MA immobilization efficiency.

This research was supported by the Russian Science Foundation (grant №23-44-00006).

PD1/PD-L1 antibody therapy is used in the clinic (atezolizumab, avelumab, durvalumab), but its effect is ambiguous, both in patients and in mouse models. The purpose of this work was to analyze the binding of commercial and laboratory-obtained monoclonal antibodies to PD-L1. Previously, we obtained monoclonal antibodies (clone B12) to the extracellular fragment PD-L1 of mouse expressed in E. Coli (exPD-L1). Primary screening of monoclonal antibodies by flow cytometry showed low B12 binding compared to commercial antibodies. Cytokine-stimulated 3D cultures, permeabilized cells, and Western blotting were used to elucidate the causes of low binding on living cells.

Permeabilization of cells B16/F10 (mouse melanoma), EL-4 (mouse lymphoma), COLO357 (human pancreatic cancer) showed binding of both mouse and human B12 PD-L1 antibodies. With the help of Western blotting, these data were confirmed. However, commercial antibodies (BioLegend, clone 10F.9G2) in this method did not bind to the mouse recombinant exPD-L1 protein, but bound to cell lysates. Cell cultivation on an anti-adhesive polyHEMA substrate led to the binding of B12 antibodies to the surface of cells under 3D cultivation conditions. Stimulation of EL-4 and B16/F10 cells in 3D cultures and subsequent incubation with Cy3-labeled B12 antibodies led to the appearance of pronounced fluorescence in the perinuclear region of cells.PDL-1.

Thus, the obtained monoclonal antibodies to mouse exPD-L1 are cross-reactive with human PD-L1 protein; PD-L1 protein translocates to the cell membrane when cultured under 3D conditions into the nucleus and, when stimulated by cytokines, its biosynthesis is activated. The difference in the binding of antibodies B12 and 10F.9G2 may mean a difference in the conformation of PD-L1 translocated to the membrane. The traffic of intracellular PD-L1 into the nucleus upon activation may mean the launch of de novo protein synthesis with an altered conformation.

Soybean is a unique legume cum oilseed crop enriched with a plethora of bioactive compounds having health-promoting properties. Its extracts serve as a primary ingredient in many drug formulations against diabetes, obesity, and spinal cord-related disorders. Strawberry is also an economically important crop with immense nutraceutical and health-beneficial abilities. Cardiovascular diseases and hypertension cause several deaths globally. The renin–angiotensin–aldosterone system regulates body hypertension and fluid balance which causes cardio diseases. Angiotensin-converting enzyme I (ACE I) is the key Zn-metallopeptidase component of the RAAS involved in the homeostasis maintenance of the cardiovascular system. The available commercial drugs for cardio diseases have many side effects and also lead to death; thus, there is a need to explore the use of phytocompounds and peptides as alternative therapies. Soy proteins and their products act against ACE I, which may provide new scope for the identification of potential scaffolds that can help in the design of safer and natural cardiovascular therapies. In the present study, the molecular basis for the selective
inhibition of 34 soy phytomolecules from phospholipids, saponins, inositols, oils, polysterols, phenolics, isoflavonoids and fatty acids and 2 strawberry molecules, namely, ellagitannin and pelargonidin-3-glucoside, along with reference compounds (captopril, lisinopril and quinapril) were evaluated. The structures were retrieved from PubChem, and in silico molecular docking approaches and dynamic simulations were performed to understand the protein–ligand interactions. Our results indicate that amongst the compounds, beta-sitosterol exhibited potential inhibitory action against ACE I. This study can be useful for the production of safer drugs against ACE following in vivo and clinical studies.

Introduction: Ciguatoxin (CTX) is a potent marine toxin known for its detrimental effects on the Central Nervous System (CNS), inducing symptoms of depression and neurological dysfunction. The nervous system's synapses' threshold for opening voltage-gated sodium channels reduces by ciguatoxin. Piperine, a bioactive compound found in black pepper, has shown promise as a potential treatment for CTX-induced CNS depression due to its neuroprotective properties.

Methods: This review comprehensively examines studies investigating the effects of CTX on CNS depression and the potential therapeutic role of piperine. Various cell models, including Mus musculus cells (N2A), Zalophus californianus tissues and many others have been utilized to elucidate the mechanisms underlying CTX-induced CNS depression. Studies employing proteomic techniques such as 2D DIGE, MALDI-TOF/TOF, LC-MS/MS, and nanoLC-MS/MS have provided insights into dysregulated proteins, pathways, and cellular responses associated with CTX toxicity. Additionally, investigation into the therapeutic effects of bioactive compound such as piperine has been conducted for marine toxins.

Results: Studies have revealed that CTX exerts its CNS depressant effects through dysregulation of calcium homeostasis, membrane depolarization, and disruption of neurotransmitter pathways. Furthermore, CTX-induced toxicity is associated with dysregulated proteins involved in neurodegenerative pathways, apoptosis, and excitotoxicity. Piperine has been shown to mitigate CTX-induced CNS depression by modulating oxidative stress, inflammation, and neurotransmitter imbalances. Mechanistically, piperine's neuroprotective effects involve activation of NRF2 pathways, inhibition of apoptotic signaling, and modulation of neuronal excitability.

Conclusion: The findings from this review underscore the potential of piperine as a therapeutic agent for mitigating CTX-induced CNS depression. More large-scale studies and clinical trials are required for subsequent research to demonstrate piperine's effectiveness and safety as a treatment for CTX intoxication. Understanding the intricate mechanisms underlying CTX-induced CNS depression and the therapeutic effects of piperine could pave the way for novel interventions in managing ciguatera fish poisoning.

Introduction

(-)-Epicatechin (EC) is a commonly consumed dietary phytochemical that possesses multiple physiological benefits for human health. Its well-established robust antioxidant activity contributes to alleviating oxidative stress and inflammation associated with various diseases. However, the stability of EC limits its potential health benefits in the human body. Thermal processing is a common method used to extract EC, but it is likely to degrade EC due to its thermal instability.

Methods

In this study, a bathing incubation assay was designed to simulate the conditions of (-)-Epicatechin (EC) in boiling water during cooking. The degradation products were monitored using ultra-performance liquid chromatography combined with electrospray ionization quadrupole tandem mass spectrometric detection (UPLC-ESI-TSQ-MS/MS).

Results

The results showed an approximately 65.2% loss of (-)-Epicatechin (EC) within the first 10 minutes, with over 99.5% of EC being degraded within 30 minutes. A total of 22 degradation products were identified based on retention time, and the full tandem mass spectrometry (MS/MS) data are being comprehensively reported for the first time.

Conclusions

The investigation into the thermal stability and resulting product transformations of (-)-Epicatechin provides a foundational framework for future inquiries into its bioavailability and functional attributes. The isolation and testing of biological activities associated with the effects reported in EC should now be pursued to identify stronger analogues.

Purine stretches, sequences of adenine (A) and guanine (G) in DNA, play critical roles in binding regulatory protein factors and influence gene expression by affecting DNA folding. Both purines can exist in the enol-amine form (often referred to as the imidazole form) and keto-imine forms. The enol-amine form is more stable and biologically significant than the keto-imine form. This enhanced stability is attributed to the fully conjugated ring system in the enol-amine form, which adheres to Hückel's rule and becomes aromatic. The presence of a delocalized pi-electron cloud within this fully conjugated ring system results in an aromatic molecule. In contrast, the keto-imine form lacks full conjugation in its ring system due to a broken double bond between the nitrogen and carbon atoms, rendering it non-aromatic. This study investigates the relationship between purine stretches and cancer development, which makes mechanistic sense considering the aromaticity of purines in the purine stretches flanking each mutation. A pronounced avoidance of typical cancer mutations of long purine stretches in typical types of cancer was observed in the public data of patients in intergenic regions, suggesting the role of intergenic sequences in chromatin reorganization and gene regulation. A statistically significant shortening of purine stretches in cancerous tumors (p-value < 0.0001) was found. The insights into the aromatic nature of purines and their stacking energies explain the role of purine stretches in DNA structure, contributing to their role in cancer progression. This research lays the groundwork for understanding the nature of purine stretches, emphasizing their importance in gene regulation and chromatin restructuring, and offers potential avenues for novel cancer therapies and insights into cancer etiology.