Bromophenols, which belong to the family of phenolic compounds, are halogenated secondary metabolites characterized by the incorporation of bromine atoms into the phenol ring structure, resulting in unique chemical properties. These compounds, synthesized as secondary metabolites by algae, exhibit different isomeric forms due to bromine substitution at different positions within the phenol ring, showing variability among species. Bromine substitution not only confers specific chemical properties but also plays an important role in the ecological functions of bromophenols by inducing increased lipophilicity, which affects solubility and reactivity, an adaptive response to external conditions. Certain genera of red algae, such as Gracilaria and Rhodomela, have been identified as important sources of bromophenols. Research on bromophenols involves extraction, commonly using solvents such as methanol or methanol-dichloromethane, and identification and structural elucidation using advanced analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy for the precise determination of structure and configuration. Bromophenols display diverse biological activities, highlighting antimicrobial, antidiabetic, antiviral and antioxidant properties, which are closely related to their specific chemical structure. The importance of understanding the chemical group of bromophenols is underlined by their role in chemical defense mechanisms, contributing to potential biotechnological applications and broader contributions to the marine ecosystem ^[1–6]. Therefore, this study is aimed to review the chemical characteristics and biological properties of bromophenols in red algae.

Marine organisms, especially brown seaweeds, have attracted a lot of attention worldwide because of their potential for use in treating a range of infectious and non-infectious diseases, being able to take part in the creation of medications and nutraceuticals intended for ingestion by humans. Brown algae are a source of compounds, including phlorotannins (PTs), that exhibit biological effects, like anti-inflammatory, antibacterial, antioxidant, anti-tumor, anti-diabetic, and UV radiation protection [1, 2]. As a polyphenol (tannin), this compound has the intrinsic capacity to scavenge and reduce free radicals. It can also present a high affinity for proteins through specific or non-specific interactions, interact with multiple receptors, control enzyme activity, cross-link biological macromolecules, inactivate microorganisms, and regulate signal transduction. These properties suggest that PTs may find widespread use in tissue engineering. Furthermore, according to related studies, at most dosages, PTs from brown seaweeds have shown minimal toxicity in invertebrates, animals (mice, rats, fish, and dogs), and humans [3]. PT algae have been commonly characterized using assays like Folin–Ciocalteu and 2,4-dimethoxybenzaldehyde (DMBA). However, due to their complex mixtures, identifying them accurately is challenging. Techniques like MS/MS coupled with HPLC aid in tentative characterization, but some authors advocate for NMR for precise identification, linking structures to HPLC conditions for a comprehensive analysis [4]. Solid liquid extraction (SLE) with hydroacetonic blends has remained the preferred method for extracting PTs and tannins in general, despite its limitations in sustainability and environmental impact. Factors like solvent polarity, pH, temperature, time, and pre-treatments are said to influence the effectiveness of solvent-based extraction procedures. However, emerging methods such as microwave-assisted extraction (MAE), pressurized liquid extraction (PLE), ultrasonic-assisted extraction (UAE), and supercritical fluid extraction (SFE) offer more eco-friendly alternatives to address these drawbacks, enhancing extraction efficiency. This communication conducts a literature review about PTs, their chemical characterization, and the most appropriate extraction methods [2, 5].

Starch, conformed by amylose and amylopectin, represents the major carbohydrate macromolecule consumed globally as a major component of staple foods. Phenolic compounds are ubiquitous secondary metabolites in plants with strong antioxidant capacities and have attracted a great deal of attention in recent decades. Besides these capabilities, polyphenols are known to interact through different bonds with polysaccharides, lipids or proteins, which impact the formed complex structure and its digestibility. Due to their hydroxyl groups, it appears as if lower MW polyphenols tend to display fewer H-bonds due to their fewer hydroxyl groups and thus weaker interactions and affinity, whereas higher MW polyphenols, such as polymerized tannins and especially proanthocyanidins, display a higher number of available H-bonds and a generally higher affinity. Native starch is usually present in two main forms: V-type inclusion complexes with hydrophobic bonds or non-inclusion crystal complexes (A- or B-type) prone to H-bonds and ionic/electrostatic interactions. The formation of the complexes depends on the starch microstructure, and also depends on the amylose/amylopectin ratio, and the ratio of crystalline and amorphous structures, with polyphenols showing higher affinity towards amylose and the hydrophobic interior of helix structures in starch. At the microstructural level, starch–polyphenol complexation leads to increased porosity and denser granules. At the rheological level, this translates into the starch showing reduced viscosity and elasticity. Moreover, this greatly impairs starch's gelatinization and retrogradation during cooking, providing a final structure more akin to resistant starch, with a final reduced hardness and adhesiveness. These changes affect the digestibility of starch by amylolytic enzymes (i.e. α-amylase) and lead to lowered glucose release from it and absorption. This review aims to present a comprehensive and summarized overview of updated knowledge on this and the remaining gaps in knowledge.

Methylmercury (MeHg) contamination in seafood poses significant health risks, particularly neurotoxicity, to human populations worldwide. Selenium acts as a protector against the toxicity of metals such as mercury and inorganic arsenic [1], but at the same time, the loss of Se bioavailability caused by these pollutants must be considered. New criteria have been proposed to assess the risks of Hg exposure, namely the Se Health Benefit Value (HBVSe) and the Benefit–Risk Value (BRV), which allows for the simultaneous evaluation of Hg exposure and dietary Se intake. Additionally, changes in mercury bioaccessibility have been attributed to cooking, which changes the conformation of native proteins [2]. Various studies have shown that the benefits of consuming seafood outweigh the risks, especially when the protective effects of selenium are considered. This comprehensive review examines the biomolecular interactions underlying the protective effects of selenium against MeHg in the human body. We will discuss the mechanisms by which selenium modulates MeHg toxicity, including its role in mitigating oxidative stress, preventing MeHg bioaccumulation, and facilitating detoxification pathways. Nevertheless, further research in this area is necessary to study the synergistic effects between the different variables to improve the understanding of the repercussions of fish and shellfish intake on health. Future research directions are proposed to elucidate the protective role of selenium against methylmercury toxicity and inform public health policies and interventions. Overall, this communication contributes to our understanding of the complex interplay between selenium and methylmercury in the human body and underscores the potential of selenium as a therapeutic agent for mitigating MeHg-related health risks.

1. Melgar, M.J, Selenium intake from tuna in Galicia (Spain): Health risk assessment and protective role against exposure to mercury and inorganic arsenic. Sci Total Environ, 2019. 694: p. 133716.
2. Torres-Escribano, S., Mercury and methylmercury bioaccessibility in swordfish. Food additives & contaminants, 2010. 27: p. 327-37

Chronic prenatal hypoxia (CPH) is one of the most common causes of neonatal mortality and postnatal disorders of the nervous system and the mental development of infants. The search for new methods to treat the effects of CPH is a high-priority problem of modern pharmacology. HIF-1α in hypoxic conditions activates mechanisms of endogenous neuroprotection and can be used as a target for pharmacological correction.

Aim of the work: To study the possibilities of the HIF-1α-modulating effects of different pharmacological agents in the model of CPH.

CPH was modeled by administering sodium nitrite (50 mg/kg) to pregnant female white rats from day 16 of gestation. The offspring were treated with the following drugs: piracetam, thiotriazoline, nikomex, tamoxifen, cerebrocurin, angiolin, glutoredoxin, l-arginine, and HSF-1 during the first 30 days of life. The concentration of HIF-1α in the plasma and brain homogenate of rats at 30 and 60 days of life was determined using the enzyme-linked immunosorbent assay.

It was found that CPH leads to a decrease in the concentration of HIF-1α in the nervous tissue of the brain and blood plasma. Drug administration results in a significant increase in the content of HIF-1α in the studied objects immediately at the end of treatment with continued positive effects on the 60th day of life. The maximum effect was demonstrated on day 30 by cerebrocurin, angiolin, and HSF1, and on day 60 by cerebrocurin, angiolin, and thiatriazolin.

Our research provides evidence that the medications being tested are an effective way to modulate HIF-1α and may be a new alternative for the treatment and prevention of nervous system disorders in children caused by CPH.

Dihydrodaidzein is a hydrogenated product of the conversion of daidzein, the main component of soy isoflavones, under the metabolic action of intestinal microorganisms. Being the intermediary metabolite of soy isoflavones, dihydrodaidzein is widely acknowledged to exhibit heightened biological activity. During intestinal transformation in vivo, dihydrodaidzein can subsequently undergo further hydroxylation to form the more active equol. Compared with its metabolic precursor, daidzein, dihydrodaidzein exhibits higher activity and broader biological effects, due to which it has gradually attracted the attention of many scientists in recent years. It has been found to have superior pharmacological activities due to its antioxidant properties, potential prevention of cardiovascular disease andosteoporosis, and estrogen-like activity. However, there is currently a scarcity of literature providing a systematic and comprehensive overview of DHD. Considering the high biological activity and potential market value of DHD, this article reviews advancements in DHD research, encompassing its sources, biosynthetic pathways, physicochemical properties, metabolism, bioavailability, biological activity, and pharmacology. Emphasis is placed on elucidating the biosynthesis biotransformation, biological activity, and pharmacology of DHD, aiming to maximize its intrinsic value and contribute to its application in the realms of medicine and clinical practice. Dihydrodaidzein suffers from low water solubility, instability, and low oral bioavailability, so emerging nanocarrier technologies can be explored to encapsulate dihydrodaidzein to enhance its solubility, cellular uptake, targeted delivery, and functional efficacy. Future endeavors should prioritize additional research to assess its bioavailability, potentially paving the way for its inclusion in future nutritional supplements.

Thyroglobulin is a marker of relapse of differentiated thyroid cancer. Currently, several B-cell epitopes have been identified in the composition of thyroglobulin using peptides containing individual antigenic determinants of TG. However, the immunopathogenetic role of these epitopes remains not entirely clear, and its study is promising for further research. Currently, the 3-dimensional structure of TG is unknown, but at the same time, the 3-dimensional structure of acetylcholinester (AChE) is known, on the basis of which it is possible to construct a mathematical model of the C-terminal region of TG, homologous to AChE. It has been shown that autoantibodies to the epitopes of TG M4-814, TgP15, 2376-2464, TgP26, and TgP41 are detected in 80%, 0%, 10%, and 7% of patients with Hashimoto's thyroiditis; in 50%, 22%, 100%, 29%, and 34% of patients with Graves' disease; and practically absent in healthy donors (Gentile F. et al.). Therefore, from the described TG epitopes, we selected five epitopes related to the C-terminal AChE, a similar region of TG, and recombinant proteins were constructed. From a collection of monoclonal antibodies to TG obtained in the laboratory, 10 mAbs interacted with recombinant AChE immobilized on the surface of the wells of polystyrene plates. Only blood sera from patients with diffuse toxic goiter and autoimmune thyroiditis with minimal levels of antibodies to TG (more than 500 IU/ml) reacted with AchE. Conclusion: in models of a fragment of the TG molecule homologous to AChE, the AG-AT bond sites remain the most probable.

Aroylhydrazones, created by combining aromatic aldehydes and hydrazides, have numerous biological effects such as analgesic, anti-inflammatory, anticancer, antimicrobial, and antibacterial. The current study reports how the presence of a chlorine atom in hydrazone molecules affects their lipophilicity and molecular characteristics.

Methods: A series of novel chloro-substituted salicylaldehyde benzoylhydrazone derivatives was created by inserting the Cl atom in the aldehyde and hydrazide moiety and changing the substituent positions. To select the lead chloro-hydrazones with suitable pharmacological properties, the molecular and bioactivity scores of the proposed compounds were evaluated using a group contribution approach.

Results: Including a chlorine atom in the salicylaldehyde or hydrazide moiety raises the value of log P. Despite minor variances, all chloro-substituted salicylaldehyde benzoyl hydrazone derivatives show acceptable lipophilicity, with log P values up to 4.51. Cl-hydrazones have a TPSA of less than 140 Ų, indicating high permeability to the cellular plasma membrane. Bioactivity scores indicate biological activity against GPCR ligands, ion channel modulators, kinase inhibitors, nuclear receptor ligands, protease inhibitors, and other enzyme targets.

Conclusion: The results revealed that all compounds are potential candidates for future drug discovery studies.

Acknowledgments: This study is financed by the European Union NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project No. BG-RRP-2.004-0004-C01.

The enzymatic hydrolysis of hemicelluloses and acetyl groups stands as a cornerstone in biofuels production, with profound implications for bioethanol and bio-hydrogen generation. Emphasizing the resilience of hemicellulose and cellulose, resilient biopolymers that comprise biomass, this study delves into the in silico exploration of acetylxylan esterase (EC 3.1.1.72), a pivotal member of carboxylic esterase hydrolases (EC 3.1.1), to unveil its crucial role in the deacetylation of xylans and xylo-oligosaccharides.

Employing a multidimensional approach, we meticulously scrutinized three-dimensional structures, encompassing X-ray crystallography-determined and AlphaFold-predicted models of acetylxylan esterase. Microorganisms under investigation include Trichoderma reesei, Acetivibrio thermocellus, Cellvibrio japonicus, Flavobacterium johnsoniae, Thermoanaerobacterium saccharolyticum, Clostridium cellulovorans, and Caldicellulosiruptor saccharolyticus.

Molecular docking and dynamic simulations were conducted to unravel the intricate interactions between acetylxylan esterase and a diverse array of chemically modified xylopyranoside ligands. These ligands, embodying various acetylation patterns, were derived from xylopyranoside, a resilient component of hemicellulose. Significantly, the strategic cross-referencing of targets from ExplorEnz, BRENDA, UniProtKB, RCSB-PDB, and PubChem databases played a pivotal role in enriching the investigation.

This exploration provides profound insights into the substrate specificity of acetylxylan esterase, underscoring its potential role in the deacetylation of diverse substrates. Furthermore, the study offers a comprehensive analysis of biotechnologically relevant applications, spanning industrial-scale enzyme production, cellulolytic and ethanologenic capabilities, and biohydrogen production, intricately linked to the investigated variants of acetylxylan esterase.

Funding and acknowledgments: This research was funded by the Romanian Ministry of Research, Innovation and Digitization through the NUCLEU Program, Contract no. 20N/05.01.2023, Project PN 23 15 04 01 (BioVal). We acknowledge for institutional support the Program 1—Development of the national research and development system and Subprogram 1.1. Institutional performance—Projects to finance excellence in RDI, Contract No. 19PFE/30.12.2021.

After Alzheimer's disease, Parkinson's disease (PD) is the second most prevalent neurological illness. Clinically, it is defined by parkinsonism, which includes stiffness, bradykinesia, resting tremor, and postural instability. Pathologically, it is characterized by the loss of substantia nigra neurons. Monoamine oxidases (MAO-A and MAO-B) are enzymes responsible for metabolizing neurotransmitters such as dopamine (DA) and adrenaline. Selective MAO-A or MAO-B inhibitors have been the focus of recent attempts to create MAO inhibitors. In addition, Parkinson's disease can be effectively treated with MAO-B inhibitors.
The objective is to elucidate the several types of interactions between enzymes and ligands and assess the stability of the resulting complexes.
Various molecular modeling methods are used to study the inhibition of the enzyme MAO-B (PDB:4a79) involved in PD, including molecular docking, molecular dynamics, MOE software, and ADME prediction.
Based on the findings, compound L30 and compound L38, the top contenders identified by molecular docking/dynamic simulations and with low energy scores, had low IC50 values (0.110 and 0.305 µM, respectively).
The combination of the two outcomes from the earlier techniques demonstrates that the compounds L30 and L38 were chosen as the most effective MAO-B inhibitors and that they also satisfy the Lipinski, Veber, and Egan rules. They are also able to traverse the BBB. Furthermore, they may be utilized to create novel pharmaceutical medicines to treat individuals with PD.