This research focuses on the fabrication of a series of xanthan gum-based hydrogels for the efficient delivery of the hydrophobic drug. The study investigates the influence of crosslinker (MBA), biopolymer (XG), and initiator (KPS) amounts on hydrogel properties. Various characterization techniques, such as PXRD, ATR-FTIR, SEM, and TGA, were utilized to analyze the fabricated hydrogels. The sol–gel analysis revealed that a higher quantity of reagents led to a greater increase in the gel fraction of the synthesized hydrogels. Porosity measurements indicated enhanced porosity with higher biopolymer and initiator amounts, while porosity decreased with increased crosslinker concentration. The incorporation of amphiphilic polymer in the hydrogel significantly improved its properties such as gel fraction, swelling ratio, porosity, drug loading, drug entrapment and drug release percentage. Notably, under alkaline conditions (pH 7.4), the synthesized hydrogel exhibited an increased swelling ratio and drug release in the comparison to acidic conditions (pH 1.2). The drug release mechanism from the synthesized hydrogel followed a Fickian diffusion pattern, and the Korsmeyer-Peppas model was identified as the most appropriate for describing drug release kinetics in the both pH 1.2 and 7.4 buffer solution. The pH-responsive nature of the developed hydrogel highlights its potential as an effective and versatile candidate for drug delivery application.

Introduction: Heightened unfolded protein responses (UPRs) are associated with many TH17-driven inflammatory diseases. However, how UPRs participate in the deregulation of TH17 cells remains elusive. Objective: We investigated the role of the UPR sensor IRE1 in TH17 cell function and the underlying mechanism. Methods: Whether and how extracellular stimuli lead to IRE1 phosphorylation was explored by using flow cytometry, Western blot, confocal microscopy, in vitro phosphorylation, and co-immunoprecipitation. T cell-specific Ern1 (encoding IRE1)-deficient cells were used to examine the effects of IRE1 on TH17 responses. Results: The UPR sensor IRE1 is highly expressed in TH17 cells relative to naïve CD4⁺ T cells. Signals of cytokines (e.g. IL-23 and IL-6) and co-stimulation induce the IRE1-XBP1s axis. Among those, IL-23 activates IRE1 in a JAK2-dependent manner. This noncanonical activation of the IRE1-XBP1s pathway promotes UPRs and cytokine secretion by both human and mouse TH17 cells. Ern1 (encoding IRE1) deficiency decreases the expression of ER stress factors and impairs the differentiation and cytokine secretion of TH17 cells. Conclusion: Our data indicate that IRE1, noncanonically activated by cytokine signals, promotes the secretory function of TH17 cells. These findings provide a novel insight into the fundamental understanding of UPRs in TH17-mediated diseases. Acknowledgments: This work was supported in part by NIH grants HL148337, AI116772, and AI142200 (X.O.Y.); DK110439 (M.L.); and GM130422 (M.C.).

Hyperglycaemia leads to an accumulation of harmful substances in the body due to a process known as glycation. In this process, carbonyl groups of sugars interact with the amino groups of other biomolecules, ultimately resulting in the formation of advanced glycation end products. These products have been implicated in various pathophysiological conditions like diabetes, Parkinson’s, Alzheimer’s, cataracts, etc. Although the exact mechanism by which AGEs bring about changes in the structure of biomolecules is not known, it is assumed that cross-linking, aggregation, oxidation, and precipitation of proteins are some probable processes that are responsible for the structural and functional changes in biomolecules. In our study, we have used glucose and BSA as the in vitro model system to study the structural alterations they produce and the reversal of these alterations induced by natural products. A range of spectroscopic and electrophoretic tools were used to assess the alteration in BSA structure. The amounts of glycation products were also quantified by colourimetric and spectrofluorometric methods. The results indicate that glucose induces severe changes in the conformation of BSA and the presence of thymoquinone suppresses these alterations. Similarly, a significant amount of glycation products were generated in the in vitro system and were inhibited by the natural product. It can be concluded that glucose brings about conformational changes in proteins and causes the accumulation of glycation products during sustained hyperglycaemia.

Chitosan (CS) derivatives are extensively employed in a range of biomedical applications due to their special qualities, which include biocompatibility, mucoadhesion, non-toxicity, and the ability to form gels. They are also promising prospects for the development of films, tablets, and systems based on nanotechnology and could be scaled up commercially and industrially. Only systems requiring a higher solubility and drug release rate can employ CS due to its poor solubility at physiological pH (>6.0). A further drawback of CS is its high degree of swelling and water adsorption in aquatic environments, which might cause quick drug release. Through the chemical modification of one amino group and two hydroxyl groups on the CS chains, the carboxymethyl moieties will alter the properties of the CS. At various pH values, the water solubility of carboxymethyl chitosan (CMC) is determined by the degree of carboxymethylation. CMC derivatives have the ability to interact with cells to promote wound healing, tissue regeneration, and cell growth. Because of their antimicrobial, emulsion stabilising, and moisture absorption/retention qualities, they are also utilised in the production of cosmetics. Current CMC derivatives with biological activity, i.e., antibacterial, anticancer, antitumor, antioxidant, and antifungal, in areas like wound healing, tissue engineering, drug/enzyme delivery, bioimaging, and cosmetics will be the main topics of this presentation.

Severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China, in December 2019, marking the onset of a profound global health crisis. The unprecedented scale of the ensuing pandemic prompted an urgent need for innovative strategies to combat COVID-19. In response, researchers and scientists worldwide directed their efforts towards identifying effective preventive and therapeutic measures. Among these, natural products have gained prominence due to their potential in offering a holistic approach to tackling the virus. This study undertook a rigorous computational approach to sift through a vast array of natural compounds, aiming to pinpoint those with promising antiviral properties against the SARS-CoV-2 main protease, RdRp and the RBM of the spike glycoprotein. Through sophisticated molecular docking simulations, this study investigated the intricate interplay between selected natural compounds and virus targets. This analysis encompassed diverse factors such as binding affinity, interaction dynamics and structural compatibility within the active sites of the target protein. The encouraging results provide a solid foundation for further in-depth exploration, including experimental validation and refinement of these compounds as potential therapeutic agents against COVID-19. The identification of novel natural antiviral compounds presents a beacon of hope for global health, offering new avenues for combatting SARS-CoV-2 and future potential viral threats. As these findings pave the way for future drug design strategies, they reinforce the collaborative and interdisciplinary approach needed to triumph over the challenges posed by COVID-19.

Metallic nanoparticles, such as gold and silver nanoparticles, are extraordinarily small particles composed of metal atoms at the nanoscale, typically ranging in size from 1 to 100 nanometers. These nanoparticles possess a plethora of unique and invaluable properties owing to their diminutive size, their exceptionally high surface-area-to-volume ratio, and the emergence of quantum effects at this scale. In this research, a computational simulation was conducted to explore the structural configurations of both silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs). Subsequently, geometry optimization techniques were applied to refine these structures. The optimized nanoparticle configurations were then systematically evaluated for their potential interactions with three specific targets within the SARS-CoV-2 virus: the Main protease (Mpro), the RNA-dependent RNA polymerase (RdRp), and the S spike glycoprotein. Notably, the results revealed that both AgNPs and AuNPs exhibited remarkable affinities for the active pockets of SARS-CoV-2 Mpro, suggesting their potential utility as inhibitors for this critical viral protein. Intriguingly, when considering RdRp, AgNPs displayed superior binding affinity compared to AuNPs, indicating their specific potential in targeting this component of the virus. Conversely, when assessing their interactions with the S spike glycoprotein, AuNPs demonstrated greater binding affinities than AgNPs, with more pocket residues being involved in this interaction. The versatility of gold and silver nanoparticles extends far beyond virology, as these materials find applications in diverse fields, including medicine, electronics, and environmental remediation. The findings presented here underscore their potential as versatile antiviral agents, providing a promising avenue for further in vitro and in vivo research to explore their efficacy in inhibiting the replication of the SARS-CoV-2 virus.

Polyetheretherketone (PEEK) is a promising biomedical material for orthopedic and dental applications due to its excellent mechanical properties, low immunogenicity, and X-ray transparency. However, it exhibits bio-inertness and limited osteoconduction. Surface modification of PEEK can effectively address this issue while preserving its favorable properties. The primary objective of this study is to create a bioactive surface on PEEK implants through surface modification. BMP-2 was immobilized onto the porous structure through an intermediate layer of photoreactive gelatin (Az-Gel) to produce a bioactive PEEK implant. Its surface characteristics and in vitro cellular behavior were systematically assessed using scanning electron microscopy (SEM), static contact angle measurements, cell proliferation assays, alkaline phosphatase activities, and cellular morphology. Our study results indicated the following: (1) A surface porous structure, with pores mostly between 0.24 µm and 0.74 µm in size and 3.5 µm in thickness, was created on PEEK implants by immersing them in concentrated sulfuric acid, as determined by SEM and Image J software analysis. (2) The hydrophobicity of the PEEK implants could be reduced by the surface porous structure, while an Az-Gel coating substantially enhanced the hydrophobicity of the samples. (3) In vitro cytological studies demonstrated that PEEK implants enhanced with BMP-2 through Az-Gel coating promoted the adhesion, spreading, proliferation, extracellular matrix secretion, and osteogenic differentiation of MC3T3-E1 cells. Surface modification of PEEK implants with BMP-2 through Az-Gel coating can enhance osseointegration and osteogenic differentiation, making it a promising material for orthopedic implants and medical devices.

High-added-value product extraction is a topic of tremendous interest and relevance, particularly when it comes to newly discovered plants from understudied arid and semi-arid zones. Ammodaucus leucotrichus, a spontaneous endemic plant indigenous to north and tropical Africa's Saharan and sub-Saharan regions, is the plant species that we chose for this goal. It is used as a condiment or flavoring agent in cuisine, as well as in traditional medicine, to cure heart disease, diabetes, allergy symptoms, and stomach ailments. In vitro tests were performed to assess the anti-inflammatory and anti-neurodegenerative effects of lipoxygenase (LOX) inhibition and anticholinesterase (AChE). The findings demonstrated the strong anti-inflammatory and anti-Alzheimer properties of Ammodaucus leucotrichus. Water was found to be a superior extraction solvent compared toethanol and was used to reach the ideal conditions at 180 ºC. Temperature had a beneficial impact on extraction yield within a range of 15.55 to 44.45%. Moreover, the EC50 values for antioxidant activity, acetylcholinesterase inhibition, and lipoxygenase inhibition were 85.51 ug/ml, 55.60 ug/mL, AChE, and LOX, respectively. In conclusion, Ammodaucus leucotrichus phenolics may be extracted using the new PLE process, which is an effective and environmentally friendly way. This allows for the production of extracts that have appealing anti-Alzheimer and anti-inflammatory properties.

This study shows that the Ammodaucus leucotrichus can be a new potential
resource of natural anti-inflammatory and anticholinesterase compounds.

"Study on Mercury exposure and different approaches for the management of Mercury toxicity"

Mercury (Hg) is a highly toxic heavy metal that causes significant risks to human health and the environment. This study explores the sources and routes of mercury exposure to humans, its toxicological effects, and the various methods of phytoremediation and bioremediation to mitigate (Reduce) mercury contamination in the environment. Mercury exposure to humans primarily occurs through the consumption of contaminated seafood, the inhalation of mercury vapour, and occupational exposure, which can lead to adverse health effects, including neurological disorders, cardiovascular issues, and developmental defects. Furthermore, mercury contamination in the environment can persist and bioaccumulate in the food chain, further exacerbating the risks to human health. Phytoremediation, a sustainable and cost-effective method, involves the use of plants to extract, stabilize, or transform mercury in contaminated soils or water. Various plant species have demonstrated the ability to accumulate and detoxify mercury through mechanisms such as phytochelation and rhizofiltration. Additionally, the genetic engineering of plants can be achieved to enhance mercury uptake, and accumulation is also a promising method used for efficient phytoremediation. Bioremediation, on the other hand, involves the use of microorganisms, such as bacteria and fungi, to remediate mercury-contaminated sites. These microorganisms can reduce mercury to less toxic forms (e.g., elemental mercury to less soluble mercuric ions) or form complexes that immobilize mercury. Apart from microbes and plants, seaweed or seaweed-derived products can be seen as an efficient alternative for the bioaccumulation of mercury. Bioremediation techniques are being continuously developed and optimized to enhance their efficiency and applicability.

Introduction: The discovery of antibiotics is considered one of the most important discoveries in the history of humanity. Bacterial antibiotic resistance has long been a growing global problem, and today, bacteria are becoming able to adapt to all known antibiotics. Projections have shown that in 2019, there were 1.27 million deaths due to antibiotic resistance. It is necessary to discover new antibacterial agents that have therapeutic potential and are drug-safe so that humanity can successfully overcome antibiotic resistance. Applying bioinformatics and chemoinformatics in microbiology can be useful to rapidly evaluate the efficacy and drug safety of potential antibacterial agents, thus avoiding the loss of resources due to unsuccessful trials.

Methods: SwissADME software was used to assess timiquinone’s pharmacokinetics, drug-likeness and medicinal chemistry friendliness, while potential therapeutic targets in Acinetobacter baumannii were assessed using the RCSB Protein Data Bank online platform tools and evaluated with a comprehensive review of the existing literature.

Results: Thymoquinone weights less than 500 g/mol fulfill the requirements for the number of rotatable bonds, proton donors and acceptors, should be easily absorbed in the intestine and can cross the blood–brain barrier, but is not a substrate for P-gp. It should not be hepatotoxic as it has no inhibitory effect on liver cytochromes. It satisfies Lipinski’s rules and is therefore a molecule that could have therapeutic effects. The most promising potential targets in Acinetobacter baumannii are the proteins AbOmpA and bap. Here, thymoquinone could induce reactive oxygen species that destabilise membrane integrity and disrupt biofilm formation by damaging the secondary and tertiary structure of Acinetobacter baumannii proteins and possibly also affect its nucleic acids, leading to cell death.

Conclusions: Bioinformatics and chemoinformatics tools can be helpful in microbiology. It seems promising to perform in vitro tests to assess the antibacterial efficacy of thymoquinone as an antibacterial agent against Acinetobacter baumannii.