Identification of the myxobacterial secondary metabolites Aurachin A and Soraphinol A as promising inhibitors of thymidylate kinase of the Monkeypox virus.

Thymidylate kinase (TMPK) of monkeypox virus (MPXV) has emerged as a promising target for potential therapeutics due to its significant role in pyrimidine metabolism. While smallpox drugs are advised for treating monkeypox, the European Medicine Agency has sanctioned Tecovirimat due to its potent nanomolar activity. Nonetheless, there is a need for monkeypox-specific therapeutic options. In this work, we employed docking-based virtual screening and molecular dynamics (MD) simulations to identify myxobacterial secondary metabolites as promising anti-viral natural compounds capable of inhibiting thymidylate kinase. The computational pharmacokinetics and manual curation of top-scoring compounds identified six lead compounds that were compared in terms of protein-ligand contacts and protein-essential dynamics. The study shows that among the six candidates, Aurachin A and the Soraphinol analogues such as Soraphinol A and Soraphinol C remain very stable compared to other compounds, enabling the active site integrity via a stable dynamics pattern. We also show that other compounds such as Phenoxan, Phenylnannolone C, and 8E-Aurafuron B remain unstable and have a negative impact on the active site integrity and may not be suitable binders for TMPK protein. Analyzing the Aurachin A and Soraphinol A binding, the established hydrogen bonds with Arg93 and the conserved hydrophobic interaction with Tyr101 are consistent with previous experimental interactions. Additionally, a deeper insight into the indole and the aromatic ring interaction through π-π stacking and π-cation interactions, as well as the background of Aurachin A and Soraphinol A as a bioactive compound, has significant implications not only for its potential as a promising drug but also for directing future drug discovery efforts targeting the TMPK protein.

The new differential diagnostic test for the lichenoid drug eruption.

The differential diagnosis between lichenoid drug eruption (LDE) and lichen planus (LP) is difficult due to similar clinical and histological signs but important for treatment and prognosis. The purpose of this study was to propose the new diagnosis method for differentiate LDE from LP. During 2015-2018, 20 patients with confirmed LDE, 13 patients with LP and 134 controls were examined and treated at the Lenoblcenter. All enrolled patients were underwent the injection of 0.5 mL of the 2% lidocaine solution by insulin syringe into the papule with following histological examination. The formation of a blister (bulla) at the site of injection was considered a positive test result. Among LDE, 18 of 20 patients were found positive for developing blister (bulla) and two results were questionable. In 12 of 13 LP patents, bulla on the site of injection was not identified and the result of one patient was nonspecific. All control patients were negative for the proposed test. The histological sections showed that the bulla has corresponded to the separation of the epidermis from the dermis. Intracutaneous injection of 0.5 mL of lidocaine into the papule is an easy highly specific and sensitive method to differentiate LDE from LP.

Corrigendum: Exploring the antibacterial and dermatitis-mitigating properties of chicken egg white-synthesized zinc oxide nano whiskers.

[This corrects the article DOI: 10.3389/fcimb.2023.1295593.].

Harnessing the power of bacterial laccases for xenobiotic degradation in water: A 10-year overview.

Industrialization and population growth are leading to the production of significant amounts of sewage containing hazardous xenobiotic compounds. These compounds pose a threat to human and animal health, as well as the overall ecosystem. To combat this issue, chemical, physical, and biological techniques have been used to remove these contaminants from water bodies affected by human activity. Biotechnological methods have proven effective in utilizing microorganisms and enzymes, particularly laccases, to address this problem. Laccases possess versatile enzymatic characteristics and have shown promise in degrading different xenobiotic compounds found in municipal, industrial, and medical wastewater. Both free enzymes and crude enzyme extracts have demonstrated success in the biotransformation of these compounds. Despite these advancements, the widespread use of laccases for bioremediation and wastewater treatment faces challenges due to the complex composition, high salt concentration, and extreme pH often present in contaminated media. These factors negatively impact protein stability, recovery, and recycling processes, hindering their large-scale application. These issues can be addressed by focusing on large-scale production, resolving operation problems, and utilizing cutting-edge genetic and protein engineering techniques. Additionally, finding novel sources of laccases, understanding their biochemical properties, enhancing their catalytic activity and thermostability, and improving their production processes are crucial steps towards overcoming these limitations. By doing so, enzyme-based biological degradation processes can be improved, resulting in more efficient removal of xenobiotics from water systems. This review summarizes the latest research on bacterial laccases over the past decade. It covers the advancements in identifying their structures, characterizing their biochemical properties, exploring their modes of action, and discovering their potential applications in the biotransformation and bioremediation of xenobiotic pollutants commonly present in water sources.

Microbiome miracles and their pioneering advances and future frontiers in cardiovascular disease.

Cardiovascular diseases (CVDs) represent a significant global health challenge, underscoring the need for innovative approaches to prevention and treatment. Recent years have seen a surge in interest in unraveling the complex relationship between the gut microbiome and cardiovascular health. This article delves into current research on the composition, diversity, and impact of the gut microbiome on CVD development. Recent advancements have elucidated the profound influence of the gut microbiome on disease progression, particularly through key mediators like Trimethylamine-N-oxide (TMAO) and other microbial metabolites. Understanding these mechanisms reveals promising therapeutic targets, including interventions aimed at modulating the gut microbiome's interaction with the immune system and its contribution to endothelial dysfunction. Harnessing this understanding, personalized medicine strategies tailored to individuals' gut microbiome profiles offer innovative avenues for reducing cardiovascular risk. As research in this field continues to evolve, there is vast potential for transformative advancements in cardiovascular medicine, paving the way for precision prevention and treatment strategies to address this global health challenge.

Exploring the antibacterial and dermatitis-mitigating properties of chicken egg white-synthesized zinc oxide nano whiskers.

Introduction: Zinc oxide nanoparticles (ZnO-NPs) have garnered considerable interest in biomedical research primarily owing to their prospective therapeutic implications in combatting pathogenic diseases and microbial infections. The primary objective of this study was to examine the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) using chicken egg white (albumin) as a bio-template. Furthermore, this study aimed to explore the potential biomedical applications of ZnO NWs in the context of infectious diseases. Methods: The NWs synthesized through biological processes were observed using electron microscopy, which allowed for detailed examination of their characteristics. The results of these investigations indicated that the NWs exhibited a size distribution ranging from approximately 10 to 100 nm. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) mapping analyses successfully corroborated the size, dimensions, and presence of biological constituents during their formation. In this study, XTT assay and confocal imaging were employed to provide evidence of the efficacy of ZnO-NWs in the eradication of bacterial biofilms. The target bacterial strains were Staphylococcus aureus and Escherichia coli. Furthermore, we sought to address pertinent concerns regarding the biocompatibility of the ZnO-NWs. This was achieved through comprehensive evaluation of the absence of cytotoxicity in normal HEK-293T and erythrocytes. Results: The findings of this investigation unequivocally confirmed the biocompatibility of the ZnO-NWs. The biosynthesized ZnO-NWs demonstrated a noteworthy capacity to mitigate the dermatitis-induced consequences induced by Staphylococcus aureus in murine models after a therapeutic intervention lasting for one week. Discussion: This study presents a comprehensive examination of the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) derived from chicken egg whites. These findings highlight the considerable potential of biosynthesized ZnO-NWs as a viable option for the development of therapeutic agents targeting infectious diseases. The antibacterial efficacy of ZnO-NWs against both susceptible and antibiotic-resistant bacterial strains, as well as their ability to eradicate biofilms, suggests their promising role in combating infectious diseases. Furthermore, the confirmed biocompatibility of ZnO-NWs opens avenues for their safe use in biomedical applications. Overall, this research underscores the therapeutic promise of ZnO-NWs and their potential significance in future biomedical advancements.

CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.

CXC chemokine receptor type 4 (CXCR4) is a member of the G protein-coupled receptors (GPCRs) superfamily and is specific for CXC chemokine ligand 12 (CXCL12, also known as SDF-1), which makes CXCL12/CXCR4 axis. CXCR4 interacts with its ligand, triggering downstream signaling pathways that influence cell proliferation chemotaxis, migration, and gene expression. The interaction also regulates physiological processes, including hematopoiesis, organogenesis, and tissue repair. Multiple evidence revealed that CXCL12/CXCR4 axis is implicated in several pathways involved in carcinogenesis and plays a key role in tumor growth, survival, angiogenesis, metastasis, and therapeutic resistance. Several CXCR4-targeting compounds have been discovered and used for preclinical and clinical cancer therapy, most of which have shown promising anti-tumor activity. In this review, we summarized the physiological signaling of the CXCL12/CXCR4 axis and described the role of this axis in tumor progression, and focused on the potential therapeutic options and strategies to block CXCR4.

The role of histological presentation in erythroderma.

BACKGROUND: Erythroderma is a serious medical condition characterized by inflamed red skin involving over 90% of the body. It can be the common presentation of different diseases, therefore clinical diagnosis can be problematic. Controversial data are reported regarding the diagnostic value of histological examination in erythroderma subjects. METHODS: A retrospective study was performed, investigating histological skin specimens of patients with a clinical diagnosis of erythroderma admitted to the Department of Dermatology of State Pediatric Medical University, Saint Petersburg, from 2001 to 2014. Histopathology examination was performed in each case by a pathologist with a special interest in the skin disease who was blind to any clinical information as well as to final diagnosis. RESULTS: Blinded histopathology examination alone was able to give the correct diagnosis in 61% (n = 50/82) of cases when compared to final diagnosis. A diagnosis of psoriasis was made in 23.2% (n = 19/82) of subjects, spongiotic dermatitis/eczema in 20.7% (n = 17/82), mycosis fungoides in 8.5% (n = 7/82), and drug eruption in 8.5%; histological diagnosis was inconclusive or not matching the final diagnosis when available in the remaining 39.1% of cases (n = 32/82). CONCLUSION: Erythroderma remains a condition difficult to study and treat. We showed that a correct judgment about its cause can be based on objective histopathological criteria in up to 60% of cases. More studies are needed to try to find out further histological and/or immunohistochemical markers that could help the clinician with the erythroderma etiology diagnostic process.

HPLC analysis of carotenoids from tomatoes using cross-linked C18 column and MS detection.

This study was conducted to analyze carotenoids from tomatoes by high-performance liquid chromatography using reversed-phase C18 silica having cross-linked end-capping with diode array and mass spectrometric detection. An efficient gradient elution system was developed to achieve good and reliable separation of both major and minor carotenoids as well as their isomers. Resolution of lycopene, ß-carotene and their isomers was 0.91-3.97 and 1.02-2.86 with cross-linked and conventional C18 column, respectively. The % recovery for zeaxanthin, lycopene and ß-carotene was found to be in the range of 89-97%. Limits of detection and quantification of 19.44 and 64.79 ng/mL for zeaxanthin, 15.6 and 52.4 ng/mL for lycopene and 8.28 and 27.61 ng/mL for ß-carotene were determined. More carotenoid compounds could be separated and detected with the new method as compared with conventional C18 column. Hyphenation of HPLC with photodiode array and mass spectrometry detectors assisted in detection of tetra-dehydrocarotenoid and fatty acid diesters of xanthophylls in tomato products. Content of all-trans-lycopene, ß-carotene and total carotenoid in different industrial tomatoes tested was found to range between 41.87 and 84.65, 0.89 and 1.50 and 53.22 and 112.60 µg/g fresh weight, respectively.