Investigation of the influence of pH and temperature on melanization and survival under oxidative stress in Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic pathogenic fungus that produces melanin during infection, an important virulence factor in Cryptococcal infections that enhances the ability of the fungus to resist immune defense. This fungus can synthesize melanin from a variety of substrates, including L-DOPA (L-3,4-dihydroxyphenylalanine). Since melanin protects the fungus from various stress factors such as oxidative, nitrosative, extreme heat and cold stress; we investigated the effects of environmental conditions on melanin production and survival. In this study, we investigated the effects of different pH values (5.6, 7.0 and 8.5) and temperatures (30 °C and 37 °C) on melanization and cell survival using a microtiter plate-based melanin production assay and an oxidative stress assay, respectively. In addition, the efficacy of compounds known to inhibit laccase involved in melanin synthesis, i.e., tunicamycin, ß-mercaptoethanol, dithiothreitol, sodium azide and caspofungin on melanization was evaluated and their sensitivity to temperature and pH changes was measured. The results showed that melanin content correlated with pH and temperature changes and that pH 8.5 and 30 °C, were best for melanin production. Besides that, melanin production protects the fungal cells from oxidative stress induced by hydrogen peroxide. Thus, changes in pH and temperature drastically alter melanin production in C. neoformans and it correlates with the fungal survival. Due to the limited antifungal repertoire and the development of resistance in cryptococcal infections, the investigation of environmental conditions in the regulation of melanization and survival of C. neoformans could be useful for future research and clinical phasing.

Hybrid Caffeic Acid-Based DHFR Inhibitors as Novel Antimicrobial and Anticancer Agents.

A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC50 value of 0.15 µM. Additionally, it exhibited significant cytotoxic properties, with an IC50 value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of homo sapiens DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (-9.9; -70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against Staphylococcus aureus (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa, with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π-cation bond with Phe92, and a salt bridge with the polar residue Asp27.

Engineered lignocellulosic based biochar to remove endocrine-disrupting chemicals: Assessment of binding mechanism.

The safety and health of aquatic organisms and humans are threatened by the increasing presence of pollutants in the environment. Endocrine disrupting chemicals are common pollutants which affect the function of endocrine and causes adverse effects on human health. These chemicals can disrupt metabolic processes by interacting with hormone receptors upon consumptions by humans or aquatic species. Several studies have reported the presence of endocrine disrupting chemicals in waterbodies, food, air and soil. These chemicals are associated with increasing occurrence of obesity, metabolic disorders, reproductive abnormalities, autism, cancer, epigenetic variation and cardiovascular risk. Conventional treatment processes are expensive, not environment friendly and unable to achieve complete removal of these harmful chemicals. In recent years, biochar from different sources has gained a considerable interest due to their adsorption efficiency with porous structure and large surface areas. biochar derived from lignocellulosic biomass are widely used as sustainable catalysts in soil remediation, carbon sequestration, removal of organic and inorganic pollutants and wastewater treatment. This review conceptualizes the production techniques of biochar from lignocellulosic biomass and explores the functionalization and interaction of biochar with endocrine-disrupting chemicals. This review also identifies the further needs of research. Overall, the environmental and health risks of endocrine-disrupting chemicals can be dealt with by biochar produced from lignocellulosic biomass as a sustainable and prominent approach.

Hazard identification of endocrine-disrupting carcinogens (EDCs) in relation to cancers in humans.

Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens.

Single-cell transcriptomics: background, technologies, applications, and challenges.

Single-cell sequencing was developed as a high-throughput tool to elucidate unusual and transient cell states that are barely visible in the bulk. This technology reveals the evolutionary status of cells and differences between populations, helps to identify unique cell subtypes and states, reveals regulatory relationships between genes, targets and molecular mechanisms in disease processes, tumor heterogeneity, the state of the immune environment, etc. However, the high cost and technical limitations of single-cell sequencing initially prevented its widespread application, but with advances in research, numerous new single-cell sequencing techniques have been discovered, lowering the cost barrier. Many single-cell sequencing platforms and bioinformatics methods have recently become commercially available, allowing researchers to make fascinating observations. They are now increasingly being used in various industries. Several protocols have been discovered in this context and each technique has unique characteristics, capabilities and challenges. This review presents the latest advancements in single-cell transcriptomics technologies. This includes single-cell transcriptomics approaches, workflows and statistical approaches to data processing, as well as the potential advances, applications, opportunities and challenges of single-cell transcriptomics technology. You will also get an overview of the entry points for spatial transcriptomics and multi-omics.

The Zanthoxylum armatum fruit’s oil exterminates Candida cells by inhibiting ergosterol biosynthesis without generating reactive oxygen species

Candida spp. is a significant cause of topical and fungal infections in humans. In addition to Candida albicans, many non-albicans species such as C. krusei, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii cause severe infections. The main antifungal agents belong to three different classes, including azoles, polyenes, and echinocandins. However, resistance to all three categories of drugs has been reported. Therefore, there is an urgent need to search for other alternatives with antifungal activity. Many herbal extracts and compounds from natural sources show excellent antifungal activity. In this study, we used an oil extract from the fruits of Zanthoxylum armatum, which showed significant antifungal activity against various Candida spp. by two different methods—minimum inhibitory concentration (MIC) and agar diffusion. In addition, we attempted to explore the possible mechanism of action in C. albicans. It was found that the antifungal activity of Z. armatum oil is fungicidal and involves a decrease in the level of ergosterol in the cell membrane. The decrease in ergosterol level resulted in increased passive diffusion of a fluorescent molecule, rhodamine6G, across the plasma membrane, indicating increased membrane fluidity. The oil-treated cells showed decreased germ tube formation, an important indicator of C. albicans’ virulence. The fungal cells also exhibited decreased attachment to the buccal epithelium, the first step toward invasion, biofilm formation, and damage to oral epithelial cells. Interestingly, unlike most antifungal agents, in which the generation of reactive oxygen species is responsible for killing, no significant effect was observed in the present study. (AU)