Exploring the frontiers of therapeutic breadth of antifungal peptides: A new avenue in antifungal drugs.

The growing prevalence of fungal infections alongside rising resistance to antifungal drugs poses a significant challenge to public health safety. At the close of the 2000s, major pharmaceutical firms began to scale back on antimicrobial research due to repeated setbacks and diminished economic gains, leaving only smaller companies and research labs to pursue new antifungal solutions. Among various natural sources explored for novel antifungal compounds, antifungal peptides (AFPs) emerge as particularly promising. Despite their potential, AFPs receive less focus than their antibacterial counterparts. These peptides have been sourced extensively from nature, including plants, animals, insects, and especially bacteria and fungi. Furthermore, with advancements in recombinant biotechnology and computational biology, AFPs can also be synthesized in lab settings, facilitating peptide production. AFPs are noted for their wide-ranging efficacy, in vitro and in vivo safety, and ability to combat biofilms. They are distinguished by their high specificity, minimal toxicity to cells, and reduced likelihood of resistance development. This review aims to comprehensively cover AFPs, including their sources-both natural and synthetic-their antifungal and biofilm-fighting capabilities in laboratory and real-world settings, their action mechanisms, and the current status of AFP research. ONE-SENTENCE SUMMARY: This comprehensive review of AFPs will be helpful for further research in antifungal research.

Molecular Mechanisms of Ischemic Stroke: A Review Integrating Clinical Imaging and Therapeutic Perspectives.

Ischemic stroke poses a significant global health challenge, necessitating ongoing exploration of its pathophysiology and treatment strategies. This comprehensive review integrates various aspects of ischemic stroke research, emphasizing crucial mechanisms, therapeutic approaches, and the role of clinical imaging in disease management. It discusses the multifaceted role of Netrin-1, highlighting its potential in promoting neurovascular repair and mitigating post-stroke neurological decline. It also examines the impact of blood-brain barrier permeability on stroke outcomes and explores alternative therapeutic targets such as statins and sphingosine-1-phosphate signaling. Neurocardiology investigations underscore the contribution of cardiac factors to post-stroke mortality, emphasizing the importance of understanding the brain-heart axis for targeted interventions. Additionally, the review advocates for early reperfusion and neuroprotective agents to counter-time-dependent excitotoxicity and inflammation, aiming to preserve tissue viability. Advanced imaging techniques, including DWI, PI, and MR angiography, are discussed for their role in evaluating ischemic penumbra evolution and guiding therapeutic decisions. By integrating molecular insights with imaging modalities, this interdisciplinary approach enhances our understanding of ischemic stroke and offers promising avenues for future research and clinical interventions to improve patient outcomes.

Revolutionizing Treatment Strategies for Autoimmune and Inflammatory Disorders: The Impact of Dipeptidyl-Peptidase 4 Inhibitors.

DPP4 (Dipeptidyl-peptidase 4) a versatile protease, emerges as a prominent player in soluble and membrane-bound forms. Its heightened expression has been intimately linked to the initiation and severity of diverse autoimmune diseases, spanning rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), inflammatory bowel disease, autoimmune diabetes, and even SARS-CoV-2 infection. Operating as a co-stimulator of T cell activity, DPP4 propels T cell proliferation by binding adenosine deaminase (ADA), thereby augmenting the breakdown of adenosine-an influential inhibitor of T cell proliferation. However, the discovery of a wide range of DPP4 inhibitors has shown promise in alleviating these diseases' signs, symptoms, and severity. The available DPP4 inhibitors have demonstrated significant effectiveness in blocking DPP4 activity. Based on the characterization of their binding mechanisms, three distinct groups of DPP4 inhibitors have been identified: saxagliptin, alogliptin, and sitagliptin, each representing a different class. Elevated levels of angiotensin-converting enzyme 2 (ACE2) expression are associated with producing various coronavirus peptidases. With its anti-inflammatory properties, Sitagliptin may assist COVID-19 patients in preventing and managing cytokine storms. This comprehensive review delves into the burgeoning realm of DPP4 inhibitors as therapeutic interventions for diverse autoimmune diseases. With a discerning focus on their efficacy, the investigation sheds light on their remarkable capacity to alleviate the burdensome signs and symptoms intricately linked to these conditions.

Etiology, pathology, and host-impaired immunity in medical implant-associated infections.

Host impaired immunity and pathogens adhesion factors are the key elements in analyzing medical implant-associated infections (MIAI). The infection chances are further influenced by surface properties of implants. This review addresses the medical implant-associated pathogens and summarizes the etiology, pathology, and host-impaired immunity in MIAI. Several bacterial and fungal pathogens have been isolated from MIAI; together, they form cross-kingdom species biofilms and support each other in different ways. The adhesion factors initiate the pathogen's adherence on the implant's surface; however, implant-induced impaired immunity promotes the pathogen's colonization and biofilm formation. Depending on the implant's surface properties, immune cell functions get slow or get exaggerated and cause immunity-induced secondary complications resulting in resistant depression and immuno-incompetent fibro-inflammatory zone that compromise implant's performance. Such consequences lead to the unavoidable and straightforward conclusion for the downstream transformation of new ideas, such as the development of multifunctional implant coatings.

Regulatory and pathogenic mechanisms in response to iron deficiency and excess in fungi.

Iron is an essential element for all eukaryote organisms because of its redox properties, which are important for many biological processes such as DNA synthesis, mitochondrial respiration, oxygen transport, lipid, and carbon metabolism. For this reason, living organisms have developed different strategies and mechanisms to optimally regulate iron acquisition, transport, storage, and uptake in different environmental responses. Moreover, iron plays an essential role during microbial infections. Saccharomyces cerevisiae has been of key importance for decrypting iron homeostasis and regulation mechanisms in eukaryotes. Specifically, the transcription factors Aft1/Aft2 and Yap5 regulate the expression of genes to control iron metabolism in response to its deficiency or excess, adapting to the cell's iron requirements and its availability in the environment. We also review which iron-related virulence factors have the most common fungal human pathogens (Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans). These factors are essential for adaptation in different host niches during pathogenesis, including different fungal-specific iron-uptake mechanisms. While being necessary for virulence, they provide hope for developing novel antifungal treatments, which are currently scarce and usually toxic for patients. In this review, we provide a compilation of the current knowledge about the metabolic response to iron deficiency and excess in fungi.

The Breadth of Bacteriophages Contributing to the Development of the Phage-Based Vaccines for COVID-19: An Ideal Platform to Design the Multiplex Vaccine.

Phages are highly ubiquitous biological agents, which means they are ideal tools for molecular biology and recombinant DNA technology. The development of a phage display technology was a turning point in the design of phage-based vaccines. Phages are now recognized as universal adjuvant-free nanovaccine platforms. Phages are well-suited for vaccine design owing to their high stability in harsh conditions and simple and inexpensive large-scale production. The aim of this review is to summarize the overall breadth of the antiviral therapeutic perspective of phages contributing to the development of phage-based vaccines for COVID-19. We show that phage vaccines induce a strong and specific humoral response by targeted phage particles carrying the epitopes of SARS-CoV-2. Further, the engineering of the T4 bacteriophage by CRISPR (clustered regularly interspaced short palindromic repeats) presents phage vaccines as a valuable platform with potential capabilities of genetic plasticity, intrinsic immunogenicity, and stability.

COVID-19 surveillance in wastewater: An epidemiological tool for the monitoring of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic has prompted a lot of questions globally regarding the range of information about the virus's possible routes of transmission, diagnostics, and therapeutic tools. Worldwide studies have pointed out the importance of monitoring and early surveillance techniques based on the identification of viral RNA in wastewater. These studies indicated the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in human feces, which is shed via excreta including mucus, feces, saliva, and sputum. Subsequently, they get dumped into wastewater, and their presence in wastewater provides a possibility of using it as a tool to help prevent and eradicate the virus. Its monitoring is still done in many regions worldwide and serves as an early "warning signal"; however, a lot of limitations of wastewater surveillance have also been identified.

Photocatalytic oxidative degradation of hydrocarbon pollutants in refinery wastewater using TiO2 as catalyst.

This study reports the photocatalytic oxidative degradation of hydrocarbon pollutants present in refinery wastewater under UV light using Fe2 O3 , MnO2 , TiO2 , and ZnO as catalysts. Among the catalysts, TiO2 exhibited the highest photocatalytic degradation activity, that is, 92, 98.8, 91.5, and 93% conversion for benzene, toluene, phenol, and naphthalene, respectively, in the model refinery wastewater under the optimum reaction conditions of pH 3, 30°C, 90-min reaction time, and 100 mg/L catalyst dose. The photocatalytic degradation of a real refinery wastewater sample containing 69.23% aliphatics, 25.36% aromatics, 3.2% oxygenates, and 2.21% naphthenic hydrocarbons under the optimum conditions revealed a net decrease in chemical oxygen demand (93.2%), that is, from 970 mg/L to 65 mg/L. GC-MS analysis of the reaction products confirmed that using UV/TiO2 system, complete photodegradation of the parent hydrocarbons occurred, but some oxygenated byproducts were also observed. This study provides useful reference information for the treatment of wastewater from oil refineries to cope with the increasing environmental issues. PRACTITIONER POINTS: Benzene, toluene, phenol and naphthalene were successfully degraded by UV/TiO2 system, under 30°C, 1 hr, pH 3 and 100 mg catalyst. Photocatalytic oxidation of Refinery wastewater (Attock Oil refinery, Pakistan), UV/ TiO2 system resulted in 93.92% COD removal. GC-MS analysis shows complete removal of parent hydrocarbons from refinery wastewater, leaving only traces of oxygenated hydrocarbons as oxidation byproducts.