INTRODUCTION: Extensively and multi-drug resistant isolates of bacteria (MDR, XDR) have caused significant health problems and are responsible for high morbidity and mortality as well. In this critical condition, the discovery, design, or development of new antibiotics is of great concern. According to this necessity, antimicrobial peptides (AMPs) suggested as promising agents. Accordingly, this study aims to evaluate the GKY25 peptide to develop its future antibacterial applications as well as confirmation of LPS neutralization. METHOD: Predictions of 3D structure and helical wheel projection analysis of the peptide were performed by I-TASSER and Heliquest servers. Binding affinity and antibacterial activity were performed using molecular docking and CAMPR4, respectively, followed by experimental binding assay as well as in vitro antibacterial assay. RESULT: GKY25 was predicted as an alpha-helical peptide, and its helicity showed probable projection of hydrophobic and positively-charged amino acid residues. Docking studies showed binding affinity of GKY25 peptide to gram-positive and outer and inner gram-negative bacterial membranes as -5.7, -6.8, and -4 kcal/mole, respectively. CAMPR4 analysis predicted the peptide as an AMP. Experimental binding assay showed that the peptide binds LPS immediately and their interaction was observed at 274 nm. CONCLUSION: Gathering all in silico and in vitro data together, GKY25 is a good drug lead that could be examined further using clinical isolates of gram-negative bacteria in vitro.

Sepsis is a syndrome involving complex pathophysiological and biochemical dysregulation. Nanotechnology can improve our understanding of the pathophysiology of sepsis and contribute to the development of novel diagnostic and therapeutic strategies to further reduce the risk of sepsis. Macrophages play a key role in the progression of sepsis, thus, macrophage-associated pathological processes are important targets for both diagnostic and treatment of sepsis. In this paper, we reviewed efforts in the past decade of nanotechnologybased solutions for manipulate macrophages in sepsis diagnosis and management according to the type of nanomaterial. We addressed the latest progress of nanoparticles targeting macrophages for early sepsis detection. Additionally, we summarized the unique advantages of macrophage-targeted nanoparticles in the treatment of sepsis. These nanoparticles can improve the dysregulation of inflammatory response in sepsis by inhibiting the release of inflammatory factors and regulating macrophage apoptosis, activity and polarization. Finally, we present future opportunities as well as challenges of novel diagnostic and therapeutic strategies with the aim of accelerating the clinical translation of nanomedicine for sepsis treatment.

Due to the high mortality rate of COVID-19 and its high variability and mutability, it is essential to know the body's defense mechanisms against this virus. Saliva has numerous functions, such as digestion, protection, and antimicrobial effects. Salivary diagnostic tests for many oral and systemic diseases will be available soon because saliva is a pool of biological markers. The most important antiviral and antibacterial compounds identified in saliva include lysozyme, lactoferrin (LF), mucins, cathelicidin, salivary secretory immunoglobulin (SIgA), chromogranin A, cathelicidin, salivary agglutinin (SAG) (gp340, DMBT1), α, β defensins, cystatin, histatins, secretory leukocyte protease inhibitor (SLPI), heat shock protein (HSP), adrenomedullin and microRNA (miRNAs). Antimicrobial peptides (AMPs) in saliva could be used in the future as models for designing effective oral microbial antibiotics. The antiviral properties of the peptides in saliva may be one of the future treatments for the COVID-19 virus. In this review, we investigate compounds with antiviral and antibacterial properties in saliva and the importance of these compounds in saliva in exposure to the COVID-19 virus. Due to the transmission route of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into the oral cavity in the lower and upper respiratory tract, studies of salivary antiviral properties in these patients are very important. Some of the antiviral effects of saliva, especially mucin, α, β-defensins, IgA, IgG, IgM, lysozyme, SAG, SLPI, and histatins, may play a greater role in neutralizing or eliminating COVID-19.

BACKGROUND: The IL-17 (interleukin 17) family consists of six structurally related pro-inflammatory cytokines, namely IL-17A to IL-17F. These cytokines have garnered significant scientific interest due to their pivotal role in the pathogenesis of various diseases. Notably, a specific subset of T-cells expresses IL-17 family members, highlighting their importance in immune responses against microbial infections. INTRODUCTION: IL-17 cytokines play a critical role in host defense mechanisms by inducing cytokines and chemokines, recruiting neutrophils, modifying T-cell differentiation, and stimulating the production of antimicrobial proteins. Maintaining an appropriate balance of IL-17 is vital for overall health. However, dysregulated production of IL-17A and other members can lead to the pathogenesis of numerous inflammatory and autoimmune diseases. METHOD: This review provides a comprehensive overview of the IL-17 family and its involvement in several inflammatory and autoimmune diseases. Relevant literature and research studies were analyzed to compile the data presented in this review. RESULTS: IL-17 cytokines, particularly IL-17A, have been implicated in the development of various inflammatory and autoimmune disorders, including multiple sclerosis, Hashimoto's thyroiditis, systemic lupus erythematosus, pyoderma gangrenosum, autoimmune hepatic disorders, rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, osteoarthritis, and graft-versus-host disease. Understanding the role of IL-17 in these diseases is crucial for developing targeted therapeutic strategies. CONCLUSION: The significant involvement of IL-17 cytokines in inflammatory and autoimmune diseases underscores their potential as therapeutic targets. Current treatments utilizing antibodies against IL-17 cytokines and IL-17RA receptors have shown promise in managing these conditions. This review consolidates the understanding of IL-17 family members and their roles, providing valuable insights for the development of novel immunomodulators to effectively treat inflammatory and autoimmune diseases.

The poor water solubility of numerous novel drug candidates presents significant challenges, particularly in terms of oral delivery. This limitation can result in various undesirable clinical implications, such as inter-patient variability, poor bioavailability, difficulties in achieving a safe therapeutic index, increased costs, and potential risks of toxicity or inefficacy. Biopharmaceutics Classification System (BCS) class II drugs face particular hurdles due to their limited solubility in the aqueous media of the gastrointestinal tract. In such cases, parenteral administration is often employed as an alternative strategy. To address these challenges, nanosuspension techniques offer a promising solution for enhancing drug solubility and overcoming oral delivery obstacles. This technique has the potential to bridge the gap between drug discovery and preclinical use by resolving problematic solubility. This literature review has delved into contemporary nanosuspension preparation technologies and the incorporation of stabilizing ingredients within the formulation. Furthermore, the manuscript explores nanosuspension strategies for both oral and parenteral/other delivery routes, and separate discussions have been presented to establish a suitable flow that addresses the challenges and strategies relevant to each administration method.

BACKGROUND: Research proved that coenzyme Q10-loaded NLC effectively removes skin wrinkles, therefore, such a formulation with good characteristics is still the research goal. OBJECTIVE: This study investigated the effect of solid lipids and surfactant type on the physical characteristics of Q10-NLC. We aimed to achieve the optimum formulation for producing NLC with long-term stability and high Entrapment efficiency (E.E.) %. We compared the experimental results with the output of the Molecular dynamic (M.D.) simulations. METHODS: To develop Q10-NLC, various solid lipids, MCT oil, and surfactants were employed. The formulations were prepared by high-shear homogenization and ultrasound methods. Stability studies were carried out 1,3, and 6 months at 4, 25, and 40°C. The optimized NLC formulations were characterized by photon correlation spectroscopy (PCS), Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR). E.E. % was determined by HPLC analysis. Atomistic M.D. simulations of two model systems were performed to gain insights into the self-assembled process of co-Q10 with other formulation components. RESULTS: Statistical analysis (Two-way ANOVA) revealed that solid lipid and surfactant factors had a significant influence on particle size, PDI, and zeta potential (***p<0.0001). According to the results, F1 and F6 formulations had desirable surface characterizations, physicochemical stability, and high E.E.%. The atomistic M.D. simulations confirmed that the F1 system (best( was more stable than the F31 system (worst). CONCLUSION: The solid lipids: tripalmitin and compritol, stabilized with 4% tween 80 and 1% span 80, have produced stable NLC with the best surface characteristics that could be a promising formulation for the delivery of Q10. Atomistic M.D. simulation has confirmed the stability of F1 in comparison to F31.

BACKGROUND: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF. OBJECTIVE: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF. METHODS: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking. RESULTS: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6. CONCLUSION: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer with a poor prognosis and limited treatment options. Previous studies show that some components of the cholinergic pathway may play important roles in the tumorigenesis of lung cancer, including LUSC. OBJECTIVE: The purpose of this study is to investigate the involvement of cholinergic genes in immune infiltration in LUSC, and identify the key genes in the pathway and analyze their potential as targets for LUSC treatment and novel drugs. METHODS: We first screened the cholinergic genes associated with immune infiltration in LUSC based on transcriptomic samples and explored the correlation between the key genes and immune infiltrating cells and immune pathways. Then, we assessed the effect of immunotherapeutic response in the high and low-expression groups of key genes in vitro. And finally, we screened potential drugs for the treatment of LUSC. RESULTS: We found that the expression of CHRNA6, the gene encoding the α6 subunit of nicotinic acetylcholine receptors (nAChR), was significantly correlated with the proportion of immune infiltrating cells in LUSC, and the high expression level of the gene was associated with poor prognosis of the disease. Also, the proportion of Tregs, M1 macrophages, and resting mast cells was correlated with the expression of CHRNA6. In addition, LUSC patients with higher CHRNA6 expression levels had better immunotherapy responses. Furthermore, we found that the drugs, i.e., adavosertib, varbulin and pyrazoloacridine, had a strong affinity with CHRNA6, with adavosertib binding most stably with the protein. CONCLUSION: CHRNA6 may be associated with immune infiltration in LUSC and affects patient prognosis and immunotherapeutic response by regulating immune cells and immune pathways. In addition, adavosertib may be a potential drug for the treatment of LUSC.