Identification of a Drug Candidate against Using Pandemic Response Box.

MAC ( complex) is a naturally occurring environmental microorganism found worldwide in sources such as soil and water. Among nontuberculous mycobacteria (NTM), MAC is the species most commonly responsible for pulmonary infections, particularly in immunocompromised individuals. In addition to pulmonary disease, extrapulmonary infections can present as disseminated, cutaneous, or lymphatic diseases.

Exploring the therapeutic potential of phytochemicals: challenges and strategies for clinical translation.

Background: Phytochemicals exhibit multi-target therapeutic potential with low toxicity, but their clinical translation is limited by poor bioavailability, unclear mechanisms, inadequate models, and structural instability. Addressing these barriers requires integrated strategies that preserve structure-function integrity and improve translational fidelity.

Purpose: This review identifies key translational barriers of phytochemicals and proposes integrated, structure-informed strategies combining delivery systems, mechanistic insights, and advanced models to preserve structure-function integrity and enable their application in precision medicine.

Live strains from the mucosa of patients with ulcerative colitis: pathogenic potential and environmental adaptations.

Unlabelled: The human gut contains a diverse range of microorganisms, including bacteria, viruses, protozoa, and fungi. Although research has predominantly focused on bacterial populations, emerging evidence highlights the significant role of the gut mycobiota, particularly in the context of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease. This study investigates the intestinal mucosal mycobiota of UC patients, aiming to isolate and characterize live fungal strains from the gut mucosa.

Functional Nanosheet Immunoswitches Reprogramming Innate Macrophages for Immunotherapy of Colorectal Cancer and Sepsis.

Macrophages are involved in the immunopathogenesis of cancer and inflammatory diseases and are a primary target for immunotherapy to reprogram the M1 and M2 phenotypes in tumor and inflammatory microenvironments. Herein, functional nanosheet immunoswitches that can bidirectionally polarize macrophages in tumor and inflammatory microenvironments are designed for effective immunotherapy of colorectal cancer and sepsis. WSe nanosheets are functionalized with palmitic acid to obtain an M1 immunoswitch (PA-WSe) that promotes the polarization of macrophages toward the M1 phenotype in the tumor microenvironment by activating the STAT1 signaling pathway.

Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis.

The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis.

Enhancing acute inflammatory and sepsis treatment: superiority of membrane receptor blockade.

Conditions such as acute pancreatitis, ulcerative colitis, delayed graft function and infections caused by a variety of microorganisms, including gram-positive and gram-negative organisms, increase the risk of sepsis and therefore mortality. Immune dysfunction is a characterization of sepsis, so timely and effective treatment strategies are needed. The conventional approaches, such as antibiotic-based treatments, face challenges such as antibiotic resistance, and cytokine-based treatments have shown limited efficacy.

Integrative analysis of single-cell RNA-seq and gut microbiome metabarcoding data elucidates macrophage dysfunction in mice with DSS-induced ulcerative colitis.

Ulcerative colitis (UC) is a significant inflammatory bowel disease caused by an abnormal immune response to gut microbes. However, there are still gaps in our understanding of how immune and metabolic changes specifically contribute to this disease. Our research aims to address this gap by examining mouse colons after inducing ulcerative colitis-like symptoms.

Exploring the potential of Toxoplasma gondii in drug development and as a delivery system.

Immune-mediated inflammatory diseases are various groups of conditions that result in immune system disorders and increased cancer risk. Despite the identification of causative cytokines and pathways, current clinical treatment for immune-mediated inflammatory diseases is limited. In addition, immune-mediated inflammatory disease treatment can increase the risk of cancer.

Colon-targeted S100A8/A9-specific peptide systems ameliorate colitis and colitis-associated colorectal cancer in mouse models.

The link between chronic inflammation and cancer development is well acknowledged. Inflammatory bowel disease including ulcerative colitis and Crohn's disease frequently promotes colon cancer development. Thus, control of intestinal inflammation is a therapeutic strategy to prevent and manage colitis-associated colorectal cancer (CRC).

Tumor-targeted liposomes with platycodin D2 promote apoptosis in colorectal cancer.

Conventional chemotherapy for colorectal cancer (CRC), though efficacious, is discouraging due to its limited targeting capability, lack of selectivity, and chemotherapy-associated side effects. With the advent of nanomedicines, a liposomal delivery system making use of a combination of anticancer phytochemicals is fast gaining popularity as one of the most promising nanoplatforms for CRC treatment. Rising evidence supports phytochemicals such as platycosides for their anticancer potency.

Correction: Kim et al. Mito-TIPTP Increases Mitochondrial Function by Repressing the Rubicon-p22phox Interaction in Colitis-Induced Mice. 2021, , 1954.

In the original publication [...

Glycan targeting nanoparticle for photodynamic immunotherapy of melanoma.

Interaction between tumour cells and macrophages enables cancer cells to evade immune detection and clearance by interfering with macrophage phagocytosis. The anti-phagocytic signals regulated by anti-phagocytic proteins are termed "don't eat me" signals; these signals include sialic acid-binding immunoglobulin-type lectin-10 (Siglec-10) and the recently revealed CD24 immune checkpoint (ICP). In this study, we demonstrate that targeting a specific glycan on CD24 exhibits the potential to inhibit ICP.

Identification of ulcerative colitis-specific immune cell signatures from public single-cell RNA-seq data.

Background: Single-cell RNA-seq enabled microscopic studies on tissue microenvironment of many diseases. Inflammatory bowel disease, an autoimmune disease, is involved with various dysfunction of immune cells, for which single-cell RNA-seq may provide us a deeper insight into the causes and mechanism of this complex disease.

Objective: In this work, we used public single-cell RNA-seq data to study tissue microenvironment around ulcerative colitis, an inflammatory bowel disease causing chronic inflammation and ulcers in large intestine.

Hierarchical cell-type identifier accurately distinguishes immune-cell subtypes enabling precise profiling of tissue microenvironment with single-cell RNA-sequencing.

Single-cell RNA-seq enabled in-depth study on tissue micro-environment and immune-profiling, where a crucial step is to annotate cell identity. Immune cells play key roles in many diseases, whereas their activities are hard to track due to their diverse and highly variable nature. Existing cell-type identifiers had limited performance for this purpose.

Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3.

CD82 is a transmembrane protein that is involved in cancer suppression and activates immune cells; however, information on the NLRP3 inflammasome is limited. Herein, we show that although CD82 suppressed the activation of the NLRP3 inflammasome in vivo and in vitro, CD82 deficiency decreased the severity of colitis in mice. Furthermore, two binding partners of CD82, NLRP3 and BRCC3, were identified.

Colon-Targeted eNAMPT-Specific Peptide Systems for Treatment of DSS-Induced Acute and Chronic Colitis in Mouse.

Nicotinamide phosphoribosyl transferase (NAMPT) is required to maintain the NAD pool, among which extracellular (e) NAMPT is associated with inflammation, mainly mediated by macrophages. However, the role of (e) NAMPT in inflammatory macrophages in ulcerative colitis is insufficiently understood. Here our analyses of single-cell RNA-seq data revealed that the levels of NAMPT and CYBB/NOX2 in macrophages were elevated in patients with colitis and in mouse models of acute and chronic colitis.

Fibroblast-targeting polymeric nanovehicles to enhance topical wound healing through promotion of PAR-2 receptor-mediated endocytosis.

The level of collagen production critically determines skin wound contraction. If an intelligent skin drug delivery technology that enables collagen production in a specific wound skin area is developed, a breakthrough in wound healing treatment would be expected. However, such an intelligent drug delivery technology has not yet been developed as much as in the field of anticancer therapy.

The strategies of NLRP3 inflammasome to combat .

Infection with the protozoan parasite () results in the activation of nucleotide-binding domain leucine-rich repeat containing receptors (NLRs), which in turn leads to inflammasome assembly and the subsequent activation of caspase-1, secretion of proinflammatory cytokines, and pyroptotic cell death. Several recent studies have addressed the role of the NLRP3 inflammasome in infection without reaching a consensus on its roles. Moreover, the mechanisms of NLRP3 inflammasome activation in different cell types remain unknown.

Pathogen-derived peptides in drug targeting and its therapeutic approach.

Peptides, short stretches of amino acids or small proteins that occupy a strategic position between proteins and amino acids, are readily accessible by chemical and biological methods. With ideal properties for forming high-affinity and specific interactions with host target proteins, they have established an important niche in the drug development spectrum complementing small molecule and biological therapeutics. Among the most successful biomedicines in use today, peptide-based drugs show great promise.

One-pot bifunctionalization of silica nanoparticles conjugated with bioorthogonal linkers: application in dual-modal imaging.

Covalent surface modification of silica nanoparticles (SNPs) offers great potential for the development of multimodal nanomaterials for biomedical applications. Herein, we report the synthesis of covalently conjugated bifunctional SNPs and their application to multimodal imaging. Bis(methallyl)silane 15 with cyclopropene and maleimide, designed as a stable bifunctional linker, was efficiently synthesized by traceless Staudiger ligation, and subsequently introduced onto the surface of monodispersed SNPs Sc(OTf)-catalyzed siloxane formation.

PE_PGRS38 Interaction With HAUSP Downregulates Antimycobacterial Host Defense TRAF6.

(Mtb) is the causative pathogen of tuberculosis (TB), which manipulates the host immunity to ensure survival and colonization in the host. Mtb possess a unique family of proteins, named PE_PGRS, associated with Mtb pathogenesis. Thus, elucidation of the functions of PE_PGRS proteins is necessary to understand TB pathogenesis.

Discovery of Rv3364c-Derived Small Molecules as Potential Therapeutic Agents to Target SNX9 for Sepsis.

The serine protease inhibitor Rv3364c of (MTB) is highly expressed in cells during MTB exposure. In this study, we showed that the WLVSKF motif of Rv3364c interacts with the BAR domain of SNX9 and inhibits endosome trafficking to interact with p47phox, thereby suppressing TLR4 inflammatory signaling in macrophages. Derived from the structure of this Rv3364c peptide motif, 2,4-diamino-6-(4--butylphenyl)-1,3,5-trazine, as a WLVSKF peptide-mimetic small molecule has been identified.

Mito-TIPTP Increases Mitochondrial Function by Repressing the Rubicon-p22phox Interaction in Colitis-Induced Mice.

The run/cysteine-rich-domain-containing Beclin1-interacting autophagy protein (Rubicon) is essential for the regulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by interacting with p22phox to trigger the production of reactive oxygen species (ROS) in immune cells. In a previous study, we demonstrated that the interaction of Rubicon with p22phox increases cellular ROS levels. The correlation between Rubicon and mitochondrial ROS (mtROS) is poorly understood.

Transition-Metal Dichalcogenide Artificial Antibodies with Multivalent Polymeric Recognition Phases for Rapid Detection and Inactivation of Pathogens.

Antibodies are recognition molecules that can bind to diverse targets ranging from pathogens to small analytes with high binding affinity and specificity, making them widely employed for sensing and therapy. However, antibodies have limitations of low stability, long production time, short shelf life, and high cost. Here, we report a facile approach for the design of luminescent artificial antibodies with nonbiological polymeric recognition phases for the sensitive detection, rapid identification, and effective inactivation of pathogenic bacteria.