Search Results (3,079)

Inflammatory bowel disease (IBD) is a chronic, heterogeneous condition characterized by recurrent intestinal inflammation and sustained mucosal barrier damage, profoundly impairing patients’ quality of life and imposing a considerable socioeconomic burden. Current therapeutic options are often constrained by low oral bioavailability, pronounced systemic toxicity, and inadequate tissue specificity, limiting their ability to achieve precise and durable efficacy. In recent years, membrane vesicle-based drug delivery systems (MV-DDSs) have shown considerable promise for precision IBD therapy owing to their excellent biocompatibility, mucosal barrier-penetrating capacity, and low immunogenicity. Building upon a systematic discussion of the roles of MV-DDSs in suppressing inflammatory signaling, modulating oxidative stress, preserving barrier integrity, reshaping the gut microbiota, and regulating programmed cell death, this review further compares the differences in key molecular targets and functional outcomes among vesicles of diverse origins and carrying distinct therapeutic payloads. These insights provide a comprehensive strategic reference and theoretical foundation for the rational design, mechanistic optimization, and clinical translation of MV-DDSs in IBD therapy. Full article

Pseudophakic bullous keratopathy (PBK) is a vision-threatening corneal complication following cataract surgery, characterised by progressive endothelial cell loss, persistent corneal oedema, and painful epithelial bullae, leading to impaired vision. Corneal transplantation, either penetrating or endothelial keratoplasty, remains the primary treatment but faces challenges such as donor tissue shortages, graft rejection, and limited graft longevity. Recently, Rho-kinase (ROCK) inhibitors have emerged as promising pharmacological alternatives. These agents enhance corneal endothelial cell proliferation, migration, and adhesion, suppress apoptosis, and promote corneal deturgescence and wound healing. Several preclinical and clinical studies have demonstrated the efficacy of ROCK inhibitors in improving corneal clarity, endothelial function, and visual acuity in PBK. Their use has been associated with reductions in corneal oedema, improved endothelial cell density, and delayed or prevented the need for corneal transplantation. A systematic literature search of PubMed, Scopus, and Web of Science databases was conducted, restricted to peer-reviewed English-language articles, ensuring comprehensive coverage. ROCK inhibitors represent a novel pharmacological strategy for PBK prevention and management, potentially reducing dependency on donor grafts. Further research is needed to determine long-term safety, optimal dosing, and efficacy. Full article

Background/Objectives: Peptide-based inorganic nanoparticles (PINPs) have emerged as promising candidates for intracellular delivery due to their unique structural and functional attributes. These hybrid nanostructures combine the high surface area and tunable optical/magnetic properties of metal cores (e.g., Au, Ag, Fe₃O₄) with the biocompatibility, targeting specificity, and responsive behavior of peptides. In particular, peptides with amphipathic or cell-penetrating features could facilitate efficient transport of molecular cargos across cellular membranes while enabling stimulus-responsive drug release in target tissues. Methods: We review key synthesis methods (especially green, peptide-mediated one-pot approaches), functionalization strategies (e.g., thiol-gold bonds, click chemistries), and characterization techniques (TEM, DLS, FTIR, etc.) that underpin PINP design. In addition, we highlight diverse peptide classes (linear, cyclic, amphipathic, self-assembling) and their roles (targeting ligands, capping/stabilizing agents, reducing agents) in constructing multifunctional nanocarriers. Results: The prospects of PINPs are considerable: they enable targeted drug delivery with imaging/theranostic capability, improve drug stability and cellular uptake, and harness peptide programmability for precision nanomedicine. However, challenges such as in vivo stability, immunogenicity, and standardization of evaluation must be addressed. Conclusions: Overall, PINPs represent multifunctional platforms that could significantly advance drug delivery and diagnostic applications in the future. Full article

Objectives: Atherosclerosis is a chronic inflammatory disease characterized by complex pathological mechanisms. Early detection of vulnerable plaques is critical for assessing rupture risk and preventing acute cardiovascular events. Conventional ultrasound contrast agents (UCAs) are limited in their ability to penetrate the vascular wall and unable to provide detailed information on plaque composition and stability. In this study, we developed biosynthetic gas vesicles (GVs) derived from Halobacterium NRC-1 as UCAs for imaging of vulnerable plaques. Methods: These GVs were functionalized with the VHPKQHR peptide (VHP), enabling specific binding to vascular cell adhesion molecule-1 (VCAM-1), a key biomarker of inflammation in atherosclerosis. In vitro evaluation of VHP-GVs was performed through contrast-enhanced ultrasound imaging using agarose gel phantoms and adhesion assays with inflammatory cell models to assess their targeting capability toward VCAM-1. In vivo ultrasound molecular imaging was performed using the Sprague Dawley (SD) rat model of early-stage atherosclerosis in the left common carotid artery to evaluate imaging efficacy. Results: Both in vitro and in vivo experiments demonstrated that VHP-GVs could effectively penetrate the vascular wall into plaques and generate robust ultrasound contrast signals for precise identification of vulnerable regions. Conclusions: This study establishes a promising tool for the early diagnosis and targeted treatment of atherosclerosis, underscoring the translational potential of biosynthetic nanobubbles in clinical practice. Full article

We report on the effect state of charge (SoC), cell format, and chemistry have on the volume and composition (H₂, CO₂, CO, CH₄, C₂H₄, C₂H₆, C₃H₆, and C₃H₈) of cell failure gas from Li-ion cells. Nickel manganese cobalt oxide (NMC) 21700 cells with a 5 Ah capacity were externally heated to failure at a 5–100% SoC under an inert atmosphere. This showed that the volume of gas increased with cell SoC (1.8 L at 5% SoC vs. 8.3 L at 100% SoC). The effect of the cell chemistry format and abuse method was also investigated using 18650, pouch, and prismatic cells (2.3–50 Ah) with Ni-based or lithium cobalt oxide (LCO) cathodes or lithium titanium oxide (LTO) anodes. The results showed that at higher SoCs, larger quantities of gas were generated; however, there was no correlation between the cell SoC and the composition of gases produced. Tests on the other cells found that the Ni-based cell generated 1.29–1.89 L/Ah of gas. The main constituents of this were H₂, CO, and CO₂; however, all other hydrocarbons were identified in varying quantities. The LTO cells generated lower volumes of gas, 0.8 L/Ah compared to Ni-based cells, and the gas was found to contain lower H₂ concentrations but higher concentrations of CO₂. The LCO cell was found to generate a gas volume of 1.2 L/Ah. This forms the final of four papers which cover a total of 213 tests on 29 cell types with six different chemistries, all tested using a single robust testing method. Full article

Fine particulate matter (PM2.5) is an environmental factor that triggers gastrointestinal diseases. However, the effects of PM2.5 on intestinal function are not fully understood. This study established an environmental exposure cell model to explore PM2.5-induced intestinal permeability alteration and its mechanisms. Intestinal barrier permeability was evaluated via trans-epithelial electrical resistance (TEER) measurement and FITC–dextran paracellular penetration analysis, followed by detection of intercellular junction protein β-catenin and its coding gene CTNNB1. Expression of inflammatory cytokines (TNF-α, IL-6) and phosphorylation of PI3K and AKT were assessed using quantitative real-time polymerase chain reaction and Western blot, respectively. Reactive oxygen species (ROS) and malondialdehyde were measured using commercial kits to observe cellular oxidative stress. The results showed that PM2.5 impaired the intestinal barrier, as indicated by reduced TEER, increased FITC–dextran penetration, down-regulated expression of β-catenin and CTNNB1. Additionally, compared with the control, inflammatory cytokines and oxidative stress markers were significantly elevated after PM2.5 exposure. The ratio of p-PI3K/PI3K and p-AKT/AKT was also up-regulated in PM2.5-exposed Caco-2 cells. Pretreatment with PI3K inhibitor LY294002 and ROS scavenger NAC modulated β-catenin expression, reduced inflammation/ROS, and alleviated the hyperpermeability of Caco-2 cells. Thus, our results reveal that PM2.5 induces PI3K/AKT-mediated inflammation and ROS generation in Caco-2 cells, leading to intestinal barrier impairment. Full article

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, analgesic, lipostatic, antiproliferative, moisturising, and anti-ageing properties through interactions with the skin’s endocannabinoid system (ECS), modulating CB1, CB2, TRPV channels, and PPARs. Preclinical and clinical evidence support its efficacy in managing acne, psoriasis (including scalp psoriasis), atopic and seborrheic dermatitis, and allergic contact dermatitis. CBD also relieves pruritus through neuroimmune modulation and promotes wound healing in conditions such as pyoderma gangrenosum and epidermolysis bullosa. In hair disorders such as androgenetic alopecia, it aids follicular regeneration. CBD shows promise in managing skin cancers (melanoma, squamous cell carcinoma, Kaposi sarcoma) and pigmentation disorders such as melasma and vitiligo. It enhances skin rejuvenation by reducing oxidative stress and boosting collagen and hydration. However, there are challenges regarding CBD’s physicochemical stability, skin penetration, and regulatory standardisation. As consumer demand for natural, multifunctional skincare grows, further research is essential to validate its long-term safety, efficacy, and optimal formulation strategies. Full article

An outbreak characterized by clinical signs of diarrhea and paralysis, occasionally progressing to fatal outcomes, occurred at an ostrich breeding facility. Conventional antibiotic treatments proved ineffective. To investigate the etiology of the disease, brain and liver specimens were collected for diagnostic analysis. An Escherichia coli (E. coli) isolate, designated strain HZDC01, was obtained from cerebral tissues, and whole-genome sequencing was performed for genomic characterization. Genomic analysis revealed that the chromosomal DNA harbors numerous resistance genes, conferring multidrug resistance through complex mechanisms. Furthermore, a p0111-type plasmid carrying the bla_CTX-M-55 gene and an IncX1-type plasmid harboring rmtB, sul1, APH(6)-Id, tet(A), AAC(3)-IIc, aadA2, bla_TEM-1B, and floR genes were identified. These plasmids carry numerous mobile genetic elements that can disseminate via horizontal gene transfer, thereby amplifying the risk of resistance-gene spread within bacterial populations. Additionally, the ibeB and ibeC genes, which encode proteins involved in the invasion of brain microvascular endothelial cells, were identified. These genes may facilitate E. coli penetration of the blood–brain barrier, potentially leading to meningitis and posing a life-threatening risk to the host. This is the first report of the isolation and characterization of extended-spectrum beta-lactamase E. coli from the brain of an ostrich with paralysis. The findings provide valuable genomic insights into the antimicrobial resistance profiles and pathogenic mechanisms of ostrich-derived E. coli isolates. Full article

Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common form of cancer worldwide, typically characterized by high mortality and significant morbidity, including pain and speech and swallowing disorders. Complete tumor tissue resection, the common first line of therapy, remains a surgical challenge with room for improvements. Because tumor cells express highly specific surface molecules serving as receptors for ligands, specific targeting ligands can be conjugated to fluorescent molecules in order to better visualize tumor borders. Targeted fluorescence-guided surgery (T-FGS) as well as tumor-targeted and near-infrared (NIR) fluorescence imaging are emerging techniques for real-time intraoperative cancer imaging. Targeting agents include nanodots or fluorophores, which have been conjugated to specific ligands like antibodies, peptides, or other synthetic moieties. This article surveys tumor-targeted ligands in recent and current preclinical studies and clinical trials related to HNSCC, highlighting common NIRF dyes used for molecular imaging and their physical properties, working concentrations, and associated risks. Smaller ligands, nanodots, dual-modality NIR dyes, and activatable agents can enhance tumor-targeting processes, resulting in faster, more penetrable, and clearer imaging, which could lead to improved clinical applications and better tumor removal rates in the future. Full article

Deoxyshikonin (DS) is a derivative of shikonin, the main compound present in Lithospermi radi, the root of Lithospermum erythrorhizon Siebold and Zucc. In this study, we investigated the antiviral effects of DS using Influenza A/PR8/34, which expresses green fluorescent protein (GFP) as well as wild-type PR8/34 H1N1 Influenza A virus (IAV). Fluorescence microscopy and flow cytometry results showed that DS from 1.25 to 5 µM significantly and dose-dependently inhibited PR8-GFP IAV infection. A plaque assay confirmed the inhibitory effect of DS against H1N1 IAV infection. Consistently, immunofluorescence results showed that DS suppresses IAV protein expression. Time-of-drug-addition and hemagglutination inhibition assays revealed that DS exhibits anti-influenza virus efficacy by blocking the viral attachment and penetration into the cells and has a direct virus-eradication effect in the early stages of infection. However, DS did not repress neuraminidase activity. Our findings suggest that DS could be used not only to protect against the early stages of IAV infection, but also to treat influenza virus infections in combination with NA inhibitors. Full article

Significant progress has been made in developing cell-based drug delivery systems that utilize the intrinsic biological properties of various cell types—erythrocytes, leukocytes, platelets, stem cells, and even spermatozoa—to improve drug targeting, bioavailability, and biocompatibility. This review presents an integrative analysis of the latest advances in cell-based drug delivery systems, focusing on their design, pharmacokinetics, cellular interactions, and therapeutic potential. We specifically focus on hybrid microrobots and membrane-coated nanocarriers as emerging biohybrid platforms. Despite these advances, translation to the clinical phase remains constrained by persistent limitations, such as immune clearance, loss of membrane integrity during cargo loading, limited tissue penetration of carrier cells, and manufacturing challenges. Finally, we highlight future directions, including CAR-cell combinations and artificial cell engineering, that promise to expand the clinical utility of cell-based drug delivery systems in oncology, infectious diseases, and regenerative medicine. Full article

Glaucoma is recognized as a chronic optic neuropathy marked by progressive optic nerve degeneration, loss of retinal ganglion cells (RGCs, the neurons responsible for transmitting visual information from the eye to the brain), disruptions in optic disc blood supply, and changes in glial cell activation. It ranks as the second most prevalent cause of irreversible visual impairment worldwide and is a resultant of increased intraocular pressure (IOP). Addressing this condition proves complex due to the inherent hindrances posed by ocular barriers, which curtail the entry of drugs into the eye. Diverse carriers such as inorganic nanoparticles, polymeric nanocarriers, hydrogels, and contact lens-based systems with distinct physical and chemical attributes are being studied for drug delivery. They have shown enhanced ocular drug bioavailability through higher penetration across ocular tissues, prolonged retention in the precorneal space, sustained drug release, and targeted delivery to specific tissues. These ingenious delivery systems can be deployed through various administration routes—intravitreal or periocular injections or systemic administration—enabling the drugs to reach affected areas, aiding in the regeneration of compromised optical nerves. This review presents a comprehensive exploration of contemporary strides in ocular delivery formulations pertaining to glaucoma. This encompasses an examination of various nanocarrier typologies, delivery routes, in vitro and in vivo effectiveness, clinical applicability, and a forward-looking perspective into potential future developments. Full article

Multi-drug resistance in human bacterial pathogens has become a significant challenge for global healthcare this century, mainly due to the widespread misuse of antibiotics worldwide. As a result, millions of people have been affected by multi-drug-resistant bacterial infections. The antibiotic development pipelines cannot cope with the need to produce new antibiotics. Therefore, more productive antibiotic development methods must be invented. This paper presents an entirely rational approach for antibacterial drug discovery based on chimeric antisense oligonucleotide targeting (ASO) of the adenylate kinase mRNA in Staphylococcus aureus. The ASO is delivered into the bacteria via the cell-penetrating oligopeptide pVEC. The pVEC-ASO1 exhibits a bactericidal effect against Staphylococcus aureus, with a 50% minimal inhibitory concentration of 500 nM. The pVEC-ASO1 has a 98% survivability rate at the same concentration on cell lines. These findings strongly suggest that this chimeric ASO is a promising antibacterial drug candidate. Moreover, this is the fifth bacterial mRNA we have successfully targeted with pVEC-ASOs, providing further evidence for the efficiency of our approach. In contrast to the previous four targets, riboswitches residing in the 5′-untranslated region, we target the coding part of mRNA found in bacteria. That suggests that our approach may have much broader therapeutic applications. Full article

Apolipoprotein A-I (apoA-I)-coated nanoemulsion particles target scavenger receptors. Adsorbed apoA-I (from the bloodstream) mediates/facilitates this targeted molecular contact, which is followed by receptor-mediated endocytosis and subsequent transcytosis of these same nanoemulsion (nanocarrier) particles across the blood–brain barrier (BBB). When the right drugs are added in advance to these high-density lipoprotein (HDL)-like nanocarriers, multifunctional combination treatment is achieved. This medication penetrates the BBB and targets particular cell-surface scavenger receptors, mainly class B type I (SR-BI). As a result, these (drug-carrying) nanoemulsions may find application in the biomedical therapy of complex medical disorders, such as dementia, as well as some aspects of aging. According to recent research, sustained inflammatory stimulation in the gut, such as via serum amyloid A (SAA), may cause the release of proinflammatory cytokines. Thus, using this “HDL-like” nanoemulsion vehicle to target drugs early (or even proactively) toward a major SAA receptor (like SR-BI), which is implicated in SAA-mediated cell-signaling processes that lead to aging and/or cognitive decline (and eventually Alzheimer’s disease or dementia), may be a useful preventive and therapeutic strategy. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), characterized by high-level β-lactam resistance and increasing multi-drug resistance, poses a severe and growing global threat to human health and public safety. This review examines MRSA’s complex resistance mechanisms, including mecA/mecC-mediated expression of low-affinity PBP2a, regulatory roles of auxiliary genes like fem and vanA, enzymatic inactivation by β-lactamases and modifying enzymes, efflux pump activity, and biofilm formation. We also systematically review novel therapeutic strategies, such as combination therapies, phage-derived biofilm disruptors, membrane-targeting silver nanoparticles, cell-penetrating antimicrobial peptides, colonization-competitive probiotics, and antibiotic-synergizing phytochemicals. These advances provide critical insights for developing effective countermeasures against MRSA, while highlighting the urgent need for global collaboration, antibiotic stewardship, and innovative drug development to combat antimicrobial resistance. Full article