Search Results (142)

Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye’s unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy. Full article

Objective: This study aimed to design and clinically evaluate a bespoke cosmetic formulation tailored to individual skin characteristics and user preferences, focusing on hydration and barrier recovery in mature, therapy-affected skin. In addition, this study aimed to explore the feasibility and short-term outcomes of a structured, biometry-driven personalization approach applied within a single-subject case study design. Materials and Methods: A personalized dermato-cosmetic formulation incorporating melatonin, astaxanthin, low-molecular-weight hyaluronic acid, allantoin, yarrow oil (Achillea millefolium), lecithin, cholesterol, and arginine was developed based on objective biophysical assessment of the skin. A clinical case evaluation was conducted in a male subject over 55 years of age (Fitzpatrick phototype III) presenting persistent xerosis and dehydration following completed oncologic therapy. Quantitative skin biometry was performed at baseline and after 28 days of daily application, assessing hydration at six anatomical sites, sebum secretion, pigmentation and erythema indices, elasticity, and stratum corneum turnover and scaling. Results: After 28 days, sebum secretion increased by more than 100%, indicating partial restoration of the lipid barrier. Hyperpigmented areas decreased from 7.2% to 2.3%, while skin elasticity improved from 25% to 44%. A reduction of 8% in the erythema index suggested decreased vascular reactivity. Hydration levels improved consistently across all evaluated sites, and epidermal renewal was enhanced, as evidenced by reduced scaling and smoother skin surface. The melanin index remained stable throughout the study period. Conclusions: This pilot evaluation shows that bespoke cosmetic formulations, customized to individual skin biometry and preferences, can yield measurable improvements in hydration, barrier repair, elasticity, pigmentation uniformity, and epidermal renewal within 28 days, even in skin compromised by previous oncologic therapy. Given the single-subject nature of this pilot evaluation, these findings cannot be generalized to broader populations but rather highlight the importance of personalization and objective skin assessment in guiding individualized dermato-cosmetic formulation strategies. Personalized dermato-cosmetology using objective biophysical assessment may be a promising future strategy for effective, consumer-centered skincare. Full article

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, often accompanied by low-grade inflammation, visceral hypersensitivity and gut microbiota dysbiosis. In this study, the therapeutic potential of Lactiplantibacillus plantarum LPPerfectus001 (L. plantarum 001) was investigated to alleviate IBS symptoms. Using an Lipopolysaccharides (LPS)-induced RAW264.7 macrophage model, L. plantarum 001 demonstrated significant anti-inflammatory properties by inhibiting Nitric Oxide production and downregulating pro-inflammatory cytokines. Furthermore, in a mouse model of IBS induced by Citrobacter rodentium infection and water avoidance stress, L. plantarum 001 intervention reduced fecal moisture, improved intestinal barrier integrity via up-regulating of ZO-1 and MUC2, and attenuated visceral hypersensitivity. Transcriptomic analysis combining with RT-qPCR revealed that L. plantarum 001 modulated the NF-κB signaling pathway and Th1/Th2 cell differentiation, reducing expression of key inflammatory genes. Additionally, 16S rRNA sequencing showed that L. plantarum 001 restored gut microbiota diversity, enriched beneficial butyrate-producing Odoribacter, and suppressed pro-inflammatory Pseudomonadota. These findings suggested that L. plantarum 001 alleviates IBS through multi-targeted mechanisms involving barrier repair, microbiota modulation, and anti-inflammatory signaling, highlighting its potential as a probiotic therapy for IBS. Full article

Spinal Cord Injury (SCI) rehabilitation is undergoing a transformative shift with the emergence of new treatment strategies. Historically, treatment options were limited, and few offered meaningful recovery. Recent work in human models has shown that neuromodulation specifically with spinal cord epidural stimulation (SCES) paired with task-specific training (TsT) can partially restore motor function such as the ability to stand, step, and perform volitional movements. Despite these advances, the recovery has been shown to plateau even with the combination of therapies. The recovery process typically leads to partial rather than complete restoration of function. This limitation arises because current approaches primarily reactivate existing circuits rather than repair the disrupted pathways. Scar tissue and loss of descending and ascending connections remain major barriers to full recovery, restricting the transmission of neural signals. We argue that the next phase of research should be a synergistic strategy building upon the successes of neuromodulation and TsT while incorporating a regenerative therapy such as stem-cell-based interventions. Whereas neuromodulation and task-specific training increases excitability and reorganizes existing networks, stem cells have the potential to repair structural damage and re-establish communication across injured regions or facilitating the establishment of dormant pathways. The future of SCI recovery relies on multi-modal synergistic interventions that are likely to maximize long-term functional outcomes. In the current perspective, we summarized the basic findings on applications of SCES on restoration of sensory-motor functions. We then projected on current interventions on utilizing stem cell therapy intervention. We highlighted the outcomes of randomized clinical trials, and the major barriers for considering the synergistic approach between SCES and stem cell intervention. We are hopeful that this perspective may lead to roundtable scientific discussion to bridge the gap on how to conduct numerous clinical trials in the field. Full article

Spinal cord injury (SCI) remains one of the most formidable challenges in regenerative medicine, often resulting in permanent loss of motor, sensory, and autonomic function. Cell-based therapies offer a promising path toward repair by providing donor neurons and glia capable of integrating into host circuits, modulating the injury environment, and restoring function. Early studies employing fetal neural tissue and neural progenitor cells (NPCs) have demonstrated proof-of-principle for survival, differentiation, and synaptic integration. More recently, pluripotent stem cell (PSC)-derived donor populations and engineered constructs have expanded the therapeutic repertoire, enabling precise specification of interneuron subtypes, astrocytes, and oligodendrocytes tailored to the injured spinal cord. Advances in genetic engineering, including CRISPR-based editing, trophic factor overexpression, and immune-evasive modifications, are giving rise to next-generation donor cells with enhanced survival and controllable integration. At the same time, biomaterials, pharmacological agents, activity-based therapies, and neuromodulation strategies are being combined with transplantation to overcome barriers and promote long-term recovery. In this review, we summarize progress in designing and engineering donor cells and tissues for SCI repair, highlight how combination strategies are reshaping the therapeutic landscape, and outline opportunities for next-generation approaches. Together, these advances point toward a future in which tailored, multimodal cell-based therapies achieve consistent and durable restoration of spinal cord function. Full article

Background: Organ transplant offers patients a second chance at life, yet chronic rejection remains a formidable barrier to long-term success. Unlike the instantaneous storm of acute rejection, chronic rejection is a slow, unremitting process that silently remodels vessels, scars tissues, and diminishes graft function. At the center of this process are macrophages, immune “shapeshifters” that can heal or harm depending on their cues. Methods: This manuscript systematically reviews and synthesizes the current evidence from experimental studies and clinical observations, as well as molecular insights, to unravel how macrophages orchestrate chronic rejection. It travels over macrophage origins alongside their dynamic polarization into pro-inflammatory (M1) or pro-repair yet fibrotic (M2) states. The discussion integrates mechanisms of recruitment, antigen presentation, vascular injury, and fibrosis, while highlighting the molecular pathways (NF-κB, inflammasomes, STAT signaling, metabolic rewiring) that shape macrophage fate. Results: Macrophages play a central role in chronic rejection. Resident macrophages, once tissue peacekeepers, amplify inflammation, while recruited monocyte-derived macrophages fuel acute injury or dysfunctional repair. Together, they initiate transplant vasculopathy through cytokines, growth factors, and matrix metalloproteinases, slowly narrowing vessels and starving grafts. Donor-derived macrophages, often overlooked, act as early sentinels and long-term architects of fibrosis, blurring the line between donor and host immunity. At the molecular level, macrophages lock into destructive programs, perpetuating a cycle of inflammation, vascular remodeling, and scarring. Conclusions: Macrophages are not passive bystanders but pivotal decision makers in chronic rejection. Their plasticity, while a source of pathology, also opens therapeutic opportunities. Emerging strategies like macrophage-targeted drugs, immune tolerance approaches, gene and exosome therapies currently offer ways to reprogram these cells and preserve graft function. By shifting the macrophage narrative from saboteurs to guardians, transplantation medicine may transform chronic rejection from an inevitability into a preventable complication, extending graft survival from fleeting years into enduring decades. Full article

Meniscal preservation is increasingly recognized as a critical determinant of long-term knee joint health, yet successful repair remains challenging due to the meniscus’s limited intrinsic healing capacity. The adult meniscus is characterized by restricted vascularity, low cellularity, a dense extracellular matrix, complex biomechanical loading, and a hostile post-injury intra-articular inflammatory environment—factors that collectively impair meniscus healing, particularly in the avascular zones. Over the past several decades, a wide range of biologic augmentation strategies have been explored to overcome these barriers, including synovial abrasion, fibrin clot implantation, marrow stimulation, platelet-derived biologics, cell-based therapies, scaffold coverage, and emerging biologic and biophysical interventions. This review summarizes the biological basis of meniscal healing, critically evaluates current and emerging biologic augmentation techniques, and integrates these approaches within a unified framework of vascular, cellular, matrix, biomechanical, and immunologic targets. Understanding and modulating the cellular and molecular mechanisms governing meniscal degeneration and repair may enable the development of more effective, mechanism-driven strategies to improve healing outcomes and reduce the risk of post-traumatic osteoarthritis. Full article

Background/Objectives: Ocular graft-versus-host disease (oGVHD) is a chronic, immune-mediated complication of allogeneic hematopoietic stem cell transplantation that can progress to corneal ulceration or perforation. These cases are often refractory to standard therapy and present a high risk of graft failure after keratoplasty. We report a case of oGVHD-related corneal perforation successfully managed with a novel amniotic membrane-assisted “envelope” technique during corneal transplantation. Case Report: A 42-year-old man with chronic oGVHD and a full-thickness corneal perforation underwent urgent repair with a lamellar patch graft completely wrapped in cryopreserved amniotic membrane, followed by penetrating keratoplasty (PKP) using an amniotic membrane envelope surrounding the donor lenticule. Results: The amniotic membrane provided a 360° biological barrier that isolated graft antigens from the inflammatory environment while supporting epithelial healing and stromal remodeling. Despite recurrent inflammatory episodes and multiple procedures—including cataract extraction, pars plana vitrectomy, and multilayer amniotic membrane transplantation—the graft remained clear and stable at 12-month follow-up, achieving a best-corrected visual acuity of 20/40. Conclusions: The amniotic membrane envelope technique may represent a valuable adjunct in managing high-risk corneal perforations secondary to oGVHD. By combining immune modulation and regenerative support, this approach can enhance tectonic stability, reduce rejection risk, and promote durable surface recovery, potentially delaying or avoiding keratoprosthesis in refractory cases. Full article

Background/Objectives: Impaired intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). Akkermansia muciniphila and its outer membrane protein Amuc_1100 can enhance this barrier, but the clinical application of Amuc_1100 is limited by the fastidious growth of its native host. This study aimed to overcome this by utilizing the robust probiotic Lacticaseibacillus paracasei L9 for targeted Amuc_1100 delivery. Methods: We engineered Lc. paracasei L9 to express Amuc_1100 via intracellular (pA-L9), secretory (pUA-L9), and surface-display (pUPA-L9) strategies. Their efficacy was assessed in Lipopolysaccharide (LPS)-induced macrophages and a dextran sulfate sodium (DSS)-induced colitis mouse model, evaluating inflammation, barrier integrity, and mucosal repair. Results: The secretory (pUA-L9) and surface-display (pUPA-L9) strains most effectively suppressed pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in macrophages. In mice, both strains alleviated colitis and outperformed native A. muciniphila in improving disease activity. Crucially, they exhibited distinct, specialized functions: pUA-L9 acted as a systemic immunomodulator, reducing pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), elevating anti-inflammatory mediators (IL-4 and IL-10), and promoting goblet cell differentiation; notably, the inhibitory effect of pUA-L9 on IL-6 expression was approximately 2-fold greater than that of pUPA-L9. In contrast, pUPA-L9 excelled in local barrier repair, uniquely restoring mucus layer integrity (Muc1, Muc2, and Tff3) and reinforcing tight junctions (ZO-1, Occludin, Claudin1, Claudin3, and Claudin4). In particular, pUPA-L9 increased Muc2 expression by approximately 3.6-fold compared with pUA-L9. Conclusions: We demonstrate that the subcellular localization of Amuc_1100 within an engineered probiotic dictates its therapeutic mode of action. The complementary effects of secretory and surface-displayed Amuc_1100 offer a novel, spatially targeted strategy for precision microbiome therapy in IBD. Full article

Specialized pro-resolving mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, actively terminate inflammation and restore tissue homeostasis. This review addresses how specialized pro-resolving mediators (SPMs) and their omega-3/omega-6 PUFA precursors influence inflammatory pathways, disease mechanisms, and therapeutic potential across major inflammatory skin disorders. MEDLINE/PubMed was searched on 4 October 2025. Eligible studies included experimental, animal, mechanistic human, and interventional research examining SPMs or omega-3/omega-6 fatty acids. Non-English articles, reviews, conference abstracts, and dietary questionnaire–only studies were excluded. Two reviewers independently screened and extracted data. Due to heterogeneity, a narrative synthesis was performed. No formal risk-of-bias assessment was undertaken Of 359 records, 57 studies were included (26 psoriasis, 24 atopic dermatitis, 7 acne; scarce hidradenitis suppurativa data). Preclinical data consistently demonstrated that SPMs modulate key inflammatory pathways, support epithelial repair, and help restore immune balance. Human studies revealed altered cutaneous and systemic lipid mediator profiles—characterized by reduced omega-3–derived SPMs and predominance of omega-6-driven inflammatory mediators—suggesting impaired resolution mechanisms across these disorders. Interventional studies showed that omega-3 supplementation may reduce inflammatory markers, improve barrier function, and alleviate clinical symptoms. Early evidence on SPMs analogues and receptor agonists indicates promising therapeutic potential, but clinical data remain sparse. The body of evidence is limited by scarce human data, small sample sizes, heterogeneous interventions and variable methods. Many studies rely on subjective or non-standardized clinical outcomes, and the predominance of experimental models further limits the translational relevance of current findings. In summary, disturbances in PUFA-derived lipid mediator pathways and insufficient activation of pro-resolving mechanisms may contribute to the persistence of cutaneous inflammation. Omega-3 supplementation and SPMs-based novel therapies therefore represent plausible adjunctive approaches; however, their therapeutic relevance requires confirmation in future mechanistic and clinical studies. Full article

Demyelinating diseases comprise a group of chronic and debilitating neurological disorders, with the destruction of the myelin sheath serving as the core pathological hallmark. The central pathogenesis involves immune-mediated damage to oligodendrocytes (Ols) and myelin breakdown, accompanied by a vicious cycle of neuroinflammation and impaired epigenetic repair. Current therapeutic strategies, including conventional immunomodulatory agents to targeted monoclonal antibodies, effectively control disease relapses but exhibit limited efficacy in promoting neural repair. Consequently, research focus is increasingly shifting towards neuroprotective and remyelination strategies. In this context, Emerging therapeutic promise stems primarily from two fronts: the advent of novel pharmaceuticals, such as remyelination-promoting drugs targeting oligodendrocyte maturation, interventions inhibiting epigenetic silencing, signal pathway inhibitors, and natural products derived from traditional Chinese medicine; the development of innovative technologies, including cell therapies, gene therapy, exosome and nanoparticle-based drug delivery systems, as well as extracellular protein degradation platforms. Nevertheless, drug development still faces challenges such as disease heterogeneity, limited blood–brain barrier penetration, long-term safety, and difficulties in translating findings from preclinical models. Future efforts should emphasize precision medicine, multi-target synergistic therapies, and the development of intelligent delivery systems, with the ultimate goal of achieving a paradigm shift from delaying disability progression to functional neural reconstruction. Full article

Multiple Sclerosis (MS) therapies effectively modulate peripheral immune responses but largely fail to promote neural repair within the central nervous system. This review evaluates whether psychedelic compounds (PSYs), via 5-HT2A activation, can fill a critical therapeutic gap: the need for agents that simultaneously suppress neuroinflammation and promote regeneration. We dissect the evidence suggesting PSYs can reprogram the neuroimmune milieu by downregulating key pro-inflammatory cytokines (e.g., TNF-α, IL-6) in glial cells while concurrently upregulating crucial neurotrophic factors (e.g., BDNF) that promote synaptic plasticity and oligodendrocyte support. However, we argue that the current evidence, largely derived from non-specific inflammation models, is insufficient to predict clinical efficacy in an autoimmune disease like MS. We critically analyze the significant translational barriers—from cardiovascular and psychiatric risks to profound legal and ethical challenges—that temper the immediate clinical promise. Finally, we propose a forward-looking perspective, suggesting that the true value of PSYs may lie not in their direct clinical use, but in uncovering novel therapeutic pathways. The emergence of non-hallucinogenic, functionally selective 5-HT2A agonists, inspired by psychedelic pharmacology, represents a more viable strategy to harness these mechanisms for MS therapy, demanding rigorous preclinical validation in disease-relevant models. Full article

Hypertension is a major public health problem worldwide, and high-salt diets are one of the main causes of hypertension. The intestinal mucosal immune system is the largest immune organ in vertebrates. Hypertension was associated with increased intestinal permeability and an inflammatory state. The bacterial communities attached to the intestinal mucosa played a significant role in the development and maturation of the autoimmune system, as well as inflammation and immunity to disease. In this review, we focused on the relationship between the impaired intestinal barrier and the development and progression of hypertension under the high-salt dietary pattern. We systematically reviewed how a high-salt diet caused hypertension by disrupting the intestinal mechanical, chemical, and microbial barriers, interacting with immunogenic isolevuglandin (IsoLG)-protein adducts and microbiota, and activating the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Meanwhile, this review also summarizes the dietary therapy for hypertension, which involves supplementing natural antihypertensive substances and adjusting dietary patterns to repair the intestinal barrier and assist in lowering blood pressure. Such measures included supplementing plant-based foods, polyunsaturated fatty acids (PFAs), probiotics, prebiotics, food–medicine homologous substances (FMHS), vitamins, and minerals, as well as transforming high-salt dietary patterns into the dietary approaches to stop hypertension (DASH), the Mediterranean diet (MD), and the ketogenic diet (KD), with the aim of providing a reference for the occurrence, development, and dietary prevention and control of high-salt hypertension. Full article

Cardiac muscle has limited proliferative potential; therefore, loss of cardiomyocytes is irreversible and can cause or exacerbate heart failure. Although both pharmacological and non-pharmacological therapies are available, these interventions act primarily on surviving myocardium to manage symptoms and reduce—rather than reverse—adverse remodeling. The only curative option for end-stage heart failure remains heart transplantation; however, its clinical use is severely constrained by the shortage of donor organs. Consequently, regenerative therapies have gained increasing attention as potential novel treatments. Among these, cardiomyocytes derived from patient-specific pluripotent stem cells (PSCs) represent a particularly promising experimental platform for cardiac regeneration. To evaluate the potential of PSCs for cardiac repair through both in vivo and in vitro approaches, we (1) examined the hallmarks of cardiomyocyte maturation and the regulatory systems that coordinate these processes, (2) reviewed recent advances in maturation protocols and derivation techniques, (3) discussed how the cellular microenvironment enhances maturation and function, and (4) identified current barriers to clinical translation. Importantly, we integrated developmental biology with protocol design to provide a mechanistic foundation for PSC-based regeneration. Specifically, insights from cardiac development—such as signaling pathways governing proliferation, alignment, and excitation-contraction coupling—were explicitly linked to the refinement of PSC differentiation and maturation protocols. This developmental perspective allows us to bridge pathology and stem-cell methodology, explaining how disruptions in native cardiac maturation can inform strategies to produce functionally mature PSC-derived cardiomyocytes. Finally, we assessed the clinical prospects of PSC-derived cardiomyocytes, highlighting both the most recent advances and the persistent translational challenges that must be addressed before widespread therapeutic use. Full article

Ischemic stroke remains a major cause of mortality and long-term disability, yet current therapeutic strategies are largely limited to reperfusion approaches such as intravenous thrombolysis and thrombectomy, which are constrained by narrow treatment windows and the risk of complications. Moreover, the blood–brain barrier (BBB) severely restricts drug penetration into the injured brain, limiting the translation of promising neuroprotective agents into clinical success. Intranasal (IN) delivery has emerged as a compelling alternative route that bypasses the BBB and enables rapid access to the central nervous system through olfactory, trigeminal, and perivascular pathways. This narrative review highlights recent advances in preclinical research on IN therapeutics for ischemic stroke, ranging from small molecules and biologics to nucleic acids and cell-based therapies. Particular emphasis is placed on the application of nanotechnology, including extracellular vesicles, liposomes, and inorganic nanoparticles, which enhance drug stability, targeting, and bioavailability. Studies demonstrate that IN delivery of growth factors, cytokines, and engineered stem cells can promote neurogenesis, angiogenesis, white matter repair, and functional recovery, while nanocarriers further expand the therapeutic potential. Overall, intranasal delivery represents a promising and non-invasive strategy to overcome the limitations of conventional stroke therapies, offering new avenues for neuroprotection and regeneration that warrant further investigation toward clinical translation. Full article