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Search Results (239)

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14 pages, 1310 KB  
Review
Current Challenges of Managing Fibrosis Post Glaucoma Surgery and Future Perspectives
by Phey Feng Lo, Seok Ting Lim, Xiaomeng Wang and Tina T. Wong
J. Clin. Med. 2025, 14(23), 8548; https://doi.org/10.3390/jcm14238548 (registering DOI) - 2 Dec 2025
Abstract
The primary cause of post-operative failure following glaucoma filtration surgery is excessive bleb scarring. Traditional anti-fibrotics such as Mitomycin C (MMC) and 5-fluorouracil (5-FU) have greatly improved bleb survival but are not without their complications. Insights gained from traditional trabeculectomy studies can be [...] Read more.
The primary cause of post-operative failure following glaucoma filtration surgery is excessive bleb scarring. Traditional anti-fibrotics such as Mitomycin C (MMC) and 5-fluorouracil (5-FU) have greatly improved bleb survival but are not without their complications. Insights gained from traditional trabeculectomy studies can be directly applied to modern minimally invasive glaucoma surgery (MIGS) techniques. As surgical techniques continue to advance and overall safety improves, there is a growing need to explore other novel therapeutics that offer increased efficacy and favourable safety profiles. This review aims to provide insight into the pathophysiology of wound healing as well as discuss current and emerging strategies being developed to address wound healing post glaucoma filtration surgery. Full article
(This article belongs to the Special Issue Glaucoma Surgery: Current Challenges and Future Perspectives)
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32 pages, 2342 KB  
Review
Hypochlorous Acid: Clinical Insights and Experience in Dermatology, Surgery, Dentistry, Ophthalmology, Rhinology, and Other Specialties
by Vanda Haralović, Mislav Mokos, Sanja Špoljar, Lorena Dolački, Mirna Šitum and Liborija Lugović-Mihić
Biomedicines 2025, 13(12), 2921; https://doi.org/10.3390/biomedicines13122921 - 28 Nov 2025
Viewed by 74
Abstract
Background: Hypochlorous acid (HOCl) is an integral component of the human innate immune system. It possesses antimicrobial properties and is available in solution, dermal spray, and scar gel forms. Objectives/Methods: This review presents data from studies on the clinical use of HOCl in [...] Read more.
Background: Hypochlorous acid (HOCl) is an integral component of the human innate immune system. It possesses antimicrobial properties and is available in solution, dermal spray, and scar gel forms. Objectives/Methods: This review presents data from studies on the clinical use of HOCl in various specialties, including dermatology, surgery, dentistry, ophthalmology, and rhinology. Results: Due to its anti-inflammatory/antimicrobial/immunomodulatory and healing properties, HOCl is advantageous in treating various skin disorders: ulcus cruris (and wound care), diabetic ulcers, atopic dermatitis, seborrheic dermatitis, pruritus, acne vulgaris, etc. Also, the application of a HOCl spray/gel after surgical procedures may prevent infection, reduce inflammation, and accelerate healing. HOCl is also effective and safe for the prevention and treatment of hypertrophic and keloid scars. Growing evidence shows a broader role for HOCl in limiting cancer cell survival and slowing tumor growth. It is also important in treating various viral infections like SARS-CoV-2 (coronavirus), influenza, and herpes, thereby helping to prevent the spread of aerosols. In addition, since HOCl is an endogenous compound naturally present in mammals with a high safety profile, it may be an effective bacterial disinfectant in dental waterlines. In ophthalmology, adjuvant treatment with HOCl ophthalmic spray can reduce the duration of antibiotic/corticosteroid use, even in severe blepharitis. To fully harness the protective/therapeutic properties of HOCl, future advancements will rely on the development of new chemical compounds and sophisticated pharmaceutical formulations. Conclusions: The majority of clinical studies have confirmed that HOC1 is useful in therapy, although the results are not entirely consistent. Further research is essential to optimize HOCl dosing and to develop controlled-release systems aimed at maximizing its anti-inflammatory and photoprotective effects while minimizing tissue irritation and damage. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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20 pages, 2042 KB  
Article
Effect of 3′,4′-Dihydroxyflavonol Eye Drops in a Rat Model of Dispase-Induced Proliferative Vitreoretinopathy
by Elsa C. Chan, Cheng Zeng, Chi D. Luu, Carla J. Abbott, Nicholas T. Chan, Keshava K. Datta, Nicholas Williamson, Penelope J. Allen and Jennifer C. Fan Gaskin
Antioxidants 2025, 14(12), 1414; https://doi.org/10.3390/antiox14121414 - 27 Nov 2025
Viewed by 109
Abstract
(1) Background: Proliferative vitreoretinopathy (PVR) is the most common cause of failure in retinal detachment surgery and often leads to blindness. Oxidative stress is known to contribute to scar formation; therefore, reducing oxidative stress may protect against PVR development. This study investigated the [...] Read more.
(1) Background: Proliferative vitreoretinopathy (PVR) is the most common cause of failure in retinal detachment surgery and often leads to blindness. Oxidative stress is known to contribute to scar formation; therefore, reducing oxidative stress may protect against PVR development. This study investigated the therapeutic effects of the antioxidant 3′,4′-dihydroxyflavonol (DiOHF) in two preclinical models of PVR. (2) Methods: A retinal pigment epithelial cell line (ARPE-19) was used to investigate the anti-fibrotic effects of DiOHF. PVR was induced in one eye of each animal using dispase. Animals then received either vehicle or DiOHF eye drops in both eyes for 28 days. Eyes were harvested for mass spectrometry to perform proteomic analysis or to quantify tissue accumulation of DiOHF. Proteomic analysis was also performed in ARPE to validate these findings. (3) Results: In DiOHF-treated eyes with induced PVR, proteomic profiles showed reduced fibrosis, inflammation, cell migration, and oxidative stress compared with vehicle-treated PVR eyes. The in vitro studies confirmed that DiOHF inhibited wound healing responses, cell contraction, proliferation, and the generation of reactive oxygen species in ARPE-19 cells. Proteomic analysis in ARPE-19 also showed a similar trend. (4) Conclusions: This study provides compelling evidence that DiOHF eye drops offer protective effects against PVR in preclinical models. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in Eye Diseases)
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24 pages, 2759 KB  
Article
Factors Released by Polarized Neutrophil-like Cells Modulate Cardiac Fibroblast Phenotype and Limit the Inflammatory Response After Myocardial Infarction
by Letitia Ciortan, Ana-Maria Gan, Sergiu Cecoltan, Mihaela Serbanescu, Andreea Cristina Mihaila, Razvan Daniel Macarie, Monica Madalina Tucureanu, Miruna Larisa Naie, Mihai Bogdan Preda, Bogdan-Paul Cosman, Galyna Bila, Rostyslav Bilyy and Elena Butoi
Biomedicines 2025, 13(11), 2829; https://doi.org/10.3390/biomedicines13112829 - 20 Nov 2025
Viewed by 277
Abstract
Background: Following myocardial infarction (MI), cardiac fibroblasts (CFs) adopt distinct phenotypes to ensure scar formation and healing. Although leukocytes are a critical driver of post-MI healing, the role of neutrophils in modulating CF phenotype remains insufficiently explored. We therefore investigated the impact [...] Read more.
Background: Following myocardial infarction (MI), cardiac fibroblasts (CFs) adopt distinct phenotypes to ensure scar formation and healing. Although leukocytes are a critical driver of post-MI healing, the role of neutrophils in modulating CF phenotype remains insufficiently explored. We therefore investigated the impact of soluble mediators released by neutrophil subtypes found post-MI—pro-inflammatory (N1) and anti-inflammatory (N2)—on shaping CFs phenotype. Methods: In vitro, human 3D grown CFs were indirectly co-cultured with N1 or N2 neutrophil-like cells using a two-chamber Transwell system. After 24 h, expression of inflammatory, remodeling, and pro-fibrotic markers was evaluated in fibroblasts and conditioned media. In vivo, soluble mediators derived from polarized mouse neutrophils (SN1 or SN2) were injected into the infarcted myocardium of C57BL/6J after MI surgery. The effects on the healing process were investigated at 1 and 7 days post-MI. Results: In vitro, CFs were found to exhibit a pro-inflammatory and matrix-degrading phenotype following indirect co-culture with N1 cells, characterized by overexpression of IL-1β, IL-6, MCP-1, and metalloproteases MMP-3/MMP-9. In vivo, both SN1 and SN2 treatments significantly reduced pro-inflammatory markers IL-1β and IL-6 gene expression at day 1 post-MI (inflammatory phase). At day 7 post-MI (resolution phase), SN1/SN2 treatments continued to limit local inflammation, while mitigating fibrotic remodeling by reducing CCN2, α-SMA, and key extracellular matrix proteins. Conclusions: Together, these findings suggest that while N1-derived mediators promote a pro-inflammatory fibroblast phenotype in vitro, factors secreted by both N1 and N2 support a more balanced reparative response in vivo, by limiting local inflammation and potentially mitigating adverse remodeling post-MI. Full article
(This article belongs to the Special Issue Coronary Artery Disease: Current Evidence and Future Perspectives)
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17 pages, 2405 KB  
Article
Botryocladia leptopoda Extracts Promote Wound Healing Ability via Antioxidant and Anti-Inflammatory Activities and Regulation of MMP/TIMP Expression
by Shin-Ping Lin, Tsung-Kai Yi, Yi-Feng Kao, Ming-Chieh Tu, Chen-Che Hsieh, Yu-Chieh Chou, Jheng-Jhe Lu, Shella Permatasari Santoso, Huey-Jine Chai and Kuan-Chen Cheng
Mar. Drugs 2025, 23(11), 444; https://doi.org/10.3390/md23110444 - 19 Nov 2025
Viewed by 371
Abstract
Wound healing is a complex process involving coordinated actions of multiple cell types. Therefore, when developing therapeutics to promote wound healing, it is essential to consider the synergistic contributions of various cells at different stages of the healing process. In this study, we [...] Read more.
Wound healing is a complex process involving coordinated actions of multiple cell types. Therefore, when developing therapeutics to promote wound healing, it is essential to consider the synergistic contributions of various cells at different stages of the healing process. In this study, we evaluated the potential of different extracts of Botryocladia leptopoda as wound-healing agents by examining their effects on antioxidant activity, cytotoxicity, cell migration, anti-inflammatory properties, and expressions of specific biomarkers associated with wound healing. Results indicated that the ethanol extract (FE) and hexane extract (HE) exhibited the highest DPPH radical scavenging activity, reaching up to 94%. The alkaline extract (AE) showed the strongest antioxidant ability in the FICA assay, with a maximum of 99%. In addition, the FE and AE provided anti-inflammatory actions that inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-6 in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Further analyses suggested that the FE and AE enhanced cell proliferation (210% and 112%) and migration (442.2% and 535.6%) and regulated wound healing-related genes, including matrix metalloproteinase 2, MMP9, and tissue inhibitor of metalloproteinase 2 (TIMP2) to avoid scar formation and accelerate wound healing. Lastly, the identification of potential compounds within the extract using the UHPLC system further supports its prospective medical applications. Taken together, these findings indicated that the FE and AE from B. leptopoda exhibited remarkable in vitro wound-healing properties, highlighting their potential for applications in pharmaceutical industries and health food development. Full article
(This article belongs to the Special Issue The Extraction and Application of Functional Components in Algae)
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26 pages, 1682 KB  
Review
Surgical Outcomes in Non-Transected and Partially Transected Peripheral Nerve Injuries
by Naveen Arunachalam Sakthiyendran, Karter Morris, Caroline J. Cushman, Evan J. Hernandez, Anceslo Idicula and Brendan J. MacKay
Brain Sci. 2025, 15(11), 1202; https://doi.org/10.3390/brainsci15111202 - 7 Nov 2025
Viewed by 770
Abstract
Background: Non-transected and partially transected peripheral nerve injuries (neuromas-in-continuity) are relatively common but understudied. Their optimal surgical management and expected outcomes remain unclear. We conducted a literature review of surgical repairs in such lesions and illustrate a case to guide decision-making. Systematic searches [...] Read more.
Background: Non-transected and partially transected peripheral nerve injuries (neuromas-in-continuity) are relatively common but understudied. Their optimal surgical management and expected outcomes remain unclear. We conducted a literature review of surgical repairs in such lesions and illustrate a case to guide decision-making. Systematic searches of PubMed and Google Scholar identified 70 eligible reports (Level I = 2, Level II = 5, Level III = 37, Level IV = 20, Level V = 4). Across studies, neurolysis of NAP-positive lesions often restored antigravity strength, while direct repair or grafting of nonconductive segments yielded meaningful recovery in ~75%. After neurolysis or reconstruction, ~77–92% of brachial plexus/axillary neuromas-in-continuity reached LSUHSC Grade ≥3. Median/ulnar lesions treated with neurolysis, biologic/vascularized coverage, or reconstruction showed reliable pain relief but variable sensory/motor recovery. Radial/PIN lesions improved in some series irrespective of NAPs. Earlier intervention, shorter gaps, distal sites, and younger age correlated with superior outcomes. Meanwhile, prolonged observation risking end-organ atrophy degraded results. Adjuncts such as electrical stimulation and wraps may aid reinnervation or reduce scarring, though high-quality evidence is limited. Conclusions: For non-transected and partially transected PNIs, a pragmatic approach emerges: Observe low-grade injuries with serial examinations. Explore early if recovery stalls (≈3–6 months). Use NAP-guided neurolysis for conductive lesions. Perform tension-free repair or grafting for nonconductive segments, adding anti-adhesive coverage when appropriate. Standardized reporting and prospective trials are needed to refine timing, technique selection, and patient-reported outcomes. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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36 pages, 1826 KB  
Review
Platelet-Rich Plasma (PRP): Molecular Mechanisms, Actions and Clinical Applications in Human Body
by Wen-Shan Wu, Li-Ru Chen and Kuo-Hu Chen
Int. J. Mol. Sci. 2025, 26(21), 10804; https://doi.org/10.3390/ijms262110804 - 6 Nov 2025
Viewed by 2534
Abstract
Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, [...] Read more.
Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, including single- or double-spin centrifugation and buffy coat techniques, influence the final composition of PRP, determining the relative proportions of platelets, leukocytes, plasma proteins, and extracellular vesicles. These components act synergistically, with platelets releasing growth factors (e.g., VEGF, PDGF, TGF-β) that stimulate angiogenesis and matrix synthesis, leukocytes providing immunomodulation, plasma proteins facilitating scaffolding, and exosomes regulating intercellular signaling. Mechanistically, PRP enhances tissue repair through four key pathways: platelet adhesion molecules promote hemostasis and cell recruitment; immunomodulation reduces pro-inflammatory cytokines and favors M2 macrophage polarization; angiogenesis supports vascular remodeling and nutrient delivery; and serotonin-mediated pathways contribute to analgesia. These processes establish a regenerative microenvironment that supports both structural repair and functional recovery. Clinically, PRP has been applied across multiple specialties. In orthopedics, it promotes tendon, cartilage, and bone healing in conditions such as tendinopathy and osteoarthritis. In dermatology, PRP enhances skin rejuvenation, scar remodeling, and hair restoration. Gynecology has adopted PRP for ovarian rejuvenation, endometrial repair, and vulvovaginal atrophy. In dentistry and oral surgery, PRP accelerates wound closure and osseointegration, while chronic wound care benefits from its angiogenic and anti-inflammatory effects. PRP has also favored gingival recession coverage, regeneration of intrabony periodontal defects, and sinus grafting. Although preparation heterogeneity remains a challenge, PRP offers a versatile, biologically active therapy with expanding clinical utility. Full article
(This article belongs to the Section Biochemistry)
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21 pages, 4106 KB  
Article
Therapeutic Effect of Alpha Linolenic Acid on Cutaneous Wound Healing in Hyperglycemic Mice: Involvement of Neurotrophins
by Thais Paulino do Prado, Flávia Cristina Zanchetta, Aline Cristina Rosa Maria, Thaiane da Silva Rios, Guilherme Rossi de Assis-Mendonça, Maria Helena Melo Lima, Dennys Esper Correa Cintra, Joseane Morari, Lício A. Velloso and Eliana P. Araújo
Pharmaceutics 2025, 17(11), 1427; https://doi.org/10.3390/pharmaceutics17111427 - 4 Nov 2025
Viewed by 554
Abstract
Background: Alpha-linolenic acid (ALA) is an essential fatty acid from the omega-3 family that plays an important role in skin homeostasis. It is known for its anti-inflammatory properties, which can contribute to wound healing. Neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF), may also [...] Read more.
Background: Alpha-linolenic acid (ALA) is an essential fatty acid from the omega-3 family that plays an important role in skin homeostasis. It is known for its anti-inflammatory properties, which can contribute to wound healing. Neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF), may also play an important role in the skin, influencing nerve regeneration and pain modulation. Objectives: This article aims to explore the therapeutic effect of ALA on wound healing in streptozotocin-induced hyperglycemic mice, with an emphasis on the involvement of neurotrophins. Methods: We used keratinocyte cultures exposed or not to ALA and male C57BL6-J mice, which were randomly divided into four groups: non-hyperglycemic treated with vehicle; non-hyperglycemic treated with ALA; hyperglycemic treated with vehicle; and hyperglycemic treated with ALA. The treatment was administered continuously via a subcutaneous osmotic pump. Results: We found that controlled ALA administration potentiates the wound healing process in hyperglycemic mice by accelerating the inflammatory phase and promoting early granulation tissue formation (73.2% ± 0.7 vs. 92.2% ± 2.8 on day 7, n = 5; p < 0.05). This is supported by the balance between the expression of vimentin, CD31, and MMP-9. Furthermore, ALA modulates proteins linked to peripheral neurogenesis and gliogenesis, such as BDNF, NTRK2, SOX-10, CNTF, CTNFR, and STAT-3. It may also promote wound healing and nerve regeneration at the wound site in hyperglycemic animals. In non-hyperglycemic mice, ALA improves the quality of scars but does not accelerate the wound healing process, even with the positive modulation of certain genes relevant to skin healing. Conclusions: Alpha-linolenic acid improves skin wound healing and increases gene expression related to nerve regeneration in wounds of hyperglycemic mice. Full article
(This article belongs to the Section Gene and Cell Therapy)
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14 pages, 1732 KB  
Review
Misleading Lesions in Gynecological Malignancies: A Case Report of Desmoid Tumor During Pregnancy and a Narrative Review of the Literature
by Emma Bonetti Palermo, Federico Ferrari, Cecilia Dell’Avalle, Ilaria Nodari, Emma Paola Ongarini, Iacopo Ghini, Andrea Giannini, Hooman Soleymani majd, Giuseppe Ciravolo and Franco Odicino
J. Clin. Med. 2025, 14(21), 7815; https://doi.org/10.3390/jcm14217815 - 3 Nov 2025
Viewed by 524
Abstract
Background: Desmoid tumors (DTs) are rare, locally aggressive soft-tissue neoplasms that often affect women of reproductive age. Pregnancy and prior abdominal surgery or trauma have been associated with tumor development and growth, while imaging frequently overlaps with abdominal-wall endometriosis. We present the [...] Read more.
Background: Desmoid tumors (DTs) are rare, locally aggressive soft-tissue neoplasms that often affect women of reproductive age. Pregnancy and prior abdominal surgery or trauma have been associated with tumor development and growth, while imaging frequently overlaps with abdominal-wall endometriosis. We present the case of a 39-year-old woman with an abdominal-wall DT and provide a narrative review of the literature focused on pregnancy/postpartum patterns, differential diagnosis, and management. Methods: A narrative review of PubMed/MEDLINE and Web of Science (January 1982–December 2024) was conducted. We included English-language case reports/series, narrative/descriptive reviews, and consensus statements relevant to DTs in pregnancy or reproductive-age women, emphasizing abdominal-wall disease. Results: The patient’s right abdominal-wall mass enlarged during pregnancy and further post-partum imaging repeatedly suggested endometriosis. En bloc resection revealed desmoid-type fibromatosis composed of bland spindle cells in a collagenous stroma, with nuclear β-catenin and lymphoid enhancer–binding factor 1 (LEF1) positivity on immunohistochemistry. Magnetic resonance imaging (MRI) at 12 months showed no recurrence. Across included studies, pregnancy and post-partum enlargement is common, abdominal-wall DTs frequently mimic scar endometriosis, and pre-operative ultrasound has limited specificity. Current practice supports watch-and-wait for stable, asymptomatic lesions and function-preserving surgery for symptomatic progression, while systemic options (anti-estrogens, low-dose chemotherapy, and tyrosine kinase inhibitors) are reserved for progressive or unresectable disease. Recurrence risk relates to age, size, site, and β-catenin status; future pregnancy is not contraindicated. Conclusions: Abdominal-wall DTs, although rare, should be considered in the differential diagnosis of reproductive-age women presenting with abdominal-wall masses, particularly during or after pregnancy. Full article
(This article belongs to the Section Oncology)
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31 pages, 821 KB  
Review
Cross-Talk Between Neutrophils and Macrophages Post-Myocardial Infarction: From Inflammatory Drivers to Therapeutic Targets
by Letitia Ciortan, Razvan Daniel Macarie, Elena Barbu, Miruna Larisa Naie, Andreea Cristina Mihaila, Mihaela Serbanescu and Elena Butoi
Int. J. Mol. Sci. 2025, 26(21), 10575; https://doi.org/10.3390/ijms262110575 - 30 Oct 2025
Viewed by 1128
Abstract
Acute myocardial infarction (MI) is a major cardiovascular event and a leading cause of mortality worldwide. Beyond the initial ischemic injury, the inflammatory and immune responses play pivotal roles in both tissue damage and subsequent healing. While the anti-inflammatory strategies targeting neutrophil-driven injury [...] Read more.
Acute myocardial infarction (MI) is a major cardiovascular event and a leading cause of mortality worldwide. Beyond the initial ischemic injury, the inflammatory and immune responses play pivotal roles in both tissue damage and subsequent healing. While the anti-inflammatory strategies targeting neutrophil-driven injury have demonstrated potential in limiting early cardiac damage, growing evidence highlights the critical role of innate immune cells beyond the acute phase. Neutrophils, traditionally associated with tissue injury, also contribute to the resolution of inflammation and initiate key repair processes. Monocytes and macrophages follow a dynamic trajectory, transitioning from pro-inflammatory to reparative states, and play essential roles in debris clearance, angiogenesis, and scar formation. In the early inflammatory phase of acute MI, immune cells such as neutrophils and monocytes are rapidly recruited and activated. While they initially amplify inflammation through the release of pro-inflammatory mediators, their subsequent transition toward anti-inflammatory and reparative phenotypes helps limit tissue damage by clearing necrotic debris from the infarcted area and contributes to the resolution of inflammation. Accumulating evidence reveals a complex crosstalk between neutrophils and macrophages post-MI, with resident macrophages being involved in neutrophil recruitment, and neutrophil-derived signals participating in monocyte recruitment and macrophage polarization, thereby coordinating the spatial and temporal phases of cardiac repair. Understanding how neutrophil-derived mediators influence macrophage responses and whether macrophage-secreted factors reciprocally modulate neutrophil behavior opens promising pathways for developing targeted therapies to limit adverse remodeling following MI. Therefore, this review aims to (i) provide an overview of the roles of neutrophils and monocytes/macrophages in the pathophysiology of myocardial infarction, (ii) explore the mechanisms of communication, particularly via neutrophil-derived secreted factors, that influence monocyte/macrophage function and impact post-MI inflammation, repair, and remodeling, and (iii) highlight the potential therapies interfering with inflammation and neutrophil/macrophage cross-talk. Full article
(This article belongs to the Special Issue Cellular and Molecular Progression of Cardiovascular Diseases)
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33 pages, 1907 KB  
Review
Topical β-Caryophyllene for Dermatologic Disorders: Mechanisms, Human Evidence, and Clinical Translation
by Amina M. Bagher
Pharmaceuticals 2025, 18(11), 1605; https://doi.org/10.3390/ph18111605 - 23 Oct 2025
Cited by 1 | Viewed by 1182
Abstract
Background: Chronic inflammatory skin disorders, including atopic dermatitis, psoriasis, acne, and chronic wounds, affect nearly two billion people worldwide, impose substantial morbidity and economic burden, and remain only partially controlled by existing therapies. The cutaneous endocannabinoid system (ECS), comprising cannabinoid receptors, endocannabinoids, and [...] Read more.
Background: Chronic inflammatory skin disorders, including atopic dermatitis, psoriasis, acne, and chronic wounds, affect nearly two billion people worldwide, impose substantial morbidity and economic burden, and remain only partially controlled by existing therapies. The cutaneous endocannabinoid system (ECS), comprising cannabinoid receptors, endocannabinoids, and their metabolic enzymes, regulates inflammation, pruritus, barrier integrity, and tissue repair; cannabinoid receptor type 2 (CB2) has emerged as a particularly relevant target. β-Caryophyllene (BCP), a dietary sesquiterpene and highly selective CB2 agonist with favorable safety and pharmacokinetic attributes, has attracted attention as a promising topical candidate. Methods: We systematically searched PubMed, Embase, and Web of Science (inception–30 July 2025) for studies on “β-caryophyllene” and dermatological outcomes, prioritizing purified BCP and analytically characterized BCP-rich fractions. Quantitative parameters, including tested concentration ranges (0.5 µM–10%) and principal mechanistic outcomes, were extracted to provide a translational context. Results: BCP penetrates the stratum corneum, suppresses NF-κB/MAPK and IL-4/TSLP pathways, enhances Nrf2-driven antioxidant defenses, and accelerates re-epithelialization and collagen remodeling. Across in vitro, in vivo, and formulation studies, BCP produced consistent anti-inflammatory and barrier-restorative effects within this concentration range. CB2 antagonism attenuated these responses, confirming receptor specificity. BCP’s volatility and autoxidation to β-caryophyllene oxide (BCPO) necessitate stability-by-design strategies using antioxidants, low-oxygen processing, and protective packaging. Human evidence, limited to BCP-rich botanicals such as Copaifera oleoresins, suggests benefits for scars, wounds, and acne but lacks compound-specific validation. Conclusions: BCP exhibits coherent CB2-mediated anti-inflammatory, antipruritic, antioxidant, and reparative actions with a favorable safety profile. Dose-defined, oxidation-controlled clinical trials of purified BCP are warranted to establish its potential as a steroid-sparing topical therapy. Full article
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25 pages, 3411 KB  
Review
Retinal Laser Therapy Mechanisms, Innovations, and Clinical Applications
by Xinyi Xie, Luqman Munir and Yannis Mantas Paulus
Photonics 2025, 12(11), 1043; https://doi.org/10.3390/photonics12111043 - 22 Oct 2025
Viewed by 1455
Abstract
Retinal laser therapy has been a mainstay for treating proliferative diabetic retinopathy, retinal vascular disease, and retinal breaks since 1961. However, conventional millisecond photocoagulation can cause permanent scarring and procedure discomfort, motivating the development of damage-sparing approaches that preserve the neurosensory retina. Clinically, [...] Read more.
Retinal laser therapy has been a mainstay for treating proliferative diabetic retinopathy, retinal vascular disease, and retinal breaks since 1961. However, conventional millisecond photocoagulation can cause permanent scarring and procedure discomfort, motivating the development of damage-sparing approaches that preserve the neurosensory retina. Clinically, panretinal photocoagulation remains effective for proliferative disease but trades off peripheral visual field and night vision. This review synthesizes development, mechanisms, and clinical evidence for laser modalities, including short-pulse selective retinal therapy (SRT), subthreshold diode micropulse (SDM), and pattern-scanning photocoagulation. We conducted a targeted narrative search of PubMed/MEDLINE, Embase, Web of Science, and trial registries (1960–September 2025), supplemented by reference list screening. We prioritized randomized/prospective studies, large cohorts, systematic reviews, mechanistic modeling, and relevant preclinical work. Pulse duration is the primary determinant of laser–tissue interaction. In the microsecond regime, SRT yields retinal pigment epithelium (RPE)-selective photodisruption via microcavitation and uses real-time optoacoustic or OCT feedback. SDM 100–300 µs delivers nondamaging thermal stress with low duty cycles and titration-based dosing. Pattern-scanning platforms improve throughput and tolerance yet remain destructive photocoagulation. Feedback-controlled SRT shows anatomic/functional benefit in chronic central serous chorioretinopathy and feasibility in diabetic macular edema. SDM can match threshold macular laser for selected DME and may reduce anti-VEGF injection burden. Sub-nanosecond “rejuvenation” lasers show no overall benefit in intermediate AMD and may be harmful in specific phenotypes. Advances in delivery, dosimetry, and closed-loop feedback aim to minimize collateral damage while retaining therapeutic effect. Key gaps include head-to-head trials (SRT vs. PDT/SDM), standardized feedback thresholds across pigmentation and devices, and long-term macular safety to guide broader clinical adoption. Full article
(This article belongs to the Special Issue Novel Techniques and Applications of Ophthalmic Optics)
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16 pages, 2928 KB  
Article
Immunomodulatory Potential of a Composite Amniotic Membrane Hydrogel for Wound Healing: Effects on Macrophage Cytokine Secretion
by Tao Wang, Zhiyuan Zhu, Wei Hua and Siliang Xue
Biomedicines 2025, 13(10), 2574; https://doi.org/10.3390/biomedicines13102574 - 21 Oct 2025
Cited by 1 | Viewed by 604
Abstract
Background: The human acellular amniotic membrane (HAAM) is widely used as a decellularized bioscaffold in tissue engineering to promote wound healing, but its clinical application is limited by poor mechanical properties, rapid degradation, and handling difficulties. This study aimed to develop a modified [...] Read more.
Background: The human acellular amniotic membrane (HAAM) is widely used as a decellularized bioscaffold in tissue engineering to promote wound healing, but its clinical application is limited by poor mechanical properties, rapid degradation, and handling difficulties. This study aimed to develop a modified amniotic membrane-based composite material loaded with vascular endothelial growth factor (VEGF) and the Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-Lalanylhydrazide]-Sphenylglycine t-butyl ester (DAPT) to enhance wound healing by modulating macrophage polarization and cytokine secretion. Methods: VEGF-loaded gellan gum-hyaluronic acid (GG-HA) hydrogels (VEGF-GG-HA) and DAPT-loaded HAAM (DAPT-HAAM) were prepared and combined to form a novel composite material (VEGF-GG-HA & DAPT-HAAM). The morphology and microstructure of the materials were characterized using scanning electron microscopy. In vitro studies were conducted using the human monocytic cell line (Tohoku Hospital Pediatrics-1, THP-1) to evaluate the effects of the materials on cell viability, cytokine secretion, and protein expression. Assessments included CCK-8 assays, ELISA, quantitative real-time PCR, Western blot analysis, and immunohistochemical staining. Results: The composite material VEGF-GG-HA & DAPT-HAAM exhibited good biocompatibility and significantly promoted THP-1 cell proliferation compared to control and single-component groups. It enhanced the secretion of IL-10, TNF-α, TGF-β, MMP1, and MMP3, while suppressing excessive TGF-β overexpression. The material also modulated macrophage polarization, showing a trend toward anti-inflammatory M2 phenotypes while maintaining pro-inflammatory signals (e.g., TNF-α) for a balanced immune response. Conclusions: The modified amniotic membrane hydrogel composite promotes wound healing through a phased immune response: it modulates macrophage polarization (balancing M1 and M2 phenotypes), enhances cytokine and matrix metalloproteinase secretion, and controls TGF-β levels. These effects contribute to improved vascular remodeling, reduced fibrosis, and prevention of scar formation, demonstrating the potential for enhanced wound management. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Regeneration)
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12 pages, 3340 KB  
Article
Navigating the Decision to Discontinue Intravitreal Injection Therapy in End-Stage Neovascular Age-Related Macular Degeneration
by Justin Bennie and David J. Ramsey
J. Pers. Med. 2025, 15(10), 487; https://doi.org/10.3390/jpm15100487 - 13 Oct 2025
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Abstract
Introduction: The management of neovascular age-related macular degeneration (nAMD) is constrained by diminishing therapeutic options for retina specialists and their patients when the disease reaches its end stages. Methods: Clinical insights emerge from two case narratives in which patients benefitted from discontinuation of [...] Read more.
Introduction: The management of neovascular age-related macular degeneration (nAMD) is constrained by diminishing therapeutic options for retina specialists and their patients when the disease reaches its end stages. Methods: Clinical insights emerge from two case narratives in which patients benefitted from discontinuation of anti-VEGF therapy. Results: Long-term management of nAMD with intravitreal injections of agents targeting vascular endothelial growth factor (VEGF) is crucial for slowing progression of the disease and is generally well-tolerated. However, vision often declines as the disease progresses over time, even with treatment. This article presents strategies for aligning therapeutic goals with their expected visual outcome when an eye has reached end-stage disease. It addresses considerations for how and when to stop treatment when vision becomes limited, taking into consideration the visual status of the fellow eye and incorporating input from low vision specialists who can better assess best-corrected visual acuity (BCVA) and optimize the visual function of patients. We also acknowledge the potential benefits of switching either the dose or the agent that targets VEGF to alter the long-term visual outcome of treatment. Finally, we discuss the importance of taking into consideration related manifestations of the disease, such as macular scarring, geographic atrophy, or other retinal or optic nerve diseases which may limit vision and thus the utility of continued nAMD treatment. Conclusions: Building a strong patient–physician relationship is essential for navigating the shared decision-making process of when to stop treatment for nAMD. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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Case Report
Cutaneous Leishmaniasis in the Immunocompromised: Diagnostic and Therapeutic Insights from a Case Documented in Central Italy
by Laura Povolo, Anna Barbiero, Michele Spinicci, Nicola Petrosillo, Alessandro Bartoloni and Lorenzo Zammarchi
Infect. Dis. Rep. 2025, 17(5), 125; https://doi.org/10.3390/idr17050125 - 8 Oct 2025
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Abstract
Introduction: Cutaneous leishmaniasis (CL) poses a number of challenges when it comes to diagnosis and treatment, due to the variety of clinical presentations that mimic other conditions and hinder the choice of the most appropriate therapeutic approach, especially in the context of immunodepression. [...] Read more.
Introduction: Cutaneous leishmaniasis (CL) poses a number of challenges when it comes to diagnosis and treatment, due to the variety of clinical presentations that mimic other conditions and hinder the choice of the most appropriate therapeutic approach, especially in the context of immunodepression. Case presentation: We present the case of a 63-year-old woman on anti-tumor necrosis factor (TNF) therapy, who underwent surgical excision for the diagnostic purposes of a chronic non-healing lesion located on her right arm. The histopathological examination revealed the presence of Leishmania amastigotes. CL relapsed in the following months, with new lesions appearing both close to the excision scar and at a different body site. At this point, in order to avoid another surgical intervention, cutaneous swabs for Leishmania Polymerase Chain Reaction (PCR) were performed on both lesions. Both samples yielded positive results, and the patient was treated with a 4-week course of miltefosine. Conclusions: These results support the use of cutaneous swabs as a highly sensitive and less invasive tool for the diagnostic workup of CL. In addition, our case prompts a reflection on the management of immunosuppressed patients with CL, with particular emphasis on the risk of reactivation or simultaneous involvement of multiple anatomical sites, thus suggesting the need for specific considerations and personalized management for this group of subjects. Full article
(This article belongs to the Section Neglected Tropical Diseases)
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