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Background Juvenile localized scleroderma is a rare pediatric inflammatory disease that primarily affects the skin and subcutaneous tissue but also has the potential to impact deeper tissues and can be associated with extracutaneous manifestations, leading to substantial impairment and disability. Management approaches vary, but in recent years, expert groups have attempted to streamline the approach to care with consensus treatment plans. Methods This retrospective cohort study included pediatric juvenile localized scleroderma patients with ≥  3 years of follow-up identified within a 21-year period (1999–2020) at a single tertiary care pediatric hospital in the USA. Data on demographics, disease characteristics, and treatment trends were analyzed, with a focus on systemic versus topical therapy and treatment trends before and after the publication of the Childhood Arthritis and Rheumatology Research Alliance juvenile localized scleroderma consensus treatment plan in 2012. Results A total of 101 juvenile localized scleroderma patients fulfilled our inclusion criteria. Sixty-three patients were treated with systemic therapy, and 38 were treated with topical therapy. Patients on systemic therapy were more commonly treated in a combined rheumatology-dermatology program (67%) or rheumatology clinic (30%), whereas those on topical therapy were primarily treated in a dermatology clinic (71%). Starting in 2013, a significantly greater percentage of all patients were treated in the combined program (47% vs. 20%, p  = 0.008), and a significantly greater percentage of patients received systemic therapy (78% vs. 55%, p  < 0.05). Conclusion This juvenile localized scleroderma cohort is one of the largest reported from a single center and demonstrated an increase in the use of systemic therapy following the publication of the Childhood Arthritis and Rheumatology Research Alliance juvenile localized scleroderma consensus treatment plan in 2012. Further studies on long-term treatment outcomes and therapeutic approaches utilized when first-line treatment failures occur are warranted.

In 2012, a European initiative called Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile localised scleroderma (JLS) is a rare disease within the group of paediatric rheumatic diseases (PRD) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians’ experience. This study aims to provide recommendations for assessment and treatment of JLS. Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was formed, mainly from Europe, and consisted of 15 experienced paediatric rheumatologists and two young fellows. Recommendations derived from a validated systematic literature review were evaluated by an online survey and subsequently discussed at two consensus meetings using a nominal group technique. Recommendations were accepted if ≥80% agreement was reached. In total, 1 overarching principle, 10 recommendations on assessment and 6 recommendations on therapy were accepted with ≥80% agreement among experts. Topics covered include assessment of skin and extracutaneous involvement and suggested treatment pathways. The SHARE initiative aims to identify best practices for treatment of patients suffering from PRDs. Within this remit, recommendations for the assessment and treatment of JLS have been formulated by an evidence-informed consensus process to produce a standard of care for patients with JLS throughout Europe.

Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal homogenized collagen synthesis. Fractional ablative laser resurfacing has been used effectively in scar treatment via abnormal collagen degradation and induction of healthy collagen synthesis. Therefore, fractional ablative laser can provide an effective modality in treatment of morphea. The study aimed at evaluating the efficacy of fractional carbon dioxide laser as a new modality for the treatment of localized scleroderma and to compare its results with the well-established method of UVA-1 phototherapy. Seventeen patients with plaque and linear morphea were included in this parallel intra-individual comparative randomized controlled clinical trial. Each with two comparable morphea lesions that were randomly assigned to either 30 sessions of low-dose (30 J/cm 2 ) UVA-1 phototherapy (340–400 nm) or 3 sessions of fractional CO 2 laser (10,600 nm-power 25 W). The response to therapy was then evaluated clinically and histopathologically via validated scoring systems. Immunohistochemical analysis of TGF-ß1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon signed rank test for paired (matched) samples and Spearman rank correlation equation were used as indicated. Comparing the two groups, there was an obvious improvement with fractional CO 2 laser that was superior to that of low-dose UVA-1 phototherapy. Statistically, there was a significant difference in the clinical scores ( p  = 0.001), collagen homogenization scores ( p  = 0.012), and patient satisfaction scores ( p  = 0.001). In conclusion, fractional carbon dioxide laser is a promising treatment modality for cases of localized morphea, with proved efficacy of this treatment on clinical and histopathological levels.

Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the ¹⁹⁸ Au β-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible ¹⁹⁸ AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of ¹⁹⁸AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable ¹⁹⁸AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.

Background Cutaneous fibrosis, particularly in localized scleroderma (LoS), poses a considerable therapeutic challenge owing to its progressive characteristics and the subsequent effects on quality of life. Although ADSCs exhibit therapeutic potential for fibrosis, their spatiotemporal mechanisms of action, particularly within fibrotic microenvironments, remain poorly characterized. This study sought to clarify the spatiotemporal dynamics and molecular mechanisms of ADSC-mediated fibrosis resolution in bleomycin (BLM)-induced murine LoS model. Methods Skin fibrosis was induced in C57BL/6J mice through daily subcutaneous injections of bleomycin (BLM) administered over a period of four weeks. GFP-labeled mouse or human ADSCs were injected into the fibrotic dorsum. ADSC distribution was tracked using fluorescence imaging and flow cytometry. Skin fibrosis was assessed histologically (H&E, Masson's trichrome, α-SMA, COL1) and molecularly (qRT-PCR for cytokines). Transcriptomic profiling (RNA-seq) of sorted GFP + ADSCs was performed on days 1, 7, and 14 post-injection. Key pathways (ROS, NF-κB, TSG-6) were validated in vitro using ADSCs and human LoS-derived fibroblasts (LoSFs) via pharmacological inhibition, gene knockdown (shTSG-6), co-culture, Western blotting, and dual-luciferase assays. Results ADSCs mitigated dermal thickening, collagen deposition, α-SMA expression, and inflammation (TNF-α, IL-6, IL-1β) over 21 days. Transcriptomics revealed a temporal hierarchy: early oxidative stress response (Day 1), followed by immunomodulation (Day 7, NF-κB, cytokine pathways), and later ECM remodeling (Day 14). Mechanistically, TGF-β induced ROS via NOX4, activating NF-κB, which directly bound the TSG-6 promoter to drive its expression. TSG-6 knockdown in ADSCs (ADSCshTSG-6) abolished their ability to suppress TGF-β/Smad signaling, collagen production, α-SMA expression, and inflammation in vitro and in vivo. Conclusion ADSCs resolve skin fibrosis through a biphasic mechanism involving initial adaptation and subsequent immunomodulation/ECM remodeling, centrally governed by a ROS-NF-κB-TSG-6 axis. TSG-6 is the critical downstream effector, disrupting the TGF-β/Smad pathway and inflammation. This study identifies TSG-6 as a key therapeutic mediator and a potential biomarker for optimizing ADSC-based therapies for fibrotic skin disorders. Graphical Abstract

Over the last two decades, the process of delivering therapeutic drugs to a patient with a controlled release profile has been a significant focus of drug delivery research. Scientists have given tremendous attention to ultrasound-responsive hydrogels for several decades. These smart nanosystems are more applicable than other stimuli-responsive drug delivery vehicles (ie UV-, pH- and thermal-, responsive materials) because they enable more efficient targeted treatment via relatively non-invasive means. Ultrasound (US) is capable of safely transporting energy through opaque and complex media with minimal loss of energy. It is capable of being localized to smaller regions and coupled to systems operating at various time scales. However, the properties enabling the US to propagate effectively in materials also make it very difficult to transform acoustic energy into other forms that may be used. Recent research from a variety of domains has attempted to deal with this issue, proving that ultrasonic effects can be used to control chemical and physical systems with remarkable specificity. By obviating the need for multiple intravenous injections, implantable US responsive hydrogel systems can enhance the quality of life for patients who undergo treatment with a varied dosage regimen. Ideally, the ease of selfdosing in these systems would lead to increased patient compliance with a particular therapy as well. However, excessive literature has been reported based on implanted US responsive hydrogel in various fields, but there is no comprehensive review article showing the strategies to control drug delivery profile. So, this review was aimed at discussing the current strategies for controlling and targeting drug delivery profiles using implantable hydrogel systems. Keywords: smart hydrogels, ultrasound, acoustic energy, cavitation, on-demand drug delivery, localized therapy

Juvenile localized scleroderma (jLS), also known as morphea, is an orphan disease. Pediatric guidelines regarding diagnosis, assessment, and management are lacking. Our objective was to develop minimum standards of care for diagnosis, assessment, and management of jLS. A systematic review was undertaken to establish the pediatric evidence for assessment and monitoring of jLS. An expert panel, including members of the Pediatric Rheumatology European Society (PRES) Scleroderma Working Group, were invited to a consensus meeting where recommendations were developed based on evidence graded by the systematic review and, where evidence was lacking, consensus opinion. A nominal technique was usedwhere 75% consensus was taken as agreement. Recommendations for diagnosis, assessment, and management were developed. Due to a lack of pediatric evidence, these were primarily consensus driven. Careful assessment for extra-cutaneous manifestations including synovitis, brain involvement, and uveitis were key features together with joint assessments between Dermatology and Rheumatology to improve and standardize care. Conclusion: Management of jLS is varied. These recommendations should help provide standardization of assessment and care for those with this rare and potentially debilitating condition.

Background : Tacrolimus, a calcineurin inhibitor, is an immunomodulating and anti-inflammatory drug that inhibits T-cell activation and production of cytokines. The elevated level of cytokines in morphea causes fibroblast proliferation and subsequent overproduction of collagen. Theoretically, tacrolimus could inhibit the pathophysiologic process of morphea. Objective : To assess whether tacrolimus 0.1% ointment is an effective treatment for active plaque morphea in a double-blind, placebo (petroleum emollient)-controlled pilot study. Methods : Ten patients with active plaque morphea were included. All patients were treated with tacrolimus 0.1% ointment and with an emollient (petrolatum) on two selected morphea plaques, applied twice daily for 12 weeks. Initial and final assessment included surface area measurements, photography, durometer scores, and clinical feature scores. Adverse reactions were recorded. Results : The scleroderma plaques treated with topical tacrolimus 0.1% improved, resulting in a significant reduction in durometer and clinical feature scores. Overall, a significant difference could be found between topical tacrolimus and petrolatum with regard to durometer score (p < 0.005) and the clinical feature score (p = 0.019). Conclusion : In this first double-blind, placebo-controlled pilot study comparing tacrolimus 0.1% ointment with petrolatum in active plaque morphea, tacrolimus 0.1% ointment was shown to be an effective treatment for this condition.

Over the last 30 years, diverse types of nano-sized drug delivery systems (nanoDDSs) have been intensively explored for cancer therapy, exploiting their passive tumor targetability with an enhanced permeability and retention effect. However, their systemic administration has aroused some unavoidable complications, including insufficient tumor-targeting efficiency, side effects due to their undesirable biodistribution, and carrier-associated toxicity. In this review, the recent studies and advancements in intratumoral nanoDDS administration are generally summarized. After identifying the factors to be considered to enhance the therapeutic efficacy of intratumoral nanoDDS administration, the experimental results on the application of intratumoral nanoDDS administration to various types of cancer therapies are discussed. Subsequently, the reports on clinical studies of intratumoral nanoDDS administration are addressed in short. Intratumoral nanoDDS administration is proven with its versatility to enhance the tumor-specific accumulation and retention of therapeutic agents for various therapeutic modalities. Specifically, it can improve the efficacy of therapeutic agents with poor bioavailability by increasing their intratumoral concentration, while minimizing the side effect of highly toxic agents by restricting their delivery to normal tissues. Intratumoral administration of nanoDDS is considered to expand its application area due to its potent ability to improve therapeutic effects and relieve the systemic toxicities of nanoDDSs.

Systemic sclerosis (SSc) and localized scleroderma (LoSc) are rare connective tissue diseases that are identified by skin thickening and hardening with different mechanisms of action. Although advancements in treatments have been achieved in recent years, these conditions remain a major cause of morbidity and currently lack a definitive cure. We sought to evaluate the efficacy and safety of platelet-rich plasma (PRP) treatment in individuals with LoSc and SSc. PubMed/Medline, Ovid-Embase, and Web of Science were systematically searched until December 27th, 2024. A citation search was also carried out, and clinical studies published in English were eligible to be included. A total of 11 studies utilized PRP to treat different conditions of scleroderma. In limited and diffuse forms of SSc, PRP resulted in the improvement of mouth handicap in systemic sclerosis (MHISS) items, skin elasticity, skin ulcer healing, and vascularization both alone and alongside hyaluronic acid, autologous fat, and stromal vascular fraction. Moreover, PRP injections led to a significant decrease in the LoSc cutaneous assessment tool (LoSCAT), as well as a reduction in pain and disease symptoms. Furthermore, patients with en coupe de sabre experienced hair regrowth after PRP treatment. The adverse effects, which can be limited or diffuse, were mild and self-limited. PRP contains a considerable number of platelets, cytokines, and growth factors. PRP is considered a safe supplementary treatment option alongside standard therapy for both LoSc and SSc, with the potential to promote improvement in these patients, either as a standalone therapy or in conjunction with other therapeutic approaches. Graphical abstract The summary of systematic review methodology (systematic search, screening, eligibility criteria, and study selection) and applications of platelet-rich plasma in treating systemic sclerosis and localized scleroderma