Search Results (84)

Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as a separate entity. Distinguishing BLS from primary BD is essential for appropriate management, and studying BLS may provide insights into BD pathogenesis. Objectives: To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024. Methods: A systematic search of PubMed, Scopus, and Embase was performed using the terms “Behçet-like syndrome”, “Behçet-like disease”, and “Pseudo-Behçet disease”. We included English-language reports of patients > 12 years old with a defined underlying etiology and Behçet-like manifestations, defined by ≥2 ICBD criteria and/or gastrointestinal involvement, mucosal ulcers, thrombosis, or non-recurrent disease. Epidemiological, clinical, laboratory, histological, and treatment data were extracted and analyzed descriptively. Results: Of 679 publications, 53 met inclusion criteria, comprising 100 patients with BLS. The median age was 44 years (IQR 22–52), with a female predominance (1:2). Fifty-three percent were from non-European countries. A genetic disorder was identified in 70% of cases, while HLA-B51 was present in 10%. Frequent manifestations included skin lesions (68%), fever (56%), intestinal involvement (43%), and joint symptoms (43%). Treatments included glucocorticoids (65%), conventional DMARDs (32%), and biologics (22%), mainly anti-TNF agents. Antiviral/antibiotic therapy was used in 9% and chemotherapy in 15%. Two patients with trisomy-8 MDS underwent allogeneic stem cell transplantation. Conclusions: Diverse conditions—including monogenic diseases, immune defects, myeloproliferative disorders, infections, and drug-related reactions—can produce Behçet-like features. Our findings highlight differences in clinical expression and treatment response across BLS etiologies. Recognizing BLS is essential for appropriate management and may contribute to a deeper understanding of BD pathogenesis and future targeted therapies. Full article

Objectives: Sialic acid (SA), a naturally occurring compound abundantly found in birds’ nests, holds immense promise for skincare applications owing to its remarkable biological properties. However, its low bioavailability, poor stability, and limited skin permeability have constrained its widespread application. Methods: To overcome these challenges, SA was encapsulated within nanoliposomes (NLPs) by the high-pressure homogenization technique to develop an advanced and efficient transdermal drug delivery system. The skincare capabilities of this novel system were comprehensively evaluated across multiple experimental platforms, including in vitro cell assays, 3D skin models, in vivo zebrafish studies, and clinical human trials. Results: The SA-loaded NLPs (SA-NLPs) substantially improved the transdermal penetration and retention of SA, facilitating enhanced cellular uptake and cell proliferation. Compared to free SA, SA-NLPs demonstrated a 246.98% increase in skin retention and 1.8-fold greater cellular uptake in HDF cells. Moreover, SA-NLPs protected cells from oxidative stress-induced damage, stimulated collagen synthesis, and effectively suppressed the secretion of matrix metalloproteinases, tyrosinase activity, and melanin production. Additionally, zebrafish-based assays provided in vivo evidence of the skincare efficacy of SA-NLPs. Notably, clinical evaluations demonstrated that a 56-day application of the SA-NLPs-containing cream resulted in a 4.20% increase in L*, 7.87% decrease in b*, 8.45% decrease in TEWL, and 4.01% reduction in wrinkle length, indicating its superior brightening, barrier-repair, and anti-aging effects. Conclusions: This multi-level, systematic investigation strongly suggests that SA-NLPs represent a highly promising transdermal delivery strategy, capable of significantly enhancing the anti-aging, barrier-repair, and skin-brightening properties of SA, thus opening new avenues for its application in the fields of dermatology and cosmeceuticals. Full article

Background and Objectives: Previous studies have shown that a major part of adverse drug reactions (ADRs) are preventable, and they contribute to increased morbidity, mortality, and costs. To our knowledge, no study investigating preventable ADRs has been carried out in Lithuania. Therefore, the aim of this study was to characterize ADRs in the intensive care unit (ICU) of a secondary care Lithuanian hospital as well as to identify drug classes and organ systems most commonly implicated in preventable and nonpreventable ADRs. Materials and Methods: This observational prospective study was conducted in an 18-bed ICU of Kaunas Hospital of the Lithuanian University of Health Sciences from 1 September 2021 to 31 August 2023. All ADRs were assessed for causality, severity, and preventability. The Anatomical Therapeutic and Chemical (ATC) system was used to classify drug classes implicated in ADRs. The organ systems affected were analyzed using the Medical Dictionary for Regulatory Activities (MedDRA). Results: A total of 154 patients with a median age of 78.8 years (range, 18–97) were enrolled into this study. There were 255 ADRs identified; preventable ADRs accounted for 87.5%. Among the preventable ADRs, the top three therapeutic subgroups were antithrombotic agents (26.5%), anti-inflammatory and antirheumatic products (22.0%), and blood substitutes and perfusion solutions (20.2%). Meanwhile, among nonpreventable ADRs, antibacterials for systemic use (62.5%) and antithrombotic agents (46.9%) were the two most common therapeutic subgroups. The gastrointestinal as well as the skin and subcutaneous tissues organ systems were more likely to be affected by nonpreventable ADRs (56.3% vs. 17.5%, p ˂ 0.05 and 12.5% vs. 0.4%, p ˂ 0.05, respectively), while the renal and urinary organ systems were more likely to be affected by preventable ADRs (38.1% vs. 6.3%, p ˂ 0.05). Conclusions: Our study showed a very high incidence of preventable ADRs (87.5%). Drugs affecting blood and blood-forming organs were most frequently implicated in these ADRs. This area deserves special attention and strategies need to be implemented to reduce the incidence of preventable ADRs and their impact on the healthcare system. Moreover, it emphasizes the need for future studies at a national level as, to our knowledge, this is the first study addressing the issues of avoidable harm at the ICU of one Lithuanian hospital. Full article

Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients. Full article

The World Health Organization included Cryptococcus neoformans and Cryptococcus gattii in its priority fungal pathogen list due to their high mortality rates and frequent treatment failures. These facts have driven research toward the discovery of new compounds for the treatment of cryptococcosis. In this study, we investigated the therapeutic potential of two complexes, [Cu(phendione)₃](ClO₄)₂·4H₂O (Cu-phendione) and [Ag(phendione)₂]ClO₄ (Ag-phendione), against drug-resistant clinical isolates of C. gattii and C. neoformans. Both complexes demonstrated anti-Cryptococcus activity, with Cu-phendione exhibiting minimum inhibitory concentration (MIC) values of 6.25 μM for C. gattii and 3.125 μM for C. neoformans, while Ag-phendione showed an MIC of 1.56 μM for both Cryptococcus species. Notably, both Cu-phendione and Ag-phendione complexes exhibited enhanced antifungal activity against reference strains of C. neoformans and C. gattii. In silico analysis identified both complexes as highly promising, exhibiting good oral bioavailability, high gastrointestinal absorption, and moderate skin permeability. Moreover, neither complex demonstrated toxicity toward sheep erythrocytes at concentrations up to 62.5 μM, with a selectivity index (SI) exceeding 10 for Cu-phendione and 40 for Ag-phendione. In vivo testing using the Galleria mellonella model demonstrated that both complexes were non-toxic, with 100% larval survival at concentrations up to 1000 μM and SI exceeding 160 following a single administration. Interestingly, larvae exposed to Cu-phendione at concentrations of 15.6–31.25 μM exhibited a significant increase in the density of hemocytes, the immune cells responsible for defense in invertebrates. Furthermore, multiple treatments with 62.5 μM of complexes caused either no larval mortality, hemocyte alterations, or changes in silk production or coloration, indicating a lack of toxicity. These findings suggest that Cu-phendione and Ag-phendione may serve as promising antifungal alternatives against Cryptococcus, with minimal host toxicity. Full article

This study deals with the extraction of active compounds for a formula (Angelica gigas, Cornus officinalis, Ganoderma lucidum, Thymus vulgaris, and Asparagus cochinchinensis) and the evaluation of its skin anti-aging properties. This formulation was inspired by the oriental medicine Gongjin-dan (Angelica gigas, Cornus officinalis, deer antler, and musk), which has been used as a restorative drug for longevity. Enzyme-based extraction and chemical purification were used to obtain a mixed fraction (GEF) enriched in glycopeptides and glycoproteins from the five herbal materials. The chemical characteristics of GEF, including the carbohydrate groups attached to the peptides and proteins, the total carbohydrate and protein contents, and the composition of monosaccharides and amino acids were determined. The chemical characteristics that were significantly different from those of the extract, generally prepared in the same ratio, were the abundance of glycopeptides and glycoproteins and the high proportions of conditionally essential amino acids (51.0%) and acidic/basic amino acids (67.7%). These are necessary components for strengthening the skin layers against aging. The in vitro skin anti-aging properties of GEF on human fibroblasts (HS68), keratinocytes (HaCaT), and adipose-derived mesenchymal stem cells (ADMSCs) were evaluated. It was found that MMP-1 gene expression was inhibited (18–28%) and fibrillin-1 protein (23–37%) was restored contrary to the effect of UV irradiation. COL1A1 and COL4A1 gene expression (25–35%), HAS2 gene expression (22–213%), and adipogenesis (15%) were facilitated. These results demonstrate the potential of GEF as a raw material for skin anti-aging and reinforce the scientific evidence supporting a traditional medicine with a long history. Full article

Plaque psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by the formation of thick, scaly plaques. The disease is driven by dysregulation of the immune response, primarily involving T-helper cells, which create a persistent inflammatory environment. In recent years, several biomarkers reflecting systemic inflammation have been identified, including indices derived from a complete blood count, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Systemic Immune-Inflammation Index (SII). The aim of our study was to explore the role of these markers in patients with psoriasis undergoing biological treatment. Medical records of 159 patients with plaque psoriasis receiving biologics were retrospectively reviewed. The NLR, PLR, and SII values were calculated from the hemograms of the patients. Additionally, demographic and psoriasis severity data were analyzed. During the 18-month follow-up, the mean NLR, PLR, SII, and CRP values were significantly decreased in comparison to the baseline (p < 0.05). No significant differences between anti-TNF, anti-IL-12/23, anti-IL-17, and anti-IL-23 drugs were identified (p > 0.05). The initial values of NLR, PLR, and SII were positively correlated with psoriasis severity. No relationship between the analyzed biomarkers and age, sex, psoriasis duration, and prior exposure to biological drugs was identified. CBC-derived biomarkers may be useful for monitoring inflammation reduction in psoriasis patients treated with biological drugs. Full article

Focusing on the anti-aging mechanism and efficient utilization of anti-aging active ingredients in the skin is an excellent strategy to mitigate aging. In this study, ribose/collagen/decarboxylated carnitine hydrochloride/palmitoyl tripeptide-1 composite nanocarriers (RCDP NCs) were synthesized using transdermal drug delivery nanotechnology. The drug delivery of composite nanocarriers and the anti-aging mechanism of RCDP NCs were studied through transdermal behavior, cell uptake, cell proliferation, antioxidant enzyme activity, lipid oxidation product expression, β—galactosidase content, autophagy vesicle number, autophagy-related protein expression, and other indicators. The results showed that the composite nanocarriers on the skin could reach a dermal depth of 460.0 μm (4 h). The uptake of RCDP NCs by keratinocytes and fibroblasts increased by 47.37% and 89.11% (4 h), respectively. RCDP NCs promoted cell proliferation, enhanced the activities of the main antioxidant enzymes, and reduced the production of the lipid oxidation product malondialdehyde (MDA). Sequestosome-1 protein (p62) decreased, whereas both the ratio of microtubule-associated protein light chain 3 II/microtubule-associated protein light chain 3 I (LC3II/LC3I) and the number of autophagosomes increased, indicating that RCDP NCs promoted autophagy. The drug delivery nanotechnology in this study achieved better transdermal application of active ingredients, which could mitigate skin aging faster and more effectively. Full article

Background/Objectives: Potato (Solanum tuberosum)-derived exosomes (SDEs) are extracellular vesicles (66 nm in diameter) with therapeutic potential. SDEs suppress matrix metallopeptidases (MMPs) 1, 2, and 9, tumor necrosis factor (TNF), and interleukin 6 (IL6), while exhibiting radical-scavenging activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro and mitigating hydrogen peroxide (H₂O₂)-induced oxidative stress in HaCaT cells. SDEs upregulate the antioxidant gene glutathione S-transferase alpha 4 (GSTA4), prevent UVB damage, and regenerate photodamaged HaCaT cells. This study evaluates SDEs’ safety and skin-enhancing properties to improve their beauty-related and medical applications. Methods: The SDEs purified via ultracentrifugation were tested for their cytotoxic effects on HaCaT cell viability in scratch wound healing assays and for skin barrier gene modulation in HaCaT keratinocytes and Detroit 551 fibroblasts. A reverse transcription–polymerase chain reaction (RT-PCR) was used to analyze the changes in skin barrier gene expression following the SDE treatment. Cosmetic prototypes containing SDEs were assessed for skin irritation, cooling effects, periorbital wrinkle reduction, elasticity, and whitening properties. Results: The cytotoxicity and human topical tests confirmed the safety of SDE application. The SDEs accelerated wound closure, elevated the skin barrier gene expression level, and improved the clinical parameters, including wrinkle reduction, elasticity enhancement, and whitening. No irritation or side effects were observed. Conclusions: This study identified natural, edible potato-derived exosomes (SDEs) as highly safe agents that significantly enhance wound healing and promote skin barrier-related gene expression. Their multifunctional anti-aging efficacy—reducing wrinkles, enhancing elasticity, and promoting whitening without irritation—positions them as promising candidates for cosmetic and dermatological innovations. These findings warrant further exploration of SDEs for therapeutic applications, including inflammatory skin disorders and drug delivery systems. Full article

Background: Liposome particles with smaller sizes could increase transdermal drug delivery efficacy for enhanced skin penetration. While microfluidic methods have enabled controlled liposome synthesis, achieving efficient production of ultrasmall nanoliposomes (NLP_US) with a size smaller than 40 nm yet remains an unmet challenge. Methods: In this study, we employed a helical-blade-strengthened co-flow focusing (HBSCF) device to efficiently synthesize NLP_US, which demonstrated superior skin permeation and retention. Results: Liposome formulation primarily contains unsaturated lecithin, which endows an unprecedented capacity to NLP_US to scavenge reactive oxygen species (ROS). Moreover, NLP_US can effectively encapsulate a broad spectrum of anti-aging agents, including coenzyme Q10 (CoQ10), while preserving its physical properties. In a photoaged skin model, topical application of CoQ10-loaded NLP_US (CoQ10@NLP_US) inhibited ultraviolet B (UVB)-induced matrix metalloproteinase-1 (MMP-1) production, and promoted collagen type I (Col-I) synthesis in skin cells, thereby effectively rejuvenating the photoaged skin. Conclusions: This study presents a straightforward and efficient method for the production of NLP_US, thereby offering a promising platform for transdermal delivery of diverse therapeutic agents. Full article

Rosacea is a common skin condition with quite a relevance. It currently affects at least 10% of the European population at some point after the age of 30. It is a chronic disorder that mainly affects the skin on the face and is characterized by outbreaks and remissions. Under normal circumstances, the skin face presents a wide range of commensal organisms, such as Staphylococcus epidermidis or Demodex folliculorum, but dysbiosis of the skin flora plays a relevant role in inflammatory processes and the development of the disease. Metronidazole (MD) is one of the main treatments indicated to reduce redness on the cheeks, nose, chin, or forehead and also to treat flushing, erythema, pimples, and other symptoms due in part to its anti-inflammatory action. On the other hand, clindamycin (CM) is another antibiotic used for rosacea, especially for its action against anaerobic and Gram-positive bacteria. Background/Objectives: This study aimed to develop an emulgel formulation that includes MD and CM, using excipients with non-comedogenic and non-irritating properties. Methods: The formulation was characterised physiochemically, rheological measurements were made, and short-term stability studies were carried out. In vitro release, permeation studies, toxicity an in vitro inflammation model were evaluated in a HaCaT cell model. To determine the interaction between the antibiotics, the minimum inhibitory concentration was determined separately and together using the broth microdilution method. To determine the formulation’s antimicrobial activity, an agar diffusion method was used. Results: The MD-CM-gel droplet size was measured by laser diffraction and the diameter obtained was less than 2.68 ± 0.18 µm in 50% of the particles. Suitable results was observed for the short-term stability. Release and permeation data revealed sustained drug release and adequate permeation through human skin. Non-toxicity was detected and the MD showed an anti-inflammatory effect with non-interference of CM. Also, there is no antagonism between the two antibiotics and the MD-CM-gel shows better results when compared to the formulations with the antibiotics separately and to commercial formulations. Conclusions: It is suggested that, following detailed preclinical and clinical studies, MD-CM-gel could be considered as an alternative for treating rosacea. Full article

Algae have great therapeutic value and have attracted a great deal of attention due to the abundance of bioactive compounds they contain, which may be the key to fighting diseases of various origins, such as skin cancer, breast cancer, or osteosarcoma. In this regard, global trends indicate that cancer is likely to become the leading cause of death and the main obstacle to increased life expectancy in the 21st century, which is related to multiple factors, including the various effects of climate change, which will continue to cause afflictions to human health. Then, excess exposure to ultraviolet radiation (UVR) causes damage to DNA, proteins, enzymes, and various cellular structures and leads to the development of cancer, premature aging of the skin (wrinkles, dryness, dilation of blood vessels, and loss of collagen and elastin), or alterations of the immune system. In addition, multidrug resistance (MDR) is characterized by the overexpression of efflux pumps, such as P-glycoprotein or P-gp, that expel chemotherapeutic drugs out of the cancer cell being the main obstacle to their efficacy. Some molecules inhibit efflux pumps when co-administered with antineoplastic agents, such as glycolipids. Mycosporin-like amino acids and glycolipids isolated from Sargassum have shown an important role as potential anticancer agents. The results show that glycolipids and mycosporin-like amino acids present in brown algae of the genus Sargassum exhibit cytotoxic effects on different types of cancer, such as breast cancer, leukemia, and osteosarcoma, which is a key criterion to be considered as a natural anti-cancer strategy; but, more in-depth in vitro studies are needed to represent them at the in vivo level, as well as their validation in preclinical assays. Full article

This comprehensive review explores the biological functions of Perilla frutescens seed proteins and peptides, highlighting their significant potential for health and therapeutic applications. This review delves into the mechanisms through which perilla peptides combat oxidative stress and protect cells from oxidative damage, encompassing free radical scavenging, metal chelating, in vivo antioxidant, and cytoprotective activities. Perilla peptides exhibit robust anti-aging properties by activating the Nrf2 pathway, enhancing cellular antioxidant capacity, and supporting skin health through the promotion of keratinocyte growth, maintenance of collagen integrity, and reduction in senescent cells. Additionally, they demonstrate antidiabetic activity by inhibiting α-amylase and α-glucosidase. The cardioprotective effects of perilla peptides are underscored by ACE-inhibitory activities and combat oxidative stress through enhanced antioxidant defenses. Further, perilla peptides contribute to improved gut health by enhancing beneficial gut flora and reinforcing intestinal barriers. In liver, kidney, and testicular health, they reduce oxidative stress and apoptotic damage while normalizing electrolyte levels and protecting against cyclophosphamide-induced reproductive and endocrine disruptions by restoring hormone synthesis. Promising anticancer potential is also demonstrated by perilla peptides through the inhibition of key cancer cell lines, alongside their anti-inflammatory and immunomodulating activities. Their anti-fatigue effects enhance exercise performance and muscle function, while perilla seed peptide nanoparticles show potential for targeted drug delivery. The diverse applications of perilla peptides support their potential as functional food additives and therapeutic agents. Full article

Background: Skin ageing, driven predominantly by oxidative stress from reactive oxygen species (ROS) induced by environmental factors like ultraviolet A (UVA) radiation, accounts for approximately 80% of extrinsic skin damage. L-glutathione (GSH), a potent antioxidant, holds promise in combating UVA-induced oxidative stress. However, its instability and limited penetration through the stratum corneum hinder its topical application. This study introduces a novel solid lipid nanoparticle (SLN)-enriched hydrogel designed to enhance GSH stability, skin penetration, and sustained release for anti-ageing applications. Methods: GSH-loaded SLNs were prepared via a double-emulsion technique and optimized using factorial design. These SLNs were incorporated into 1–3% (w/v) Carbopol hydrogels to produce a semi-solid formulation. The hydrogel’s characteristics, including morphology, mechanical and rheological properties, drug release, stability, antioxidant activity, cytotoxicity, and skin penetration, were evaluated. Results: SEM and FTIR confirmed the uniform dispersion of SLNs within the hydrogel. The formulation exhibited desirable properties, including gel strength (5.1 ± 0.5 g), spreadability (33.6 ± 1.9 g·s), pseudoplasticity, and elasticity. In vitro studies revealed a biphasic GSH release profile, with sustained release over 72 h and over 70% cumulative release. The hydrogel significantly improved antioxidant capacity, protecting human fibroblasts from UVA-induced oxidative stress and enhancing cell viability. Stability studies indicated that 4 °C was optimal for storage over three months. Notably, the hydrogel enhanced GSH penetration through the stratum corneum by 3.7-fold. Conclusions: This SLN-enriched hydrogel effectively improves GSH topical delivery and antioxidant efficacy, providing a promising platform for anti-ageing and other bioactive compounds with similar delivery challenges. Full article

Late-onset Alzheimer’s disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of sodium thiosulfate (STS) as a possible multi-targeting treatment option for LOAD. Sulfur is widely available in our environment and is responsible for forming organosulfur compounds that are known to be associated with a wide range of biological activities in the brain. STS is known to have (i) antioxidant and (ii) anti-inflammatory properties; (iii) chelation properties for calcium and the pro-oxidative cation metals such as iron and copper; (iv) donor properties for hydrogen sulfide production; (v) possible restorative properties for brain endothelial-cell-derived bioavailable nitric oxide. Thus, it becomes apparent that STS has the potential for neuroprotection and neuromodulation and may allow for an attenuation of the progressive nature of neurodegeneration and impaired cognition in LOAD. STS has been successfully used to prevent cisplatin oxidative-stress-induced ototoxicity in the treatment of head and neck and solid cancers, cyanide and arsenic poisoning, and fungal skin diseases. Most recently, intravenous STS has become part of the treatment plan for calciphylaxis globally due to vascular calcification and ischemia-induced skin necrosis and ulceration. Side effects have been minimal with reports of metabolic acidosis and increased anion gap; as with any drug treatment, there is also the possibility of allergic reactions, possible long-term osteoporosis from animal studies to date, and minor side-effects of nausea, headache, and rhinorrhea if infused too rapidly. While STS poorly penetrates the intact blood–brain barrier(s) (BBBs), it could readily penetrate BBBs that are dysfunctional and disrupted to deliver its neuroprotective and neuromodulating effects in addition to its ability to penetrate the blood–cerebrospinal fluid barrier of the choroid plexus. Novel strategies such as the future use of nano-technology may be helpful in allowing an increased entry of STS into the brain. Full article