Search Results (264)

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. Full article

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

Neonatal calves possess an immature and naïve immune system and are reliant on the intake of maternal colostrum for the passive transfer of immunoglobulins. Maternal antibodies delivered to the calf via colostrum, are crucial to prevent calfhood diseases and death. Failure of transfer of passive immunity (FTPI) is a condition in which calves do not acquire enough maternal antibodies, mostly in the form of IgG, due to inadequate colostrum quality or delayed colostrum feeding. The diagnosis and risk factors for FTPI have been widely studied in dairy cattle; however, in beef calves, the research interest in the topic is relatively recent, and the most adequate diagnostic and preventative methods are still in development, making it difficult to define recommendations for the assessment and prevention of FTPI in cow–calf operations. The objective of this scoping review is to identify the published literature on best practices for colostrum management and transfer of passive immunity (TPI) in neonatal beef calves. The literature was searched using three electronic databases (CAB Direct, Scopus, and PubMed) for publications from 2003 to 2025. The search process was performed during the period from May to July 2023, and was repeated in January 2025. All screening processes were performed using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). A total of 800 studies were initially identified through database searches. After removing duplicates, 346 studies were screened based on their titles and abstracts, leading to the exclusion of 260 studies. The remaining 86 studies underwent full-text screening, and 58 studies were considered eligible for data extraction. Hand-searching the references from published review papers on the subject yielded an additional five studies, bringing the total to 63 included articles. The prevalence of FTPI has been estimated to be between 5.8% and 34.5% in beef calves. Factors studied related to colostrum management include quality and quantity of colostrum intake, the timing and method of colostrum feeding, and the microbial content of the colostrum. Studies on risk factors related to the calf include the topics calf sex, twin status, calf vigor, weight, month of birth, cortisol and epinephrine concentrations, and the administration of nonsteroidal anti-inflammatory drugs to calves after difficult calving. The dam-related risk factors studied include dam body condition score and udder conformation, breed, parity, genetics, prepartum vaccinations and nutrition, calving area and difficulty, and the administration of nonsteroidal anti-inflammatory drugs at C-section. Most importantly for beef systems, calves with low vigor and a weak suckling reflex are at high risk for FTPI; therefore, these calves should be given extra attention to ensure an adequate consumption of colostrum. While serum IgG levels of < 8 g/L or < 10 g/L have been suggested as cutoffs for the diagnosis of FTPI, 16 g/L and 24 g/L have emerged as cutoffs for adequate and optimal serum IgG levels in beef calves. Several field-ready diagnostics have been compared in various studies to the reference standards for measuring indicators of TPI in beef calves, where results often differ between models or manufacturers. Therefore, care must be taken when interpreting these results. Full article

Perfluorononanoic acid (PFNA) is a ubiquitous persistent environmental pollutant, and several studies have found significant links between atopic dermatitis (AD) and prenatal exposure to PFNA. However, the relationship between PFNA and AD remains unclear. In this study, 2,4-dinitrochlorobenzene (DNCB)-treated female BALB/c mice were used as AD models to investigate the effects of PFNA and its potential mechanisms. These mice were topically applied with 5 mg/kg PFNA per day for 15 days. The results demonstrated that PFNA significantly increased AD lesion severity and clinical symptoms, including dermatitis score, ear thickness, and epidermal thickness. In addition, PFNA also increased the serum IgE level, splenic atrophy, and upregulated the expression of TNF-α, IL-6, and IL-1β, genes that are associated with skin inflammatory factors. In addition, Western blot results showed that PFNA treatment upregulated the expression of p-JNK protein. Additionally, cellular experiments indicated that RAW264.7 macrophages and mouse brain microvascular endothelial (bEnd.3) cells treated with PFNA at concentrations of 0.01–100 μM for 72 h showed no changes in cell viability. However, 100 μM PFNA upregulated the mRNA expression levels of the pro-inflammatory cytokines IL-1β and IL-6, as well as the protein expression of p-JNK, in RAW264.7 cells induced with 1 mg/mL LPS for 2 h. Similarly, PFNA increased TNF-α and IL-6 mRNA expression and p-JNK protein expression in bEnd.3 cells stimulated with 20 ng/mL TNF-α for 0.5 h. Based on these findings, we can conclude that PFNA may aggravate atopic dermatitis by promoting inflammation. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease stemming from genetic susceptibility and environmental factors. It is characterized by immune dysregulation, increased mast cell activity, elevated levels of immunoglobulin E (IgE), and excessive proinflammatory mediator expression. These factors contribute to hallmark symptoms such as pruritus, erythema, and skin barrier dysfunction. In this study, we investigated the antioxidant and anti-inflammatory effects of Taraxacum mongolicum (WTM) water extract, as well as its skin barrier regulation and immune functions in AD. In the present study, we explored the therapeutic efficacy and underlying mechanisms of WTM in a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB). Mice were administered WTM orally or topically for 14 consecutive days. The results demonstrated that WTM treatment significantly alleviated clinical severity, showing reductions in skin lesion scores, epidermal thickness, mast cell infiltration, and scratching behavior, compared to the DNCB-treated group. Mechanistically, WTM reduced serum levels of IgE and proinflammatory cytokines (IL-4, IL-6, IL-1β, TNF-α, and IL-31) while suppressing the expression of the JAK/STAT/TSLP signaling pathway in skin tissues. Furthermore, WTM inhibited the TLR4/NF-κB and MAPK pathways and enhanced antioxidant defense by elevating superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. These findings indicate that WTM attenuates DNCB-induced AD progression in mice, likely through the dual modulation of inflammatory signaling and oxidative stress. These findings suggest that WTM may modulate the immune response and alleviate AD symptoms by inhibiting the TLR4/NF-κB, MAPK, and JAK/STAT/TSLP pathways. Full article

In the context of modern dermocosmetic development, multifunctional topical gel-cream formulations must be efficient for both therapeutic efficacy and cosmetic applications. This study presents a comparative physicochemical and pharmacotechnical analysis of three topical gel-cream formulations developed by Brand Chanand^®: Acne Control Cleanser (ACC), Acne Face Cream (AFC), and Gentle Cream Cleanser Serum Control, Regenerating, Hydrating, Calming (IRC). Each formulation is enriched with a specific blend of bioactive compounds, including botanical oils, vitamins, and proteins, designed to treat acne, to support skin regeneration, and to maintain the skin barrier. A multidisciplinary approach was used, including Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR), differential scanning calorimetry (DSC), rheological evaluation, pH and density determination, spreadability analysis, and oxidative stability testing to evaluate the products. Antioxidant capacity was assessed through multiple in vitro assays. The results demonstrated that all three gel-cream formulations exhibit pseudoplastic rheological behaviour, suitable for topical application. AFC showed the highest oxidative stability and antioxidant activity, while IRC presented superior spreadability and cosmetic efficacy, likely due to its complex composition. ACC displayed faster absorption and was ideal for targeted use on oily or acne-prone skin. The differences observed in the stability and performance suggest that the ingredient synergy, base composition, and solubility profiles show notable variations in dermato-cosmetic formulations. These findings highlight the formulation–performance relationship in topical gel-cream formulations and support the development of new cosmetic products tailored for sensitive and acne-prone skin. Full article

This review explores the potential role of topical insulin drops in corneal regeneration by analyzing the mechanism of action and clinical outcomes. Corneal integrity restoration is crucial for ocular surface healing. This review synthesizes the current literature on topical insulin for neurotrophic keratopathy (NK), highlighting its mechanism of action, therapeutic potential, and clinical outcomes. Recent studies report high rates of epithelial regeneration, suggesting that topical insulin may be an effective adjunct or alternative to conventional treatments. Further randomized controlled trials are needed to confirm its long-term efficacy and optimal dosing. Methods: Considering the limited regenerative capacity of the corneal epithelium in NK and the increasing interest in novel therapy, we review the existing literature to evaluate the role and extent of topical insulin’s contribution to corneal healing by applying the PICO framework, which allows for a clear and systematic approach to literature selection and evaluation. The literature search and study selection were conducted manually following PRISMA guidelines. Conclusions: Most of the studies resulting from the selection have small samples, and there is a lack of large, randomized clinical trials. The evidence reviewed in this study suggests that topical insulin is a promising therapy for promoting corneal healing in neurotrophic keratopathy. While clinical trials have demonstrated significant epithelial regeneration, optimal dosing and long-term safety require further investigation. Compared to conventional treatments such as autologous serum or growth factor therapy, insulin eye drops provide a cost-effective alternative. Additional research through controlled trials is needed to formulate standardized therapeutic protocols and verify long-term outcomes. Full article

Novel senotherapeutics are needed to reverse aging-related skin decline. The research question addressed was whether mesoglycan, a clinically approved glycosaminoglycan formulation known to enhance perfusion, angiogenesis, and VEGF-A signaling, possesses therapeutic potential for rejuvenating photo aged human skin. To test this, we treated full-thickness photoaged facial human skin samples (mean age: 72 ± 5 years) from seven women ex vivo. The samples were treated with topical or medium-delivered mesoglycan (100, 200, and 300 µM) for 6 days under serum-free conditions that accelerate skin aging. Biomarkers associated with aging were assessed using quantitative immunohistomorphometry. Mesoglycan treatment improved key skin aging biomarkers at all doses. Compared to vehicle-treated skin, mesoglycan broadly enhanced epidermal structure and function, improved pigmentation-related markers, reduced cellular senescence, boosted mitochondrial performance and antioxidant defenses, and improved dermal matrix structure and microvasculature density. Notably, mesoglycan also upregulated VEGF-A and VEGFR2, promoting skin rejuvenation. Medium-delivered mesoglycan produced stronger overall effects, while rete ridge reappearance was observed exclusively after topical application. Mesoglycan demonstrates senotherapeutic potential in photoaged human skin, acting via complementary pathways, including VEGF-A upregulation. Although medium-delivered mesoglycan yielded the greatest biomarker improvements topical application restored rete ridges, a sign of epidermal reorganization and also significantly enhanced basement membrane structure, pigmentation, mitochondrial function and antioxidant defenses, while avoiding systemic exposure, making it the safer and more feasible route for localized skin anti-aging. Full article

A 10-year-old male neutered British Shorthair cat with diabetes mellitus presented with an acute onset of unilateral swelling, erythema, alopecia and coalescing ulcerations of the face and periocular skin. Initial clinical differential diagnoses were trauma, infections (including feline respiratory viruses), arthropod bites, and eosinophilic dermatoses such as eosinophilic granuloma complex, mosquito-bite hypersensitivity and cutaneous adverse drug reaction. Histopathology revealed fulminant furunculosis with abundant eosinophils and vasculitis. Initial topical glucocorticoid treatment partially improved the clinical signs but severely raised serum glucose levels. As a result, systemic glucocorticoids and ciclosporin were not considered optimal treatments, and the off-label and short-term use of oclacitinib was chosen with the owner’s informed consent. This treatment induced fast remission of clinical signs with no recurrence for 17 months. Secondary fusion of the eyelids caused by cicatrization was surgically reconstructed to restore full function. Full article

Background and Objectives: The gut–liver axis plays a crucial role in the development of post-surgical infections. Surgery-induced dysbiosis can lead to increased bacterial translocation, impairing the liver’s detoxification capacity and negatively affecting surgical outcomes. Following liver surgery, approximately a third of the patients develop bacterial infections, with a high risk of bacteremia or even sepsis-related liver failure and death. The potential advantages of administering pro- or synbiotics before/after surgery remain a topic of discussion. Therefore, a systematic review of randomized clinical trials comparing patients with and without supplementation and their outcomes and effects after liver resection (LR) or liver transplantation (LT) was conducted. Materials and Methods: A computer-based search of electronic databases was conducted to gather randomized controlled trials (RCTs) that focused on probiotic/synbiotic use during the perioperative period for liver surgery patients. Two researchers independently screened the studies, extracted the data, evaluated the risk of bias, and performed a meta-analysis using RevMan Web. Results: Our research revealed 19 relevant randomized controlled studies that included a total of 1698 patients on the perioperative use of pro-/symbiotic administration in liver surgery. Eight studies were performed on liver transplantation (LT), and 11 studies were performed for liver resection (LR). The results of the meta-analysis demonstrated that the probiotic group exhibited lower rates of postoperative infectious complications (OR = 0.34; 95%CI 0.25 to 0.45; p < 0.0001), hospital stay duration (SMD = −0.13; 95%CI −0.25 to −0.00; p = 0.05), lower serum endotoxin levels (SMD = −0.39%CI −0.59 to −19; p < 0.0001), and white blood cell counts (SMD = −SMD = −0.35; 95%CI −0.56 to −0.13; p = 0.002) compared to the control group. Further, with regard to liver function, we observed significant postoperative differences in alanine aminotransferase (ALT)-levels (SMD = −0.46; 95%CI −0.63 to −0.29; p < 0.0001), aspartate aminotransferase (AST) levels (SMD = −0.53; 95%CI −0.71 to −0.34; p < 0.0001), bilirubin levels (SMD = −0.35; 95%CI −0.50 to −0.19; p < 0.0001), and international ratio (INR) levels (SMD = −0.1; 95%CI −0.12 to −0.08; p ≤ 0.0001), favoring the symbiotic group compared to the control group. Conclusions: The use of pro-/synbiotics during the perioperative period reduces the risk of postoperative infections, support postoperative liver function, and recovery and shortens hospital stays for liver surgery patients. However, they do not appear to particularly aid in inflammation reduction. Full article

Thelazia callipaeda (T. callipaeda) is a zoonotic ocular parasite that poses a public health risk. Current treatment depends on mechanical parasite extraction and specific prophylactic anthelmintics, but direct ocular deworming agents are limited and expensive, and mechanical removal is often incomplete, causing animal stress and ocular injury. Levamisole eye drops have been applied; however, their efficacy and safety remain undefined. We established a standardized T. callipaeda viability assessment system (TVAS) and an animal infection model to evaluate candidate drugs. In vivo, 5 mg/mL levamisole was administered at escalating frequencies. Ocular symptoms, complete blood count (CBC), and serum biochemistry were measured, and cytotoxicity was assessed using Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays on rabbit conjunctival epithelial cells (RCECs).Four doses of 5 mg/mL levamisole applied at 30 min intervals cleared T. callipaeda from infected eyes within 2 h without significant changes in CBC, serum biochemistry, or ocular symptom scores. CCK-8 and LDH assays indicated minimal cytotoxicity in RCECs within 4 h. However, prolonged exposure (6–12 h) led to a significant decrease in RCEC viability, suggesting potential cytotoxicity with extended use and highlighting the need for further safety evaluation. A regimen of four topical administrations of 5 mg/mL levamisole at 30 min intervals cleared T. callipaeda from infected eyes with minimal cytotoxicity, supporting its safety and efficacy as a topical treatment. Full article

Vitamin D, a hormone synthesized in the skin through ultraviolet B radiation (UVB), plays a crucial role not only in calcium and phosphate homeostasis but also in regulating skin homeostasis and modulating immune responses. In keratinocytes, vitamin D is converted to its active form, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D), which interacts with the vitamin D receptor (VDR) to regulate gene expression involved in proliferation, differentiation, and antimicrobial defense. Dysregulation of this pathway has been implicated in inflammatory skin diseases such as psoriasis, atopic dermatitis, acne vulgaris, and hidradenitis suppurativa. These conditions are associated with altered epidermal differentiation, immune imbalance, and microbial interactions, where vitamin D plays a modulatory role by suppressing proinflammatory cytokines, enhancing antimicrobial peptide synthesis, and restoring skin barrier integrity. Topical vitamin D analogues have shown therapeutic benefits in psoriasis, while emerging evidence supports the adjunctive role of vitamin D supplementation in acne, hidradenitis suppurativa, and atopic dermatitis. Despite promising associations between low serum vitamin D levels and disease severity, a causal relationship remains uncertain. This review integrates molecular mechanisms with clinical findings, emphasizing the role of vitamin D in cutaneous physiology and pathology, and highlights the need for further research into targeted supplementation strategies in dermatological disorders. Full article

Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role of lipid metabolism in the health of the central nervous system. The aim of our work was to provide an update on this topic, with a focus on clinical practice from an endocrinological point of view. Endocrinologists, being experts in the management of dyslipidemias, can play a key role in the prevention and treatment of neurodegenerative conditions, through precocious and effective lipid profile optimization. Methods: The literature was scanned to identify clinical trials and correlation studies on the association between dyslipidemia, statin therapy, and the following neurodegenerative diseases: Alzheimer’s disease (AD), Parkisons’s disease (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). Results: Impaired lipid homeostasis, such as that frequently observed in patients affected by obesity and diabetes, is related to neurodegenerative diseases, such as AD, PD, and other cognitive deficits related to aging. AD and related dementias are now a real priority health problem. In the United States, there are approximately 7 million subjects aged 65 and older living with AD and related dementias, and this number is projected to grow to 12 million in the coming decades. Lipid-lowering therapy with statins is an effective strategy in reducing serum low-density lipoprotein cholesterol to normal range concentrations and, therefore, cardiovascular disease risk; moreover, statins have been reported to have a positive effect on neurodegenerative diseases. Conclusions: Several pieces of research have found inconsistent information following our review. There was no association between statin use and ALS incidence. More positive evidence has emerged regarding statin use and AD/PD. However, further large-scale prospective randomized control trials are required to properly understand this issue. Full article

Kidney transplantation is the most effective replacement therapy for kidney failure, providing the best outcomes in terms of patient survival and offering a better quality of life. However, despite the progressive improvement in kidney survival, the recurrence of original disease remains one of the most important causes of graft loss and a major challenge that requires clinical vigilance throughout the transplant’s duration. Additionally, the type and severity of recurrence affect both treatment options and graft survival. This is especially true for the recurrence of systemic diseases. In this narrative review, we will discuss the timing, frequency, severity, and treatment of post-transplant recurrence in three systemic diseases: lupus nephritis (LN), Antineutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (ANCA-GN), and Henoch–Schönlein purpura (HSP). The recurrence of lupus nephritis is less common than that of primary focal segmental glomerulosclerosis or C3 glomerulopathy. Its severity can range from mild mesangial to diffuse proliferative forms, with varying prognoses and treatment options, much like the original disease. In some patients with LN, as well as in those with ANCA-GN or HSP, the reactivation of the primary disease can affect other organs besides the kidneys, potentially leading to life-threatening conditions. These cases may require a multidisciplinary approach, making these transplants clinically more challenging. Extrarenal flare-ups often necessitate an increase in immunosuppression, which in turn raises the risk of infections. In these autoimmune diseases, the role of immunological tests in determining the timing of kidney transplants remains a topic of ongoing debate. However, elevated levels of certain immunological markers, such as anti-dsDNA antibodies, ANCA titers, or serum immunoglobulin A may indicate a reactivation of the disease, suggesting the need for more intensive patient monitoring. Full article

Although the pathogenesis of the neurodegenerative phenomena of Huntington’s disease (HD) is not well known, in the last 30 years, numerous data have been published that suggest a possible role of oxidative stress. The majority of studies regarding this issue were performed in different experimental models of this disease (neurotoxic models such as intraperitoneal injection of 3-nitropropionic acid or intrastriatal injection of quinolinic acid, transgenic animal models for HD, and cell cultures) and, less frequently, in samples of brain tissue, plasma/serum, blood cells, and other tissues from patients with a genetic–molecular diagnosis of presymptomatic and symptomatic HD compared to healthy controls. In this narrative review, we have summarized the data from the main studies in which oxidative stress parameters have been measured both in patients with HD and in experimental models of the same disease, as well as the few studies on gene variants involved in oxidative stress in patients with HD. Most studies addressing this issue in experimental models of HD have shown an increase in markers or oxidative stress, a decrease in antioxidant substances, or both. However, the results of studies on patients with HD have not been conclusive as few studies have been published on the matter. However, a meta-analysis of blood studies on HD patients (including a pool of serum and blood cell studies) has shown an increase in lipid peroxidation markers, OH8dG concentrations, and GPx activity and a decrease in GSH levels. Future prospective and multicenter studies with a long-term follow-up period involving a large number of HD patients and healthy controls are needed to address this topic. Full article