Search Results (356)

Columnaris disease is a highly contagious infection that affects nearly all freshwater fish species worldwide. Grass carp, one of the most economically significant freshwater fish species in China, is particularly susceptible to the disease, leading to large-scale mortality. Flavobacterium columnare and F. covae are the primary pathogens causing columnaris disease in Chinese grass carp aquaculture. Herein, we compare mortality rates, replication rates of typical columnaris symptoms, histopathological changes, and bacterial content in the tissues of grass carp following infection using four challenge models. The mortality rate in grass carp challenged via intraperitoneal injection was 86.7%. All fish infected via intramuscular and intradermal injections died, while immersion resulted in lower mortality. Gill corrosion rates were 67%, 53%, and 87%, respectively, in the intramuscular injection, intradermal injection, and immersion groups. Correspondingly, skin ulceration rates were 75%, 91%, and 63%. However, surface symptoms in the intraperitoneal injection group were milder. Histopathological analysis revealed similar lesions in grass carp subjected to immersion, intramuscular, and intradermal infection, which differed from carp infected via intraperitoneal injection. The trends in bacterial loads in the gills and skin were similar, although the absolute bacterial content varied between tissues. Bacterial loads in the immersion and intraperitoneal injection groups were lower than those in the other groups. Based on these findings, we determined that the optimal model for simulating columnaris disease in grass carp is the intradermal injection of F. covae in 10–12 cm fish. The infection model generated via intradermal injection resembles natural F. covae infection and can serve as a good tool for evaluating the protective effect of anti-F. covae infection vaccines in grass carp. Full article

Background: Androgenetic alopecia (AGA) is the most prevalent form of hair loss in humans. Oral minoxidil and dutasteride are widely used treatments, while intradermal dutasteride mesotherapy has recently gained interest as a complementary approach. However, comparative studies in real-world settings are lacking. Objective: The aim was to compare the effectiveness and safety of four AGA therapies: oral minoxidil alone (OM), OM plus oral dutasteride (OM + OD), OM plus mesotherapy (OM + MD), and a combination of all three (CT). Methods: A retrospective study was conducted, including 280 adult patients (mean age 35 ± 9.4 years) with AGA, excluding those with recent treatment (last 3 months) or other hair loss disorders. The therapeutic response was assessed by comparing treatment outcomes from standardized clinical images at 6 and 12 months using a four-point improvement scale. Patient satisfaction was also assessed using a four-point subjective scale. Results: Participants were divided into four treatment groups. In total, 74 patients (26.4%) were treated with OM, 65 patients (23.2%) with OM + OD, 61 patients (21.8%) with OM + MD, and 80 patients (28.6%) with CT. At 12 months, group 4 treated with CT showed significantly better results in both frontal and vertex areas (p < 0.001), while group 3 (OM + MD) performed best at 6 months in the vertex. Side effects were mild and infrequent, with hypertrichosis being the most common. Erectile dysfunction was reported with a lower incidence than reported in the literature: two patients (3.1%) in group 2 (OM + OD) and three (3.8%) patients in CT. Overall, no serious adverse events were detected. Conclusions: Combining oral minoxidil, oral dutasteride, and mesotherapy with dutasteride yields the most effective results for AGA with a favorable safety profile. Full article

Background/Objectives: Streptococcus suis (SS), an important zoonotic pathogen, has caused significant economic losses to the global pig industry. Existing commercial vaccines for SS mainly provide effective protection against a single serotype. Due to the existence of many serotypes and their robust immune evasion capabilities, the development of multi-component subunit vaccines or multi-epitope vaccines that provide effective cross-protection against different strains of SS is a key focus of current research. Methods: We applied two-dimensional electrophoresis (2-DE) and immunoblotting to screen for candidate immunogens among the immunogenic cell wall proteins of SS. BALB/c mice were immunized intradermally with a multi-component, multi-epitope vaccine. The vaccine’s safety and immunogenicity were assessed via clinical monitoring, antibody titer detection, cytokine assays, and survival curve analyses. Results: In this study, eight immunogenic cell wall proteins (GH25, Pk, PdhA, Ldh, ExoA, Pgk, MalX, and Dnak) were successfully identified using MALDI-TOF-MS, all of which could induce high IgG antibody titers. Based on the conservation and immunoprotection demonstrated by these eight protective antigenic proteins, PdhA, Ldh, and MalX were screened to construct a multi-component subunit vaccine as a candidate vaccine for providing cross-protection against SS isolates of multiple serotypes. Challenge studies showed that mice immunized with the multi-component subunit vaccine (PdhA, Ldh, and MalX) were protected against challenges with the SS2 virulent strain ZY05719 (62.5% protection) and the SSChz virulent strain CZ130302 (75% protection). Subsequently, we utilized immunoinformatics techniques to design a novel multi-epitope vaccine (MVPLM) derived from the immunogenic proteins PdhA, Ldh, and MalX. However, challenge tests revealed that the MVPLM offered limited protection against SS. Conclusions: These data demonstrate that a multi-component subunit vaccine composed of PdhA, Ldh, and MalX proteins shows promise as a candidate universal vaccine against multiple SS serotypes. Full article

Background and Clinical Significance: Granulomatous reactions are rare but clinically significant complications of aesthetic procedures involving dermal fillers, particularly in individuals with underlying immune dysregulation. These reactions present diagnostic and therapeutic challenges, especially when associated with undiagnosed or latent autoimmune diseases. This case illustrates the interaction between filler composition, immune status, and the risk of delayed inflammatory responses, underscoring the need for thorough patient evaluation and individualized management strategies. Case Presentation: A 49-year-old woman developed delayed-onset subcutaneous nodules following midface augmentation with two filler types: a monophasic, cross-linked hyaluronic acid gel (concentration 20 mg/mL, 1.0 mL per side) injected into the deep malar fat pads, and a calcium hydroxyapatite suspension (30% CaHA microspheres in a carboxymethylcellulose carrier, 0.5 mL per side) placed in the subdermal plane along the zygomatic arch. The procedure was performed in a single session using a 22 G blunt cannula, with no immediate adverse events. High-resolution ultrasound demonstrated hypoechoic inflammatory nodules without systemic symptoms. A retrospective review of her medical history revealed a latent, previously undisclosed diagnosis of granulomatosis with polyangiitis (GPA). The immune-adjuvant properties of calcium hydroxyapatite likely triggered a localized pro-inflammatory response in this predisposed patient. A conservative, staged, non-invasive therapeutic protocol—saline infiltration, intradermal polynucleotide injections, and manual lymphatic drainage—achieved complete clinical and radiological resolution without systemic immunosuppression or surgical intervention. Conclusions: This case highlights the critical importance of pre-procedural immunological assessment in aesthetic medicine. Subclinical autoimmune conditions may predispose patients to delayed granulomatous reactions after filler injections. An individualized, conservative management strategy can effectively resolve such complications while minimizing the risks associated with aggressive treatment. Greater awareness of immune-mediated responses to dermal fillers is essential to ensure patient safety and optimize clinical outcomes. Full article

Antibodies are indispensable for protection against biological toxins and pathogens, yet their conventional liquid formulations impose severe constraints, including dosing inaccuracy caused by residual fluid remaining in the syringe and limited user convenience such as pain caused by fluid-induced tissue distension and nerve stimulation as well as instability in ambient temperature, and the requirement for low-temperature storage and logistics. These limitations critically impair rapid deployment during golden hour following acute exposure. Here, we report an antibody-integrated solid-to-gel microfilm—demonstrated with a 100 µg anti-BoNT/A dose—jet-printed and low-temperature dried directly onto metal needles for consistent, on-demand use. Upon intradermal insertion, the microfilm fully dissolves within 5 min, driven by hydration-induced swelling of a hyaluronic acid (HA) support layer and rapid release of the antibody. Time-resolved microscopy and UV–vis analysis showed a decrease in residual solid from 2.34 mm³ to 0 over 300 s, with a concomitant rise at 187 nm indicative of complete dissolution. The solid formulation maintained ambient-temperature stability for 3–6 months with pharmacokinetics comparable to conventional subcutaneous liquid injections. In a lethal BoNT/A challenge, treated mice achieved 100% survival for 12 days, whereas controls succumbed within 16 h. Full article

Background: Melasma is a chronic, relapsing pigmented skin disease with challenging and unsatisfactory treatment outcomes. This study aims to compare the efficacy and safety of different treatments for melasma. Methods: We conducted a comprehensive search of PubMed and EMBASE databases to identify randomized controlled clinical trials (RCTs) for melasma treatment modalities between January 2022 and January 2025. Relative efficacy refers to the comparison of the improvement in melasma severity before and after treatment for all modalities of interest at a specific time point. The Melasma Area Severity Index (MASI) (also known as modified MASI (mMASI) or half-MASI score) was defined as the efficacy index. Safety refers to the incidence of the most common adverse events. The quality of the included trials was assessed using the GRADE method. Results: The analysis included 14 clinical trials with 15 treatment modalities involving 738 women who met the inclusion criteria. The mean difference in efficacy index showed that intradermal PRP (platelet-rich plasma) and intradermal PRP + oTXA (oral tranexamic acid) were the best treatment options compared with HQ4%, intradermal TXA, intradermal PRGF (plasma rich in growth factor) + HQ4 (hydroquinone 4%), followed by intradermal TXALaser (intradermal TXA + Q-switched fractional 1064-nmNd:YAG lasers). The efficacy indices of other modalities were comparable. Most treatment-related adverse events were mild, were well tolerated, or resolved with treatment. The quality of evidence was generally high. Conclusions: This NMA showed that intradermal PRP in combination or alone is an effective and safe treatment option for melasma. PRP may be a direction for the development of new melasma treatment options in the future, but well-designed, comprehensive, large-scale randomized controlled trials are needed to verify it. Full article

We hereby present a case of a 51-year-old woman with a pigmented nodule in the right axillary region. Histopathological examination revealed features consistent with an intradermal nevus. Notably, adjacent to the nevus, intralymphatic protrusion and lymphatic invasion were observed, comprising cells with morphological and immunohistochemical characteristics consistent with nevus cells. Next-generation sequencing revealed the BRAF V600E mutation. To date, 26 similar cases involving intralymphatic nevus cell protrusion and lymphatic invasion have been reported in the literature. Although this finding is rare and may pose a diagnostic challenge for pathologists, it should not be interpreted as indicative of malignancy. Rather, it must be assessed in the context of the lesion’s overall histological architecture. Full article

Biocompatibility evaluation of medical devices is essential for ensuring safety, with ISO 10993 series being the standard. However, these tests can be time-consuming and resource-intensive. This study assessed the early-stage biocompatibility of a collagen matrix derived from porcine dermis using three selective ISO tests: in vitro cytotoxicity, in vivo sensitization, and irritation. Collagen was hydrolyzed, purified from miniature pig skin, and then processed into porous sheets via lyophilization. Extracts were prepared using both polar and non-polar extraction vehicles for biological testing. Cytotoxicity testing with mouse fibroblast cells showed no significant cytotoxic effects, with cell morphology and viability comparable to controls. Sensitization testing in guinea pigs, involving intradermal and topical exposure, revealed no allergic responses. Irritation testing in rabbits showed no signs of irritation. The cytotoxicity test took 3 days, the sensitization test 28 days, and the irritation test 7 days, all of which proved suitable for early biocompatibility screening. These results confirmed that the collagen matrix is non-cytotoxic, non-sensitizing, and non-irritant for a month. The use of these three tests enables early identification of unsafe materials, reducing time, cost, and animal use before advancing to more complex ISO 10993 studies. Therefore, they are appropriate and necessary for early feasibility decisions in medical device development. Full article

Wound healing remains a significant clinical challenge worldwide, and effective management strategies are essential for improving outcomes. This study investigates the therapeutic potential of the AcuCool™ system, a novel multifunctional device that combines high-velocity CO₂ cryotherapy with intradermal delivery of epidermal growth factor (EGF), in promoting wound healing. Using a full-thickness skin wound model in Sprague Dawley rats, we compared the effects of Device+EGF treatment to those of conventional microneedling-based EGF delivery and untreated controls. Macroscopic assessments revealed significantly accelerated wound closure in the Device+EGF group. Histological analysis showed enhanced re-epithelialization, reduced inflammatory cell infiltration, and increased collagen deposition. Molecular evaluations further demonstrated downregulation of pro-inflammatory markers (TNF-α, IL-1β, MCP-1) and upregulation of remodeling-related genes including TGF-β1, Collagen I, and Vimentin. In addition, nitrite assays confirmed reduced local nitric oxide levels, indicating suppression of oxidative stress. The AcuCool™ platform offers precise, non-invasive drug delivery with dual physical and biochemical therapeutic mechanisms, enabling superior control of inflammation and tissue regeneration. These findings suggest that AcuCool™ represents a promising therapeutic strategy for accelerating wound healing in acute models. While further studies are warranted in chronic wound settings, this approach may hold translational potential for future clinical applications. Full article

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article

Background and Objectives: Spitz tumors represent a diagnostic challenge in dermatopathology due to their large spectrum of morphological characteristics and overlap with malignant lesions, especially in pathology departments where molecular pathology is not available. Even though most Spitz lesions are benign, the uncertainty around their biological behavior necessitates an integrated approach in daily practice. The objective of our study was to evaluate the epidemiological, macroscopic, and histopathological characteristics of Spitz lesions in accordance with WHO Classification of Skin Tumours. Materials and Methods: We performed a retrospective, descriptive, and hypothesis-generating study on Spitz tumors diagnosed between 2018 and 2024 in the Clinical Pathology Department of the Mures Clinical County Hospital, Romania. We included 10 cases and analyzed their macroscopic characteristics (localization, shape, dimension, and color), microscopic characteristics (cellular types, cytologic atypia, pagetoid migration, mitoses, and the type of lesion), and immunohistochemical profile. Results: The study population was composed of young patients with an average age of 20.2 years old, with a slight predominance of female gender. Most lesions were Spitz nevi, intradermic, or compound, with a fusiform, epithelioid, or rhomboid cell shape. Pagetoid migration and cytological atypia were seen in fewer cases. The Ki 67 proliferation index was under 5% in all cases. The main limitation of this study involved the low number of cases and the lack of molecular testing, which limited the molecular characterization of Spitz tumors. Complete excision was performed in all cases. Conclusions: In the absence of molecular testing, our study emphasizes the importance of clinical–morphological assessment using immunohistochemistry in establishing a correct diagnosis in Spitz lesions. Our results confirm that most of the Spitz lesions were benign and provide a basis for future research with a multidisciplinary approach, including molecular testing. Full article

Skin aging is commonly characterized by increased wrinkles, loss of elasticity, and hyperpigmentation, significantly affecting personal appearance and quality of life. Although botulinum toxin type A (BTX-A) has been widely applied in cosmetic anti-wrinkle treatments, its intrinsic cytotoxicity limits broader clinical applications. In this study, we developed a novel exosome-based BTX-A composite delivery system designed to synergize the anti-aging properties of exosomes with the wrinkle-reducing effects of BTX-A while reducing toxicity. Human adipose-derived mesenchymal stem cells were genetically modified via lentiviral transduction to overexpress Synaptic Vesicle Glycoprotein 2C (SV2C), the receptor of BTX-A, thereby producing SV2C-enriched functionalized exosomes (EXO^SV2C). These exosomes (2.0 × 10⁷ particles/mL) were incubated with BTX-A (3 U/mL) to generate the EXO^SV2C-BTX-A complex. In vitro, EXO^SV2C-BTX-A significantly promoted the proliferation and migration of human dermal fibroblasts and effectively alleviated D-galactose (D-gal)-induced cellular senescence and collagen type I loss. These effects were superior to those observed with either BTX-A or exosomes alone. In vivo, intradermal injection of EXO^SV2C-BTX-A for 28 days markedly suppressed D-gal-induced skin aging in 8-week-old male KM mice, as evidenced by reduced malondialdehyde levels in dermal tissue, enhanced collagen type I expression, and preserved skin structure. Notably, the composite exhibited significantly lower toxicity compared to free BTX-A. Collectively, these findings highlight EXO^SV2C-BTX-A as a promising exosome-mediated BTX-A delivery platform with enhanced anti-aging efficacy and improved biocompatibility, offering a potential therapeutic strategy for skin rejuvenation. Full article

Background and Clinical Significance: Osteonevus of Nanta is a rare histological phenomenon characterized by bone formation within a benign melanocytic nevus, most commonly in intradermal nevi of the head and neck. Although osteonevus of Nanta is rare, ossification in a cellular blue nevus is even more uncommon. To date, only one case of a cellular blue nevus with ossification has been documented. This case report adds to the limited literature and emphasizes the clinical importance of recognizing this rare phenomenon, as osteonevus of Nanta has been potentially associated with malignant melanoma. Case Presentation: A 72-year-old woman presented with an asymptomatic, pigmented scalp lesion that had recently increased in size. On clinical examination, the tumor appeared as a well-demarcated, firm, and nodular mass with dark blueish to violet pigmentation that measured 15 × 12 × 7 mm. To ensure a definitive diagnosis and rule out malignancy, the lesion was excised with narrow margins. Histological examination revealed a cellular blue nevus with prominent osseous metaplasia. Due to the absence of clear margins, a wider re-excision was performed. No residual tumor was found, and the patient remained asymptomatic with no recurrence. Conclusions: This case represents only the second published example of a cellular blue nevus with ossification. While osteonevus of Nanta is benign, its potential association with malignant melanoma, as well as its clinical resemblance to malignant entities such as nodular melanoma, malignant blue nevus, and pigmented basal cell carcinoma, underscores the need for thorough clinical and histopathologic evaluation. Full article

Background: Melasma is an acquired hyperpigmentation disorder with multifactorial etiologies and limited response to conventional therapies. Recent evidence suggests that Botulinum Toxin A (BoNT-A) may modulate ultraviolet (UV)-induced pigmentation and offer therapeutic benefits. Objective: We sought to evaluate the efficacy and safety of two intradermal dilutions of Letibotulinum toxin A (LetiBoNT-A) in Thai patients with melasma. Methods: In this randomized, double-blind, split-face study, 30 participants aged 32–62 years received a single intradermal injection of LetiBoNT-A, with 20 units administered per cheek. A 1:5 dilution was injected on one side of the face, and a 1:10 dilution was injected on the contralateral side. Outcomes were evaluated over a 6-month period using the Hemi-modified Melasma Area and Severity Index (Hemi-mMASI), VISIA^® brown spot analysis, and quantitative assessments of skin texture. Results: Both dilutions significantly improved Hemi-mMASI scores (1:5, p = 0.043; 1:10, p = 0.002) and brown spots (1:5, p = 0.002; 1:10, p < 0.001). The 1:10 dilution showed earlier and more sustained improvements. Subgroup analysis revealed greater reductions in Hemi-mMASI scores among patients with telangiectatic melasma, particularly with the 1:10 dilution, though they were not statistically significant. Additionally, the 1:10 dilution significantly reduced pore volume, pore area, and sebum levels. One case of transient facial asymmetry was reported with the 1:5 dilution. Conclusions: LetiBoNT-A is a safe and effective adjunct in melasma treatment. The 1:10 dilution offered superior clinical outcomes. Full article

Background/Objectives: Lawsonia intracellularis is a bacterium that causes Proliferative Enteropathy, an enteric infection characterized mainly by diarrhea and growth retardation, leading to important economic losses. Acute and chronic infections are easily diagnosed, and their control by vaccination has been proven efficacious. However, subclinical infections, despite being very prevalent, often remain underdiagnosed and uncontrolled in practice. Scarce research is available on the control of subclinical infections by vaccination, and the benefit in these scenarios remains to be elucidated. Two field trials were carried out to (1) determine the association between the growth and fecal shedding of L. intracellularis in unvaccinated and intramuscularly vaccinated pigs in a farm with subclinical infection and (2) assess the impact of intradermal vaccination against L. intracellularis on clinical performance and carcass quality in a herd with subclinical infection. Methods: A pig herd with subclinical infection was selected. Pigs were vaccinated intramuscularly (study 1) or intradermally (study 2) at weaning. Fecal shedding, performance, clinical parameters, and carcass quality were investigated. Results: Growth was negatively associated with the fecal load of L. intracellularis in non-vaccinated pigs, whereas in vaccinated pigs, growth performance was not impacted by fecal load (study 1). Vaccinated pigs presented a significantly lower fecal load, lower prevalence of tail biting (31.7%) compared with controls (54.2%), less back fat, and a greater Lean Meat percentage (study 2). Conclusions: Vaccination against L. intracellularis in a herd with subclinical infection and low fecal bacterial shedding led to a reduction in fecal shedding, a lower prevalence of tail biting, and an improvement in carcass quality. Full article