Granzyme B inhibition reduces autoantibody-induced dermal-epidermal separation in an ex vivo model of epidermolysis bullosa acquisita.

The pemphigoid disease epidermolysis bullosa acquisita (EBA) is an autoimmune blistering skin disease characterized by autoantibodies against type VII collagen (COL7), immune cell infiltrates at the dermal-epidermal junction and subepidermal blistering. Proteases, particularly granzyme B (GzmB), have been established as therapeutic targets for the treatment of EBA and other pemphigoid diseases. We investigated the impact of the novel GzmB inhibitor SNT-6935 on anti-COL7 IgG-induced subepidermal blistering in a well-established EBA ex vivo model. Our findings demonstrate that pharmacological targeting of GzmB with its selective inhibitor SNT-6935 significantly reduced autoantibody-induced dermal-epidermal separation in human skin cryosections. Interestingly, treatment of skin cryosections with recombinant human GzmB alone did not cause dermal-epidermal separation, suggesting that additional mechanisms alongside GzmB are required for tissue damage in EBA. In conclusion, our study highlights the significant contribution of GzmB to the pathogenesis of EBA and supports the notion of GzmB as a therapeutic target in EBA and other pemphigoid diseases.

Dr. Upendranath Brahmachari: The Unsung Hero of Indian Medical Research.

Upendranath Brahmachari (1873-1946) was a prominent Indian scientist and physician renowned for his groundbreaking work in tropical medicine. He is most famous for discovering urea stibamine, a highly effective treatment for kala-azar (visceral leishmaniasis), a deadly parasitic disease. This discovery had a significant impact on public health, saving countless lives in India and beyond. Born in Jamalpur, Bihar, Brahmachari pursued medical education at the University of Calcutta, where he later became a professor. His dedication to medical science earned him numerous accolades, including a knighthood in 1934. In 1929, Brahmachari was nominated for the Nobel Prize in Physiology or Medicine in recognition of his work on urea stibamine. Although he did not win, the nomination underscored the global significance of his contributions. In addition to his scientific achievements, Brahmachari was active in public service, advocating for improved healthcare and medical education in India. His legacy continues to inspire medical professionals and researchers worldwide.

Use of 'stacked' dermal template: Biodegradable temporising matrix to close a large myelomeningocele defect in a newborn.

Background: Myelomeningocele is a severe and complex congenital malformation of the central nervous system. Failure of neural tube closure at around four weeks of gestation results in an open communication between the neural placode and the external environment with varied functional impairment. Surgery is usually required. Objectives: The primary goals of surgical management are to preserve neural function and minimise infection. Reconstruction is dependent upon the site and size of the defect as well as the quality of the surrounding soft tissues. Surgeons may employ a range of reconstructive techniques in order to achieve closure. Skin substitutes, also known as dermal regeneration templates, have also been utilised. Discussion: In our unit, we use NovoSorb Biodegradable Temporising Matrix to reconstruct full-thickness skin and soft tissue defects. It is a synthetic, biodegradable, dermal regeneration template, composed of polyurethane foam bonded to a transparent sealing membrane and typically requires a two stage reconstruction. Integration and vascularisation take approximately three weeks. After this time, the recipient wound bed is suitable for split thickness skin grafting. A further benefit of dermal regeneration templates is the possibility of 'stacking' layers, which serves to increase the thickness of the final construct and to minimise overall contour defects. The authors present the case of a one-day-old full-term neonate with a large lumbosacral myelomeningocele that was successfully managed with staged, stacked NovoSorb Biodegradable Temporising Matrix and split thickness skin grafting. The authors believe this is the first case in which a 'stacked' dermal regeneration templates has been used to achieve healing of a primary myelomeningocele defect. Lay Summary: Background: NovoSorb Biodegradable Temporising Matrix (BTM) is a dermal regeneration template (DRT) and is used to reconstruct wounds following full-thickness skin and soft tissue loss resulting from burn injury, trauma, infection or surgery. It is composed of 2-millimetre thick, synthetic, biodegradable polyurethane foam bonded to a transparent (non-biodegradable) sealing membrane. Like all DRTs, it acts as a scaffold for cellular integration and vascularisation to eventually form a 'neo-dermis'. This is usually apparent from around three weeks. A second stage procedure can then be performed, with removal of the outer sealing membrane and split thickness skin grafting of the vascularised layer.Objectives: Myelomeningocele is a severe and complex congenital malformation of the central nervous system and forms the group of anomalies commonly referred to as neural tube defects (NTDs). Neural tube closure usually occurs at around four weeks of gestation and failure to do so, results in an open communication between the neural placode and the external environment. The degree of functional impairment varies but can include: lower limb paralysis; sensory loss; bladder and bowel dysfunction. In order to preserve neural function and minimise the risk of infection, surgery is usually required to close the defect. Reconstruction is varied and is dependent upon the site and size of the defect as well as the quality of the surrounding soft tissues. The use of local flaps has the potential complication of skin necrosis. Muscle based flaps may be debilitating and limit future functionality and worsen postural development. We were presented with a one-day-old neonate with a large lumbosacral myelomeningocele. A DRT (NovoSorb BTM) was selected as the primary reconstruction. Firstly, selection provided relatively low risk, with minimal morbidity and preserved the full complement of flap based reconstructive options for a later stage should instrumentation be required. Secondly, NovoSorb BTM conferred a robust seal over the dural repair with no demonstrable cerebrospinal fluid leak. Thirdly, the ability to add layers ('stack') of NovoSorb BTM in stages, once integration and vascularisation of the previous layer is complete, allows reconstruction of deeper contour defects.Discussion: We have illustrated the successful use of NovoSorb BTM as a DRT to achieve closure of a large lumbosacral myelomeningocele without complication and with longstanding stability. We believe this technique provides reconstructive teams with an alternative option that is effective, safe and reproducible and which spares local tissues for future elective reconstructive procedures, should they be required.

Acellular Dermal Matrix: Imaging Features With Histopathology Correlation.

Acellular dermal matrix (ADM) is an immunologically inert graft, typically from cadaveric skin, often used in postmastectomy breast reconstruction. Created from decellularized dermal tissues that have been treated to remove DNA and antigenic donor cells (leaving extracellular matrix), ADM is often used as a structural scaffold or sling to reinforce and support the structure and position of a breast implant during postoperative integration in implant-based breast reconstruction; ADM can also be used to fill cosmetic defects. Advantages of ADM use include improved cosmesis and reduced capsular contracture rates. On US, ADM can be seen as a subtle band with variable echogenicity adjacent to the implant. When folded on itself or redundant, ADM may present as a palpable oval mass with indistinct or circumscribed margins and variable echogenicity. On mammography, ADM can be seen as a circumscribed oval equal density mass when redundant and folded on itself; a layered appearance may be evident on tomosynthesis. On MRI, presence and absence of enhancement have been documented. Imaging findings likely vary depending on the degree of host tissue remodeling and incorporation, and when biopsied, histopathologically, ADM may be difficult to distinguish from scarring. Successful imaging diagnosis of ADM is aided by clinical knowledge of the intraoperative use and configuration of ADM, which may help differentiate ADM from new or recurrent malignancy and avoid unnecessary biopsy.

Assessment of Pain and Satisfaction After Orofacial Harmonization Procedures.

AIMS: This long-term study assessed satisfaction and pain levels following facial aesthetic procedures. The study also aimed to correlate expectations, and psychological and social well-being immediately and after one month, describe perceived age, and assess differences in satisfaction between injectable fillers and other Orofacial Harmonization procedures such as hyaluronic acid treatments (for dark circles, nasolabial fold lips, malar, jaw), botulinum toxin injections, enzymatic lipolysis of the double chin, micro-needling, and PDO threads. METHODS: Data were collected immediately after the procedures and then again 30 days later. Among the participants, 159 (92.4%) were females and 13 (7.6%) were males, who completed FACE-Q questionnaires addressing perceived age, expectations, psychological and social well-being, satisfaction, and facial appearance, as well as the visual pain scale. RESULTS: The average age of the patients treated in the Dental Clinics in Brazil was 40.4 years (SD± 12.7), with 48.8% of participants perceiving themselves as older immediately after the procedures, decreasing to 47.7% after 30 days, and pain intensity was reported as low. The total number of Orofacial Harmonization procedures performed was 256. Satisfaction after 30 days was high, especially among those who received fillers. The psychological and social function scales were positively correlated with satisfaction with the decision, result, and appearance scales. Fillers showed a significant improvement in perceived age appearance, with half of the patients feeling younger after 30 days. The patients exhibited high satisfaction levels in one-month post-aesthetic orofacial harmonization procedures. Despite initially high expectations, patients reported enhanced psychological and social well-being, along with minimal pain during interventions CONCLUSION: Positive correlations were observed between satisfaction, decision-making, result perception, and appearance. Injectable fillers notably improved perceived aging, with a significant portion of patients initially perceiving themselves as older than their actual age, but later feeling younger post-procedure. Fillers also yielded superior satisfaction and pain relief compared to alternative interventions. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Endogenous electric field coupling Mxene sponge for diabetic wound management: haemostatic, antibacterial, and healing.

Improper management of diabetic wound effusion and disruption of the endogenous electric field can lead to passive healing of damaged tissue, affecting the process of tissue cascade repair. This study developed an extracellular matrix sponge scaffold (K1P6@Mxene) by incorporating Mxene into an acellular dermal stroma-hydroxypropyl chitosan interpenetrating network structure. This scaffold is designed to couple with the endogenous electric field and promote precise tissue remodelling in diabetic wounds. The fibrous structure of the sponge closely resembles that of a natural extracellular matrix, providing a conducive microenvironment for cells to adhere grow, and exchange oxygen. Additionally, the inclusion of Mxene enhances antibacterial activity(98.89%) and electrical conductivity within the scaffold. Simultaneously, K1P6@Mxene exhibits excellent water absorption (39 times) and porosity (91%). It actively interacts with the endogenous electric field to guide cell migration and growth on the wound surface upon absorbing wound exudate. In in vivo experiments, the K1P6@Mxene sponge reduced the inflammatory response in diabetic wounds, increased collagen deposition and arrangement, promoted microvascular regeneration, Facilitate expedited re-epithelialization of wounds, minimize scar formation, and accelerate the healing process of diabetic wounds by 7 days. Therefore, this extracellular matrix sponge scaffold, combined with an endogenous electric field, presents an appealing approach for the comprehensive repair of diabetic wounds.

Treatment of a Congenital Melocytic Giant Naevi at Age 39 Using Split-Thickness Skin Graft Over an Artificial Dermal Scaffold Through 2-Step Operation: A Novel Technique and Literature Review.

Congenital melanocytic nevus is a benign proliferation seen from birth. However, malignant transformation can be observed in later ages, so the removal of especially large and giant nevi is recommended during childhood. Nevertheless, there are no cases reported in the literature regarding excision of giant congenital melanocytic nevi in advanced age. This article presents the first case of a 39-year-old patient with a giant congenital melanocytic nevus covering 10% of the total body surface area, who underwent treatment with a 2-step operation. The nevus was located on the back, covering 10% of the total body surface area. The patient underwent en-bloc excision. A bilayer dermal matrix was applied over the fascia. Subsequently, a split-thickness skin graft was applied to the entire area. Full re-epithelialization was achieved within a total of 35 days. Thanks to the applied dermal scaffold, the area became pliable.

Reconstruction of Complex Upper Extremity Wounds With Novosorb Biodegradable Temporizing Matrix Versus Integra Collagen-Chondroitin Silicone: A Cost Analysis.

Background: Reconstruction of upper extremity wounds with dermal matrices can reduce the length of hospitalization and surgical complexity without compromising functional outcomes. We aimed to compare costs between Novosorb biodegradable temporizing matrix (BTM) and Integra collagen-chondroitin silicone (CCS) bilayer. Methods: A chart review was performed for patients with isolated upper extremity traumatic wounds who underwent reconstruction with either BTM or CCS between January 2017 and May 2022. Demographic data, surgical procedures, outcomes, and costs were collected for analysis. Results: Twenty-seven patients were included: 18 BTM and 9 CCS. There were no differences in age, sex, wound size, or dermal template size. Skin grafting was required less frequently in BTM compared with CCS (44.4% vs 55.6%, P = .013). Time to skin graft was longer in the BTM group (43.4 days vs 21.4 days, P = .002). The BTM group experienced fewer complications (33.3% vs 55.6%, P = .002). The mean number of secondary procedures required after template placement was 0.67 in BTM compared with 1.56 in CCS, P = .049. When factoring in the cost of product, the cost of reconstruction with BTM was significantly lower than CCS ($1361.92 vs $3185.71, P = .049). Conclusions: Novosorb BTM is a more cost-effective option when compared with CCS for reconstruction of upper extremity soft tissue defects.

Choline-based ionic liquids enhance the dermal delivery of cyclosporine a for potential treatment of psoriasis.

Psoriasis is a prevalent chronic disease affecting 2-3% of the global population. Cyclosporine A (CyA) has been widely used with great promise in the treatment of moderate to severe psoriasis despite various side effects associated with its systemic administration. Topical administration of CyA circumvents systemic side effects; however, the poor water solubility and large molecular weight of CyA pose challenges for dermal delivery. In this study, choline-based ionic liquids (ILs) were used to enhance the dermal delivery of CyA for the potential treatment of psoriasis. All four ILs tested significantly improved the solubility of CyA, which was greater than that of the control group with dimethyl sulfoxide (DMSO) as a solubilizer (20%, w/w). The saturated solubility of CyA in two of the ILs, choline geranate ([Ch][Ge]) and choline ricinoleate ([Ch][Ra]), reached more than 90 mg/mL, and the solubilization capability of the ILs except [Ch][Ci] was resistant to water dilution. The negligible change in CyA content determined by high-performance liquid chromatography and the secondary structure detected by circular dichroism spectroscopy confirmed the stability of CyA in the ILs. At 4 h in the in vitro penetration test, the amount of CyA retained in the skin in the IL groups was slightly greater than that in the control group (20% DMSO). The water content of the ILs significantly affected their penetration ability. When the water content increased from 10 to 70%, the dermal delivery of CyA first increased, peaked at a water content of 30%, and then decreased. The dermal delivery ability of [Ch][Ge] and [Ch][Ra] with a water content of 70% was still comparable to that of 20% DMSO. Moreover, CyA-loaded ILs (0.5%, w/w) significantly relieved the symptoms of psoriasis in an imiquimod (IMQ)-induced mouse model, and the levels of inflammatory factors, including tumor necrosis factor α, interleukin 22 and interleukin 17, in the affected area were reduced by 71.7%, 75.6%, and 89.3%, respectively. The IL tested, choline sorbate ([Ch][So]), showed low cytotoxicity to human immortalized epidermal cells (HaCaT). After 7 days of consecutive application, [Ch][So] did not cause significant irritation. In conclusion, ILs demonstrate promising potential for the dermal delivery of CyA for the treatment of psoriasis.

Bisphenols in daily clothes from conventional and recycled material: evaluation of dermal exposure to potentially toxic substances.

Given the increasing concern about chemical exposure from textiles, our study examines the risks of dermal exposure to bisphenol A (BPA), bisphenol S (BPS), bisphenol B (BPB) and bisphenol F (BPF) from conventional and recycled textiles for adults, aiming to obtain new data, assess exposure, and evaluate the impact of washing on bisphenol levels. A total of 57 textile samples (33 from recycled and 24 from conventional material) were subjected to ultrasound-assisted extraction (UAE) followed by ultra-high performance liquid chromatography with tandem mass spectrometry analysis (UHPLC-MS/MS). The BPA and BPS concentrations varied widely (BPA: < 0.050 to 625 ng/g, BPS: 0.277-2,474 ng/g). The median BPA content in recycled textiles (13.5 ng/g) was almost twice as high as that of 7.66 ng/g in conventional textiles. BPS showed a median of 1.85 ng/g in recycled textiles and 3.42 ng/g in conventional textiles, indicating a shift from BPA to BPS in manufacturing practices. Simulated laundry experiments showed an overall reduction in bisphenols concentrations after washing. The study also assessed potential health implications via dermal exposure to dry and sweat-wet textiles compared to a tolerable daily intake (TDI) of 0.2 ng/kg bw/day for BPA set by the European Food Safety Authority (EFSA). Exposure from dry textiles remained below this threshold, while exposure from wet textiles often exceeded it, indicating an increased risk under conditions that simulate sweating or humidity. By finding the widespread presence of bisphenols in textiles, our study emphasises the importance of being aware of the potential risks associated with recycling materials as well as the benefits.

Antioxidant, Apoptotic, and Wound Healing Effects of Xantolis cambodiana Extracts in Normal Human Dermal Fibroblasts.

Xantolis cambodiana has demonstrated significant antioxidant properties; however, the mechanisms underlying its protective effects against oxidative stress in cellular systems remain unexplored. This work investigated the efficacy of methanolic extracts in exhibiting oxidative damage and examined their mechanisms. The methanolic extract had a high phenolic content (116.89 ± 29.01 mg GAE/g FW) and exhibited scavenging of 2,2-diphenyl-1-picrylhydrazyl radicals with an IC50 value of 42.35 ± 9.20 µg/ml. In addition, it had the highest antioxidant activity based on ferric-reducing antioxidant power (467.45 ± 50.74 mg AA/100 g). Normal human dermal fibroblast (NHDF) cells were pretreated with the methanolic extract in a hydrogen peroxide (H2O2; 500 mM)-induced oxidative stress model, which resulted in a significant decrease in apoptosis and autophagy. Not only did the methanolic extract reduce mitochondrial membrane potential, it also stimulated NHDF cell migration and reduced reactive oxygen species production through mitochondrial dysfunction in the H2O-induced stress model. These findings suggested that the methanolic extract (25 µg/ml) attenuated H2O2-induced oxidative stress in NHDF cells, significantly reducing apoptosis, autophagy, and mitochondrial dysfunction. Thus, this extract has the potential to support the wound healing process due to its antioxidant activity.

Unraveling the role of MiR-181 in skin fibrosis pathogenesis by targeting NUDT21.

Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by widespread fibrosis in the skin and several internal organs. Nudix Hydrolase 21 (NUDT2 or CFIm25) downregulation in fibroblasts is known to play detrimental roles in both skin and lung fibrosis. This study aims to investigate the upstream mechanisms that lead to NUDT21 repression in skin fibrosis. We identified transforming growth factor ß (TGFß1) as the primary cytokine that downregulated NUDT21 in normal skin fibroblasts. In the bleomycin-induced dermal fibrosis model, consistent with the peak activation of TGFß1 at the late fibrotic stage, NUDT21 was downregulated at this stage, and delayed NUDT21 knockdown during this fibrotic phase led to enhanced fibrotic response to bleomycin. Further investigation suggested TGFß downregulated NUDT21 through microRNA (miRNA) 181a and 181b induction. Both miR-181a and miR-181b were elevated in bleomycin-induced skin fibrosis in mice and primary fibroblasts isolated from SSc patients, and they directly targeted NUDT21 and led to its downregulation in skin fibroblasts. Functional studies demonstrated that miR-181a and miR-181b inhibitors attenuated bleomycin-induced skin fibrosis in mice in association with decreased NUDT21 expression, while miR-181a and miR-181b mimics promoted bleomycin-induced fibrosis. Overall, these findings suggest a novel role for miR-181a/b in SSc pathogenesis by repressing NUDT21 expression.

Should the Dermatological Assessment of Patients with Inflammatory Bowel Disease Become Standard during Qualifications for Biological Treatment? A Retrospective, Single-Center Experience from a Tertiary Center.

Background: Oncological anxiety associated with biological therapy is a particular challenge in inflammatory bowel disease (IBD), and it has raised questions about the need for the dermatological assessment of the skin before starting biological therapy. Methods: The aim of this study was to assess the frequency of dermal lesions, including cutaneous malignancies, in IBD patients. This retrospective, single-center study evaluated 805 IBD patients who qualified for biological treatment and were subjected to a dermatological assessment. Results: Dermal lesions (DLs) were found in 15.5% (125) of IBD patients. A risk factor for DLs was higher with body mass index (OR = 1.08, 95% CI [1.02; 1.14], p = 0.007). Surprisingly, there was no effect of thiopurines between the groups with and without DLs (90.4% vs. 84.6%, MD = 0.06, 95% CI [0.01; 0.12], p = 0.118). Moreover, cutaneous malignancies were diagnosed in 9 cases (1.1%), including 4 basal cell carcinomas, 4 squamous cell carcinomas, and 1 melanoma skin cancer. Only 13.4% of patients complied with our strict policy of skin surveillance every 6-8 months. Conclusions: DLs, including cutaneous malignancies, are common in patients with IBD, making skin monitoring at the initiation of biological treatment an extremely useful tool. The lack of effect of the drugs used suggests that skin surveillance is necessary in all IBD patients. The low compliance of skin monitoring among immunosuppressed patients indicates the need for better education on the prevention of cutaneous malignancies.

Studies on cytocompatibility of human dermal fibroblasts on carbon nanofiber nanoparticle-containing bioprinted constructs.

Functional nanocomposite-based printable inks impart strength, mechanical stability, and bioactivity to the printed matrix due to the presence of nanomaterials or nanostructures. Carbonaceous nanomaterials are known to improve the electrical conductivity, osteoconductivity, mechanical, and thermal properties of printed materials. In the current work, we have incorporated carbon nanofiber nanoparticles (CNF NPs) into methacrylated gelatin (GelMA) to investigate whether the resulting nanocomposite printable ink constructs (GelMA-CNF NPs) promote cell proliferation. Two kinds of printable constructs, cell-laden bioink and biomaterial ink, were prepared by incorporating various concentrations of CNF NPs (50, 100, and 150 µg/mL). The CNF NPs improved the mechanical strength and dielectric properties of the printed constructs. The in vitro cell line studies using normal human dermal fibroblasts (nHDF) demonstrated that CNF NPs are involved in cell-material interaction without affecting cellular morphology. Though the presence of NPs did not affect cellular viability on the initial days of treatment, it caused cytotoxicity to the cells on days 4 and 7 of the treatment. A significant level of cytotoxicity was observed in the highly CNF-concentrated bioink scaffolds (100 and 150 µg/mL). The unfavorable outcomes of the current work necessitate further study of employing functionalized CNF NPs to achieve enhanced cell proliferation in GelMA-CNF NPs-based bioprinted constructs and advance the application of skin tissue regeneration.

Hypoxia and Foxn1 alter the proteomic signature of dermal fibroblasts to redirect scarless wound healing to scar-forming skin wound healing in Foxn1-/- mice.

BACKGROUND: Foxn1-/- deficient mice are a rare model of regenerative skin wound healing among mammals. In wounded skin, the transcription factor Foxn1 interacting with hypoxia-regulated factors affects re-epithelialization, epithelial-mesenchymal transition (EMT) and dermal white adipose tissue (dWAT) reestablishment and is thus a factor regulating scar-forming/reparative healing. Here, we hypothesized that transcriptional crosstalk between Foxn1 and Hif-1α controls the switch from scarless (regenerative) to scar-present (reparative) skin wound healing. To verify this hypothesis, we examined (i) the effect of hypoxia/normoxia and Foxn1 signalling on the proteomic signature of Foxn1-/- (regenerative) dermal fibroblasts (DFs) and then (ii) explored the effect of Hif-1α or Foxn1/Hif-1α introduced by a lentiviral (LV) delivery vector to injured skin of regenerative Foxn1-/- mice with particular attention to the remodelling phase of healing. RESULTS: We showed that hypoxic conditions and Foxn1 stimulation modified the proteome of Foxn1-/- DFs. Hypoxic conditions upregulated DF protein profiles, particularly those related to extracellular matrix (ECM) composition: plasminogen activator inhibitor-1 (Pai-1), Sdc4, Plod2, Plod1, Lox, Loxl2, Itga2, Vldlr, Ftl1, Vegfa, Hmox1, Fth1, and F3. We found that Pai-1 was stimulated by hypoxic conditions in regenerative Foxn1-/- DFs but was released by DFs to the culture media exclusively upon hypoxia and Foxn1 stimulation. We also found higher levels of Pai-1 protein in DFs isolated from Foxn1+/+ mice (reparative/scar-forming) than in DFs isolated from Foxn1-/- (regenerative/scarless) mice and triggered by injury increase in Foxn1 and Pai-1 protein in the skin of mice with active Foxn1 (Foxn1+/+ mice). Then, we demonstrated that the introduction of Foxn1 and Hif-1α via lentiviral injection into the wounded skin of regenerative Foxn1-/- mice activates reparative/scar-forming healing by increasing the wounded skin area and decreasing hyaluronic acid deposition and the collagen type III to I ratio. We also identified a stimulatory effect of LV-Foxn1 + LV-Hif-1α injection in the wounded skin of Foxn1-/- mice on Pai-1 protein levels. CONCLUSIONS: The present data highlight the effect of hypoxia and Foxn1 on the protein profile and functionality of regenerative Foxn1-/- DFs and demonstrate that the introduction of Foxn1 and Hif-1α into the wounded skin of regenerative Foxn1-/- mice activates reparative/scar-forming healing.

A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis.

In a recent phase 2a clinical trial, the candidate leishmaniasis vaccine ChAd63-KH was shown to be safe and immunogenic in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). However, its value as a stand-alone therapeutic was unknown. To assess the therapeutic efficacy of ChAd63-KH, we conducted a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov: NCT03969134). Primary outcomes were safety and efficacy (≥90% improvement in clinical disease). Secondary outcomes were change in severity grade and vaccine-induced immune response. 86 participants with uncomplicated PKDL of ≥6 month duration were randomized to receive ChAd63-KH (7.5 × 1010 viral particles, once by the intramuscular route) or placebo. 75 participants (87%) completed the trial as per protocol. No severe or serious adverse events were observed. At day 90 post-vaccination, 6/40 (15%) and 4/35 (11%) participants in the vaccine and placebo groups, respectively, showed ≥90% clinical improvement (risk ratio [RR] 1.31 [95% confidence interval (CI), 0.40-4.28], p = 0.742). There were also no significant differences in PKDL severity grade between study arms. Whole-blood transcriptomic analysis identified transcriptional modules associated with interferon responses and monocyte and dendritic cell activation. Thus, a single vaccination with ChAd63-KH showed no therapeutic efficacy in this subset of Sudanese patients with PKDL.

Infants exposure to chemicals in diapers: A review and perspective.

Diapers are a staple care product for infants, yet concerns persist regarding the potential risks posed by dermal exposure to chemicals through their usage. This review provides a comprehensive summary of reported chemicals, highlighting the frequent detection of polychlorodibenzo-p-dioxins (PCDDs), phthalates (PAEs), volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), bisphenols (BPs), organotins, and heavy metals. Disposable diapers commonly exhibit higher concentrations of VOCs, PAEs, BPs, and heavy metals than other chemicals. Our estimation reveals formaldehyde as posing the highest dermal exposure dose, reaching up to 0.018 mg/kg bw/day. Conversely, perfluorooctanoic acid (PFOA) exhibits lower exposure, but its non-cancer hazard quotient (0.062) is the highest. In most scenarios, the risk of chemical exposure through diapers for infants is deemed acceptable, while the risk is higher under some extreme exposure scenarios. Using the cancer slope factor recently suggested by U.S. EPA, the cancer risk in diapers raised by PFOA is 5.5 × 10-5. It should be noted that our estimation is approximately 1000-10,000 folds lower than some previous estimations. The high uncertainties associated with exposure and risk estimations are primarily raised by unclear parameters related to chemical migration coefficients, absorption factors, concentrations, and toxicity data for skin exposure, which requires research attention in future. Besides that, future research endeavors should prioritize the identification of potential toxic chemicals and the development of hygiene guidelines and standards.

Primary Dermal Melanoma.

Primary dermal melanoma (PDM) is a rare subtype of melanoma with an estimated incidence of less than 1%. PDM presents entirely in the dermis or subcutis and histopathologically mimics cutaneous metastases of melanoma due to its lack of connection to the overlying epidermis. A thorough history and examination, including imaging evaluation for metastatic disease, will reveal no prior history or concurrent lesion of primary cutaneous or metastatic melanoma. Despite its histopathologic similarities to melanoma metastasis, PDM is associated with an unexpectedly favorable prognosis. This review discusses the clinical and histopathologic features of PDM as a distinct subtype of melanoma, as well as the current approach to clinical staging and management.

Biodegradable polymers and platelet-rich plasma causing visual impairment: a literature review.

BACKGROUND: Dermal fillers are widely used for facial rejuvenation and esthetic enhancement, offering temporary solutions for aging and volume loss. Despite their general safety, a rare but severe complication associated with these fillers is visual impairment, including blindness. This underscores the need for a thorough understanding of risks associated with various filler materials. Historical cases of blindness following filler injections date back to 1963, with increasing reports linked to the expansion of the cosmetic filler industry. While hyaluronic acid (HA) and autologous fat have been extensively studied, other fillers such as calcium hydroxylapatite and poly-l-lactic acid (PLLA) are less understood. OBJECTIVE: This systematic review aims to address gaps in the literature by providing a comprehensive overview of visual impairment caused by fillers other than HA and autologous fat. We systematically examine the prevalence, causes, clinical features, and treatment outcomes associated with these less common fillers. MATERIALS AND METHODS: A comprehensive literature search was conducted across databases including PubMed, Scopus, and Google Scholar using terms related to visual impairment and dermal fillers. Studies published between 2014 and 2021, including observational studies and case reports, were included. Studies were selected based on predefined inclusion and exclusion criteria, and a PRISMA flow diagram was used to illustrate the study selection process. RESULTS: The review identifies and summarizes cases of visual impairment associated with calcium hydroxylapatite, poly-d,l-lactic acid (PDLLA), and PLLA fillers. Key findings reveal that visual impairment following these fillers is rare but can occur suddenly or within a few days of the procedure. Cases of delayed onset up to two weeks are also noted, emphasizing the need for extended post-procedure monitoring. DISCUSSION: The review highlights unique insights into the risks associated with non-HA fillers, such as the heightened risk in the periorbital region and other facial areas. It explores mechanisms of complications, including retrograde flow of emboli leading to retinal ischemia. The discussion also covers emergency protocols and preventative measures, providing valuable guidance for managing and mitigating risks. CONCLUSIONS: Visual impairment caused by fillers other than HA and autologous fat, while rare, represents a serious complication that requires careful attention. This review contributes new perspectives on the differential risks of various fillers, symptom onset variability, and anatomical risk factors. Emphasizing the importance of proper patient selection, technique, and monitoring, it calls for further research to better understand and prevent these complications, ultimately aiming for safer and more effective use of soft-tissue fillers.

Developmental regulation of dermal adipose tissue by BCL11b.

The distinct anatomic environment in which adipose tissues arise during organogenesis is a principle determinant of their adult expansion capacity. Metabolic disease results from a deficiency in hyperplastic adipose expansion within the dermal/subcutaneous depot; thus, understanding the embryonic origins of dermal adipose is imperative. Using single-cell transcriptomics throughout murine embryogenesis, we characterized cell populations, including Bcl11b + cells, that regulate the development of dermal white adipose tissue (dWAT). We discovered that BCL11b expression modulates the Wnt signaling microenvironment to enable adipogenic differentiation in the dermal compartment. Subcutaneous and visceral adipose arises from a distinct population of Nefl + cells during embryonic organogenesis, whereas Pi16 + /Dpp4 + fibroadipogenic progenitors support obesity-stimulated hypertrophic expansion in the adult. Together, these results highlight the unique regulatory pathways used by anatomically distinct adipose depots, with important implications for human metabolic disease.