Cannabis sativa L. essential oil: chemical characterisation and antimicrobial activity against methicillin-resistant Staphylococcus pseudintermedius.

Cannabis sativa L. essential oil has attracted the interest of the scientific community thanks to its numerous biological activities. Several studies have evaluated EOs as alternative therapeutic approaches to limit the use of antibiotics; the present study aimed to evaluate the in vitro inhibitory and bactericidal activity of the essential oils obtained from the leaves and inflorescences of two hemp genotypes against twenty-one multidrug-resistant, methicillin-resistant Staphylococcus pseudintermedius strains isolated from canine clinical samples. Both EOs were mainly represented by sesquiterpene hydrocarbons, with a prevalence of ß-caryophyllene and α-humulene. However, different relative amounts of phytocannabinoids were also detected. Microbiological results evidenced better outcomes for the EO characterised by the highest content of phytocannabinoids, which in turn showed no differences among the tested strains. Nevertheless, both the EOs showed better inhibitory and bactericidal activities than their main constituent, ß-caryophyllene, tested individually, highlighting the presence of synergistic effects among the EO compounds.

Matrix Metalloproteinases on Skin Photoaging.

BACKGROUND: Skin aging is characterized by an imbalance between the generation and degradation of extracellular matrix molecules (ECM). Matrix metalloproteinases (MMPs) are the primary enzymes responsible for ECM breakdown. Intrinsic and extrinsic stimuli can induce different MMPs. However, there is limited literature especially on the summary of skin MMPs and potential inhibitors. OBJECTIVE: We aim to focus on the upregulation of MMP expression or activity in skin cells following exposure to UV radiation. We also would like to offer valuable insights into potential clinical applications of MMP inhibitors for mitigating skin aging. METHODS: This article presents the summary of prior research, which involved an extensive literature search across diverse academic databases including Web of Science and PubMed. RESULTS: Our findings offer a comprehensive insight into the effects of MMPs on skin aging after UV irradiation, including their substrate preferences and distinct roles in this process. Additionally, a comprehensive list of natural plant and animal extracts, proteins, polypeptides, amino acids, as well as natural and synthetic compounds that serve as inhibitors for MMPs is compiled. CONCLUSION: Skin aging is a complex process influenced by environmental factors and MMPs. Research focuses on UV-induced skin damage and the formation of Advanced Glycosylation End Products (AGEs), leading to wrinkles and impaired functionality. Inhibiting MMPs is crucial for maintaining youthful skin. Natural sources of MMP inhibitor substances, such as extracts from plants and animals, offer a safer approach to obtain inhibitors through dietary supplements. Studying isolated active ingredients can contribute to developing targeted MMP inhibitors.

Prospective therapeutic studies of disseminated extranodal large B-cell lymphoma including intravascular large B-cell lymphoma.

This study aimed to establish a standard treatment for disseminated extranodal large B-cell lymphoma, including intravascular large B-cell lymphoma (DEN-LBCL/IVL), and to validate the clinical diagnostic criteria we proposed. Between 2006 and 2016, 22 patients were enrolled in a clinical trial conducted by the Hokuriku Hematology Oncology Study Group. The first cycle of chemotherapy consisted of dose-reduced cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with delayed administration of rituximab. From the second to the sixth cycle, patients received conventional rituximab and CHOP therapy. The primary endpoint was overall survival (OS), while the secondary endpoints included the complete response (CR) rate and time to treatment failure (TTF). The results showed a CR rate of 73%, a median OS of 65 months, and a median TTF of 45 months. These findings indicate that patients with DEN-LBCL/IVL were effectively treated with our new chemoimmunotherapy regimen. Our clinical diagnostic criteria are useful for identifying patients who require early intervention.

Unveiling the Mechanism of Liangxue Siwu Decoction in Treating Rosacea Through Network Pharmacology and in-vitro Experimental Validation.

Background: Rosacea, a recurring dermatological disorder, demands effective therapeutic approaches. Traditional Chinese medicine, particularly Liangxue Siwu Decoction (LXSWD), has shown promise in managing inflammatory skin diseases, such as rosacea. This study focuses on uncovering LXSWD's specific effects on the inflammatory symptoms of rosacea. Objective: Our research investigates LXSWD's therapeutic effectiveness in rosacea treatment and delves into its underlying mechanisms. Methods: Network pharmacology was utilized to identify LXSWD's key components and their targets in rosacea management, which were then validated by molecular docking. An in vivo rosacea-like model in LL-37-induced mice was developed, subdividing them into control, model, and LXSWD groups. The LXSWD group received oral administration (25.0 g/kg/day) for six days before model induction. Post-treatment evaluations included skin tissue analyses to verify our network pharmacology predictions. Results: Key active ingredients in LXSWD, such as quercetin, kaempferol, and luteolin, were identified alongside central target proteins like TNF and MMPs. Our molecular docking study confirmed the interactions between these ingredients and targets. Analyses through GO and KEGG pathways indicated LXSWD's role in mitigating inflammation, particularly influencing the TNF and IL-17 pathways. LXSWD treatment in vivo markedly alleviated LL-37-induced symptoms in mice, showing a marked reduction in inflammatory cytokines (p < 0.05) and modulation of crucial genes (p < 0.05). These results, supported by immunofluorescence analysis and Western blot, underline the modulatory effects of LXSWD on MMPs, offering significant protection against rosacea's inflammation alterations (p < 0.05). Conclusion: Integrating network pharmacology, molecular docking, and in vivo experiments, this study elucidates LXSWD's potential mechanisms in rosacea treatment. It offers a novel theoretical framework for its clinical use in managing rosacea.

Beyond the pale: Insights into hypopigmented mycosis fungoides - A case report.

Hypopigmented mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma, a type of extranodal non-Hodgkin lymphoma. This report presents the case of a 9-year-old boy with a 2-year history of asymptomatic, hypopigmented skin lesions that were resistant to topical treatment. He was initially treated for a fungal skin infection and had received multiple courses of topical antifungals and steroids but showed no improvement, which led to further evaluation and a referral to a dermatologist. A skin biopsy was performed, and the diagnosis of hypopigmented MF was confirmed through skin histopathology and immunohistochemistry study. His lesions responded well to cycles of narrowband ultraviolet B phototherapy, showing almost complete clearance after 4 months without any side effects.

The Causal Relationship Between Physical Activity and Skin Cancer Risk: An Univariable Mendelian Randomization Study.

Background: The existing observational research on the relationship between physical activity (PA) and skin cancer (SC) is contentious, which points to the intricate nature of their association and underscores the imperative for more nuanced research to untangle the causal dynamics at play. The aim of this article is to delve deeper into this complex relationship, seeking to clarify whether PA serves as a protective factor against SC, or contributes to its risk. Methods: We utilized data from the genome-wide association study (GWAS) of PA from GWAS Catalog (include self-reported moderate to vigorous PA (MVPA), self-reported vigorous PA (VPA), and accelerometer-based average-accelerated PA). The data of SC is from FinnGen. All of the participants are of European ancestry. We used two-sample Mendelian Randomization (TSMR) to analyze the causal relationship between PA and SC.The research was conducted using inverse variance weighted (IVW) method as the primary approach, and MR Egger regression as supplementary analytical method. To ensure the robustness of the results, Cochran's Q-test and MR pleiotropy residual sum and outlier (MR-PRESSO) global tests were used to measure sensitivity. Results: Our analysis indicated that average-accelerated PA was associated with an increased risk of SC (ORIVW = 0.94, 95% CI 0.93-0.96, P < 0.001). While neither MVPA (ORIVW = 0.99, 95% CI 0.67-1.47, P = 0.962) nor VPA (ORIVW = 0.80, 95% CI 0.29-2.18, P = 0.656) shows causal relationship on risk of SC. Conclusion: Our research suggests that PA is associated with a decrease in SC, provides a new perspective for future SC prevention. Our research findings bolster the hypothesis that increased levels of PA, characterized by average acceleration, are associated with a reduced risk of developing skin cancer. This has filled the gap of research on the causal relationship between PA and SC, and could pave the way for novel preventive strategies against skin cancer.

Case report: Malignant epithelioid angiosarcoma in a Chinese female patient.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal tumors that exhibit characteristic epithelioid or spindle cell morphology and typically grow around blood vessels. These tumors are characterized by the expression of melanocytic and smooth muscle markers, such as HMB-45, Melan-A, and smooth muscle actin, indicating a dual differentiation phenotype. PEComas are extremely rare diseases, and patients typically have a very poor prognosis. Here, we report a case of malignant cutaneous PEComa with pulmonary metastasis in a Chinese female and review relevant literature. The patient underwent surgical resection of a soft tissue tumor in the left upper arm under general anesthesia, and the subsequent pathological findings suggested a tumor with perivascular epithelioid cell differentiation (PEComa). The patient received adjuvant chemotherapy and radiotherapy after surgical resection, along with monitoring through computed tomography (CT) scans. Three months later, pulmonary metastasis was detected, but both the cutaneous PEComa in the left upper limb and the pulmonary metastatic lesions were stably controlled under active management and treatment. This is a rare case worth reporting and studying, and therefore, we conducted a long-term follow-up, and we hope to provide help for the clinical treatment of PEComa.

An organotypic human melanoma-in-skin model as an in vitro tool for testing Vγ9Vδ2-T cell-based immunotherapy.

Background: Despite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in vitro in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model. Materials and methods: Vγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days. Results: Vγ9Vδ2-T cells remained viable for up to 3 days and were in close proximity to or within tumor nests. Upon Mel-RhS dissociation, a fraction was shown to be decorated by melanoma-associated chondroitin sulfate proteoglycan (MCSP), demonstrating their ability to actively navigate the tumor microenvironment and trogocytose cancer cells. Investigation into the apparent trogocytosis revealed an enhanced activated state of MCSP-decorated Vγ9Vδ2-T cells, evidenced by increased expression levels of 4-1BB, NKp44, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), compared with their MCSP- counterpart. These findings suggest that Vγ9Vδ2-T cells, upon successfully contacting melanoma cells, actively recognize and acquire MCSP from these malignant cells. Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential. Conclusions: This study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy.

Feasibility of using electrodermal activity responses to assess level of crowdedness of pedestrian paths.

As urban populations grow, it's imperative to evaluate and enhance the quality of pedestrian paths from the user's perspective. Crowdedness, associated with discomfort and safety, is crucial in determining the overall walking quality and user experience. Previously utilized methods for measuring crowdedness, such as travel diaries and floating population surveys, were limited to collecting perceptual data from sporadic surveys with restricted spatial coverage. Similarly, methods based on CCTV or mobile service data have been used but present issues with blind spots and fail to consider pedestrian perspectives. Against this background, this study explores the feasibility of assessing crowdedness levels by measuring subjects' physiological responses in a laboratory setting based on visual images of real and virtual environments. This study hypothesizes that the amount of people or vehicles passing by affects the electrodermal activity (EDA) of pedestrians, indicating the comfort level of using the environment. Experimental EDA data were measured using a wearable device while the subjects were watching videos showing different pedestrian traffic flows. Representative EDA signal features (e.g., skin conductance responses) were extracted after data pre-processing. Noticeable changes in EDA responses are observed when subjects countered specific environmental variations, such as differing volumes of passing people, on pedestrian paths. The findings suggest that EDA data can be instrumental in differentiating crowdedness levels on pedestrian paths. This study contributes to the body of knowledge by demonstrating the potential of EDA data to characterize the crowdedness experienced by pedestrians. This aids in the development of a novel, quantitative method to gauge pedestrian path crowdedness and to discern contributing factors, such as path width.

Hybrid construction of tissue-engineered nerve graft using skin derived precursors induced neurons and Schwann cells to enhance peripheral neuroregeneration.

Peripheral nerve injury is a major challenge in clinical treatment due to the limited intrinsic capacity for nerve regeneration. Tissue engineering approaches offer promising solutions by providing biomimetic scaffolds and cell sources to promote nerve regeneration. In the present work, we investigated the potential role of skin-derived progenitors (SKPs), which are induced into neurons and Schwann cells (SCs), and their extracellular matrix in tissue-engineered nerve grafts (TENGs) to enhance peripheral neuroregeneration. SKPs were induced to differentiate into neurons and SCs in vitro and incorporated into nerve grafts composed of a biocompatible scaffold including chitosan neural conduit and silk fibroin filaments. In vivo experiments using a rat model of peripheral nerve injury showed that TENGs significantly enhanced nerve regeneration compared to the scaffold control group, catching up with the autograft group. Histological analysis showed improved axonal regrowth, myelination and functional recovery in animals treated with these TENGs. In addition, immunohistochemical staining confirmed the presence of induced neurons and SCs within the regenerated nerve tissue. Our results suggest that SKP-induced neurons and SCs in tissue-engineered nerve grafts have great potential for promoting peripheral nerve regeneration and represent a promising approach for clinical translation in the treatment of peripheral nerve injury. Further optimization and characterization of these engineered constructs is warranted to improve their clinical applicability and efficacy.

Evaluation of the photothermal effects of the subdermal high-power laser in the skin of an experimental rat model.

The aim of the present study was to evaluate the photothermal effects of a subdermal high-power diode laser at a wavelength (λ) of 1470 nm in the skin of rats. Twenty male Wistar rats were used, divided into 2 groups: placebo laser (PL) and active laser (AL). A high-power diode laser equipment was applied to 5 subdermal vectors on the animal's back region. The results demonstrated that active laser animals showed a better arrangement of collagen fiber bands, an increase in the thickness of the dermis and the number of vessels. Furthermore, animals treated with active laser showed an increased immunoexpression of TGF-ß and VEGF compared to the placebo. The present work demonstrated that the subdermal high-power diode laser increases the vascularization and the expression of factors that enhance skin regeneration and may be promising resource in the esthetic and dermatology clinical treatment of skin rejuvenation.

Ectoin attenuates cortisone-induced skin issues by suppression GR signaling and the UVB-induced overexpression of 11ß-HSD1.

BACKGROUND: Accelerated pace of modern work and lifestyles subject individuals to various external and psychological stressors, which, in turn, can trigger additional stress through visible signs of fatigue, hair loss, and obesity. As the primary stress hormone affecting skin health, cortisol connects to the glucocorticoid receptor (GR) to aggravate skin issues induced by stress. This activation depends on the expression of 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) in skin cells, which locally converts cortisone-produced by the central and peripheral hypothalamic-pituitary-adrenal axis-into its active form. METHODS: Our study delves deeper into stress's adverse effects on the skin, including the disruption of keratinocyte structural proteins, the loss of basement membrane proteins, and the degradation of collagen. RESULTS: Remarkably, we discovered that Ectoin, an amino acid derivative obtained from halophilic bacteria, is capable of mitigating the inhibitory impacts of cortisone on the expression of cutaneous functional proteins, including involucrin, loricrin, laminin-5, and claudin-1. Moreover, Ectoin reduces the suppressive effect of stress on collagen and hyaluronic acid synthesis by impeding GR signal transduction. Additionally, Ectoin counterbalances the UVB-induced overexpression of 11ß-HSD1, thereby diminishing the concentration of endogenous glucocorticoids. CONCLUSION: Our findings illuminate the significant potential of Ectoin as a preventative agent against stress-induced skin maladies.

3D printed multi-coupled bioinspired skin-electronic interfaces with enhanced adhesion for monitoring and treatment.

Skin-electronic interfaces have broad applications in fields such as diagnostics, therapy, health monitoring, and smart wearables. However, they face various challenges in practical use. For instance, in wet environments, the cohesion of the material may be compromised, and under dynamic conditions, maintaining conformal adhesion becomes difficult, leading to reduced sensitivity and fidelity of electrical signal transmission. The key scientific issue lies in forming a stable and tight mechanical-electronic coupling at the tissue-electronic interface. Here, inspired by octopus sucker structures and snail mucus, we propose a strategy for hydrogel skin-electronic interfaces based on multi-coupled bioinspired adhesion and introduce an ultrasound (US)-mediated interfacial toughness enhancement mechanism. Ultimately, using digital light processing micro-nano additive manufacturing technology (DLP 3D), we have developed a multifunctional, diagnostic-therapeutic integrated patch (PAMS). This patch exhibits moderate water swelling properties, a maximum deformation of up to 460 %, high sensitivity (GF=4.73), and tough and controllable bioadhesion (shear strength increased by 109.29 %). Apart from outstanding mechanical and electronic properties, the patch also demonstrates good biocompatibility, anti-bacterial properties, photothermal properties, and resistance to freezing at -20°C. Experimental results show that this skin-electronic interface can sensitively monitor temperature, motion, and electrocardiogram signals. Utilizing a rat frostbite model, we have demonstrated that this skin-electronic interface can effectively accelerate the wound healing process as a wound patch. This research offers a promising strategy for improving the performance of bioelectronic devices and personalized diagnostics and therapeutics in the future. STATEMENT OF SIGNIFICANCE: Establishing stable and tight mechanical-electronic coupling at the tissue-electronic interface is essential for the diverse applications of bioelectronic devices. This study aims to develop a multifunctional, diagnostic-therapeutic integrated hydrogel skin-electronic interface patch with enhanced interfacial toughness. The patch is based on a multi-coupled bioinspired adhesive-enhanced mechanism, allowing for personalized 3D printing customization. It can be used as a high-performance diagnostic-therapeutic sensor and effectively promote frostbite wound healing. We anticipate that this research will provide new insights for constructing the next generation of multifunctional integrated high-performance bioelectronic interfaces.

The skinny on skin: The role of skin-aware professionals in skin cancer surveillance.

BACKGROUND: Licensed nonmedical, skin-aware professionals (e.g., hairdressers, massage therapists, etc.) have the potential to identify skin cancer, but baseline knowledge may not be sufficient to accomplish this goal. Following educational intervention, self-efficacy is one of the best surrogate metrics for behavior change. Curricula that increase knowledge and confidence levels can improve screening behaviors, but few have been tested for efficacy in this population AIMS: We assessed whether an online curriculum could reliably improve skin screening knowledge, attitudes, and behaviors of nonmedical professionals PATIENTS/METHODS: Skin-aware professionals were recruited through the Oregon Health Authority and IMPACT Melanoma TM. Participants completed a pre-survey, online training module, post-survey, and one-year follow-up survey. We evaluated participants' indicated levels of concern for suspicious and nonsuspicious lesions relative to "gold standard" physician ratings. We also assessed confidence and self-reported behavior change regarding talking to clients about skin cancer and recommending they see a provider to evaluate suspicious lesions RESULTS: The pre-survey was completed by 9872 skin-aware professionals; 5434 completed the post-survey, and 162 completed the one-year follow-up survey. Participants showed a significant improvement in ability to indicate the correct level of concern for all lesion types in concordance with "gold standard" physician ratings (p < 0.001). Participants reported increased comfort levels in discussing health-related topics with their clients posttraining CONCLUSIONS: Our training module effectively increased skin-aware professionals' knowledge, confidence, and concern for malignant lesions. Skin-aware professionals may serve as a valuable extension of the skin self-exam, but additional studies are needed to evaluate the impact of these curricula long-term, including potential downstream consequences.

Comparing GBA1-Parkinson's disease and idiopathic Parkinson's disease: α-Synuclein oligomers and synaptic density as biomarkers in the skin biopsy.

The main genetic risk factors for Parkinson's disease (PD) are presently represented by variants in GBA1 gene encoding for the ß-glucocerebrosidase (GCase). Searching for a peripheral biomarker that can be used for selecting and monitoring patients in clinical trials targeting GBA1-associated PD (GBA1-PD) is a current challenge. We previously demonstrated that α-synuclein oligomers expressed as proximity ligation assay (PLA) score in synaptic terminals of skin biopsy are a reliable biomarker for distinguishing idiopathic PD (iPD) from healthy controls (HC). This cross-sectional study investigates an unexplored cohort of GBA1-PD (n = 27) compared to 28 HC, and 36 iPD cases to (i) analyze α-synuclein oligomers and quantify them throughout PLA score, (ii) investigate GCase expression in brain and synaptic terminals targeting the sweat gland, (iii) unravel indicators that could differentiate patients with specific GBA1 mutations. PLA score discriminates GBA1-PD from HC with sensitivity = 88.9% (95% CI 70.84-97.65), specificity = 88.5% (95% CI 69.85-97.55), and PPV = 88.9% (95% CI 73.24-95.90), AUC value = 0.927 (95% CI 0.859-0.996). No difference was found between GBA1-PD patients and iPD, suggesting a common pathological pathway based on α-synuclein oligomers. GCase score did not differ in GBA1-PD, iPD, and HC in the synaptic terminals, whereas a positive correlation was found between PLA score and GCase score. Moreover, a significant increase in synaptic density was observed in GBA1-PD compared to iPD and HC (P < 0.0001). Employing ROC curve to discriminate GBA1-PD from iPD, we found an AUC value for synaptic density = 0.855 (95% CI 0.749-0.961) with sensitivity = 85.2% (95% CI 66.27%-95.81%), specificity = 77.1% (95% CI 59.86%-89.58%), and PPV = 74.19% (60.53%-84.35%). The highest synaptic density values were observed in p.N409S patients. This work points out to the value of both PLA score and synaptic density in distinguishing GBA1-PD from iPD and to their potential to stratify and monitor patients in the context of new pathway-specific therapeutic options.

Efficient Permeable Monolithic Hybrid Tribo-Piezo-Electromagnetic Nanogenerator Based on Topological-Insulator-Composite.

Escalating energy demands of self-independent on-skin/wearable electronics impose challenges on corresponding power sources to offer greater power density, permeability, and stretchability. Here, a high-efficient breathable and stretchable monolithic hybrid triboelectric-piezoelectric-electromagnetic nanogenerator-based electronic skin (TPEG-skin) is reported via sandwiching a liquid metal mesh with two-layer topological insulator-piezoelectric polymer composite nanofibers. TPEG-skin concurrently extracts biomechanical energy (from body motions) and electromagnetic radiations (from adjacent appliances), operating as epidermal power sources and whole-body self-powered sensors. Topological insulators with conductive surface states supply notably enhanced triboelectric and piezoelectric effects, endowing TPEG-skin with a 288 V output voltage (10 N, 4 Hz), ∼3 times that of state-of-the-art devices. Liquid metal meshes serve as breathable electrodes and extract ambient electromagnetic pollution (±60 V, ±1.6 µA cm-2). TPEG-skin implements self-powered physiological and body motion monitoring and system-level human-machine interactions. This study provides compatible energy strategies for on-skin/wearable electronics with high power density, monolithic device integration, and multifunctionality.