Dermal Cells Research Articles

Cumulative learning based segmentation aided cell mixtures classification in digital holographic microscopy

The tumor microenvironment consists of several components like tumor cells, normal healthy cells, extracellular matrix, secreted factors, and other non-cellular components. The interaction among these components is crucial for tumor progression and metastasis. Identifying the presence of tumor cells among the normal healthy cells during the initial stages of cancer will aid in its early detection and treatment. One of the main features that differentiates a cancer cell from a normal healthy cell distinctively is its morphology. In this study, the effectiveness of machine learning algorithms is evaluated in classifying cells co-cultured in a Petri dish. To achieve this, digital holographic microscopy is used to capture the quantitative phase images of human dermal fibroblast and A375 human melanoma cancer cells co-cultured at 1:1, 1:2, and 2:1 ratios. Cell segmentation was performed using a cumulative learning approach. Subsequently, morphological and phase-based features were extracted to train the machine learning algorithms for binary classification of cells. Phase-based features in addition to the morphological features were found to provide improved performance of the classifier. The classifier demonstrated an average F1-score of 0.9 during testing.

Thermal Wave and Pennes’ Models of Bioheat Transfer in Human Skin: A Transient Comparative Analysis

The primary focus of this study is to analyze comparative heat transfer in a two-dimensional (2D) multilayered human skin using thermal waves and Pennes' bioheat transfer models. The model comprises the epidermis, dermis, hypodermis tissue, and inner cells, and aims to understand their response to microwave (MW) power and electromagnetic (EM) frequency. The system of equations involves EM wave frequency and bioheat equations and uses the finite element method (FEM) for solving. It encompasses a range of microwave power levels (4-16 W), frequencies (0.9-4 GHz), and exposure durations (0-180 s). It examines how MW power and frequency affect temperature predictions due to different relaxation times. The results are visually represented, illustrating microwave power dissipation, isothermal profiles within the skin tissue, temperature trends at several locations, relaxation times, specific absorption rate (SAR), and the mean surface temperature of the multilayered dermal cell. Thermal analysis shows that Pennes' equation predicts higher temperatures than the thermal wave model of bioheat transfer (TWMBT). A notable disparity in temperature evolution is observed between the two models, especially in high-frequency transient heating scenarios. The TWMBT forecasts a delay in heat transfer, offering valuable insights into the more realistic short-term thermal behavior that the classical Pennes' model fails to capture. This comparative study underscores the significance of selecting an appropriate bioheat transfer model for precise thermal analysis in biomedical applications, such as hyperthermia treatment and thermal diagnostics. The findings emphasize the potential of the TWMBT to enhance the accuracy of thermal treatments in clinical settings.

Use of Albumin In Situ Hybridization to Diagnose Cutaneous Metastatic Hepatocellular Carcinoma With Poorly Differentiated Features: A Case Report and Review of the Literature.

Hepatocellular carcinoma (HCC) rarely metastasizes to the skin. When it occurs, it is often poorly differentiated making the diagnosis challenging. There exists a male predominance, and clinical presentation usually includes papules or nodules resembling pyogenic granulomas or dermal deposits. Histopathology shows malignant dermal cells. Hepatoid features including nests or cords of cells arranged in a trabecular or pseudoglandular pattern, sinusoidal formation, or the presence of bile exist in less than 50% of cases. Limitations exist with immunohistochemical staining, particularly in poorly differentiated neoplasms. Albumin in situ hybridization is more sensitive for detecting poorly differentiated HCC. Immunostaining in conjugation with albumin in situ hybridization enhances the detection of metastatic hepatocellular carcinoma. We report the case of a 74-year-old man with a history of HCC and a stable lung metastasis who presented with painful, growing bumps on his nose for 2 months. Examination revealed multiple, pink to white, shiny dermal-based papules with telangiectasias involving the right nasal tip and naris. Alpha-fetoprotein level was markedly elevated. Computed tomography showed expanding right lower lobe lung nodules. Histopathology of the cutaneous biopsy revealed features of a poorly differentiated basaloid carcinoma. Immunohistochemical staining was diffusely positive for glypican-3, focally positive for arginase-1, and negative for hepatocyte paraffin 1. Albumin in situ hybridization was diffusely positive, clinching the diagnosis of HCC. Metastatic HCC is a rare encounter for dermatopathologists. We aim to increase awareness of its occurrence in patients with advanced HCC and highlight the importance of clinical correlation when faced with poorly differentiated or unusual-looking basaloid neoplasms.

Human adipose and umbilical cord mesenchymal stem cell-derived extracellular vesicles mitigate photoaging via TIMP1/Notch1

UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.

Electrospun zinc oxide nanoscaffolds: a targeted and selective anticancer approach

This study aims to prepare, characterize, and evaluate zinc oxide nanoscaffolds (ZnO NSs) as a potential anticancer drug that selectively targets malignant cells while remaining non-toxic to normal cells. Electrospun NSs were fabricated and loaded with varying concentrations of ZnO nanoparticles (NPs). The uniform morphology of the fabricated samples was confirmed through Field Emission Scanning Electron Microscope (FESEM) imaging. Elemental composition was investigated using Energy Dispersive X-ray spectroscopy (EDX), Fourier Transform Infrared (FTIR), and X-ray diffraction (XRD) analyses. Biocompatibility and cytotoxicity were assessed using the (3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) (MTT) assay and flow cytometry. The water uptake and degradation properties of the electrospun NSs were also examined. Furthermore, a cumulative release profile was generated to assess the release behavior of ZnO NSs. The prepared ZnO NSs demonstrated negligible toxicity toward normal human dermal cells. Conversely, the four used concentrations of ZnO NSs displayed substantial cytotoxicity and induced apoptosis in various cancer cell lines. The observed effects were concentration-dependent. Notably, ZnO NSs 8% exhibited the most significant reduction in cell viability against the MCF7 cell line. The findings from this study indicate the potential of ZnO NSs as an effective anticancer agent, with the ZnO NSs 8% demonstrating the most pronounced impact. This research introduces a novel application of electrospun zinc oxide nanoscaffolds, demonstrating their capacity for selective anticancer activity, particularly against breast carcinoma, while preserving normal cell viability. The study presents a significant advancement in the use of nanomaterial for targeted cancer therapy.

Fabrication and Characterization of Biocompatible Multilayered Elastomer Hybrid with Enhanced Water Permeation Resistance for Packaging of Implantable Biomedical Devices

This study presents the synthesis and characterization of hexadecyl-modified SiO2 (HD-SiO2) nanoparticles and their application in the fabrication of a multilayered elastomer hybrid sheet to enhance water resistance in implantable biomedical devices. The surface modification of SiO2 nanoparticles was confirmed via FT-IR and TGA analyses, showing the successful grafting of hydrophobic hexadecyl groups. FE-SEM and DLS analyses revealed spherical HD-SiO2 nanoparticles with an average size of 360 nm. A multilayered elastomer hybrid sheet, consisting of a PDMS-based circuit-protecting body, a water resistance layer of HD-SiO2, a planarization layer, and a biocompatible layer of polydopamine, was fabricated and characterized. The water resistance layer exhibited superhydrophobic properties, with a water contact angle of 154.7° and a 27% reduction in water vapor transmission rate (WVTR) compared to the circuit-protecting body alone. The device packaged with both the circuit-protecting body and water resistance layer demonstrated a tenfold increase in operational lifespan in water medium compared to the device without the water resistance layer. Cytotoxicity and cell proliferation tests on human dermal fibroblast cells (HDFn) confirmed the biocompatibility of the multilayered sheet, with no significant cytotoxicity observed over 48 h.

Cannabidiol (CBD) modulates the transcriptional profile of ethanol-exposed human dermal fibroblast cells.

Cannabidiol (CBD) is abundant in the Cannabis sativa plant and exhibits complex immunomodulatory, anxiolytic, antioxidant, and antiepileptic properties. Several studies suggest that CBD could be used for different purposes in alcohol use disorder (AUD) and alcohol-related injuries to the brain and the liver. In this study, we focused on analyzing transcriptional alterations in human dermal fibroblasts (HDFs) cell line challenged simultaneously with ethanol and CBD as an ethanol-protective agent. We aimed to expose the genes and pathways responsible for at least some of the CBD effects in those cells that can be related to the AUD. Transcriptome analysis was performed using HDFs cell line that expresses both cannabinoid receptors and can metabolize ethanol through alcohol dehydrogenase activity. Fibroblasts are also responsible for the progression of liver fibrosis, a common comorbidity in AUD. With the use of a cellular test, we found that CBD at the lowest applied concentration (0.75μM) was able to stimulate depressed metabolism and reduce the level of apoptosis of cells treated with different concentrations of ethanol to the level observed in the control cells. Similar observations were made at the transcriptome level, in which cells treated with ethanol and CBD had similar expression profiles to the control cells. CBD also affects several genes connected with extracellular matrix formation (especially its collagen constituent), which can have potential implications for, e.g., fibrosis process.

Antiaging in a Bottle: Bioactive Competency of Plasma-Generated Nitric Oxide Water for Modulation of Aging-Related Signature in Human Dermal Cells.

Nitric oxide (NO), a potential therapeutic antiaging molecule, modulates various physiological and cellular processes. However, alterations in endogenous NO levels brought on by aging impact multiple organ systems and heighten susceptibility to age-related skin diseases. This correlation underscores the importance of investigating NO-based antiaging interventions. Nonthermal plasma-generated NO is a promising avenue for cosmetic and regenerative medicine due to its capacity to stimulate cellular growth. Herein, we examine the potential of plasma-generated nitric oxide water (NOW) as a bioactive agent in human dermal fibroblasts, emphasizing gene expression patterns linked to extracellular matrix (ECM) breakdown and cellular senescence. The findings of our study indicate that administering NOW at lower dosages enhances cell migration and proliferation. Moreover, the genetic signatures associated with ECM synthesis, antioxidant defense, and antisenescence pathways have been analyzed in NOW-exposed cells. Notably, the downregulation of ECM-degrading enzyme transcripts─collagenase, elastase, and hyaluronidase─suggests NOW's potential in mitigating the intrinsic skin aging phenomena, emphasizing the promise of NO-based interventions in advancing antiaging strategies within regenerative medicine.

Antioxidative and Anti-Atopic Dermatitis Effects of Peptides Derived from Hydrolyzed Sebastes schlegelii Tail By-Products.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with significant morbidity, including pruritus, recurrent skin lesions, and immune dysregulation. This study aimed to investigate the antioxidative and anti-AD effects of peptides derived from hydrolyzed Sebastes schlegelii (Korea rockfish) tail by-products. Hydrolysates were prepared using various enzymes, including Alcalase, Flavourzyme, Neutrase, and Protamex. Among them, Protamex hydrolysates demonstrated the highest ABTS radical scavenging activity with an RC50 value of 69.69 ± 0.41 µg/mL. Peptides were further isolated from the Protamex hydrolysate using dialysis, fast protein liquid chromatography (FPLC), and high-performance liquid chromatography (HPLC). The most active peptide, STPO-B-II, exhibited a single peak and was identified as a sequence of Glu-Leu-Ala-Lys-Thr-Trp-His-Asp-Met-Lys, designated as MP003. In vivo experiments were conducted using a 2,4-dinitrochlorbenzene (DNCB)-induced AD model in NC/Nga mice. The isolated peptide, MP003, showed significantly reduced AD symptoms, including erythema, lichenification, and collagen deposition. Additionally, MP003 decreased epidermal and dermal thickness, eosinophil, and mast cell infiltration and downregulated the expression of pro-inflammatory cytokines IL-1β, IL-6, and IgE in serum and skin tissues. These findings suggest that peptides derived from Sebastes schlegelii tail by-products may serve as potential therapeutic agents for AD.

EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.

EPHB4 (ephrin receptor B4) and the RASA1 (p120 Ras GTPase-activating protein) are necessary for the development of lymphatic vessel (LV) valves. However, precisely how EPHB4 and RASA1 regulate LV valve development is unknown. In this study, we examine the mechanisms by which EPHB4 and RASA1 regulate the development of LV valves. We used LV-specific inducible EPHB4-deficient mice and EPHB4 knockin mice that express a form of EPHB4 that is unable to bind RASA1 yet retains protein tyrosine kinase activity (EPHB4 2YP) to study the role of EPHB4 and RASA1 in LV valve development in the embryo and LV valve maintenance in adults. We also used human dermal lymphatic endothelial cells in vitro to study the role of EPHB4 and RASA1 as regulators of LV valve specification induced by oscillatory shear stress, considered the trigger for LV valve specification in vivo. LV valve specification, continued valve development postspecification, and LV valve maintenance were blocked upon induced loss of EPHB4 in LV. LV specification and maintenance were also impaired in EPHB4 2YP mice. Defects in LV development were reversed by inhibition of the Ras-MAPK (mitogen-activated protein kinase) signaling pathway. In human dermal lymphatic endothelial cells, loss of expression of EPHB4 or its ephrin b2 ligand, loss of expression of RASA1, and inhibition of physical interaction between EPHB4 and RASA1 resulted in dysregulated oscillatory shear stress-induced Ras-MAPK activation and impaired expression of LV specification markers that could be rescued by Ras-MAPK pathway inhibition. The same results were observed when human dermal lymphatic endothelial cells were stimulated with the Yoda1 agonist of the PIEZO1 oscillatory shear stress sensor. Although Yoda1 increased the number of LV valves when administered to wild-type embryos, it did not increase LV valve number when administered to EPHB4 2YP embryos. EPHB4 is necessary for LV valve specification, continued valve development postspecification, and valve maintenance. LV valve specification requires physical interaction between EPHB4 and RASA1 to limit activation of the Ras-MAPK pathway in lymphatic endothelial cells. Specifically, EPHB4-RASA1 physical interaction is necessary to dampen Ras-MAPK activation induced through the PIEZO1 oscillatory shear stress sensor. These findings reveal the mechanism by which EPHB4 and RASA1 regulate the development of LV valves.

Understanding host's response to staphylococcal scalded skinsyndrome.

The aim of this review was to summarise the current knowledge on host-related factors that contribute to the development and severity of staphylococcal scalded skin syndrome (SSSS) in children. A comprehensive assessment and analysis of the existing literature on SSSS clinical features, pathogenesis and susceptibility factors. SSSS is a blistering skin disease caused by circulating exfoliative toxins (ETs) of Staphylococcus aureus (S. aureus), almost exclusively affecting infants, young children and immunocompromised individuals. ETs possess serine protease activity and target desmoglein-1 (Dsg-1) in the superficial epidermis. While the role of S. aureus ETs and site of action are well-described, other host factors such as impaired immune responses to ETs, poor renal clearance and genetic factors are crucial for the onset of and/or the severity of SSSS in children. The fate of desmosomal fractions after cleavage by ETs, as well as the role of dermal inflammatory cell infiltrates remain to be elucidated.

A prenatal skin atlas reveals immune regulation of human skin morphogenesis.

Human prenatal skin is populated by innate immune cells, including macrophages, but whether they act solely in immunity or have additional functions in morphogenesis is unclear. Here we assembled a comprehensive multi-omics reference atlas of prenatal human skin (7-17 post-conception weeks), combining single-cell and spatial transcriptomics data, to characterize the microanatomical tissue niches of the skin. This atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles, is implicated inscarless wound healing and is crucial for skin angiogenesis. We systematically compared a hair-bearing skin organoid (SkO) model derived from human embryonic stem cells and induced pluripotent stem cells to prenatal and adult skin1. The SkO model closely recapitulated in vivo skin epidermal and dermal cell types during hair follicle development and expression of genes implicated in the pathogenesis of genetic hair and skin disorders. However, the SkO model lacked immune cells and had markedly reduced endothelial cell heterogeneity and quantity. Our in vivo prenatal skin cell atlas indicated that macrophages and macrophage-derived growth factors have a role in driving endothelial development. Indeed, vascular network remodelling was enhanced following transfer of autologous macrophages derived from induced pluripotent stem cells into SkO cultures. Innate immune cells are therefore key players in skin morphogenesis beyond their conventional role in immunity, a function they achieve through crosstalk with non-immune cells.

Photochemical Synthesis of Sericin-Coated Gold Nanorods and Their Antibacterial Activity under Low-Level Near-Infrared Light.

Gold nanorods (GNRs) are unique nanoparticles with easily functionalized surfaces, multiple synthesis methods, photothermal conversion, and surface plasmon resonance effects. These properties make GNRs suitable for various biological applications. However, a rapid synthesis of GNRs using less toxic chemicals is needed. The photochemical method is a viable option that can synthesize GNRs quickly while using fewer chemicals. A photochemical method is reported for the synthesis of GNRs using Irgacure-2959 as a reducing agent. This method could be used to synthesize GNRs with a rod-like shape within 30 min. Additionally, GNRs were coated with sericin (GNRs-SC) to further reduce their toxicity in human dermal fibroblast adult cells. Low-level near-infrared (NIR) light was applied to enhance the photothermal therapy of both GNRs and GNRs-SC. The results showed that GNRs and GNRs-SC under low-level NIR light have enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli, as well as antibiofilm activity against S. aureus. Furthermore, GNRs-SC showed good biocompatibility with antibacterial and antibiofilm activities. These results indicate that GNRs-SC are good candidates for various biological applications.

Curcumin-loaded zein nanoparticles: A quality by design approach for enhanced drug delivery and cytotoxicity against cancer cells

Zein, a maize protein, has been explored for constructing potential biomaterial due to its hydrophobic nature, self-assembly capability, and biocompatibility. In its nanoparticulate form, zein is a promising material for drug delivery applications, particularly in cancer treatment. Despite the importance of colloidal stability for effective drug delivery, systematic studies investigating the effect of various surface modifying agents (MAs) on the zein nanoparticles (ZNPs)-based formulations are limited. This study employs quality-by-design (QbD) approach to optimize curcumin-loaded ZNPs, enhancing colloidal stability, size, and drug-encapsulation efficiency using different MAs for potential cancer therapy. Gum arabic (GA) emerged as the optimal stabilizer, with GA-stabilized curcumin-loaded ZNPs (GA-Cur-ZNPs) achieving a particle size of 184.8 ± 2.85 nm, zeta potential of −23.4 ± 0.56 mV and 87.1 ±1.55 % drug encapsulation efficiency, along with excellent colloidal stability over two months. The optimal formulation also demonstrated sustained release of Cur over 72 h. GA-Cur-ZNPs demonstrated lower IC50 values and higher anti-proliferative effects on three different cancer cell lines compared to the free drug, while also exhibiting superior intracellular uptake. With negligible toxicity to human dermal fibroblast cells, the optimized Cur-GA-ZNPs show promise for safe and effective killing of cancer cells.

Aptamer-guided graphene oxide quantum dots for targeted suicide gene therapy in an organoid model of luminal breast cancer

Breast cancer is one of the most common cancers in women. One of the best therapeutic methods against breast cancer is gene therapy, while having an appropriate gene carrier is the biggest challenge of gene therapy. Hence, developing carriers with low cytotoxicity and high gene transfection efficiency, and preferentially with the selective function of gene delivery is a critical demand for this method. In the present study, we introduce a novel targeted carrier to deliver the inducible caspase-9 suicide gene (pLVSIN-iC9) into breast cancer cells. The carrier is composed of graphene oxide quantum dots decorated with polyethyleneimine, and S2.2; an aptamer with high affinity to MUC1 (GOQD-PEI/S2.2). Due to the overexpression of MUC1 in breast cancer cells, the designed GOQD-PEI/S2.2/pLVSIN-iC9 can selectively target cancer cells. Moreover, to better mimic solid tumor conditions, and to evaluate the selective effect of the GOQD-PEI/S2.2/pLVSIN-iC9, an organoid model derived from human dermal fibroblasts (HDF) and MCF-7 cells (coculture organoid) was generated and characterized. The results demonstrate that the coculture organoid model adapts the tissue structure of luminal breast cancer, as well. Therefore, the organoids were subjected to treatment with targeted gene therapy using GOQD-PEI/S2.2/pLVSIN-iC9. Our evidence supports the targeted killing effect of iC9 on the breast cancer cells of the organoids and suggests the good potential of the newly introduced carriers in targeted gene delivery.

Comprehensive analysis of Hibisci mutabilis Folium extract's mechanisms in alleviating UV-induced skin photoaging through enhanced network pharmacology and experimental validation.

Skin photoaging induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation manifests as skin roughness, desquamation, pigmentation, and wrinkle formation. Current treatments, such as sunscreen, hormones, and antioxidants, have limitations and side effects. Traditional Chinese Medicine Hibisci Mutabilis Folium (HMF), or Mu-Fu-Rong-Ye in Chinese name, refers to the dried leaves of the plant Hibiscus mutabilis L., which belongs to the Malvaceae family. It has been used traditionally to treat acute mastitis, parotitis, neurodermatitis, burns. The reported activities of HMF include anti-inflammatory and anti-oxidant effects. However, the therapeutic potential of HMF in preventing and treating UV-induced skin photoaging remains unexplored. This study aimed to investigate the protective effects of HMF extract (EHMF) against UV-induced skin photoaging and the underlying mechanisms of action, by using network pharmacology and experimental verification. Network pharmacology was employed to identify the effective chemical components of EHMF. Potential targets were identified via PPI network analysis. Representative compounds were characterized using UPLC-MS/MS. In vitro validation involved assessing HaCaT cell viability, observing live/dead cell staining through fluorescence microscopy, and measuring inflammatory factors using ELISA. For in vivo validation, a UV-induced skin photoaging mice model was treated transdermally with EHMF or Methotrexate daily for 7 days. Dermatitis severity, skin morphology, and collagen fiber pathology were evaluated. Inflammatory cytokine and protein expression in dorsal skin lesions was confirmed using Elisa Kits, Western blot and immunohistochemistry. A total of 22 active ingredients of EHMF were identified. GO enrichment and KEGG pathway analyses revealed a focus on inflammatory signaling pathways. In vitro experiments showed that EHMF significantly reduced UV-induced inflammatory factors in HaCaT cells and improved cell survival rates. In vivo, EHMF alleviated back skin lesions in UV-exposed mice, reducing epidermal and dermal thickening and pathological inflammatory cell infiltration. It also decreased abnormal MMP-9 expression and collagen fiber proliferation, along with levels of inflammatory factors like TNF-α, IL-6, IL-17, and EGFR. Western blot and immunohistochemistry results indicated that the over-activation of the AKT-STAT3 signaling pathway was inhibited. EHMF effectively reduced UV-induced skin damage, inflammation, and wrinkles, providing strong support for its clinical application as a dermatological agent.

Establishment of the first dermal fibroblast cell line derived from the Indo-Pacific Bottlenose Dolphin (Tursiops aduncus) and its response to pollutant exposure

The Indo-Pacific bottlenose dolphin (Tursiops aduncus), classified as a new species since 1998, is underexplored in ecotoxicology owing to ethical constraints and the lack of specific in vitro models. Herein, we established the first skin fibroblast cell line (TaSF) from an Indo-Pacific bottlenose dolphin stranded along the Pearl River Estuary, China. TaSF cells exhibited strong proliferation in early passages but ceased mitosis at passage 19, likely owing to reaching the Hayflick limit. Morphology and immunofluorescence tests confirmed the fibroblastic nature of these cells. Karyotyping revealed 21 pairs of autosomes and 1 pair of sex chromosomes (XY), consistent with many cetaceans. To facilitate long-term future studies, TaSF cells were immortalized with exogenous simian virus 40 T antigen, creating the TaSFT cell line. The cytotoxic effects of 27 contaminants, including 6 organotins (OTs), 10 per- and polyfluoroalkyl substances (PFASs), and 11 phthalates (PAEs), on TaSFT cells were evaluated after 24-h exposure. Among these chemicals, OTs exhibited the strongest cytotoxicity, and both OTs and PFASs showed structure-related toxicity. These findings confirm the feasibility of TaSFT cells as a novel tool for ecotoxicity research on the Indo-Pacific bottlenose dolphin and highlight the need for further investigation into the environmental contaminant pressures on this species.

Investigating the Effect of Polypyrrole-Gelatin/Silk Fibroin Hydrogel Mediated Pulsed Electrical Stimulation for Skin Regeneration.

In clinical practice to treat complex injuries, the application of electrical stimulation (ES) directly to the skin complicates the wound. In this work, the effect of a conductive hydrogel mediated electric field on skin regeneration is investigated. Polypyrrole incorporated matrices of gelatin and silk fibroin were prepared by two-step interfacial polymerization. The maximum electrical conductivity of 10-4 S cm-1 was achieved when 200 mM polypyrrole was loaded. Mechanically stable and cytocompatible hydrogels were evidenced to have antioxidant and blood compatible characteristics. Human dermal fibroblast cells responded to pulsed stimulation of 100 or 300 mV mm-1 as observed from the increased expressions of TGFβ1, αSMA, and COLIAI genes. Further, the increase in the αSMA protein expression with the magnitude of electrical stimulation also suggested transdifferentiation of the fibroblast to myofibroblast. Moreover, Raman spectroscopy identified two fingerprint regions (collagen and lipid) to differentiate ES treated and nontreated samples. Therefore, the combination of hydrogels and electrical stimulation has potential therapeutic effects for accelerating the rate of skin regeneration.

ONCOLYTIC ACTIVITY OF HUMAN RESPIRATORY SYNCYTIAL VIRUS.

Oncolytic viruses (OVs) are emerging as novel tools in cancer therapy. Oncolytic virotherapy offers an attractive therapeutic combination of tumor-specific killing and immune co-stimulation, therefore amplifying the host immune response against tumors. Moreover, OVs can be engineered for the expression of different immunostimulatory molecules to optimize and enhance the efficacy of oncolytic virotherapy. The effectiveness of OVs has been demonstrated in many preclinical studies for different types of cancers to achieve the aim of personalized cancer therapy. Human respiratory syncytial virus (RSV), an RNA virus of the Pneumoviridae family causes severe lower respiratory tract infections in infants and immunocompromised individuals. Interestingly, the oncolytic activity of RSV demonstrated in human prostate, hepatocellular, and dermal cancer cells is mostly mediated via apoptotic cell death associated with the impaired NF-κB activation or with the defect of the IFNα/β-induced STAT-1 activation. At the same time, the studies on cervical cancer revealed that RSV infection resulted in autophagy activation and apoptosis through the ROS-BAX and TNF- α-mediated pathways. The rational combinations of OVs, including RSV, with other approaches may benefit patients whose response to conventional therapies is limited. Here, we discuss the oncolytic activity of RSV and its potential use against different types of cancer.

Food hydroxycinnamic acids alleviate ageing in dermal cells

Dermal damage is inducible by several factors including UV exposure, oxidative stress and inflammation exacerbating skin senescence and degradation of the skin elastic fibers accumulated in ageing accordingly. Which, phenolics of food hydroxycinnamates with a myriad of health benefits are potentially applicable for ageing treatment. Particularly those of food hydroxycinnamic acids, i.e., caffeic, sinapic and rosmarinic acids, that would be efficient against skin ageing. Effectiveness of caffeic, sinapic and rosmarinic acids alleviating ageing was indicated in human dermal fibroblasts (HDF) and co-culture of human keratinocytes (HaCaT) and HDF. Caffeic acid was exhibited as the strongest (p < 0.01) anti-senescent phenolic examined. The studied food hydroxycinnamic acids were shown to induce collagen synthesis in aged HDF with the noted activities inhibiting MMP-1 and IL-6. Their photoaging protections were proved in the co-culture model with significant (p < 0.001) inhibitions against IL-6, IL-8, MMP-1 and MMP-9 (collagen and elastin degrading enzymes). Which, caffeic acid was demonstrated as the most potent photoaging agent among its counterparts. Caffeic, sinapic and rosmarinic acids were proved to be the efficient nutrients for ageing treatment. These functional food hydroxycinnamates are proven on their anti-senescent and photoprotection activities, and capable to maintain homeostasis of dermal cells. Food-derived hydroxycinnamic acids are therefore recommended for innovative product alleviates skin ageing.Graphical