Skin Epithelium Research Articles

Epicutaneous Staphylococcus aureusexposure triggers lung inflammation via epithelia-intrinsic IL-36R signaling

Abstract Allergic diseases have been increasing recently and affect nearly 20% of the human population, including 200 million people with atopic dermatitis (AD), 250 million people with food allergies, and 600 million people with allergic rhinitis or asthma. The atopic march is the concept whereby having early-in-life AD and a dysfunctional skin barrier during initial allergen sensitization increases the predisposition of allergic diseases at distant epithelial sites (e.g., asthma). We have previously shown that IL-36R signaling was required to exacerbate the progression from AD-like skin inflammation to subsequent allergic lung inflammation in mice. However, whether IL-36R acts directly on the skin and/or lung epithelia to trigger the progression towards lung inflammation is not entirely clear. To address this gap in knowledge, we performed our allergic lung inflammation model in WT, IL-36R−/−, keratinocyte-specific IL-36R deficient (K14-cre×IL-36R fl/fl), and lung epithelial-specific IL-36R deficient (Nkx2-1-cre×IL-36R fl/fl) mice, whereby first epicutaneous Staphylococcus aureus and cockroach antigen (CrA) exposure initiates AD-like skin inflammation, which is followed by intratracheal CrA exposure to trigger subsequent allergic lung inflammation. Evaluation of skin and lung inflammation by image, histologic and flow cytometric analyses revealed that both keratinocyte- and lung epithelial-intrinsic IL-36R signaling were required for the development of lung inflammation, weight loss, and neutrophil lung infiltration despite no differences in circulating neutrophils. Collectively, our findings suggest that IL-36R signaling in skin and lung epithelia is a critical mechanism for the progression of the atopic march. NIAMS: R01AR073665 and LEO Foundation: LF-OC-22-000953; SJN is funded by NIAMS 1T32AR074920

Comparison of MMR Vaccine V/S 5-Fluorouracil in Treatment of Palmo-plantar Warts

Background: Human papilloma virus is a large group of DNA containing viruses that infect squamous epithelium of skin or uncornified mucous membrane. Aim: To compare the outcomes of MMR vaccine V/S 5 fluorouracil in treatment of palmo-plantar warts in patients among male and female patients. Study Design: Experimental study. Methodology: In order to collect the data, simple random sampling technique was used. Enrolled patients (n=102) were divided into two groups. Group-A received intra-lesional MMR vaccine (0.1-0.5mal) while other group received intra-lesional 5-Fluorouracil (0.1-0.5mal) injection. Both groups received intra-lesional injections in warts at 2 weekly interval for 3 months. SPSS v 23 evaluated data. Chi-square test was used to compare the gender distribution, results, responder and recurrence between both groups with p-value less than 0.05 as significant. Results: Mean age of the patients of group A was 30.5 ± 6.0 and the mean age of patients of group B was 28.2 ± 8.7 years. In Group A, 33 patients (58.9%) were responders, while in Group B, 43 patients (76.8%) were responders. P-value (0.043) suggested that the difference in response rate between the two groups was statistically significant. Practical Implication: This study compared the efficacy of two different treatment options that were commonly used in palmo-planter warts management. Secondly, it added to local literature regarding their efficacy in comparison to each-other. Conclusion: It was concluded that intra-lesional 5-FU was more safe and effective treatment in comparison to injection MMR for palmo-planter warts as it showed high response rate with low recurrence. Keywords: Efficacy, MMR Vaccine, Response Rate, 5-Flourouracil and Intra-lesional Injection.

ASSOCIATION BETWEEN PEMPHIGUS AND PSORIASIS: A SYSTEMATIC REVIEW

Pemphigus vulgaris, foliaceus, paraneoplastic, IgA, and herpetiformis are autoimmune bullous diseases. Epidemiologically heterogeneous symptoms characterize pemphigus. The first non-HLA genes related with PV have been found, and our knowledge of pemphigus frequency, which varies widely between populations, has increased. Pemphigus causes blisters and lesions. This polymorphism is also linked to many comorbidities, including autoimmune illnesses, hematological malignancies, and psoriasis. Psoriasis is a T cell-mediated papulosquamous skin illness that results from immune system dysregulation. It is characterized by severe inflammatory and hyperproliferative alterations in the affected areas of the skin. Psoriasis has traditionally been linked to bullous pemphigoid, which is a subepidermal autoimmune bullous illness. Pemphigus is a group of IgG-mediated blistering diseases that affect the skin and mucous membranes' squamous epithelium. Pemphigus causes painful intraepidermal blisters and erosions. Pemphigus disease is chronic and autoimmune, which has increased research into its link with other autoimmune and autoinflammatory disorders. Pemphigus and psoriasis have been reported to co-occur, however their relationship is uncertain. Yet, there are also additional biological plausible reasons for this link. The "epitope spreading phenomena" may have caused the disease. This occurs when a primary autoimmune or inflammatory response damages tissue. Hence, the immune system can now detect some protein components, triggering a subsequent autoimmune reaction. Psoriasis patients are three times more likely to develop pemphigus. Psoriasis doctors should know about this epidemiological trend.

Dynamics of clinical symptoms of damage to the shin of newborn Ukraini-an red dairy breed under industrial exploitation conditions

The analysis of the data of the 5-year monitoring of the visual (in points) examination of the firstborns (n = 1113) of the newly created Ukrainian red milk (URD) breed for the assessment of the clinical condition of the lateral surface of the lower leg under the conditions of unharnessed keeping on rubber mats is presented. An increase in the number of cows with damage to the epithelium of the leg skin (“gateway of infection”) along the chronological axis (2018–22), namely: from 33.88 ± 3.97 % to 55.95 ± 5.94 % (P < 0.01). Pronounced inflammatory phenomena (purulent-necrotic) in the area of the tibial joint increased by 15.05 % (P < 0.01), and symptoms of severe damage to all tissues of the tibial area with signs of lameness increased from 0.96 ± 0.96 % to 4.11 ± 0.95 % (P < 0.05). The dynamics of the increase in the symptom complex of shin pathologies in firstborns showed a positive correlative relationship with the growth of milk productivity (in 2018, the average milk yield for 305 days of lactation was 6999.13 kg, and in 2020 – 8947.25 kg). Still, the trend of increasing clinical damage to firstborns' shins remained even after the drop in productivity in 2021 to 7995.00 kilograms of milk. The analysis of the results of the study showed a tendency to decrease the adaptive properties of young cows of the URD breed, which probably can be connected with a high degree of Holsteinization of the population of the newly created breed, during which the negative microevolutionary consequences of the rapid transformation of the genotype were manifested, which require further research.

MiRNAs as Predictors of Barrier Integrity.

The human body has several barriers that protect its integrity and shield it from mechanical, chemical, and microbial harm. The various barriers include the skin, intestinal and respiratory epithelia, blood-brain barrier (BBB), and immune system. In the present review, the focus is on the physical barriers that are formed by cell layers. The barrier function is influenced by the molecular microenvironment of the cells forming the barriers. The integrity of the barrier cell layers is maintained by the intricate balance of protein expression that is partly regulated by microRNAs (miRNAs) both in the intracellular space and the extracellular microenvironment. The detection of changes in miRNA patterns has become a major focus of diagnostic, prognostic, and disease progression, as well as therapy-response, markers using a great variety of detection systems in recent years. In the present review, we highlight the importance of liquid biopsies in assessing barrier integrity and challenges in differential miRNA detection.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Actomyosin contractility in olfactory placode neurons opens the skin epithelium to form the zebrafish nostril.

Despite their barrier function, epithelia can locally lose their integrity to create physiological openings during morphogenesis. The mechanisms driving the formation of these epithelial breaks are only starting to be investigated. Here, we study the formation of the zebrafish nostril (the olfactory orifice), which opens in the skin epithelium to expose the olfactory neurons to external odorant cues. Combining live imaging, drug treatments, laser ablation, and tissue-specific functional perturbations, we characterize a mechanical interplay between olfactory placode neurons and the skin, which plays a crucial role in the formation of the orifice: the neurons pull on the overlying skin cells in an actomyosin-dependent manner which, in combination with a local reorganization of the skin epithelium, triggers the opening of the orifice. This work identifies an original mechanism to break an epithelial sheet, in which an adjacent group of cells mechanically assists the epithelium to induce its local rupture.

Morphopathogenesis of Adult Acquired Cholesteatoma.

Background and Objectives. The aim of this study was to compare the distribution of proliferation markers (Ki-67, NF-κβ), tissue-remodeling factors (MMP-2, MMP-9, TIMP-2, TIMP-4), vascular endothelial growth factor (VEGF), interleukins (IL-1 and IL-10), human beta defensins (HβD-2 and HβD-4) and Sonic hedgehog gene protein in cholesteatoma and control skin. Methods. Nineteen patient cholesteatoma tissues and seven control skin materials from cadavers were included in the study and stained immunohistochemically. Results. Statistically discernible differences were found between the following: the Ki-67 in the matrix and the Ki-67 in the skin epithelium (p = 0.000); the Ki-67 in the perimatrix and the Ki-67 in the connective tissue (p = 0.010); the NF-κβ in the cholesteatoma matrix and the NF-κβ in the epithelium (p = 0.001); the MMP-9 in the matrix and the MMP-9 in the epithelium (p = 0.008); the HβD-2 in the perimatrix and the HβD-2 in the connective tissue (p = 0.004); and the Shh in the cholesteatoma's perimatrix and the Shh in the skin's connective tissue (p = 0.000). Conclusion. The elevation of Ki-67 and NF-κβ suggests the induction of cellular proliferation in the cholesteatoma. Intercorrelations between VEGF, NF-κβ and TIMP-2 induce neo-angiogenesis in adult cholesteatoma. The similarity in the expression of IL-1 and IL-10 suggests the dysregulation of the local immune status in cholesteatoma. The overexpression of the Sonic hedgehog gene protein in the cholesteatoma proves the selective local stimulation of perimatrix development.

Purinergic signaling during Marek’s disease in chickens

Purinergic receptors (PRs) have been reported as potential therapeutic targets for many viral infections including herpesviruses, which urges the investigation into their role in Marek’s disease (MD), a herpesvirus induced cancer in chickens that is an important pathogen for the poultry industry. MD is caused by MD virus (MDV) that has a similar viral life cycle as human varicella zoster virus in that it is shed from infected epithelial skin cells and enters the host through the respiratory route. In this report, PR responses during natural MDV infection and disease progression was examined in MD-resistant white Leghorns (WL) and MD-susceptible Pure Columbian (PC) chickens during natural infection. Whole lung lavage cells (WLLC) and liver tissue samples were collected from chickens infected but showing no clinical signs of MD (Infected) or presenting with clinical disease (Diseased). RNA was extracted followed by RT-qPCR analysis with gene specific primers against members of the P1, P2X, and P2Y PR families. Differential expression (p < 0.05) was observed in breed and disease conditions. Some PRs showed tissue specific expression (P1A1, P2X1, and P2X6 in WLLC) whereas others responded to MDV infection only in MD-susceptible (PC) chickens (P1A2A, P2X1, P2X5, P2X7). P2Y PRs had differential expression in both chicken lines in response to MDV infection and MD progression. This study is the first to our knowledge to examine PR responses during MDV infection and disease progression. These results suggest PR signaling may an important area of research for MDV replication and MD.

The use of 585 and 1064 nm laser for the treatment of basal cell skin cancer

Background. Basal cell skin cancer is the most common malignant epithelial skin neoplasm in fair-skinned people and accounts for two-thirds of all skin cancers in this population. Tumor lesions have a supporting vascular network that serves as a target for vascular selective lasers.&#x0D; Aims. To assess the effects of laser radiation at a wavelength of 585 and 1064 nm on the vasculature of various forms of basal cell skin cancer using dermatoscopy and in vivo confocal microscopy.&#x0D; Materials and methods. The study included 20 patients with 20 lesions of histologically confirmed basal cell skin cancer treated with a pulsed dye laser (wavelength 585 nm) and a long-pulse neodymium laser (wavelength 1064 nm) in the conditions of the consultative and diagnostic center of the Federal State Budgetary Institution GNTSDK of the Ministry of Health RF in the period from 2021 to 2022. The effectiveness of therapy was assessed using non-invasive methods for examining the skin.&#x0D; Results. According to the results of the two-year follow-up period, 100% effectiveness of therapy in both groups is noted, in 2 patients treated with a neodymium laser, the formation of hypertrophic scars in the treatment area is noted.&#x0D; Conclusions. Treatment of patients with basal cell skin cancer with selective vascular lasers may be an effective treatment option. Additional studies with a larger sample of observations and a long monitoring period are needed to confirm the effectiveness of this treatment method.

Human Papillomavirus: Detection Method and Infection

The Human Papilloma Virus (HPV) is a small non-enveloped DNA virus, around 8000 bp in size and only humans become its host by infecting skin epithelial tissue, human oral mucosa and anogenital epithelium. Human Papillomavirus is often found in patients and is ranked as the second most malignant disease in women, belonging to the Alphapapillomavirus genus. HPV infection can be identified through the structure of the HPV virus itself and the particles contained therein which initiate the carcinogenic process of its host. The research methods used in this study are literature studies. The literature study method is a series of activities related to the method of collecting library data, reading, recording and managing research materials. The method often used to detect HPV is the polymerase chain reaction (PCR). The viral cell reproduction process is aided by activated proteins E1, E2, E4, E5, E6, and E7, which also delay apoptosis and alter the host cell cycle in various ways to cause cell alterations that result in cancer cells.

DMARD treatment and skin cancer : Recognition, state of knowledge and prevention

Epithelial tumors differ in cellular origin, risk factors, incidence, and treatment. This article discusses the extent to which the use of disease-modifying antirheumatic drugs (DMARD) is associated with an increased risk for the development of skin tumors and for which substances the risk may be increased. In addition, some practical dermatological recommendations for rheumatologists are presented. The most frequent tumors of the skin are classified according to their cellular origin into malignant melanoma (MM) and so-called keratinocyte cancer (KC). The clinical presentation of these tumors differs and also the risk for the development of these epithelial skin tumors under DMARD treatment varies depending on the drug and tumor entity. As rheumatologists frequently see these patients for follow-up, it is essential to know the clinical findings as well as the corresponding risk factors of the specific tumor entities. Agenerally valid and reliable estimation of the risk for the development of epithelial skin tumors under DMARD treatment can only be formulated in the form of tendencies at the present time due to the lack of data. The relevant literature shows that regular intensive dermatological screening is recommended. Patients undergoing immunosuppressive or immune-modulating treatment should be instructed in self-inspection of the skin, receive regular dermatological check-ups and be instructed in strict UV protection methods. Lesions that do not heal or recurrently bleed should be referred for apunch biopsy to rule out or diagnose an epithelial skin tumor, as should atypical inflammatory lesions that do not heal with the use of topical glucocorticoids. An interdisciplinary approach in patient management is the key to success in ensuring the maximum quality of life with the lowest possible risk of developing epithelial skin tumors for these patients.

Senso-immunology: The Emerging Connection between Pain and Immunity.

The sensory and immune systems have been studied independently for a long time, whereas the interaction between the two has received little attention. We have carried out research to understand the interaction between the sensory and immune systems and have found that inflammation and bone destruction caused by fungal infection are suppressed by nociceptors. Furthermore, we have elucidated the molecular mechanism whereby fungal receptors are expressed on nociceptors and skin epithelium, how they cooperate to generate fungal pain, and how colitis and bone metabolism are regulated by mechanosensors expressed on the gut epithelium. Recently, we found that nociceptors prevent septic death by inhibiting microglia via nociceptor-derived hormones. This review summarizes our current state of knowledge on pain biology and outlines the mechanisms whereby pain and immunity interact. Our findings indicate that the sensory and immune systems share a variety of molecules and interact with each other to regulate our pathological and homeostatic conditions. This prompted us to advocate the interdisciplinary science named "senso-immunology," and this emerging field is expected to generate new ideas in both physiology and immunology, leading to the development of novel drugs to treat pain and inflammation.

A Clinico-Mycological and Histopathological Study of Recurrent Dermatophytosis

Background: A few recent studies have shown fungal elements within the hair follicle epithelium, which may act as a reservoir and responsible for recurrent dermatophytosis. Objectives: To assess the clinical patterns, mycological profile, and histopathology of recurrent dermatophytosis and to determine the prevalence of fungal hyphae in the hair follicle epithelium and other appendages. Materials and Methods: One hundred and fifty clinically diagnosed cases of recurrent dermatophytic infection were included. Skin samples were taken for direct microscopy, fungal culture, and histopathological analysis. Haematoxylin and eosin and special staining with periodic acid Schiff (PAS) and Gomori's methenamine silver (GMS) were performed to detect the fungal hyphae in the skin and hair follicle epithelium. Results: The most common clinical pattern observed was tinea corporis et cruris in 64 patients (42.66%). On direct microscopy and fungal culture, positive results were obtained in 116 cases (77.33%) and 78 (52%) cases, respectively. Presence of fungal hyphae in the stratum corneum, hair follicle, and acrosyringium was seen in 107 patients (71.33%), 47 patients (31.33%), and five patients (3.33%), respectively. Out of the 52 cases with hair follicle and eccrine gland involvement, history of fixed drug combinations (FDC) cream use was present in 42 cases (80.76%) and absent in ten cases (19.24%) (P = 0.000062). Limitations: Skin samples were taken only from a single skin lesion. Higher incidence of follicular invasion may have been detected if multiple biopsy samples were taken. Conclusion: Hair follicle/eccrine sweat gland involvement was observed in nearly one-third of the patients, which may act as a reservoir and may be responsible for recurrence and chronicity. Histopathology should be considered as an important adjuvant tool in recurrent dermatophytosis to establish the extent of the infection, which guides the further management.

Immunohistochemical expression of connective tissue growth factor in skin tags

Background:Skin tags (STs), also known as acrochordons, are the most common fibro epithelial skin tumours. Connective tissue growth factor (CTGF) is a novel peptide that exhibits platelet-derived growth factor-like activities and is produced by skin fibroblasts after activation with transforming growth factor-beta (TGF-β).The aim of this research was to evaluate the immunohistochemical expression of connective tissue growth factor in skin tags to provide an insight about its role in the pathogenesis of the disease. Methods: This prospective case-control research was carried out on 20 skin tags’ cases clinically and histopathologically diagnosed, and 10 healthy individuals of matched age and sex, served as control group.All cases were subjected to dermatological examination, skin biopsy and immunohistochemical staining. Results: There was significant difference between the cases and controls regarding epidermal (Acanthosis, hyperkeratosis, papillomatosis) and dermal changes (perivascular inflammatory infiltrate, fibroblasts, collagen arrangement) (P value

A Comparative Study of Therapeutic Efficacy of BCG Immunotherapy (50 Cases) and Vitamin D (50 Cases) in Cutaneous Warts (Total 100 Cases)

Background: Human papilloma virus infects the epithelium of skin or mucosal cells to cause warts. Most of the current therapeutic modalities are ablative, act only on targeted lesions, and lack a well-defined treatment endpoint. These procedures have high recurrence rates, side effects and are not effective over distant warts. Intralesional immunotherapy acts on cell mediated immunity to treat local as well as distant lesions. Aims and objectives: To evaluate the efficacy and safety of intralesional BCG and intralesional VITAMIN D and to compare efficacy and safety of intralesional BCG and intralesional VITAMIN D in the treatment of patients with cutaneous warts. Materials and Methods: This study included 100 adult patients with single or multiple warts of different size, number and duration with or without distance warts. Each patient was randomly assigned into Group 1 (BCG : 0.1mL of 1mg/mL) and Group 2 (vitamin D3 : 0.2mL of 15mg/mL). One or two warts were injected per session at interval of 21 days for three sessions. Response was assessed. Adverse effects were noted. Cases were further followed up after 3 months without any treatment to assess for any recurrences. In both the groups, standard medical treatment will be also given. Standard digital photographs were taken at each visit to support the data. Results: The BCG group had the maximum patients with complete response (36 of 50, 72%) followed by VITAMIN D group (24 of 50, 48%). No major adverse drug reactions were reported in any of the group. Limitations: Small sample size and absence of control group were the main limitations of our study. Conclusion: Immunotherapy offers a safe, effective and affordable approach in the patients with multiple cutaneous viral warts with lesser side effects and recurrence rate. Keywords: BCG, VITAMIN D, WARTS

Analysis of the kinetics of the eyelids of little owl Athene noctua

AbstractThis study gives a comprehensive description of eyelids movement in little owl and discusses the impact of some surrounding conditions in their kinetic performance. The present study used the video's recording technique to record the kinetic activity of eyelids, besides the anatomical and histological studies of the eyelid's structure. The fundamental eyelid movements can be uniquely and reliably characterized by their anatomical relationship that was confirmed via video recording for their kinetic activity. The levator palpebrae muscle is considered a main generating motor for the upper eyelid; in the little owl, this muscle splits into multiple directions and is distinguished from the levator palpebrae superioris (Lps) and the levator anguli oculi (Lao) muscle. That anatomical pattern of insertion increases the movement of the upper lid. On the other side, the contraction of depressor palpebrae inferioris (Dpi) muscle and the active upward forces of levator palpebrae muscle help in increasing the opening of the eye's fissure. However, the closure process is produced from the passive downward forces and relaxation of the levator palpebrae superioris (Lps), levator anguli oculi (Lao), and depressor palpebrae inferioris muscle, as well as the contraction of retractor anguli oculi lateralis (Raol) and medialis (Raom) muscle. The present results also recorded that nictitating membrane's (Nm) movement is reversely proportionate to the level of kinetic of other eyelids. The mobility of Nm in little owl occurs under the effect of artificial external stress. These anatomical data and sequence video recordings have confirmed that the upper eyelid moves more compared to other eyelids. The authors also suggest that the mobility of eyelids may get stimulated through external pressure force of some surrounding structure like the periorbital sheet. Also, the histological study exhibited that the structure of two eyelids is very similar in the little owl and the variability is showing in the number of cell layers that forms their epithelium of skin and palpebral surfaces, the distribution of pigment granules, and degree of keratinization on their surface. That variability in the histological characters of eyelids may counteract the abrasive forces occurring during the opening and closing processes.

Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer

Autophagy is a ubiquitous degradation mechanism, which plays a critical role in cellular homeostasis. To test whether autophagy suppresses or supports the growth of tumors in the epidermis of the skin, we inactivated the essential autophagy gene Atg7 specifically in the epidermal keratinocytes of mice (Atg7∆ep) and subjected such mutant mice and fully autophagy-competent mice to tumorigenesis. The lack of epithelial Atg7 did not prevent tumor formation in response to 7, 12-dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O tetradecanoylphorbol-13-acetate (TPA) as the promoter of tumor growth. However, the number of tumors per mouse was reduced in mice with epithelial Atg7 deficiency. In the K5-SOS&nbsp;EGFRwa2/wa2 mouse model, epithelial tumors were initiated by Son of sevenless (SOS) in response to wounding. Within 12 weeks after tumor initiation, 60% of the autophagy-competent K5-SOS&nbsp;EGFRwa2/wa2 mice had tumors of 1 cm diameter and had to be sacrificed, whereas none of the Atg7∆ep&nbsp;K5-SOS&nbsp;EGFRwa2/wa2 mice formed tumors of this size. In summary, the deletion of Atg7 reduced the growth of epithelial tumors in these two mouse models of skin cancer. Thus, our data show that the inhibition of autophagy limits the growth of epithelial skin tumors.

218 The Impact of Tissue Biomechanics on Epidermal Integrity in Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB) is an inherited skin disorder, characterized by mutations in the gene encoding for collagen VII. DEB manifests in chronic skin fragility with blistering at the dermal-epidermal junction. Unremitting injury and inflammation evoke progressive fibrosis of skin and other epithelia in DEB. Here, we aimed to understand consequences of this with respect to biomechanics, epidermal integrity and barrier function. To this end, we followed changes in skin biomechanics with age in DEB mice using atomic force microscopy and its consequences using lipidomics, followed by validating molecular analyses in human DEB donor skin.

Triptonide Inhibits the Cervical Cancer Cell Growth via Downregulating the RTKs and Inactivating the Akt-mTOR Pathway.

The high incidence and mortality of cervical cancer (CC) require an urgent need for exploring novel valuable therapeutics. Triptonide (TN) is a small molecule monomer extracted from the Chinese herb Tripterygium wilfordii Hook. Our results showed that TN, at only nanomolar concentrations, strongly inhibited growth, colony formation, proliferation, migration, and invasion of established and primary human cervical cancer cells. TN induced apoptosis and cell cycle arrest in cervical cancer cells. Moreover, cervical cancer cell in vitro migration and invasion were suppressed by TN. It was however noncytotoxic and proapoptotic to normal cervical epithelial cells and human skin fibroblast cells. Gene set enrichment analysis (GSEA) of RNA sequencing data of differentially expressed genes (DEGs) in TN-treated cervical cancer cells implied that DEGs were enriched in the receptor tyrosine kinase (RTK) signaling and PI3K-Akt-mTOR cascade. In cervical cancer cells, RTKs, including EGFR and PDGFRα, were significantly downregulated and Akt-mTOR activation was largely inhibited after TN treatment. In vivo, oral administration of TN significantly inhibited subcutaneous cervical cancer xenograft growth in nude mice. EGFR and PDGFRα downregulation as well as Akt-mTOR inactivation was detected in TN-treated HeLa xenograft tumor tissues. Thus, TN inhibits human cervical cancer cell growth in vitro and in vivo. Its anticervical cancer activity was associated with RTK downregulation and Akt-mTOR inactivation.