Back Skin Research Articles

C-LTMRs evoke wet dog shakes via the spinoparabrachial pathway

Many hairy mammals perform rapid oscillations of their body, called wet dog shakes, to remove water and irritants from their back hairy skin. The somatosensory mechanisms that underlie this behavior are unclear. We report that Piezo2-dependent mechanosensation mediates wet dog shakes evoked by water or oil droplets applied to back hairy skin of mice. Unmyelinated C-fiber low-threshold mechanoreceptors (C-LTMRs) were activated by oil droplets, and their optogenetic activation elicited wet dog shakes. Ablation of C-LTMRs attenuated this behavior. Moreover, C-LTMRs synaptically couple to spinoparabrachial neurons, and optogenetically inhibiting spinoparabrachial neuron synapses and excitatory neurons in the parabrachial nucleus impaired both oil droplet– and C-LTMR–evoked wet dog shakes. Thus, a C-LTMR–spinoparabrachial pathway promotes wet dog shakes for removal of water and mechanical irritants from back hairy skin.

Arctiin Alleviates Atopic Dermatitis Against Inflammation and Pyroptosis Through Suppressing TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD Signaling Pathways.

Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD. AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ. ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade. ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.

Exploring Black Soybean Extract Cream for Inflammatory Dermatitis—Toward Radiation Dermatitis Relief

We aimed to evaluate the effect of black soybean extract cream (BSEC) on 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis in murine models mimicking inflammatory dermatitis observed in humans. In this DNCB-induced model, BALB/c mice were spread with 100 μL of 2% DNCB twice a week for two weeks to induce skin inflammation on the shaved back skin; then, a placebo or BSEC that consisted of the volatile fraction derived from the seeds of Glycine max (L.) Merr. was applied to the DNCB-sensitized mice for 7 days. Gross visual analysis was conducted to assess the impact of BSEC on dermatitis, and an enzyme-linked immunosorbent assay (ELISA) was subsequently performed to detect inflammatory cytokines in the presence or absence of BSEC after DNCB sensitization. Lastly, the possible mechanisms responsible for the effects of BSEC on inflammatory dermatitis were investigated in a human leukemia monocytic cell line, THP-1. Our study showed that BSEC displayed antioxidant and anti-inflammatory effects. BSEC has the ability to diminish dermatitis, and all three experiments demonstrated that BSEC effectively reduced the progression of dermatitis while significantly suppressing inflammatory responses in the preclinical models. Consequently, BSEC exhibited promising phytotherapy for inflammatory dermatitis, potentially attributed to its anti-inflammatory and antioxidant properties.

Infrared-A to improve mood: an exploratory study of water-filtered infrared-A (wIRA) exposure.

Diurnal preference to eveningness might predispose to depression. There is preliminary evidence of infrared-A (IR-A) induced whole-body hyperthermia (WBH) in the treatment of depression. In this exploratory study with 19 adults, we investigated the effects of a 20-min exposure of water-filtered IR-A (wIRA) to the skin of back and buttock area, without inducing WBH, on mood and assessed the outcome by diurnal preference (#R19047, approval on 7 May 2019). The skin received irradiation with an integrated power of 102.4W in the wavelength region of 550-1350nm and a total dose of 123kJ over the total area of 0.0483m2. The diurnal preference was assessed with a 6-item version of the Morningness-Eveningness Questionnaire (mMEQ). The 40-item Profile of Mood States (POMS) questionnaire was used to assess total mood disturbance (TMD). Core temperature was measured 30min before, during and 30min after the irradiation. Skin surface temperature was measured on baseline and every two minutes during the irradiation. The TMD improved immediately after the exposure, and this positive effect lasted for 24h (p = 0.001) as well as for 2weeks (p = 0.02). Concerning the diurnal preference, the positive effect on mood was immediate and lasted for 24h in evening types (p = 0.02) and for 2weeks in morning types (p = 0.04). During the exposure, core body temperature was constantly lower in morning types compared to evening types. This study gives us new information on the effects of near-infrared radiation, without inducing WBH, through the skin on mood.

The Extended Corset with Bra Strap: Refinements in the Corset Trunkplasty Technique.

The corset trunkplasty was introduced by Moya et al. in 2009 (Moya and Sharma inJPRAS 62:56-64, 2009). It is a modified abdominoplasty technique that combines vertical and high lateral incisions to achieve an hourglass shape in post-massive weight loss patients. Like the traditional fleur-de-lis abdominoplasty (Dellon in Aesth Plast Surg 9:27-32, 1985) it results in a midline scar, as well as additional transverse breast fold scars, however the lack of tissue undermining reduces the risk of skin necrosis and wound-healing problems. Since its original description, it has been promoted as a practical, cost- and time-efficient procedure in the massive weight loss patient population (Loh et al. in J Plast Reconstr Aesthet Surg 74:2303-2310, 2021). The senior author (PM), has performed 43 extended corset trunkplasties since 2018. Drawbacks of the original technique include migration of the midline scar over time, stretch and enlargement of the umbilicus giving an unnatural appearance, high, unsightly lateral scars, upper back skin redundancy relative to the anterior skin tightening, and persistence of tissue excess in the flanks and lower back. Over time, the senior author has refined his technique to overcome these post-operative complications and thus improve overall aesthetic appearance and patient satisfaction.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Local Heating Profile to Manage Lower Back Pain in an Automotive Seat: A Pilot Study.

Lower back pain (LBP) is one of the most prevalent health losses in adults worldwide. Historically, heat has been successfully used for treating pain and relieving tight muscles. Given the effective contact with the occupant's back and proximity to the heat source, coupled with increasing commute times, automotive seats offer an opportunity to intervene. Fifteen adults (nine female) who experienced acute, subacute, and chronic lower back pain were recruited to examine the effectiveness of heat delivered to the lower back in providing temporary pain relief. Participants sat in a car seat for 38 min on two days, which included a 5-min baseline followed by a 33-min intervention; control, or localized. For the control condition, participants sat for 33 min without any thermal devices on, while the localized condition heated and maintained the seat surface temperature of the lower seat back area to ~45 °C. Over the 33-min control condition, the back skin temperature increased by ~1-2 °C and did not impact the subjective LBP. Heating the lower back for 33 min to ~39 °C reduced the subjective LBP by 10%. We demonstrated that lower back pain can be alleviated from an automotive seat providing heat to the lower back within normal commute times in those with lower back pain.

MrgprA3+ Primary Sensory Neurons Mediate Acute Allergic Itch Responses in Atopic Dermatitis Model Mice.

Itch is a prominent symptom of atopic dermatitis (AD). However, the underlying mechanism remains complex and has not yet been fully elucidated. Mas-related G protein-coupled receptor A3 (MrgprA3) has emerged attention as a marker of primary sensory neurons that specifically transmit itch signals; however, its involvement in AD-related itch has not been extensively explored. In this study, we developed an AD itch mouse model by repeatedly applying house dust mite (HDM) extract to barrier-impaired skin via a special diet. To clarify the role of MrgprA3+ neurons in itch behavior in our AD model, we adopted a toxin receptor-mediated cell knockout strategy using transgenic mice in which the diphtheria toxin receptor (DTR) gene was placed under the control of the Mrgpra3 promoter. When the HDM extract was repeatedly applied to the face and back skin of special diet-fed mice, the mice exhibited AD-like dry and eczematous skin lesions accompanied by three types of itch-related behaviors:1) spontaneous scratching, 2) acute scratching after antigen challenge, and 3) light touch-evoked scratching. Upon diphtheria toxin administration, substantial depletion of DTR+/MrgprA3+ neurons was observed in the dorsal root ganglion. Ablation of MrgprA3+ neurons suppressed acute itch responses after HDM application, whereas spontaneous and touch-evoked itch behaviors remained unaffected. Our findings unequivocally demonstrate that in our AD model, MrgprA3+ primary sensory neurons mediate acute allergic itch responses, whereas these neurons are not involved in spontaneous itch or alloknesis.

THE RISK OF SKIN IRRITATION OF CLARTÉ IN EXPERIMENTAL RABBITS

CLARTÉ is an external genital hygiene product, thus assessing skin irritation is an important test before commercializing the product for the community. Objectives: The study evaluated the local irritation on healthy rabbit skin of CLARTÉ manufactured and supplied by VIHECO PHARMA., JSC. Methods: The study was conducted according to the guidelines of the Vietnam Ministry of Health, ISO 10993-10, and OECD on skin irritation assessment for topical products. Three healthy white New Zealand rabbits were shaved off the fur on the back. Animals were applied directly 0.5 mL of CLARTÉ solution on the back skin and covered the application sites with a 2,5 cm × 2,5 cm non-occlusive dressing for 4 hours. We evaluated the irritation index including erythema and edema on the skin at 1, 24, 48, and 72 hours after removing the patches. Results: Three rabbits were still healthy, and living normally. There was very slight or well-defined erythema and very slight edema on the rabbit's skin applied by CLARTÉ after the first 24-hour treatment. The irritation index of CLARTE’ was 0.44, corresponding to negligible skin irritation during 72 hours of continuous monitoring. Conclusions: CLARTÉ product applied topically caused negligible irritation on healthy rabbit skin.

α-Arbutin ameliorates UVA-induced photoaging through regulation of the SIRT3/PGC-1α pathway.

Owing to its tyrosinase inhibitory activity, α-arbutin has been added to several skin care products as a skin-lightening agent. However, the protective effect of α-arbutin against ultraviolet A (UVA)-induced photoaging has not been well investigated. The present study was designed to investigate the photoprotective effect and mechanism of α-arbutin against UVA-induced photoaging. In vitro experiments, HaCaT cells were treated with UVA at a dose of 3J/cm2 to evaluate the anti-photoaging effect of α-arbutin. α-Arbutin was found to exhibit a strong antioxidant effect by increasing glutathione (GSH) level and inhibiting reactive oxygen species (ROS) production. Meanwhile, α-arbutin markedly improved the expression of sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) proteins, initiating downstream signaling to increase mitochondrial membrane potential and mediate mitochondrial biogenesis, and improve mitochondrial structure significantly. In vivo analysis, the mice with shaved back hair were irradiated with a cumulative UVA dose of 10J/cm2 and a cumulative ultraviolet B (UVB) dose of 0.63J/cm2. The animal experiments demonstrated that α-arbutin increased the expression of SIRT3 and PGC-1α proteins in the back skin of mice, thereby reducing UV-induced skin damage. In conclusion, α-arbutin protects HaCaT cells and mice from UVA damage by regulating SIRT3/PGC-1α signaling pathway.

Physiologically-based pharmacokinetic model of in vitro porcine ear skin permeation for drug delivery research.

In silico techniques, such as physiologically based pharmacokinetic modeling (PBKP), are recently gaining importance. Computational methods in drug discovery and development and the generic drugs industry enhance research effectiveness by saving time and money and avoiding ethical issues. One key advantage is the ability to conduct toxicology studies without risking harm to living beings. This study aimed to repurpose the multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) PBPK model for simulation permeation through porcine ear skin under in vitro conditions. The work was divided into four steps: (1) the development of a pig ear skin model based on a previously collected dataset; (2) testing the model's ability to discriminate permeation between pig ear, human abdomen, and human back skin; (3) development of a caffeine permeation model; and (4) testing the caffeine model's performance against in vitro generated data sourced from the scientific literature. Data from 31 manuscripts were used for the development of the pig skin model. Based on these data, values specific to pig skin were found for 22 parameters of the MPML MechDermA model. The model was able to discriminate permeation between pig and human skin. A caffeine model was developed and used to simulate seven experiments identified in the literature. The model's performance was assessed by comparing simulated to observed results. Based on a visual check, all simulations were considered acceptable, whereas three out of seven experiments met the twofold difference criterion. The variability of the experimental data was considered the biggest challenge for reliable model assessment.

Lymphatic endothelial cell-specific NRAS p.Q61R mutant embryos show abnormal lymphatic vessel morphogenesis.

Generalized lymphatic anomaly (GLA) and kaposiform lymphangiomatosis (KLA) are rare congenital disorders that arise through anomalous embryogenesis of the lymphatic system. A somatic activating NRAS p.Q61R variant has been recently detected in GLA and KLA tissues, suggesting that the NRAS p.Q61R variant plays an important role in the development of these diseases. To address this role, we studied the effect of the NRAS p.Q61R variant in lymphatic endothelial cells (LECs) on the structure of the lymphatics during embryonic and postnatal lymphangiogenesis applying inducible, LEC-specific NRAS p.Q61R variant in mice. Lox-stop-Lox NrasQ61R mice were crossed with Prox1-CreERT2 mice expressing tamoxifen-inducible Cre recombinase specifically in LECs. Whole-mount immunostaining of embryonic back skin using an antibody against the LEC surface marker VEGFR3 showed considerably greater lymphatic vessel width in LEC-specific NRAS p.Q61R mutant embryos than in littermate controls. These mutant embryos also showed a significant reduction in the number of lymphatic vessel branches. Furthermore, immunofluorescence staining of whole-mount embryonic back skin using an antibody against the LEC-specific nuclear marker Prox1 showed a large increase in the number of LECs in LEC-specific NRAS p.Q61R mutants. In contrast, postnatal induction of the NRAS p.Q61R variant in LECs did not cause abnormal lymphatic vessel morphogenesis. These results suggest that the NRAS p.Q61R variant in LECs plays a role in development of lymphatic anomalies. While this model does not directly reflect the human pathology of GLA and KLA, there are overlapping features, suggesting that further study of this model may help in studying GLA and KLA mechanisms.

A Comparative Blast Mitigation Performance Evaluation of Metallic Sandwich Panels with Honeycomb, Corrugated, Auxetic, and Foam Cores

Due to the high energy absorption capability and excellent bending strength of the sandwich panels, they are mostly preferred as protective structures against explosive blast attacks. The evaluation of their blast-mitigation characteristics through experiments is highly dangerous, costly, time-consuming, and polluting for the environment. Therefore, in this presented work, a series of numerical analyses were performed to evaluate the blast mitigation of the outstanding sandwich panels with honeycomb, corrugated, auxetic, and foam cores. The masses of sandwich panels were kept constant, and their areal densities were maintained constant throughout the study to effectively compare their performance under identical air blast loading conditions. To apply the air blast loads to the designed sandwiches, 1–3[Formula: see text]kg of spherical-shaped trinitrotoluene charges were used for a 100[Formula: see text]mm stand-off distance. The sandwiches are made of high-strength AL-6XN steel and crushable aluminum foam. The rate-dependent Johnson–Cook constitutive model of plasticity and the crushable foam model with volumetric hardening were used for the evaluation of sandwich panels’ plastic deformations. The findings of the work depicted that the honeycomb core is more efficient than the other core structures of the same masses because the sandwich panels with honeycomb core provide smaller back skin deflections, globalized core crushing, and higher core energy absorption than the other sandwich panels for extreme conditions of air blast loading.

Lactate triggers KAT8-mediated LTBP1 lactylation at lysine 752 to promote skin rejuvenation by inducing collagen synthesis in fibroblasts

Decreased collagen synthesis by fibroblasts is a key aspect of skin aging. Poly-L-Lactic Acid (PLLA) is a bioabsorbable material that can release lactate continuously, stimulating endogenous collagen synthesis in the skin. Herein, this study aimed to investigate the impact of PLLA-released lactate on collagen production in fibroblasts for skin rejuvenation. Human fibroblasts were exposed to varying concentrations of PLLA in vitro, while PLLA was injected into the back skin of aged mice in vivo. Safety and efficacy of PLLA on collagen synthesis and skin rejuvenation were evaluated through Calcein-AM/PI staining, EdU proliferation assay, and analysis of collagen I and collagen III expression in fibroblasts using western blotting and immunofluorescence. To elucidate the underlying mechanisms, lactate contents in cell-free supernatant and cell lysates from PLLA-treated fibroblasts, as well as total lysine lactylation (Pan Kla) levels were measured. Additionally, we found that fibroblasts can uptake extracellular lactate released from PLLA through monocarboxylate transporter-1 (MCT1) to facilitate latent-transforming growth factor beta-binding protein 1 (LTBP1) lactylation at lysine 752 (K752) via a KAT8-dependent mechanism, then increases the protein levels of collagen I and collagen III in fibroblasts. Overall, this study highlights a valuable insight into lactylation modification of non-histone protein for skin rejuvenation.

Effect and mechanism of Tricholoma matsutake extract combined with bakuchiol and ergothioneine on UVB-induced skin aging.

Aging is a physiological phenomenon in the process of life, and skin aging has a significant impact on human appearance. Therefore, the search for methods to delay skin aging is of great significance for improving the quality of human life. This study investigated the anti-photoaging effect of Tricholoma matsutake (T) extract composition combined with bakuchiol (B) and ergothioneine (E), and explored its potential mechanism through transcriptome, metabolomics, and network pharmacology. 57 main chemical components are identified from the ethanol extract of T. matsutake (T), including D-carnitine (24.55%), α,α-trehalose (15.56%), DL malic acid (8.99%), D-(-)-quinic acid (7.46%), erucamide (7.04%) and so on. After TBE treatment, inflammation of the mice dorsal skin is significantly minimized. Hematoxylin and eosin (H&E) staining and toluidine blue staining reveal that TBE has an anti-inflammatory effect on the back skin tissue of mice. Masson staining shows that TBE has a repair effect on mice dorsal skin tissue. In addition, the inflammatory factors (IL-1β, IL-6, TNF-α) in the mice dorsal skin tissues are significantly reduced but collagen (COL-1) is significantly increased. By cellular immunofluorescence assay, TBE is shown to promote PPAR-α expression in cells. Transcriptomics, metabolomics, and network pharmacology have revealed that TBE can regulate exogenous stimuli and cancer-related signaling pathways to prevent skin aging. The results suggest that TBE can be a beneficial supplement to natural anti-aging.

Establishment of a promising vitiligo mouse model for pathogenesis and treatment studies

AimsVitiligo is a chronic dermatological condition characterized by the progressive loss of melanocytes, for which traditional therapy has shown limited efficacy. This study aimed to establish a vitiligo model with easy operability, high repeatability, and stable depigmentation to provide a foundation for studying the pathogenesis and developing novel therapies for vitiligo.Methods(1) Establishing vitiligo model: Firstly, deliver B16F10 cells to the back skin of C57BL/6 J via intradermal injection (day 0), and the CD4 depletion antibody was injected intraperitoneally on day 4 and 10. Secondly, the melanoma was surgically removed on day 12. Thirdly, CD8 antibody was administered intraperitoneally every fourth day till day 30. (2) Identification of vitiligo model: H&E staining, immunohistochemistry, and immunofluorescence were used to detect the melanocytes. The melanin was detected by transmission electron microscopy (TEM), Lillie ferrous sulfate staining and L-DOPA staining.Results(1) The back skin and hair began to appear white on day 30. Melanin loss reached peak on day 60; (2) Hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence results showed melanocytes were reduced. L-DOPA staining, Lillie ferrous sulfate staining and TEM results showed that melanin decreased in the epidermis.ConclusionWe successfully establishment a vitiligo mouse model which can be more capable to simulate the pathogenesis of human vitiligo and provide an important basis for the study of pathogenesis and therapy of vitiligo.

Effects of fan cooling with an air-perfused rucksack on physiological and perceptual strains in young men while running in uncompensable hot environment.

Cooling devices reduce thermal strain during pre-, between-, and postexercise. However, their efficacy during moderate/intensity runs in hot conditions with airflow equivalent to the running speed remains unclear. This study assessed physiological and perceptual responses to neck and upper back fan-cooling through an air-perfused rucksack under such conditions. Ten young men ran at 60% V̇O<inf>2peak</inf> for 30 min in 35 °C, 50% relative humidity with (FAN) and without (CON) air-perfused rucksacks with a hood in a randomized order. Headwind equal to running speed was provided in both conditions. The fan-cooling trial consisted of upper back and neck fan cooling with airflow at 4-5 m/s via two fans attached on either side of the rucksack. Rectal and skin temperatures, whole-body thermal sensation, thermal comfort, and changes in body mass were measured. Upper back skin temperature and thermal sensation were significantly lower throughout the exercise in the FAN than in the CON, whereas thermal comfort was significantly higher at 15-40 min in the FAN (all P≤0.05). Heart rate elevation during 30 min of running was attenuated in the FAN compared to that in the CON (P≤0.05). No significant differences in rectal and mean skin temperatures, or total body mass loss were observed between the two trials. These results indicate that additional fan-cooling on the upper back and neck during running in uncompensable hot conditions with a headwind had limited physiological benefits. However, whole-body-based thermal sensation and comfort are partially improved with the use of an air-perfused rucksack.

DNMT inhibitor, 5-aza-2′-deoxycytidine mitigates di(2-ethylhexyl) phthalate-induced aggravation of psoriasiform inflammation in mice via reduction in global DNA methylation in dermal and peripheral compartments

Psoriasis is classified as an autoimmune disorder characterized by abnormal immune response leading to the development of chronic dermal inflammation. Most individuals have a genetic vulnerability that may be further influenced by epigenetic changes occurring due to multiple variables such as pollutant exposure. Epigenetic modifications such as DNA methylation possess a dynamic nature, enabling cellular differentiation and adaptation by controlling gene expression. Di(2-ethylhexyl) phthalate (DEHP) and psoriatic inflammation are known to cause modification of DNA methylation via DNA methyltransferase (DNMT). However, it is not known whether DEHP, a ubiquitous plasticizer affects psoriatic inflammation via DNMT modulation. Therefore, this study investigated the effect of DNMT inhibitor, 5-aza-2′-deoxycytidine (AZA) on DEHP-induced changes in the expression of DNMT1, global DNA methylation, and anti-/inflammatory parameters (p-STAT3, IL-17A, IL-6, iNOS, IL-10, Foxp3, Nrf2, HO-1) in the skin and the peripheral adaptive/ myeloid immune cells (CD4+ T cells/CD11b+ cells) in imiquimod (IMQ) model of psoriasiform inflammation. Further, psoriasis-associated clinical/histopathological features (ear thickness, ear weight, ear PASI score, MPO activity, and H&E staining of the ear and the back skin) were also analyzed in IMQ model. Our data show that IMQ-treated mice with DEHP exposure had increased DNMT1 expression and DNA methylation which was associated with elevated inflammatory (p-STAT3, IL-17A, IL-6, iNOS) and downregulated anti-inflammatory mediators (IL-10, Foxp3, Nrf2, HO-1) in the peripheral immune cells (CD4+ T cells/CD11b+ cells) and the skin as compared to IMQ-treated mice. Treatment with DNMT1 inhibitor caused reduction in inflammatory and elevation in anti-inflammatory parameters with significant improvement in clinical/histopathological symptoms in both IMQ-treated and DEHP-exposed IMQ-treated mice. In conclusion, our study shows strong evidence indicating that DNMT1 plays an important role in DEHP-induced exacerbation of psoriasiform inflammation in mice through hypermethylation of DNA.

Composition and diversity of 16S rRNA based skin bacterial microbiome in healthy horses

Characterization of microbiota structure on the skin of healthy horses is important for further development of modulation strategies to ensure optimal bacterial composition for physiological processes. This requirement is also supported by the relatively high incidence of dermatological diseases in horses and thus the need to manage them therapeutically. The taxonomic analysis of skin samples (n = 30) from five different body parts of clinically healthy Shetlands ponies females (neck, back, abdomen, pastern, muzzle) kept under homogeneous conditions (in open stalls with paddock, feed with dry hay, green grass ad libitum and granulated feed) was performed using amplification of V3—V4 region of the 16S rRNA gene. Results indicate that bacteria associated with healthy equine skin represent 18 phyla, 29 classes and 119 families. The most abundant phyla were Proteobacteria (30.8 ± 9.1%) followed by Actinobacteriota (20.4 ± 7.6%), Firmicutes (19.5 ± 10.1%), Bacteroidota (8.5 ± 5.0%) and Deinococcota (7.2 ± 14.8%). Among 229 genera identified, Corynebacterium (7.4 ± 6.5%) was the most abundant genus in skin sites of horses, followed by Deinococcus (7.1 ± 14.9%) and Macrococcus (5.0 ± 8.2%). Indices for the richness and diversity of species within bacterial populations for five regions of horses skin revealed no significant variations observed for species richness (Chao1, p-value 0.2001) but significant result for species evenness (Shannon, p-value 0.0049) with maximum on the neck and minimum on the back skin site. The clustering was seen across samples from different skin sites but also across samples collected from individual horses.

Cutaneous Application of Capsaicin Cream Reduces Clinical Signs of Experimental Colitis and Repairs Intestinal Barrier Integrity by Modulating the Gut Microbiota and Tight Junction Proteins.

Capsaicin, a pungent compound in chili peppers, is described as having potent anti-inflammatory, antioxidant, and antimicrobial properties. It is also described as a potential modulator of the immune system and intestinal microbiota. Oral or rectal administration of capsaicin has been studied to treat or prevent colitis. However, those vias are often not well accepted due to the burning sensation that capsaicin can cause. Our objective was to evaluate whether the application of capsaicin skin creams (0.075%) would be effective in improving inflammation and epithelial barrier function as well as the composition of the gut microbiota in a model of mild colitis induced by dextran sulfate sodium (1.5%). The results showed that the cutaneous application of capsaicin reversed weight loss and decreased colon shortening and diarrhea, all typical signs of colitis. There was also an improvement in the intestinal epithelial barrier, preserving proteins from tight junctions. We also evaluated the biodistribution of 99mtechnetium-radiolabeled capsaicin (99mTc-CAPS) applied to the back skin of the animals. We found significant concentrations of 99 mTc-Cap in the colon and small intestine after 2 and 4 h of administration. In addition, there was an increased expression of capsaicin receptor TRPV1 in the colon. Moreover, animals with colitis receiving cutaneous capsaicin presented a better short-chain fatty acid profile and increased levels of SIgA, suggesting increased microbiota diversity. In conclusion, our work opens avenues for further studies to better understand capsaicin's potential benefits and mechanisms in addressing colitis through cutaneous application.

Innate lymphoid cell-based immunomodulatory hydrogel microspheres containing Cutibacterium acnes extracellular vesicles for the treatment of psoriasis

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus, and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo, CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. Statement of significanceCutibacterium acnes, which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system.However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation.