Janus Kinase Inhibitors Ameliorated Gastrointestinal Amyloidosis and Hypoalbuminemia in Persistent Dermatitis Mouse Model

Malnutrition is not only regarded as a complication of rheumatoid arthritis and inflammatory bowel disease but also that of inflammatory skin disease; however, the mechanisms and efficacy of its treatment have not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of malnutrition in inflammatory skin conditions and efficacy of its treatment. We employed spontaneous skin inflammation mice models overexpressing human caspase-1 in the epidermal keratinocytes. Body weight, nutrition level, and α1-antitrypsin fecal concentration were measured. The gastrointestinal tract was histologically and functionally investigated. Fluorescein isothiocyanate (FITC)-dextran was forcibly fed on an empty stomach, and plasma FITC-dextran was measured. The treatment efficacy of antibodies against tumor necrosis factor-α (TNF-α) and interleukin (IL)-α/β as well as Janus kinase (JAK) inhibitors was investigated. Compared with wild-type littermates, the inflammatory skin mice models showed a lowered body weight, reduction of serum albumin level, amyloid deposition in the stomach, small intestine, and large intestine, and increased α1-antitrypsin fecal concentration. However, the plasma FITC-dextran was unchanged between the dermatitis models and wild-type littermates. The over-produced serum amyloid A1 in the liver was detected in the plasma in the dermatitis model. Antibodies against TNF-α and IL-α/β showed partial effects on amyloid deposition; however, JAK inhibitors improved gastrointestinal amyloidosis with the improvement of skin symptoms. Chronic dermatitis is closely related to secondary amyloidosis in the gastrointestinal tract, resulting in hypoalbuminemia. Therefore, active control of skin inflammation is essential for preventing gastrointestinal complications.     

Indigo Pulverata Levis (Chung-Dae,Persicaria tinctoria) Alleviates Atopic Dermatitis-like Inflammatory Responses In Vivo and In Vitro

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with a type 2 T helper cell (Th2) immune response. The Indigo Pulverata Levis extract (CHD) is used in traditional Southeast Asian medicine; however, its beneficial effects on AD remain uninvestigated. Therefore, we investigated the therapeutic effects of CHD in 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mice and tumor necrosis factor (TNF)-α- and interferon gamma (IFN)-γ-stimulated HaCaT cells. We evaluated immune cell infiltration, skin thickness, and the serum IgE and TNF-α levels in DNCB-induced AD mice. Moreover, we measured the expression levels of pro-inflammatory cytokines, mitogen-activated protein kinase (MAPK), and the nuclear factor-kappa B (NF-κB) in the mice dorsal skin. We also studied the effect of CHD on the translocation of NF-κB p65 and inflammatory chemokines in HaCaT cells. Our in vivo results revealed that CHD reduced the dermis and epidermis thicknesses and inhibited immune cell infiltration. Furthermore, it suppressed the proinflammatory cytokine expression and MAPK and NF-κB phosphorylations in the skin tissue and decreased serum IgE and TNF-α levels. In vitro results indicated that CHD downregulated inflammatory chemokines and blocked NF-κB p65 translocation. Thus, we deduced that CHD is a potential drug candidate for AD treatment.     

Deacetylasperulosidic Acid Ameliorates Pruritus,Immune Imbalance,and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice

The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.     

Isolation and identification of Treponema pedis and Treponema phagedenis-like organisms from bovine digital dermatitis lesions found in dairy cattle in Turkey

The isolation and identification of microorganisms associated with digital dermatitis (DD) in Turkish dairy cattle was investigated using punch skin biopsy samples from typical clinical lesions; they were collected from dairy farms and abattoirs in 5 different geographical locations in Turkey. Morphological characteristics and flagellation types were examined using a transmission electron microscope, and their enzyme profiles by enzyme activation kits; their catalase reaction characteristics were evaluated by the addition of 3% H₂O₂. Their phylogenies were identified using 16S rRNA and the results compared with known gene bank data. Bacterial cells were 5.0 to 18.2 µm long, 0.2 to 0.5 µm wide, and their minimum number of periplasmic flagellum was 4 (4:8:4) with a maximum of 8 (8:16:8). All isolates were catalase negative. Of the spirochetes isolated and identified, group I organisms showed close similarity with Treponema pedis (99% genetic homology), whereas those in group II were similar to Treponema phagedenis (98% homology). This is the first report of specific sub-groups of Treponema spp., isolated from Turkish dairy cattle presenting with DD lesions, being associated with this disease; these morphotypes were similar to those found globally in housed dairy cattle units and are probably significant microorganisms associated with the aetiopathogensis of this infectious disease causing acute bovine lameness. These results suggest that the distribution of DD-associated treponemes is not specific to particular geographic regions of Turkey.     

Skin Microbiota in Atopic Dermatitis

The skin microbiota represents an ecosystem composed of numerous microbial species interacting with each other, as well as with host epithelial and immune cells. The microbiota provides health benefits to the host by supporting essential functions of the skin and inhibiting colonization with pathogens. However, the disturbance of the microbial balance can result in dysbiosis and promote skin diseases, such as atopic dermatitis (AD). This review provides a current overview of the skin microbiota involvement in AD and its complex interplay with host immune response mechanisms, as well as novel therapeutic strategies for treating AD focused on restoring skin microbial homeostasis.     

Recovery from udder cleft dermatitis in dairy cows

Udder cleft dermatitis (UCD) is a common skin problem in dairy cows, localized at the fore udder attachment or between the udder halves. The main objectives of this study were to investigate spontaneous recovery from UCD in a longitudinal study and to investigate the treatment effect on UCD of a topical spray containing chelated copper and zinc in an additional treatment trial. Spontaneous recovery was investigated during a 1-yr longitudinal study in which 7 Swedish dairy herds were visited 9 times each, at 6-wk intervals. During the visits, all cows milked in the milking parlor were examined for mild and severe UCD, udder conformation traits, hygiene, and hock lesions. Additional cow and herd data were obtained from the Swedish official milk recording scheme. Recovery was defined as 2 consecutive observations of no UCD after a UCD case (1 or more consecutive observations of UCD). The recovery rate was calculated and factors associated with recovery were analyzed using discrete-time survival analysis. A treatment study was conducted in 4 of the herds after completion of the longitudinal study. Cows with UCD were allocated to treatment or a control group, and cows in the treatment group were treated once every day for 14 to 28 d. At follow-up visits on d 14, 28, and 56, all cows were scored for UCD. To investigate the effect of treatment, an ordered logistic regression model was used, with UCD score on d 56 (no, mild, or severe) as the outcome. Other potential explanatory variables were also included in the model. A total of 38% (126 of 329) of the cows in the longitudinal study made a spontaneous recovery from UCD. A long duration of UCD, severe lesions and higher parity reduced the chance of recovery. Among the recovered cows, 47% (59 of 126 cows) had a recurrent case of UCD after the recovery. In the treatment study, there was no difference in UCD score on d 56 between the treatment and control groups. Factors that affected the UCD score on d 56 were the duration of UCD before the treatment study started, UCD score on d 1 and udder conformation. Our findings emphasize the importance of further studies to identify effective treatment regimens as well as further studies to unravel the pathophysiology of UCD to improve the recommendations on how to prevent these lesions.     

Health Effects of Probiotics on the Skin

Skin is the largest organ of the body and is constantly exposed to physical, chemical, bacterial, and fungal challenges. It is well known that probiotics are helpful for specific disorders and different clinical studies have indicated that probiotics have special effects in cutaneous apparatus directly or indirectly that can be considerable from versatile aspects. Probiotic bacteriotherapy can have great potential in preventing and treating the skin diseases including eczema, atopic dermatitis, acne, and allergic inflammation or in skin hypersensitivity, UV-induced skin damage, wound protection, and as a cosmetic product. The current paper comprehensively reviews the different health effects of probiotics on the skin.     

Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3^β-actin mice). We found that SRG3^β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3^β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.     

An observational study on the management of digital dermatitis through a repeated risk assessment on 19 Dutch dairy herds

The etiopathogenesis of bovine digital dermatitis (DD) is not well understood, but its risk factors on dairy farms have been studied extensively. The objective of this study was to identify associations between a DD risk score [determined by a DD risk assessment questionnaire (RAQ)] and DD prevalence (determined by an in-parlor M-score). We also investigated whether feedback for farmers on their DD management using the DD RAQ resulted in changes that decreased DD prevalence in their herds. The DD RAQ consisted of multiple-choice questions related to foot health, housing, and general management that were used to create a total risk score (TRS). In 2016 and 2018, the DD RAQ—together with a DD prevalence determination in the lactating herd—was used on 19 Dutch dairy farms from 1 veterinary practice. After each visit, farmers and their consulting veterinarians received a 1-page summary that identified herd-specific strengths and weaknesses in DD management. In 2018, the summary included suggestions for improvement. In 2019, farmers and veterinarians were contacted to ask whether the use of the DD RAQ and the 1-page summary had led them to implement changes in their DD management in 2016 and 2018. We tested the association between TRS and DD prevalence using linear mixed model analysis. The TRS ranged from 13 to 65% and 20 to 68% in 2016 and 2018, respectively. Herd DD prevalence ranged from 15 to 59% and 27 to 69% in 2016 and 2018, respectively. For both years, the DD RAQ identified that DIM, herd size, and breed were often present in a manner associated with increased risk for DD. The linear mixed model analysis identified that each 10-point increase in TRS was associated with an increase in herd DD prevalence of less than 1%. The association between TRS and herd DD prevalence was caused mainly by risk factors related to housing. We found no important relationship between change in TRS and change in DD prevalence between the 2 visits. Only a few farmers indicated some form of change in their DD management following a visit. Veterinarians in general said that they discussed the 1-page summaries and DD control with farmers during a routine visit, but the majority admitted a lack of follow-up. We propose that the DD RAQ could be used as a tool to start a discussion on DD control on farm, but simply undertaking a DD RAQ and providing a 1-page summary of the results was insufficient to initiate behavioral change that led to a decrease in DD prevalence.     

Prevalence and risk factors for udder cleft dermatitis in dairy cattle

Udder cleft dermatitis (UCD) is a skin lesion in dairy cattle mostly located at the anterior junction between the udder and the abdominal wall or between the front quarters. Relatively little is known about causative factors for UCD, and few studies have investigated prevalence and risk factors of UCD. Therefore, the aim of this study was to investigate the prevalence of UCD in a random sample of dairy herds with freestalls and milking parlors in a county of Sweden. Thirty dairy herds participated in the study. Each herd was visited once at milking, when every third cow was investigated for presence of UCD. Associations between UCD and milk production, breed, parity, days in milk, claw health, and udder health on the herd and cow levels were also investigated. In addition, a case-control study was performed in 6 herds with a high prevalence of UCD to investigate associations between udder conformation or mange and UCD. Udder cleft dermatitis was found in 18.4% of the 1,084 cows included in the study. The within-herd cow prevalence varied between zero and 39%, with an average of 18.5%. Risk factors for UCD at the herd level were a high proportion of Swedish Red cows and a high production level. At the cow level, breed, parity, and production level were identified as risk factors. The highest risk of having UCD was found in high-producing Swedish Red cows that had calved at least 3 times. Veterinary-treated clinical mastitis was associated with UCD, but cow composite somatic cell count was not. A strong anterior udder attachment was a protective factor, but signs of mange had no association with UCD. The primary cause of UCD is still unclear, and more research is needed to identify the best ways to prevent the development of this animal welfare problem.