ID1high/activin Ahigh glioblastoma cells contribute to resistance to anti-angiogenesis therapy through malformed vasculature.

Although bevacizumab (BVZ), a representative drug for anti-angiogenesis therapy (AAT), is used as a first-line treatment for patients with glioblastoma (GBM), its efficacy is notably limited. Whereas several mechanisms have been proposed to explain the acquisition of AAT resistance, the specific underlying mechanisms have yet to be sufficiently ascertained. Here, we established that inhibitor of differentiation 1 (ID1)high/activin Ahigh glioblastoma cell confers resistance to BVZ. The bipotent effect of activin A during its active phase was demonstrated to reduce vasculature dependence in tumorigenesis. In response to a temporary exposure to activin A, this cytokine was found to induce endothelial-to-mesenchymal transition via the Smad3/Slug axis, whereas prolonged exposure led to endothelial apoptosis. ID1 tumors showing resistance to BVZ were established to be characterized by a hypovascular structure, hyperpermeability, and scattered hypoxic regions. Using a GBM mouse model, we demonstrated that AAT resistance can be overcome by administering therapy based on a combination of BVZ and SB431542, a Smad2/3 inhibitor, which contributed to enhancing survival. These findings offer valuable insights that could contribute to the development of new strategies for treating AAT-resistant GBM.

Long-term skeletodental changes with early and late treatment using modified C-palatal plates in hyperdivergent Class II adolescents.

OBJECTIVES: To compare skeletodental changes between early and late treatment groups using modified C-palatal plates (MCPP) and long-term retention outcomes in hyperdivergent Class II adolescents. MATERIALS AND METHODS: Seventy-one hyperdivergent Class II patients were divided into four groups according to treatment modality and treatment timing: group 1, early treatment with MCPP (n = 16; 9.9 ± 0.9 years); group 2, late treatment with MCPP (n = 19; 12.3 ± 0.8 years); group 3, early treatment with headgear (HG; n = 18; 9.6 ± 0.8 years); and group 4, late treatment with HG (n = 18; 12.1 ± 1.2 years). Lateral cephalograms were taken and skeletal and dental variables were measured. For statistical analysis, paired t-tests, independent t-tests, and multiple regression were performed. RESULTS: The early MCPP group showed a more significant decrease in mandibular plane angle than the late MCPP group did, and vertical control was more efficient in the early group than in the late group. In the MCPP groups, both FMA and SN-GoGn were increased with late treatment but decreased with early treatment, and the difference was statistically significant (P < .01). The early-treatment MCPP group had a significant decrease in SN-GoGn of 0.6° compared with an increase of 1.7° in the early treatment HG group (P < .01). Posttreatment stability of both the early and late MCPP groups was maintained in long-term retention. CONCLUSIONS: Early MCPP showed more significant vertical control than late MCPP. However, there was no difference in long-term stability between early and late groups.

Development of the Korean construction job exposure matrix (KoConJEM) based on experts' judgment using the 60 consolidated occupations for construction workers.

BACKGROUND: This study was conducted as an effort to develop a Korean construction job exposure matrix (KoConJEM) based on 60 occupations recently consolidated by the construction workers mutual aid association for use by the construction industry. METHODS: The probability, intensity, and prevalence of exposure to 26 hazardous agents for 60 consolidated occupations were evaluated as binary (Yes/No) or four categories (1 to 4) by 30 industrial hygiene experts. The score for risk was calculated by multiplying the exposure intensity by the prevalence of exposure. Fleiss' kappa for each hazardous agent and occupation was used to determine agreement among the 30 experts. The JEM was expressed on a heatmap and a web-based dashboard to facilitate comparison of factors affecting exposure according to each occupation and hazardous agent. RESULTS: Awkward posture, heat/cold, heavy lifting, and noise were hazardous agents regarded as exposure is probable by at least one or more experts in all occupations, while exposure to asphalt fumes was considered hazardous in the smallest number of occupations (n = 5). Based on the degree of agreement among experts, more than half of the harmful factors and most occupations showed fair to good results. The highest risk value was 16 for awkward posture for most occupations other than safety officer. CONCLUSIONS: The KoConJEM provides information on the probability, intensity, and prevalence of exposure to harmful factors, including most occupations employing construction workers; therefore, it may be useful in the conduct of epidemiological studies on assessment of health risk for construction workers.

Treatment outcome and long-term stability of orthognathic surgery for facial asymmetry: A systematic review and meta-analysis.

Objective: : This systematic review aimed to provide a comparative analysis of the treatment outcomes, including hard and soft tissues, postoperative stability, temporomandibular disorders (TMD), and quality of life (QoL), in patients with facial asymmetry who underwent orthognathic surgery. Methods: : The primary objective was to address the question, "How do different factors related to surgery affect the outcomes and stability of orthognathic surgery in the correction of facial asymmetry?" A meta-analysis was conducted on the outcome parameters, such as skeletal, dental, and soft tissue symmetry, TMD, QoL, and relapse, using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Subgroup analyses were conducted considering surgery-related factors such as surgical techniques (one-jaw vs. two-jaw), use of the surgery-first approach, utilization of computer simulation, and analytical methods employed to evaluate asymmetry (2D vs. 3D). Results: : Forty-nine articles met the inclusion criteria. The meta-analysis demonstrated a significant improvement in the symmetry of hard and soft tissues. The subgroup analysis indicated that the treatment outcomes showed significant improvement, regardless of the factors related to surgery. Changes in TMD signs and symptoms varied according to the surgical technique used. Quality of life improved in the facial, oral, and social domains. Skeletal relapse was observed during the follow-up. Conclusions: : Our findings support the positive outcomes of orthognathic surgery in the treatment of facial asymmetry in terms of skeletal and soft tissue improvements, stability, relief of TMD symptoms, and enhancement of QoL. However, most of the included studies showed a low certainty of evidence and high heterogeneity.

Clinical, demographic factors, and substance use among Hispanic and non-Hispanic young adult childhood cancer survivors.

PURPOSE: The purpose of this study is to examine the protective and risk factors of substance use behaviors (tobacco, marijuana, e-cigarette, and alcohol) among young adult childhood cancer survivors. The study focused on clinical (receipt of cancer-related follow-up care, treatment intensity, late effects, depressive symptoms, self-rated health) and demographic (race/ethnicity, neighborhood socioeconomic status) factors and their associations with substance use. METHODS: Participants were from the Project Forward cohort, a population-based study of young adult survivors of childhood cancers. Participants (N = 1166, Mage = 25.1 years) were recruited through the Los Angeles Cancer Surveillance Program (Cancer Registry covering Los Angeles County, California). Multivariate path analyses were performed with substance use as the outcome variables and clinical and demographic factors as independent variables. Covariates included age and sex. FINDING: Substance use was positively associated with depressive symptoms, and inversely associated with cancer-related follow-up care, female sex, age, Hispanic ethnicity, treatment intensity, and self-rated health. Neighborhood SES was inversely associated with tobacco use, while being positively associated with binge drinking and e-cigarette use. The results highlight the interrelationship between the clinical and demographic variables and their associations with different substance use. CONCLUSION: Findings support the need for effective interventions targeting substance use behavior among CCS. This will help improve long-term outcomes and mitigate the risk for early morbidity.

Migrasomal autophagosomes relieve endoplasmic reticulum stress in glioblastoma cells.

BACKGROUND: Glioblastoma (GBM) is more difficult to treat than other intractable adult tumors. The main reason that GBM is so difficult to treat is that it is highly infiltrative. Migrasomes are newly discovered membrane structures observed in migrating cells. Thus, they can be generated from GBM cells that have the ability to migrate along the brain parenchyma. However, the function of migrasomes has not yet been elucidated in GBM cells. RESULTS: Here, we describe the composition and function of migrasomes generated along with GBM cell migration. Proteomic analysis revealed that LC3B-positive autophagosomes were abundant in the migrasomes of GBM cells. An increased number of migrasomes was observed following treatment with chloroquine (CQ) or inhibition of the expression of STX17 and SNAP29, which are involved in autophagosome/lysosome fusion. Furthermore, depletion of ITGA5 or TSPAN4 did not relieve endoplasmic reticulum (ER) stress in cells, resulting in cell death. CONCLUSIONS: Taken together, our study suggests that increasing the number of autophagosomes, through inhibition of autophagosome/lysosome fusion, generates migrasomes that have the capacity to alleviate cellular stress.

Accuracy and clinical validity of automated cephalometric analysis using convolutional neural networks.

BACKGROUND: This study aimed to assess the error range of cephalometric measurements based on the landmarks detected using cascaded CNNs and determine how horizontal and vertical positional errors of individual landmarks affect lateral cephalometric measurements. METHODS: In total, 120 lateral cephalograms were obtained consecutively from patients (mean age, 32.5 ± 11.6) who visited the Asan Medical Center, Seoul, Korea, for orthodontic treatment between 2019 and 2021. An automated lateral cephalometric analysis model previously developed from a nationwide multi-centre database was used to digitize the lateral cephalograms. The horizontal and vertical landmark position error attributable to the AI model was defined as the distance between the landmark identified by the human and that identified by the AI model on the x- and y-axes. The differences between the cephalometric measurements based on the landmarks identified by the AI model vs those identified by the human examiner were assessed. The association between the lateral cephalometric measurements and the positioning errors in the landmarks comprising the cephalometric measurement was assessed. RESULTS: The mean difference in the angular and linear measurements based on AI vs human landmark localization was .99 ± 1.05°, and .80 ± .82 mm, respectively. Significant differences between the measurements derived from AI-based and human localization were observed for all cephalometric variables except SNA, pog-Nperp, facial angle, SN-GoGn, FMA, Bjork sum, U1-SN, U1-FH, IMPA, L1-NB (angular) and interincisal angle. CONCLUSIONS: The errors in landmark positions, especially those that define reference planes, may significantly affect cephalometric measurements. The possibility of errors generated by automated lateral cephalometric analysis systems should be considered when using such systems for orthodontic diagnoses.

Accuracy of posteroanterior cephalogram landmarks and measurements identification using a cascaded convolutional neural network algorithm: A multicenter study.

Objective: : To quantify the effects of midline-related landmark identification on midline deviation measurements in posteroanterior (PA) cephalograms using a cascaded convolutional neural network (CNN). Methods: : A total of 2,903 PA cephalogram images obtained from 9 university hospitals were divided into training, internal validation, and test sets (n = 2,150, 376, and 377). As the gold standard, 2 orthodontic professors marked the bilateral landmarks, including the frontozygomatic suture point and latero-orbitale (LO), and the midline landmarks, including the crista galli, anterior nasal spine (ANS), upper dental midpoint (UDM), lower dental midpoint (LDM), and menton (Me). For the test, Examiner-1 and Examiner-2 (3-year and 1-year orthodontic residents) and the Cascaded-CNN models marked the landmarks. After point-to-point errors of landmark identification, the successful detection rate (SDR) and distance and direction of the midline landmark deviation from the midsagittal line (ANS-mid, UDM-mid, LDM-mid, and Me-mid) were measured, and statistical analysis was performed. Results: : The cascaded-CNN algorithm showed a clinically acceptable level of point-to-point error (1.26 mm vs. 1.57 mm in Examiner-1 and 1.75 mm in Examiner-2). The average SDR within the 2 mm range was 83.2%, with high accuracy at the LO (right, 96.9%; left, 97.1%), and UDM (96.9%). The absolute measurement errors were less than 1 mm for ANS-mid, UDM-mid, and LDM-mid compared with the gold standard. Conclusions: : The cascaded-CNN model may be considered an effective tool for the auto-identification of midline landmarks and quantification of midline deviation in PA cephalograms of adult patients, regardless of variations in the image acquisition method.

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion.

Jagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-ß signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-ß signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.

Novel Procedure for Automatic Registration between Cone-Beam Computed Tomography and Intraoral Scan Data Supported with 3D Segmentation.

In contemporary practice, intraoral scans and cone-beam computed tomography (CBCT) are widely adopted techniques for tooth localization and the acquisition of comprehensive three-dimensional models. Despite their utility, each dataset presents inherent merits and limitations, prompting the pursuit of an amalgamated solution for optimization. Thus, this research introduces a novel 3D registration approach aimed at harmonizing these distinct datasets to offer a holistic perspective. In the pre-processing phase, a retrained Mask-RCNN is deployed on both sagittal and panoramic projections to partition upper and lower teeth from the encompassing CBCT raw data. Simultaneously, a chromatic classification model is proposed for segregating gingival tissue from tooth structures in intraoral scan data. Subsequently, the segregated datasets are aligned based on dental crowns, employing the robust RANSAC and ICP algorithms. To assess the proposed methodology's efficacy, the Euclidean distance between corresponding points is statistically evaluated. Additionally, dental experts, including two orthodontists and an experienced general dentist, evaluate the clinical potential by measuring distances between landmarks on tooth surfaces. The computed error in corresponding point distances between intraoral scan data and CBCT data in the automatically registered datasets utilizing the proposed technique is quantified at 0.234 ± 0.019 mm, which is significantly below the 0.3 mm CBCT voxel size. Moreover, the average measurement discrepancy among expert-identified landmarks ranges from 0.368 to 1.079 mm, underscoring the promise of the proposed method.

Precautions and possibilities in orthodontic treatment of periodontally compromised patients: Current recommendations.

OBJECTIVE: Orthodontic treatment plays a crucial role in achieving optimal dental esthetics and functional occlusion. However, when periodontally compromised patients are involved, additional precautions and considerations are critical. This article aims to provide up-to-date recommendations for the orthodontic treatment of periodontally compromised patients. CLINICAL CONSIDERATIONS: Comprehensive diagnosis of the patient's periodontal status, inherent malocclusion, and secondary malocclusion resulting from periodontal disease are essential for achieving optimal esthetics and functional occlusion. This can be facilitated through the use of a simplified checklist. Prior to orthodontic treatment, pre-existing periodontal diseases should be managed. Light and controlled forces should be used to minimize the risk of adverse effects on the periodontium, and any potential traumatic occlusion during tooth movement should be minimized. Furthermore, careful anchorage management is required, and proper application of temporary anchorage devices can significantly expand the scope of orthodontic treatment. Finally, treatment results are maintained by ongoing supportive periodontal therapy even during the retention period. CONCLUSIONS: This article presents clinical cases demonstrating the importance of accurate diagnosis in orthodontics and periodontics and the positive impact of orthodontic treatment on patients with pre-existing periodontal diseases. CLINICAL SIGNIFICANCE: An up-to-date orthodontic treatment protocol for periodontally compromised patients is presented.

Orthognathic surgical planning using graph CNN with dual embedding module: External validations with multi-hospital datasets.

BACKGROUND AND OBJECTIVE: Despite recent development of AI, prediction of the surgical movement in the maxilla and mandible by OGS might be more difficult than that of tooth movement by orthodontic treatment. To evaluate the prediction accuracy of the surgical movement using pairs of pre-(T0) and post-surgical (T1) lateral cephalograms (lat-ceph) of orthognathic surgery (OGS) patients and dual embedding module-graph convolution neural network (DEM-GCNN) model. METHODS: 599 pairs from 3 institutions were used as training, internal validation, and internal test sets and 201 pairs from other 6 institutions were used as external test set. DEM-GCNN model (IEM, learning the lat-ceph images; LTEM, learning the landmarks) was developed to predict the amount and direction of surgical movement of ANS and PNS in the maxilla and B-point and Md1crown in the mandible. The distance between T1 landmark coordinates actually moved by OGS (ground truth) and predicted by DEM-GCNN model and pre-existed CNN-based Model-C (learning the lat-ceph images) was compared. RESULTS: In both internal and external tests, DEM-GCNN did not exhibit significant difference from ground truth in all landmarks (ANS, PNS, B-point, Md1crown, all P > 0.05). When the accumulated successful detection rate for each landmark was compared, DEM-GCNN showed higher values than Model-C in both the internal and external tests. In violin plots exhibiting the error distribution of the prediction results, both internal and external tests showed that DEM-GCNN had significant performance improvement in PNS, ANS, B-point, Md1crown than Model-C. DEM-GCNN showed significantly lower prediction error values than Model-C (one-jaw surgery, B-point, Md1crown, all P < 0.005; two-jaw surgery, PNS, ANS, all P < 0.05; B point, Md1crown, all P < 0.005). CONCLUSION: We developed a robust OGS planning model with maximized generalizability despite diverse qualities of lat-cephs from 9 institutions.

The prediction of sagittal chin point relapse following two-jaw surgery using machine learning.

The study aimed to identify critical factors associated with the surgical stability of pogonion (Pog) by applying machine learning (ML) to predict relapse following two-jaw orthognathic surgery (2 J-OGJ). The sample set comprised 227 patients (110 males and 117 females, 207 training and 20 test sets). Using lateral cephalograms taken at the initial evaluation (T0), pretreatment (T1), after (T2) 2 J-OGS, and post treatment (T3), 55 linear and angular skeletal and dental surgical movements (T2-T1) were measured. Six ML modes were utilized, including classification and regression trees (CART), conditional inference tree (CTREE), and random forest (RF). The training samples were classified into three groups; highly significant (HS) (≥ 4), significant (S) (≥ 2 and < 4), and insignificant (N), depending on Pog relapse. RF indicated that the most important variable that affected relapse rank prediction was ramus inclination (RI), CTREE and CART revealed that a clockwise rotation of more than 3.7 and 1.8 degrees of RI was a risk factor for HS and S groups, respectively. RF, CTREE, and CART were practical tools for predicting surgical stability. More than 1.8 degrees of CW rotation of the ramus during surgery would lead to significant Pog relapse.

Annexin A2 Stabilizes Oncogenic JAG1 Intracellular Domain by Inhibiting Proteasomal Degradation in Glioblastoma Cells.

Glioblastoma (GBM) is the most lethal brain cancer, causing inevitable deaths of patients owing to frequent relapses of cancer stem cells (CSCs). The significance of the NOTCH signaling pathway in CSCs has been well recognized; however, there is no NOTCH-selective treatment applicable to patients with GBM. We recently reported that Jagged1 (JAG1), a NOTCH ligand, drives a NOTCH receptor-independent signaling pathway via JAG1 intracellular domain (JICD1) as a crucial signal that renders CSC properties. Therefore, mechanisms regulating the JICD1 signaling pathway should be elucidated to further develop a selective therapeutic regimen. Here, we identified annexin A2 (ANXA2) as an essential modulator to stabilize intrinsically disordered JICD1. The binding of ANXA2 to JICD1 prevents the proteasomal degradation of JICD1 by heat shock protein-70/90 and carboxy-terminus of Hsc70 interacting protein E3 ligase. Furthermore, JICD1-driven propagation and tumor aggressiveness were inhibited by ANXA2 knockdown. Taken together, our findings show that ANXA2 maintains the function of the NOTCH receptor-independent JICD1 signaling pathway by stabilizing JICD1, and the targeted suppression of JICD1-driven CSC properties can be achieved by blocking its interaction with ANXA2.

Association with Combined Occupational Hazards Exposure and Risk of Metabolic Syndrome: A Workers' Health Examination Cohort 2012-2021.

Background: This study aimed to evaluate the association between exposure to occupational hazards and the metabolic syndrome. A secondary objective was to analyze the additive and multiplicative effects of exposure to risk factors. Methods: This retrospective cohort was based on 31,615 health examinees at the Pusan National University Yangsan Hospital in Republic of Korea from 2012-2021. Demographic and behavior-related risk factors were treated as confounding factors, whereas three physical factors, 19 organic solvents and aerosols, and 13 metals and dust were considered occupational risk factors. Time-dependent Cox regression analysis was used to calculate hazard ratios. Results: The risk of metabolic syndrome was significantly higher in night shift workers (hazard ratio = 1.45: 95% confidence interval = 1.36-1.54) and workers who were exposed to noise (1.15:1.07-1.24). Exposure to some other risk factors was also significantly associated with a higher risk of metabolic syndrome. They were dimethylformamide, acetonitrile, trichloroethylene, xylene, styrene, toluene, dichloromethane, copper, antimony, lead, copper, iron, welding fume, and manganese. Among the 28 significant pairs, 19 exhibited both positive additive and multiplicative effects. Conclusions: Exposure to single or combined occupational risk factors may increase the risk of developing metabolic syndrome. Working conditions should be monitored and improved to reduce exposure to occupational hazards and prevent the development of the metabolic syndrome.

Occupational asthma related to indoor air pollution in a worker at an indoor air gun shooting range: a case report.

Background: Indoor air pollution can cause and exacerbate asthma. We report a previously undescribed case of occupational asthma related to indoor air pollution in a worker at an indoor air gun shooting range and highlight the potential risk of developing occupational asthma in this environment. Case presentation: A 31-year-old man presented with dyspnea, cough, and sputum and was diagnosed with asthma complicated by pneumonia. Objective evidence of asthma was obtained by performing a methacholine bronchial provocation test. It was suspected that the patient had occupational asthma, which began one month after changing jobs to work within the indoor air gun shooting range. The highest peak expiratory flow (PEF) diurnal variability on working days was 15%, but the highest variation was 24%, with 4 days out of 4 weeks having a variation of over 20% related to workplace exposure. Conversely, the diurnal variability on the rest days was 7%, and no day showed a variation exceeding 20%. The difference in the average PEF between working and rest days was 52 L/min. PEF deterioration during working days and improvement on rest days were noted. Conclusions: The results obtained from the in-depth analysis of the PEF were adequate to diagnose the patient with occupational asthma. Exposure to indoor air pollution and lead and the patient's atopy and allergic rhinitis may have contributed to the development of occupational asthma.

Incidence rates of injury, musculoskeletal, skin, pulmonary and chronic diseases among construction workers by classification of occupations in South Korea: a 1,027 subject-based cohort of the Korean Construction Worker's Cohort (KCWC).

Background: The objective of this study is to investigate the differences in incidence rates of targeted diseases by classification of occupations among construction workers in Korea. Methods: In a subject-based cohort of the Korean Construction Worker's Cohort, we surveyed a total of 1,027 construction workers. As occupational exposure, the classification of occupations was developed using two axes: construction business and job type. To analyze disease incidence, we linked survey data with National Health Insurance Service data. Eleven target disease categories with high prevalence or estimated work-relatedness among construction workers were evaluated in our study. The average incidence rates were calculated as cases per 1,000 person-years (PY). Results: Injury, poisoning, and certain other consequences of external causes had the highest incidence rate of 344.08 per 1,000 PY, followed by disease of the musculoskeletal system and connective tissue for 208.64 and diseases of the skin and subcutaneous tissue for 197.87 in our cohort. We especially found that chronic obstructive pulmonary disease was more common in construction painters, civil engineering welders, and civil engineering frame mold carpenters, asthma in construction painters, landscape, and construction water proofers, interstitial lung diseases in construction water proofers. Conclusions: This is the first study to systematically classify complex construction occupations in order to analyze occupational diseases in Korean construction workers. There were differences in disease incidences among construction workers based on the classification of occupations. It is necessary to develop customized occupational safety and health policies for high-risk occupations for each disease in the construction industry.

Induction of autophagy improves skin and hair conditions in dogs with underlying diseases.

Background: Autophagy was reported to play a crucial role in maintaining general and skin health. Methods: The study used a synthesized autophagy inducer (AI) (Aquatide™ cospharm Inc.; Daejeon, Korea), for evaluating the effects of autophagy on skin and hair in dogs. Twenty-two dogs with poor skin and hair which were diagnosed with canine atopic dermatitis (CAD) or pituitary-dependent hyperadrenocorticism (PDH) were included. Clinical scores using Canine Atopic Dermatitis Extent and Severity Index-04 (CADESI-04), Pruritus Visual Analog Scale (PVAS) and skin barrier function using measurement of transepidermal water loss (TEWL) were evaluated and canine keratinocytes were also used in vitro investigation of pro-inflammatory cytokines after AI treatment. Results: In the AI group, clinical scores and skin barrier function were improved at week 8 significantly compared to in the other groups. In particular, the AI significantly improved the hair surface damage at 8 weeks compared to the baseline. In vitro, the AI reduced pro-inflammatory cytokines by activating the 78-kDa glucose-regulated protein (GRP78). Conclusion: AI improve skin barrier function and hair damage and reduce pro-inflammatory cytokines by inhibiting reactive oxygen species (ROS) production in dogs.