In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein.

The novel coronavirus disease 2019 has stimulated the rapid development of new biological therapeutics to inhibit SARS-CoV-2 infection; however, this remains a challenging task. In a previous study using structural analysis, we revealed that human cyclophilin A inhibits the entry of SARS-CoV-2 into host cells by interfering with the interaction of the receptor-binding domain of the spike protein with angiotensin-converting enzyme 2 on the host cell surface, highlighting its potential for antiviral therapy. For a comprehensive experimental validation, in this study, we verified the antiviral effects of human cyclophilin A against SARS-CoV-2, including its variants, using in vitro assays and experiments on an in vivo mouse model. Human cyclophilin A demonstrated a highly effective antiviral effect, with an 85% survival rate upon SARS-CoV-2 infection. It also reduced viral titers, inflammation in the lungs and brain, and cytokine release in the serum, suggesting a controlled immune response and potentially faster recovery. Overall, our study provides insights into the potential of human cyclophilin A as a therapeutic agent against SARS-CoV-2, which should guide future clinical trials that might provide an additional therapeutic option for patients.

Correction: The emerging role of medical foods and therapeutic potential of medical food-derived exosomes.

[This corrects the article DOI: 10.1039/D3NA00649B.].

Synergistic vesicle-vector systems for targeted delivery.

With the immense progress in drug delivery systems (DDS) and the rise of nanotechnology, challenges such as target specificity remain. The vesicle-vector system (VVS) is a delivery system that uses lipid-based vesicles as vectors for a targeted drug delivery. When modified with target-probing materials, these vesicles become powerful vectors for drug delivery with high target specificity. In this review, we discuss three general types of VVS based on different modification strategies: (1) vesicle-probes; (2) vesicle-vesicles; and (3) genetically engineered vesicles. The synthesis of each VVS type and their corresponding properties that are advantageous for targeted drug delivery, are also highlighted. The applications, challenges, and limitations of VVS are briefly examined. Finally, we share a number of insights and perspectives regarding the future of VVS as a targeted drug delivery system at the nanoscale.

Pathogenic Factors and Recent Study on the Rapid Detection of Shiga Toxin-Producing Escherichia coli (STEC).

This comprehensive review delves into the pathogenicity and detection of Shiga Toxin-Producing Escherichia coli (STEC), shedding light on its various genetic and clinical manifestations. STEC originating from E. coli acquires pathogenicity through mobility and genetic elements. The pathogenicity of STEC is explored in terms of clinical progression, complications, and key toxins such as Shiga toxin (Stx). Stx1 and Stx2 are two distinct Stx types exhibiting different toxicities, with Stx2 often associated with severe diseases. This review also delves into Subtilase cytotoxin, an additional cytotoxin produced by some STEC strains. Pathogenic mechanisms of STEC, such as attaching and effacing intestinal lesions, are discussed, with a focus on roles of genetic factors. Plasmids in STEC can confer unique pathogenicity. Hybridization with other pathogenic E. coli can create more lethal pathogens. This review covers a range of detection methods, ranging from DNA amplification to antigen detection techniques, emphasizing the need for innovative approaches to improve the sensitivity and speed of STEC diagnosis. In conclusion, understanding diverse aspects of STEC pathogenicity and exploring enhanced diagnostic methods are critical to addressing this foodborne pathogen effectively. Pathology of Shiga toxin toxicity. STEC-derived Shiga toxin consists of one A subunit and five B subunits. Pathological symptoms of the disease can progress to HUS within two weeks after the onset of diarrhea. Shiga toxin intoxication is also associated with many complications, such as neurological and cardiac complications. This figure was reconstructed based on data from Bruyand et al.

The emerging role of medical foods and therapeutic potential of medical food-derived exosomes.

Medical food is consumed for the purpose of improving specific nutritional requirements or disease conditions, such as inflammation, diabetes, and cancer. It involves partial or exclusive feeding for fulfilling unique nutritional requirements of patients and is different from medicine, consisting of basic nutrients, such as polyphenols, vitamins, sugars, proteins, lipids, and other functional ingredients to nourish the patients. Recently, studies on extracellular vesicles (exosomes) with therapeutic and drug carrier potential have been actively conducted. In addition, there have been attempts to utilize exosomes as medical food components. Consequently, the application of exosomes is expanding in different fields with increasing research being conducted on their stability and safety. Herein, we introduced the current trends of medical food and the potential utilization of exosomes in them. Moreover, we proposed Medi-Exo, a exosome-based medical food. Furthermore, we comprehensively elucidate various disease aspects between medical food-derived exosomes (Medi-Exo) and therapeutic natural bionanocomposites. This review highlights the therapeutic challenges regarding Medi-Exo and its potential health benefits.

Clinical Manifestations and Genotype of Primary Ciliary Dyskinesia Diagnosed in Korea: Multicenter Study.

PURPOSE: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder that leads to secondary ciliary dysfunction. PCD is a rare disease, and data on it are limited in Korea. This study systematically evaluated the clinical symptoms, diagnostic characteristics, and treatment modalities of pediatric PCD in Korea. METHODS: This Korean nationwide, multicenter study, conducted between January 2000 and August 2022, reviewed the medical records of pediatric patients diagnosed with PCD. Prospective studies have been added to determine whether additional genetic testing is warranted in some patients. RESULTS: Overall, 41 patients were diagnosed with PCD in 15 medical institutions. The mean age at diagnosis was 11.8 ± 5.4 years (range: 0.5 months-18.9 years). Most patients (40/41) were born full term, 15 (36.6%) had neonatal respiratory symptoms, and 12 (29.3%) had a history of admission to the neonatal intensive care unit. The most common complaint (58.5%) was chronic nasal symptoms. Thirty-three patients were diagnosed with transmission electron microscopy (TEM) and 12 patients by genetic studies. TEM mostly identified outer dynein arm defects (alone or combined with inner dynein arm defects, n = 17). The genes with the highest mutation rates were DNAH5 (3 cases) and DNAAF1 (3 cases). Rare genotypes (RPGR, HYDIN, NME5) were found as well. Chest computed tomography revealed bronchiectasis in 33 out of 41 patients. Among them, 15 patients had a PrImary CiliAry DyskinesiA Rule score of over 5 points. CONCLUSIONS: To our knowledge, this is the first multicenter study to report the clinical characteristics, diagnostic methods, and genotypes of PCD in Korea. These results can be used as basic data for further PCD research.

Synergistic outcomes of Chlorella-bacterial cellulose based hydrogel as an ethylene scavenger.

Increasing the freshness of vegetables requires the elimination of ethylene, which can be done through chemical methods. However, the development of eco-friendly approaches is required for environmental reasons. Chlorella vulgaris (C. vulgaris) was selected as a new biological material for demonstrating an excellent performance in ethylene removal. To support C. vulgaris, bacterial cellulose (BC) produced by Gluconacetobacter hansenii (G. hansenii) was chosen due to its high water content and biodegradability. To increase BC productivity, UV-induced mutant G. hansenii was isolated, and they produced high yields of BC (9.80 ±â€¯0.52 g/L). Furthermore, comparative transcriptome analysis revealed metabolic flux changes toward UDP-glucose accumulation and enhanced BC production. BC-based hydrogels (BC hydrogels) were successfully prepared using a 2.4 % carboxymethyl cellulose (CMC) and 1 % agar mixture. We used Chlorella-BC hydrogels as an ethylene scavenger, which reduced 90 % of ethylene even when the immobilized C. vulgaris was preserved for 14 days at room temperature without media supplementation. We demonstrated for the first time the potential of BC hydrogels to integrate C. vulgaris as a sustainable ethylene absorber for green food packaging and biomass technology.

Pneumatically Driven Microfluidic Platform and Fully Automated Particle Concentration System for the Capture and Enrichment of Pathogens.

In this study, we developed a pneumatically driven microfluidic platform (PDMFP) operated by a fully automated particle concentration system (FAPCS) for the pretreatment of micro- and nano-sized materials. The proposed PDMFP comprises a 3D network with a curved fluidic chamber and channel, five on/off pneumatic valves for blocking fluid flow, and a sieve valve for sequential trapping of microbeads and target particles. Using this setup, concentrated targets are automatically released into an outlet port. The FAPCS mainly comprises solenoid valves, glass reservoirs, a regulator, pressure sensor, main printed circuit board, and liquid crystal display touch panel. All pneumatic valves in the microfluidic platform as well as the working fluids in the glass reservoirs are controlled using FAPCS. The flow rate of the working fluids is measured to demonstrate the sequential programed operation of the proposed pretreatment process using FAPCS. In our study, we successfully achieved rapid and efficient enrichment using PDMFP-FAPCS with fluorescence-labeled Escherichia coli. With pretreatment-10 min for the microbead concentration and 25 min for target binding-almost all the target bacteria could be captured. A total of 526 Gram-negative bacteria were attached to 82 beads, whereas Gram-positive bacteria were attached to only 2 of the 100 beads. Finally, we evaluated the PDMFP-FAPCS for SARS-CoV-2 receptor-binding domain (RBD)-based outer membrane vesicles (OMVs) (RBD-OMVs). Specific probes involved in PDMFP-FAPCS successfully isolated RBD-OMVs. Thus, PDMFP-FAPCS exhibits excellent enrichment of particles, including microbes and nanovesicles, and is an effective pretreatment platform for disease diagnosis and investigation.

Bovine Colostrum Exosomes Are a Promising Natural Bacteriostatic Agent against Staphylococcus aureus.

Bioactive molecules and immune factors in the bovine colostrum (BC) are important elements of passive immunity that prevent bacterial infection. However, the mechanisms underlying the antimicrobial activity of BC are not fully understood. We assessed the antibacterial properties of BC-derived exosomes (BC-Exo) and found that they had bacteriostatic, anti-hemolytic, and biofilm-eradication effects on Staphylococcus aureus. Moreover, cell surface deformation and reduced ATP production were observed following BC-Exo treatment. The most reasonable explanation for this finding is that BC-Exo has a strong inhibitory effect on the oxidative phosphorylation pathway in S. aureus. We demonstrated, for the first time, that BC-Exo can exhibit clear antimicrobial activity against S. aureus. Our findings constitute an important basis for future antibiotic discovery.

Distinction of Male and Female Trees of Ginkgo biloba Using LAMP.

Ginkgo biloba is utilized as food, medicine, wood, and street trees among other things. The objective of this study was to develop a loop-mediated isothermal amplification (LAMP) assay for gender distinction of G. biloba. Male-specific SCAR gene can be utilized to identify G. biloba gender using LAMP. The optimized LAMP conditions, temperature 60 °C, 2-mM MgSO4, and [F3/B3]:[FIP/BIP] primer ratio of 1:4 were selected as final conditions. The G. biloba SCAR LAMP displayed a sensitivity of 10 ng when amplified by concentration under the optimum conditions. Additionally, it demonstrated a particular response in male with SYBR Green I in LAMP analysis that can be a more powerful tool for field and scale-up applications. Our work represents a first attempt to identify G. biloba gender using LAMP and offers an efficient and reliable tool for roadside landscaping.

Clinical characteristics of pediatric patients infected with SARS-CoV-2 versus common human coronaviruses: a national multicenter study.

BACKGROUND: Human coronaviruses (HCoV) cause mild upper respiratory infections; however, in 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, causing an acute respiratory disease pandemic. Coronaviruses exhibit marked epidemiological and clinical differences. PURPOSE: This study compared the clinical, laboratory, and radiographic findings of children infected with SARS-CoV-2 versus HCoV. METHODS: SARS-CoV-2 data were obtained from the Korea Disease Control and Prevention Agency (KDCA) registry and 4 dedicated coronavirus disease 2019 (COVID-19) hospitals. Medical records of children admitted with a single HCoV infection from January 2015 to March 2020 were collected from 10 secondary/tertiary hospitals. Clinical data included age, sex, underlying disease, symptoms, test results, imaging findings, treatment, and length of hospital stay. RESULTS: We compared the clinical characteristics of children infected with HCoV (n=475) to those of children infected with SARS-CoV-2 (272 from KDCA, 218 from COVID-19 hospitals). HCoV patients were younger than KDCA patients (older than 9 years:3.6% vs. 75.7%; P<0.001) and patients at COVID-19 hospitals (2.0±2.9 vs 11.3±5.3; P<0.001). Patients with SARS-CoV-2 infection had a lower rate of fever (26.6% vs. 66.7%; P<0.001) and fewer respiratory symptoms than those with HCoV infection. Clinical severity, as determined by oxygen therapy and medication usage, was worse in children with HCoV infection. Children and adolescents with SARS-CoV-2 had less severe symptoms. CONCLUSION: Children and adolescents with COVID-19 had a milder clinical course and less severe disease than those with HCoV in terms of symptoms at admission, examination findings, and laboratory and radiology results.

Analysis of Factors Affecting the Rate of Latent Tuberculosis Infection and Management in Pediatrics.

The incidence of tuberculosis remains high in South Korea; the management of latent tuberculosis infection (LTBI) has become the prime target for reducing the infection rate. The management of pediatric LTBI is especially crucial because children can serve as a long-term source of infection upon developing active tuberculosis. Therefore, it is important to assess pediatric LTBI using contact investigation and follow-up. We conducted a retrospective study on children aged between 0 and 18 years who visited our hospital for tuberculosis contact screening from February 2012 to February 2021. Tuberculosis index cases and their clinical characteristics were also reviewed retrospectively. A total of 350 children were investigated, and 68 of 247 (27.5%) were diagnosed with LTBI. The rate of LTBI (r = 7.98, p < 0.001) and the risk of loss to follow-up (r = 27.038, p < 0.001) were higher in cases with close household contact. Sputum (r = 10.992, p < 0.001) and positive acid-fast bacillus (AFB) stain (r = 4.458, p = 0.001) in tuberculosis index cases were related to the diagnosis of LTBI in pediatric contacts. Active management is needed for tuberculosis screening in pediatric contacts, especially when the contacts are older and the index case is within the family, and when the index case has sputum and has tested positive for AFB smear.

Cardiac biomarkers and detection methods for myocardial infarction.

Background: A significant heart attack known as a myocardial infarction (MI) occurs when the blood supply to the heart is suddenly interrupted, harming the heart muscles due to a lack of oxygen. The incidence of myocardial infarction is increasing worldwide. A relationship between COVID-19 and myocardial infarction due to the recent COVID-19 pandemic has also been revealed. Objective: We propose a biomarker and a method that can be used for the diagnosis of myocardial infarction, and an aptamer-based approach. Results: For the diagnosis of myocardial infarction, an algorithm-based diagnosis method was developed using electrocardiogram data. A diagnosis method through biomarker detection was then developed. Conclusion: Myocardial infarction is a disease that is difficult to diagnose based on the aspect of a single factor. For this reason, it is necessary to use a combination of various methods to diagnose myocardial infarction quickly and accurately. In addition, new materials such as aptamers must be grafted and integrated into new ways. Purpose of Review: The incidence of myocardial infarction is increasing worldwide, and some studies are being conducted on the association between COVID-19 and myocardial infarction. The key to properly treating myocardial infarction is early detection, thus we aim to do this by offering both tools and techniques as well as the most recent diagnostic techniques. Recent Findings: Myocardial infarction is diagnosed using an electrocardiogram and echocardiogram, which utilize cardiac signals. It is required to identify biomarkers of myocardial infarction and use biomarker-based ELISA, SPR, gold nanoparticle, and aptamer technologies in order to correctly diagnose myocardial infarction.

A Comparison of Clinical Features of Youth with and without Rhinitis Signs and Symptoms Who Are Hospitalized for Headache.

Headache and allergic rhinitis (AR) are common in children and often co-occur. We investigated the clinical characteristics of pediatric headaches and the association of AR and chronic headaches. We retrospectively reviewed the medical records of patients admitted to our pediatric inpatient and outpatient clinics with complaints of headache between January 2017 and June 2020 for headache-specific history, AR signs and symptoms, allergy skin prick test, inhalant multiple allergen simultaneous test results, laboratory and imaging findings, and medication history. The patients were divided into three subgroups: AR, non-AR, and headache groups, reporting 45.7% patients with headache alone, 13.7% with additional AR, and 31.6% with abnormal imaging findings, suggesting that headache was combined with sinusitis (24.3%) or mastoiditis (7.3%). Furthermore, 6% of the patients had both AR and sinusitis. Body mass index (BMI) differed significantly between the AR and the non-AR and headache groups (p = 0.03). The BMI differed significantly according to headache severity (p ˂ 0.001). The most common allergen was "dust or mites" (41.1%). Acetaminophen (35.9%) was the most commonly used painkiller. The coexistence of AR and headache may indicate that these conditions share a similar pathophysiology. Better management of allergies may facilitate diagnosis, treatment, and prophylaxis of headaches.

Broussonetia × hanjiana (Moraceae) microsatellite markers for species and ploidy determination developed using next-generation sequencing.

BACKGROUND: Broussonetia × hanjiana has been considered a hybrid owing to its morphology, which is intermediate between that of B. papyrifera (L.) L'Her. ex Vent. and B. kazinoki Siebold. A recent study demonstrated the hybrid origin of B. × hanjiana in Korea using molecular markers. In this study, we developed microsatellite markers for B. × hanjiana using next-generation sequencing and cross-species transferability analysis. METHODS AND RESULTS: A total of 432 primers were designed from 205,819 contigs. Among them, 24 microsatellite markers showing polymorphisms were used to evaluate the population genetic characteristics. The observed heterozygosity (HO) and expected heterozygosity (HE) were 0.835 and 0.628, respectively. The cross-species transferability of these markers was evaluated in two closely related species of Broussonetia; all 24 markers showed cross-species amplification. Using flow cytometry, diploid and triploid individuals were identified in B. × hanjiana. In particular, the BR137 marker showed evidence of two parent species (B. papyripera and B. kazinoki), with a hybrid pattern observed in B. × hanjiana, demonstrating its utility for species identification and ploidy assessment. CONCLUSIONS: The new B. × hanjiana microsatellite markers can be useful in genetic studies of closely related B. papyripera, B. kazinoki, and B. × hanjiana.

Application of a Cold Dry Air Provocation Test in Pediatric Patients with Asthma.

Asthma is a chronic inflammatory airway disease characterized by reversible airway obstruction and airway hyperreactivity. We proposed a cold dry air (CDA) provocation test and investigated its application in pediatric patients with asthma. We enrolled 72 children and adolescents older than 5 years who presented to our hospital with chronic cough, shortness of breath, and wheezing. We analyzed the results of allergy, pulmonary function, methacholine provocation, and CDA provocation tests. The FEV1 change 5 min after the provocation was recorded as CDA5 dFEV1; that after 15 min was recorded as CDA15 dFEV1. PT10 was the provocation time causing a 10% decrease in FEV1; a decrease of >10% in dFEV1 was considered a positive CDA test. Among the 72 subjects, 51 were diagnosed with asthma. A positive CDA test in patients with asthma correlated with non-eosinophilic asthma. In patients with asthma, sputum eosinophils and eosinophil cationic protein (ECP) levels of the patients with a positive CDA test were significantly lower than those of patients with a negative test. CDA5 dFEV1 correlated with PC20 and total immunoglobulin E. CDA15 dFEV1 correlated with PC20, sputum eosinophils, and ECP. PT10 became shorter as the peripheral blood eosinophil, FVC, FEV1, FEV1/FVC, and FEF25-75 decreased. The CDA provocation test showed airway hyperreactivity to non-specific stimuli, a high correlation with non-eosinophilic asthma, and the possibility of assessing asthma severity via PT10.

Human Resource Practices for Corporate Social Responsibility: Evidence From Korean Firms.

Human resource management (HRM) in managing environmental, social, governance (ESG), or corporate social responsibility (CSR) initiatives has been recently raised. Yet, little attention has been paid to integrating CSR and HRM. Our primary goal was to identify how and whether certain HR practices are critical for developing employee capability to operate in firms with active CSR initiatives. We first examine the impact of external CSR activities on firm-level work outcomes. Moreover, we attempt to identify a choice of particular HR practices that could be aligned with external CSR activities. We then empirically examine how each HR practice interacts with external CSR activities that influence employee retention and labor productivity. Using three longitudinal datasets conducted by the government-sponsored research institution over 154 publicly traded Korean firms for five waves of survey years, the results show that external CSR has a limited impact on employee retention and labor productivity. However, when external CSR activities are combined with a specific set of HR practices, including person-organization fit-based selection, performance-based pay, extensive investment of training and development, and employee suggestion program, the impact of external CSR on employee work outcomes is more substantial. The results indicate that external CSR and a particular set of HR practices as internal CSR can be complementary and generate a positive interaction on creating sustainable human capabilities.

Structure based innovative approach to analyze aptaprobe-GPC3 complexes in hepatocellular carcinoma.

BACKGROUND: Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is a biomarker of hepatocellular carcinoma (HCC) progression. Aptamers specifically binding to target biomolecules have recently emerged as clinical disease diagnosis targets. Here, we describe 3D structure-based aptaprobe platforms for detecting GPC3, such as aptablotting, aptaprobe-based sandwich assay (ALISA), and aptaprobe-based imaging analysis. RESULTS: For preparing the aptaprobe-GPC3 platforms, we obtained 12 high affinity aptamer candidates (GPC3_1 to GPC3_12) that specifically bind to target GPC3 molecules. Structure-based molecular interactions identified distinct aptatopic residues responsible for binding to the paratopic nucleotide sequences (nt-paratope) of GPC3 aptaprobes. Sandwichable and overlapped aptaprobes were selected through structural analysis. The aptaprobe specificity for using in HCC diagnostics were verified through Aptablotting and ALISA. Moreover, aptaprobe-based imaging showed that the binding property of GPC3_3 and their GPC3 specificity were maintained in HCC xenograft models, which may indicate a new HCC imaging diagnosis. CONCLUSION: Aptaprobe has the potential to be used as an affinity reagent to detect the target in vivo and in vitro diagnosing system.

Identification of tissue of origin in cancer of unknown primary using a targeted bisulfite sequencing panel.

Aim: To construct a targeted bisulfite sequencing panel predicting origin of cancer of unknown primary. Methods: A bisulfite sequencing panel targeting 2793 tissue-specific markers was performed in 100 clinical samples. Results: The authors' prediction model showed 0.85 accuracy for the 'first-ranked' tissue type and 0.93 accuracy for the 'second-ranked' tissue type using 2793 tissue-specific markers and 0.84 accuracy for the 'first-ranked' tissue type and 0.92 accuracy for the 'second-ranked' tissue type when the number of tissue-specific markers was reduced to 514. Conclusion: Targeted bisulfite sequencing is a useful method for predicting the tissue of origin in patients with cancer of unknown primary.

When patients with cancer present with tumors that have migrated from elsewhere in the body, it is difficult for clinicians to identify where the cancer originated. DNA methylation profiling is a promising test to help identify where the cancer originated because it reflects cell of origin and is compatible with formalin-fixed, paraffin-embedded tissues. Because next-generation sequencing has already been implemented in clinical laboratories, the authors developed a targeted bisulfite sequencing panel that could predict the tissue of origin using genomic DNA extracted from formalin-fixed, paraffin-embedded tissues. The authors found that a hybrid capture-based targeted bisulfite sequencing panel is a useful method for predicting the tissue of origin in patients with cancer of unknown primary origin in clinical practice.

The Role of Collagen VI α6 Chain Gene in Atopic Dermatitis.

BACKGROUND: In a previous study, we carried out whole-exome sequencing to identify genetic variants associated with early onset atopic dermatitis (AD) in Koreans and found that collagen VI α6 chain (COL6A6) gene polymorphisms are associated. COL6A6 is one of the chains that makes up the triple helix of collagen VI, and little is known about its role in AD. OBJECTIVE: To identify how COL6A6 changes in AD and clarify its role. METHODS: Immunohistochemical staining for COL6A6 was performed on tissues of AD, other skin diseases, and healthy controls. Human keratinocytes and fibroblasts were exposed to inflammatory cytokines and cultured to evaluate changes in COL6A6 expression. COL6A6 small interfering RNA (siRNA) was transfected into cells to identify the role of COL6A6. RESULTS: Total COL6A6 mRNA was higher in AD than in controls. In AD tissues, COL6A6 mRNA decreased significantly in the epidermis compared to controls, whereas COL6A6 protein was increased in the dermis. In the cultured cells, COL6A6 mRNA was suppressed in the epidermis by interleukin (IL)-4 and IL-13, whereas COL6A6 protein was induced in the dermis. In the COL6A6 siRNA-transfected keratinocyte, mRNA of FLG, LOR, and CASP14 decreased compared to controls; in contrast, mRNA of MMP1 increased. CONCLUSION: The reduction of epidermal COL6A6 due to the genetic mutation can cause skin barrier damage and it can contributes to the early onset of AD. COL6A6 is induced by IL-4 and IL-13, and it may play a role in fibrotic remodeling and inflammatory processes, which are major features of AD.