Postprandial glycemic response to a high-protein diabetes-specific nutritional shake compared to isocaloric instant oatmeal in people with type 2 diabetes: a randomized, controlled, crossover trial.

Introduction: Minimizing postprandial glucose response is an important goal for overall diabetes management. Diabetes-specific nutritional shakes (DSNS) have been clinically shown to minimize postprandial glucose response in people with type 2 diabetes (T2DM) compared to high-glycemic foods. However, it is unknown how a high-protein, low-fat DSNS impacts the GLP-1 response. Methods: We tested the postprandial glucose, insulin, and GLP-1 response to a high-protein, low-fat diabetes-specific nutritional shake (DSNS-HP) compared to isocaloric instant oatmeal (IOM) in a randomized, controlled, crossover study in adults with T2DM (n = 24). Participants were randomly selected to receive IOM or DSNS-HP on two test days. Glucose, insulin, and total GLP-1 concentration were measured at baseline and 15, 30, 45, 60, 90, 120, 180, and 240 min postprandially. Results: Compared to IOM, the glucose-positive area under the curve (pAUC) was significantly lower (P = .021). DSNS-HP significantly increased GLP-1 pAUC response by 213% (P <.001) with a corresponding increase in insulin pAUC (P = .033) compared to IOM. Discussion: A high-protein, low-fat DSNS leads to favorable changes in GLP-1 response and is a suitable option to minimize blood glucose response in people with type 2 diabetes.

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging.

Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals, but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. Thus, we compared whole genome sequencing data from an original dog with that of cloned dogs, identifying candidate somatic mutations that were disproportionately located within genes previously implicated in aging. The substitutional signature of cloning-specific somatic mutations mirrored the uniform distribution characteristic of the signature associated with human aging. Further analysis of genes revealed significant enrichment of traits associated with body size as well as the molecular mechanisms underlying neuronal function and tumorigenesis. Overall, the somatic mutations found in cloned dogs may indicate a conserved mechanism driving aging across species and a broad spectrum of pathway alterations.

The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.

RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.

Real-world safety and effectiveness of secukinumab in adult patients with moderate to severe plaque psoriasis: results from postmarketing surveillance in Korea.

Background: Secukinumab, a fully human monoclonal antibody, was approved in Korea for the treatment of moderate to severe psoriasis in September 2015. Objectives: To assess the safety and effectiveness of secukinumab in patients with moderate to severe psoriasis in Korea. Design: Multicenter, real-world, noninterventional study conducted over 6 years. Methods: Adults with moderate to severe psoriasis were enrolled. Safety was assessed by evaluating adverse events (AEs), treatment-related AEs, and serious AEs (SAEs). Effectiveness was assessed using the change in absolute Psoriasis Area and Severity Index (PASI) score, percentage of patients achieving PASI 75/90/100 and PASI ⩽2; at weeks 12 and 24. Results: Overall, 829 and 542 patients were included in the safety and effectiveness sets, respectively. AEs, treatment-related AEs, and SAEs occurred in 29.0%, 9.5%, and 4.1% of patients, with incidence rates of 39.43, 12.98, and 5.59 per 100 patient years, respectively. The absolute PASI score decreased from 16.1 ± 7.1 (baseline) to 1.6 ± 2.4 (week 24), with a similar reduction in biologic-naïve (16.4 ± 7.3 to 1.5 ± 2.2) and biologic-experienced (14.8 ± 5.9 to 2.4 ± 3.2) groups. At week 24, PASI 75/90/100 was achieved by 95.1%, 62.4%, and 24.9% of patients. At week 24, PASI 75/90 were higher in biologic-naïve (96.6%/65.8%) than biologic-experienced patients (88.3%/48.6%), whereas PASI 100 was similar in both cohorts (24.1% and 28.6%). A similar trend in PASI ⩽ 2 was observed in both cohorts. Conclusion: Secukinumab showed sustained effectiveness and favorable safety profile in adult patients with moderate to severe psoriasis in Korea.

Epidemiological analysis of the patients with psoriasis in Asian countries and region using the same clinical case cards between 2020 and 2022.

Although many epidemiological surveys for patients with psoriasis have been reported based on individual countries or facilities, there has been no study encompassing the major countries or the region in Asia. The Asian Society for Psoriasis (ASP) has been conducting an epidemiological study across various Asian countries and regions to elucidate the and compare the epidemiology of psoriasis. A total of 1948 cases were analyzed, with 938 cases from Japan, 530 cases from China, 325 cases from Korea, 141 cases from Chinese Taipei, and 14 cases from Thailand, all of which were enrolled between 2020 and 2022. In the Asian region total, the male-female ratio was 1.87:1 and the peak age at disease onset was 20-29 years. The proportion of psoriasis vulgaris (PsV), psoriatic arthritis (PsA), and pustular psoriasis (PP) was 80.1%, 17.7%, and 2.2%, respectively, and PsA was more commonly associated with nail symptoms than psoriasis vulgaris (PsV). Of the patients, 13% had a familial history of psoriasis and the most frequently affected family member was the father. Regarding treatment, 78.3% of the patients received topical medications, 9.0% underwent phototherapy, 34.0% received oral medications, and 36.1% were treated with biological agents. This study provided valuable information on the epidemiology and treatment of psoriasis using the registry data collected with the common reporting form in the same period in major Asian countries and regions. Male predominance is a distinctive feature of psoriasis in Asia. This epidemiological data registry in the ASP will continue afterwards.

Effectiveness of breath acetone monitoring in reducing body fat and improving body composition: a randomized controlled study.

When attempts to lose body fat mass frequently fail, breath acetone (BA) monitoring may assist fat mass loss during a low-carbohydrate diet as it can provide real-time body fat oxidation levels. This randomized controlled study aimed to evaluate the effectiveness of monitoring BA levels and providing feedback on fat oxidation during a three-week low-carbohydrate diet intervention. Forty-seven participants (mean age = 27.8 ± 4.4 years, 53.3% females, body mass index = 24.1 ± 3.4 kg m-2) were randomly assigned to three groups (1:1:1 ratio): daily BA assessment with a low-carbohydrate diet, body weight assessment (body scale (BS)) with a low-carbohydrate diet, and low-carbohydrate diet only. Primary outcome was the change in fat mass and secondary outcomes were the changes in body weight and body composition. Forty-five participants completed the study (compliance rate: 95.7%). Fat mass was significantly reduced in all three groups (allP< 0.05); however, the greatest reduction in fat mass was observed in the BA group compared to the BS (differences in changes in fat mass, -1.1 kg; 95% confidence interval: -2.3, -0.2;P= 0.040) and control (differences in changes in fat mass, -1.3 kg; 95% confidence interval: -2.1, -0.4;P= 0.013) groups. The BA group showed significantly greater reductions in body weight and visceral fat mass than the BS and control groups (allP< 0.05). In addition, the percent body fat and skeletal muscle mass were significantly reduced in both BA and BS groups (allP< 0.05). However, no significant differences were found in changes in body fat percentage and skeletal muscle mass between the study groups. Monitoring BA levels, which could have motivated participants to adhere more closely to the low-carbohydrate diet, to assess body fat oxidation rates may be an effective intervention for reducing body fat mass (compared to body weight assessment or control conditions). This approach could be beneficial for individuals seeking to manage body fat and prevent obesity.

Preparation and characterization of water-reducible polyester resin based on waste PET for insulation varnish.

Water-reducible polyester resin (WRPE) for insulation varnish was prepared from waste polyethylene terephthalate (PET), glycerol (GL), and phthalic anhydride (PA) via depolymerization and condensation. PET was depolymerized via glycolysis at different molar ratios of PET/GL (PET repeating unit/GL molar ratios: 1.6, 1.3, and 1.0) with zinc acetate as a catalyst at 220-230 °C. The resulting glycolytic products (GPs) were reacted with PA at contents of 5, 7.5, 10, 12.5, and 15 wt%, based on the total weight. The prepared WRPEs were dissolved in phenol, neutralized with aqueous ammonia to pH = 7-7.5, and diluted in water. The WRPEs were cured with hexamethoxymethyl melamine resin (HMMM, WRPE : HMMM = 70 : 30, based on the dry mass) at 140 °C for 2 h. The formation of GPs, WRPE, and WRPE-HMMM was investigated using Fourier transformer infrared spectroscopy and proton nuclear magnetic resonance spectroscopy; the thermal properties were characterized using thermogravimetric analysis and differential scanning calorimetry. The electrical insulation strength and volume resistivity of the cured films with PA content were investigated. This strength and volume resistivity first increased with increasing PA content and then decreased above 10 wt%. The results show that WRPE with a PA content of 10 wt% exhibits optimal insulation properties.

The effect of a short-term ketogenic diet on exercise efficiency during graded exercise in healthy adults.

OBJECTIVE: We examined the effects of short-term KD on exercise efficiency and hormonal response during and after the graded exercise testing. METHODS: Fourteen untrained healthy adults (8 males, 6 females, age 26.4 ± 3.1 [SD] years; BMI 24.8 ± 4.6 kg/m2; peak VO2max 54.0 ± 5.8 ml/kg FFM/min) completed 3-days of a mixed diet (MD) followed by another 3-days of KD after 3-days of washout period. Upon completion of each diet arm, participants underwent graded exercise testing with low- (LIE; 40% of VO2max), moderate- (MIE; 55%), and high-intensity exercise (HIE; 70%). Exercise efficiency was calculated as work done (kcal/min)/energy expenditure (kcal/min). RESULTS: Fat oxidation during the recovery period was higher in KD vs. MD. Despite identical workload during HIE, participants after having KD vs. MD showed higher energy expenditure and lower exercise efficiency (10.1 ± 0.7 vs. 12.5 ± 0.3%, p < .01). After KD, free fatty acid (FFA) concentrations were higher during MIE and recovery vs. resting, and beta-hydroxybutylate (BOHB) was lower at HIE vs. resting. Cortisol concentrations after KD was higher during recovery vs. resting, with no significant changes during graded exercise testing after MD. CONCLUSIONS: Our data suggest that short-term KD is favorable to fat metabolism leading increased circulating FFA and BOHB during LIE to MIE. However, it is notable that KD may cause 1) exercise inefficiency manifested by increased energy expenditure and 2) elevated exercise stress during HIE and recovery. Trial registration: KCT0005172, International Clinical Trials Registry Platform.

Assessment of Effects of Low-Level Light Therapy on Scalp Condition and Hair Growth.

Background: The appearance of the scalp and hair is very important aesthetically regardless of age or sex. Although there are many drugs and treatment methods for scalp problems and hair loss, the treatment response is still insufficient. Aims and Objectives: To evaluate the efficacy of low-level light therapy in a helmet-like device. Materials and Methods: This study was designed as a 24-week trial with 50 participants. All participants used a helmet-shaped device emitting 630-690, 820-880, and 910-970 nm light wavelengths, for 20 minutes, daily for 24 weeks. A phototrichogram for hair density and thickness, Global Aesthetic Improvement Scale score, erythema index, and sebum secretions of the scalp were evaluated at baseline and at 12 and 24 weeks. Results: After 24 weeks of treatment, hair density and hair thickness were found to have significantly increased (P <.01 and P =0.013, respectively) and sebum secretion of vertex area had decreased significantly (P <.01). Of 49 participants, 73.47% of the participants showed improvement in the overall appearance of the scalp (n = 36). Conclusion: A helmet-like low-level light therapy device can improve the appearance of the hair, with thickening and increase in the density of the hair, and can improve scalp condition by decreasing sebum secretion.

Insensitive Effects of Inflammatory Cytokines on the Reference Genes of Synovial Fluid Resident-Mesenchymal Stem Cells Derived from Rheumatoid Arthritis Patients.

Mesenchymal stem cells derived from rheumatoid arthritis patients (RA-MSCs) provide an understanding of a variety of cellular and immunological responses within the inflammatory milieu. Sustained exposure of MSCs to inflammatory cytokines is likely to exert an influence on genetic variations, including reference genes (RGs). The sensitive effect of cytokines on the reference genes of RA-SF-MSCs may be a variation factor affecting patient-derived MSCs as well as the accuracy and reliability of data. Here, we comparatively evaluated the stability levels of nine RG candidates, namely GAPDH, ACTB, B2M, EEF1A1, TBP, RPLP0, PPIA, YWHAZ, and HPRT1, to find the most stable ones. Alteration of the RG expression was evaluated in MSCs derived from the SF of healthy donors (H-SF-MSCs) and in RA-SF-MSCs using the geNorm and NormFinder software programs. The results showed that TBP, PPIA, and YWHAZ were the most stable RGs for the normalization of H-SF-MSCs and RA-SF-MSCs using RT-qPCR, whereas ACTB, the most commonly used RG, was less stable and performed poorly. Additionally, the sensitivity of RG expression upon exposure to proinflammatory cytokines (TNF-α and IL-1ß) was evaluated. RG stability was sensitive in the H-SF-MSCs exposed to TNF-α and IL-1ß but insensitive in the RA-SF-MSCs. Furthermore, the normalization of IDO expression using ACTB falsely diminished the magnitude of biological significance, which was further confirmed with a functional analysis and an IDO activity assay. In conclusion, the results suggest that TBP, PPIA, and YWHAZ can be used in SF-MSCs, regardless of their exposure to inflammatory cytokines.

Serious infections and tuberculosis in psoriasis patients receiving systemic therapy in Korea: a nationwide population-based cohort study.

BACKGROUND: Psoriasis itself, as well as its immunomodulatory drugs, may alter the immune system, increasing the risk of infections. Recent research has indicated that patients with psoriasis are at an increased risk of developing severe infections including tuberculosis. OBJECTIVES: To evaluate and compare the incidence of serious infectious diseases in Korea between patients with psoriasis and participants without psoriasis regarding each treatment modality. MATERIALS & METHODS: This nationwide cohort study utilized claims data based on the National Health Insurance Service between January 2005 and December 2018. RESULTS: In total, 293,073 patients with psoriasis enrolled for the analysis of serious infection and 272,400 patients enrolled for the analysis of tuberculosis. Participants without psoriasis matched by age and sex (1:1 ratio) were also enrolled. For serious infection overall, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.21 (1.20-1.23), 1.23 (1.17-1.28), and 1.33 (1.09-1.63) for the non-systemic, non-biologic systemic, and biologic groups, respectively. For tuberculosis overall, the aHRs were 1.15 (1.10-1.20), 1.32 (1.10-1.57), and 6.72 (4.28-10.56) for the non-systemic, non-biologic systemic, and biologic groups, respectively. CONCLUSION: This study reveals that the risk of serious infection and tuberculosis in patients with psoriasis was significantly higher than in participants without psoriasis. Moreover, patients with psoriasis who received systemic therapy other than phototherapy had a higher risk of these infections compared to those without psoriasis. Also, biologics appeared to increase the risk of tuberculosis in patients with psoriasis. Dermatologists should consider these potential risks when selecting treatment modalities for psoriasis.

Basic Therapeutic Approach for Patients with Plaque Psoriasis: Korean Expert Consensus Using the Modified Delphi Method.

BACKGROUND: Currently, there is no consensus on the treatment of psoriasis in Korean patients. OBJECTIVE: This study aimed to establish a consensus on the basic therapeutic principles for Korean patients with plaque psoriasis. METHODS: Using the modified Delphi method, a steering committee proposed 53 statements for the first Delphi round, which covered five subjects: (1) the goal of treatment and evaluation of disease severity, (2) topical therapy, (3) phototherapy, (4) conventional systemic therapy, and (5) biologic therapy. The panel of dermatologists scored the level of agreement for each statement on a ten-point scale with scores ranging from 1 (strongly disagree) to 10 (strongly agree). After discussing the results of the first round, the committee reformulated 41 statements. Finally, consensus was defined as more than 70% of the second round scores being ≥7. RESULTS: The panel participants strongly agreed that the ideal treatment goals for Korean patients with plaque psoriasis should include complete skin clearance and high dermatological quality of life. A strong consensus was also reached on the use of topical agents for psoriasis of any severity, the consideration of phototherapy before biologics therapy, the conventional systemic agents for moderate-to-severe psoriasis, and the recommendation of biologic for retractable psoriasis to conventional systemic therapy and phototherapy. CONCLUSION: This modified Delphi panel established an expert consensus on the therapeutic approach for Korean patients with plaque psoriasis. This consensus may improve the treatment outcomes for psoriasis in Korea.

Development of Agrobacterium-mediated in planta transformation protocol through coleoptile in rice.

Genetic modification of rice is mainly carried out by Agrobacterium-mediated transformation of callus accompanied by tissue culture. It is time consuming, laborious and unapplicable for cultivars unable to induce callus. In this study, we have reported a novel gene transfer protocol that involves pulling out primary leaf from coleoptile and injection of Agrobacterium culture into the empty channel. Out of 25 plants survived after injection of Agrobacterium tumefaciens EHA105 culture harboring pCAMBIA1301-RD29A-AtDREB1A, 8 T0 plants revealed the expected size of around 811 bp corresponding to AtDREB1A gene and Southern blotting analysis on 18 T1 plants suggested introgression of AtDREB1A. 3 T2 lines (7-9, 12-3, 18-6) exhibited accumulation of free proline and soluble sugars, yet increase of chlorophyll content, but decrease of electrolyte leakage and methane dicarboxylic aldehyde under cold stress condition at the vegetative growth stage. Yield components investigation on T2 lines showed earlier heading date and no yield loss compared to wild type plants grown under normal condition. GUS expression analysis and integrated transgene detection in T0 and T1 plants followed by evaluation of cold stress tolerance in T2 lines suggest the advantage of this in planta transformation protocol to obtain transgenic rice.

Increased risk of suicidality in patients with psoriasis: A Nationwide cohort study in Korea.

BACKGROUND: Psoriasis has a devastating psychological impact on patients' quality of life. However, the relationship between suicidality and psoriasis remains unclear. OBJECTIVE: This study analysed and compared the risk of suicidality (suicidal ideation, suicide attempt and completed suicide) between patients with psoriasis and the general population. METHODS: This nationwide, population-based, retrospective, cohort study analysed the Korean National Health Insurance Service claim data from 2005 to 2018. RESULTS: The study included 348,439 patients with psoriasis aged over 18 years and with age- and sex-matched controls. The risk of suicidality was higher in the psoriasis group than in the control group [adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI), 1.18-1.24]. The aHR of suicidality was higher in the psoriatic arthritis group (aHR, 1.46; 95% CI, 1.39-1.54) than in the psoriasis-alone group (aHR, 1.17; 95% CI, 1.13-1.20). However, the severity of psoriasis and suicidality showed no correlation (mild psoriasis group: aHR, 1.22; 95% CI, 1.18-1.25; moderate-to-severe psoriasis group: aHR, 1.16; 95% CI, 1.10-1.23). CONCLUSION: Patients with psoriasis have an increased risk of suicidality. In particular, the presence of arthritis in patients had a more significant effect on the risk of suicidality.

Analysis of the Microbiome of the Ear Canal in Normal Individuals and Patients with Chronic Otitis Externa.

BACKGROUND: Recently, microbiome research has been actively conducted for various skin areas. However, no study has yet compared the microbiome of bacteria and fungi in the ear canal of healthy individuals and patients with chronic otitis externa in Korea. OBJECTIVE: This study aimed to investigate the difference in the distribution of fungal and bacterial microbial communities in ear canal samples of healthy individuals and patients with chronic otitis externa. METHODS: In 24 patients with bilateral chronic otitis externa and 24 healthy controls, cotton swabs were used to obtain samples from the bilateral ear canal. To characterize the fungal and bacterial communities, we sequenced and analyzed the 16S rRNA V4-V5 and ITS1 regions using Quantitative Insights into Microbial Ecology 2, respectively. RESULTS: The alpha diversity analysis for bacteria and fungi confirmed that both richness and evenness decreased in the patient group. The beta diversity analysis for bacteria confirmed that these parameters differed between the control and patient groups. The beta diversity analysis for fungi showed no difference between the groups. CONCLUSION: We observed different skin microbiomes in the patients with chronic otitis externa compared with those in the healthy individuals.

KLK6/PAR1 Axis Promotes Tumor Growth and Metastasis by Regulating Cross-Talk between Tumor Cells and Macrophages.

Kallikrein-related peptidase (KLK)6 is associated with inflammatory diseases and neoplastic progression. KLK6 is aberrantly expressed in several solid tumors and regulates cancer development, metastatic progression, and drug resistance. However, the function of KLK6 in the tumor microenvironment remains unclear. This study aimed to determine the role of KLK6 in the tumor microenvironment. Here, we uncovered the mechanism underlying KLK6-mediated cross-talk between cancer cells and macrophages. Compared with wild-type mice, KLK6-/- mice showed less tumor growth and metastasis in the B16F10 melanoma and Lewis lung carcinoma (LLC) xenograft model. Mechanistically, KLK6 promoted the secretion of tumor necrosis factor-alpha (TNF-α) from macrophages via the activation of protease-activated receptor-1 (PAR1) in an autocrine manner. TNF-α secreted from macrophages induced the release of the C-X-C motif chemokine ligand 1 (CXCL1) from melanoma and lung carcinoma cells in a paracrine manner. The introduction of recombinant KLK6 protein in KLK6-/- mice rescued the production of TNF-α and CXCL1, tumor growth, and metastasis. Inhibition of PAR1 activity suppressed these malignant phenotypes rescued by rKLK6 in vitro and in vivo. Our findings suggest that KLK6 functions as an important molecular link between macrophages and cancer cells during malignant progression, thereby providing opportunities for therapeutic intervention.

Blastocyst complementation and interspecies chimeras in gene edited pigs.

The only curative therapy for many endstage diseases is allograft organ transplantation. Due to the limited supply of donor organs, relatively few patients are recipients of a transplanted organ. Therefore, new strategies are warranted to address this unmet need. Using gene editing technologies, somatic cell nuclear transfer and human induced pluripotent stem cell technologies, interspecies chimeric organs have been pursued with promising results. In this review, we highlight the overall technical strategy, the successful early results and the hurdles that need to be addressed in order for these approaches to produce a successful organ that could be transplanted in patients with endstage diseases.

HPRT1 Most Suitable Reference Gene for Accurate Normalization of mRNA Expression in Canine Dermal Tissues with Radiation Therapy.

Reference genes are crucial in molecular biological studies as an internal control for gene re-search as they exhibit consistent expression patterns across many tissue types. In canines, radiation therapy is the most important therapeutic tool to cure various diseases like cancer. However, when using radiation for therapeutic strategy, radiation exposure to healthy tissues leads to some possible side effects such as acute radiation-induced skin injury and alters gene expression. Therefore, the analysis of a change in reference gene expression during the skin recovery process after radiation therapy is essential in healthy canine tissue. In the present study, we analyzed eight reference genes (ACTB, GAPDH, YWHAZ, GUSB, HPRT1, RPL4, RPS5, and TBP) in canine dermal tissues at 0, 1, 2, 3, 4, 5, 7, and 9 weeks of radiation exposure that affected the skin condition of canines. The stability of reference genes is determined by evaluating radiation therapy's effect on healthy canine dermal tissue. Epidermal marker, Keratin 10 expression varies each week after irradiation, and HPRT1 is found to be the most suitable for normalization of mRNA expression in radiation-exposed canine dermal tissues. Changes in the gene expression level were evaluated by using a reliable tool such as quantitative real-time polymerase chain reaction (qRT-PCR). In order to achieve a valid qRT-PCR result, the most stable reference genes used for normalization after the radiation exposure process are important. Therefore, the current study was designed to evaluate the most stable reference gene for the post-irradiation canine tissues. After radiation exposure, the alternation of reference gene expression was estimated by three algorithms (geNorm, Normfinder, and Bestkeeper). The RG validation programs (GeNorm and NormFinder) suggested that HPRT1, RPL4, and TBP were suitable for normalization in qRT-PCR. Furthermore, three algorithms suggested that HPRT1 was the most stable reference gene for normalization with qRT-PCR results, regardless of before and after radiation exposure. Whereas GAPDH was found to be the most unstable reference gene. In addition, the use of stable or unstable reference genes for the normalization of Keratin 10 expression showed statistical differences. Therefore, we observed that, to obtain accurate and suitable PCR results of the canine tissues with and without radiation exposure, the HPRT1 reference gene is recommended for normalization with its high stability. Additionally, the use of RGs such as HPRT1, RPL4, and TBP for normalization in qRT-PCR experiments is recommended for post-radiation canine tissues to generate more accurate and reliable data. These results will provide fundamental information regarding internal controls for gene expression studies and can be used for the analysis of gene patterns in regenerative medicine.

Risk of malignancy in patients with psoriasis according to treatment modalities in Korea: a nationwide cohort study.

Intrinsic immunologic disparity of psoriasis itself, along with chronic inflammation and immunomodulatory anti-psoriatic treatments could be associated with increased risk of malignancy. We aimed to estimate the risk of malignancy in patients with psoriasis by treatment modality compared with that in individuals without psoriasis in Korea. We conducted a nationwide cohort study using the claims database of the National Health Insurance Service from January 2005 to December 2018. A total of 255,471 patients with psoriasis, and age- and sex-matched non-psoriasis participants (1:1 ratio) were enrolled. The adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] for malignancy without nonmelanoma skin cancer (NMSC) were 1.10 [1.08-1.12] in patients with psoriasis, 1.13 [1.00-1.27], 1.05 [0.97-1.13], and 1.24 [0.84-1.83] in phototherapy, non-biologic systemics, and biologics cohort, respectively. Among the non-biologic systemics cohort, patients treated with cyclosporin showed higher risk of malignancy without NMSC (aHR [95% CI], 1.20 [1.04-1.39]). The risk of malignancy without NMSC in patients with psoriasis was higher than that in individuals without psoriasis. Phototherapy and biologics were not associated with significant increase of risk; however, cyclosporin appeared to increase its risk. Dermatologists should be vigilant about this potential risk while managing patients with psoriasis.