Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Identification and validation of PCDHGA12 and PRRX1 methylation for detecting lung cancer in bronchial washing sample.

Bronchoscopy is a frequently used initial diagnostic procedure for patients with suspected lung cancer (LC). Cytological examinations of bronchial washing (BW) samples obtained during bronchoscopy often yield inconclusive results regarding LC diagnosis. The present study aimed to identify molecular biomarkers as a non-invasive method for LC diagnosis. Aberrant DNA methylation is used as a useful biomarker for LC. Therefore, microarray-based methylation profiling analyses on 13 patient-matched tumor tissues at stages I-III vs. non-tumor tissues were performed, and a group of highly differentially methylated genes was identified. A subsequent analysis using bisulfite-pyrosequencing with additional tissues and cell lines revealed six methylated genes [ADAM metallopeptidase with thrombospondin type 1 motif 20, forkhead box C2 (mesenchyme forkhead 1), NK2 transcription factor related, locus 5 (Drosophila), oligodendrocyte transcription factor 3, protocadherin γ subfamily A 12 (PCDHGA12) and paired related homeobox 1 (PRRX1)] associated with LC. Next, a highly sensitive and accurate detection method, linear target enrichment-quantitative methylation-specific PCR in a single closed tube, was applied for clinical validation using BW samples from patients with LC (n=68) and individuals with benign diseases (n=33). PCDHGA12 and PRRX1 methylation were identified as the best-performing biomarkers to detect LC. The two-marker combination showed a sensitivity of 82.4% and a specificity of 87.9%, with an area under the curve of 0.891. Notably, the sensitivity for small cell LC was 100%. The two-marker combination had a positive predictive value of 93.3% and a negative predictive value of 70.7%. The sensitivity was higher than that of cytology, which only had a sensitivity of 50%. The methylation status of the two-marker combination showed no association with sex, age or stage, but was associated with tumor location and histology. In conclusion, the present study showed that the regulatory regions of PCDHGA12 and PRRX1 are highly methylated in LC and can be used to detect LC in BW specimens as a diagnostic adjunct to cytology in clinical practice.

Integrative analysis of RNA-sequencing and microarray for the identification of adverse effects of UVB exposure on human skin.

Background: Ultraviolet B (UVB) from sunlight represents a major environmental factor that causes toxic effects resulting in structural and functional cutaneous abnormalities in most living organisms. Although numerous studies have indicated the biological mechanisms linking UVB exposure and cutaneous manifestations, they have typically originated from a single study performed under limited conditions. Methods: We accessed all publicly accessible expression data of various skin cell types exposed to UVB, including skin biopsies, keratinocytes, and fibroblasts. We performed biological network analysis to identify the molecular mechanisms and identify genetic biomarkers. Results: We interpreted the inflammatory response and carcinogenesis as major UVB-induced signaling alternations and identified three candidate biomarkers (IL1B, CCL2, and LIF). Moreover, we confirmed that these three biomarkers contribute to the survival probability of patients with cutaneous melanoma, the most aggressive and lethal form of skin cancer. Conclusion: Our findings will aid the understanding of UVB-induced cutaneous toxicity and the accompanying molecular mechanisms. In addition, the three candidate biomarkers that change molecular signals due to UVB exposure of skin might be related to the survival rate of patients with cutaneous melanoma.

Liposome-assisted penetration and antiaging effects of collagen in a 3D skin model.

BACKGROUND: Collagen is a major component of the extracellular matrix that supports the epidermal layers of the skin; thus, many strategies have been made to enhance the topical delivery of collagen for antiaging purposes. In addition, our previous study indicated that liposome can help the penetration of active ingredients into the skin. AIMS: To produce stable collagen-encapsulated liposomes to improve the topical delivery of collagen. METHODS: Collagen-encapsulated liposomes were fabricated using high-pressure homogenization method. The colloidal stability and adhesion ability were confirmed using dynamic light scattering, and spectrofluorophotometer, respectively. Keratinocyte differentiations of 3D skin before and after treatment with collagen-encapsulated liposomes were confirmed by real-time PCR. RESULTS: In comparison with native collagen, collagen-encapsulated liposomes enhanced collagen retention in artificial membranes by twofold, even after repeated washings with water. In addition, real-time PCR results indicated that 3D skin treated with collagen-encapsulated liposomes exhibited higher levels of collagen, keratin, and involucrin, even after ethanol treatment. CONCLUSION: Liposomes could serve as efficient delivery vehicles for collagen, thereby enhancing its antiaging effects.

Combined Non-Thermal Microbial Inactivation Techniques to Enhance the Effectiveness of Starter Cultures for Kimchi Fermentation.

For quality standardization, the application of functional lactic acid bacteria (LAB) as starter cultures for food fermentation is a well-known method in the fermented food industry. This study assessed the effect of adding a non-thermally microbial inactivated starter culture to kimchi, a traditional Korean food, in standardizing its quality. In this study, pretreatment based on sterilization processes, namely, slightly acidic electrolyzed water (SAEW) disinfection and ultraviolet C light-emitting diode (UVC-LED) of raw and subsidiary kimchi materials were used to reduce the initial microorganisms in them, thereby increasing the efficiency and value of the kimchi LAB starter during fermentation. Pretreatment sterilization effectively suppressed microorganisms that threatened the sanitary value and quality of kimchi. In addition, pretreatment based on sterilization effectively reduced the number of initial microbial colonies in kimchi, creating an environment in which kimchi LAB starters could settle or dominate, compared to non-sterilized kimchi. These differences in the initial microbial composition following the sterilization process and the addition of kimchi LAB starters led to differences in the metabolites that positively affect the taste and flavor of kimchi. The combined processing technology used in our study, that is, pre-sterilization and LAB addition, may be a powerful approach for kimchi quality standardization.

Comparison of inactivation kinetics of Yersinia enterocolitica in vegan and non-vegan kimchi during fermentation.

Yersinia enterocolitica is occasionally detected in kimchi, a traditional food prepared from fermented vegetables. Changes in growth properties of Y. enterocolitica during kimchi fermentation are largely unknown. We investigated the viability of Y. enterocolitica during the fermentation of vegan and non-vegan kimchi at different temperatures. Changes in Y. enterocolitica population, pH, and titratable acidity were measured for 24 days. In a suspension test with kimchi juice, populations of three Y. enterocolitica strains were above 3.30 log10 CFU/mL at pH > 5 for 7 days. Yersinia enterocolitica counts in vegan kimchi were considerably reduced at 0 °C and 6 °C. During fermentation at 6 °C, Y. enterocolitica populations in non-vegan kimchi and vegan kimchi were not detected starting from days 14 and 10, respectively. In kimchi samples stored at 0 °C and 6 °C, Y. enterocolitica survival correlated with pH changes during fermentation; in samples stored for up to 24 days, Y. enterocolitica was not detected. According to the k max values from the "log-linear with shoulder and tail" model, Y. enterocolitica was more sensitive to vegan kimchi fermentation than to non-vegan kimchi fermentation. Our findings provide an important basis for ensuring the safe production of kimchi without Y. enterocolitica contamination. Further research is necessary to elucidate the mechanism of Y. enterocolitica inactivation and the major bacterial and physicochemical factors involved in kimchi fermentation.

Analysis of Risk Factors for Delayed Graft Function After Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF) is a serious complication associated with worsening outcomes in kidney transplantation. To facilitate DGF risk reduction, this study aimed to identify the incidence and modifiable risk factors of this condition in kidney transplant patients. METHODS: This retrospective chart review included 220 patients who underwent kidney transplants between 2012 and 2021 at our kidney transplant center. Delayed graft function was defined as the requirement of hemodialysis within a week of transplantation. Clinical data from patients with DGF and those without this condition were compared to identify risk factors of DGF. RESULTS: Of 205 eligible patients, 20 (9.76%) developed DGF. In the univariate analysis, high hemoglobin level, deceased-donor type, and longer warm and cold ischemic times were significantly associated with DGF (P < .05). In the variable selection in logistic regression analysis, high hemoglobin level, with a cutoff value of 11.35 g/dL, and deceased-donor transplants were associated with higher DGF incidence (P < .05 for both factors). CONCLUSIONS: Our findings newly demonstrated that DGF occurred more frequently in patients with hemoglobin level >11.35 g/dL. As such, improvement in kidney transplantation outcomes could be achieved by reducing this modifiable risk factor.

Graft-Versus-Host Disease Developed After En Bloc Kidney Transplant From a Pediatric Donor: A Case Report.

Graft-versus-host disease is a rare but a potentially fatal complication that can occur after kidney transplant. Furthermore, graft-versus-host disease after kidney transplant has been reported in only a few studies. We present a rare case of graft-versus-host disease in a patient who underwent kidney transplant. A patient who underwent hemodialysis received an en bloc kidney transplantfrom a pediatric donor, and the graft function was excellent. Mild diarrhea started on postoperative day 25. Six days after the onset of diarrhea, pancytopenia worsened and fever persisted. However, there were no test findings indicating infection or adverse medical effects. Graft-versus-host disease was diagnosed after a short tandem repeat evaluation of lymphocytes from the recipient's peripheral blood, which revealed 4.7% donor cells.The findings in this study provide insight into cases where symptoms such as fever and pancytopenia of unknown cause appear after kidney transplant, and we suggest that it is necessary to differentiate these symptoms from graft-versus-host disease.

Clinical evaluation of the brightening effect of chitosan-based cationic liposomes.

BACKGROUND: Cationic liposomes can enhance the permeability of drugs in 3-D skin. Chitosan is considered a safe material for percutaneous delivery; thus, this study uses chitosan-incorporated cationic liposomes. AIMS: This study investigated the improvement in skin brightness, melanin, and melasma after treatment niacinamide-incorporated chitosan cationic liposomes. METHODS: A skin brightening agent, niacinamide, was formulated into cationic liposomes to facilitate percutaneous absorption and was clinically tested in 21 Korean female subjects. Cationic liposomes were prepared using a high-pressure homogenizer after mixing an oil phase containing lecithin and cholesterol and an aqueous phase containing niacinamide and chitosan. RESULTS: The cationic liposomes exhibited stability over 28 days, with a particle size of 255-275 nm and zeta potential of 10-14 mV. Cationic liposomes containing niacinamide and a control formulation were applied to the left and right side of the face, respectively, twice daily for 28 days. Skin brightness, melanin index, and area of melasma were significantly enhanced where cationic liposomes were used, in comparison with formulations without cationic liposomes, demonstrating a 1.38-2.08-fold improvement. CONCLUSION: Thus, we established that chitosan liposomes augmented the percutaneous absorption of niacinamide and improved the appearance of the skin.

Integrative analysis to explore the biological association between environmental skin diseases and ambient particulate matter.

Although numerous experimental studies have suggested a significant association between ambient particulate matter (PM) and respiratory damage, the etiological relationship between ambient PM and environmental skin diseases is not clearly understood. Here, we aimed to explore the association between PM and skin diseases through biological big data analysis. Differential gene expression profiles associated with PM and environmental skin diseases were retrieved from public genome databases. The co-expression among them was analyzed using a text-mining-based network analysis software. Activation/inhibition patterns from RNA-sequencing data performed with PM2.5-treated normal human epidermal keratinocytes (NHEK) were overlapped to select key regulators of the analyzed pathways. We explored the adverse effects of PM on the skin and attempted to elucidate their relationships using public genome data. We found that changes in upstream regulators and inflammatory signaling networks mediated by MMP-1, MMP-9, PLAU, S100A9, IL-6, and S100A8 were predicted as the key pathways underlying PM-induced skin diseases. Our integrative approach using a literature-based co-expression analysis and experimental validation not only improves the reliability of prediction but also provides assistance to clarify underlying mechanisms of ambient PM-induced dermal toxicity that can be applied to screen the relationship between other chemicals and adverse effects.

Attachment Type, Thickness, and Volume of the Posterior Meniscofemoral Ligament and Meniscal Pathology.

Several studies have investigated the relationship between the thickness of the posterior meniscofemoral ligament (pMFL) and the presence of a discoid meniscus. We investigated the correlation between meniscal pathology and anatomic features of pMFL such as attachment type, thickness, and volume. We retrospectively evaluated 191 patients who underwent knee MRI. MR images were reviewed to assess the attachment type of the pMFL on the medial femoral condyle (high vs. low), the thickness of the pMFL, and the presence of a meniscal tear or a discoid meniscus. The pMFL volume was quantified by using three-dimensional (3D) segmentation software. The relationship between the frequency of medial or lateral meniscal tear and anatomic features of pMFL were analyzed using Chi-square, Fisher's exact, or Mann-Whitney U test. High type pMFLs had significantly greater thickness and volume than low type pMFLs (p < 0.001). Patients with degenerative lateral meniscal tear had significantly higher thickness and volume of the pMFL than patients with intact lateral meniscus (p < 0.05). The pMFL thickness and volume were not significantly related to traumatic lateral meniscal tear, medial meniscal tear, and discoid meniscus. High type pMFLs tended to be thicker and larger than low type pMFLs and higher thickness and volume of the pMFL was significantly related to the degenerative lateral meniscal tear. However, the attachment type of the pMFL itself was not significantly related to the lateral meniscal tear as well as the medial meniscal tear.

Chronic infrared-A irradiation-induced photoaging of human dermal fibroblasts from different donors at physiological temperature.

BACKGROUND: In this study, we examined cellular responses to acute and chronic IRA irradiation at mild and natural levels of exposure in two types of human fibroblasts, each isolated from a different donor, at physiological temperature (34°C). METHOD: Two types of human dermal fibroblasts (derived from a 20- and 50-year-old women, respectively) were exposed to different repeat numbers of IRA exposure (3, 6, 10, and 14 times; 42 mW/cm2 ) at a frequency of 3-4 times per week (4 h per irradiation). Cellular responses to acute and chronic IRA irradiation were examined by reactive oxygen species (ROS) level, apoptotic signals, cellular morphology, and collagen level. RESULTS: We demonstrated that chronic IRA irradiation-induced severe cellular damage, including prolonged cell proliferation, increased intracellular ROS levels, activated cellular apoptosis, and elongated cell morphology, whereas acute IRA irradiation had negligible effects at 34°C. In addition, it was evident that the degree of cellular damage due to IRA irradiation differed according to the type of fibroblasts. CONCLUSIONS: Considering the severe cellular damage induced by chronic IRA irradiation without heat, continuous exposure of skin to IRA irradiation during daily life may be harmful enough to induce photoaging.

A Novel Heterozygous ACAN Variant in a Short Patient Born Small for Gestational Age with Recurrent Patellar Dislocation: A Case Report

ACAN variants can manifest as various clinical features, including short stature, advanced bone age (BA), and skeletal defects. Here, we report rare clinical manifestations of ACAN defects in a 9 year, 5 month-old girl born small for gestational age (SGA), who presented with short stature, and was initially diagnosed with idiopathic growth hormone deficiency. She displayed several dysmorphic features, including genu valgum, cubitus valgus, and recurrent patellar dislocations. She presented with progressive advancement of BA compared with chronological age. Whole exome sequencing confirmed the presence of a novel heterozygous nonsense variant, c.1968C>G, p.(Tyr656*), in ACAN. ACAN variants should be considered in short stature patients born SGA with joint problems, particularly those with recurrent patellar dislocation and genu valgum.

In vivo determination of the Infrared-A protection factor on human skin.

BACKGROUND: Chronic exposure to infrared A (IR-A) irradiation causes photoaging. However, daily or acute exposure to IR-A rarely induces erythema or pigmentation. Thus, evaluation of the physiological changes taking place on the skin surface is insufficient for clinical investigations. MATERIALS AND METHODS: We fabricated a novel device to obtain the IR-A protection factor (IPF) on human skin. This device consists of an artificial light source that mimics the actual IR-A intensity of sunlight, and a spectrophotometer to measure the spectral reflectance on the skin surface. The IPF can be determined by measuring the difference in spectral reflectance on the skin before and after the use of products and can be verified by the statistical criterion. A validation study was performed using different light intensities and two experimenters. Finally, we monitored the IPF on 12 commercial cosmetics. RESULTS: After considering the IPF and L*-values, we selected the optimal sample and performed a validation study. Neither the intensity of IR-A irradiation or the experimenters significantly affected the IPF. 12 commercial products exhibited their own IPF values and were verified by statistical criteria, with one exception. CONCLUSION: The present IPF evaluation method was concluded to be robust and reliable. This method is simple and safe for the subjects, and could be helpful for the development of IR-A protection products and the confirmation of product performances.

Comparison Study of the Effects of Cationic Liposomes on Delivery across 3D Skin Tissue and Whitening Effects in Pigmented 3D Skin.

Charged phospholipids are employed to formulate liposomes with different surface charges to enhance the permeation of active ingredients through epidermal layers. Although 3D skin tissue is widely employed as an alternative to permeation studies using animal skin, only a small number of studies have compared the difference between these skin models. Liposomal delivery strategies are investigated herein, through 3D skin tissue based on their surface charges. Cationic, anionic, and neutral liposomes are formulated and their size, zeta-potential, and morphology are characterized using dynamic light scattering and cryogenic-transmission electron microscopy (cryo-TEM). A Franz diffusion cell is employed to determine the delivery efficiency of various liposomes, where all liposomes do not exhibit any recognizable difference of permeation through the synthetic membrane. When the fluorescence liposomes are applied to 3D skin, considerable fluorescence intensity is observed at the stratum cornea and epithelium layers. Compared to other liposomes, cationic liposomes exhibit the highest fluorescence intensity, suggesting the enhanced permeation of liposomes through the 3D skin layers. Finally, the ability of niacinamide (NA)-incorporated liposomes to suppress melanin transfer in pigmented 3D skin is examined, where cationic liposomes exhibit the highest degree of whitening effects.

Proteomic evaluation of kimchi, a traditional Korean fermented vegetable, and comparison of kimchi manufactured in China and Korea.

Kimchi is a traditional Korean fermented vegetable, which is also widely consumed in Japan and China. However, little is known about the kimchi proteome. In this study, Korean and Chinese kimchi proteomes were evaluated by shotgun proteomics. A total of 250 proteins were annotated, and 29 of these were expressed at > 1% of the average relative abundance. Discrimination of the geographical origins of Korean and Chinese kimchi samples was possible using multivariate analysis of the proteomic data, and 23 proteins were expressed differently between the two types (p < 0.001), and represent possible markers to discriminate between Chinese and Korean kimchi. This study provides important insights into the kimchi proteome and illustrates the proteomic differences caused by geographical origin.

Ultraviolet light screen using cholesteric liquid crystal capsules on the basis of selective reflection.

Sunscreen can protect human skin from sunlight by decreasing exposure to ultraviolet (UV) light, specifically UV-B and UV-A. In this study, a new type of UV screen system is proposed using cholesteric liquid crystal (CLC) capable of selectively reflecting UV-A within the human skin temperature range of 32-36 °C. Polycaprolactone (PCL) capsules with CLC mixture which had a helical chiral pitch corresponding to the wavelength of UV light were made by a solvent evaporation method. The average diameter of the capsules was about 34 µm. Consequently, it was confirmed that the CLC mixture (COC : CN = 80 : 20) could reflect UV-A light over 350-380 nm within the human skin temperature range. Also, it was confirmed that the CLC/PCL microcapsules could block UV light over 290-400 nm by about 6%.

Genomic approach to explore altered signaling networks of olfaction in response to diesel exhaust particles in mice.

Airborne pollutants have detrimental effect on the human body and the environment. Diesel exhaust particles (DEPs) are known to be major component of particulate matter (PM) and cause respiratory diseases and neurotoxicity. However, the effects of air pollutants on the sensory nervous system, especially on the olfactory sense, have not been well studied. Herein, we aimed to explore DEP-induced changes in the olfactory perception process. Olfactory sensitivity test was performed after DEP inhalation in mice. Microarray was conducted to determine the differentially expressed genes, which were then utilized to build a network focused on neurotoxicity. Exposure to DEPs significantly reduced sniffing in mice, indicating a disturbance in the olfactory perception process. Through network analysis, we proposed five genes (Cfap69, Cyp26b1, Il1b, Il6, and Synpr) as biomarker candidates for DEP-mediated olfactory dysfunction. Changes in their expression might provoke malfunction of sensory transduction by inhibiting olfactory receptors, neurite outgrowth, and axonal guidance as well as lead to failure of recovery from neuroinflammatory damage through inhibition of nerve regeneration. Thus, we suggest the potential mechanism underlying DEPs-mediated olfactory disorders using genomic approach. Our study will be helpful to future researchers to assess an individual's olfactory vulnerability following exposure to inhalational environmental hazards.

Effective association of ceramide-coassembled lipid nanovehicles with stratum corneum for improved skin barrier function and enhanced skin penetration.

Herein, we report on a ceramide-coassembled lipid nanovehicle (CLNV) system that can enhance the penetration of active ingredients through the skin barrier by taking advantage of molecular associations between ceramide and lipids in the stratum corneum (SC) layer. For this purpose, we fabricated CLNVs consisting of an asymmetric lipid and a cholesterol derivative. They showed excellent long-term dispersion stability without molecular crystallization of ceramide. Upon forming a stable aqueous dispersion, the CLNVs retained their initial vehicle structure even under harsh conditions including high storage temperatures or salinity conditions. From in vitro skin barrier recovery tests, we observed that topical treatment with CLNVs induced the SC to restore its lamellar structure to the same condition as that prior to chemical damage. An in vivo skin penetration study additionally confirmed that skin penetration was enhanced, since the CLNVs were able to effectively interact with the SC layer. From these results, the CLNVs with robust molecular layer endow various applications in wide range applications including transdermal pharmaceutics delivery systems and cosmetics field.

Factors Affecting Posttraumatic Stress Disorder in South Korean Trauma Nurses.

Trauma nurses are exposed to suffering, death and dying, and vicarious trauma, which may result in nurses experiencing posttraumatic stress disorder (PTSD). This study aims to investigate the extent of PTSD and the effect of the frequency of traumatic events, coping strategies, and social support on PTSD in South Korean trauma nurses. A cross-sectional study was conducted. Participants were 145 trauma nurses recruited from 6 regional trauma centers in Korea. The data were collected through convenience sampling using self-administered questionnaires, including the Korean version of Impact of Event Scale-Revised (IES-R-K), the frequency of traumatic events, coping strategies, and social support. The data were analyzed with descriptive statistics, t test, analysis of variance, Pearson's correlation coefficients, and multiple linear regression. The prevalence of IES-R-K score of 25 or more (indicating a high risk of PTSD) was detected in 57.2% of the trauma nurses. The frequency of traumatic events, work at traumatic emergency units, dysfunctional coping, emotion-focused coping, and social support were found to be significantly associated with PTSD. Therefore, it is necessary to develop PTSD management programs in order to provide effective coping strategies and social support for relieving PTSD symptoms. At the same time, efforts to improve the working environment are needed.