Association between prevalence and severity of chronic kidney disease and employment status: a nationwide study in Korea.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing globally, and understanding the association between CKD and employment status is crucial. This cross-sectional study aimed to investigate the association of CKD with employment and occupation type among patients with CKD. METHODS: We analyzed data from 36,732 Korean adults aged ≥ 30 years, who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2021. CKD was detected based on the estimated glomerular filtration rate, and the employment status of the participants was classified into distinct categories: full-time permanent employment, unemployment, self-employment, and precarious employment. We analyzed the data using multiple logistic regression. RESULTS: We observed a significant association between CKD and a higher likelihood of unemployment compared to that in individuals without CKD (odds ratio, 1.70; 95% confidence interval, 1.47-1.96). This association was more prominent in patients with severe CKD. In the multivariable logistic analysis, patients with CKD had a higher likelihood for precarious employment (odds ratio, 1.29; 95% confidence interval, 0.92-1.88), self-employment (odds ratio, 1.3; 95% confidence interval, 0.90-1.88), and unemployment (odds ratio, 2.10; 95% confidence interval, 1.51-2.92) compared to individuals without CKD. CONCLUSIONS: Our study demonstrated that CKD is associated with a higher likelihood of unemployment and engagement in precarious employment. These findings highlight the challenges faced by patients with CKD in obtaining stable employment and emphasize the need for interventions to improve the employment outcomes of individuals with CKD.

Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

Health-related quality of life instrument with 8 items to measure health-related quality of life among family caregivers of people with dementia: A pilot validation study.

BACKGROUND: The health-related quality of life instrument with 8 items (HINT-8) was developed to measure health-related quality of life (HRQoL) in Korea. However, the HINT-8 has not yet been validated among the family caregivers of people with dementia (PwD). DESIGN: A cross-sectional pilot study. OBJECTIVE: The study aimed to examine the convergent and discriminant validity of the HINT-8 among family caregivers of individuals with dementia. SAMPLE: Forty-seven family caregivers of PwD. MEASUREMENTS: HINT-8 was compared with the 5-level EQ-5D (EQ-5D-5L) to assess its convergent and discriminant validity. Additionally, the association between the two instruments assessing HRQoL was examined using the short-form Bédard-Zarit Burden Interview (SZBI). RESULTS: The HINT-8 was a promising and valid HRQoL instrument for family caregivers of PwD. There was a significantly high correlation between the overall HINT-8 and EQ-5D-5L indices (r = 0.85, p < .001). The HINT-8 had acceptable psychometric properties compared to the commonly used EQ-5D-5L, as indicated by the subdomains associated with family caregivers' burden measured by the SZBI. CONCLUSION: Future studies should compare the HINT-8 with existing dementia carer-specific QoL instruments among a larger study sample to enhance its statistical power and confirm its reliability and structural validity.

Caregiving burden and healthcare utilization in family caregivers of people with dementia: Long term impact of the public family caregiver intervention.

Despite community-based interventions to decrease the caregiving burden on family caregivers of people with dementia (PwD), long-term assessment of community-based public programs is lacking. Therefore, the study aims to identify the long-term effects of community-based dementia caregiver intervention on the caregiving burden and healthcare utilization among family caregivers for PwD. Additionally, we investigated the predictors of caregiving burden and healthcare utilization. Of the participants, 32 (76%) intervention and 15 (38%) control groups responded to the one-year follow-up. We assessed caregiver burden using the short-form Zarit Burden Interview (sZBI) and collected healthcare utilization data using questionnaire at baseline and 12 months. Compared with the control group, the intervention group did not experience a reduction in caregiving burden and healthcare utilization. Predictors of caregivers' perceived burden were spouses as the primary caregiver and having multiple comorbidities. The predictors identified in this study should be considered when implementing public family support programs.

Gender differences in pharmacokinetics of perfluoropentanoic acid using non-linear mixed-effect modeling in rats.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been used in various industrial applications for many years. Long-chain PFASs are ubiquitous in wildlife and are reported to have a long elimination half-life in biological systems. Moreover, significant gender difference exists in the elimination of PFASs, where less is eliminated in male than in female. Recently, PFASs manufacturers and agencies have tried to replace the use of long-chain PFASs with short-chain PFASs, since they are expected to exhibit less bioaccumulation potential. Nevertheless, the potential risk and the pharmacokinetic (PK) characteristics of the short-chain PFASs still remain unknown. This study aims to fill the knowledge gap on short-chain PFASs, perfluoropentanoic acid (PFPeA), in terms of its PK properties using non-linear mixed-effect modeling and to explore gender differences in rats. Animal studies were carried out following oral or intravenous administration of PFPeA in male and female rats at a dose of 0.5-10 mg/kg. Plasma, urine, feces and nine tissues were collected and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. PK findings revealed that the clearance and the inter-compartmental clearance were 1.75 and 3.12 times higher in female rats than in male rats, respectively. According to the result, PFPeA is eliminated more rapidly in female rats than in male rats. Also, the tissue distribution study confirmed that distribution characteristics exhibited gender difference. This study provides scientific evidence for conducting further investigation into short-chain PFASs, biomonitoring plans and decision making regarding human health risk assessment.

Extracellular Vesicles Derived from Senescent Fibroblasts Attenuate the Dermal Effect on Keratinocyte Differentiation.

The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how human dermal fibroblasts (HDFs) accelerate EV production during senescence and the effects of senescence-associated EVs on epidermal homeostasis. Replicative senescent HDFs were assessed with senescence-associated ß-galactosidase staining and the expression of senescence-related markers. Isolated EVs were characterized by dynamic light scattering and EV marker expression. EVs secreted from untreated young or senescent HDFs, or from those treated with a nSMase inhibitor, antioxidant, and lysosomal activity regulators, were determined by sandwich ELISA for CD81. Human epidermal keratinocytes were treated with young- and senescent HDF-derived EVs. Compared to young HDFs, senescent HDFs produced relatively high levels of EVs due to the increased nSMase activity, oxidative stress, and altered lysosomal activity. The nSMase inhibitor, antioxidant, and agents that recovered lysosomal activity reduced EV secretion in senescent HDFs. Relative to young HDF-derived EVs, senescent HDF-derived EVs were less supportive in keratinocyte differentiation and barrier function but increased proinflammatory cytokine IL-6 levels. Our study suggests that dermis-derived EVs may regulate epidermal homeostasis by reflecting cellular status, which provides insight as to how the dermis communicates with the epidermis and influences skin senescence.

A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits.

Age-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet. The aim of this study was to evaluate pharmacokinetics (PKs) and tissue distribution of CK41016, a novel candidate for dry AMD, after intravenous (IV) or eye drop administration in rats and rabbits. In addition, a simple and sensitive bioanalytical method for CK41016 using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was developed. PK parameters were estimated by compartmental analysis using a WinNonlin® software version 8.1 (a Certara™ company). A PK model of CK41016 was well-described by the two-compartment model. The tissue-to-plasma partition coefficient (Kp) of CK41016 was the highest in the vitreous humor of rats and the cornea of rabbits after eye drop administration. In addition, the Caco-2 cell transporter assay confirmed that CK41016 was not an active substrate for the efflux transporter. In summary, the PKs and tissue distribution of CK41016 were successfully evaluated and investigated whether this drug was a substrate of efflux transporters.

Monitoring Culicine Mosquitoes (Diptera: Culicidae) as a Vector of Flavivirus in Incheon Metropolitan City and Hwaseong-Si, Gyeonggi-Do, Korea, during 2019.

The flaviviruses are small single-stranded RNA viruses that are typically transmitted by mosquitoes or tick vectors and are etiological agents of acute zoonotic infections. The viruses are found around the world and account for significant cases of human diseases. We investigated population of culicine mosquitoes in central region of Korean Peninsula, Incheon Metropolitan City and Hwaseong-si. Aedes vexans nipponii was the most frequently collected mosquitoes (56.5%), followed by Ochlerotatus dorsalis (23.6%), Anopheles spp. (10.9%), and Culex pipiens complex (5.9%). In rural regions of Hwaseong, Aedes vexans nipponii was the highest population (62.9%), followed by Ochlerotatus dorsalis (23.9%) and Anopheles spp. (12.0%). In another rural region of Incheon (habitat of migratory birds), Culex pipiens complex was the highest population (31.4%), followed by Ochlerotatus dorsalis (30.5%), and Aedes vexans vexans (27.5%). Culex pipiens complex was the predominant species in the urban region (84.7%). Culicine mosquitoes were identified at the species level, pooled up to 30 mosquitoes each, and tested for flaviviral RNA using the SYBR Green-based RT-PCR and confirmed by cDNA sequencing. Three of the assayed 2,683 pools (989 pools without Anopheles spp.) were positive for Culex flaviviruses, an insect-specific virus, from Culex pipiens pallens collected at the habitats for migratory birds in Incheon. The maximum likelihood estimation (the estimated number) for Culex pipiens pallens positive for Culex flavivirus was 25. Although viruses responsible for mosquito-borne diseases were not identified, we encourage intensified monitoring and long-term surveillance of both vector and viruses in the interest of global public health.

Staphylococcus aureus-derived extracellular vesicles induce monocyte recruitment by activating human dermal microvascular endothelial cells in vitro.

BACKGROUND: Atopic dermatitis (AD) represents the most common inflammatory skin disorder in children showing massive infiltration of immune cells. The colonization of AD-afflicted skin by Staphylococcus aureus and S. aureus-derived extracellular vesicles (SEVs) has been associated with AD pathogenesis; however, the molecular mechanism underlying SEV-mediated inflammatory responses remains unclear. OBJECTIVE: We investigated how SEVs can mediate inflammatory responses in AD pathogenesis by examining the effect of SEVs on human dermal microvascular endothelia cells (HDMECs). METHODS: HDMECs were treated with SEVs, and the expression of cell adhesion molecules or cytokines was assessed using RT-qPCR, Western blot or cytokine array analyses. The receptor for SEVs and related signalling molecules in HDMECs were addressed and verified via gene knockdown or inhibitor experiments. The recruitment assay of human THP-1 monocytic cells on HDMECs was performed after SEV treatment in the presence or absence of the verified receptor or signalling molecule. RESULTS: SEVs, but not other gram-positive bacteria-derived extracellular vesicles, directly activated HDMECs by increasing the expression of cell adhesion molecules (E-selectin, VCAM1 and ICAM1) and that of IL-6, the inflammatory cytokine; consequently, they enhanced the recruitment of THP-1 monocytic cells to HDMECs. The SEV-induced HDMEC activation was dependent on Toll-like receptor 4 and the NF-κB signalling pathway, which was rapidly activated within 1 hour post-treatment and followed by an upregulation of cell adhesion molecules and IL-6 at later time-points. Moreover, SEV-mediated HDMEC responses were more rapid and intense than those induced by the same protein concentrations of S. aureus extracts. CONCLUSIONS & CLINICAL RELEVANCE: SEVs as proinflammatory factors could mediate immune cell infiltration in AD by efficiently inducing endothelial cell activation and monocyte recruitment, which may provide insights into alleviating the S. aureus-mediated onset or progression of AD and its phenotypes.

Exploring sex differences in human health risk assessment for PFNA and PFDA using a PBPK model.

Perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), which are classified as perfluoroalkyl and polyfluoroalkyl substances (PFASs), have been widely used in industrial applications as a surface protectant. PFASs have been detected in wildlife and in humans around the globe. The purposes of this study are to develop and validate a physiologically based pharmacokinetic (PBPK) model for detecting PFNA and PFDA in male and female rats, and to apply the model to a human health risk assessment regarding the sex difference. A PBPK model of PFNA and PFDA was established based on an in vivo study in male and female rats. Analytes in biological samples (plasma, nine tissues, urine, and feces) were determined by ultra-liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) method. PFNA and PFDA showed a gender differences in the elimination half-life and volume of distribution. The tissue-plasma partition coefficients were the highest in the liver in both male and female rats. The predicted rat plasma and urine concentrations simulated and fitted were in good agreement with the observed values. The PBPK models of PFNA and PFDA in male and female rats were then extrapolated to a human PBPK model based on human physiological parameters. The external doses were calculated at 3.35 ng/kg/day (male) and 17.0 ng/kg/day (female) for PFNA and 0.530 ng/kg/day (male) and 0.661 ng/kg/day (female) for PFDA. Human risk assessment was estimated using Korean biomonitoring values considering the gender differences. This study provides valuable insight into human health risk assessment regarding PFNA and PFDA exposure.

Machine Learning-Based Fast Banknote Serial Number Recognition Using Knowledge Distillation and Bayesian Optimization.

We investigated a machine-learning-based fast banknote serial number recognition method. Unlike existing methods, the proposed method not only recognizes multi-digit serial numbers simultaneously but also detects the region of interest for the serial number automatically from the input image. Furthermore, the proposed method uses knowledge distillation to compress a cumbersome deep-learning model into a simple model to achieve faster computation. To automatically decide hyperparameters for knowledge distillation, we applied the Bayesian optimization method. In experiments using Japanese Yen, Korean Won, and Euro banknotes, the proposed method showed significant improvement in computation time while maintaining a performance comparable to a sequential region of interest (ROI) detection and classification method.

Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study.

Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was performed on dual columns (Kinetex® C18 column and Capcell core C18 column) with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m/z 328.9→228.8, 328.9→228.9, 409.4→248.8, and 246.8→212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05⁻50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects.

Extracellular vesicles derived from Gram-negative bacteria, such as Escherichia coli, induce emphysema mainly via IL-17A-mediated neutrophilic inflammation.

Recent evidence indicates that Gram-negative bacteria-derived extracellular vesicles (EVs) in indoor dust can evoke neutrophilic pulmonary inflammation, which is a key pathology of chronic obstructive pulmonary disease (COPD). Escherichia coli is a ubiquitous bacterium present in indoor dust and secretes nanometer-sized vesicles into the extracellular milieu. In the current study, we evaluated the role of E. coli-derived EVs on the development of COPD, such as emphysema. E. coli EVs were prepared by sequential ultrafiltration and ultracentrifugation. COPD phenotypes and immune responses were evaluated in C57BL/6 wild-type (WT), IFN-γ-deficient, or IL-17A-deficient mice after airway exposure to E. coli EVs. The present study showed that indoor dust from a bed mattress harbors E. coli EVs. Airway exposure to E. coli EVs increased the production of proinflammatory cytokines, such as TNF-α and IL-6. In addition, the repeated inhalation of E. coli EVs for 4 wk induced neutrophilic inflammation and emphysema, which are associated with enhanced elastase activity. Emphysema and elastase activity enhanced by E. coli EVs were reversed by the absence of IFN-γ or IL-17A genes. In addition, during the early period, lung inflammation is dependent on IL-17A and TNF-α, but not on IFN-γ, and also on TLR4. Moreover, the production of IFN-γ is eliminated by the absence of IL-17A, whereas IL-17A production is not abolished by IFN-γ absence. Taken together, the present data suggest that E. coli-derived EVs induce IL-17A-dependent neutrophilic inflammation and thereby emphysema, possibly via upregulation of elastase activity.

Attenuation of collagen-induced arthritis by hyperbaric oxygen therapy through altering immune balance in favor of regulatory T cells.

Hyperbaric oxygen (HBO2) therapy is currently used for the treatment of chronic wounds, radiation-induced soft tissue necrosis, several oxygen-deficiency conditions and decompression sickness. In addition to the current indications, much empirical and experimental data suggest that HBO2 therapy may benefit autoimmune diseases by suppressing immunity, but the underlying mechanism is not well understood. Therefore, in the present study, we investigated whether HBO2 prevents the development of collagen-induced arthritis (CIA) in association with alteration of the immune balance between pro-inflammatory Th17 and anti-inflammatory regulatory T cells (Tregs). Arthritis was induced in DBA/1 mice by intradermal injection of type II collagen. Animals received either no treatment or 90 minutes of HBO2 (100% oxygen, at 2.0 ATA) daily beginning three days prior to the injection and were monitored for the development of arthritis. Six weeks later, joint tissues and spleens were analyzed for the alteration of immune balance between Th17 and Tregs by immunohistochemistry (IHC) or Western blot. Injection of collagen-induced extensive arthritis and extramedullary hematopoiesis in the spleens. Meanwhile, joint swelling and inflammatory tissue damages as well as extramedullary hematopoiesis were significantly less severe in the mice treated with HBO2. Both IHC and Western blot showed a decrease of FOXP3 and an increase of pSTAT3 expressions in the joints and spleens of the mice injected with collagen. This suggested that the systemic immune balance was biased toward Th17 cells, which was reversed by HBO2 therapy. These results suggested acute CIA associated with an immune balance favoring Th17 was attenuated by HBO2 in parallel with restoration of the immune balance to favor Tregs.

In vivo kinetic biodistribution of nano-sized outer membrane vesicles derived from bacteria.

Evaluation of kinetic distribution and behaviors of nanoparticles in vivo provides crucial clues into their roles in living organisms. Extracellular vesicles are evolutionary conserved nanoparticles, known to play important biological functions in intercellular, inter-species, and inter-kingdom communication. In this study, the first kinetic analysis of the biodistribution of outer membrane vesicles (OMVs)-bacterial extracellular vesicles-with immune-modulatory functions is performed. OMVs, injected intraperitoneally, spread to the whole mouse body and accumulate in the liver, lung, spleen, and kidney within 3 h of administration. As an early systemic inflammation response, increased levels of TNF-α and IL-6 are observed in serum and bronchoalveolar lavage fluid. In addition, the number of leukocytes and platelets in the blood is decreased. OMVs and cytokine concentrations, as well as body temperature are gradually decreased 6 h after OMV injection, in concomitance with the formation of eye exudates, and of an increase in ICAM-1 levels in the lung. Following OMV elimination, most of the inflammatory signs are reverted, 12 h post-injection. However, leukocytes in bronchoalveolar lavage fluid are increased as a late reaction. Taken together, these results suggest that OMVs are effective mediators of long distance communication in vivo.

Development of cost-effective and fast KIR genotyping by multiplex PCR-SSP.

Killer-cell immunoglobulin-like receptors (KIR) control natural killer (NK) cell functions by recognizing HLA molecules and modulating the activity of NK cells. The KIR gene cluster contains polymorphic and highly homologous genes. Diversity of the KIR region is achieved through differences in gene content, allelic polymorphism, and gene copy number, which result in unrelated individuals having different KIR genotypes and individualized immune responses that are relevant to multiple aspects of human health and disease. Therefore, KIR genotyping is increasingly used in epidemiological studies. Here, we developed multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP) to compensate for the shortcomings of the conventional PCR-SSP method, which is most commonly used for KIR analysis. Multiplex PCR-SSP method involves six multiplex reactions that detect 16 KIR genes and distinguish variant types of some KIR genes by adding two reactions. The assay was evaluated in a blind survey using a panel of 40 reference DNA standards from the UCLA KIR Exchange Program. The results are 100% concordant with the genotype determined using Luminex-based reverse sequence-specific oligonucleotide typing systems. Additionally, we investigated the currently known 16 KIR genes and their common variants in 120 unrelated Korean individuals. The results were consistent with the KIR genotype previously reported by Hwang et al. This multiplex PCR-SSP is an efficient method for analyzing KIR genotypes in both small- and large-scale studies with minimal labor, reagents, and DNA. Furthermore, by providing a better definition of KIR polymorphisms it can contribute to developments in immunogenetics.

Interprofessional Educational Needs for Shared Governance of Integrated Care.

Introduction: This study investigated the educational needs of integrated care among professionals in the public sector of healthcare and social care services in South Korea. Methods: A cross-sectional secondary data analysis was performed. Original data were obtained from 10 metropolitan communities with a convenience sample of 210 integrated care professionals. The Borich Needs Assessment Model and the Locus for Focus Model were used to examine the priority educational needs of each integrated care professional. Results: This study analyzed the key details of educational needs in integrated care by focusing on the competencies of integrated care approaches for person-centered care, interprofessional collaboration, and community involvement. The core educational needs of community care administrators, care coordinators, healthcare and social care providers, and community health champions, which are common to all professionals, and the specific educational needs for each type of professional were demonstrated, which contained specific content to implement integrated care. Conclusion: This study provides an opportunity to comprehensively understand the educational needs of integrated care professionals based on their competencies. They want better interprofessional cooperation through networking and collaborative strategies. The results of this study may be utilized as fundamental data by future instructors to provide evidence-based education programs.

Genomic analysis uncovers that cold-inducible RNA binding protein is associated with estrogen receptor in breast cancer.

BACKGROUND: RNA-binding proteins (RBPs) perform various biological functions in humans and are associated with several diseases, including cancer. Therefore, RBPs have emerged as novel therapeutic targets. Although recent investigations have shown that RBPs have crucial functions in breast cancer (BC), detailed research is underway to determine the RBPs that are closely related to cancers. OBJECTIVE: To provide an insight into estrogen receptor (ER) regulation by cold-inducible RNA binding protein (CIRBP) as a novel therapeutic target. RESULTS: By analyzing the genomic data, we identified a potential RBP in BC. We found that CIRBP is highly correlated with ER function and influences clinical outcomes, such as patient survival and endocrine therapy responsiveness. In addition, CIRBP influences the proliferation of BC cells by directly binding to ER-RNA. CONCLUSION: Our results suggest that CIRBP is a novel upstream regulator of ER and that the interplay between CIRBP and ER may be associated with the clinical relevance of BC.

Association of KIR Genes with Middle East Respiratory Syndrome Coronavirus Infection in South Koreans.

BACKGROUND: Middle East respiratory syndrome (MERS) is a lower respiratory tract disease caused by a beta coronavirus (CoV) called MERS-CoV, characterized by a high mortality rate. We aimed to evaluate the association between genetic variation in killer cell immunoglobulin-like receptors (KIRs) and the risk of MERS in South Koreans. METHODS: KIR genes were genotyped by multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP). A case-control study was performed to identify the odds ratios (OR) of KIR genes for MERS and the association of KIR genes and their ligands, human leukocyte antigens (HLA) genes. RESULTS: KIR2DS4D and KIR3DP1F showed higher frequencies in the group of all patients infected with MERS-CoV than in the control group (p = 0.023, OR = 2.4; p = 0.039, OR = 2.7). KIR2DL1, KIR2DP1, and KIR3DP1D were significantly associated with moderate/mild (Mo/Mi) cases. KIR2DL2, KIR2DS1, and KIR3DP1F were affected in severe cases. When we investigated the association between KIR genes and their ligands in MERS patient and control groups, KIR3DL1+/Bw4(80I)+, KIR3DL1+/Bw6+, KIR3DL1+/Bw6-, KIR2DS1+/C2+, and KIR3DS+/Bw4(80I)+ were associated with MERS. KIR3DL1+/Bw6- was found in Mo/Mi cases. KIR2DS1+/C2+ and KIR2DS2+/C1+ were found in severe cases. CONCLUSION: Further investigations are needed to prove the various immune responses of MERS-CoV-infected cells according to variations in the KIR gene and ligand gene. A treatment strategy based on current research on the KIR gene and MERS-CoV will suggest potential treatment targets.

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.