Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Successful treatment with rituximab in anti-phospholipid syndrome nephropathy associated with systemic lupus erythematosus: A case report and literature review.

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency.

Fibronectin glomerulopathy in an elderly patient with FN1 gene mutation: a case report and literature review.

BACKGROUND: Fibronectin glomerulopathy (FNG) is a rare autosomal dominant glomerulopathy that can lead to nephrotic syndrome. Here we report the case of an elderly patient diagnosed with FNG, exhibiting nephrotic-range proteinuria, with a 2-year follow-up. CASE PRESENTATION: A 75-year-old Korean female visited the nephrology clinic after experiencing generalized edema for 2 months. Her serum creatinine was 1.36 mg/dL, and urine protein-to-creatinine ratio was 3.99 g/g. Kidney biopsy revealed mesangial and subendothelial dense deposits, and immunohistochemistry for fibronectin showed strong positivity in the glomerulus. The patient's family history included non-specific renal disease in her mother and two siblings. Genetic testing of the fibronectin 1 (FN1) gene showed Y973C mutation. She received conservative treatment, including angiotensin II receptor blockers (ARB). Two years after biopsy, the patient has preserved renal function and reduced proteinuria. CONCLUSION: We report the case of a 75-year-old patient with nephrotic-range proteinuria, who was diagnosed with FNG, and found to harbor a FN1 gene mutation. In this case, conservative treatment including ARB yielded reduction of proteinuria and preservation of renal function.

Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Functional disability and suicidal ideation in Korean older adults: the moderating role of socioeconomic status.

OBJECTIVES: Although the relationship between functional disability and suicidal ideation among older adults has been well documented, limited research exists regarding how socioeconomic status might moderate the relationship between functional disability and suicidal ideation. The objective of this study is to identify the relationship between functional disability and suicidal ideation and assess how SES moderates this relationship among Korean older adults. METHODS: Using data from wave 3 of the Korean Retirement and Income Study, this study has conducted a linear regression analysis with interaction terms. RESULTS: There are three main findings. First, the main effects of Activities of Daily Living, Instrumental Activities of Daily Living, and economic status on suicidal ideation were identified. Second, functional disability is identified as a serious risk factor for suicidal ideation among Korean older individuals who express dissatisfaction with their economic circumstances. Last, the moderating effect of economic condition and education on the relationship between functional disability and suicidal ideation exhibited some differences. CONCLUSION: This study suggests that the interactions of functional disability and economic status yield a significant predictive effect on suicidal ideation in South Korea.

Phylogenetic Analysis Based on Whole Genome Sequences, Antibiotic Resistance, and Virulence of Salmonella enterica Clinical Isolates from South Korea.

Salmonella is a major cause of foodborne disease and frequently causes human salmonellosis in South Korea. In this study, we investigated the genome diversity, antimicrobial resistance, and virulence of clinical isolates of Salmonella enterica from South Korea. We collected 42 S. enterica subsp. enterica isolates from two hospitals in South Korea. Whole genome sequences were determined. Serovars and sequence types (STs) based on multilocus sequence typing (MLST) were identified from whole genome sequences. Phylogenetic trees based on whole genome sequences and a minimum spanning tree based on MLST were constructed. Human serum resistance assays and gentamicin protection assays were performed to assess in vitro virulence. Nineteen serovars were identified among 42 clinical isolates, including nine Salmonella Typhi isolates. There were inconsistencies between serogroups and phylogenetic clusters in the phylogenetic tree and minimum spanning tree, but high clonality of S. Typhi was observed. Salmonella Typhi isolates were divided into two clusters, corresponding to ST1 and ST2. Isolates of serovars Typhimurium and I4,[5],12:i:- clustered into a group, and a hybrid isolate between the two serovars was identified. Four ciprofloxacin-resistant isolates were identified among nine S. Typhi isolates, and all isolates of S. Enteritidis and S. Panama were resistant to colistin. The gentamicin protection assay revealed that serogroup D1 was significantly less virulent than the other serogroups. Our study suggests high diversity of S. enterica clinical isolates from South Korea and non-monophyly of serogroups. In addition, subgroups of S. Typhi isolates and a hybrid isolate between serovars Typhimurium and I4,[5],12:i:- were identified.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Factors Related to General Sexual Behavior of Children Under 10 Years Old in Korea.

The risk factors for intrusive or problematic sexual behavior in a specific population, including abused or clinically referred children, have been occasionally explored. However, sexual behaviors broadly in the general population have not been investigated. This study aimed to determine whether child characteristics, exposure to trauma, family factors, and exposure to sexuality, which were proposed as predictors of sexual behavior problems in previous studies, significantly affected the general sexual behaviors of children under 10 years in the Korean population. The parents of 652 children aged 3-9 years in a Korean community completed questionnaires, including the Child Sexual Behavior Inventory, the Korean version of the Child Behavior Checklist, Trauma Symptom for Young Children, the Korean version of the Family Inventory of Life and Change, the Dysfunctional Parenting Scale, and exposure to trauma and sexuality. Regression analysis indicated that children's age, externalizing behavior problems, post-traumatic symptoms, exposure to trauma, and exposure to sexuality were significant predictors of overall sexual behaviors. Therefore, it may be helpful to explore trauma and exposure to sexuality even to understand a child's general sexual behavior. In addition, psychoeducation can help parents monitor and reset family boundaries and sexual exposure that can affect children's sexual behavior.

The Current Status and Future Perspectives of Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Endometrial Cancer.

Endometrial cancer (EC) is a gynecological neoplasm that is increasing in occurrence and mortality rates. Although endometrial cancer in the early stages shows a relatively favorable prognosis, there is an increase in cancer-related mortality rates in the advanced or recurrent endometrial carcinoma population and patients in the metastatic setting. This discrepancy has presented an opportunity for research and development of target therapies in this population. After obtaining promising results with hematologic cancers, chimeric antigen receptor (CAR)-T cell immunotherapy is gaining acceptance as a treatment for solid neoplasms. This treatment platform allows T cells to express tumor-specific CARs on the cell surface, which are administered to the patient to treat neoplastic cells. Given that CAR-T cell therapy has shown potential and clinical benefit compared to other T cell treatment platforms, additional research is required to overcome physiological limitations such as CAR-T cell depletion, immunosuppressive tumor microenvironment, and the lack of specific target molecules. Different approaches and development are ongoing to overcome these complications. This review examines CAR-T cell therapy's current use for endometrial carcinomas. We also discuss the significant adverse effects and limitations of this immunotherapeutic approach. Finally, we consolidate signal-seeking early-phase clinical trials and advancements that have shown promising results, leading to the approval of new immunotherapeutic agents for the disease.

The effect of hepatic steatosis on liver volume determined by proton density fat fraction and deep learning-measured liver volume.

OBJECTIVES: We aimed to evaluate the effect of hepatic steatosis (HS) on liver volume and to develop a formula to estimate lean liver volume correcting the HS effect. METHODS: This retrospective study included healthy adult liver donors who underwent gadoxetic acid-enhanced MRI and proton density fat fraction (PDFF) measurement from 2015 to 2019. The degree of HS was graded at 5% PDFF intervals from grade 0 (no HS; PDFF < 5.5%). Liver volume was measured with hepatobiliary phase MRI using deep learning algorithm, and standard liver volume (SLV) was calculated as the reference lean liver volume. The association between liver volume and SLV ratio with PDFF grades was evaluated using Spearman's correlation (ρ). The effect of PDFF grades on liver volume was evaluated using the multivariable linear regression model. RESULTS: The study population included 1038 donors (mean age, 31 ± 9 years; 689 men). Mean liver volume to SLV ratio increased according to PDFF grades (ρ = 0.234, p < 0.001). The multivariable analysis indicated that SLV (ß = 1.004, p < 0.001) and PDFF grade*SLV (ß = 0.044, p < 0.001) independently affected liver volume, suggesting a 4.4% increase in liver volume per one-point increment in the PDFF grade. PDFF-adjusted lean liver volume was estimated using the formula, liver volume/[1.004 + 0.044 × PDFF grade]. The mean estimated lean liver volume to SLV ratio approximated to one for all PDFF grades, with no significant association with PDFF grades (p = 0.851). CONCLUSION: HS increases liver volume. The formula to estimate lean liver volume may be useful to adjust for the effect of HS on liver volume. KEY POINTS: • Hepatic steatosis increases liver volume. • The presented formula to estimate lean liver volume using MRI-measured proton density fat fraction and liver volume may be useful to adjust for the effect of hepatic steatosis on measured liver volume.

Re-identification and Characterization of Multidrug-Resistant Corynebacterium haemomassiliense-Like Organisms from Humans.

Recently, non-diphtheriae Corynebacterium spp. have been increasingly reported in patients. In addition, several novel species of Corynebacterium isolated from humans. Here, we report two cases of human infections caused by Corynebacterium haemomassiliense-like organisms, which had not been identified at the species level by MALDI-TOF MS analysis. They were revealed to be closely related to C. haemomassiliense, a recently described species by three housekeeping genes (16S rRNA, rpoB, and gyrA) and phenotypic features. Both strains were multidrug-resistant but susceptible to vancomycin, meropenem, and linezolid. Our report suggests that human infections by the recently described Corynebacterium species may not be limited to a specific region, in addition to difficulty of classifying the genus Corynebacterium.

Caproiciproducens faecalis sp. nov., Isolated from Cow Faeces.

The bacterial strain AGMB10547T was isolated from cow faeces deposited by the National Institute of Animal Science in Cheonan, Republic of Korea. The strain AGMB10547T possessed the phenotypic, biochemical and chemotaxonomic characteristics of the bacteria of the family Oscillospiraceae. The isolate was obligately anaerobic, non-motile, Gram-positive and rod-shaped bacteria. The growth of strain AGMB10547T occurred within 35-40 °C (optimum at 37 °C), at pH 6-7 (optimum of 7) and in the presence of 0.5-2.0% (w/v) NaCl. Based on 16S rRNA gene sequence similarity, strain AGMB10547T belonged to the genus Caproiciproducens and was most closely related to Caproiciproducens galactitolivorans BS-1T (96.9%). The DNA G+C content was 49.0 mol%. The major cellular fatty acids (> 10%) of the isolate were C14:0, C14:0 DMA, C16:1 ω9c and C16:0. The average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH) values between strain AGMB10547T and C. galactitolivorans BS-1T were 75.5% and 19.2%. Based on the phenotypic, genotypic, biochemical and chemotaxonomic analyses, strain AGMB10547T represents a novel species of the genus Caproiciproducens, for which the name Caproiciproducens faecalis sp. nov. is proposed. The type strain AGMB10547T (=KCTC 25200T=NBRC 115006T=GDMCC 1.2575T).

Renal Sarcoidosis-like Reaction Induced by PD-1 Inhibitor Treatment in Non-Small Cell Lung Cancer: A Case Report and Literature Review.

Monoclonal antibodies directed against immune checkpoint proteins have been widely used to treat various cancers and have resulted in favorable clinical outcomes. Despite these beneficial properties, immune checkpoint inhibitors (ICIs) can induce side effects called immune-related adverse events, including sarcoidosis-like reactions (SLR) across multiple organs. Here, we report a case of renal SLR after ICI treatment, and we review the related literature. A 66-year-old Korean patient with non-small cell lung cancer was referred to the nephrology clinic for renal failure after the 14th pembrolizumab treatment dose. A renal biopsy revealed multiple epithelioid cell granulomas, with several lymphoid aggregates in the renal interstitium and a moderate degree of inflammatory cell infiltration in the tubulointerstitium. A moderate dose of steroid therapy was initiated, and the serum creatinine level partially recovered after four weeks of treatment. Judicious monitoring of renal SLR is, therefore, required during ICI therapy, and a timely diagnosis by renal biopsy and appropriate treatment are important.

Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report.

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.

Lycopus lucidus Turcz Water Extract Ameliorates the Metabolic Disorder by Up-Regulated Major Urinary Protein Expression in High-Fat Diet-Induced Obesity.

Despite a century of research on obesity, metabolic disorders and their complications, including dyslipidemia, insulin resistance, and fatty liver disease remain a serious global health problem. Lycopus lucidus Turcz (LT) is a traditional medicine used for its anti-inflammatory properties that has not been evaluated for its efficacy in improving obesity. In this study, mice were fed a normal diet (n = 10) or obesity was induced with a high-fat diet (HFD, n = 20, 60% kcal from fat) for 4 weeks. The HFD mice were then divided into two groups, one of which received LT supplementation with water extract for 13 weeks [HFD (n = 10) or HFD with LT water extract (n = 10, 1.5%)]. LT reduced body and adipose tissue weight by elevating energy expenditure by increasing fatty oxidation in epididymal white adipose tissue (eWAT) and muscle. LT ameliorated dyslipidemia and hepatic steatosis by restricting lipogenesis. Additionally, LT normalized the impaired glucose homeostasis by diet-induced obesity to improve pancreatic islet dysfunction with increasing hepatic major urinary protein expression. Moreover, LT attenuated the inflammation and collagen accumulation in the liver and eWAT. In conclusion, these results suggest that LT can treat obesity-related metabolic disorders such as adiposity, dyslipidemia, hepatic steatosis, insulin resistance, and inflammation.

SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1) impairs human brain vessel cells.

Increasing evidence suggests incomplete recovery of COVID-19 patients, who continue to suffer from cardiovascular diseases, including cerebral vascular disorders (CVD) and neurological symptoms. Recent findings indicate that some of the damaging effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in the brain, may be induced by the spike protein, leading to the disruption of the initial blood-brain barrier (BBB). SARS-CoV-2-infected cells and animals exhibit age-dependent pathogenesis. In this study, we identified endothelial BACE1 as a critical mediator of BBB disruption and cellular senescence induced by the SARS-CoV-2 spike S1 subunit protein. Increased BACE1 in human brain microvascular endothelial cells (HBMVEC) decreases the levels of tight junction proteins, including ZO-1, occludin, and claudins. Moreover, BACE1 overexpression leads to the accumulation of p16 and p21, typical hallmarks of cellular senescence. Our findings show that the SARS-CoV-2 spike S1 subunit protein upregulated BACE1 expression in HBMVECs, causing endothelial leakage. In addition, the SARS-CoV-2 spike S1 subunit protein induced p16 and p21 expression, indicating BACE1-mediated cellular senescence, confirmed by ß-Gal staining in HBMVECs. In conclusion, this study demonstrated that BACE1-mediated endothelial cell damage and senescence may be linked to CVD after COVID-19 infection.

Succinivibrio faecicola sp. nov., isolated from cow faeces.

A Gram-stain-negative, obligately anaerobic, non-motile, non-spore-forming, helical rod-shaped bacterium, designated AGMB01872T, was isolated from faeces of a cow deposited in the National Institute of Animal Science (Wanju, Republic of Korea). Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain AGMB01872T was most closely related to Succinivibrio dextrinosolvens DSM 3072T (= KCTC 25222T, 96.6 %) which belonged to the family Succinivibrionaceae. Growth was occurred at 30-40 °C (optimum, 37 °C), pH 6-7 (optimum, pH 7) and in the presence of 0.5-1.0 % (w/v) NaCl. The genomic DNA G+C content of strain AGMB01872T was 35.9 mol%. The average nucleotide identity value between strain AGMB01872T and S. dextrinosolvens DSM 3072T was 72.1 %. Cells of strain AGMB01872T utilized d-glucose, maltose, d-xylose and l-arabinose. The major fatty acids (>10 %) were C14 : 0 (23.9 %), C16 : 0 (29.4 %), summed feature 5 (10.8 %) and summed feature 10 (30.3 %). The major end-product of glucose fermentation was succinate. Based on the phenotypic, phylogenetic, biochemical, genotypic and chemotaxonomic data, AGMB01872T represents a novel species within the genus Succinivibrio, for which the name Succinivibrio feacicola sp. nov. is proposed. The type strain is AGMB01872T (= KCTC 25201T=NBRC 115007T=GDMCC 1.2573T).

Control of a nosocomial measles outbreak among previously vaccinated adults in a population with high vaccine coverage: Korea, 2019.

We describe a measles outbreak among previously vaccinated healthcare workers (HCWs) and inpatients and the control measures implemented at a tertiary care hospital in 2019. Case-patients were laboratory-confirmed measles with throat swabs tested by quantitative polymerase chain reactions (PCR), during April-May 2019. Medical histories and documented immunization records were obtained. We compared attack rates (ARs) among HCWs by occupational subgroup and age and examined the outbreak-associated costs. The index case was not ascertained. Among 26 measles case-patients (22 HCWs, four inpatients) aged 18-28 years, 25 had previously received measles-mumps-rubella (MMR) vaccine (12/26, 46% (two doses); 13/26, 50% (one dose)), and 16 (62%) had positive results of measles IgG prior to measles diagnosis. ARs were higher among HCWs aged < 30 years (1.88%), especially in the subgroup under 25 years of age (2.22%). Control measures included work restrictions for seronegative HCWs (218/2320, 9.4%) in immunity verification, administration of the MMR vaccine (207 HCWs) or intravenous immunoglobulin (2 HCWs and 11 inpatients), enhanced health surveillance of HCWs, and mandatory assessment of patients with measles-like symptoms at the infectious diseases screening units. The hospital spent 90,417,132 Korean won (US $79,733) in response to the outbreak. Measles outbreaks can occur in healthcare settings despite high population immunity, highlighting the importance of stronger vaccination policies, particularly among young HCWs. Moreover, an effective outbreak response comprising immunization activities and enhanced surveillance of HCWs and patients to rapidly detect measles-like symptoms at a prodromal phase is essential to control nosocomial measles outbreaks.

Molecular cloning, expression analysis of interleukin 17D (cysteine knot cytokine) from Amphiprion clarkii and their functional characterization and NFκB pathway activation using FHM cells.

Interleukin 17D (IL-17D), a pro-inflammatory cytokine, is a signature cytokine of T helper 17 (Th17) cells. However, studies characterizing the functions of IL-17D in teleost are scarce. Therefore, we aimed to characterize the properties of IL-17D in Amphiprion clarkii. We performed spatial and temporal expression, AcIL-17D-mediated antibacterial and inflammatory gene expression, NFκB pathway-related gene expression analyses, and bacterial colony counting and cell protection assays. We found that AcIL-17D contains a 630 bp coding sequence and encodes 210 amino acids. The spatial expression analysis of AcIL-17D in 12 tissues showed ubiquitous expression, with the highest expression in the brain, followed by blood and skin. Temporal expression analysis of AcIL-17D in blood showed upregulated expression at 6 and 24 h (polyinosinic: polycytidylic acid and lipopolysaccharide), 12 h (all stimulants), and 48 h (polyinosinic: polycytidylic acid and Vibrio harveyi). AcIL-17D expression in the blood gradually decreased at later hours in response to all the stimulants. After treatment of fathead minnow (FHM) cells with different recombinant AcIL-17D concentrations, the downstream gene expression analysis showed increased expression of antimicrobial genes in the FHM cells, namely [NK-Lysin (NKL), Hepcidin antimicrobial peptide-1 (HAMP-1), Defensin-ß (DEFB1)] and some inflammatory genes such as IL-1ß, TNF-α, IL-11, and STAT3. Further nuclear factor κB (NFκB) subunits (NFκB1, NFκB2, RelA, and Rel-B) showed upregulated gene expression at 12 and 24 h. The bacterial colony counting assay using FHM cells showed lower bacterial colony counts in rAcIL-17D-treated cells than in control. Furthermore, the Water-Soluble Tetrazolium Salt (WST -1) assay confirmed the ability of rAcIL-17D in the protection of FHM cells from bacterial infection and conducted the Hoechst 33342 staining upon treatment with rAcIL-17D and rMBP. Therefore, our findings provide important insights into the activation of IL-17D pathway genes in FHM cells, the protective role of AcIL-17D against bacterial infection, and host defense mechanisms in teleost.

Transient induction of telomerase expression mediates senescence and reduces tumorigenesis in primary fibroblasts.

Telomerase is an enzymatic ribonucleoprotein complex that acts as a reverse transcriptase in the elongation of telomeres. Telomerase activity is well documented in embryonic stem cells and the vast majority of tumor cells, but its role in somatic cells remains to be understood. Here, we report an unexpected function of telomerase during cellular senescence and tumorigenesis. We crossed Tert heterozygous knockout mice (mTert+/- ) for 26 generations, during which time there was progressive shortening of telomeres, and obtained primary skin fibroblasts from mTert+/+ and mTert-/- progeny of the 26th cross. As a consequence of insufficient telomerase activities in prior generations, both mTert+/+ and mTert-/- fibroblasts showed comparable and extremely short telomere length. However, mTert-/- cells approached cellular senescence faster and exhibited a significantly higher rate of malignant transformation than mTert+/+ cells. Furthermore, an evident up-regulation of telomerase reverse-transcriptase (TERT) expression was detected in mTert+/+ cells at the presenescence stage. Moreover, removal or down-regulation of TERT expression in mTert+/+ and human primary fibroblast cells via CRISPR/Cas9 or shRNA recapitulated mTert-/- phenotypes of accelerated senescence and transformation, and overexpression of TERT in mTert-/- cells rescued these phenotypes. Taking these data together, this study suggests that TERT has a previously underappreciated, protective role in buffering senescence stresses due to short, dysfunctional telomeres, and preventing malignant transformation.