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Background: MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed. Methods: MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT–PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. Results: Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay. Conclusion: MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.

Summary Sarcopenia means the progressive loss of skeletal muscle mass and strength with aging. In this study, we found that insulin resistance, chronic kidney disease stage 3, and osteoporosis at the femur neck were closely associated with sarcopenia in elderly men. These conditions modified to slow down the progression of sarcopenia. Introduction Sarcopenia is known to have multiple contributing factors; however, its modifiable risk factors have not yet been determined. The aim of this study was to identify the most influential and modifiable risk factors for sarcopenia in elderly. Methods This was a population-based, cross-sectional study using data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV), 2008–2009. This study included 940 men and 1,324 women aged 65 years and older who completed a body composition analysis using dual-energy X-ray absorptiometry. Sarcopenia was defined as an appendicular skeletal muscle mass divided by height 2 of less than 1 standard deviation below the sex-specific mean for a younger reference group. Results Using univariate analysis, age, body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), limitations in daily activities, regular exercise, high-risk drinking, family income, osteoporosis, daily energy, and protein intake were associated with sarcopenia in men; age, BMI, limitations in daily activities, regular exercise, occupation, osteoporosis at the total hip, and daily energy intake were associated with sarcopenia in women. In the multivariate logistic regression analysis, HOMA-IR ≥2.5 (odds ratio [OR] for sarcopenia, 2.27; 95 % confidence interval [CI], 1.21–4.25), chronic kidney disease stage 3 (OR, 3.13; 95 % CI, 1.14–8.61), and osteoporosis at the femur neck (OR, 6.83; 95 % CI, 1.08–43.41) were identified as risk factors for sarcopenia in men. Conclusions Insulin resistance, chronic kidney disease, and osteoporosis at the femur neck should be modified to prevent the acceleration of skeletal muscle loss in elderly men.

Purpose Raoultella ornithinolytica is not well known as a clinical pathogen. We performed a retrospective review of R. ornithinolytica bacteremia to investigate its clinical features, antimicrobial susceptibility, and overall patient outcomes. Methods R. ornithinolytica bacteremia cases were collected from an electronic database of all cases of bacteremia over a 10-year period. Medical records were retrospectively reviewed. Demographic data, clinical information, the presence of underlying comorbidities, the results of antimicrobial susceptibility testing, and the antimicrobial regimen administered were investigated. Results R. ornithinolytica was isolated from blood culture specimens in 16 cases. The majority of these patients had an underlying malignant condition of advanced stage (15 patients, 94 %). Seven of these patients had a solid tumor with lesions or metastases that extended to the bile duct or biliary tract. Neutropenic fever following hematologic stem cell transplantation was found in three cases. No resistance to piperacillin/tazobactam or imipenem was found. Four cases showed resistance to cefoxitin, while one of these cases showed resistance to multiple cephalosporins. In overall outcomes, seven patients (44 %) did not recover from the infection and subsequently expired. Conclusions R. ornithinolytica bacteremia occurs mainly in patients with underlying malignancies. The overall outcome was not favorable, despite favorable antimicrobial susceptibility test results. The findings of this study contradict those of other studies that demonstrated that infection from Raoultella species have good prognoses.

It is uncertain whether an initial inappropriate empirical antibiotic treatment of coagulase-negative staphylococci (CoNS) bacteremia adversely affects the outcome. A retrospective cohort study of CoNS bacteremia was performed at the Dongguk University Ilsan Hospital during a 3-year period. During the study period, 109 patients with CoNS bacteremia were enrolled. The median age of the patients was 72 years and most (96 %, 105/109) had one or more comorbid diseases. Among the participants, 29 % (32/109) received an appropriate empirical antimicrobial therapy. The 30-day mortality was 24 % (26/109) and CoNS bacteremia-related mortality was 14 % (15/109). There was no difference in the CoNS bacteremia-related mortality between the group with an inappropriate empirical treatment (13 %, 10/77) and that with an appropriate treatment (16 %, 5/32) ( p  = 0.46). In the multivariate analysis using the Cox regression analysis method, Pitt bacteremia scores [hazard ratio (HR) 1.48; 95 % confidence interval (CI) 1.09–2.01; p  = 0.01] and retention of eradicable focus (HR 5.0; 95 % CI 1.39–17.9; p  = 0.01) were found to be associated with CoNS bacteremia-related mortality. The results suggest that inappropriate empirical therapy might not necessarily be associated with the 30-day mortality or CoNS bacteremia-related mortality. Conversely, Pitt bacteremia scores and retention of eradicable focus were associated with poor outcomes.

Patients with liver cirrhosis (LC) have impaired immunity and are, thus, predisposed to infection. Few studies have attempted to evaluate group B streptococcal (GBS) bacteremia in LC patients. A retrospective study of patients with GBS bacteremia was performed at the Dongguk University Ilsan Hospital and National Health Insurance Service Ilsan Hospital over a 13-year period (October 2000 to July 2013). During the study period, 97 patients with GBS bacteremia were enrolled. The median age of the patients was 67 years and 54 % were men. Among them, 23 (24 %) patients were classified as LC patients. The 30-day mortality rate of LC patients was significantly higher than that of patients with other diseases (26 % vs. 8 %, p  = 0.03). The multivariate analysis indicated that LC was associated with an increased risk of 30-day mortality [hazard ratio (HR) 5.0; 95 % confidence interval (CI) 1.53–16.3; p  = 0.008], as well as age (HR 1.07; 95 % CI 1.03–1.13; p  = 0.02) and high Pitt bacteremia score (HR 1.23; 95 % CI 1.02–1.46; p  = 0.03). The probability of survival at day 30 was significantly different for the Child–Pugh class C and the Child–Pugh classes A or B (44 % vs. 93 %, respectively; p  = 0.01 by the log-rank test). The mortality rates of LC patients with GBS bacteremia were significantly higher than those of patients with other diseases. The severity of hepatic dysfunction plays an important role in the development of adverse events. Cirrhosis-specific scores such as the Child–Pugh class might be useful for predicting the prognosis of GBS bacteremia in LC patients.

BackgroundThe mortality rate of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is relatively higher than that of those with other vasculitides. Various biomarkers are developed to predict outcome of AAV. Recently, a novel index, triglyceride (TG) glucose-body mass index (BMI) (TyG-BMI) was introduced to predict insulin resistance (IR), cardiovascular disease, cerebrovascular accidents in general population. Given that IR and its related diseases such as CVD and CVA are generally major risk factors for all-cause mortality in the general population, it could be assumed that TyG-BMI could be a robust predictor of all-cause mortality in AAV patients.ObjectivesThis study aimed to investigated whether TyG-BMI and a new index using TyG-BMI (NITGB) could predict all-cause mortality in nonobese patients with AAV.MethodsThe medical records of 78 nonobese AAV patients (BMI < 23.0 kg/m2 for Asian) were retrospectively reviewed. TyG-BMI was calculated by the equation: Ln [triglyceride × fasting glucose/2] × BMI. To develop NITGB, we assigned a weight of a number close to an 0.1 decimal integer to each variable according to the slopes for independent variables with P-value < 0.1 in the multivariable Cox analysis.ResultsThe median age was 54.3 years and five patients died. When nonobese AAV patients were divided into two groups based on TyG-BMI ≥ 187.74, those with TyG-BMI ≥ 187.74 exhibited a significantly higher risk for all-cause mortality than those without (RR 9.450). Since age (HR 1.324), Birmingham vasculitis activity score (BVAS; HR 1.212), and TyG-BMI ≥ 187.74 (HR 12.168) were independently associated with all-cause mortality, NITGB was developed as follow: age + 0.2 × BVAS + 2.5 × TyG-BMI ≥ 187.74. When nonobese AAV patients were divided into two groups based on NITGB ≥ 27.36, those with NITGB ≥ 27.36 showed a significantly higher risk for all-cause mortality than those without (RR 284.000).ConclusionBoth nonobese AAV patients with TyG-BMI ≥ 187.74 and those with NITGB ≥ 27.36 exhibited significantly higher cumulative rates of all-cause mortality than those without. NITGB along with TyG-BMI could predict all-cause mortality in nonobese AAV patients.References[1]Wallace ZS, Fu X, Harkness T, Stone JH, Zhang Y, Choi H. All-cause and cause-specific mortality in ANCA-associated vasculitis: overall and according to ANCA type. Rheumatology (Oxford). 2020;59(9):2308-2315.[2]Murray CJ, Atkinson C, Bhalla K, et al. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013 Aug 14;310(6):591-608.[3]Er LK, Wu S, Chou HH, et al. Triglyceride Glucose-Body Mass Index Is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals. PLoS One. 2016;11(3):e0149731.[4]Du Z, Xing L, Lin M, Sun Y. Estimate of prevalent ischemic stroke from triglyceride glucose-body mass index in the general population. BMC Cardiovasc Disord. 2020;20(1):483.Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/- ) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.

Peptide chips are an emerging technology that could replace many of the bioanalytical methods currently used in drug discovery, diagnostics, and cell biology. Despite the promise of these chips, their development for quantitative assays has been limited by several factors, including a lack of well-defined surface chemistries to immobilize peptides, the heterogeneous presentation of immobilized ligands, and nonspecific adsorption of protein to the substrate. This paper describes a peptide chip that overcomes these limitations, and demonstrates its utility in activity assays of the nonreceptor tyrosine kinase c-Src. The chip was prepared by the Diels–Alder-mediated immobilization of the kinase substrate AcIYGEFKKKC-NH 2 on a self-assembled monolayer of alkanethiolates on gold. Phosphorylation of the immobilized peptides was characterized by surface plasmon resonance, fluorescence, and phosphorimaging. Three inhibitors of the enzyme were quantitatively evaluated in an array format on a single, homogeneous substrate.

In this study, we reported on the design of a multiplex real-time PCR assay based on SYBR Green I, incorporating dual priming adenine-thymine (AT)-rich primers for direct detection of MRSA from nasal samples. The multiplex real-time polymerase chain reaction (RT-PCR) assay reported in this study is based on SYBR Green I with incorporation of six dual priming AT-rich primers designed from the SCCmec/orf junction. A string (4–6 bp) of low-melting bases, such as adenine and thymine, was incorporated into the primers, which virtually divided a single primer in two functional regions, thus decreasing non-specific PCR products. The analytical sensitivity and specificity of the RT-PCR assay was determined with genomic DNA of reference strains (MRSA, MSSA, and MRCoNS). RT-PCR assay was performed for analysis of 72 nasal swab specimens, and the results were confirmed by use of a culture method. Furthermore, the results of RT-PCR were compared with LightCycler MRSA advance test. The multiplex RT-PCR assay reproducibly detected a minimum of 1 pg genomic DNA (31.5 copy of genome) of MRSA reference strains and clinical isolates, with a specific melting peak at 83.5 ± 1.5°C, and neither fluorescence nor a melting peak was detected in non-target isolates. The concordance rate between RT-PCR assay and culture method was 87.5% with Cohen's kappa value (κ) 0.75, which showed good agreement between the two assays. The sensitivity, specificity, positive predictive value, and negative predictive value of the assay were 93.5%, 82.9%, 80.5%, and 94.4%, respectively. In a comparative study for the detection of 72 nasal samples, the sensitivity, specificity, positive predictive value, and negative predictive value of the multiplex RT-PCR assay with respect to LightCycler MRSA advance test was 84.2%, 88.2%, 89%, and, 83.3%, respectively. The results of RT-PCR assay demonstrated high specificity (88.2%) and positive predictive value (89%) for the direct detection of MRSA from nasal samples.