Correction: The Correlation Between NAFLD and Serum Uric Acid to Serum Creatinine Ratio.

[This corrects the article DOI: 10.1371/journal.pone.0288666.].

The correlation between NAFLD and serum uric acid to serum creatinine ratio.

BACKGROUND: With the prevalence of non-alcoholic fatty liver disease (NAFLD) increasing worldwide, many noninvasive techniques have been used to improve its diagnosis. Recently, the serum uric acid/creatinine (sUA/sCr) ratio was identified as an indicator of fatty liver disease. Therefore, we examined the relationship between sUA/sCr levels and ultrasound-diagnosed NAFLD in Korean adults. METHODS: This study included 16,666 20-year-olds or older who received health checkups at a university hospital's health promotion center from January to December 2021. Among them, 11,791 non-patients with and without NAFLD were analyzed, excluding those without abdominal ultrasound, those without data on fatty liver, cancer, or chronic kidney disease severity, those with a history of alcohol abuse, and those with serum hs-CRP <5 mg/L. The odds ratio (OR) and 95% confidence interval (CI) of the sUA/sCr ratio according to the presence or absence of fatty liver disease and severity were calculated after correcting for confounding variables using logistic regression analysis. The receiver operating characteristic (ROC) curve and area under the curve (AUC) of the sUA/sCr ratio confirmed and compared the sensitivity and specificity of NAFLD and serum uric acid. RESULTS: sUA/sCr increased with fatty liver severity, and the post-correction OR in the NAFLD group was 1.183 (95% CI: 1.137-1.231) compared to the group without NAFLD. Concerning the fatty liver severity, the post-correction OR in the mild NAFLD group increased to 1.147 (95% CI: 1.099-1.196), and that in the moderate-to-severe NAFLD group increased to 1.275 (95% CI: 1.212-1.341) compared to the group without NAFLD. The sensitivity of sUA/sCr to fatty liver severity was 57.9% for the non-NAFLD group, 56.7% for the mild NAFLD group, and 59.0% for the moderate-to-severe NAFLD group; the specificity of sUA/sCr to fatty liver severity 61.4% for the non-NAFLD group, 57.3% for the mild NAFLD group, and 65.2% for the moderate-to-severe NAFLD group. CONCLUSION: NAFLD severity is associated with sUA/sCR.

Data resource profile: the Korea National Hospital Discharge In-depth Injury Survey.

The Korea National Hospital Discharge In-depth Injury Survey (KNHDIS), which was started in 2005, is a national probability survey of general hospitals in Korea with 100 or more beds conducted by the Korea Disease Control and Prevention Agency (KDCA). The KNHDIS captures approximately 9% of discharged cases from sampled hospitals using a 2-stage stratified cluster sampling scheme, among which 13% are injury related cases, defined as S00-T98 (injury, poisoning, and certain other consequences of external causes) using International Classification of Diseases, 10th revision codes. The KNHDIS collects information on characteristics of injury-related discharges in order to understand the scale of injuries, identify risk factors, and provide data supporting prevention policies and intervention strategies. The types of data captured include the hospitals' information, detailed clinical information, and injury-related codes such as the mechanism, activities undertaken when injured (sports, leisure activities, work, treatment, and education), external causes of the injury, and location of the occurrence of the injury based on the International Classification of External Causes of Injuries. Furthermore, the means of transportation, risk factors for suicide, and toxic substances are recoreded. Annual reports of the KNHDIS are publicly accessible to browse via the KDCA website (http://www.kdca.go.kr) and microdata are available free of charge upon request via email (kcdcinjury@korea.kr).

Optimized biodegradable polymeric reservoir-mediated local and sustained co-delivery of dendritic cells and oncolytic adenovirus co-expressing IL-12 and GM-CSF for cancer immunotherapy.

Administration of dendritic cells (DCs) combined with oncolytic adenovirus (Ad) expressing antitumor cytokines induces a potent antitumor effect and antitumor immunity by ameliorating the immunosuppressive tumor microenvironment. However, this combination therapy has significant limitations due to rapid dissemination and inactivation of the therapeutics at the tumor site, necessitating multiple injections of both therapeutics. To overcome these limitations, we have utilized gelatin-based hydrogel to co-deliver oncolytic Ad co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (oAd) and DCs for sustained release of both therapeutics. The injectable and biodegradable hydrogels were prepared by mixing the polymer solutions containing horseradish peroxidase and hydrogen peroxide. Gel matrix enabled sustained release of both oAd and DCs while preserving their biological activity over a considerable time period, leading to efficient retention of both therapeutics in tumor tissue. Further, tumors treated with oAd- and DC-loaded gel (oAd+DC/gel) showed a significantly greater expression level of IL-12, GM-CSF, and interferon-γ (IFN-γ) than either single treatment (oAd or DC) or oAd in combination with DC (oAd+DC), resulting in efficient activation of both endogenous and exogenous DCs, migration of DCs to draining lymph nodes, and tumor infiltration of CD4+ and CD8+ T cells. Moreover, oAd+DC/gel resulted in a significantly higher number of tumor-specific IFN-γ-secreting immune cells compared with oAd+DC. Lastly, oAd+DC/gel significantly attenuated tumor-mediated thymic atrophy, which is associated with immunosuppression in the tumor microenvironment, compared with oAd+DC. Taken together, these results demonstrate that gelatin gel-mediated co-delivery of oncolytic Ad and DCs might be a promising strategy to efficiently retain both therapeutics in tumor tissue and induce a potent antitumor immune response for an extended time period via a single administration.

Association between volume and glucose metabolism of abdominal adipose tissue in healthy population.

OBJECTIVE: We investigated the association of adipose tissue volume and metabolic activity with cardiometabolic risk factors. METHODS: 232 healthy subjects (43.23±4.09y) having 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) results were included. Clinical information, anthropometry and laboratory results were obtained. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was obtained from FDG PET/CT. Metabolic activity was presented as mean standardised uptake value (SUV). Adipose tissue parameters were compared with clinical and biochemical factors. Independent factors affecting adipose tissue volume were assessed. RESULTS: Both SAT and VAT volume showed strong positive correlation with most of cardiometabolic risk factors. Among them, lipid profiles, insulin and C-reactive protein (CRP) had more significant relationship with SUV of SAT than that of VAT. On the contrary, glucose, glycated hemoglobin, and degree of fatty liver showed more significant correlation with SUV of VAT. BMI, age, sex and CRP were independent predictors of SAT volume. BMI, age, triglyceride, CRP and fatty liver were independent variables predicting VAT volume. Adding SUV of adipose tissue improved the model performance. CONCLUSION: This study demonstrated that metabolic activities of SAT and VAT were differently correlated with risk factors, suggesting different biologic mechanism for obesity.

Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats.

In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM.

Development of porous PLGA/PEI1.8k biodegradable microspheres for the delivery of mesenchymal stem cells (MSCs).

Multipotent mesenchymal stem cells (MSCs) promise a therapeutic alternative for many debilitating and incurable diseases. However, one of the major limitations for the therapeutic application of human MSC (hMSC) is the lengthy ex vivo expansion time for preparing a sufficient amount of cells due to the low engraftment rate after transplantation. To solve this conundrum, a porous biodegradable polymeric microsphere was investigated as a potential scaffold for the delivery of MSCs. The modified water/oil/water (W1/O/W2) double emulsion solvent evaporation method was used for the construction of porous microspheres. PEI1.8k was blended with poly(lactic-co-glycolic acid) (PLGA) to enhance electrostatic cellular attachment to the microspheres. The porous PLGA/PEI1.8k (PPP) particles demonstrated an average particle size of 290µm and an average pore size of 14.3µm, providing a micro-carrier for the MSC delivery. PPP particles allowed for better attachment of rMSCs than non-porous PLGA/PEI1.8k (NPP) particles and non-porous (NP) and porous PLGA (PP) microspheres. rMSC successfully grew on the PPP particles for 2weeks in vitro. Next, PPP particles loaded with 3 different amounts of hMSC showed increased in vivo engraftment rates and maintained the stemness characteristics of hMSC compared with hMSCs-alone group in rats 2weeks after intramyocardial administration. These customized PPP particles for MSC delivery are a biodegradable and injectable scaffold that can be used for clinical applications.

Ghrelin receptor is activated by naringin and naringenin, constituents of a prokinetic agent Poncirus fructus.

ETHNOPHARMACOLOGICAL RELEVANCE: Poncirus fructus (PF), also known as a dried immature fruit of Poncirus trifoliata (L.) Raf. (Rutaceae), has long been traditionally used for the various gastrointestinal disorders in Eastern Asia. AIM OF STUDY: The aqueous extract of PF (PF-W) has the strong prokinetic effect, yet the underlying mechanism is still elusive. The present study investigated whether PF-W has any effect on motilin receptor or ghrelin receptor, since these receptors enhance intestinal motility when activated. MATERIALS AND METHODS: The effect of PF-W and its components on motilin or ghrelin receptor was determined by calcium imaging and whole-cell patch clamp methods. RESULTS: PF-W activates the ghrelin receptor, but not the motilin receptor, resulting in a transient increase of intracellular calcium levels. Furthermore, among various constituents of PF, only naringin and naringenin evoked the intracellular calcium augmentation via the ghrelin receptor. Moreover, cortistatin-8 - a ghrelin receptor inhibitor - specifically blocked naringin- and naringenin-induced calcium increases. In addition, naringin and naringenin induced inward currents in ghrelin receptor-expressing cells under whole-cell patch clamp configuration. CONCLUSION: PF-W activates the ghrelin receptor, and naringin and naringenin are key constituents responsible for the activation of ghrelin receptor. Therefore, the present study suggests that the ghrelin receptor is a molecular entity responsible for the strong prokinetic activity of PF-W.

Axonal neuropathy-associated TRPV4 regulates neurotrophic factor-derived axonal growth.

Spinal muscular atrophy and hereditary motor and sensory neuropathies are characterized by muscle weakness and atrophy caused by the degenerations of peripheral motor and sensory nerves. Recent advances in genetics have resulted in the identification of missense mutations in TRPV4 in patients with these hereditary neuropathies. Neurodegeneration caused by Ca(2+) overload due to the gain-of-function mutation of TRPV4 was suggested as the molecular mechanism for the neuropathies. Despite the importance of TRPV4 mutations in causing neuropathies, the precise role of TRPV4 in the sensory/motor neurons is unknown. Here, we report that TRPV4 mediates neurotrophic factor-derived neuritogenesis in developing peripheral neurons. TRPV4 was found to be highly expressed in sensory and spinal motor neurons in early development as well as in the adult, and the overexpression or chemical activation of TRPV4 was found to promote neuritogenesis in sensory neurons as well as PC12 cells, whereas its knockdown and pharmacologic inhibition had the opposite effect. More importantly, nerve growth factor or cAMP treatment up-regulated the expression of phospholipase A(2) and TRPV4. Neurotrophic factor-derived neuritogenesis appears to be regulated by the phospholipase A(2)-mediated TRPV4 pathway. These findings show that TRPV4 mediates neurotrophic factor-induced neuritogenesis in developing peripheral nerves. Because neurotrophic factors are essential for the maintenance of peripheral nerves, these findings suggest that aberrant TRPV4 activity may lead to some types of pathology of sensory and motor nerves.

Parameters to guide retreatment after initial intravenous immunoglobulin therapy in kawasaki disease.

BACKGROUND AND OBJECTIVES: We sought to determine parameters to guide the decision of retreatment in patients with Kawasaki disease (KD) who remained febrile after initial intravenous immunoglobulin (IVIG). SUBJECTS AND METHODS: A total of 129 children with KD were studied prospectively. Patients were treated with IVIG 2 to 9 days after the onset of disease. Laboratory measures, such as white blood cell (WBC), percentage of neutrophils, C-reactive protein (CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP), were determined before and 48 to 72 hours after IVIG treatment. Patients were classified into IVIG-responsive and IVIG-resistant groups, based on the response to IVIG. RESULTS: Of a total of 129 patients, 107 patients (83%) completely responded to a single IVIG therapy and only 22 patients (17%) required retreatment: 14 had persistent fever and 8 had recrudescent fever. There was no significant difference between the groups in age, gender distribution, and duration of fever to IVIG initiation, but coronary artery lesions developed significantly more often in the resistant group than in the responsive group (31.8% vs. 2.8%, p=0.000). Compared with pre-IVIG data, post-IVIG levels of WBC, percentage of neutrophils, CRP, and NT-proBNP decreased to within the normal range in the responsive group, whereas they remained high in the resistant group. Multivariate logistic regression indicated that neutrophil counts, CRP, and NT-proBNP were independent parameters of retreatment. CONCLUSION: Additional therapy at an early stage of the disease should be administered for febrile patients who have high values of CRP, NT-proBNP, and/or neutrophil counts after IVIG therapy.

The association between metabolic syndrome and prostate-specific antigen levels.

OBJECTIVES: Prostate-specific antigen (PSA) levels are affected by many factors. Metabolic syndrome (MS) is a common metabolic disorder related to the increasing prevalence of obesity. The relationship between MS and PSA is currently unknown, however. The aim of this study was to examine whether PSA levels were affected by MS. METHODS: We evaluated the association between MS and PSA in a group of 2007 men (aged 30 to 79 years) without prostate cancer who received a general health checkup. Men with abnormal digital rectal examination findings or PSA values higher than 3.0 ng/mL were considered abnormal and excluded from the study. MS was defined according to the modified National Cholesterol Education Program Third Adult Treatment Panel guidelines. Eligible men were classified according to the number of each component and the presence or absence of MS. RESULTS: PSA levels, as a whole, were inversely correlated with MS (P = 0.043). An increased number of MS components was significantly associated with linear decreasing trends of PSA levels (P-trend < 0.001). When a multivariate analysis was performed with age and each MS, age (P < 0.001), abdominal obesity (P = 0.001), and an impaired fasting glucose level (P = 0.047) were strongly associated with PSA levels. CONCLUSIONS: MS is associated with decreased PSA levels. When determining whether to perform prostate biopsy as part of early prostate cancer detection, MS should be considered as a factor associated with reduced PSA in men presenting with marginal PSA levels.