Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further ...validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test.
< .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively;
< .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively;
= .71) and version 2005 (weighted κ = 0.54 vs 0.46;
< .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% 92 of 111 vs 68% 75 of 111, respectively;
< .001), without any difference in sensitivity (89% 85 of 96 vs 84% 81 of 96;
= .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license.
See also the editorial by Choyke in this issue.
Of all of the strategies for controlling reverse osmosis (RO) membrane fouling, chemical cleaning is indispensable. To study the effects of chemical cleaning on membrane foulant removal, a ...comparative analysis of RO membranes before and after common alkaline and acid cleaning was conducted by dissecting lead and terminal RO membranes in a full-scale municipal wastewater reclamation plant. Most foulants on the membranes were removed by chemical cleaning processes. Calcium was the major inorganic component of the foulants because of its highest concentration in the feed water. Aluminum and iron were also abundant elements on the membranes due to their high deposition ratios and low removal efficiencies. Hydrophilic neutrals (HIN) and hydrophobic neutrals (HON) were the two largest dissolved organic matter (DOM) fractions on the membranes before cleaning. HIN and hydrophilic acids (HIA) were not effectively removed. Chemical cleaning removed 94% and 90% of the total bacteria on the lead and tail membranes and considerably changed the structure of the microbial communities. Bacteria excessively producing extracellular polymeric substance (EPS), such as Pseudomonas and Zoogloea, were much more resistant to the chemical cleaning process. After cleaning, the membrane microbial community structures were more similar to those in the feed water than the structures on the membranes before cleaning. These results shed light on the effects of cleaning in a full-scale RO plant, improves our understanding of the removal of foulants and provides potential research directions for cleaning methods and RO pretreatment processes.
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•Chemical cleaning effects were analyzed by autopsy from a full-scale RO plant.•Al and Fe had high deposition ratios and low removal efficiencies by the cleaning.•Hydrophilic neutral and hydrophilic acids had strong resistance to the cleaning.•Chemical cleaning process considerably changed the microbial communities.•Bacteria with excessive EPS production were more resistant to the cleaning process.
Hydrogen sulfide (H
S) is previously described as a potentially lethal toxic gas. However, this gasotransmitter is also endogenously generated by the actions of cystathionine-β-synthase (CBS), ...cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in mammalian systems, thus belonging to the family of gasotransmitters after nitric oxide (NO) and carbon monoxide (CO). The physiological or pathological significance of H
S has been extensively expanded for decades. Growing evidence has revealed that H
S exerts cytoprotective functions in the cardiovascular, nervous, and gastrointestinal systems by modulating numerous signaling pathways. With the continuous advancement of microarray and next-generation sequencing technologies, noncoding RNAs (ncRNAs) have gained recognition as key players in human health and diseases due to their considerable potential as predictive biomarkers and therapeutic targets. Coincidentally, H
S and ncRNAs are not independent regulators but interact with each other during the development and progression of human diseases. Specifically, ncRNAs might serve as downstream mediators of H
S or act on H
S-generating enzymes to govern endogenous H
S production. The purpose of this review is to summarize the interactive regulatory roles of H
S and ncRNAs in the initiation and development of various diseases and explore their potential health and therapeutic benefits. This review will also highlight the importance of cross talk between H
S and ncRNAs in disease therapy.
MicroRNAs (miRNAs) are a novel class of small non-coding RNAs that negatively regulate gene expression at the posttranscriptional level by binding to the 3′ untranslated region of target mRNAs ...leading to their translational inhibition or sometimes degradation. We uncovered a previously unknown alteration in temporal expression of a large set of miRNAs following a contusive spinal cord injury (SCI) in adult rats using microarray analysis. These altered miRNAs can be classified into 3 categories: (1) up-regulation, (2) down-regulation and (3) an early up-regulation at 4 h followed by down-regulation at 1 and 7 days post-SCI. The bioinformatics analysis indicates that the potential targets for miRNAs altered after SCI include genes encoding components that are involved in the inflammation, oxidation, and apoptosis that are known to play important roles in the pathogenesis of SCI. These findings suggest that abnormal expression of miRNAs may contribute to the pathogenesis of SCI and are potential targets for therapeutic interventions following SCI.
Objective
The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the ...pathogenesis of spinal cord injury (SCI).
Methods
A combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice.
Results
SCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI‐induced cPLA2 activation was mediated by the extracellular signal‐regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide‐1‐phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI.
Interpretation
cPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI. ANN NEUROL 2014;75:644–658
Phenotypic switch of vascular smooth muscle cells (VSMCs) is characterized by increased expressions of VSMC synthetic markers and decreased levels of VSMC contractile markers, which is an important ...step for VSMC proliferation and migration during the development and progression of cardiovascular diseases including atherosclerosis. Chicoric acid (CA) is identified to exert powerful cardiovascular protective effects. However, little is known about the effects of CA on VSMC biology. Herein, in cultured VSMCs, we showed that pretreatment with CA dose-dependently suppressed platelet-derived growth factor type BB (PDGF-BB)-induced VSMC phenotypic alteration, proliferation and migration. Mechanistically, PDGF-BB-treated VSMCs exhibited higher mammalian target of rapamycin (mTOR) and P70S6K phosphorylation, which was attenuated by CA pretreatment, diphenyleneiodonium chloride (DPI), reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) and nuclear factor-κB (NFκB) inhibitor Bay117082. PDGF-BB-triggered ROS production and p65-NFκB activation were inhibited by CA. In addition, both NAC and DPI abolished PDGF-BB-evoked p65-NFκB nuclear translocation, phosphorylation and degradation of Inhibitor κBα (IκBα). Of note, blockade of ROS/NFκB/mTOR/P70S6K signaling cascade prevented PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration. CA treatment prevented intimal hyperplasia and vascular remodeling in rat models of carotid artery ligation in vivo. These results suggest that CA impedes PDGF-BB-induced VSMC phenotypic switching, proliferation, migration and neointima formation via inhibition of ROS/NFκB/mTOR/P70S6K signaling cascade.
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•Chicoric acid attenuated PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration.•Chicoric acid antagonized the activated ROS/NFκB/mTOR/P70S6K signaling pathway in VSMCs.•Chicoric acid treatment prevented intimal hyperplasia in rat models of carotid artery ligation.
Although clinically approved hepatitis B virus (HBV) polymerase inhibitors (lamivudine‐3TC, entecavir, etc.) serve as effective therapeutics, the virus can easily generate resistance to them. ...Therefore, the treatment of HBV infection remains a public health problem. Numerous studies have shown that natural products have prospective anti‐HBV activity. The purpose of this study was to isolate and extract des(rhamnosyl) verbascoside from Lindernia ruellioides (Colsm.) Pennell and explore its anti‐HBV and hepatoprotective effects. Anti‐HBV activity was evaluated in HepG2.2.15 cells, a human hepatocellular carcinoma cell line with HBV‐stable infection, and its protective effect was evaluated in HL‐7702 cells, a normal human liver cell line. HepG2.2.15 cells maintained normal growth morphology within the selected concentration range of des(rhamnosyl) verbascoside. It also inhibited the expression of HBV antigens and HBV DNA in a dose‐ and time‐dependent manner in vitro. Further, western blot experiments showed that it could downregulate HBV X protein (HBx) expression in a dose‐dependent manner. In the H2O2‐induced hepatocyte injury model, the cell‐survival rate of the HL‐7702 cells with the highest drug dose reached 85.25%, which was significantly improved compared with that of the model group. Most of the cells returned to normal morphology, showing polygonal or fusiform structures. Thus, it may be stated that des(rhamnosyl) verbascoside exhibits anti‐HBV activity and hepatoprotective effects in vitro and may exert an anti‐HBV effect via antigen inhibition, HBV DNA secretion, and HBx protein expression.
Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic ...biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.
The phenotypic transformation from differentiated to dedifferentiated vascular smooth muscle cells (VSMCs) plays a crucial role in VSMC proliferation and vascular remodeling in many cardiovascular ...diseases including hypertension. Nesfatin-1, a multifunctional adipocytokine, is critically involved in the regulation of blood pressure. However, it is still largely unexplored whether nesfatin-1 is a potential candidate in VSMC phenotypic switch and proliferation in hypertension. Experiments were carried out in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), human VSMCs and primary rat aortic VSMCs. We showed that the expression of nesfatin-1 was upregulated in media layer of the aorta in SHR and SHR-derived VSMCs. Nesfatin-1 promoted VSMC phenotypic transformation, accelerated cell cycle progression and proliferation. Knockdown of nesfatin-1 inhibited the VSMC phenotype switch from a contractile to a synthetic state, attenuated cell cycle progression and retarded VSMC proliferation in SHR-derived VSMCs. Moreover, nesfatin-1-activated PI3K/Akt/mTOR signaling was abolished by JAK/STAT inhibitor WP1066, and the increased phosphorylation levels of JAK2/STAT3 in response to nesfatin-1 were suppressed by inhibition of PI3K/Akt/mTOR in VSMCs. Pharmacological blockade of the forming feedback loop between PI3K/Akt/mTOR and JAK2/STAT3 prevented the proliferation of nesfatin-1-incubated VSMCs and primary VSMCs from SHR. Chronic intraperitoneal injection of nesfatin-1 caused severe hypertension and cardiovascular remodeling in normal rats. In contrast, silencing of nesfatin-1 gene ameliorated hypertension, phenotype switching, and vascular remodeling in the aorta of SHR. Therefore, our data identified nesfatin-1 as a key modulator in hypertension and vascular remodeling by facilitating VSMC phenotypic switching and proliferation.
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•Nesfatin-1 promoted VSMC phenotypic transformation, cell cycle progression and proliferation.•PI3K/Akt/mTOR and JAK2/STAT formed a mutual transactivation loop in VSMCs response to nesfatin-1.•Chronic peripheral nesfatin-1 administration caused severe hypertension and cardiovascular remodeling in rats.•Silencing of nesfatin-1 gene ameliorated hypertension, phenotype switching, and vascular remodeling in the aorta of SHR.
Spinal cord injury (SCI) is devastating, causing sensorimotor impairments and paralysis. Persisting functional limitations on physical activity negatively affect overall health in individuals with ...SCI. Physical training may improve motor function by affecting cellular and molecular responses of motor pathways in the central nervous system (CNS) after SCI. Although motoneurons form the final common path for motor output from the CNS, little is known concerning the effect of exercise training on spared motoneurons below the level of injury. Here we examined the effect of treadmill training on morphological, trophic, and synaptic changes in the lumbar motoneuron pool and on behavior recovery after a moderate contusive SCI inflicted at the 9th thoracic vertebral level (T9) using an Infinite Horizon (IH, 200 kDyne) impactor. We found that treadmill training significantly improved locomotor function, assessed by Basso–Beattie–Bresnahan (BBB) locomotor rating scale, and reduced foot drops, assessed by grid walking performance, as compared with non-training. Additionally, treadmill training significantly increased the total neurite length per lumbar motoneuron innervating the soleus and tibialis anterior muscles of the hindlimbs as compared to non-training. Moreover, treadmill training significantly increased the expression of a neurotrophin brain-derived neurotrophic factor (BDNF) in the lumbar motoneurons as compared to non-training. Finally, treadmill training significantly increased synaptic density, identified by synaptophysin immunoreactivity, in the lumbar motoneuron pool as compared to non-training. However, the density of serotonergic terminals in the same regions did not show a significant difference between treadmill training and non-training. Thus, our study provides a biological basis for exercise training as an effective medical practice to improve recovery after SCI. Such an effect may be mediated by synaptic plasticity, and neurotrophic modification in the spared lumbar motoneuron pool caudal to a thoracic contusive SCI.
•Treadmill training promoted dendritic plasticity of motoneurons of antagonist hindlimb muscles.•Treadmill training increased expression of BDNF in lumbar motoneurons following SCI.•Treadmill training increased synapse density in the lumbar motoneuron pool following SCI.•Treadmill training improved motor functional recovery.
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