Comparison Between the Stereoscopic Virtual Reality Display System and Conventional Computed Tomography Workstation in the Diagnosis and Characterization of Cerebral Arteriovenous Malformations.

It is difficult to accurately understand the angioarchitecture of cerebral arteriovenous malformations (CAVMs) before surgery using existing imaging methods. This study aimed to evaluate the ability of the stereoscopic virtual reality display system (SVRDS) to display the angioarchitecture of CAVMs by comparing its accuracy with that of the conventional computed tomography workstation (CCTW). Nineteen patients with CAVM confirmed on digital subtraction angiography (DSA) or during surgery were studied. Computed tomography angiography images in the SVRDS and CCTW were retrospectively analyzed by two experienced neuroradiologists using a double-blind method. Angioarchitectural parameters, such as the location and size of the nidus, type and number of the arterial feeders and draining veins, and draining pattern of the vessels, were recorded and compared. The diameter of the nidus ranged from 1.1 to 9 cm. Both CCTW and SVRDS correctly diagnosed the location of the nidus in 19 patients with CAVM. Among the 19 patients, 35 arterial feeders and 25 draining veins were confirmed on DSA and during surgery. With the DSA and intraoperative results as the gold standard bases, the CCTW misjudged one arterial feeder and one draining vein and missed three arterial feeders and two draining veins; meanwhile, the SVRDS missed only two arterial feeders. SVRDS had some advantages in displaying nidus, arterial branches, and draining veins of the CAVM compared with CCTW, as well as SVRDS could more intuitively display the overall angio-architectural spatial picture of CAVM.

Effects of grape seed-derived proanthocyanidin B2 pretreatment on oxidative stress, endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells in renal ischemia-reperfusion injury model of mice.

PURPOSE: To investigate the effect of grape seed-derived proanthocyanidin B2 (GSPB2) pretreatment on acute renal ischemia-reperfusion injury model of mice. METHODS: 50 mice were divided into 5 groups: Sham group: mice were treated with right nephrectomy. GSPB2 group: GSPB2 was injected intraperitoneally 45 min before right nephrectomy. IRI group: right kidney was resected and the left renal arteriovenous vessel was blocked for 45 min. GSPB2 + IRI group: GSPB2 was intraperitoneally injected 45 min before IRI established. GSPB2 + BRU + IRI group: GSPB2 and brusatol (BRU) were injected intraperitoneally 45 min before IRI established. Creatinine and urea nitrogen of mice were detected, and the kidney morphology and pathological changes of each group were detected by HE staining, PAS staining and transmission electron microscopy. Expressions of Nrf2, HO-1, GRP78, CHOP, and cleaved-caspase3 were detected by immunofluorescence staining and western blotting. RESULTS: Morphology and mitochondrial damages of kidney in GSPB2 + IRI group were significantly alleviated than those in IRI group. Expression levels of Nrf2 and HO-1 were significantly higher in GSPB2 + IRI group than those in IRI group. Expression levels of GRP78, CHOP and cleaved-caspase3 were significantly lower in GSPB2 + IRI group than those in IRI group. However, compared to GSPB2 + IRI group, protective effects of GSPB2 pretreatment were weakened in GSPB2 + BRU + IRI group. CONCLUSIONS: GSPB2 pretreatment could alleviate oxidative stress damage and reduce apoptosis of renal tubular epithelial cells, which might be related to activating the antioxidant system, up-regulating the expression of Nrf2 and HO-1, inhibiting the expressions of GRP78, CHOP and cleaved-caspase3. However, the protective effect could be reversed by brusatol.

Putamen Structure and Function in Familial Risk for Depression: A Multimodal Imaging Study.

BACKGROUND: The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression. METHODS: The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N-acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively. RESULTS: After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, ß-left = -0.17, ß-right = -0.15, ps = .002), N-acetylaspartate/creatine ratio (ß-left= -0.40, ß-right= -0.37, ps < .0001), and activation modulated by valence (ß-left = -0.22, ß-right = -0.27, ps < .05) than low-risk individuals. Volume differences were greater at younger ages, and N-acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (ß-left = -0.72, p = .013; ß-right = -0.83, p = .037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 ≤ r ≤ 0.33). CONCLUSIONS: Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them.

Construction of Glycolytic Regulator Gene Signature to Predict the Prognosis and Tumor Immune Cell Infiltration Levels for Prostate Cancer.

Prostate cancer (PCa) is the commonly generated noncutaneous neoplasm among men worldwide. Glycolysis had been validated to promote cancer progression. However, the clinical significance of glycolytic regulators in PCa was not well understood. Here, we discovered that glycolytic regulators were dysregulated in PCa samples using GSE8511, GSE6919, and GEPIA. By detecting the expression of these regulators in PCa samples, we found that SLC2A1, SLC2A3, HK2, PFKFB2, TPI1, PKM2, and LDHA had higher expression in PCa compared with normal tissues. Moreover, both higher expression of TPI1, ALDOA, ENO1, LDHA, and PKM and lower expression of LDHB and HK2 were significantly related to shorter progression-free survival time in PCa. Of note, an 8 gene-based risk score was further constructed and confirmed to have a good performance in predicting progression-free survival (PFS) time in PCa. The signature risk score significantly correlated with NK cell, neutrophil cell, macrophage M2 cell, and myeloid dendritic cell infiltration levels in PCa. After bioinformatics analysis, our data suggested glycolytic regulators participated in the regulation of multiple nonmetabolic biological processes, such as RNA transport, biosynthesis of antibiotics, and cell cycle. We recapitulate that the glycolytic regulator signature was a prospective indicator for prognosis and immune cell infiltration levels in PCa.

High Expression of SLC16A1 as a Biomarker to Predict Poor Prognosis of Urological Cancers.

OBJECTIVE: Tumor metabolism has always been the focus of cancer research. SLC16A1, as a key factor in catalysis of monocarboxylate transport across the plasma membrane, has been found to be associated with the occurrence and metastasis of a variety of cancers, but its prognostic significance and mechanism in different tumors are still unclear. METHODS: Based on the gene expression matrix and clinical information of human cancer tissues acquired from TCGA and GTEX databases, the differential expression of SLC16A1 in different tumors and normal tissues was analyzed. To confirm the association between its expression, the mutation of MMRS gene, and the expression level of DNMTs. Univariate Cox regression was applied to analyze the association between SLC16A1 expression and patient prognosis. The effect of SLC16A1 expression on patient survival was examined by Kaplan Meier analysis. GSEA was used to identify related signaling pathways. RESULTS: The expression of SLC16A1 was differentially expressed in most tumors, especially in the urinary tract where it is commonly highly expressed, and differential expression of SLC16A1 in different clinical stages. SLC16A1 expression was significantly positively correlated with MMRS gene mutation and DNMTS expression. Moreover, high SLC16A1 expression was associated with poorer overall survival (OS) and progression-free survival (PFS) in urological cancers. In particular, the results of the enrichment analysis showed that SLC16A1 was associated with processes such as cell adhesion and many signaling pathways affecting cell cycle were significantly enriched in the group with high-expressed SLC16A1. CONCLUSION: SLC16A1 expression was upregulated in urological cancer. SLC16A1 may promote tumor development by regulating the epigenetic process of urological cancer and demonstrated a great potential as a prognostic biomarker of urological cancer patients.

Combined T2 SPAIR, Dynamic Enhancement and DW Imaging Reliably Detect T Staging and Grading of Bladder Cancer With 3.0T MRI.

OBJECTIVES: To evaluate bladder cancer by integrating multiple imaging features acquired using multimodal 3.0T magnetic resonance imaging (MRI). METHODS: We prospectively enrolled 163 consecutive patients including 142 men (mean age, 65.2 years) and 21 women (mean age, 65.8 years). We evaluated the efficiency and reliability of the multiple imaging modalities including T2-weighted spectral attenuated inversion recovery (SPAIR) imaging, dynamic contrast-enhanced (DCE) imaging and diffusion-weighted (DW) imaging, and the imaging feature, apparent diffusion coefficient (ADC) in the identification of the T staging and grading. We compared our imaging findings with the results of histological examination using McNemar's test. We reported the results under the significance of p < 0.05. Approval for the study was obtained from the local institutional review board. RESULTS: The sensitivity and specificity using T2 SPAIR plus DW imaging (sensitivity: 85.2%; specificity: 93.2%), DCE plus DW imaging (sensitivity: 92.4%; specificity: 96.8%), and all the three imaging modalities combined, i.e., T2 SPAIR plus DCE plus DW imaging (sensitivity: 92.5%; specificity: 97.4%), were significantly greater than using T2 SPAIR imaging alone (sensitivity: 74.1%; specificity: 72.2%). One hundred six (93.0%) lesions showed a thin, pedicle arch-like shape and thus primarily demonstrated to be in Ta stage; by contrast, a large number of lesions (137 [85.6%]) were sessile and were found to be in T1 stage. The differences in the ADC were significant between low-grade (877.57 ± 24.15) and high-grade (699.54 ± 23.82) lesions (P < .01). CONCLUSIONS: T2 SPAIR and DCE plus DW imaging provided useful information for evaluating T staging and grading in bladder cancer. Those imaging features to distinguish Ta stage from T1 stage were presented.

Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia reperfusion in mice.

PURPOSE: To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR). METHODS: Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot. RESULTS: Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B. CONCLUSION: GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.

Precise pulmonary scanning and reducing medical radiation exposure by developing a clinically applicable intelligent CT system: Toward improving patient care.

BACKGROUND: Interstitial lung disease requires frequent re-examination, which directly causes excessive cumulative radiation exposure. To date, AI has not been applied to CT for enhancing clinical care; thus, we hypothesize AI may empower CT with intelligence to realize automatic and accurate pulmonary scanning, thus dramatically decrease medical radiation exposure without compromising patient care. METHODS: Facial boundary detection was realized by recognizing adjacent jaw position through training and testing a region proposal network (RPN) on 76,882 human faces using a preinstalled 2-dimensional camera; the lung-fields was then segmented by V-Net on another training set with 314 subjects and calculated the moving distance of the scanning couch based on a pre-generated calibration table. A multi-cohort study, including 1,186 patients was used for validation and radiation dose quantification under three clinical scenarios. FINDINGS: A U-HAPPY (United imaging Human Automatic Planbox for PulmonarY) scanning CT was designed. Error distance of RPN was 4·46±0·02 pixels with a success rate of 98·7% in training set and 2·23±0·10 pixels with 100% success rate in testing set. Average Dice's coefficient was 0·99 in training set and 0·96 in testing set. A calibration table with 1,344,000 matches was generated to support the linkage between camera and scanner. This real-time automation makes an accurate plan-box to cover exact location and area needed to scan, thus reducing amounts of radiation exposures significantly (all, P<0·001). INTERPRETATION: U-HAPPY CT designed for pulmonary imaging acquisition standardization is promising for reducing patient risk and optimizing public health expenditures. FUNDING: The National Natural Science Foundation of China.

Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia reperfusion in mice

Abstract Purpose To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR). Methods Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot. Results Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B. Conclusion GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.

Effect of ozone oxidative preconditioning on inflammation and oxidative stress injury in rat model of renal transplantation.

PURPOSE: To investigate the effect of ozone oxidative preconditioning (OzoneOP) on inflammation and oxidative stress injury in rat model of renal transplantation. METHODS: Thirty six male Sprague Dawley (SD) rats were randomly divided into three groups. Sham group: rats were treated with opening and closing abdomen. Kidney transplantation group (KT group): SD rat received the donor's left kidney derived from another SD rat. Ozone oxidative preconditioning and kidney transplantation (OOP+KT group): donor SD rats received OzoneOP treatments by transrectal insufflations before kidney transplantation. After transplantation, parameters of renal function of recipients were determined. Morphology and pathological changes of renal allograft were examined. Expression of NF-κBp65, HMGB-1 were also determined by Western-blot. RESULTS: Compared to KT group, the morphology and pathological damages of renal allograft were less serious in OOP+KT group. Meanwhile, levels of SOD and GSH-Px of renal allograft in OOP+KT group were higher than those in KT group respectively. Western-blot showed that the expressions of NF-κBp65 and HMGB-1 in OOP+KT group were obviously less than those in KT group. CONCLUSION: Ozone oxidative preconditioning could attenuate the inflammatory reaction and oxidative stress injury in renal allograft, which might be related with the enhancement of anti-oxidative system and suppression of inflammatory reaction.

Effect of ozone oxidative preconditioning on inflammation and oxidative stress injury in rat model of renal transplantation

Abstract Purpose: To investigate the effect of ozone oxidative preconditioning (OzoneOP) on inflammation and oxidative stress injury in rat model of renal transplantation. Methods: Thirty six male Sprague Dawley (SD) rats were randomly divided into three groups. Sham group: rats were treated with opening and closing abdomen. Kidney transplantation group (KT group): SD rat received the donor's left kidney derived from another SD rat. Ozone oxidative preconditioning and kidney transplantation (OOP+KT group): donor SD rats received OzoneOP treatments by transrectal insufflations before kidney transplantation. After transplantation, parameters of renal function of recipients were determined. Morphology and pathological changes of renal allograft were examined. Expression of NF-κBp65, HMGB-1 were also determined by Western-blot. Results: Compared to KT group, the morphology and pathological damages of renal allograft were less serious in OOP+KT group. Meanwhile, levels of SOD and GSH-Px of renal allograft in OOP+KT group were higher than those in KT group respectively. Western-blot showed that the expressions of NF-κBp65 and HMGB-1 in OOP+KT group were obviously less than those in KT group. Conclusion: Ozone oxidative preconditioning could attenuate the inflammatory reaction and oxidative stress injury in renal allograft, which might be related with the enhancement of anti-oxidative system and suppression of inflammatory reaction.

Multivariate Deep Learning Classification of Alzheimer's Disease Based on Hierarchical Partner Matching Independent Component Analysis.

Machine learning and pattern recognition have been widely investigated in order to look for the biomarkers of Alzheimer's disease (AD). However, most existing methods extract features by seed-based correlation, which not only requires prior information but also ignores the relationship between resting state functional magnetic resonance imaging (rs-fMRI) voxels. In this study, we proposed a deep learning classification framework with multivariate data-driven based feature extraction for automatic diagnosis of AD. Specifically, a three-level hierarchical partner matching independent components analysis (3LHPM-ICA) approach was proposed first in order to address the issues in spatial individual ICA, including the uncertainty of the numbers of components, the randomness of initial values, and the correspondence of ICs of multiple subjects, resulting in stable and reliable ICs which were applied as the intrinsic brain functional connectivity (FC) features. Second, Granger causality (GC) was utilized to infer directional interaction between the ICs that were identified by the 3LHPM-ICA method and extract the effective connectivity features. Finally, a deep learning classification framework was developed to distinguish AD from controls by fusing the functional and effective connectivities. A resting state fMRI dataset containing 34 AD patients and 34 normal controls (NCs) was applied to the multivariate deep learning platform, leading to a classification accuracy of 95.59%, with a sensitivity of 97.06% and a specificity of 94.12% with leave-one-out cross validation (LOOCV). The experimental results demonstrated that the measures of neural connectivities of ICA and GC followed by deep learning classification represented the most powerful methods of distinguishing AD clinical data from NCs, and these aberrant brain connectivities might serve as robust brain biomarkers for AD. This approach also allows for expansion of the methodology to classify other psychiatric disorders.

Verbal-spatial IQ discrepancies impact brain activation associated with the resolution of cognitive conflict in children and adolescents.

Verbal-spatial discrepancies are common in healthy individuals and in those with neurodevelopmental disorders associated with cognitive control deficits including: Autism Spectrum Disorder, Non-Verbal Learning Disability, Fragile X, 22q11 deletion, and Turner Syndrome. Previous data from healthy individuals suggest that the magnitude of the difference between verbal IQ (VIQ) and performance IQ (PIQ) scores (the VIQ>PIQ discrepancy) is associated with reduced thickness in frontal and parietal cortices (inferior frontal, anterior cingulate, inferior parietal lobule, and supramarginal gyrus) that support cognitive control. Unknown is whether the VIQ>PIQ discrepancy is associated with functional deficits in these areas in healthy or ill children and adolescents. We assessed the effects of the VIQ>PIQ discrepancy on fMRI BOLD response during the resolution of cognitive conflict in 55 healthy children and adolescents during performance of a Simon Spatial Incompatibility task. As the magnitude of the VIQ>PIQ discrepancy increased, activation of fronto-striatal, limbic, and temporal regions decreased during conflict resolution (p < .05, corrected). In exploratory analyses, the VIQ>PIQ discrepancy was associated with reduced functional connectivity from right inferior frontal gyrus to right thalamus and increased functional connectivity to right supramarginal gyrus (ps < .03, uncorrected). The VIQ>PIQ discrepancy may be an important aspect of an individual's cognitive profile and likely contributes to, or is associated with, deficient cognitive control processes characteristic of many childhood disorders.

Effects of apigenin on the expression levels of B-cell lymphoma-2, Fas and Fas ligand in renal ischemia-reperfusion injury in rats.

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo. Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro. Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro. In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats.

Overexpression of Pleomorphic Adenoma Gene-Like 2 Is a Novel Poor Prognostic Marker of Prostate Cancer.

Pleomorphic adenoma gene like-2 (PLAGL2) is a member of the PLAG gene family. Previous studies have revealed that overexpression of PLAGL2 is associated with many human cancers. However, it has been reported that PLAGL2 also plays as a tumor suppressor. The precise role of PLAGL2 in prostate cancer (PCa) is still unknown. The aim of this study was to investigate the expression and prognostic value of PLAGL2 in PCa. Data from microarray datasets demonstrated that the DNA copy number and mRNA level of PLAGL2 were significantly increased in PCa compared with normal prostate. qRT-PCR and western blot analysis from paired PCa samples and prostate cell lines confirmed upregulated mRNA and protein expression levels in PCa. Immunohistochemistry analysis showed that staining of PLAGL2 in PCa tissues was significantly higher than that in benign prostatic hyperplasia (BPH) tissues. In addition, the high expression of PLAGL2 was only involved in preoperative PSA, but was not related to age, Gleason score, seminal vesicle invasion, surgical margin status, clinical stage and positive lymph node metastasis. Moreover, our results showed that PLAGL2 was an independent prognostic factor for biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients, and overexpressed PLAGL2 was related to early development of BCR and poor OS. In conclusion, our findings suggest that PLAGL2 is overexpressed in PCa. The increased expression of PLAGL2 correlates to PCa progression following radical prostatectomy and may serve as a novel poor prognostic marker for PCa.

Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model.

PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.

Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model

ABSTRACT PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.

Ozone therapy ameliorates tubulointerstitial inflammation by regulating TLR4 in adenine-induced CKD rats.

Tubulointerstitium inflammation is a common pathway aggravating chronic kidney disease (CKD) progression and the mechanism is partly associated with excessive activation of toll-like receptor 4 (TLR4) in tubulointerstitium. Ozone therapy is demonstrated to alleviate inflammation in some experiments. The aim of this study is to examine whether ozone therapy could ameliorate chronic tubulointerstitium inflammation by suppressing TLR4 in adenine-induced CKD rats. Sprague-Dawley rats were fed with 0.75% adenine-containing diet to induce CKD and tubulointerstitium inflammation injury. Ozone therapy (1.1 mg/kg) was simultaneously administrated by rectal insufflations (i.r.). After 4 weeks, serum and kidney samples were collected for detection. Renal function and systemic electrolyte were detected. Renal pathological changes were assessed by hematoxylin-eosin (H&E) staining and Masson trichrome (MT) staining. Immunohistochemistry, Western blot and Real-time PCR were applied to evaluate tubulointerstitium inflammation as well as the expression of TLR4 and phosphorylated nuclear factor kappa B P65 (p-NF-κB P65) in rats. The results showed ozone therapy improved serious renal insufficiency, systemic electrolyte disorder and tubulointerstitium morphology damages in adenine-induced CKD rats. In addition, ozone therapy suppressed excessive activation of TLR4 and p-NF-κB P65 in the tubulointerstitium of adenine-induced CKD rats, accompanied by the reduction of inflammation-related cytokines including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). The protein expression of TLR4 was positively correlated with the protein expression levels of MCP-1 (r = 0.7863, p < 0.01) and TNF-α (r = 0.7547, p < 0.01) in CKD rats. These findings indicated ozone therapy could attenuate tubulointerstitium inflammation injury in adenine-induced CKD rats and the mechanism might associate with the mediation of TLR4.

Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression of prostate cancer in vivo.

Recently, lysine-specific demethylase 1 (LSD1) was identified as the first histone demethylase. LSD1 interacted with androgen receptor (AR) and promoted androgen-dependent transcription of target genes, such as PSA, by ligand-induced demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9). Meanwhile, the phenomenon of epithelial-mesenchymal transition (EMT) had received considerable attention in tumor recurrence and metastasis. This study examined the effect of Pargyline (an inhibitor of LSD1) on the process of EMT in vitro and in vivo. SCID mice were injected subcutaneously with LNCap cells. Pargyline was given intraperitoneally or not after castration (implemented with Bilateral orchidectomy), then PSA levels in serum and tumor were determined to assess time to androgen-independent progression. The results showed that LSD1 expression was up-regulated when PCa progressed to Castration Resistant Prostate Cancer (CRPC). Pargyline reduced LNCap cells migration and invasion ability, and inhibited the process of EMT by up-regulating expression of E-cadherin, and down-regulating expressions of N-cadherin and Vimentin in vitro and in vivo. Although, Pargyline did not change the level of AR, it reduced PSA expression both in vitro and in vivo. Furthermore, Pargyline delayed prostate cancer transition from androgen-dependent to androgen-independent state (CRPC). These findings indicated that inhibition of LSD1 might be a promise adjunctive therapy with androgen deprivation therapy (ADT) for locally advanced or metastatic prostate cancer.

Metformin attenuated the inflammation after renal ischemia/reperfusion and suppressed apoptosis of renal tubular epithelial cell in rats.

PURPOSE: To investigate the effect of metformin on renal tubular epithelial cell apoptosis and inflammation after kidney ischemia/ reperfusion in rats. METHODS: Eighteen SD rats were randomly divided into three groups: Sham (S), Ischemia/reperfusion (I/R), and Metformin (E). Before establishing the I/R model, group E was administered metformin for three days, while groups S and I/R were administered equal volumes of saline. After three days, a right nephrectomy was performed on all groups, after which the left kidneys of groups E and I/R rats were subjected to 45 min renal ischemia. Renal function, histology, and cell apoptosis were assessed. AMPK, pAMPK, COX-2, and Caspase 3 were also detected. RESULTS: Compared to I/R group, Caspase 3 and COX-2 levels were decreased in group E. COX-2, Caspase3 and pAMPK levels were higher in groups E and I/R than in group S. The pAMPK level of group E was higher than that of I/R group, while COX-2 and caspase 3 were lower in group E than they were in the other groups. There was no significant difference between E and I/R groups in AMPK levels. CONCLUSION: Metformin preconditioning attenuated the inflammation caused by ischemia/reperfusion and inhibited the apoptosis of renal tubular epithelial cells.