HLA B eplet mismatches in the context of delayed graft function and low tacrolimus trough levels are risk factors influencing the generation of de novo donor-specific antibodies and acute rejection in the early stage after kidney transplantation.

BACKGROUND: De novo donor-specific antibody (dnDSA) generation and acute rejection (AR) are the main factors affecting long-term graft survival. This study aims to investigate human leukocyte antigen (HLA) eplet mismatching (MM), delayed graft function (DGF), and tacrolimus (TAC) trough levels on the occurrence of dnDSA and AR in the early stages after kidney transplantation (KT). METHODS: This retrospective study included 526 cases of deceased donation KT. The effects of DGF, HLA eplet MM, and TAC trough levels on dnDSA and AR occurrence were analyzed with logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed the independent risk factor of dnDSA generation was HLA B eplet MM (OR: 1.201, 95% CI: 1.007-1.431, P = 0.041). The independent risk factors of AR occurrence include DGF (OR: 4.045, 95% CI: 1.047-15.626, P = 0.043), HLA B eplet MM (OR: 1.090, 95% CI: 1.000-1.187, P = 0.050), and TAC trough levels at 12 months (OR: 0.750, 95% CI: 565-0.997, P = 0.048). HLA B eplet MM combined with DGF and TAC trough levels at 12 months increased the predictive value of dnDSA (AUC 0.735) and AR (AUC 0.730) occurrence. HLA B eplet MM > 9 and TAC trough levels below 5.95 ng/mL at 12 months could increase the risk of early AR occurrence. CONCLUSIONS: HLA B eplet MM, DGF, and TAC trough levels at 12 months after KT could affect the occurrence of dnDSA and AR in the early stage of KT.

Y-box protein-1 modulates circSPECC1 to promote glioma tumorigenesis via miR-615-5p/HIP1/AKT axis.

Y-box binding protein-1 (YB-1) is upregulated in glioma and plays an important role in its occurrence and drug resistance. However, the involved regulatory processes and downstream pathways are still unclear. Since various circular RNAs (circRNAs) and microRNAs (miRNAs) also play roles in the pathogenesis of glioma, we hypothesize that YB-1 may exert its function through a circRNA-miRNA-protein interaction network. In this study, we use the RNA binding protein immunoprecipitation assay and quantitative reverse transcription polymerase chain reaction to determine the circRNAs involved in the regulation of YB-1 and further elucidate their biological functions. The level of circSPECC1 (hsa_circ_0000745) modulated by YB-1 is significantly upregulated in the U251 and U87 glioma cell lines. Downregulation of circSPECC1 markedly inhibits the proliferation and invasiveness of U251 and U87 cells by inducing apoptosis. Bioinformatics analysis reveals that miR-615-5p could interact with circSPECC1 and huntingtin-interacting protein-1 (HIP-1). Then we determine the interactions between miR-615-5p, circSPECC1, and HIP1 using dual luciferase reporter system and pull-down assays. Mechanistic analysis indicates that the downregulation of circSPECC1 results in a decreased HIP1 expression. This study demonstrates that circSPECC1 modulated by YB-1 is increased in glioma cell lines. In addition, circSPECC1 promotes glioma growth through the upregulation of HIP1 by sponging miR-615-5p and targeting the HIP1/AKT pathway. This indicates that YB-1 and circSPECC1 may both be promising targets for glioma treatment.

Dynamic contrast-enhanced MRI perfusion parameters are imaging biomarkers for angiogenesis in lung cancer.

BACKGROUND: Quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may have the potential to reflect angiogenesis and proliferation of pulmonary neoplasms. PURPOSE: To verify whether DCE-MRI can identify pulmonary neoplasm property and evaluate the correlation of DCE-MRI perfusion parameters with microvessel density (MVD) and Ki-67 in lung cancer. MATERIAL AND METHODS: This study enrolled 65 patients with one pulmonary neoplasm who underwent computed tomography-guided percutaneous lung biopsy with pathological diagnosis (43 malignant, 22 benign; mean age = 59.71 ± 11.72 years). All patients did DCE-MRI before biopsy. Quantitative MRI parameters including endothelial transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space (EES) volume (Ve) were calculated by extended Tofts linear model. MVD was evaluated by CD34-expressing tumor vessels. Proliferation was assessed by Ki-67 staining. The correlations of parameters with MVD and Ki-67 expression were analyzed. RESULTS: Ktrans and Kep values were significantly increased in malignant lesions compared to benign lesions (P = 0.001 and 0.022, respectively), whereas no statistical difference in Ve was found. The CD34 expression was positively correlated to Ktrans (r = 0.608; P = 0.004) and Kep (r = 0.556; P = 0.001). Subsequent subtype analyses also showed positive correlations of Ktrans and Kep with MVD in adenocarcinoma group (r = 0.550 and 0.563; P = 0.012 and 0.015, respectively). No significant correlation was found between these parameters and Ki-67. CONCLUSION: Ktrans and Kep may distinguish benign and malignant pulmonary neoplasm. Ktrans and Kep, with their positive correlation to MVD, can be used as non-invasive parameters reflecting lung cancer angiogenesis.

Chicken interferon-induced transmembrane protein 1 promotes replication of coronavirus infectious bronchitis virus in a cell-specific manner.

Interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral proteins that inhibit numerous virus infections by impeding viral entry into target cells. However, increasing evidence suggests diverse functions of IFITMs in virus infection, especially with the coronavirus. We analyzed the effect of chicken interferon-induced transmembrane proteins (chIFITMs) on coronavirus infectious bronchitis virus (IBV) infection in vitro. We demonstrated that the antiviral effects of IFITMs are dependent on cell and virus types. The overexpression of chIFITM1 dramatically promoted the replication of IBV Beaudette strain in the chicken hepatocellular carcinoma cell line, LMH. Mechanistically, chIFITMs share roughly the same subcellular localization in different host cells, and overexpressed of chIFITM1 have no effect of viral attachment and entry. Further studies revealed that mutations of amino acids at key positions (60KSRD63, 68KDFV71) in the intracellular loop domain (CIL) caused loss of the promoted function. Interaction with downstream proteins in co-response to viral infection could be the primary reason behind variable functions of chIFITM1 in different cells. In all, our study explored the functions of chIFITMs in viral infection from a new perspective.

Angiosarcoma of the visceral organs: A morphological, immunohistochemical, and C-MYC status analysis.

Visceral angiosarcomas are rare malignant tumors with poor prognosis. The pathogenesis remains unclear. Herein, we describe the morphological, immunohistochemical, and C-MYC status of a series of visceral angiosarcomas. We evaluated the clinicopathologic and C-MYC status of visceral angiosarcomas (n = 12) and compared them to a control series of angiosarcomas arising in cutaneous (n = 15) and soft tissue structures (n = 15). Clinical follow-up data were obtained for all patients and exhibited high metastasis and mortality rates. Malignant endothelial cells displayed a range of morphological features including nonepithelioid, epithelioid, and mixed features, forming vasoformative (n = 6), solid (n = 4) or mixed (n = 2) architectures. Epithelioid morphology was present in 4/12 tumors. Mitoses ranged from 3 to 60 per 10 high-power fields. Necrosis was observed in 10/12 tumors. By immunohistochemistry, all angiosarcomas expressed at least 2 markers of endothelial differentiation, including CD31, CD34, vWF, ERG, and Fli-1. Eight cases of C-MYC amplification and 5 cases of C-MYC translocation were detected. Our data showed that visceral angiosarcoma is more common in women, and the clinical presentations of patient age and tumor size were significantly different between the study and control groups. No significant difference in staining between the visceral angiosarcoma and control groups was observed for endothelial markers, while different C-MYC statuses were detected.

Donor-specific antibodies, glomerulitis, and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts.

BACKGROUND: The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation. METHODS: This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses. RESULTS: In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (P < 0.001), glomerulitis (P < 0.001), peritubular capillaritis (P < 0.001), and human leukocyte antigen (HLA) B eplet MM (P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy. CONCLUSIONS: PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.

Genetic characterisation for Yan'an Han population in Northern Shaanxi Province, China, via 38Y-STRs using Yfiler™ Platinum.

BACKGROUND: Haplotype/allele frequency data of Y-chromosomal STR loci in ethnically diverse populations are essential for forensics, anthropology and genealogy. However, genetic structure and forensic characterisation of the Chinese Han population residing in Yan'an, in the Northern Shaanxi Province, remain unclear. AIM: To assess forensic efficiency for 38 Y-Chromosomal STR loci in Yan'an Han population and reveal the population genetic relationships between Yan'an Han and other populations at a nationwide and worldwide level. SUBJECTS AND METHODS: 719 healthy unrelated males were genotyped using the Yfiler™ Platinum system. Haplotype/allele frequencies and forensic parameters were calculated. Multi-dimensional scaling plots (MDS) and neighbor-joining (N-J) tree were used to explore the population structure based on the pairwise gene distances (Rst). RESULTS: A total of 707 haplotypes were identified, among which 697 unique haplotypes were observed (98.59%). The overall haplotype diversity (HD) and discrimination capacity (DC) were 0.9999 and 0.9833, respectively. Comprehensive population comparisons showed Yan'an Han is genetically closer to linguistically similar populations in China, and more related to East Asian populations around the world. CONCLUSION: The present results give a unique insight into the Yan'an Han population via the set of 38 Y-STRs, which can be used for forensic practice and human genetics research.

Haplotype diversity and phylogenetic characteristics for Guanzhong Han population from Northwest China via 38 Y-STRs using Yfiler™ Platinum Amplification System.

BACKGROUND: For better application in human forensic cases and population genetics research, it is imperative to investigate the genetic characteristics of Guanzhong Han population using enhanced Y-chromosomal short tandem repeats (Y-STR) detecting system with higher discriminating power than previous ones. METHODS: In this study, 38 Y-STRs were profiled in 430 unrelated Chinese Han male individuals from Guanzhong region of Shaanxi Province, Northwest China, using the Yfiler™ Platinum PCR Amplification Kit. Haplotype frequencies and forensic parameters were calculated. Comprehensive population comparisons with geographically/ethnically different populations in China and other worldwide countries were performed. RESULTS: A total of 422 different haplotypes were observed with the overall haplotype diversity (HD), discriminatory power (DC) and haplotype match probability (HMP) were 0.9999, 0.9814, and 0.0024, respectively. Guanzhong Han showed genetically affinity with Han ethnicity from Shanxi and Henan provinces, while far distant from Tibetan populations. CONCLUSION: This study offered a unique insight into Guanzhong Han population, the 38 Y-STRs included in the the Yfiler™ Platinum system are highly polymorphic and informative and can be used for forensic practice and human genetic research.

Effect and mechanism of YB-1 knockdown on glioma cell growth, migration, and apoptosis.

Y-box binding protein 1 (YB-1) is manifested as its involvement in cell proliferation and differentiation and malignant cell transformation. Overexpression of YB-1 is associated with glioma progression and patient survival. The aim of this study is to investigate the influence of YB-1 knockdown on glioma cell progression and reveal the mechanisms of YB-1 knockdown on glioma cell growth, migration, and apoptosis. It was found that the knockdown of YB-1 decreased the mRNA and protein levels of YB-1 in U251 glioma cells. The knockdown of YB-1 significantly inhibited cell proliferation, colony formation, and migration in vitro and tumor growth in vivo. Proteome and phosphoproteome data revealed that YB-1 is involved in glioma progression through regulating the expression and phosphorylation of major proteins involved in cell cycle, adhesion, and apoptosis. The main regulated proteins included CCNB1, CCNDBP1, CDK2, CDK3, ADGRG1, CDH-2, MMP14, AIFM1, HO-1, and BAX. Furthermore, it was also found that YB-1 knockdown is associated with the hypo-phosphorylation of ErbB, mTOR, HIF-1, cGMP-PKG, and insulin signaling pathways, and proteoglycans in cancer. Our findings indicated that YB-1 plays a key role in glioma progression in multiple ways, including regulating the expression and phosphorylation of major proteins associated with cell cycle, adhesion, and apoptosis.

Na+/K+­ATPase DR region­specific antibody protects U251 cells against hypoxia reperfusion­induced injury via the PI3K/AKT and ERK pathways.

Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and to the death of brain tissue or cerebral infarction/ischemic stroke. In the present study, an Na+/K+­ATPase (NKA) DR region­specific antibody (DRSAb) was established and purified and it was demonstrated that DRSAb induced a protective effect on human astrocytes (U251) via the phosphoinositide 3­kinase (PI3K)/AKT and extracellular signal­regulated protein kinase (ERK) signaling pathways. The binding of DRSAb on NKA was revealed using flow cytometry. High signals were detected on U251 cells incubated with DRSAb, but not with control sera or BSA. The viability of the hypoxia/reperfusion (H/R)­treated cells was markedly increased by DRSAb administration of 0.3­0.5 µM. The optimal concentration of DRSAb was 0.4 µM for attenuation of the injury induced by H/R. The administration of 0.4 µM DRSAb markedly reduced the number of apoptotic cells compared with control sera. The application of PD98059, an ERK inhibitor, and LY­294002, an AKT inhibitor, attenuated the protective effect induced by DRSAb in the U251 cells subjected to H/R. Furthermore, the application of LY294002 prior to incubation with DRSAb eliminated the activation of ERK1/2, whereas the use of PD98059 failed to attenuate the effect of DRSAb on PI3K/AKT activation. These results indicated that the protective effects of DRSAb against H/R injury in U251 cells occurred via stimulation of the PI3K/AKT and ERK signaling pathways.

Lipoprotein lipase and phospholipid transfer protein overexpression in human glioma cells and their effect on cell growth, apoptosis, and migration.

Glioma is one of the common tumors in brain. The expression level of lipoprotein lipase (LPL) or phospholipid transfer protein (PLTP) may influence glioma progression and its relationship with clinical and pathological parameters. The clinical significance of LPL or PLTP expression in glioma has not been established. In the present study, the LPL and PLTP levels in glioma tumors were investigated and the relationship between the LPL and PLTP level and the grade of malignant glioma was analyzed, with the aim to provide new ideas for the diagnosis and treatment of gliomas in clinical and basic research settings. LPL and PLTP mRNA and protein levels were significantly higher in Grade IV glioma than those in the lower grade tumors (P < 0.01). Double immunofluorescent staining showed that the levels of LPL and PLTP were significantly associated with the pathological grade of glioma (P = 0.005). The levels of LPL and PLTP were increased with the shortened survival of glioma patients (P < 0.001). Knockdown of LPL and PLTP led to decreased cell growth and migration but increased apoptosis in vitro Additionally, cell cycle-related cyclins and their partners were found to be down-regulated while cyclin-dependent kinase inhibitors p16, p21, and Rb were up-regulated. Furthermore, knockdown of LPL or PLTP resulted in the up-regulation of pro-apoptotic molecules and the down-regulation of anti-apoptotic molecules. Ablation of LPL or PLTP in U251 cells resulted in the down-regulation of epithelial mesenchymal transition markers and invasion molecules matrix metalloproteinases. LPL and PLTP appear to be novel glioma-associated proteins and play a role in the progression of human glioma.

YB-1, a new biomarker of glioma progression, is associated with the prognosis of glioma patients.

Y box protein 1 (YB-1) is a multifunctional cellular protein expressed in various cancers, and is a potential target in cancer therapy. Although there is evidence showing that YB-1 plays a role in human cancers, the clinical significance of YB-1 expression in glioma has not been established. In the present study, we investigated the YB-1 level in glioma tumors and analyzed the relationship between the YB-1 level and the grade of malignant glioma, with the aim of providing new ideas for the diagnosis and treatment of gliomas in clinical and basic research settings. A total of 108 patients, comprising 14, 31, 30, and 33 with gliomas of Grades I, II, III, and IV, respectively, were included in this study. The mRNA and protein levels of YB-1 were found to be significantly different between Grade IV and lower-grade tumors. The YB-1 levels in cerebrospinal fluid were significantly higher in Grades III and IV glioma patients than in Grades I and II patients. Immunofluorescence staining was used to detect the levels of YB-1 in the cytoplasm and the nucleus, and results indicated that the intracellular distribution was significantly associated with the pathological grade of glioma. A higher level of YB-1 was associated with shortened survival, suggesting that YB-1 plays a role in the progression of human glioma.

Interleukin-18 -137 G/C and -607 C/A polymorphisms and Alzheimer's disease risk: a meta-analysis.

The -137 G/C and -607 C/A polymorphisms in interleukin-18 (IL-18) gene have been reported to be associated with Alzheimer's disease (AD) risk, but the results are inconclusive. Considering a single study may lack the power to provide reliable conclusion, we performed a meta-analysis to investigate the association between the IL-18 -137 G/C and -607 C/A polymorphisms and AD susceptibility. A comprehensive literature search of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were conducted before September 1, 2015. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. Five eligible studies with a total of 1536 subjects were finally included in this meta-analysis. For the IL-18 -137 G/C polymorphism, a significantly decreased risk was detected in patients carrying the C allele of -137 G/C in all study subjects in allele model (C vs. G: OR = 0.816, 95 % CI = 0.680-0.980, p = 0.029). Moreover, stratification by ethnicity indicated markedly association between the -137 G/C C allele and AD risk in Asians. For the IL-18 -607 C/A polymorphism, a significantly decreased risk was found in patients carrying the A allele of -607 C/A in all study subjects in dominant model (AA + CA vs. CC: OR = 0.696, 95 % CI = 0.529-0.915, p = 0.010). However, the results suggested no significant association between the -607 C/A polymorphism and AD susceptibility when stratified by ethnicity. Our present meta-analysis suggests that the C allele carrier of IL-18 -137 G/C was associated with decreased risk for AD in Asians. Further well-designed case-control studies with larger sample size and more ethnic groups are needed to confirm these conclusions.

Clinical significance of perineural invasion in stages II and III colorectal cancer.

PURPOSE: This study aimed to determine the prognostic value of perineural invasion (PNI) in patients with colorectal cancer (CRC), particularly patients with TNM stage II and stage III. METHODS: A total of 159 CRC patients who had undergone radical resection were retrospectively analyzed. Histopathological evaluation of tissue samples was conducted on hematoxylin and eosin-stained sections. PNI was considered positive when cancer cells were observed inside the nerve sheath, or when at least 33% of the nerve periphery was surrounded by cancer cells. A 3-tier grading system (PNI0, PNI1, PNI2) based on the depth of PNI was used to assess the localization of PNI in the bowel. PNI and other prognostic factors were evaluated by survival analysis. RESULTS: PNI status in CRC significantly affected postoperative overall survival (P<0.001). The five-year survival rates for PNI-negative and PNI-positive patients were 77% and 32%, respectively. PNI was closely correlated with tumor gross type, tumor grade, depth of invasion, lymph node metastasis, clinical stage, vessel invasion, tumor budding grade, and tumor growth pattern. Multivariate analysis revealed that PNI was an independent prognostic factor (HR=2.223, P=0.003). The survival of PNI-positive patients was significantly poorer than that of PNI-negative patients in stages II and III (P=0.003 and P=0.008, respectively). The overall survival of colorectal patients was in the descending order of PNI-negative at stage II, PNI-positive at stage II/PNI-negative at stage III, and PNI-positive at stage III (P<0.001). When the PNI status and T stage were considered together, overall survival curves of the PNI2 patients were significantly worse than those of PNI1 patients in pT4 stage (P=0.019). CONCLUSIONS: PNI is a poor independent prognostic factor for CRC. It could complement classic TNM staging classification in stratifying CRC patients in stages II and III. Assessment of the site-specific distribution of PNI may further enhance the impact of PNI contribution to the prognosis of CRC.

[Relationship between histopathologic characteristics and epidermal growth factor receptor mutation in lung adenocarcinoma].

OBJECTIVE: To correlate morphological features with mutations of epidermal growth factor receptor (EGFR) in lung adenocarcinomas. METHODS: According to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification, a total of 72 surgically resected lung adenocarcinomas were collected and classified into different histological subtypes and different cell types (hobnail, columnar and polygonal). EGFR gene mutation was detected with the amplification refractory mutation method provided by the EGFR mutation test kit. The correlation between these subtypes and EGFR mutations were evaluated. RESULTS: Mutations of EGFR were detected in 48.6% (35/72) of lung adenocarcinomas; 19del and L858R were major mutational types (88.6%, 31/35). EGFR mutations were associated with female gender, non-smoking status, and well to moderately differentiated tumor histology. EGFR mutation types were not associated with age, smoking index, lymph node metastasis, stage, status of whether have or not have inclusion bodies or psammoma bodies and mitotic level. Correlations were observed between acinar and papillary adenocarcinoma subtypes and EGFR mutations according to the new classification. EGFR mutation was rare in the subtype of solid adenocarcinoma with mucin production and almost never observed in special subtypes (mainly mucinous and colloid adenocarcinoma). In addition, EGFR mutation was associated with the hobnail cell type. CONCLUSION: Lung adenocarcinomas of predominate acinar and papillary histological subtypes with hobnail cell morphology are good predictors for EGFR mutations.

High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction.

Basement membrane degradation and blood-brain barrier damage appear after cerebral infarction, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke-prone spontaneously hypertensive rats by intragastric administration of high-sodium water (1.3% NaCl) for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone spontaneously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregulation is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodium water-induced focal cerebral infarction.

Protective effect of truncated Na+/K+-ATPase ß on ischemia/reperfusion-induced renal injury in rats.

Renal ischemia/reperfusion(I/R) is an important injury part of ischemic acute renal failure, and it is also the main factor that affects the early functional recovery and the long-term survival of transplanted kidney in renal transplantation. In this study, we cloned and expressed truncated Na+/K+-ATPase ß(tNKAß) and demonstrated that tNKAß could activate NKA α subunit and induce protective effect on human kidney-2(HK-2) cells via PKCɛ signal pathway. The half maximum effective concentrations (EC50) of tNKAß were 0.24 µM. Furthermore, the application of EAVSLKPT (PKCɛ inhibitor) could abolish the protective effect of tNKAß in HK-2 cells subjected to ischemia/reperfusion. To identify the protective effect of tNKAß against the I/R injury in the kidney, Sprague-Dawley rats were treated with tNKAß (75 mg/kg) for 2 h before ischemia. The tNKAß-treated group demonstrated a significant improvement in renal function with a lower serum creatinine and blood urea nitrogen (BUN) levels on postoperative days 1-6. Renal sections obtained from rats of the I/R group showed serious renal injury which included degeneration of tubular structure, tubular dilation, swelling and necrosis, luminal congestion, and muddy brown casts formed by sloughing of severely damaged tubular epithelial cells. However, sections of rats that were administered with tNKAß 2 h before reperfusion showed marked reduction of the histological features of renal injury compared with kidneys that were subjected to I/R only. In conclusion, the protective effects of tNKAß against renal I/R injury have been evaluated for the first time, and these protective effects may occur via stimulation of PKCɛ pathways.

Application of Real-Time Tissue Elastography with a Low Frequency Convex Array Probe: A Noninvasive Approach to Differential Diagnosis of Liver Tumors.

To evaluate diagnostic performance of real-time tissue elastography (RTE) with a low frequency convex array probe for distinguishing benign from malignant hepatic tumors through trans-abdominal examination, elasticity images of 210 liver tumors were obtained by EUB-7500 (Hitachi Medical Systems and 3.5 MHz probe) and eventually 121 liver tumors were analyzed in the study. Elasticity images were classified into four types, from type a to d. Regarding type a or b as benign tumors and type c or d as malignant ones, sensitivity, specificity, and accuracy were calculated and the consistency between the findings of RTE and the pathohistological diagnosis was evaluated. The sensitivity, specificity, and accuracy were separately 97.2%, 88.0%, and 93.4% (P < 0.001). Moreover, there was a good consistency between the findings of RTE and the pathological diagnosis (kappa value 0.86). Among elasticity images of all the malignant tumors, the hepatocellular carcinomas (HCCs) mainly appeared in type c, and liver metastatic cancers in type d. Thus, RTE utilized as a novel noninvasive imaging examination method enables us to distinguish benign from malignant liver tumors. Moreover, it provides certain information for the differential diagnosis between HCCs and liver metastatic cancers.