bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust Production of Cytomegalovirus pp65-Specific T Cells Using a Fully Automated IFN-γ Cytokine Capture System
Authors: Kim Nayoun , Nam Young-Sun , Im Keon-Il , Lim Jung-Yeon , Jeon Young-Woo , Song Yunejin , Lee Jong Wook , Cho Seok-Goo
Published: October 2017

Background: Cytomegalovirus(CMV)-related diseases are a serious cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). CMV-specific cytotoxic T lymphocytes (CMV-CTLs) have been reported as an alternative to antiviral drugs that provide long-term CMV-specific immunity without major side effects. However, their application has been limited by the prolonged manufacturing process required. Methods: In this study, we applied the IFN-γ cytokine capture system (CCS) using the fully automated CliniMACS Prodigy device for rapid production of CMV-CTLs, which may be applicable in clinically urgent CMV-related diseases. Five validation runs were performed using apheresis samples from randomly selected CMV-seropositive healthy blood donors. Successive processes, including antigen stimulation, anti-IFN-γ labeling, magnetic enrichment and elution, were then performed automatically using the CliniMACS Prodigy, which took approximately 13 h. Results: The original apheresis samples consisted mainly of CD45RA+ CD62L+ naïve T cells as well as 0.3% IFN-γ-secreting CD3+ T cells that showed a response to the CMV pp65 antigen (CD3+ IFN-γ+ cells). Following IFN-γ enrichment, the target fraction contained 51.3% CD3+ IFN-γ+ cells with a reduction in naïve T cells and selection of CD45RA- CD62L- and CD45RA+ CD62L- memory T cells. Furthermore, extended culture of these isolated cells revealed functional activity, including efficient proliferation, sustained antigen-specific IFN-γ secretion, and cytotoxicity against pp65-pulsed target cells. Conclusion: The findings reported here suggest that the IFN-γ CCS by the CliniMACS Prodigy is a simple and robust approach to produce CMV-CTLs, which may be applicable for the treatment of clinically urgent CMV-related diseases.
Juvenile Xanthogranuloma in a Pediatric Patient with Langerhans Cell Histiocytosis
Authors: Ram Radha , Marolf Marissa D. , Chévez-Barrios Patricia , Herce Honey H.
Published: October 2017

Purpose: To report a case of juvenile xanthogranuloma that simulated a chalazion and to discuss the association between juvenile xanthogranuloma and Langerhans cell histiocytosis. Method: Case report and review of literature. Results: A 13-year-old boy with a prior history of Langerhans cell histiocytosis was referred to our clinic for a possible chalazion. The patient had undergone treatment for Langerhans cell histiocytosis 10 years prior. The patient underwent an excisional biopsy. Histopathology revealed a proliferation of histiocytes and lymphocytes with Touton giant cells, consistent with a diagnosis of juvenile xanthogranuloma. Conclusions: Though the relationship between Langerhans cell histiocytosis and juvenile xanthogranuloma has yet to be fully elucidated, juvenile xanthogranuloma should be included in the differential diagnosis for any former Langerhans cell histiocytosis patient presenting with a new cutaneous lesion.
A Subjective Rating Scale for Initial Assessment of Sudden Unilateral Sensorineural Hearing Loss
Authors: Ungar Omer J. , Cavel Oren , Oron Yahav , Wengier Anat , Wasserzug Oshri , Handzel Ophir
Published: October 2017

Objective: To examine the value of a subjective numerical rating scale (NRS) in the initial evaluation of patients suspected of suffering from unilateral sudden sensorineural hearing loss (SSNHL) until a formal audiogram is available. Study Design: Prospective noncontrolled clinical study. Methods: Thirty-one consecutive patients referred to the emergency department due to suspected unilateral SSNHL and with no other aural pathology by history or physical examination were enrolled. Patients were asked to characterize the severity of their hearing loss using an NRS of 1 (normal hearing) to 6 (complete deafness). SSNHL was defined as an SNHL of at least 30 dB over 3 consecutive frequencies that occurred in 3 days or less. A formal audiogram was obtained subsequently as soon as available. Results: Twenty-four patients were treated with steroids and met the audiometric criteria of SSNHL. All scored their NRS as 3 or more. None of the 7 patients whose NRS grades were ≤2.5 met the criteria for SSNHL. Two patients were treated with steroids although their hearing did not meet the audiometric criteria for SSNHL as the hearing loss was limited to 2 consecutive frequencies. The NRS score for both was <3. Conclusion: In addition to the patient's history and physical examination, a NRS can be a useful tool in the preliminary assessment of patients suspected of having SSNHL until audiometry becomes available. In the scale of 1-6, an NRS score of 3 or more reliably predicts the need to treat the patient with steroids according to the accepted criteria.
In vitro Validation of Quantitative Light-Induced Fluorescence for the Diagnosis of Enamel Fluorosis in Permanent Teeth
Authors: Cuevas-Espinosa D.M. , Martinez-Mier E.A. , Ando M. , Castiblanco G.A. , Cortes F. , Rincon-Bermudez C.M. , Martignon S.
Published: October 2017

This study aimed to validate quantitative light-induced fluorescence (QLF) as a diagnostic tool for mild and moderate enamel fluorosis in permanent teeth, comparing it to visual diagnosis and histological assessment completed using polarized light microscopy (PLM). The buccal surfaces of 139 teeth were visually classified using the Thylstrup and Fejerskov Index (TFI) into sound (TFI 0; n = 17), mild (TFI 1-2; n = 69), and moderate (TFI 3-4; n = 43) fluorosis. Fluorosis was then assessed with QLF (variables ΔF, A, and ΔQ at 5-, 15-, and 30-radiance thresholds) using as reference areas the entire surface and a region of interest (ROI), identified as the most representative region of a fluorosis lesion. PLM images of longitudinal thin sections including the ROI were assessed for histological changes. Correlations among TFI, PLM, and QLF were determined. A receiver-operating characteristic curve was conducted to determine QLF's diagnostic accuracy when compared to the TFI and PLM assessments. This was used to assess the probability that the images were correctly ranked according to severity as determined by PLM and TFI. A positive correlation was found between QLF and PLM, and between QLF and TFI. QLF showed the highest sensitivity and specificity for the diagnosis of mild fluorosis. There was also a strong agreement between TFI and PLM. The selection of a ROI resulted in a stronger correlation with TFI and PLM than when the entire surface was used. The study results indicate that defining an ROI for QLF assessments is a valid method for the diagnosis of mild and moderate enamel fluorosis.
Troponin I Levels in Asymptomatic Hemodialysis Patients
Authors: Castini Diego , Persampieri Simone , Floreani Riccardo , Galassi Andrea , Biondi Maria Luisa , Carugo Stefano , Cozzolino Mario
Published: October 2017

Background: End-stage renal disease (ESRD) represents a situation in which persistently elevated levels of cardiac troponins I (cTnI) are frequently found in the absence of clinically evident cardiac disease. Moreover, the effect of hemodialysis (HD) on cTnI levels is not definitively elucidated. The aim of this study was to investigate the effects of HD on cTnI levels in ESRD patients. Methods: We enrolled 30 asymptomatic ESRD patients on maintenance HD. All the patients were dialyzed thrice weekly. We compared each other's cTnI levels obtained before HD sessions (pre-HD) and cTnI levels obtained before and after HD sessions (post-HD). Results: The median value of baseline cTnI, measured before the first dialysis session of the week, was 0.018 ng/mL (interquartile range 0.012-0.051) and elevated levels (>0.034 ng/mL) were found in 9 (30%) patients. Pre-HD cTnI levels showed a statistically significant decrease between the first and the second weekly HD sessions (from 0.018 to 0.016 ng/mL; p = 0.002), while no difference was observed between the second and the third sessions over the week. Finally, no statistically significant differences were found between pre-HD and post-HD cTnI levels, considering each HD session and the averaged cTnI values. Conclusions: Our results indicate that HD does not significantly affect cTnI levels. Even when statistically significant, the observed changes were without clinical relevance indicating that HD does not affect by itself the diagnostic accuracy of cTnI assay in ESRD patients.
Tomographic Structural Changes of Retinal Layers after Internal Limiting Membrane Peeling for Macular Hole Surgery
Authors: Faria Mun Yueh , Ferreira Nuno P. , Cristóvao Diana M. , Mano Sofia , Sousa David Cordeiro , Monteiro-Grillo Manuel
Published: October 2017

Purpose: To highlight tomographic structural changes of retinal layers after internal limiting membrane (ILM) peeling in macular hole surgery. Methods: Nonrandomized prospective, interventional study in 38 eyes (34 patients) subjected to pars plana vitrectomy and ILM peeling for idiopathic macular hole. Retinal layers were assessed in nasal and temporal regions before and 6 months after surgery using spectral domain optical coherence tomography. Results: Total retinal thickness increased in the nasal region and decreased in the temporal region. The retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) showed thinning on both nasal and temporal sides of the fovea. The thickness of the outer plexiform layer (OPL) increased. The outer nuclear layer (ONL) and outer retinal layers (ORL) increased in thickness after surgery in both nasal and temporal regions. Conclusion: ILM peeling is associated with important alterations in the inner retinal layer architecture, with thinning of the RNFL-GCL-IPL complex and thickening of OPL, ONL, and ORL. These structural alterations can help explain functional outcome and could give indications regarding the extent of ILM peeling, even though peeling seems important for higher rate of hole closure.
Globular Adiponectin Attenuated H2O2-Induced Apoptosis in Rat Chondrocytes by Inducing Autophagy Through the AMPK/ mTOR Pathway
Authors: Hu Junzheng , Cui Weiding , Ding Wenxiao , Gu Yanqing , Wang Zhen , Fan Weimin
Published: October 2017

Background/Aims: Chondrocyte apoptosis is closely related to the development and progression of osteoarthritis. Global adiponectin (gAPN), secreted from adipose tissue, possesses potent anti-inflammatory and antiapoptotic properties in various cell types. This study aimed to investigate the role of autophagy induced by gAPN in the suppression of H2O2-induced apoptosis and the potential mechanism of gAPN-induced autophagy in chondrocytes. Methods: H2O2 was used to induce apoptotic injury in rat chondrocytes. CCK-8 assay was performed to determine the viability of cells treated with different concentrations of gAPN with or without H2O2. Cell apoptosis was detected by flow cytometry and TUNEL staining. Mitochondrial membrane potential was examined using JC-1 fluorescence staining assay. The autophagy inhibitors 3-MA and Bafilomycin A1 were used to treat cells and then evaluate the effect of gAPN-induced autophagy. To determine the downstream pathway, chondrocytes were preincubated with the AMPK inhibitor Compound C. Beclin-1, LC3B, P62 and apoptosis-related proteins were identified by Western blot analysis. Results: H2O2 (400 µM)-induced chondrocytes apoptosis and caspase-3 activation were attenuated by gAPN (0.5 µg/mL). gAPN increased Bcl-2 expression and decreased Bax expression. The loss of mitochondrial membrane potential induced by H2O2 was also abolished by gAPN. Furthermore, the antiapoptotic effect of gAPN was related to gAPN-induced autophagy by increased formation of Beclin-1 and LC3B and P62 degradation. In particular, the inhibition of gAPN-induced autophagy by 3-MA prevented the protective effect of gAPN on apoptosis induced by H2O2. Moreover, gAPN increased p-AMPK expression and decreased p-mTOR expression. Compound C partly suppressed the expression of autophagy-related proteins and restored the expression of p-mTOR suppressed by gAPN. Thus, the AMPK/mTOR pathway played an important role in the induction of autophagy and protection of H2O2-induced chondrocytes apoptosis by gAPN. Conclusions: gAPN protected chondrocytes from H2O2-induced apoptosis by inducing autophagy possibly associated with AMPK/mTOR signal-pathway activation.
Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups
Authors: Sveinsdóttir Kristbjörg , Länsberg John-Kalle , Sveinsdóttir Snjólaug , Garwicz Martin , Ohlsson Lennart , Hellström Ann , Smith Lois , Gram Magnus , Ley David
Published: October 2017

Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p < 0.05) than in the T group. Postnatal weight development correlated with circulating IGF-1 (r2 = 0.89) independently of gestational age at birth and postnatal age. The proliferative (Ki-67-positive) portion of the external granular layer (EGL) was decreased in the PT group at postnatal day 2 (P2) compared to in the T group (p = 0.01). Purkinje cells exhibited decreased calbindin staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population.
Humoral Immune Response in Mice Elicited by Combined Yeast-Derived Hepatitis B Virus Core, Surface, and Mosaic Surface Antigens
Authors: Granovski Vladimir , Yokosawa Jonny , Rodrigues-Granovski Vanessa , Castro Carlos Cueto , Urbina Alfonso Camacho , Granovski Nikolai
Published: October 2017

Background: Although successful, the second-generation hepatitis B vaccine programs around the world have a small group of immunized individuals that does not respond efficiently to the vaccination. Other issues of these vaccines are individuals that are low or nonresponders and/or have incomplete protection against heterologous hepatitis B virus (HBV) genotypes/subtypes and against HBV escape mutants. In addition, there are approximately 240 million people chronically infected with HBV worldwide and 620,000 deaths per year caused by the infection. Methods: In this study we developed three Hansenula polymorpha plasmids containing the following sequences: (a) HBsAg subtype ayw, (b) HBcAg sequence subtype adw2, and (c) chimeric HBsAg (adw4/ ayw) - preS1 (adw2) - 3 repetitions of preS2 (genotypes A, B, and C). The sequences were successfully expressed and the antigens purified. Using Balb/c mice the antigens were tested in different dosage combinations. Results: Three antigens were obtained at a high purity level and with high reproducibility. We also assessed their immunogenic properties, showing that the antigens, individually or in combination, generated anti-HBs, anti-preS1, anti-preS2, and anti-HBc antibodies efficiently in mice. Conclusions: The formulation tests showed that a combination of 0.02 μg of HBs, 0.2 μg of preS1-preS2-HBs, and 0.02 μg of HBc was effective in eliciting specific antibodies in mice.
Spontaneous Remission of Severe Systemic Langerhans Cell Histiocytosis with Bladder Involvement: A Case Study
Authors: Magaton Isotta M. , Tzankov Alexandar , Krasniqi Fatime , Rottenburger Christof , Zanetti-Daellenbach Rosanna , Grendelmeier Peter , Heinzelmann-Schwarz Viola  , Mayr Michael , Schwab Fabienne D.
Published: October 2017

Background: The clinical presentation of Langerhans cell histiocytosis (LCH) is heterogeneous ranging from single-organ involvement to systemic disease causing substantial morbidity and mortality. We describe an unusual course of severe multisystem LCH with spontaneous remission. Case Presentation: We report on a 45-year-old Caucasian woman with cervical cancer, FIGO stage IVB. Five months after the end of combined radiochemotherapy and brachytherapy, the patient was readmitted because of severe dysuria. Sterile leukocyturia was seen, and cystoscopy revealed only 3 unspecific small mucosal lesions compatible with postradiation cystitis. Incidentally, a computed tomography (CT) scan of the body showed diffuse micronodular and cystic lesions in lungs and hypodense lesions in the liver. Biopsies revealed infiltrations of CD1a and Langerin (CD207)-positive histiocytes in the lung, liver, and bladder. Additionally, positron emission tomography-CT (PET-CT) was compatible with bone involvement. Retrospective analysis revealed that the increase in alkaline phosphatase might have been a surrogate of bone marrow infiltration with osseous activity. Repeated pneumothoraces occurred, and only one course of vinblastine-prednisolone could be applied. Despite ongoing tobacco consumption and without further therapy, PET-CT showed considerable remission 2 months later. However, despite stable remission, documented by serial PET and conventional CT scans, persistent infiltration of the bladder by Langerhans histiocytes could still be demonstrated 17 months later. Unfortunately, cervical cancer recurred and progressed. Conclusion: Multisystem LCH may rapidly occur, may be oligosymptomatic and, even in high-risk cases, remission without specific therapy might occur. Whether alkaline phosphatase might be a surrogate to monitor osseous disease activity has to be further explored.
Endometriosis: A Rare Cause of Large Bowel Obstruction
Authors: Alexandrino Gonçalo , Lourenço Luís Carvalho , Carvalho Rita , Sobrinho Cisaltina , Horta David Valadas , Reis Jorge
Published: October 2017

Large bowel obstruction can result in significant morbidity and mortality, especially in cases of acute complete obstruction. There are many possible causes, the most common in adults being colorectal cancer. Endometriosis is a benign disease, and the most affected extragenital location is the bowel, especially the rectosigmoid junction. However, transmural involvement and acute occlusion are very rare events. We report an exceptional case of acute large bowel obstruction as the initial presentation of endometriosis. The differential diagnosis of colorectal carcinoma may be challenging, and this case emphasizes the need to consider intestinal endometriosis in females at a fertile age presenting with gastrointestinal symptoms and an intestinal mass causing complete large bowel obstruction.
Nevus Comedonicus: Case Report
Authors: Timbó Renata Pinto Fernandes , Gomes Maria Kátia , Falcão Eduardo Mastrangelo Marinho , Ramos-e-Silva Marcia
Published: October 2017

Nevus comedonicus is a rare cutaneous anomaly, characterized by the clustering of papules with firm, blackened horny buffers. It in general has a zosteriform pattern and affects both genders equally. In some patients, there is formation of cysts, abscesses, and fistulas, aggravating its psychosocial impact. The association with extracutaneous lesions characterizes the nevus comedonicus syndrome. Despite several therapeutic options, the result is unsatisfactory in most cases. We report the case of a man with an exuberant congenital lesion, affecting the left suprascapular region, arm, and forearm.
Repair of an Autologous Saphenous Vein Graft Aneurysm Ten Years after Renal Artery Reconstruction during Live Donor Renal Transplantation
Authors: Oelschlaeger Markus , Sokolakis Ioannis , Kalogirou Charis , Frey Lea , Riedmiller Hubertus , Kübler Hubert , Kellersmann Richard , Vergho Daniel
Published: October 2017

Saphenous vein graft (SVG) aneurysms (SVGA) after renal transplantation represents a rare vascular complication with subsequent challenging multidisciplinary treatment. We present a case of a 30-year-old female who received a live donor kidney transplantation for end-stage renal disease that was caused due to the hemolytic uremic syndrome. Postoperatively, an insufficient graft perfusion due to an arterial kinking was noted and repaired using an autologous SVG interposition. Ten years later, a 3-cm aneurysm of the SVG at the anastomotic site with the common iliac artery was discovered. Multidisciplinary surgical exploration with excision of the aneurysm-carrying vein graft and interposition of a new autologous SVG was successfully carried out with preservation of renal allograft's function. Treatment of SVGA after rental transplantation with a new autologous SVG is challenging but feasible, requiring a multidisciplinary approach in order to guarantee successful rates and to prevent allograft loss.
MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva
Authors: Wiegand Conrad , Savelsbergh Andreas , Heusser Peter
Published: October 2017

MicroRNAs (miRNAs) play a central role in the regulation of many cellular processes including physiological and psychological stress reaction pathways. Psychological stress is an important factor for the genesis and maintenance of many diseases. Several miRNAs have already been described to be involved in its regulation. The presence of miRNAs in all body fluids implies a widespread role in communication throughout the whole organism and together with their stability makes them formidable candidates as biomarkers. Alterations of stress-associated miRNA expression levels have been found in the brain and whole blood of humans and animals. In this paper, we review the participation of miRNAs in stress-reactive processes as well as their usability as salivary biomarkers of such processes. In conclusion, we suggest that salivary miRNAs may be useful as noninvasive biomarkers to assess epigenetic regulation processes of chronic or acute psychological stress reactions.
Vanishing Tumor in a Liver Graft from a Hepatitis B Virus Surface Antigen-Positive Donor
Authors: Fuchino Mayo , Tajiri Kazuto , Minemura Masami , Sugiyama Toshiro
Published: October 2017

We report a case of vanishing tumor considered as inflammatory pseudotumor (IPT) found in the liver after living donor liver transplantation (LDLT) from a hepatitis B virus surface antigen-positive donor. The radiological findings were similar to those of hepatocellular carcinoma (HCC). However, the tumor disappeared completely within several months and was suggested to have been an IPT. IPT is known to be associated with biliary duct operation or biliary infection, and it can show various enhancement patterns in radiological studies, sometimes resembling HCC. It should be considered in the differential diagnosis of a liver tumor in patients with LDLT.
Predictors of Persistence of Risky Drinking in Adults: An 11-Year Follow-Up Study
Authors: Härkönen Janne , Aalto Mauri , Suvisaari Jaana , Lintonen Tomi , Mäki-Opas Tomi , Peña Sebastian , Mäkelä Pia
Published: October 2017

Aim: To examine the long-term predictors of persistence of risky drinking in a baseline group of risky drinkers in whom alcohol use disorder had not been diagnosed. Methods: The data was derived from a representative sample of the Finnish adult population aged 30 years or more, surveyed at 2 time points in the years 2000 (n = 5,726) and 2011 (n = 3,848, 67.2% of the baseline sample). Risky drinking was defined using BSQF-measurement (for men, 21 standard UK drinks or more per week; for women 14+ drinks) and not having alcohol abuse or alcohol dependence. The sample of risky drinkers in baseline comprised 642 persons, of whom 380 (59.2%) people provided follow-up data. Multivariable logistic regression models were estimated to identify determinants of persistence of risky drinking. Results: The rate for persistence of risky drinking was 48.7%. Persistence was predicted by daily smoking, low physical activity, and male gender, whereas higher age and later onset of drinking predicted cessation of risky drinking. Daily smoking remained an independent predictor after adjusting for other risk factors. Conclusions: Health behaviour predicts the persistence of risky drinking in a study population of adults aged 30 and over. These factors should be taken into account when assessing the long-term prognosis on risky drinking.
Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer
Authors: Liu Lin , Li Dan , Chen Zhengqi , Yang Jian , Ma Yushui , Cai Haidong , Shan Chengxiang , Lv Zhongwei , Zhang Xiaoping
Published: October 2017

Aims: Anaplastic thyroid cancer(ATC) is one of the most aggressive solid tumors. Mutations in the p53 gene are common in anaplastic thyroid cancer, but the effects of p53 mutations are yet to be elucidated. Here, we investigated the role of p53 in ATC. Methods: p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured using immunohistochemistry, qRT-PCR, western blot, immunofluorescence in ATC tissues and cell line 8505c. Luciferase reporter assay was performed to examine the effect of wild-type p53 on NIS. Radioiodide uptake assay and flow cytometry analysis were used to detect the role of wild-type p53 on radioiodide uptake.and cell apoptosis in ATC cell line. Results: We showed that the p53 mutation can be detected in ATC tissues. Furthermore, we demonstrated that wild-type p53 transactivated the NIS promoter. In 8505c cells transfected with wild-type p53, treatment with radioiodine resulted in increased radioiodine uptake and increased apoptotic cell death compared with 8505c cells harboring the p53 mutation. Conclusion: In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.
Epigallocatechin-3-Gallate Inhibits Matrix Metalloproteinase-9 and Monocyte Chemotactic Protein-1 Expression Through the 67-κDa Laminin Receptor and the TLR4/MAPK/NF-κB Signalling Pathway in Lipopolysaccharide-Induced Macrophages
Authors: Li Ya-Fei , Wang Hao , Fan Yi , Shi Hao-jie , Wang Qi-Ming , Chen Bing-rui , Khurwolah Mohammad Reeaze , Long Qing-qing , Wang Si-Bo , Wang Ze-Mu , Wang Lian-Sheng
Published: October 2017

Background/Aims: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, has been shown to prevent cardiovascular diseases. Previously, Matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1) and toll-like receptor 4 (TLR4) were confirmed to play an important role in atherosclerosis and plaque instability. Both TLR4 and its negative regulator, Toll-interacting protein (Tollip), could be mediated by EGCG. The present study aimed to examine the effect of physiological concentration of EGCG (1 µM) on the expression of MMP-9 and MCP-1 in lipopolysaccharide (LPS)-induced macrophages and the potential mechanisms underlying its actions. Methods: The RAW264.7 cell line was used. Western blot was used to determine MCP-1, TLR4, Tollip, Mitogen-activated protein kinase (MAPK) and Nuclear factor-κB (NF-κB) protein expression. MMP-9 activity was assayed by gelatine zymography. The mRNA expression of MMP-9 and MCP-1 was measured by realtime polymerase chain reaction (RT-PCR). Results: EGCG (1 µM) significantly suppressed the expression of MMP-9 and MCP-1 and inhibited MAPK and NF-κB in LPS-induced macrophages but was blocked by Tollip silencing. The expression of LPS-induced MMP-9 and MCP-1 and the phosphorylation of the ERK1/2, P38 and NF-κB pathway proteins decreased after TLR4 siRNA treatment. Furthermore, EGCG mediated TLR4 and Tollip expression through binding to 67-kDa laminin receptor (67LR). Conclusion: The results of our study suggested that EGCG (1 µM) suppresses the TLR4/MAPK/NF-κB signalling pathway, decreases the expression of the plaque instability-mediating cytokines MMP-9 and MCP-1, and might prove to be effective in stabilizing atherosclerotic plaque.
Mitochondrial Genome Encoded Proteins Expression Disorder, the Possible Mechanism of the Heart Disease in Metabolic Syndrome
Authors: Zheng Ningning , Wei Dan , Dai Bo , Zheng Lanyan , Zhao Mingyi , Xin Na , Chi Zhihong , Zhao Yiting , Ma Tingxian , Jahane Rabita , Sun Luning
Published: October 2017

Background/Aims: The direct consequence of metabolic syndrome (MS) is the increased morbidity and mortality caused by the heart disease. We tried to explain why the heart is more severely damaged during MS from the point of mitochondria, the center of cellular metabolism. Methods: 1. The classic diet induced MS rat model was used to observe the morphological changes of mitochondria by transmission electron microscope (TEM); 2. The expression of mitochondrial DNA (mt-DNA) encoded proteins was observed by immunohistochemistry and Western blot; 3. The expression of mitochondrial ribosomal proteins (MRPs) was observed by real-time PCR. Results: 1. The mitochondrial volume increased but the number was normal in myocardial cells of the MS rats. But in the hepatocytes and skeletal muscle cells, the mitochondrial number decreased; 2.The mt-DNA encoded protein cytochrome b increased significantly in heart but decreased in liver and the ATPase6 increased in liver but decreased in heart of the MS rats; 3. The mRNA levels of MRPS23, MRPL27, MRPL45 and MRPL48 elevated in heart but down-regulated in liver of the MS rats. Conclusion: The morphologic and functional alterations of mitochondrion in MS were tissue specific. Heart displays a distinctive pattern of mitochondrial metabolic status compared with other tissues.
MiRNA Expression Profile of the Myocardial Tissue of Pigs with Coronary Microembolization
Authors: Su Qiang , Li Lang , Zhao Jinmin , Sun Yuhan , Yang Huafeng
Published: October 2017

Background/Aims: Coronary microembolization (CME) is a serious complication of coronary heart disease and is considered as a strong predictor of poor long-term prognosis and major cardiac adverse events. Here, we identified differentially expressed microRNAs (miRNAs) in the myocardial tissue of CME pigs, and predicted and analyzed the possible functions of their target genes. Methods: Twelve Bama mini-pigs were randomly assigned to the sham and CME group (n = 6 in each group). The two groups were compared with regard to heart function, area of infarction, cardiomyocyte apoptosis, and myocardial expression of TNF-α, IL-1β and IL-6. Further, miRNA chip analysis was used to screen for differentially expressed miRNAs, and the results were validated by real-time PCR. Bioinformatics methods were used to predict and analyze the functions of the target genes of the identified miRNAs. Results: The model CME pigs showed significantly increased expression of TNF-α, IL-1β and IL-6, as well as micro-infarction lesions and cell apoptosis in the myocardial tissue. Thus, the model was established successfully. In the myocardial tissue of the CME pigs, the expression of ssc-miR-92b-5p, ssc-miR-491, ssc-miR-874, ssc-miR-425-3p, ssc-miR-376a-5p, ssc-miR-370, ssc-miR-30c-3p, ssc-miR-493-5p and ssc-miR-323 was significantly increased, whereas the expression of ssc-miR-136 and ssc-miR-142-3p was significantly decreased. GO and KEGG pathway analysis indicated that the target genes of these miRNAs are mainly associated with cell proliferation, apoptosis, necrosis, inflammation, and fibrosis. Conclusion: The differentially expressed miRNAs identified in the myocardial tissue of CME pigs could be new biomarkers or potential treatment targets for CME.
Luteinizing Hormone and GATA4 Action in the Adrenocortical Tumorigenesis of Gonadectomized Female Mice
Authors: Doroszko Milena , Chrusciel Marcin , Stelmaszewska Joanna , Slezak Tomasz , Rivero-Muller Adolfo , Padzik Artur , Anisimowicz Slawomir , Wolczynski Slawomir , Huhtaniemi Ilpo , Toppari Jorma , Rahman Nafis A.
Published: October 2017

Background/Aims: Physiological role of luteinizing hormone (LH) and its receptor (LHCGR) in adrenal remains unknown. In inhibin-α/Simian Virus 40 T antigen (SV40Tag) (inhα/Tag) mice, gonadectomy-induced (OVX) elevated LH triggers the growth of transcription factor GATA4 (GATA4)-positive adrenocortical tumors in a hyperplasia-adenoma-adenocarcinoma sequence. Methods: We investigated the role of LHCGR in tumor induction, by crossbreeding inhα/Tag with Lhcgr knockout (LuRKO) mice. By knocking out Lhcgr and Gata4 in Cα1 adrenocortical cells (Lhcgr-ko, Gata4-ko) we tested their role in tumor progression. Results: Adrenal tumors of OVX inhα/Tag mice develop from the hyperplastic cells localized in the topmost layer of zona fasciculata. OVX inhα/Tag/LuRKO only developed SV40Tag positive hyperplastic cells that were GATA4 negative, cleaved caspase-3 positive and did not progress into adenoma. In contrast to Lhcgr-ko, Gata4-ko Cα1 cells presented decreased proliferation, increased apoptosis, decreased expression of Inha, SV40Tag and Lhcgr tumor markers, as well as up-regulated adrenal- and down-regulated sex steroid gene expression. Both Gata4-ko and Lhcgr-ko Cα1 cells had decreased expression of steroidogenic genes resulting in decreased basal progesterone production. Conclusion: Our data indicate that LH/LHCGR signaling is critical for the adrenal cell reprogramming by GATA4 induction prompting adenoma formation and gonadal-like phenotype of the adrenocortical tumors in inhα/Tag mice.
Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis
Authors: Jiang Zhonghua , Yu Tingting , Fan Zhining , Yang Hongmei , Lin Xin
Published: October 2017

Background/Aims: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. Methods: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. Results: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. Conclusion: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.
Edaravone Attenuates the Proinflammatory Response in Amyloid-β-Treated Microglia by Inhibiting NLRP3 Inflammasome-Mediated IL-1β Secretion
Authors: Wang Hong-Mei , Zhang Ting , Huang Jian-Kang , Xiang Jing-Yan , Chen Jing-jiong , Fu Jian-Liang , Zhao Yu-Wu
Published: October 2017

Background/Aims: Microglial activation is an important pathological feature in the brains of patients with Alzheimer’s disease (AD), and amyloid-β (Aβ) peptides play a crucial role in microglial activation. In addition, edaravone (EDA) was recently shown to suppress oxidative stress and proinflammatory cytokine production in APPswePS1dE9 (APP/PS1) mice. However, the mechanism by which EDA inhibits the Aβ-induced proinflammatory response in microglia is poorly understood. Methods: The mitochondrial membrane potential (∆ψm) was evaluated using JC-1 staining. Intracellular reactive oxygen species (ROS) and mitochondrial ROS levels were detected using CM-H2DCFDA and MitoSOXTM Red, respectively. The levels of CD11b, NLRP3, pro-caspase-1 and manganese superoxide dismutase (SOD-2) were observed by western blotting, and the levels of interleukin-1beta (IL-1β) in culture supernatants were quantified using an ELISA kit. Results: Aβ induced microglia activation and mitochondrial dysfunction. In addition, mitochondrial dysfunction was associated with ROS accumulation and activation of the NLRP3 inflammasome. Importantly, Aβ induced activation of the NLRP3 inflammasome, leading to caspase-1 activation and IL-1β release in microglia. Moreover, EDA obviously attenuated the depolarization of ∆ψm, reduced mitochondria-derived ROS production and increased SOD-2 activity, resulting in the suppression of NLRP3 inflammasome-mediated IL-1β secretion in Aβ-treated microglia. Conclusion: EDA is a mitochondria-targeted antioxidant and exhibits anti-inflammatory effects on Aβ-treated microglia.
Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer
Authors: Yang Xiang , Bai Fan , Xu Yichen , Chen Yitian , Chen Longbang
Published: October 2017

Background/Aims: Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells. Methods: We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP) -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients’ chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor. Results: Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells. Conclusion: Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.
Exogenous H2S Protects Against Diabetic Cardiomyopathy by Activating Autophagy via the AMPK/mTOR Pathway
Authors: Yang Fan , Zhang Linxue , Gao Zhaopeng , Sun Xiaojiao , Yu Miao , Dong Shiyun , Wu Jichao , Zhao Yajun , Xu Changqing , Zhang Weihua , Lu Fanghao
Published: October 2017

Background/Aim: Autophagy plays an important role in cellular homeostasis through the disposal and recycling of cellular components. Hydrogen sulphide (H2S) is the third endogenous gas that has been shown to confer cardiac protective effects. Given the regulation of autophagy in cardioprotection, this study aimed to investigate the protective effects of H2S via autophagy during high glucose treatment. Methods: This study investigated the content of H2S in the plasma as well as myocardial, ultrastructural changes in mitochondria and autophagosomes. This study also investigated the apoptotic rate using Hoechst/PI as well as expression of autophagy-associated proteins and mitochondrial apoptotic proteins in H9C2 cells treated with or without GYY4137. Mitochondria of cardiac tissues were isolated and RCR and ADP/O were also detected. AMPK knockdown was performed with siRNA transfection. Results: In a STZ-induced diabetic model, NaHS treatment not only increased the expression of p-AMPK in diabetic group but further activated cell autophagy. Following 48h high glucose, autophagosomes and cell viability were reduced. The present results showed that autophagy could be induced by H2S, which was verified by autophagic ultrastructural observation and LC3-I/LC3-II conversion. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. The expressions levels of autophagic-related proteins were significantly elevated. Moreover, H2S activated the AMPK/rapamycin (mTOR) signalling pathway. Conclusions: Our findings demonstrated that H2S decreases oxidative stress and protects against mitochondria injury, activates autophagy, and eventually leads to cardiac protection via the AMPK/mTOR pathway.
IL-27 Modulates Chemokine Production in TNF-α -Stimulated Human Oral Epithelial Cells
Authors: Hosokawa Yoshitaka , Hosokawa Ikuko , Ozaki Kazumi , Matsuo Takashi
Published: October 2017

Background/Aims: Interleukin-27 (IL-27) is a cytokine which belongs to the IL-12 family. However, the role of IL-27 in the pathogenesis of periodontal disease is uncertain. The aim of this study was to examine the effect of IL-27 on chemokine production in TNF-α-stimulated human oral epithelial cells (TR146). Methods: We measured chemokine production in TR146 by ELISA. We used western blot analysis to detect the phosphorylation levels of signal transduction molecules, including STAT1 and STAT3 in TR146. We used inhibitors to examine the role of STAT1 and STAT3 activation. Results: IL-27 increased CXCR3 ligands production in TNF-α-stimulated TR146. Meanwhile, IL-27 suppressed IL-8 and CCL20 production induced by TNF-α. STAT1 phosphorylation level in IL-27 and TNF-α-stimulated TR146 was enhanced in comparison to TNF-α-stimulated TR146. STAT3 phosphorylation level in IL-27-treated TR146 did not change by TNF-α. Both STAT1 inhibitor and STAT3 inhibitor decreased CXCR3 ligands production. STAT1 inhibitor overrode the inhibitory effect of IL-27 on IL-8 and CCL20 production in TNF-α-stimulated TR146. Meanwhile, STAT3 inhibitor did not modulate IL-8 and CCL20 production. Conclusion: IL-27 might control leukocyte migration in periodontal lesion by modulating chemokine production from epithelial cells.
XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer
Authors: Zhang Yong-zhou , An Ji-Hong , Liu Yu-Xin , Wu Xian-Chuang , Han Shan-Shan , Ren Xue-qun , Qin Chang-Jiang
Published: October 2017

Background/Aims: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. Methods: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression. Following treatment with 5-FU, the effect of XRCC2 on proliferation was evaluated via a CCK-8 assay, the effects on cell cycle distribution and apoptosis were analyzed using flow cytometry, and γH2AX foci formation assays were performed to examine the influence of 5-FU on DNA Double-strand breaks(DSBs) repair in CRC cells. Results: XRCC2 expression in CRC tissues was significantly higher than that in normal tissues, and this increased XRCC2 expression was associated with advanced T staging, M staging, TNM staging, Duke’s staging, and greater liver and lymph node metastases. XRCC2 expression might be an independent prognostic indicator for CRC patients. Patients with negative XRCC2 expression exhibit greater sensitivity to treatment with 5-FU-based chemotherapy than those with positive XRCC2 expression. Moreover, our observations revealed that the knockdown of XRCC2 in CRC cells increased the sensitivities to 5-FU in terms of cell proliferation, apoptosis and cell cycle arrest. DNA DSBs repair was slower in the XRCC2-deficient cells than in the XRCC2-wild type cells. Conclusion: Our study demonstrated that XRCC2 might play an important role in CRC and function as a novel prognostic indicator and that the down-regulation of XRCC2 may be useful for sensitizing CRC cells during 5-FU chemotherapy.
Altered Expression Pattern of CD55 and CD59 on Red Blood Cells in Anemia of Chronic Kidney Disease
Authors: Al-Faris Lama , Al-Humood Salah , Behbehani Fatma , Sallam Husam
Published: October 2017

Objective: The aim of this study was to investigate the expression pattern of CD55 and CD59 on red blood cells (RBCs) in anemic chronic kidney disease (CKD) patients, and factors that might influence their expression. Subjects and Methods: Nighty-one adult anemic CKD patients and 80 healthy controls (HCs) were enrolled. Anemic CKD patients were divided into 3 subgroups based on receiving erythropoietin and renal replacement therapies. Flow cytometric analysis of CD55 and CD59 expression was performed on RBCs from blood samples obtained from CKD patients and HCs. Results: CD59 deficiency was significantly higher among CKD patients than HCs (n = 68, 74.7%, vs. n = 13, 16.3%, respectively; p < 0.001). The median proportions of CD55- and CD59-deficient RBCs in CKD patients were significantly higher compared to HCs (0.34 vs. 0.15, and 4.3 vs. 2.0, p < 0.001 and p < 0.001, respectively). The mean fluorescence intensity (MFI) of CD55 and CD59 expression was significantly lower in CKD patients compared to HCs (1.2 vs. 2.8, and 17.0 vs. 20.3, p < 0.04 and p < 0. 001, respectively). The hemoglobin level was inversely correlated with the proportions of CD55- and CD59-deficient RBCs (r = -0.37, p < 0.001, and r = -0.22, p < 0.02, respectively). The number of CD59-deficient patients was significantly different between the 3 subgroups of CKD patients (p = 0.001), and a significant difference was present in the MFI of CD55 and CD59 expression among the 3 subgroups (p = 0.04 and p = 0.03, respectively). Conclusion: The expression pattern of CD55 and CD59 on RBCs is altered in anemic CKD patients, which could play a role in the pathogenesis of anemia in CKD.