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The present study aimed to investigate the roles of cancer-associated fibroblasts (CAFs), matrix metalloproteinase-9 (MMP-9) and lymphatic vessel density (LVD) during the progression from adenocarcinoma in situ (AIS) to invasive lung adenocarcinoma (IAC). A total of 77 patients with stage 0-IA lung adenocarcinoma were enrolled. The expression levels of a-smooth muscle actin, MMP-9 and D2-40 were immunohistochemically analyzed. Survival analysis was performed using the Kaplan-Meier method. In the non-invasive component, the proportion of CAFs and the expression levels of MMP-9 increased from AIS to IAC; however, the LVD was not significantly different. CAFs were positively correlated with levels of MMP-9. The LVD had no significant correlation with CAFs and MMP-9. In the invasive component, CAFs, MMP-9 and LVD were significantly higher in IAC compared with in minimally invasive adenocarcinoma. CAFs, MMP-9 and LVD were all positively correlated with each other. The micropapillary subtype in IAC was associated with overall survival (OS). The LVD in IAC, but not MMP-9 and CAFs, was associated with OS. CAFs, MMP-9 and LVD were involved in the progression from AIS to IAC. CAFs exhibited a strong association with MMP-9 levels in the non-invasive and invasive components. The increase in the proportion of CAFs and the expression levels of MMP-9 may have been an early event before the adenocarcinoma became invasive. Once the adenocarcinoma was invasive, the LVD served an important role in tumor invasion and metastasis, and hence may be used as a prognostic marker of poor OS in stage IA IAC. [ABSTRACT FROM AUTHOR]

Heterotopic Warthin's tumor (WT) arising from the cervical lymph nodes is uncommon and WT presenting concomitantly with classical Hodgkin's lymphoma has only been previously reported three times in English literature. The current study presents an unusual case of classical Hodgkin lymphoma (CHL) involving the heterotopic WT in a 59-year-old male. Histopathologic examination revealied a WT with extensive expansion of mixed-cellularity CHL in a lymph node in the right of the neck. Clinical staging was determined as stage IA disease. The patient received four courses of chemotherapy and local consolidative radiotherapy, no evidence of disseminated lymphoma was observed over the 6-month follow-up. To the best of our knowledge, this is the first well documented collision tumor between CHL and heterotopic WT of the cervical lymph nodes. The present case also expands the anatomical site of malignant lymphomas associated with WT. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. For decades, the unilateral 6-hydroxydopamine (6-OHDA) rat model has been employed to investigate the pathogenesis and therapy of PD. However, the behavior and associated pathological features of the model long term have not previously been described dynamically. In the present study, the unilateral model was established by 6-OHDA injection in the striatum. The PD rat model was determined 2 weeks following surgery, according to the apomorphine (APO)-induced rotations, cylinder, rotarod and open field tests. TH-positive neurons and fibers in the substantia nigra pars compacta (SNpc) and striatum, respectively, and glial activation in the SNpc, determined by glial fibrillary acidic protein (GFAP) expression for astrocytes and CD11b (Mac1) expression for microglia, were detected by immunohistological staining. Correlation analysis was performed to understand the association between PD-associated behavior and pathology. The behavioral impairment progressively deteriorated during the process of experiment. In addition, the decrease in TH-positive neurons was associated with an increase in GFAPand Mac1-positive cells in the SNpc. Linear regression analysis indicated the association between behavioral and pathological changes. The results of the present study indicate that the APO-induced rotation, cylinder and rotarod tests are all sensitive and reliable strategies to predict the loss of TH+ neurons. These results provide a potential intervention time-point and a comprehensive evaluation index system for assessment of PD therapeutic strategies using the hemiparkinsonian rat. [ABSTRACT FROM AUTHOR]

Gram-negative (GN) bacterial infection is a main cause of bovine mastitis. The cluster of differentiation (CD) 14 gene serves an essential role in GN bacterium-induced innate immune response. CD14 works as a bacterial lipopolysaccharide (LPS) receptor, combines with LPS-liposaccharide binding protein complex, and causes cellular activation. However, the effects of CD14 single nucleotide polymorphisms (SNPs) on morbidity of clinical mastitis remain unclear. In the present study, To investigate the polymorphisms of CD14 gene and its effects on cows' susceptibility to mastitis, polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) assay was used to detect SNPs of CD14 gene in 134 Chinese Holsteins. SNPs were identified in PCR products amplified with 3 sets of primers in CD14 exon 2. A total of three SNPs were located in that exon: g.528 A→C (147Ser→Arg) in allele B; g.612 A→G (175Asn→Asp) in allele D; and g.1022 A→G in allele F (synonymous mutation). The SNPs in alleles B and D affected the secondary structure of CD14. A 3-dimensional (3D) structural analysis predicted three potential protein forms with a similar structure and indicated that the changes of the above-mentioned alleles were on the concave surface of the protein. In more detail, 147 Ser→Arg induced a protein kinase C phosphorylation site to move forward, as assessed by the motif analysis. The morbidity rate of AB (mixed type g.528 A/C) and CD (mixed type g.612 A/G) was the highest among all genotypes presented in the current study, and via of tumor necrosis factor-α and interleukin-6 mRNA levels were upregulated in animals of this genotype compared with others. Taken together, the CD14 SNPs identified in the present study, may be closely associated with the morbidity of mastitis. [ABSTRACT FROM AUTHOR]

The present study investigated the inhibitory effect of curcumin on human breast cancer MCF-7 cells and investigated the potential underlying molecular mechanisms. MCF-7 cells were cultured with curcumin at different concentrations and time points. The effects of curcumin treatment on breast cancer cell proliferation were studied using a MTT assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to assess the mRNA and protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) and inhibitor of NF-κB-α (IκBα). The proliferation of MCF-7 cells in the group treated with curcumin was markedly decreased compared with the control, with the greatest inhibitory effect at a concentration of 20 µM. The expression of Bax mRNA was increased and Bcl-2 mRNA expression was decreased compared with the control. Additionally, protein expression of NF-κB and IκB was increased. The data indicate that curcumin is able to inhibit breast cancer cell proliferation, possibly by regulating the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Previous studies have reported that angelicin exerted antiproliferative effects on several types of tumor cell. However, to the best of our knowledge, the effects of angelicin monotherapy on human liver cancer remain to be investigated. In the present study, the antitumor activity of angelicin was evaluated in vitro and in vivo, and the molecular mechanisms underlying its effects were investigated. The present results revealed that angelicin induced apoptosis in liver cancer cells in a dose‑ and time‑dependent manner. Furthermore, in HepG2 and Huh‑7 cells, angelicin‑induced apoptosis was demonstrated to be mitochondria dependent, involving the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase/RAC‑α serine/threonine‑protein kinase signaling pathway. In addition, administration of angelicin to mice bearing liver tumor xenografts inhibited tumor growth, without producing significant secondary adverse effects. These results suggested that angelicin may have potential as a novel therapeutic agent for the treatment of patients with liver cancer. [ABSTRACT FROM AUTHOR]

A previous study from our group using an in vivo model demonstrated that diet induced.obesity increases the risk of gastric cancer and may prompt its growth. However, the molecular mechanisms underlying this association remain unclear and require further investigation. The aim of the present study was to investigate the potential molecular mechanisms through which obesity affects gastric cancer growth. In a subcutaneous mouse model, tumors were significantly larger in obese mice compared with non.obese and lean mice. In addition, markedly increased levels of Sirt1 and YAP protein were observed in the nucleus of cells from subcutaneous tumors from obese mice compared with those from lean mice. Murine forestomach carcinoma (MFC) cells treated with 5% sera from obese mice exhibited significantly increased expression of Sirt1 and YAP compared with MFC cells treated with sera from lean mice. In addition, a positive correlation was observed between Sirt1 expression and YAP expression, and between Sirt1 expression and serum visfatin levels in mice. These results suggested that diet-induced obesity could promote murine gastric cancer growth by modulating the Sirt1/YAP signaling pathway. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-17 has been implicated in a variety of inflammatory lung diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI). Therefore, the aim of the present study was to confirm whether the increase in IL-17 expression following ALI enhances expression of inflammatory cytokines/chemokines through activation of the extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)-κB signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury; which, in turn, can be blocked by an IL-17 antagonist. The authors indicated that levels of IL-17 mRNA and protein were elevated in the bronchoalveolar lavage fluid (BALF) and lung tissues of ALI rats, and upregulation of IL-17 resulted in the enhanced severity of lung injury. Moreover, treatment with an IL-17 neutralizing antibody significantly inhibited the increases of parameters of ALI in rats, as evidenced by decreased histologic scores, BALF exudate volume, protein leakage and wet-to-dry weight ratio. In addition, management of IL-17 may markedly mitigate LPS-induced pulmonary inflammation, as reflected by the reduced levels of a multitude of proinflammatory cytokines in BALF. Of note, blockade of IL-17 effectively inhibited LPS-induced expression and activation of p-ERK1/2 and nuclear factor (NF)-κB p65 in lung tissues, and suppressed nuclear translocation of NF-κB p65. These results indicated that IL-17 serves an important role in LPS-induced ALI via stimulation of the ERK1/2 and NF-κB signaling pathway, and serves as a potential therapeutic target for treating LPS-induced ALI. [ABSTRACT FROM AUTHOR]

Despite the successes of bone marrow mesenchymal stem cell (BMSC) transplantation for the treatment of spinal cord injuries, only a small fraction of grafted cells migrate to the target areas. Therefore, there remains a need for more efficient strategies of BMSC delivery. The present study was designed to explore this. Rat models of spinal cord injury (SCI) were established and exposed to phosphate buffered saline (control), BMSCs or BMSCs + erythropoietin (EPO). Basso, Beattie and Bresnahan (BBB) locomotor scale and grid walk tests were then utilized to estimate neurological rehabilitation. Additionally, the following assays were performed: Immunofluorescence localization of BMSCs to the site of SCI; the transwell migration assay to detect in vitro cellular migration; the terminal deoxynucleotidyl transferase dUTP nick end labeling assay to determine the apoptotic index of the lesion; and western blotting analysis to evaluate the expression of vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) at the site of SCI. The BBB scores of the BMSC + EPO treated group were significantly increased compared with the BMSC treatment group (P<0.05). For example, BMSC + EPO treated rats had a significantly decreased number of hind limb slips compared with the BMSC treatment group (P<0.05). Furthermore, EPO significantly increased the migration capacity of BMSCs compared with the control group (P<0.001). In addition, the apoptotic index of the BMSC + EPO group was significantly decreased compared with the BMSC group (P<0.05). Green fluorescent protein-labeled BMSCs were detected at the site of SCI in the BMSC and BMSCs + EPO groups, with the signal being notably stronger in the latter. Moreover, the expression of VEGF and BDNF in the BMSCs + EPO group was significantly increased compared with the BMSC group (P<0.05). In conclusion, the results of the present study indicate that EPO can facilitate the recruitment of BMSCs to sites of SCI, increase expression of BDNF and VEGF, and accelerate recovery of neurological function following SCI. [ABSTRACT FROM AUTHOR]

Hemophilia B occurs due to a deficiency in human blood coagulation factor IX (hFIX). Currently, no effective treatment for hemophilia B has been identified, and gene therapy has been considered the most appropriate treatment. Mesenchymal stem cells (MSCs) have homing abilities and low immunogenicity, and therefore they may be potential cell carriers for targeted drug delivery to lesional tissues. The present study constructed an adeno-associated virus integration site 1 (AAVS1)-targeted vector termed AAVS1-green fluorescent protein (GFP)-hFIX and a zinc finger nuclease (ZFN) expression vector. Nucleofection was used to co-transfect the targeting vector and the ZFN expression vector into human MSCs. The GFP-positive cells were selected using flow cytometry. Site-specific integration clones were obtained following the monoclonal culture, subsequent detections were performed using polymerase chain reaction and Southern blotting. Following the confirmation of stem cell traits of the site-specific integration MSCs, the in vivo and in vitro expression levels of hFIX were detected. The results demonstrated that the hFIX gene was successfully transfected into the AAVS1 locus in human MSCs. The clones with the site-specific integration retained stem cell traits of the MSCs. In addition, hFIX was effectively expressed in vivo and in vitro. No significant differences in expression levels were identified among the individual clones. In conclusion, the present study demonstrated that the exogenous gene hFIX was effectively expressed following site-specific targeting into the AAVS1 locus in MSCs; therefore, MSCs may be used as potential cell carriers for gene therapy of hemophilia B. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the effect of complex prescription on the pharmacokinetics of baicalin, rhynochophylline and gastrodin in Tiangou antihypertensive capsule. After administration, rat plasma was collected at different time-points. High-performance liquid chromatography was used to determine the content of baicalin, rhynochophylline and gastrodin in plasma. Two peaks occurred in the baicalin concentration-time curve. No significant difference was found for the peak concentration time (tmax) and area under concentration-time curve (AUC) of baicalin between the complex prescription and baicalin groups. The peak concentration (Cmax) of baicalin in the complex prescription group was significantly decreased, while no significant difference was found for the absorption factor (Ka) and AUC of baicalin between the complex prescription and gastrodin groups. The elimination factor (Ke) of gastrodin in the complex prescription group was significantly decreased, while the apparent volume of distribution (Vd) of gastrodin was significantly increased. No significant difference was found for AUC of baicalin between the complex prescription and rhynochophylline groups. Levels of Ka and Ke of rhynochophylline were lower in the complex prescription group while Vd was higher. Thus, complex prescription made plasma concentration-time curve more smooth. By contrast, the Tiangou antihypertensive capsule improved the distribution of baicalin, rhynochophylline and gastrodin in vivo. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the functional mechanisms of osteopontin (Opn) and chemokine-like factor 1 (Cklf1) during the development and progression of abdominal aortic aneurysms (AAA) in rats. Healthy adult Sprague-Dawley rats (n=30) were randomly divided into the AAA, control and sham groups (10 rats/group) and experimental rat models of AAA were generated by enzyme perfusion in abdominal aorta for 30 min. The AAA formation was assessed by measuring the aortal diameter and hematoxylin and eosin staining as well as specific staining to detect the structural changes of the aorta and inflammatory cell infiltration. Immunohistochemistry, western blot analysis and statistical analysis were also performed to examine the expression levels of Opn, Cklf1 and matrix metalloproteinase (MMP)-2 in the arterial tissue. Rat models of AAA were successfully established by protease perfusion. After perfusion, the diameter expansion rate of abdominal aorta was significantly higher (P<0.01) compared to controls, elastin present at the middle layer was significantly reduced and inflammatory cell infiltration was significantly higher in AAA rats. The expression of Opn, Cklf1 and MMP-2 in the AAA group was significantly increased compared to the control group (P<0.05) as revealed by immunohistochemical staining. The western blot analysis revealed that, the expression levels of Opn, Cklf1 and MMP-2 in the AAA group were significantly higher than the sham and control groups (P<0.01). We also found that the expression of Opn and MMP-2 was positively correlated. In conclusion, in rat models of AAA, Opn and Cklf1 function synergistically to upregulate the expression of MMP-2, causing accelerated degradation of extracellular matrix and eventually leading to the development and progression of AAA. [ABSTRACT FROM AUTHOR]

Wogonin is considered to be an inhibitor of myeloid cell leukemia 1 and B-cell lymphoma 2, and a potential antitumor drug due to its ability to induce apoptosis in certain cancer cells; however, few previous studies have reported on wogonin-induced autophagy. The aim of the present study was to investigate the influence of wogonin on autophagy in human pancreatic cancer cells (HPCCs), elucidate its mechanism, and identify strategies to increase its effectiveness as an anti-cancer treatment. HPCCs were treated with wogonin and autophagy was detected in the cells. The mechanism of wogonin-related autophagy was investigated, and the antioxidant N-acetyl-L-cysteine (NAC) was used to assess the role of reactive oxygen species (ROS) in wogonin-related autophagy. The results demonstrated that wogonin may induce autophagy by activating the Beclin-1/phosphatidylinositol-3-kinase and ROS pathways in HPCCs, and may enhance ROS generation, followed by the activation of the AKT/ULK1/4E-BP1/CYLD pathway and inhibition of the mammalian target of rapamycin signaling pathway. The incubation of HPCCs with wogonin and the antioxidant NAC, revealed that the effects of wogonin-enhanced ROS generation on autophagy-related molecules were inhibited, contributing to the inhibition of autophagy and increasing the cell death ratio through apoptosis activation in HPCCs. These studies suggest that autophagy activation, via the ROS pathway, by the antitumor drug wogonin in HPCCs may partially reduce the antitumor effects of the drug, and that the antioxidant NAC may enhance the antitumor effectiveness of wogonin via the inhibition of ROS-enhanced autophagy and the subsequent promotion of apoptosis. Therefore, the present research suggests that wogonin combined with NAC may be a novel combination therapy for clinical pancreatic cancer therapy trials. [ABSTRACT FROM AUTHOR]

Although cryptococcal meningitis (CM) typically occurs in immunocompromised hosts, immunocompetent humans are susceptible to CM. In humans with an intact immune system, CM presents with signs and symptoms typical of meningitis, including fever, headache and neck stiffness. The present study reported the case of a female immunocompetent patient who presented visual blurring in both eyes and bilateral papilledema for ~1 month. Following hospital admission, the patient was diagnosed with optic nerve inflammation and was treated with intravenous methylprednisolone and oral prednisone. However, the initial symptoms failed to improve and the patient developed a headache. The microscopic examination and India ink test performed using the cerebrospinal fluid of the patient showed the presence of Cryptococcus neoformans. Following combined treatment with amphotericin B and fluconazole, the patient made a full recovery with total resolution of the initial symptoms. This case demonstrates that CM in immunocompetent patients may initially include eye symptoms, which may result in a delayed diagnosis of CM. [ABSTRACT FROM AUTHOR]

Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were -1.96 (-2.60, -1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (-0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (-0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of -2.27 (-4.36, -0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of -1.52 (-3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer. [ABSTRACT FROM AUTHOR]

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with chronic inflammatory activity and disrupted insulin signaling, leading to insulin resistance (IR). The present study investigated the benefits of neurolytic celiac plexus block (NCPB) on IR in a rat NIDDM model. Goto-Kakizaki rats fed a high-fat, high-glucose diet to induce signs of NIDDM were randomly divided into NCPB and control groups; these received daily bilateral 0.5% lidocaine or 0.9% saline injections into the celiac plexus, respectively. Following 14 and 28 daily injections, rats were subject to oral glucose tolerance tests (OGTTs) or sacrificed for the analysis of serum free fatty acids (FFAs), serum inflammatory cytokines and skeletal muscle insulin signaling. Compared with controls, rats in the NCPB group demonstrated significantly (P<0.05) lower baseline, 60-min and 120-min OGTT values, lower 120-min serum insulin, lower IR [higher insulin sensitivity index (ISI1) and lower ISI2) and lower serum FFAs, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Conversely, NCPB rats exhibited higher basal and insulin-stimulated skeletal muscle glucose uptake and higher skeletal muscle insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 expression. There were no differences between the groups in insulin receptor β (Rβ) or Akt expression; however Rβ-Y1162/Y1163 and Akt-S473 phosphorylation levels were higher and IRS-1-S307 phosphorylation were lower in NCPB rats than in the controls. These results indicate that NCPB improved insulin signaling and reduced IR, possibly by inhibiting inflammatory cytokine release. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is the leading cause of mortality and disabilities among all trauma cases. Following TBI, damage to axons results in τ protein hyperphosphorylation leading to microtubule instability and τ-mediated neurodegeneration. In addition, τ protein is proteolytically cleaved and is able to access the cerebrospinal fluid (CSF) and serum; thus, this protein may serve as a potential biomarker in the diagnosis of injury severity and outcome prediction. Although a limited number of studies have investigated the CSF τ protein levels after TBI, the data are divergent and conflicting, and investigations into the serum τ protein levels have yet to be conducted. Therefore, the present study aimed to examine the serum τ protein levels in the full spectrum of TBI patients on days 0-14 after TBI, using an enzyme-linked immunosorbent assay. The protein levels were compared to the initial Glasgow Coma Score (GCS) and the Extended Glasgow Outcome Scale (GOS-E), which are used to represent the injury severity and patient outcome, respectively. In total, 56 patients, including 20 patients with mild TBI (GCS, 13-15), 19 patients with moderate TBI (GCS, 9-12) and 17 patients with severe TBI (GCS, 3-8), were included in the current study. The outcome was assessed 1 year after the injury and patients were classified into the good outcome (40 cases; GOS-E, 5-8) and poor outcome groups (16 cases; GOS-E, 1-4). The results indicated that serum τ protein levels increased soon after TBI and reached a peak value at ~2 days after the injury. The serum τ protein levels were significantly higher in the severe TBI group compared with those in the mild and moderate TBI groups (P<0.0001). Univariate analysis indicated that poor outcome was significantly associated with higher serum τ protein levels on day 2 (P<0.0001). A receiver operating characteristic curve demonstrated that a τ protein level of >116.04 pg/ml on day 2 resulted in a 93.75% sensitivity and 92.50% specificity for predicting a poor outcome. Furthermore, a τ protein level of >372.1 pg/ml on day 2 yielded 100% sensitivity and 83.33% specificity for 1 year mortality in the severe TBI group. In conclusion, the present study suggests that serum τ protein may serve as a potential biomarker for evaluating the injury severity and predicting the outcome of TBI patients. [ABSTRACT FROM AUTHOR]

Infection is one of the most severe complications of total knee prosthesis implantation. The present study reported the case of a 74-year-old female that developed a Staphylococcus epidermidis infection following a cemented total knee arthroplasty. A routine blood test revealed neutropenia and anemia, while S. epidermidis was detected in the peripheral blood and bone marrow. In the present case, S. epidermidis infection led to acute arrest of hematopoiesis (AAH), also known as aplastic crisis, which is the temporary cessation of red cell production. The development of AAH secondary to S. epidermidis infection is rare and, to the best of our knowledge, this is the first case reported in the literature. The present study increased our knowledge of this rare disease and its characteristics, which will enable physicians to be aware of the development of AAH as a rare complication of S. epidermidis infection. [ABSTRACT FROM AUTHOR]

α-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP. The 3 cases demonstrated resistance to multiple drugs, including epidermal growth factor receptor inhibitors, despite the presence of wild-type Kirsten rat sarcoma viral oncogene homolog (K-RAS; codons 12 and 13), neuroblastoma-RAS (codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (V600E). We propose that hepatoid histological features or a positive AFP finding by immunohistochemistry are sufficient for a diagnosis of AFP-producing colorectal adenocarcinoma. Furthermore, we speculates that autocrine HGF/c-Met activation may be capable of inducing the dedifferentiation [ABSTRACT FROM AUTHOR]

The mechanisms leading to high rates of malignancy and recurrence of human intrahepatic cholangiocarcinoma (ICC) remain unclear. It is difficult to diagnose and assess the prognosis of patients with ICC in the clinic due to the lack of specific biomarkers. In addition, long non.coding RNAs (lncRNAs) have been reported to serve important roles in certain types of tumorigenesis however a role in ICC remains to be reported. The aim of the current study was to screen for genes and lncRNAs that are abnormally expressed in ICC and to investigate their biological and clinicopathological significance in ICC. The global gene and lncRNA expression profiles in ICC were measured using bioinformatics analysis. Carbamoyl.phosphate synthase 1 (CPS1) and its lncRNA CPS1 intronic transcript 1 (CPS1.IT1) were observed to be upregulated in ICC. The expression of CPS1 and CPS1.IT1 was measured in 31 tissue samples from patients with ICC and a number of cell lines. The effects of CPS1 and CPS1.IT1 on the proliferation and apoptosis of the ICC.9810 cell line were measured. In addition, the clinicopathological features and survival rates of patients with ICC with respect to the gene and lncRNA expression status were analyzed. CPS1 and CPS1.IT1 were co.upregulated in ICC tissues compared with non.cancerous tissues. Knockdown of CPS1 andor CPS1.IT1 reduced the proliferation and increased the apoptosis of ICC.9810 cells. Additionally, clinical analysis indicated that CPS1 and CPS1.IT1 were associated with poor liver function and reduced survival rates when the relative expression values were greater than 4 in cancer tissues. The comparisons between the high CPS1 expression group and the low expression group indicated significant differences in international normalized ratio (P=0.048), total protein (P=0.049), indirect bilirubin (P=0.025), alkaline phosphatase (P=0.003) and disease.free survival (P=0.034). In addition, there were differential trends in CA19.9 (P=0.068), globulin (P=0.052) and total bilirubin (P=0.066). The comparisons between the high CPS1.IT1 expression group and the low expression group indicated significant differences in lymphatic invasion (P=0.045), carbohydrate antigen 19.9 (P=0.044), disease.free survival (P=0.026), and non.significant differential trends in alkaline phosphatase were observed (P=0.085). In conclusion, CPS1 and CPS1.IT1 may serve an important role in ICC development by promoting the proliferation of ICC cells. Furthermore, CPS1 and CPS1.IT1 were associated with poor liver function and reduced survival rates. Thus, CPS1 and CPS1.IT1 may be potential prognostic indicators for patients with ICC. [ABSTRACT FROM AUTHOR]

Inflammation is a major contributing factor in the development of diabetic microvascular complications, regardless of whether improved glycaemic control is achieved. Studies have increasingly indicated that fenofibrate, a lipid-lowering therapeutic agent in clinical use, exerts a potential anti-inflammatory effect, which is mediated by sirtuin 1 (SIRT1; an NAD+-dependent deacetylase) in endothelial cells. The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR). The data demonstrated that high glucose treatment in human retinal endothelial cells (HRECs) inhibited the expression and deacetylase activity of SIRT1. The reduction of SIRT1 expression and deacetylase activity persisted following a return to normal glucose levels. Furthermore, nuclear factor-B expression was observed to be negatively correlated with SIRT1 expression and activity in HRECs under high glucose levels and the subsequent return to normal glucose levels. Fenofibrate treatment abrogated these changes. Knockdown of SIRT1 attenuated the effect of fenofibrate on high glucose-induced NF-B expression. In addition, fenofibrate upregulated SIRT1 expression through peroxisome proliferator-activated receptor a in high glucose-induced metabolic memory. These findings indicate that fenofibrate is important in anti-inflammatory processes and suppresses the cellular metabolic memory of high glucose-induced stress via the SIRT1-dependent signalling pathway. Thus, treatment with fenofibrate may offer a promising therapeutic strategy for halting the development of DR and other complications of diabetes. [ABSTRACT FROM AUTHOR]

Male accessory breast cancer is an extremely rare tumor. Several risk factors have been identified, including genetic and hormonal abnormalities. Accessory breast carcinoma usually occurs under the axilla or in the inguinal region. Clinical diagnosis is frequently delayed due to the general lack of awareness among physicians and patients. In the present study, the case of a 63-year-old male patient who was diagnosed with accessory breast cancer at a local advanced stage was reported. However, the patient was successfully treated with endocrine therapy. [ABSTRACT FROM AUTHOR]

Determining the molecular phenotype is a key to understanding and predicting the metastatic potential and the prognosis for patients with lung cancer. Our previous study demonstrated that increased expression of cyclin-dependent kinase 5 (CDK5) in patients with non-small cell lung cancer (NSCLC) is associated with a poorer prognosis. The present study aimed to further investigate the underlying mechanism of CDK5 in vitro and in vivo using the A549 human NSCLC cell line. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to quantify the proliferation of the A549 cells; migration assay and invasiveness assays were performed using Transwell chambers and wound healing assays were used to assess cell motility, which was assessed by measuring the movement of cells. Inhibition of CDK5 by roscovitine and small interfering (si)RNA was used to investigate the mechanism of CDK5 in the process of A549 lung cancer cell proliferation, migration and invasion. The results demonstrated that functional inhibition of CDK5 using roscovitine and siRNA markedly suppressed the proliferation of A549 cells and resulted in a reduced tumor mass in vivo. In addition, the hinhibition of CDK5 reduced the migration and invasiveness of the A549 cells in vitro and in vivo. Notably, CDK5 inhibition also impaired tumor cell cytoskeletal remodeling and led to loss of cell polarity, which may partially explain the reduction of A549 cell mobility and invasiveness. The results of the present study revealed that CDK5 may be important in the regulation of migration and invasiveness in NSCLC through its effects on cytoskeletal remodeling. [ABSTRACT FROM AUTHOR]

Lumbar disc herniation (LDH) is a common cause of lumbosacral radiculopathy. An autoimmune response to a herniated nucleus pulposus (NP) has been suggested to play an important role in the initiation of radiculopathy. Interleukin-17 (IL-17) is a cytokine associated with inflammation and autoimmunity. The presence of IL-17 has been studied in patients with LDH; however, extensive investigation into the expression of IL-17 in different disc pathologies of LDH has not yet been conducted. The aim of the present study was to investigate the role of neovascularization and hypertrophic chondrocytes in herniated intervertebral lumbar discs. Fifty-two intervertebral lumbar disc specimens were extracted from 46 patients with LDH and were subsequently classified as either contained or non-contained disc herniation (CDH and NCDH, respectively). The specimens were stained with hematoxylin and eosin or toluidine blue, or were immunostained with polyclonal antibodies to IL-17 using the streptavidin-peroxidase method. The neovascular tissue and staining results were graded to establish the histological differences between the two herniation types. The intervertebral discs (IVDs) obtained from patients with NCDH showed significantly more neovascularization and granulation tissue than the discs obtained from patients with CDH (P<0.05). Furthermore, hypertrophic chondrocytes were more abundant in the NCDH specimens than in the CDH specimens (P<0.05). Similarly, the number of IL-17-immunoreactive cells was significantly higher in the NCDH specimens than that in the CDH specimens (P<0.01). In conclusion, local inflammation and autoreactive immune activation may play an important role in the pathogenesis of LDH. These results also suggest a role of chondrocytes in the repair of herniated IVDs. [ABSTRACT FROM AUTHOR]

The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the role of eIF2α in cardiomyocyte apoptosis and evaluate the cardioprotective role of salubrinal in a rat myocardial infarction (MI) model. Rat left anterior descending coronary arteries were ligated and the classical proteins involved in the endoplasmic reticulum stress (ERS)-induced apoptotic pathway were analyzed using quantitative polymerase chain reaction and western blot analysis. Salubrinal was administered to the rats and cardiomyocyte apoptosis and infarct size were evaluated by a specific staining method. Compared with the sham surgery group, the rate of cardiomyocyte apoptosis in the MI group was increased with the development of the disease. It was also demonstrated that the mRNA and protein levels of GRP78, caspase-12, CHOP and the protein expression of p-eIF2α were increased in the MI group. Furthermore, the results showed that treatment with salubrinal can decrease cardiomyocyte apoptosis and infarct size by increasing eIF2α phosphorylation and decreasing the expression of caspase-12 and CHOP. The present study suggests that salubrinal protects against ER stress-induced rat cadiomyocyte apoptosis via suppressing the dephosphorylation of eIF2α in the ERS-associated pathway. [ABSTRACT FROM AUTHOR]

Paclitaxel-coated balloons (PCBs) have become attractive alternative treatment options for patients with in-stent restenosis (ISR); however, the safety and efficacy of PCBs in comparison with those of conventional therapies are less well defined. The aim of this meta-analysis was to systematically review the efficacy and safety of PCBs for patients with ISR using comparisons with control groups. Electronic databases, such as MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, were searched, and eligible studies that compared PCBs with uncoated balloons (UCBs) or drug-eluting stents (DESs) in patients with ISR were considered. Subgroup analyses were performed with different control groups. Nine studies (1,488 patients, 1,608 lesions) were included in the meta-analysis. Compared with patients who underwent UCB angioplasty, those who underwent PCB angioplasty exhibited a clear superiority in late lumen loss (LLL) [weighted mean difference (WMD), -0.46; 95% confidence interval (CI), (-0.59)-(-0.34); P<0.00001] and major adverse cardiac events (MACEs) [odds ratio (OR), 0.21; 95% CI, 0.13-0.33; P<0.00001]. The OR for myocardial infarction (MI) (OR, 0.46; 95% CI, 0.15-1.47; P=0.19) did not reach statistical significance. PCBs were associated with similar outcomes when compared with DESs with regard to LLL (WMD, -0.04; 95% CI, -0.18-0.10; P=0.57), MACEs (OR, 0.74; 95% CI, 0.36-1.53; P=0.42) and the ORs for all endpoints, including total mortality, target lesion revascularization, MI, stent thrombosis and binary restenosis, and no statistically significant differences were found. This meta-analysis showed that PCBs are associated with superior outcomes when compared with UCBs in the management of ISR, and are at least as efficacious and as well tolerated as DESs. [ABSTRACT FROM AUTHOR]

The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood-brain-tumor barrier. In the present study, cyclic Arginine-Glycine-Aspartic acid-D-Tyrosine-Lysine [c(RGDyK)], that has a high binding affinity to integrin avβ3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid-polyethylene glycol (DTX-PLA-PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine-Glycine-Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX-PLA-PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non-targeted micelles showed limited transport ability. Furthermore, RGD-linked micelles showed marked anti-glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand-mediated drug delivery may improve the efficacy of brain cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC) transplantation has been proposed as a promising therapeutic strategy for ischemic myocardium repair following myocardial infarction. Differentiation of MSCs into cardiomyocyte-like cells prior to cell transplantation is advantageous in improving their potential clinical benefits for cardiac repair. In the present study, we isolated and cultured porcine MSCs and evaluated the synergistic effect of 5-azacytidine (5-AZA) treatment and insulin-like growth factor-1 (IGF-1) gene manipulation on MSC differentiation into cardiomyocyte-like cells. Our results demonstrated that 5-AZA treatment alone induced a limited cardiomyocyte-like differentiation effect in vitro. Overexpression of the IGF-1 gene in MSCs improved the induction effect of 5-AZA, while knockdown of the IGF-1 gene attenuated the differentiation. These results suggest that IGF-1 is a significant stimulus affecting the cardiomyocyte-like differentiation of porcine MSCs. In addition, the combination of IGF-1 gene manipulation and 5-AZA treatment provides a new strategy to obtain more committed differentiated cardiomyocyte-like cells from porcine MSCs prior to cell transplantation. [ABSTRACT FROM AUTHOR]

This study used a streptozotocin (STZ)-induced rat model of diabetes to investigate whether Ras-related C3 botulinum toxin substrate 1 (Rac1) was involved in the pathogenesis of diabetic retinopathy. The effects of Rac1 inhibition on vascular endothelial (VE)-cadherin and β-catenin expression in high glucose-induced rat retinal endothelial cells (RRECs) were additionally examined. Rac1 activation in the retinas from STZ-induced diabetic rats and in high glucose-induced RRECs was measured by reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. The expression levels of VE-cadherin and β-catenin were also examined with or without Rac1 inhibition through small interfering (si)RNA transfection. STZ-induced diabetes was associated with an increase in the vascular permeability of the retina. Furthermore, Rac1 activation was increased in the retina of STZ-induced diabetic rats and in high glucose-induced RRECs compared with that in the controls. Immunohistochemistry showed that immunostaining of Rac1 was localized in the outer plexiform, inner nuclear, inner plexiform and ganglion cell layers and in the retinal microvasculature of rats. The expression of β-catenin was increased in the retinas of the diabetic rats at four, eight and 12 weeks after the induction of diabetes compared with that in the controls. Additionally, Rac1 activation was required for the high glucose-induced VE-cadherin expression decrease and for β-catenin expression in high glucose-induced RRECs. Rac1 inhibition by Rac1-siRNA transfection effectively prevented hyperpermeability, β-catenin expression and the VE-cadherin expression decrease in high glucose-induced RRECs. In conclusion, diabetes affects the expression of Rac1 in the retina. Rac1 may be involved in the diabetes-induced damage and/or alterations to the blood-retinal barrier through changes in VE-cadherin and β-catenin expression. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the T helper 1 (Th1)/Th2 cytokine shift and its clinical significance in the peripheral blood and tumor tissues of non-small cell lung cancer (NSCLC) patients. In total, 124 NSCLC patients who were admitted to Xinxiang Central Hospital were selected, along with 124 healthy individuals undergoing physical examination at the same hospital during this period (as controls). ELISA was conducted to detect the Th1 and Th2 cytokine levels in the peripheral blood of patients in the two groups prior to and following radical surgery treatment. In addition, the Th1 and Th2 cytokine levels in the peripheral blood of the observation group were measured following surgery to analyze the correlation between relapse and survival. Compared with the control group, interleukin 4 (IL-4) and IL-10 concentrations in the peripheral blood of the observation group, prior to and following surgery, were significantly higher, whilst IL-2 and interferon-γ (INF-γ) concentrations were significantly lower (P<0.05). In the observation group, the IL-4 and IL-10 concentrations were significantly decreased following surgery, as compared with prior to surgery (P<0.05), whilst the IL-2 and INF-γ concentrations increased significantly (P<0.05). The one- and three-year cumulative relapse frequencies of patients with postoperative IL-4 abnormalities were significantly increased compared with those in patients with normal IL-4 levels following surgery (P<0.05), and the median survival time and survival rate significantly decreased in patients with postoperative IL-4 abnormalities (P<0.05). In terms of the three-year cumulative relapse rate, median survival time, and one- and three-year cumulative survival rate, patients with postoperative IL-2, IL-10 and INF-γ level abnormalities did not present any statistical significance compared with those without such abnormalities (P>0.05). In conclusion, Th2 cytokines dominate the peripheral blood of NSCLC patients and radical surgery treatment may improve the Th1/Th2 shift in patients. Furthermore, postoperative IL-4 levels were observed to correlate with relapse and the survival rate of patients; therefore, IL-4 may be considered as an auxiliary in the postoperative diagnosis during clinical practice. [ABSTRACT FROM AUTHOR]

The long-term urodynamics of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer remain unclear in the clinical setting. The present prospective observational study was conducted between January 2010 and December 2012 to evaluate the 6-month and 12-month follow-up data of urodynamic changes of bladder cancer patients who were initially treated by laparoscopic radical cystectomy with orthotopic ileal neobladder. A total of 53 eligible patients were included, and all patients were followed up for at least 12 months, with a median time of 18 months. During the follow-up period, no patients reported difficulty urinating, and the daily frequency of urination and the urine output were gradually improved with time. Dynamic urodynamic examinations showed that the maximum flow rate (11.4±1.1 vs. 7.3±1.4 ml/sec; P<0.001), residual urine content (22.8±10.5 vs. 40.7±12.7 ml; P<0.001), maximum bladder capacity (373.8±62.2 vs. 229.7±56.3 ml; P<0.001) and maximum bladder pressure during filling (35.8±6.7 vs. 26.4±7.0 cm H2O; P<0.001) at 12 months were all improved significantly compared with that at 6 months after the initial surgical treatment. However, there were no significant differences in maximum bladder pressure during voiding (75.7±24.7 vs. 73.1±24.7 cm H2O; P=0.618) and bladder compliance (26.9±13 vs. 27.4±13.1 cm H2O; P=0.848) at 12 and 6 months after initial surgical treatment. In conclusion, the urodynamics of this orthotopic ileal neobladder gradually improve, and its long-term urine storage and voiding functions are acceptable. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the inhibitory effect of sodium houttuyfonate (SH) on synovial cell proliferation in vitro. Primary cells were obtained from the synovial tissue of a patient with rheumatoid arthritis (RA). The cells were divided into five treatment groups as follows: the control group (group 1), 25 µg/ml SH-treated group (group 2), 50 µg/ml SH-treated group (group 3), 100 µg/ml SH-treated group (group 4) and the 200 µg/ml SH-treated group (group 5). Following seven days of treatment, the proliferation rate of the synovial cells was then detected using an MTT assay. The expression level of proliferative synovial cells markedly decreased in the SH-treated groups in a dose-dependent manner compared with the control group. In conclusion, the present study demonstrated that SH was able to inhibit the proliferation of synovial cells obtained from a patient with RA. These results provide a potential theoretical basis for the development of a safe and effective treatment against RA in the future. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the protection of allogeneic bone marrow mesenchymal stem cells (BMSCs) on an ischaemia/reperfusion (I/R)-induced acute kidney injury (AKI) rat model and to investigate the underlying mechanisms. The BMSCs were isolated and cultured from adult Sprague-Dawley (SD) rats and the I/R-induced AKI model was established by bilateral clamping of renal pedicles for 60 min. Following successfully establishing the AKI model, 1x106 BMSCs were administered by intrarenal injection. All animals were randomly divided into four groups (n=10 in each): 1 (sham control), 2 (I/R), 3 (I/R + culture medium) and 4 (I/R + BMSCs). Serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured in all four groups at 24 and 72 h. Three days post-surgery, the level of inflammatory factors, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in the kidney was analysed by quantitative polymerase chain reaction. Three days following surgery, mRNA expression levels of IL-6 and TNF-α were significantly lower, however, the expression level of VEGF was significantly higher in group 4 compared with groups 2 and 3 (P<0.05). By contrast, the immunofluorescence results showed that the injected BMSCs differentiated into vascular endothelial cells. In conclusion, the present study identified that intrarenal administration of BMSCs improved I/R-induced AKI through the anti-inflammatory effect and a paracrine mechanism and therefore, may be hypothesised for the use in clinical trials. [ABSTRACT FROM AUTHOR]

Intracranial germinomas (IG) are rare tumors that typically occur in the pineal gland and suprasellar region of the brain. IG can be successfully treated with radiation therapy and its recurrence is rare. The present study reports the case of a patient with IG involving the pineal and suprasellar regions. The patient was treated with radiotherapy, achieving significant remission. However, recurrence was discovered 10 months later. The patient was subsequently treated with chemotherapy and radiotherapy, resulting in gradual remission. The patient had recovered 2 months later and was in good health. The entire evolution process, including magnetic resonance (MR) imaging and MR spectroscopy findings, are described herein. The present case suggests that MR spectroscopy may be useful for monitoring the effects of treatment. [ABSTRACT FROM AUTHOR]

Histiocytic necrotizing lymphadenitis (HNL) is a unique form of self-limiting lymphadenitis with an unknown cause. The majority of cases resolve within several months and the disease has a low recurrence rate of 3-4%. In the present study, a prolonged recurrent case of HNL was reported. A 44-year-old female developed recurrent HNL with generalized lymphadenopathy 14 years after the original episode. [ABSTRACT FROM AUTHOR]

Neurothekeomas are unusual benign soft tissue tumors of the peripheral nervous system, which commonly occur on the head, neck and upper extremities of young females in the second and third decades of life. This is the first case report of neurothekeoma developing simultaneously in the thoracic and lumbar area in a 51-year-old male. The two tumors were completely excised along the capsule under local anaesthesia and the incisions were closed in layers following adequate hemostasis. Histopathologically, the examination of the microscopic slides from the thoracic and lumbar masses revealed the presence of spindle and similar epithelioid cells arranged in fascicles, often in a geographical pattern, in a background of myxoid stroma. The immunohistochemical analysis demonstrated that the tumor cells were positive for vimentin, CD57 and actin and negative for S-100 protein, HMB-45 and CD34. The tumors were diagnosed as neurothekeomas. The patient remains alive and well on follow-up at 7 years, without evidence of recurrence. [ABSTRACT FROM AUTHOR]

A 61-year-old female was referred to The First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, China) due to a right adrenal tumor. A pre-oper-ative transcutaneous fine-needle aspiration biopsy and right adrenalectomy were performed, and pathological analysis resulted in the diagnosis of pleomorphic rhabdomyosarcoma (RMS). Primary pleomorphic RMS of the adrenal gland in an adult is a rare condition. To the best of our knowledge, this is the first case of pleomorphic RMS of the adrenal gland in an adult diagnosed by light microscopy and immunohisto-chemical stains. [ABSTRACT FROM AUTHOR]

Anthracyclic (ANT) drugs are widely used for patients with malignant tumors and can markedly prolong the disease-free survival rate of patients. As its clinical application becomes more common, information regarding serious cardiotoxicity as a result of ANT treatment is becoming understood. However, to the best of our knowledge, delayed-onset cardiotoxicity due to ANT use has not been studied sufficiently. The present report describes a 36-year-old male patient who presented to Guiqian International General Hospital (Guiyang, China) with a complaint of dyspnea in the last 10 days. Substantially elevated B-type natriuretic peptide levels and echocardiography showing enlargement of the entire heart, of the patient suggested that severe heart failure was the cause of his symptoms. However, the cause of this potential heart failure was not apparent until the patient was questioned about his cancer treatment history. Following consultation to evaluate the assessment of end-stage heart failure, currently only anti-heart failure treatment and symptomatic treatment can be provided. The present report describes this case and reviews the existing literature to provide a basis for the diagnosis and treatment of patients with delayed-onset heart failure following ANT treatment. [ABSTRACT FROM AUTHOR]

Long non‑coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) has been reported to exert an important role in acute lung injury (ALI). The present study aimed to investigate the potential underlying mechanism of CASC2 in ALI progression. Reverse transcription‑quantitative PCR was conducted to examine the expression of CASC2, microRNA (miR/miRNA)‑27b and TGF‑β activated kinase 1 and MAP3K7‑binding protein 2 (TAB2) in A549 cells. Cell viability and apoptosis were analyzed using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and flow cytometry. Enzyme‑linked immunosorbent assay was used to measure the levels of inflammatory‑related cytokines to assess the inflammatory response, including interleukin‑1β (IL‑1β), IL‑6 and tumor necrosis factor α (TNF‑α). The binding sites of miR‑27b in CASC2 or TAB2 were predicted using LncBase or microT‑CDS software, following which dual‑luciferase reporter and RNA binding protein immunoprecipitation assays were performed to confirm the target relationship between miR‑27b and CASC2 or TAB2. The protein expression of TAB2 was detected by western blotting. The decreased viability, and increased apoptosis and inflammatory responses were attenuated by the accumulation of CASC2 in lipopolysaccharide (LPS)‑stimulated A549 cells. CASC2 could directly bind to miR‑27b in A549 cells. CASC2 protected A549 cells from LPS‑triggered injury by downregulating miR‑27b. TAB2 was a target of miR‑27b in A549 cells. The influence of miR‑27b depletion was reversed by the silencing of TAB2 in an ALI cell model. CASC2 could increase the expression of TAB2 by serving as a competing endogenous RNA of miR‑27b in A549 cells. Collectively, the results suggested that CASC2 attenuated LPS‑induced injury in the ALI cell model by modulating the miR‑27b/TAB2 axis. [ABSTRACT FROM AUTHOR]

Insufficient invasion of trophoblasts is correlated with the development of preeclampsia (PE). MicroRNA (miR)‑491‑5p has been reported to be implicated in human cancer cell invasion; however, whether miR‑491‑5p is involved in the development of PE remains largely unclear. The aim of the present study was to investigate the role of miR‑491‑5p in trophoblastic invasion in vitro and to determine its underlying mechanism of action. The expression levels of miR‑491‑5p were validated using reverse transcription‑quantitative PCR. The effects of miR‑491‑5p on trophoblast cell invasion were evaluated in vitro. Then, the association between miR‑491‑5p and its downstream target was investigated in both cell lines and clinical specimens. miR‑491‑5p expression levels were observed to be significantly increased in the placental tissues from patients with PE. The invasive capacity of HTR‑8/SVneo trophoblast cells was suppressed following the upregulation of miR‑491‑5p and increased following the inhibition of miR‑491‑5p. Matrix metalloproteinase‑9 (MMP‑9), a well‑known regulator of trophoblast cell invasion, was discovered to be a direct target of miR‑491‑5p in HTR‑8/SVneo trophoblast cells. Moreover, miR‑491‑5p expression levels were found to be inversely correlated with MMP‑9 expression levels in placental tissues from patients with PE. The overexpression of MMP‑9 partly attenuated the inhibitory effects of miR‑491‑5p on HTR‑8/SVneo trophoblast cells invasion. Collectively, these findings suggested that the aberrant expression of miR‑491‑5p may contribute to PE through suppressing trophoblast invasion, thus highlighting the novel roles of miR‑491‑5p in the molecular pathogenesis of PE. The present study also showed that the miR‑491‑5p/MMP‑9 axis may be an effective biomarker or a viable drug target for therapeutic intervention in PE. [ABSTRACT FROM AUTHOR]

Myxoma is rare in the upper leg. The current study presents the case of a large tumor in the right upper leg. The tumor extended to pelvic cavity and was found to be connected with a cystic and solid neoplasm that was adjacent to the ascending colon in the right lower quadrant. The large tumor of the upper leg had existed for 15 years and had ulcerated through the skin 4 days prior to admittance. Palliative surgery was performed, with histological findings of a myxoma. Since appendiceal mucinous neoplasms may invade organizations outside of the mucous layer of the appendix and cause secondary peritoneal myxoma, this myxoma of the upper leg probably originated from an appendiceal mucinous neoplasm. [ABSTRACT FROM AUTHOR]

Metastatic cystic lesions may be considered as target lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. However, cystic lesions are considered as non-measurable according to RECIST 1.0. Krukenberg tumors are cystic metastases from gastric cancer. The aim of the present case report was to address the question of whether a Krukenberg tumor can be considered as a target lesion. A 30-year-old female patient was diagnosed with stage IV gastric cancer 6 months after parturition. Subsequently, the patient received two courses of oxaliplatin/capecitabine plus trastuzumab (OCT) treatment. The response evaluation was considered as stable disease. However, after four courses of OCT, the cystic target lesion in the right pelvic cavity exhibited an increase in diameter of >40%. After one more cycle of OCT, contrast-enhanced magnetic resonance imaging (MRI) revealed that the diameter of the cystic mass lesion had decreased by >35% and a further two cycles of treatment were administered. After the last OCT cycle, the levels of the tumor markers cancer antigen (CA) 125, CA19-9 and CA153 had markedly increased, although the cystic mass had decreased in size. Eventually, positron emission tomography-computed tomography (PET/CT) was used to assess the efficacy of treatment. A new lesion was identified, indicating progressive disease. The present case demonstrated that the Krukenberg tumor may be considered as a non-target lesion. In addition, tumor markers and PET/CT yielded results complementary to those of contrast-enhanced MRI in the therapeutic assessment of advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Haishengsu (HSS) is an active natural extract isolated from Tegillarca granosa, which has previously been demonstrated to inhibit the proliferation of several types of cancer cells in vitro. Our previous study indicated that HSS may induce apoptosis to suppress growth of human hepatocellular carcinoma BEL‑7402 cells by activating Fas pathway. The present study demonstrated that HSS treatment induces the in vitro apoptosis of BEL‑7402 cells via the mitochondrial‑mediated apoptotic pathway detected by DNA fragmentation assay, caspase activity assay and transmission electron microscopy assay, and inhibits tumor xenograft growth in vivo. Alterations in apoptotic regulatory proteins were detected, including decreased expression of B‑cell lymphoma2 (Bcl‑2), upregulation of Bcl‑2‑associated X protein and mitochondrial cytochrome c release, and downstream activation of apoptotic signaling. Furthermore, apoptotic induction was caspase‑dependent, as indicated by cleavage of the caspase substrate, poly (ADP‑ribose) polymerase. Oral administration of 62.5‑250 mg/kg HSS markedly educed the growth of hepatocellular carcinoma tumor xenografts in nude mice. In addition, immunohistochemical staining for caspase‑3 protein and transmission electron microscopy further indicated the induction of apoptosis in these tumor tissues. Taken together, the present study demonstrated that HSS may effectively induce apoptosis to suppress the growth of BEL‑7402 cells in vitro and in vivo, and therefore may hold promise for further development as a novel cancer therapy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify differentially expressed molecular functions (DEMFs) for breast cancer using the Gibbs sampling approach. Molecular functions (MFs) were obtained on the basis of the Bayesian Approach for Geneset Selection package. Subsequently, MFs were converted into Markov chains (MCs) prior to calculating their probabilities, utilizing the MC Monte Carlo algorithm. DEMFs were identified with probabilities ≥0.8 and the gene compositions were studied. Finally, a co‑expression network was constructed via the empirical Bayes method and a pathway enrichment analysis of genes in DEMFs was performed. A total of 396 MFs were identified and all transformed to MCs. With the threshold, 2 DEMFs (structural molecule activity and protein heterodimerization activity) were obtained. The DEMFs were comprised of 297 genes, 259 of which were mapped to the co‑expression network. These 297 genes were identified to be enriched in 10 pathways, and ribosome was the most significant pathway. The results of the present study revealed 2 DEMFs (structural molecule activity and protein heterodimerization activity) which may be associated with the pathological molecular mechanisms underlying breast cancer, based on Gibbs sampling. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS) is the most common type of soft-tissue sarcoma in children. Immunotherapy has been proposed as a treatment for this deadly tumor. In the present study, the cytotoxicity of ex vivo expanded γδ T cells on RMS cell lines was evaluated and the molecular interactions involved were investigated. γδ T cells were expanded in vitro using peripheral blood mononuclear cells from 5 healthy donors and were stimulated with zoledronic acid (Zol) and interleukin 2. RMS cell lines RD and A-673 were used as target cells. The cytotoxicity of the γδ T cells against RMS was assessed in vitro and in vivo. γδ T cells were cytotoxic to RMS cells. Importantly, Zol markedly increased their cytotoxic potential. RMS cells treated with Zol-stimulated γδ T cells to produce interferon γ. γδ T cell-mediated cytotoxicity was primarily through the T cell receptor-dependent signaling pathway in blocking studies. Transfer of γδ T cells together with Zol into nude mice induced the regression of RD tumor xenotransplants. The results of the present study provide the rationale for the clinical evaluation of γδ T cells in RMS. [ABSTRACT FROM AUTHOR]

Steroid-induced avascular necrosis of the femoral head (SANFH) is a mainly bilateral complication of steroid therapy that involves extensive necrosis, and frequently occurs in young and middle-aged individuals, with a high disability rate. Autophagy is an intracellular lysosomal degradation process occurring in numerous diseases. However, the effect of dexamethasone (DXM)-induced autophagy on osteoblasts is unclear. The aim of the present study was to investigate the effects of autophagy on SANFH. In the present study, femoral head of SANFH patients was collected, and the autophagy in the samples was evaluated. In addition, cell proliferation, membrane integrity and differentiation of osteoblasts were also detected to confirm the effect of DXM on a mouse osteoblasts cell MC3T3-E1 in vitro. Beclin 1 and microtubule-associated protein 1 light chain 3 were used as the markers of autophagy, while the autophagy inhibitor 3-methyladenine (3-MA) was used to investigate the role of autophagy in DXM-challenged osteoblasts. Immunohistochemistry results demonstrated that Beclin1 was markedly increased in the femoral head of SANFH patients. Furthermore, the treatment of osteoblasts with DXM decreased cell viability, increased lactate dehydrogenase activity in the cell culture supernatant, and reduced the alkaline phosphatase activity and bone morphogenetic protein-2 expression in osteoblasts in vitro. By contrast, 3-MA treatment attenuated the cell injury induced by DXM. The present study indicates that overactivated autophagy may be an important factor contributing to SANFH, and autophagy may be a potential target for the prevention of SANFH. [ABSTRACT FROM AUTHOR]

Axis inhibition protein 1 (AXIN1) is characterized as a tumor suppressor in numerous types of cancer. However, the functional role of AXIN1 in the testicular germ cell tumors (TGCTs) remains unclear. The human embryonal carcinoma-derived cell line NTera2 was transfected with a recombinant AXIN1 expression vector (pcDNA3.1‑AXIN1) and/or a small interfering RNA (siRNA) directed against AXIN1 (siAXIN). Following transfection, the mRNA and protein levels of AXIN1 were determined via reverse transcription‑quantitative polymerase chain reaction analysis and western blotting, respectively. In addition, cell viability, apoptosis and the expression of apoptosis‑associated proteins [apoptosis regulator Bax (Bax) and B‑cell lymphoma (Bcl)‑2] and phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway proteins [phosphorylated (p)‑mTOR, mTOR, p‑AKT, AKT, P‑70S ribosomal protein S6 (S6) and S6] were assessed. AXIN1 mRNA and protein levels were increased following transfection with pcDNA3.1‑AXIN1 and decreased following transfection with siAXIN1 compared with their respective control groups. After overexpression of AXIN1, NTera2 cell viability and expression of Bcl‑2, p‑mTOR p‑AKT and p‑S6 protein was decreased, while apoptosis and Bax protein levels were increased, compared with the control group. However, there was no significant difference in AXIN1 mRNA expression, apoptosis or Bax/Bcl‑2 protein expression when NTera2 cells were simultaneously transfected with pcDNA3.1‑AXIN1+siAXIN1. In conclusion, the results of the present study indicate that overexpression of AXIN1 protects against TGCTs via inhibiting the PI3K/AKT/mTOR signaling pathway, suggesting that AXIN1 may be a potential target for gene therapy in TGCTs. [ABSTRACT FROM AUTHOR]

Damage of retinal ganglion cells (RGCs) is the major consequence of glaucoma and regeneration of RGCs is extremely difficult once the damage has occurred. Retinal stem cells (RSCs) are considered an ideal choice for RGC regeneration. Pigmented cells from the ciliary margin (PCMs) have great retinal differentiation potential and may be an ideal RSC candidate. However, the ciliary margin is too small, so the number of cells that can be obtained is limited. Bone marrow‑derived mesenchymal stem cells (BMMSCs) are another type of stem cell that have been previously investigated for RGC regeneration. BMMSCs expand sufficiently, whereas the retinal differentiation of BMMSCs is insufficient. The aim of the present study was to investigate whether the co‑culture of PCMs and BMMSCs may combine the advantages of both cell types to establish a novel and effective stem cell source for RGC regeneration. Primary rat PCMs and BMMSCs were isolated and co‑cultured. Cell growth was observed by an inverted microscope and proliferation was monitored by an MTT assay. Cell cycle analysis was performed by using a flow cytometer, while the expression of the photoreceptor‑specific homeobox gene (cone‑rod homeobox, Crx) was determined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In addition, retinal differentiation was confirmed by immunofluorescence staining of major markers of retinal differentiation, including rhodopsin, visual system homeobox 2 and heparin sulfate. The co‑cultured cells expanded successfully, in a similar way to BMMSCs. In addition, the expression of Crx and retinal markers were significantly upregulated following BMMSC and PCM co‑culture. The results of the present study demonstrated that the co‑culture of BMMSCs and PCMs may be used as a source of RSCs. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in the interleukin-4 receptor (IL-4R) gene have been identified as having a close association with asthma severity in different populations. In our previous studies, a close association between asthma and a distinctive palm dermatoglyphic pattern was observed; however, the clinical implication and underlying genetic mechanisms of this particular palm pattern have not been clarified. Whether this particular palm pattern is associated with asthma severity and IL-4R SNPs was assessed in the present study. A case cohort study was conducted in 400 patients with allergic asthma and in 200 healthy controls. DNA was extracted from peripheral blood leukocytes for analysis of 11 IL-4R SNPs associated with asthma via polymerase chain reaction. There are two SNPs, rs1805012 and rs3024608, which are associated with asthma (rs1805012, dominant model; P=0.03 and rs3024608, codominant model; P=0.029), and two SNPs, rs1805010 and rs3024608, which are associated with the positive palm pattern (rs1805010, log-additive model; P=0.031 and rs3024608, codominant model; P=0.016). The SNP of rs3024608 is associated with asthma and the positive palm pattern. Thus, genetic variation in IL-4R may be associated with the development of asthma and the distinctive palm pattern; however, further investigations are required to identify the connection between asthma and palm dermatoglyphic patterns. [ABSTRACT FROM AUTHOR]