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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been involved in the pathogenesis and progression of several cancers. However, the exact effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in PGI-DLBCL patients. Quantitative real-time Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably up-regulated in PGI-DLBCL tissues as compared to that of paired adjacent non-tumor tissues (P

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) is still a consolidation treatment choice for relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL) patients and some aggressive B-cell NHL as frontline therapy. Due to the shortage of carmustine, we switched to idarubicin-substituted BEAC (IEAC) conditioning regimen. We retrospectively compared the outcomes of 72 aggressive B-cell NHL patients treated with IEAC or BEAC regimens followed by ASCT as upfront consolidative treatment. The median time to neutrophil and platelet reconstitution showed no difference between IEAC and BEAC groups. IEAC regimen was well tolerated without increase of adverse events. Transplant-related mortality didn’t occur. The overall survival (OS) and progression-free survival (PFS) of IEAC group (33 and 23 months) were a little longer than that of BEAC group (30 and 18 months). However, due to the small sample numbers, there’s no significant difference in OS and PFS between IEAC and BEAC group with DLBCL or MCL. Multivariate analysis showed that AnnArbor staging, IPI score, lactate dehydrogenase level, remission of disease, modified regimen were related with PFS and OS. In conclusion, IEAC regimen was well tolerated and replacement with idarubicin could be an alternative when carmustine was not available.

Reduced bone formation in patients with T-cell acute lymphoblastic leukemia (T-ALL) may be related to the interaction between tumour cells and bone marrow stromal cells (BMSCs). The miRNAs in extracellular vesicles derived from leukemia cells play an essential role in regulating the function of BMSCs; however, the regulatory mechanisms remain unclear. The expression of miR-34a-5p in T-ALL patients and cells was measured by quantitative real-time PCR. BMSCs were co-cultured with extracellular vesicles isolated from T-ALL cells in mineralization medium. The osteogenic differentiation of BMSCs was evaluated by Alizarin Red S staining, alkaline phosphatase (ALP) staining, and detection of osteogenic differentiation markers. A dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-34a-5p and Wnt family member 1 (WNT1). MiR-34a-5p expression was upregulated in T-ALL patients and Jurkat cells. After BMSCs were co-cultured with extracellular vesicles derived from T-ALL cells, osteogenic differentiation of BMSCs was inhibited, and bone mineralization and ALP activity were decreased compared to those of control cells. MiR-34a-5p knockdown in T-ALL cells restored osteogenic differentiation of BMSCs co-cultured with extracellular vesicles. In addition, miR-34a-5p targets and negatively regulates WNT1 expression. In conclusion, our results demonstrated that knockdown of miR-34a-5p in extracellular vesicles derived from T-ALL cells promoted osteogenic differentiation of BMSCs by regulating WNT1.

Bombyxin, as an insulin-like insect hormone, was discovered in the silkmoth Bombyx mori. It can regulate the metabolism of trehalose and glycogen in Bombyx mori, but whether it has glucose absorption and glycogen synthesis effect on mammalian cells was not clear. BombyxinII (BbxII) and mutant BbxII (mBbxII) genes were cloned into pcDNA3.1(+) vector, respectively; then, gene vectors were transfected into 293FT cells using Lipofectamine 2000. Levels of mRNA and protein expression of BbxII and mBbxII were detected by PCR and Western blot in 293FT cells, respectively. Glucose consumption and glycogenesis were determined by glucose oxidase-peroxidase (GOD-POD) and periodic acid-Schiff (PAS) staining in HepG2 cells; the PI3K signaling pathway was inhibited with wortmannin S1952 in HepG2 cells. Result showed that BbxII and mBbxII genes were being successfully expressed in 293FT cells, respectively. The expression protein of BbxII gene is 10kd pre-bombyxinII, and yet, the expression protein of mBbxII gene is 4kd mature bombyxinII. Only the 4kd bombyxinII showed increased glucose uptake and glycogenesis in HepG2 cells, and the ability of increasing glucose uptake was equal to the human insulin (10 nM). PI3K-wortmannin S1952 inhibitor can decrease the glycogen synthesis induced by bombyxin II protein in HepG2 cells. In conclusion, mature bombyxin II may adjust glucose absorption and glycogen synthesis in HepG2 cells through the PI3K signaling pathway.

Background Chromosomal abnormalities play an important role in classification and prognostication of myelodysplastic syndromes (MDS) patients. However, more than 50% low risk MDS patients harbor a normal karyotype. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MDS patients. Methods To characterize the subset of MDS with normal karyotype or failed chromosome banding analysis, we analyzed 144 patient samples with normal karyotype or undetectable through regular chromosome banding, which were subjected to parallel comparison via fluorescence in situ hybridization (FISH) and MLPA. Results MLPA identifies copy number changes in 16.7% of 144 MDS patients and we observed a significant difference in overall survival (OS) (median OS: undefined vs 27 months, p=0.0071) in patients with normal karyotype proved by MLPA, versus aberrant karyotype cohort as determined by MLPA. Interestingly, patients with undetectable karyotype via regular chromosome banding indicated inferior outcome. Conclusion Collectively, MDS patients with normal or undetectable karyotype via chromosome banding analysis can be further clarified by MLPA, providing more prognostic information that benefit for individualized therapy.

Background Variability in the anatomy and orientation of the triangle of Koch (TK) complicates ablation procedures involving the atrioventricular (AV) node. We used CT angiography (CTA) to assess the anatomical TK orientation, the CS ostium direction, and the relationship between the two, and we validated an individualized CS-guided projection during ablation procedures. Methods In 104 patients without structural heart disease undergoing computed tomography (CT) angiography, TK orientations were determined in relation to the coronary sinus ostium (CSo) as well as two standard right anterior oblique (RAO) projection angles (30o and 45o) commonly used in ablation procedures. Results A CS-guided RAO projection (RAOCS) was shown to best track the orientation of the TK compared to RAO30° and 45°, with TK orientation strongly correlating with the CSo direction (r = 0.86, P Conclusion In hearts with a normal structure, the CSo direction offers a reliable predictor of the TK orientation which can be used to guide the projection of the TK during ablation procedures.

Uncoupling protein 2 (UCP2) is primarily expressed in the myocardium and is closely related to myocardial ischemia/reperfusion injury and myocardial metabolism. To explore the effects and the mechanisms of UCP2 on atorvastatin-mediated myocardium protection, the rat model of myocardial ischemia was established by ligation of the left anterior descending coronary arteries (LADs). The rats were divided into the sham operation (SO) group, myocardial infarction (MI) group and MI-atorvastatin group. The study that atorvastatin reduced myocardial remodeling and improved the disturbed myocardial energy metabolism after MI. Furthermore, the mechanisms of myocardial metabolic remodeling affected by atorvastatin were explored. The atorvastatin group showed a significantly decreased expression of UCP2 mRNA and protein. Furthermore, the primary rat cardiomyocytes were cultured and treated with angiotensin II (Ang II) to induce cardiomyocyte hypertrophy. The results showed that in the atorvastatin group, the surface area of the cardiomyocytes, the total protein content per unit of cells, and the expression of the UCP2 protein were significantly decreased. These data suggested that atorvastatin significantly attenuated the myocardial remodeling by downregulating the expression of UCP2 that was found to improve the myocardial energy metabolism, inhibit myocardial hypertrophy, and eventually reduce myocardial remodeling.

We retrospectively analyzed a large study to investigate the association of hepatitis B virus (HBV) with aggressive B cell non-Hodgkin's lymphoma (aggressive B-NHL) in China, where HBV is endemic. HBV was present in 39 aggressive B-NHL patients (10.46%), 13 indolent B-NHL patients (5.09%), 12 multiple myeloma (MM) patients (3.67%), and 5 solitary plasmacytoma (SP) patients (6.67%). HBV infection was significantly associated with increased risks for aggressive B-NHL (P

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a common marginal zone lymphoma. The stomach is the relatively common origin of the MALT lymphoma, now termed as extranodal marginal zone B-cell lymphoma. Gastric MALT lymphoma has good prognosis due to clinical response to treatment and favourable overall survival. In this study, clinical characteristics and treatment of patients of early gastric MALT lymphoma were retrospectively analysed.Seventy patients with stages I-II MALT-lymphoma treated from April 2003 to August 2015 were included. The most common symptoms were abdominal discomfort, nausea, vomiting and other digestive symptoms. Helicobacter pylori eradication was done in patients with proven H. pylori infection. Patients in whom H. pylori eradication therapy was not effective, alternative treatments options including chemotherapy, radiotherapy and surgery, were given.Fifty two patients with H. pylori infection underwent anti-H. pylori therapy, the total effective rate of anti-H. pylori treatment was 92.3 per cent (48/52). Thirty two patients were given anti-tumour treatment, including chemotherapy, radiotherapy and surgery. The total effective rate was 90.6 per cent (29/32). The five-year overall survival rate and five-year progression-free survival rate were 93.4 and 84.2 per cent, respectively.For patients with early gastric MALT lymphoma, anti-H. pylori treatment may be effective. Patients with poor results of anti-H. pylori treatment need to be treated with anti-tumour therapy.

This study aimed to explore the effects of lncRNA BCAR4 on the viability and aggressiveness of non-small cell lung cancer (NSCLC) cells. qRT-PCR was used to determine the expression of BCAR4 and GLI2 downstream genes in NSCLC tissues and cell lines. Chromatin isolation by RNA purification (CHIRP) and Western blot were employed to measure the expression of the GLI2 downstream proteins. Ki-67 expression in nude mice tumors was tested by immunohistochemistry. MTT assay, wound healing assay, and Transwell assay were used to assess NSCLC cell viability and aggressiveness, respectively. Tumor xenograft was conducted to determine the effects of BCAR4 and GLI2 on NSCLC tumorigenesis in vivo. The expression of BCAR4 in NSCLC tissues and cells was significantly higher than the normal level. The overexpression of BCAR4 promoted NSCLC cell viability, migration, and invasion. The suppression of BCAR4 and GLI2 showed the opposite effects. The overexpression of BCAR4 led to an increase in the expression of GLI2 downstream proteins, while the suppression of BCAR4 and GLI2 reduced their expression. In a tumor xenograft assay, the tumors in mice of the BCAR4 group showed the biggest volume, while those in mice of the si-GLI2 group showed the smallest volume. Ki-67 showed much higher levels in the BCAR4 overexpression group but much lower levels in the si-GLI2 group. In summary, the cooperative mechanism of lncRNA BCAR4 and GLI2 might provide a new opportunity for treating NSCLC.

To evaluate the expression of tumor-associated macrophages (TAMs) and Toll-like receptor 4 (TLR4) in diffuse large B-cell lymphoma (DLBCL) and their correlation with patient clinical characteristics, we detected using immunohistochemistry in 81 specimens of patients with DLBCL. The correlation between protein expression levels and clinical parameters, as well as the association between CD68 and TLR4 were analyzed. The number of CD68 TAMs was closely related to β2-microglobulin (P = .028 and P < .05), whereas there was no significant correlation between the number of CD68 TAMs and other clinical factors. Toll-like receptor 4 was related to tumor size and peripheral blood lymphocyte to monocyte ratio. The Spearman correlation coefficient indicated a significant positive correlation between CD68 TAMs and TLR4 expression (r = 0.240; P = .038, P = .05). These results, on one hand, indicated that TLR4-induced inflammatory responses may affect TAM infiltration and accumulation, and that TAMs and TLR4 may interact to play important roles in DLBCL microenvironment regulating the tumor growth, but, on the other hand demonstrated that both of TAMs and TLR4 had not only one side on DLBCL growth.

We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited.

The aim of this study was to evaluate the relationship of prognosis of patients with multiple myeloma having extramedullary involvement (EMM) with the 18F- fluorodeoxyglucose(18F-FDG) maximum standardized uptake value and the expression of Ki-67 in biopsy samples. Sixty-five patients were newly diagnosed with multiple myeloma presenting with EMM at our hospital from January 2005 to January 2015. Of these 65 patients, 20 were enrolled in this study. Over the last decade, both the maximum standardized uptake value and Ki-67 expression in these extramedullary lesions significantly correlated with progression-free survival, respectively ( P= .039, P =.009). After combining—the maximum standardized uptake value and the Ki-67 expression as an integral—there was a significant correlation between both the overall survival ( P = .027) and progression-free survival ( P= .014). Patients have poor outcomes when EMM is detected at presentation. Both the maximum standardized uptake value and Ki-67 expression could aid in accurately evaluating EMM patient prognosis.

Rationale: Anti-thrombosis therapy for atrial fibrillation (AF) management and stroke prevention is an important aspect of disease management. Novel oral anticoagulants (NOACs) are recommended by guidelines for AF management. However, if one can switch one NOAC to another when the former showed a poor effect has not been fully determined. Patient concerns: A 52-year-old man was admitted to our center for heart failure and AF with a thrombus in the left atrium. Diagnoses: Cardiomyopathy was diagnosed by cardiac magnetic resonance (CMR) and echocardiography. Interventions: He was prescribed rivaroxaban (20 mg daily) as treatment, and dabigatran (150 mg twice daily) was used when the thrombus was found to be non-response to rivaroxaban. Outcomes: The rivaroxaban did not diminish the atrial thrombus, and dabigatran was given instead which finally eliminated the thrombus. Lessons: Individualized responsiveness to NOACs should be considered and paid more attention to during clinical practice.

Solitary plasmacytoma of bone (SPB) is a rare tumor that represents a minority of patients with plasma cell localized malignancy characterized by a single osteolytic bone lesion. The molecular mechanism underlying the genesis of SPB has remained enigmatic. Signal transducers and activators of transcription-3 (STAT3) is often activated in human cancers and is implicated in tumorigenesis. In the present work, the immunohistochemical expression of pSTAT3 (the active isoform of STAT3) and its potential downstream mediators (Bcl-2, Bcl-xL, c-Myc, cyclin D1, VEGF, cIAP-2, Mcl-1, and survivin) were examined, clinical features were investigated, and relative prognostic factors were analyzed. Positive expression of Bcl-2 was observed in 46.7 % (14/30) of patients, c-Myc in 36.7 % (11/30), and cyclin D1 in 23.3 % (7/30). By univariate analysis, Bcl-2 expression was found to be closely associated with shorter overall survival (OS) and progression-free survival. Bcl-2 and c-Myc positive expression were also found to be a factor that affect time to progression to multiple myeloma. In conclusion, results showed Bcl-2 expression to be a clinically significant prognostic indicator for SPB patients and constitutive activated STAT3 may not be the sole primary regulatory mechanism.

The tuberculin skin test, which involves monitoring the immune reaction to an injection of Purified Protein Derivative (PPD), has been the most widely used method for detecting infection with Mycobacterium tuberculosis since its development in 1930s. Until recently, the molecular composition of PPD was unknown. This thwarted the discovery of improved skin testing reagents and drastically hindered efforts to define the mechanism of action. Proteomic evaluation of PPD combined with a detailed analysis in the guinea pig model of tuberculosis led to further definition of the molecular composition of PPD. This communication reviews the history and current status of PPD, in addition to describing candidate next-generation PPD reagents, based on the use of an individual protein or protein cocktails.

Identification of Mycobacterium tuberculosis antigens inducing cellular immune responses is required to improve the diagnosis of and vaccine development against tuberculosis. To identify the antigens of M. tuberculosis that differentiated between tuberculosis (TB) patients and healthy contacts based on T cell reactivity, the culture filtrate of in vitro grown M. tuberculosis was fractionated by two-dimensional liquid phase electrophoresis and tested for the ability to stimulate T cells in a whole blood assay. This approach separated the culture filtrate into 350 fractions with sufficient protein quantity (at least 200 microg of protein) for mass spectrometry and immunological analyses. High levels of interferon-gamma (IFN-gamma) secretion were induced by 105 fractions in healthy contacts compared with TB patients (p < 0.05). Most interesting was the identification of 10 fractions that specifically induced strong IFN-gamma production in the healthy contact population but not in TB patients. Other immunological measurements showed 42 fractions that induced significant lymphocyte proliferative responses in the healthy contact group compared with the TB patients. The tumor necrosis factor-alpha response for most of the fractions did not significantly differ in the tested groups, and the interleukin-4 response was below the detectable range for all fractions and both study groups. Proteomic characterization of the 105 fractions that induced a significant IFN-gamma response in the healthy contacts compared with the TB patients led to the identification of 59 proteins of which 24 represented potentially novel T cell antigens. Likewise, the protein identification in the 10 healthy "contact-specific fractions" revealed 16 proteins that are key candidates as vaccine or diagnostic targets.

After half a century of success in combating infectious diseases with vaccination and antibiotics, emerging and reemerging epidemics present a new threat to human health. Meanwhile, the rapid pace of viral and microbial genomics research, largely based on the success of genomics technologies, offers new data-generating platforms and a revolutionary knowledge base for better understanding the diseases and the associated pathogens. Systematic molecular biology studies using genomics information and technologies have helped to elucidate mechanisms of virulence and pathogenicity, whereas genomics-based medical genetic studies have been used to better understand pathogen susceptibility. This progress may lead to the development of effective and safe vaccines in the future. Here we highlight the ongoing historical transition in the field of infectious disease research and clinical practice in the new era of genomics.

Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties, cytotoxic activities against multiple human cancer cells, inducing apoptosis and differentiation of some human cancer cells. The purpose of this study is to confirm its anticancer activity on human glioma cells, and to elucidate mechanism of its activity. Human glioma cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation after treatment with tanshinone IIA. Its effect of apoptosis induction was detected through EB/AO staining, cell cycle analysis and the expressions of ADPRTL1 and CYP1A1 genes, the differentiation induction effect was investigated through morphology, mRNA and protein expressions of GFAP and nestin genes by RT-PCR and immunocytochemistry. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth, IC(50) was 100 ng/ml, and it significantly inhibited colony formation and BrdU incorporation of human glioma cells. After treatment with 25-100 ng/ml of tanshinone IIA, the apoptotic cells increased significantly (P0.01), the cells in G(0)/G(1) phase increased (P0.01), and decreased in S phase, ADPRTL1 and CYP1A1 mRNA expression increased 1-2 folds. The cells treated with 100 ng/ml tanshinone IIA demonstrated astrocytes or neuron-like morphology, GFAP mRNA and protein expressions increased, nestin mRNA and protein expressions decreased significantly. The findings in this study suggested that tanshinone IIA exhibited strong effects on growth inhibition and induction of apoptosis and differentiation in human glioma cells. It might serve as a novel promising differentiation-inducing and/or therapeutic agent for human gliomas, and need to be investigated further.

To investigate the proliferation inhibitory role and mechanism of PI3Kδ inhibitor CAL-101 on multiple myeloma (MM) cells, and to provide new therapeutic options for MM treatment.MM cell lines U266 and RPMI8226 cells were treated with various concentrations of CAL-101. MTT assay and CalcuSyn software were performed to determine the inhibitory effect of CAL-101 and the synergistic effect with PCI- 32765, SAHA (suberoylanilide hydroxamic acid), BTZ (Bortezomib) on MM cells. The protein expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ processed by CAL-101 were analyzed by Western blot.CAL-101 at concentration of 15, 20, 25, 30 and 40 μmol/L could induce significant dose-dependent proliferation inhibition on U266 cells after treatment for 48 hours. The cell proliferation inhibition rates were (33.54 ± 1.23)%, (41.72 ± 1.78)%, (53.67 ± 2.01)%, (68.97 ± 2.11)% and (79.25 ± 1.92)%, respectively. Similar results were found in RPMI8226 cell line. Western blots showed high expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ in cell lines and MM primary cells. p-AKT and p-ERK protein expression levels were down-regulated significantly by CAL-101 treatment. Synergistic effect has been verified between CAL-101 and PCI-32765, SAHA and Bortezomib in U266 cell line, and PCI-32765, Bortezomib in RPMI8226 cell line with CI values less than 1.CAL-101 could inhibit proliferation of MM cell lines. High levels of p-AKT, p-ERK, AKT, ERK and PI3Kδ protein expression were observed in both cell lines and primary cells. Down-regulation of p-AKT and p-ERK probably related with the mechanism of CAL-101 in MM cell proliferation inhibition. CAL-101 has significant synergistic effect with PCI-32765, SAHA and BTZ.

To provide suitable models for human GBM cancer stem cells in vitro and in vivo, and investigate their biological characteristics, a new human GBM cancer stem-like cell line, WJ2, was established in this experiment through serial passages from adherent monolayer culture to nonadherent tumor sphere culture in turns; Its partial biological characteristics were studied through cell proliferation and tumor sphere assay; cell cycle distribution, side population, and CD133 phenotype were analyzed with FCM. The expressions of CD133, Nestin, and GFAP of cancer stem-like cells and xenograft tumor cells were detected with RT-PCR and immunohistochemistry. Biological characterization, side population, CD133 phenotype and CD133 Nestin, BCRP-1, Wnt-1 gene expression revealed the stemness of this cancer stem-like cell line. Tumorigenicity heterotransplanted in nude mice; histopathological characteristics of xenograft tumor, and expressions of CD133, Nestin, and GFAP of xenograft tumor cells indicated that xenograft tumors recapitulated the phenotype and biological characterization of human primary GBM. All findings of this experimental study suggested that WJ(2) cancer stem-like cell line could accurately mimic human GBM cancer stem cell in vitro and in vivo; it would be useful in the cellular and molecular studies as well as in testing novel therapies of CSC-based anti-cancer therapies for human GBM.

Fig fruit latex (FFL) contains significant amounts of polyphenolic compounds and can serve as a source of antioxidants after human consumption. The purpose of this study is to confirm anticancer activity of FFL against human cancer cells and to further elucidate its mechanism of activity. Human glioblastoma, hepatocellular carcinoma, and normal liver cells were used for in vitro tests of FFL effects. Those tests included cytotoxicity, colony formation inhibition, Brdu incorporation, acridine orange/ethidium bromide (AO/EB) staining for apoptotic cells, cell cycle distribution through flow cytometry (FCM), and ADP-ribosyltransferase (NAD+; poly(ADP-ribose) polymerase)-like 1 (ADPERL1) mRNA expression through RT-PCR in response to FFL treatment. After FFL treatment, the proliferation, colony formation, and Brdu labeling indices of cancer cells decreased (P