[Analysis of Factors Influencing Overall Survival and Prognosis of AML Patients Over 50 Years Old].

OBJECTIVE: To explore the overall survival and prognostic factors of patients over 50 years old with acute myeloid leukemia (AML). METHODS: The clinical data of 222 AML patients aged over 50 years in our hospital from January 2016 and June 2021 were retrospectively analyzed. Kaplan-Meier method was used to evaluate the overall survival (OS) rate, and Cox regression model to evaluate the prognostic factors. RESULTS: The 1-year and 3-year OS rates of all patients were 46.8% and 28.8%, respectively. The recurrence rate of patients who achieved remission during follow-up time was 57%. Both univariate and multivariate analysis showed that advanced age, MLL family fusion gene, PHF6 gene mutation, TP53 gene mutation, intolerance to standard chemotherapy, incomplete remission, complex karyotype, +mar karyotype and inv(3) karyotype were significantly correlated with prognosis (all P <0.05). Negative fusion gene and positive AML- ETO fusion gene had no obvious survival advantage in this population. In patients with complete remission, there was no significant survival advantage in those who achieved minimal residual disease negative. CONCLUSION: AML patients aged over 50 years have a poor outcome and high recurrence rate. The prognosis is affected by multiple factors and has its own characteristics.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

[Real-World Efficacy and Safety of China-Made Flumatinib Mesylate in the Treatment of Chronic Myeloid Leukemia in Chronic Phase].

OBJECTIVE: To evaluate the efficacy and safty of China-made flumatinib mesylate in the treatment of chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 42 CML-CP patients treated with Chinese produced flumatinib (oral, 600 mg, 1/d) were included in the study, including 14 newly diagnosed patients and 28 patients underwent conversion therapy. The hematological, cytogenetic and molecular response and safety were observed and evaluated after 3, 6 and 12 months of treatment. RESULTS: 35 patients were treated for more than 3 months, among which 31 patients were treated for more than 6 months and 17 patients were treated for more than 12 months. After 3 months of treatment, 33 patients underwent hematological, cytogenetic and molecular examination. Of these, 32 patients achieved complete hematological response (CHR), 13 patients achieved complete cytogenetic response (CCyR), 20 patients showed BCR-ABLIS≤10% and 7 patients reached major molecular response (MMR). After 6 months of treatment, all 30 patients who could evaluate efficacy achieved CHR, of which 17 patients achieved CCyR, 18 patients showed BCR-ABLIS≤1% and 16 patients reached MMR. After 12 months of treatment, all 17 patients were evaluated for efficacy, all achieved CHR, 10 patients obtained CCyR, 7 patients reached MMR. Grade III or IV thrombocytopenia, leukopenia and anemia occurred in 7, 2 and 1 patients, respectively. The non-hematological adverse reactions were diarrhea in 6 cases, renal function damage in 4 cases, rash and pruritus in 3 cases, liver function damage in 3 cases, nausea in 1 case, fever in 1 case, bone/joint or muscle pain in 1 case. CONCLUSION: In the real world, China-made flumatinib mesylate has a positive short-term efficacy and reliable safety in the treatment of CML-CP patients, whether as first-line treatment or second- and third-line conversion therapy.

[Efficacy of CLAE Chemotherapy Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Leukemia].

OBJECTIVE: To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL). METHODS: CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation. RESULTS: 2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD. CONCLUSION: CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

[Effect of CXCR4 on the Treatment Response and Prognosis of Carfilzomib in Multiple Myeloma].

OBJECTIVE: To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma. METHODS: Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified. RESULTS: 44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013). CONCLUSION: CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.

[Efficacy of Micro-Transplantation Consolidation Therapy for Patients with Acute Myeloid Leukemia after Complete Remission].

OBJECTIVE: To investigate the efficacy and safety of micro-transplantation in acute myeloid leukemia (AML). METHODS: The clinical data of 13 adult AML patients who received micro-transplantation as consolidation therapy from July 2014 to October 2019 was retrospectively analyzed, and the adverse reactions and efficacy of micro-transplantation were followed up. RESULTS: Eight patients received micro-transpantation were still in complete remission, 5 patients relapsed after micro-transplantation, 1 of them received umbilical cord blood micro-transplantation after remission by reinduction, and all of the 13 patients have survived till now. The median overall survival time was 13 months, and the median relapse-free survival time was 12 months. All 13 patients developed grade 2-4 hematological adverse reactions. The median recovery time of neutrophils and platesets was 13 (11-15) and 15 (13-17) days, respectively. None of the 13 patients developed acute or chronic graft versus host disease. Twelve patients suffered from different infections, however, there were no serious organ function injury complications happened. CONCLUSION: The micro-transplomtation of HLA-incompatible stem cells derived from peripheral blood or umbilical and blood is an effective regimen for the consolidation therapy of AML, especially for the patients suffered from low and moderate risk of AML or the aged AML patients.

[Significance of Targeted Sequencing Assay for Patients with Suspected Myeloid Malignancies].

OBJECTIVE: To investigate the clinical significance of the targeted next-generation sequencing assay for patients with suspected myeloid malignancies. METHODS: A total of 39 hematopenia patients with suspected myeloid malignamies in Department of Hematology of The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2018 to April 2019 were treated, 20 hot spot genes of myelodysplastic syndrome (MDS) were detected. RESULTS: Regarding the diagnostic type, there were 7 cases of idiopathic cytopenia of undetermined significance (ICUS), 8 cases of clonal cytopenias of undetermined significance (CCUS) and 24 cases of myeloid myeloid malignancies which included 18 cases of MDS, 4 cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 2 cases of acute myeloid leukemia. Positive mutation was detected in 70.8% (17/24) of myeloid malignancy patients , and 72.7% (16/22) in MDS and MDS/MPN patients. The main mutation types were ASXL1, TET2 and RUNX1. Compared with gene negative group, there were no significant differences in sex, age (＜60 years old or ≥60 years old), proportion of bone marrow blast cells (＜5% or≥5%) and cytogenetics (good, medium and poor) (P＞0.05). Furthermore, all 8 CCUS patients showed positive mutation, and the incidence of double or multiple mutation in CCUS group was significantly lower than that of the MDS and MDS/MPN group (37.5% vs 54.5%) (P=0.002). The mutation types between the two groups were similar, and there was no significant difference in variant allele frequency (P＞0.05). CONCLUSION: Our results suggest that there are high rates of double or multiple mutations in myeloid malignancies, especially in patients with MDS and MDS/MPN. Targeted sequencing assay can improve the diagnosis of myeloid malignancies, and guide clinical treatment.

[Clinical Analysis of 66 Patients with Essential Thrombocytopenia].

OBJECTIVE: To investigate the clinical characteristics of essential thrombocytopenia (ET) patients with positive mutations including JAK2, CALR, MPL, or negative mutations. METHODS: A total of 66 newly diagnosed ET cases from January 2016 to December 2018 in Department of Hematology, Huaian No.1 People's Hospital affiliated to Nanjing Medical University were analyzed. Statistical analysis data included the patient's sex, age, symptoms, thrombosis and embolism events, spleen omegaly, platelet count (Plt), leukocyte (WBC) count, hemoglobin (Hb), fibrinogen (FIB), thrombus elastic diagram (TEG), serum potassium, blood glucose (GLU), lactate dehydrogenase (LDH), JAK2, CALR and MPL mutations, treatment options, and efficacy. RESULTS: All the patients were not MPL-positive, and divided in three groups: JAK2 mutation (46 cases, 69.7%), CALR mutation (9 cases, 13.6%) and gene negative mutation (11 cases, 16.7%) group. The average age of patients in the JAK2 mutation group was 63.2 years old, and significantly higher than that in the CALR mutation group (51.8 year) and gene negative group (50.2 year) (P＜0.05). Compared with the JAK2 mutation group and gene negative group, the CALR mutation group had lower WBC count (6.3×109/L vs 13.79×109/L) (P=0.003) (6.3×109/L vs 9.70×109/L) (P=0.009). Also the Hb level of patients in CALR mutation group was lower than the JAK2 mutation group (121.22 g/L vs 136.2 g/L) (P=0.036). However, there was higher tumor burden in the CALR mutation group, compared with the gene negative mutation group (300.11 U/L vs 227.4 U/L) (P=0. 033). There was no significant difference among the three groups, such as the Plt counts, serum potassium level, GLU level and FIB level (P＞0.05). In addition, thrombus and embolism appeared in 30.3% (20/66) cases. 18.2% (12/66) cases were complicated with hyperkalemia, which significantly correlated with Plt counts (r=0.518). TEG was performed in 34 patients, of which 41.2% (14/34) had abnormal TEG and 55.9% (19/34) were accompanied by Plt count ＞ 1 000 ×109/L, but there was no significant correlation between them (r=0.134). After routine clinical treatment, all the 66 cases achieved partial or complete hematological remission, but the disease usually repeated. Until now 4.5% (3/66) cases had been converted to myelofibrosis (MF) all with JAK2 mutation, but without advancing to acute myeloid leukemia. CONCLUSION: ET patients with JAK2 mutation have higher incidence, moreover were in older age. However, the patients with CALR mutations display lower WBC count and Hb level, but higher tumor burden. In short, the multiple gene mutations of ET showed different clinical features closely relates with the prognosis, thus providing guidance for the clinical diagnosis and treatment.

[Therapeutic Response and Prognosis of Adult Acute Myeloid Leukemia with Chromosome Karyotype Abnormalities].

OBJECTIVE: To investigate the efficacy and prognosis of acute myeloid leukemia (AML) patients with chromosome karyotype abnormalities. METHODS: The clinical features and treatment responses of 91 patients with AML were collected and analyzed retrospectively. The efficacy and survival rate of the AML patients with normal and abnormal chromosome karyotype were compared. RESULTS: Chromosome translocations and monosomal karyotypes were the main heterogeneity of AML. There was no significant difference in complete remission rate and overall response rate between the normal and abnormal karyotype groups, but the recurrence rate was higher in abnormal karyotype group. There was no significant difference in response of AML patients received the standard "3+7 regimen" and pre-excitation chemotherapy in the treatment of normal and abnormal karyotype groups. The relapse free survival time (RFS) was longer in the normal karyotype group, but there was no significant difference in overall survival time (OS). CONCLUSION: The abnormal karyotype of AML is an independent prognostic factor, monosomal karyotype shows a poor prognosis, and the recurrence rate in AML patients with monosomal karyotype is higher.

Genistein and daidzein induce apoptosis of colon cancer cells by inhibiting the accumulation of lipid droplets.

AIM: The purpose of this study was to investigate the possible mechanisms of genistein (GEN) and daidzein (DAI) in inducing apoptosis of colon cancer cells by inhibition of lipid droplets (LDs) accumulation. METHODS: HT-29 cells were used and treated by GEN or DAI in this paper. LDs accumulation was induced and inhibited by oleic acid (OA) and C75, respectively. The expression changes of LDs-related markers were confirmed by semiquantitative real time-PCR (RT-PCR), Western blotting, and immunofluorescence staining. RESULTS: GEN and DAI effectively reduced the LDs accumulation and downregulated the expression of Perilipin-1, ADRP and Tip-47 family proteins and vimentin levels. GEN and DAI significantly induced the mRNA expression of PPAR-γ, Fas, FABP, glycerol-3-phosphate acyltransferase (GPAT3), and microsomal TG transfer protein (MTTP), and reduced the mRNA expression of UCP2. Furthermore, the results showed a decrease of PI3K expression by GEN and DAI when compared with OA treatment, and both GEN and DAI can increase the expression of FOXO3a and caspase-8 significantly when these proteins were decreased by OA treatment. GEN is more effective than DAI in inducing cell apoptosis. CONCLUSION: Our results demonstrated that GEN and DAI inhibit the accumulation of LDs by regulating LDs-related factors and lead to a final apoptosis of colon cancer cells. These results may provide important new insights into the possible molecular mechanisms of isoflavones in anti-obesity and anti-tumor functions.

Systematic expression profiling analysis mines dys-regulated modules in active tuberculosis based on re-weighted protein-protein interaction network and attract algorithm.

About 90% of tuberculosis (TB) patients latently infected with Mycobacterium tuberculosis (Mtb) show no symptoms, yet have a 10% chance in lifetime to progress active TB. Nevertheless, current diagnosis approaches need improvement in efficiency and sensitivity. The objective of this work was to detect potential signatures for active TB to further improve the understanding of the biological roles of functional modules involved in this disease. First, targeted networks of active TB and control groups were established via re-weighting protein-protein interaction (PPI) networks using Pearson's correlation coefficient (PCC). Candidate modules were detected from the targeted networks, and the modules with Jaccard score >0.7 were defined as attractors. After that, identification of dys-regulated modules was conducted from the attractors using attract method, Subsequently, gene oncology (GO) enrichment analyses were implemented for genes in the dys-regulated modules. We obtained 33 and 65 candidate modules from the targeted networks of control and active TB groups, respectively. Overall, 13 attractors were identified. Using the cut-off criteria of false discovery rate <0.05, there were 4 dys-regulated modules (Module 1, 2, 3, and 4). Based on the GO annotation results, genes in Modules 1, 2 and 4 were only involved in translation. Most genes in Module 1, 2 and 4 were associated with ribosomes. Accordingly, these dys-regulated modules might serve as potential biomarkers of active TB, facilitating the development for a more efficient, and sensitive diagnostic assay for active TB.

Noninvasive Diagnosis of Hepatic Steatosis Using Fat Attenuation Parameter Measured by FibroTouch and a New Algorithm in CHB Patients.

BACKGROUND: Chronic hepatitis B (CHB) remains a major public health problem worldwide, and the prevalence of CHB patients with hepatic steatosis is gradually increasing. Noninvasive approaches for the assessment of hepatic steatosis have been developed as alternatives to liver biopsy. OBJECTIVES: This study evaluated the diagnostic performance of the fat attenuation parameter (FAP) measured by transient elastography (FibroTouch) and a new algorithm to assess hepatic steatosis in CHB patients, in comparison to liver biopsy as the gold standard. METHODS: Two hundred fifty-four CHB patients underwent simultaneous liver biopsy, biochemical blood testing, and FibroTouch examination. A new algorithm based on four factors (FAP; body mass index, BMI; high-density lipoprotein, HDL; apolipoprotein B, APOB) was defined as follows: fatty index = 10*ep/ (1+ep), and P = -2.75 + 0.028 ln FAP (dB/m) + 0.409 ln BMI (Kg/m2) - 2.482 ln HDL (mmol/L) + 1.979 ln APOB (g/L). The performances of FAP and fatty index were assessed by area under the ROC curve (AUROC). RESULTS: The difference in FAP was significant (P < 0.001) between CHB-only patients and CHB patients with hepatic steatosis. The cytokeratin 18 fragment (CK18-M65) level was significantly higher in CHB patients with non-alcoholic steatohepatitis (NASH) compared with CHB patients without NASH (P < 0.05). The optimal cutoff FAP values for hepatic steatosis of > 0, ≥ 5%, ≥ 10%, ≥ 20%, and ≥ 30% were 224.1, 230.6, 235.5, 246.9, and 261.1 dB/m, and AUROCs were 0.833, 0.801, 0.915, 0.917, and 0.972, respectively. The optimal cutoff value of fatty index for the diagnosis of hepatic steatosis was 1.5 and the AUROC was 0.807. CONCLUSIONS: FAP is an accurate, reliable, and noninvasive approach that can also be combined with other metabolic biomarkers to comprehensively detect and quantify hepatic steatosis.

[Expression of Btk and NFκB in Acute Lymphoblastic Leukemia Cells and Its Significance].

OBJECTIVE: To evaluate the role of Btk and NFκB in the incidence, development, prognosis and therapeutic efficacy for acute lymphoblastic leukemia(ALL) through detecting their expression in leukemia cells. METHODS: Bone marrow samples from 51 ALL patients were collected, and the mononuclear cells were separated by Ficoll density gradient centrifugation. The expressions of Btk and NFκB at RNA and protein levels were detected by RT-PCR and Western blot respectively. RESULTS: (1)At protein level, Btk and NFκB were expressed in all newly diagnosed 51 ALL patients, among them 38 patients had higher expression level of Btk, 34 patients had high NFκB expression level. The expression of Btk and NFκB was higher in the cells from newly diagnosed ALL patients than that in the cells from patients in CR(P<0.05), and the expression of Btk and NFκB was higher in relapsed ALL patients. (2)The expression of Btk and NFκB in the ALL patients was followed-up higher expression of Btk: among the 38 newly diagnosed B-ALL cases, 27 experienced CR (71%) and 12 of which achieved CR after one course chemotherapy (one course CR) (31%). Moreover, 16 out of the 27 CR patients relapsed after a short period (less than 6 months) (59%). On the contrary, among the 13 patients with low Btk expression, 11 achieved CR (84.6%) after one course and 1 relapsed (8 months after CR) (7.6%). A similar pattern of NFκB expression was observed. CONCLUSION: Btk and NFκ B may play an important role in the incidence and progression of ALL, possibly serving as the potential therapeutic targets of ALL and the indexes for prognosis.

[Influence of Co-inhibiting mTORC2 and HSP90 on Proliferation Apoptosis of Multiple Myeloma Cells].

UNLABELLED: Objective：To explore the influence of co-inhibiting mTORC2 and HSP90 on the proliferation and apoptosis of multiple myeloma(MM) cell line U266. METHODS: During culture, the human MM cell line U266 were treated with 20 nmol/L of rapamycin, 600 nmol/L 17-AAG, 20 nmol/L of rapamycin + 600 nmol/L 17-AGG and phosphate-buffered saline (PBS), then the growth inhibition rate, morphologic changes, apoptosis rate and the expression of caspase 3 and ATK protein in U266 cells were compared and analyzed. RESULTS: The rapamycin and 17-AAG both could inhibit the growth of U266 cells, while the inhibitory effect of rapamycin in combination with 17-AAG on growth of U266 cells was significantly higher them that of rapamycin and 17-AAG alone and control (PBS); the apoptosis rate of U266 cells treated with rapamycin, 17-AAG and their combination was higher than that of control PBS groups, and the efficacy of 2 drug conbination was higher than that of control PBS group, and the efficacy of 2 drug combination was superior to single drug. The expression levels of caspase 3 and ATK in U266 cells treated with rapamycin, 17-AAG and their combination were higher and lower than those in control group respectively, and the efficacy of 2 drug combination was superior to signle drug. There were significant difference between them (P<0.05). CONCLUSION: The co-inhibition of mTORC2 and HSP90 can suppress the proliferation and induce the apoptosis of MM cells.

[Influence of Fe3O4Magnetic Nanoparticles Combined with As2O3 and Adriamycin on Raji Cell Apoptosis and Autophagy].

OBJECTIVE: To explore the effect of magnetic iron nanoparticles ( Fe3O4- MNP) in combination with arsenic trioxide and adriamycin on apoptosis and autophagy of Raji cells, a non-Hodgkin's lymphoma (NHL) cell line. METHODS: The growth inhibition rate of Raji cells was analyzed by MTT assay, the cells apoptosis and intracellular concentration of ADM were determined by flow cytometry (FCM), the expression levels of apoptosis-related proteins such as BCL-2, NFκB, Survivin, BAX, P53, and Caspase-3, and related to autophagy-proteins, such as LC3, Beclin-1, and P62/SQSTM1 were detected by Western blot. RESULTS: The growth inhibition of Raji cells in the group of ADM + As2O3were higher than that in the group of ADM or As2O3alone, however, lower than that in the group of Fe3O4- MNP combined with ADM and As2O3(ADM+As2O3+ MNP) (P < 0.05). The apoptotic rate and accumulation of intracellular ADM in the group of Fe3O4- MNP combined with ADM and As2O3were significantly higher than those in control, ADM, As2O3, and ADM plus As2O3groups (P < 0.05). The upregulation of BAX, P53 and Caspase-3 expression and the down regulation of BCL-2, NFκB, and Survivin expression at protein level were more remarkable in the group of ADM+As2O3 + MNP, compared with the other groups (P < 0.05). Moreover, the expressions of LC3 and Beclin-1 proteins in the group of ADM+As2O3+ MNP were higher, while the expression of P62/SQSTM1 was lower than that in other groups (P < 0.05). CONCLUSION: The Fe3O4 - MNP combined with ADM and As2O3can increase the antitumor efficacy on Raji cells by promoting apoptosis and inducing autophagy. It would be a promising strategy for malignant lymphoma therapy.

Emerging roles of Krüppel-like factor 4 in cancer and cancer stem cells.

Cancer stem cells (CSCs) are rare subpopulations within tumors which are recognized as culprits in cancer recurrence, drug resistance and metastasis. However, the molecular mechanisms of how CSCs are regulated remain elusive. Kruppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse functions in cell differentiation, proliferation, embryogenesis and pluripotency. Recent progress has highlighted the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for better therapeutics of cancer disease, it is crucial to develop a deeper understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we summarized the current understanding of the transcriptional regulation of KLF4 in CSCs, and discussed the functional implications of targeting CSCs for potential cancer therapeutics.

Immunomodulatory activity of macromolecular polysaccharide isolated from Grifola frondosa.

The present study was designed to evaluate the immune-modulating effects of the polysaccharide from Grifola frondosa (GFP) by using mouse peritoneal macrophage and cytoxan (CTX) induced immunosuppression models. Our results from the phagocytotic and mononuclear phagocytic system function assays showed that GFP-A (one component from GFP) stimulated the phagocytosis of the phagocytes. The splenocyte proliferation assay showed that GFP-A acted the effect combing ConA or LPS in splenocyte proliferation. The results showed that GFP-A increased indices of thymus and spleen, the levels of LDH and ACP in the spleen, the mRNA levels of IL-1ß, IL-2, IL-6 and IFN-γ in splenocyte. And GFP-A also significantly increased the expression of CD4(+) and CD8(+) splenic T lymphocytes, which were suppressed by the CTX in peripheral blood. In conclusion, our results indicate that the GFP-A is involved in immunomodulatory effects leading to its modulatory effects on immunosuppression.

MiR-143 and rat embryo implantation.

BACKGROUND: To study the role of miR-143 during embryo implantation in rat. METHODS: MiR-143 expression in rat early pregnancy was detected by Northern blot. The relation between miR-143 and Lifr predicted and confirmed by bioinformatics method, dual-luciferase activity assay, Western blot and immunohistochemistry. The role of miR-143 was detected by MTS, Edu and ranswell chamber assays. RESULTS: The expression level of miR-143 on gestation day 5-8 (g.d. 5-8) was higher than on g.d. 3-4 in uteri of pregnant rat. MiR-143 was mainly localized in the superficial stroma/primary decidual zone, luminal and glandular epithelia. The expression of miR-143 was not significantly influenced by pseudopregnancy, but the activation of delayed implantation and experimentally induced decidualization significantly promoted miR-143 expression. Over-expression of miR-143 in human endometrial stromal cells (ESCs) inhibited cell proliferation, migration and invasion. Knockdown of miR-143 promoted cell proliferation and invasion. The results of recombinant luciferase reporters showed that miR-143 could bind to the 3¢-untranslated region (UTR) of leukemia inhibitory factor receptor (Lifr) to inhibit Lifr translation. CONCLUSIONS: Uterine miR-143 may be involved in the successful pregnancy, especially during the process of blastocyst implantation through regulating Lifr. GENERAL SIGNIFICANCE: This study may have the potential to provide new insights into the understanding of miR-143 function during embryo implantation.

Surfactin-induced apoptosis through ROS-ERS-Ca2+-ERK pathways in HepG2 cells.

Although surfactin is able to inhibit cancer cell proliferation and to induce cancer cell apoptosis, the molecular mechanism responsible for this process remain elusive. In this study, the signaling network underlying the apoptosis of human hepatoma (HepG2) cells induced by surfactin was investigated. It is found that the reaction oxygen species (ROS) production and intracellular calcium ([Ca(2+)]i) accumulation are both induced HepG2 cells apoptosis. The [Ca(2+)]i exaltation was partly depended on the Ca(2+) release from inositol 1,4,5-trisphosphate (IP3) and ryanodine (Ry) receptors channels, which both triggered endoplasmic reticulum stress (ERS). The results showed that surfactin induced the ROS production and ROS production led to ERS. The occurrence of ERS increased the [Ca(2+)]i level and the processes associated with blocking extracellular signal-regulated kinase (ERK) pathway. According to a comprehensive review of all the evidence, it is concluded that surfactin induces apoptosis of HepG2 cells through a ROS-ERS-Ca(2+) mediated ERK pathway.