Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014.

Nasopharyngeal swabs were collected from patients through the influenza surveillance network of the CDC of Guangdong. All specimens between 2009 and 2014 were checked for influenza virus using MDCK cells and further subtyped. Of those collected, 542 H1N1pdm09, 230 A(H3N2)and 448 B viruses selected at random were subjected to fluorescence-based NAI assays. Viral RNA was extracted from resistant isolates, and their NA genes were amplified by RT-PCR. Alignment of nucleotides and amino acids was performed. We performed structural modelling and simulations of mutants using Modeller 9.x and AutoDock and analyzed conformations and binding affinities. All tested seasonal type B and H3N2 viruses from 2009 to 2014 remained sensitive to oseltamivir. However, there were five strains (out of 198 tested isolates acquired between June and September 2013) that were resistant to oseltamivir. Another three resistant strains were identified among isolates from March to April 2014. We found that 2013/2014 oseltamivir-resistant strains and 2012/2013/2014 oseltamivir-sensitive strains had all or some of the following mutations: N44S, N200S,V241I, I321V,N369K, N386 K and K432E. MutationsV241I, N369K, N386K and K432E, alone or in conjunction with H275Y, had a significant impact on the binding pattern and affinity of oseltamivir for neuraminidase, rendering neuraminidase less susceptible.

Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis.

The aim of this study was to evaluate the clinical significance of circulating tight junction (TJ) proteins as biomarkers reflecting of leukaemia central nervous system (CNS) metastasis. TJs [claudin5 (CLDN5), occludin (OCLN) and ZO-1] concentrations were measured in serum and cerebrospinal fluid (CSF) samples obtained from 45 leukaemia patients. Serum ZO-1 was significantly higher (p < 0.05), but CSF ZO-1 levels were not significantly higher in the CNS leukaemia (CNSL) compared to the non-CNSL. The CNSL patients also had a lower CLDN5/ZO1 ratio in both serum and CSF than in non-CNSL patients (p < 0.05). The TJ index was negatively associated with WBCCSF , ALBCSF and BBB values in leukaemia patients. Among all of the parameters studied, CLDN5CSF had the highest specificity in discriminating between CNSL and non-CNSL patients. Therefore, analysing serum and CSF levels of CLDN5, OCLN and the CLDN5/ZO1 ratio is valuable in evaluating the potential of leukaemia CNS metastasis. Copyright © 2016 John Wiley & Sons, Ltd.

Diagnostic value of platelet indices and bone marrow megakaryocytic parameters in immune thrombocytopenic purpura.

Platelet indices could mirror megakaryopoietic activity in immune thrombocytopenic purpura (ITP), but its specificity and sensitivity need to be studied. The diagnostic performance of platelet indices was analyzed by receiver-operating characteristic curves, and the probability of true positive (sensitivity) and true negative (specificity) in predicting ITP, myelodysplasia, or controls was determined. Mean platelet volume (MPV) was higher, whereas plateletcrit (PCT) was significantly lower in ITP than in myelodysplasia and controls. The platelet distribution width in ITP patients was lower than in myelodysplasia, but higher than in controls. Increased megakaryocytes were only observed in ITP. A strong positive correlation was found between MPV and quantities of granular megakaryocytes, whereas a negative relationship existed between MPV and platelet-form megakaryocytes. In receiver-operating characteristic analysis, MPV and PCT gave a sensitivity of 70.3% (89.8%) and specificity of 74.8% (84.7%) at a cutoff of 9.35 (0.085) in diagnosis of ITP. Combined parallel test of MPV and PCT increased the sensitivity to 97.5 with 64.1% specificity, whereas series test increased the specificity to 94.7 with 62.7% sensitivity. Our results suggest that MPV, PCT, and platelet distribution width represent megakaryopoietic activity in bone marrow and may be reliable markers in ITP diagnosis.

The use of human umbilical cord blood serum is beneficial for the continuous production of hepatitis C virus.

In this study we investigated if human umbilical cord blood serum (CBS) is a suitable replacement for foetal bovine serum (FBS) in cultures of human hepatoma cell line Huh7.5, particularly regarding its capacity to maintain high growth rates, differentiation status and its ability to support robust hepatitis C virus (HCV) infection. Generally, CBS-cultured Huh7.5 cells remained comparable to FBS-cultured cells, and proliferated equally well. Albumin secretion, a hepatocyte differentiation marker, had increased 8x in CBS; however, most other hepatocyte markers we tested had not changed. Surprisingly, CBS-cultured cells were able to sustain very high levels of HCV production, and HCV infection in CBS-cultured cells did not induce cell lysis, which is typically seen in HCV-infected cells cultured in FBS. We discuss some of the differences between CBS, adult human serum and FBS that may explain the differences observed.

Risk factors for the evaluation of potential central nervous system metastasis in Burkitt's lymphoma: a case study and literature review.

Burkitt's lymphoma (BL) is a malignancy of B lymphocytes. The rapid growth rate and frequent systemic spread result in most patients presenting with advanced disease at diagnosis. Cerebrospinal fluid cytology is the gold standard (with very high accuracy) for diagnosing BL central nervous system (CNS) metastasis; however, the low sensitivity of this method limits its clinical applications. Here, we report a case of BL with CNS metastasis. The levels of vascular endothelial growth factor (VEGF)-A and VEGF-C in the serum and cerebrospinal fluid were used to evaluate the status of BL remission and recurrence. Comparisons were made between VEGF and the other risk factors used in evaluating CNS metastasis. Although not in strict accordance, VEGF levels mirrored the disease course. Therefore, VEGF may reflect the status of BL CNS metastasis. Understanding the role of VEGF in CNS metastasis may help to improve the staging and risk classification of BL as well as the investigation of targeted therapy.

Clinical and laboratory features parameters of human granulocytic anaplasmosis (HGA) in patients admitted to hospital in Guangdong Province, China.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is an acute tick-borne infectious disease with increasing morbidity and mortality, but is rarely considered in clinical practice. Because human-to-human transfusion or nosocomial transmission can occur, diagnosis is difficult when the history of tick bites is not clear. METHODS: We present clinical features and laboratory data of HGA patients who had no clear tick bite history. RESULTS: All patients in the study presented with a high fever, petechiae, purpura, nose bleeding and leukopenia, and patients had abnormally high levels of serum ferritin and C-reactive protein. Morulae in leukocytes were observed in three patients. Foamy histiocytes and slight erythrophagocytic activity were only found in severely ill patients. CONCLUSION: In patients with fever and thrombocytopenia in whom no other diagnosis is evident on clinical assessment, HGA should be considered in the differential diagnosis, and tested for serologically if possible. For patients in whom the diagnosis of HGA is possible, and to whom tetracyclines can safely be given, it is apparent that these drugs hasten recovery and improve the prognosis.

The prognostic significance of serum and cerebrospinal fluid MMP-9, CCL2 and sVCAM-1 in leukemia CNS metastasis.

Metastasis to the central nervous system (CNS) is the primary obstacle in leukemia treatment. Matrix metalloproteinase-9 (MMP-9), chemokine ligand-2 (CCL2) and soluble vascular adhesion molecule-1 (sVCAM-1) play crucial roles in tumor cell adhesion, motivation and survival, but their roles in leukemia CNS metastasis remain to be elucidated. We investigated the prognostic significance of serum and cerebrospinal fluid (CSF) MMP-9, CCL2 and sVCAM-1 in leukemia patients to explore their potential as predictive biomarkers of the development of CNS leukemia (CNSL). MMP-9, CCL2 and sVCAM-1 were measured in paired CSF and serum samples collecting from 33 leukemia patients with or without CNS metastasis. Other risk factors related to CNSL prognosis were also analyzed. sVCAM-1Serum and CCL2Serum/CSF were significantly higher in the CNSL group than in the non-CNSL group and the controls (p < 0.05). MMP-9Serum was insignificantly lower in the CNSL group than in the non-CNSL group and the controls (p > 0.05). No differences were found for the sVCAM-1Serum, CCL2Serum, and MMP-9Serum levels between non-CNSL patients and controls (p > 0.05). MMP-9CSF was significantly higher in the CNSL group than both the non-CNSL and the control groups (p < 0.05). The indexes of sVCAM-1, CCL2, and MMP-9 in the CNSL group were lower than in the controls (p < 0.05). Positive correlations were determined between the MMP-9CSF and the ALBCSF/BBB value/WBCCSF, between sVCAM-1Serum and the WBCCSF/BBB value. Negative correlations existed between MMP-9Serum and the ALBCSF/BBB value/WBCCSF, and between the CCL2 index and ALBCSF. sVCAM-1Serum was positively associated with event-free survival (EFS), and patients with higher levels of ALBCSF, MMP-9CSF/Serum, CCL2CSF/Serum, and sVCAM-1CSF/Serum had shorter EFS. MMP-9CSF, CCL2CSF and sVCAM-1CSF are the first three principal components analyzed by cluster and principal component analysis. Our data suggest that MMP-9, CCL2 and sVCAM-1 in the CSF may be more potent than serum in predicting the possibility of leukemia metastatic CNS and the outcome of CNSL patients.

Distribution of EV71 receptors SCARB2 and PSGL-1 in human tissues.

The aim of this study was to investigate the distribution of Enterovirus 71 (EV71) receptors SCARB2 and PSGL-1 in human tissues. The samples were chosen from archived specimens, and the profiles of two receptors were detected in the gastrointestinal tract, lung, and brain in situ by immunohistochemistry. SCARB2 was detected in all the tissues studied, and strong staining was observed in the gastric fundus gland, mucosal and glandular epithelia of the intestine. Similar expression was found in bronchial epithelia and pneumocytes. In addition, SCARB2 was observed in the esophagus/gastric mucosal epithelia, neuron, glial cells, and blood vessels and the perivascular tissues of the brain. By comparison, PSGL-1 was expressed weakly in the mucosal and glandular epithelia of the small intestine and colon. PSGL-1 was expressed in a few bronchial epithelia, and weak staining was observed in the pneumocytes. However, PSGL-1 was found easily in the lamina propria of all the tissues studied, and strong staining of PSGL-1 was also observed in the neurons and glial cells. The distribution of the SCARB2 and PSGL-1 in human gastrointestinal tract, lung, and brain tissues correlated with the distribution of pathological changes seen in EV71 infection. The widespread prevalence of these receptors may help explain the multiple organ involvement in infection with EV71.

Regulation of hepcidin through GDF-15 in cancer-related anemia.

BACKGROUND: High prevalence and unresponsiveness to erythropoiesis-stimulating agents are 2 major limitations to the treatment of cancer-related anemia (CRA). They are often related to the dis-regulation of iron metabolism regulated by hepcidin, but the regulatory pathway of hepcidin in CRA is poorly understood. Enhanced GDF-15 levels contribute to the cancer progression and metastasis, and also have been found to suppress hepcidin expression in anemia characterized by ineffective erythropoiesis. The pathophysiological mechanisms and the relationship of GDF-15 and hepcidin in CRA remain to be elucidated. METHODS: The concentrations of hepcidin and GDF-15 as well as the hematological and the iron parameters were determined in sera from 131 patients with cancer and 40 healthy controls. RESULTS: Serum GDF-15 levels were increased significantly in patients with the severe CRA, compared with the mild or no CRA patients and the controls. Increasing GDF-15 levels corresponded to decreasing hepcidin concentrations. A trend toward a correlation between high levels of GDF-15 and poor prognosis of cancer was also found. Elevation of GDF-15 concentrations suppressed hepcidin expression at high concentrations. CONCLUSIONS: Our findings suggest that tumor progression results in increased GDF-15 secretion, which may down-regulate hepcidin expression, resulting in iron overload in cancer patients; this phenomenon has also been found in some patients with sideropenic anemia due to chronic blood loss.

The association of serum vascular endothelial growth factor and ferritin in diabetic microvascular disease.

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic microvascular disease. Most diabetes patients have higher serum levels of ferritin that may participate in diabetic vascular complications through high oxidative stress induced by iron. However, the mechanistic link between ferritin and VEGF is obscure. The study investigated the association of VEGF and ferritin in patients with diabetic microvascular disease. PATIENTS AND METHODS: Sixty patients with type 2 diabetes mellitus (T2DM) and 26 healthy individuals were selected in this study. Serum ferritin, VEGF, hematological parameters, and clinical data were assessed in this cohort. The Spearman rank method was used to evaluate the associations among them. RESULTS: Serum levels of VEGF and ferritin were significantly higher in diabetes patients compared with the controls; levels of both were elevated with development of the disease. There were positive correlations between VEGF and glucose levels and between VEGF and ferritin in diabetes groups, especially in patients with diabetic retinopathy. Positive correlations were also found between VEGF level and the parameters of age, hemoglobin, and albumin in patients with diabetes hypertension. CONCLUSIONS: Our data suggest that high ferritin levels in T2DM are closely related to the development of diabetic vascular complications through interaction with VEGF.

The effect of hepatitis B virus infection on hepcidin expression in hepatitis B patients.

BACKGROUND: Hepcidin is a central regulator of iron metabolism. As hepcidin is produced mainly by hepatocytes, pathologic changes in the liver may affect hepcidin production. Abnormal hepcidin expression has been reported following liver injury, including liver cirrhosis, alcoholic liver disease, and chronic hepatitis B and hepatitis C. However, it is unclear whether there is a dose-dependent relationship between hepcidin expression and hepatitis B virus load. The aim of this study was to characterize hepcidin levels in patients with different hepatitis B virus (HBV) DNA levels. METHODS: We investigated serum hepcidin levels in 71 patients with different HBV DNA loads, 10 patients with hepatocelluar carcinoma (HCC), and 13 healthy individuals. The relationships between hepcidin expression and hematological/liver functional parameters, iron, and inflammatory indicators were also analyzed. RESULTS: Serum IL-6, ferritin, and hepcidin levels were significantly higher in patients with hepatitis B and in HCC patients than in controls (P<0.05), and strong positive correlations were found between hepcidin and ferritin, AST, ALT, GGT, ALP, TBIL, IBIL, and AFU, as well as between log [hepcidin] and log [HBV], respectively. There were no significant differences in hematological parameters, including WBC, Hb, and platelets among hepatitis B patients, nor was a correlation found between hepcidin and any hematological parameters. CONCLUSION: Our results indicate that hepcidin expression is regulated by iron and inflammatory factors in hepatitis B infection patients, and that the virus load can affect hepcidin production.

The role of insulin-like growth factor I and hypoxia inducible factor 1α in vascular endothelial growth factor expression in type 2 diabetes.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in diabetic vascular complications, and its expression is affected directly or indirectly by hypoxia inducible factor-1α (HIF-1α) and insulin-like growth factor-I (IGF-I) in tumors and certain normal cell lines. However, little is known about the role of HIF-1α/ IGF-I in VEGF expression in patients with diabetic vascular complications. The aim of this study was to elucidate the associations between HIF-1α, IGF-I, and VEGF in type 2 diabetes mellitus (T2DM) patients with or without vascular complications. METHODS: Sixty patients with T2DM, with(A), and without vascular disease (B) and 26 controls were enrolled. Clinical parameters, HIF-1α, IGF-I and VEGF were assessed in the study and associations among them were analyzed by Spearman rank correlation. RESULTS: Serum levels of VEGF, HIF-1α and IGF-I were significantly higher in the diabetic patients than in the controls. Positive correlations existed between VEGF and HIF-1α and between HIF-1α and IL-6 in both groups A and B and in the control group. CONCLUSIONS: Our data demonstrate that HIF-1α and IL-6 could regulate VEGF expression, and that higher levels of HIF-1α, IL-6, and VEGF may contribute to the pathogenesis of diabetic micro-angiopathy.

The soluble VEGF receptor 1 and 2 expression in cerebral spinal fluid as an indicator for leukemia central nervous system metastasis.

Over-expression of vascular endothelial growth factor A (VEGF-A) is correlated with leukemia metastasis. VEGF-A acts by binding to its membrane receptors R1 and R2 present in soluble forms (sVEGFR1, sVEGFR2) with different functions. sVEGFR could inhibit VEGF-A bioactivities, associated with favorable prognosis in solid tumors. However, its role is obscure in central nervous system leukemia (CNSL). The aim of this study was to investigate sVEGFR1, R2 as biomarkers in CNSL. Paired cerebrospinal fluid (CSF) and serum samples were collected from 35 leukemia cases with or without CNS metastasis. Levels of sVEGFR1 and sVEGFR2 in both CSF (sVEGFR1CSF, sVEGFR2CSF) and serum (sVEGFR1Serum, sVEGFR2Serum) were detected by ELISA. Other risk factors related to CNSL prognosis were also analyzed. sVEGFRSerum levels were 2.54-fold (sVEGFR1) and 25.6-fold (sVEGFR2) higher than sVEGFRCSF in both leukemic groups. sVEGFR1CSF in CNSL were 33 % higher than in the non-CNSL, and the levels of sVEGFR2CSF and sVEGFR2Serum had the same trend. Elevated sVEGFR1CSF and sVEGFR2CSF is closely correlated with blood-brain barrier (BBB) values and WBCCSF that is an indicator of CNSL disease burden. Cox regression analysis showed that the sVEGFR2CSF had a positive effect on event-free survival. Our data suggest that sVEGFR2CSF may be more potent than sVEGFR1CSF in predicting the outcome of leukemia patients, the balance between sVEGFR2CSF and VEGF-ACSF levels might be crucial for the progression of CNSL.

Expression and significance of vascular endothelial growth factor A and C in leukemia central nervous system metastasis.

Metastasis to the central nervous system (CNS) is an obstacle for leukemia treatment, the mechanisms of which remain to be elucidated. VEGF-A and VEGF-C are suspected to participate in this process. Paired of cerebrospinal fluid (CSF) and serum samples were collected from leukemia and control cases. Levels of VEGF-A and VEGF-C in both CSF (VEGF-ACSF, VEGF-CCSF) and serum (VEGF-ASerum, VEGF-CSerum) were detected by ELISA. Our data show that higher levels of VEGF-ACSF are closely related to CNS leukemia (CNSL), and VEGF-ACSF may be a better predictor than the other risk factors elucidating the pathogenesis and development of CNSL.

Hepcidin expression in patients with acute leukaemia.

BACKGROUND: Hepcidin plays a central role in iron homeostasis, which is regulated by iron stores, the rate of erythropoiesis, inflammation, and hypoxia. Aberrant expression of hepcidin was found in many diseases, however, there is scant information on hepcidin expression in acute leukemia (AL). MATERIALS AND METHODS: 32 patients with AL which diagnosis according to FAB criteria were studied. Serum hepcidin levels, erythropoietin (EPO), interleukin-6 (IL-6), hematological parameters, intracellular and extracellular iron store were evaluated. RESULTS: Hepcidin was elevated significantly with increased iron storage in patients at onset of AL when erythropoiesis was depressed by blast cells, then decreased significantly with AL remission, while soluble transferrin receptor (sTfR) concentration was elevated. Negative correlations were found between serum hepcidin and erythropoietic markers including RBC, Hb, Ret and sTfR. Positive correlations were shown between hepcidin and ferritin, between hepcidin and ratio of sideroblasts, as well as between hepcidin and IL-6. CONCLUSIONS: Hepcidin production was regulated by iron stores, inflammation and erythropoietic activity in AL patients. Erythropoietic activity may play the main role among the regulators of hepcidin expresssion.

Hepcidin expression and iron parameters change in Type 2 diabetic patients.

AIM: Iron may contribute to the pathogenesis of Type 2 diabetes mellitus (DM). The aim of this study was to determine iron regulator hepcidin and iron metabolic parameters in Type 2 DM patients, the relationships among them were evaluated in this specific sub-groups. MATERIALS AND METHODS: The study included sixty-four people: 34 cases of diabetes and 30 age-matched controls. Serum hepcidin, IL-6, hsCRP, ferritin, sTfR, EPO as well as other clinical parameters were detected, and the associations between hepcidin levels and iron/inflammatory parameters were analyzed in diabetes and the controls. RESULTS: Serum ferritin and hepcidin levels in diabetic patients were significant higher than the controls (p<0.001 respectively). A positive correlation between hepcidin and ferritin, as well as between ferritin and IL-6 levels was existed in diabetes and the control groups (p<0.001 respectively). CONCLUSION: All of these data demonstrated that the higher hepcidin levels in diabetic patients may be due to those higher ferritin and IL-6 levels, the elevated hepcidin might have adaptive value through down-regulated iron absorb and play an important role in pathogenesis of Type 2 DM.

Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia.

Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.

Lycorine induces apoptosis and down-regulation of Mcl-1 in human leukemia cells.

Lycorine is an alkaloid isolated from the bulb of the Amaryllidaceae Lycoris. Here, we report that treatment with lycorine resulted in survival inhibition and apoptosis induction in human leukemia cell lines. Lycorine induced apoptosis in human leukemia cells via intrinsic mitochondria pathway and caused a rapid-turnover of protein level of Mcl-1 which occurred before caspases activation. Furthermore, pronounced apoptosis accompanied by the down-regulation of Mcl-1 was also observed in blasts from patients with acute myeloid leukemia. Our findings suggest that lycorine may be a good candidate therapeutic agent against leukemia in worth of further evaluation.

The correlation between cytokine production by cerebral cortical glial cells and brain lateralization in mice.

Objectives. This study aims to explore the relationship among the levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) produced by cortical glial cells, and identify any correlation between neuromodulation and brain lateralization. Material and Methods. Cortical glial cells from Balb/c neonatal mice were cultured in vitro and the effects of treating or not treating these cells from both hemispheres with lipopolysaccharide (LPS) (10 µg/mL) for 24 hours were tested. The levels of IL-1ß, IL-6, and TNF-α in left and right cortical glial cell cultures and the time course of any changes were compared. Rusults. The production of IL-1ß and TNF-α had no significant difference between right and left cortex in the untreated group within 24 hours. IL-6 was significantly higher in the right than the left cortical glial cells. In the LPS-treated group, increased levels of IL-1ß, TNF-α, and IL-6 were found, particularly for IL-6, and all were significantly increased in cortical glia cells from the right side. The time course shows that the expression of IL-1ß in right cortex and IL-6 in both sides is time-dependent (p < 0.05). Conclusion. Lipopolysaccharide increases cytokine production in both cerebral cortices, three cytokines have different expression time course within 72 hours, but only IL-1ß in right cortex and IL-6 releasing is time-dependent, and more so on the right side than the left in 24 hours. We proposed the increased immunosuppressive activity of right cortex was due to the higher expression of IL-1ß, TNF-α, and IL-6 in the right cortical glial cells, whereas there would be more immunoenhancement activity of the left cortex due to the lower levels of these three kinds of cytokines, this being a less pronounced effect than that on the right side. One of the reasons for the brain lateralization may be the different production of cytokines by the cortical glial cells on either side.

Matrine-induced apoptosis in leukemia U937 cells: involvement of caspases activation and MAPK-independent pathways.

It is reported that matrine, one of the major effective compounds isolated from the root of Sophora flavescens Ait., has anti-leukemia activity. In this study, we find that the treatment of leukemia U937 cells with matrine results in induction of apoptosis. Analysis of the mechanism underling this apoptotic event showed activation of caspases-9, -3, and -7, and release of cytochrome C from mitochondria to cytosol, and cleavage of poly(ADP-ribose) polymerase. Matrine did not alter the level of bcl-2 and bcl-xL as well as bax. In addition, no correlation was found between matrine administration and activation of the three major MAPK subfamilies (Erk1/2, p38, JNK/SAPK). The results indicate that matrine induces apoptosis in U937 cells via a cytochrome C-triggered caspase activation pathway.