Ineffective erythropoiesis is recognized as the principal reason of non-transfusional iron overload. In the process of expanded erythropoiesis, the apoptosis of erythroblasts induces the up-regulation of GDF15. GDF15 suppresses hepcidin production by the hepatocytes. Subsequently, low hepcidin levels increase iron absorption from the intestine resulting in iron overload. Physiological dose of GDF15 can promote the growth and differentiation of erythroid progenitors, but the high dose of GDF15 can suppress the secretion of hepcidin. The regulation of GDF15 may also be related to iron levels, epigenetic regulation and hypoxia. In this article the GDF15 and its expression and distribution, roles of GDF15 in erythropoiesis and iron overload, as well as the regulation factors of GDF15 are reviewed.
Erythropoiesis ; Growth Differentiation Factor 15 ; metabolism ; Humans ; Iron Overload

Objective To investigate the processing characteristics of locative prepositions in patients with Chinese aphasia,and to provide the theoretical evidence for the rehabilitation of aphasia.Methods Twenty aphasic patients caused by left-hemisphere stroke and twenty matched normal controls were studied.Using the locative prepo- sition repeating task(single words,locative preposition phrases and words in sentences),the comprehension task, filling-gap task,the visual-spatial function task and the short-term memory task,we compared the performance be- tween these two groups.Results The aphasic patients had more difficulty in repeating locative prepositions in sen- tences,in comprehension task and filling-gap task,their short term memory was impaired.Both groups did well in re- peating single words and phrases.Conclusion The processing of locative prepositions was impaired in Chinese aphasics.The repetition of locative prepositions was more difficult than that of phrases and single words.The preposi- tions were often omitted.It might be due to the impairment of their short-term memory,or it might have something to do with role they played in the syntactic structure.The latter might also impact the comprehension and filling-gap score.We should make plans before rehabilitation therapy.

Objective To investigate the radiosensitization effects of the combination treatment of clioquinol (CQ) and zinc on human cervical cell line HeLa in vitro.Methods Cells were divided into the 4 groups:controls,drug,radiation,and combined drug and radiation group.Cytotoxic effect of CQ and zinc on cell viability was determined by CCK-8 assay.Radiosensitization effect of CQ and zinc on HeLa cells was detected by colongenic assay,and the single-hit multi-target model was used to stimulate the doseresponse curve of survival and to calculate radiosensitization parameters.The cell cycle and apoptosis of HeLa cells were analyzed with flow cytometry.Luciferase reporter assay was used to study NF-κB activity of HeLa cells.Results The combination of CQ and zinc inhibited cell growth in a dose-dependent manner (F =188.00,P ＜ 0.01).The mean lethal dose was 3.16 and 2.04 Gy for radiation group and combined drug and radiation group,respectively,and hence the SER was 1.55.Compared with the radiation group,the ratio of G2-phase cells in the combined drug and radiation group decreased(t =10.39,P ＜ 0.05),the apoptosis rate increased at 24 h post-irradiation (t =5.64,P ＜ 0.01),and the NF-κB activity decreased (t =21.42,P ＜ 0.05).Compared to the control group,the NF-κB activity increased in the radiation group(t=6.23,P＜0.05),but decreased in the drug group(t =12.48,P＜0.05).Conclusions The combination of CQ and zinc could increase the radiosensitivity of HeLa cells by decreasing the ratio of G2-phase cells,increasing apoptosis and the inhibiting of NF-κB activity.

BACKGROUNDThe mortality and disability associated with progressing ischemic stroke are much higher than general ischemic stroke. This study was conducted to determine the risk factors for progressing ischemic stroke in the Han population of northeast China.

METHODSA total of 2511 patients with ischemic stroke within 24 hours admitted to Department of Neurology, First Affiliated Hospital of Harbin Medical University were studied, from November 2007 to May 2009. All of the patients were classified into the progressing or non-progressing group according to the scores of the Scandinavian Neurological Stroke Scale. Fifteen putative risk factors were evaluated. The influence of risk factors for progressing ischemic stroke was analyzed with the simple Logistic analysis, the multiple Logistic analysis, and the stepwise Logistic regression model. All the statistical analysis was performed by SAS 9.1.

RESULTSTotally 359 (14.3%) patients met the criteria for progressing ischemic stroke. The Logistic analysis showed that age, family stroke history, smoking history, hypertension on admission, a drop in blood pressure after admission to the hospital, high serum glucose on admission, and fever were related to progressing ischemic stroke in the Han population of northeast China.

CONCLUSIONPeople of the ischemic stroke with these factors are more likely to develop progressing ischemic stroke.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Regression Analysis ; Risk Factors ; Stroke ; epidemiology ; Young Adult

Liver cirrhosis is the leading cause of liver-related death globally, and the most common causes of liver cirrhosis are chronic hepatitis B and C, alcoholic liver disease, and nonalcoholic fatty liver disease. Recent studies have shown that despite an increase in the number of deaths due to liver cirrhosis around the world, there is a reduction in age-standardized death. In China, there are increases in number of patients with liver cirrhosis, prevalence rate of liver cirrhosis, number of deaths due to liver cirrhosis, and mortality rate of liver cirrhosis, while there are reductions in age-standardized prevalence rate and mortality rate; chronic hepatitis B remains the main cause of liver cirrhosis, with a gradual increase in the proportion of liver cirrhosis cases caused by alcoholic and nonalcoholic fatty liver diseases.

AIMTo study the alkaloid constituents of the hairy roots of Ipomoea batatas Lam.

METHODSChromatographic methods were used for isolation and purification. The structure was elucidated on the basis of spectral data.

RESULTSAn alkaloid was isolated from the hairy roots of Ipomoea batatas.

CONCLUSIONThe compound is a novel indole-type alkaloid, which is named as ipomine A.

Indole Alkaloids ; chemistry ; isolation & purification ; Ipomoea batatas ; chemistry ; Molecular Conformation ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo investigate the role of Xuebijing injection(XBJI, traditional Chinese medicine), in inhibiting TLR4--NF-kappaB--IL-1beta pathway of myocardial hypoxia/reoxygenation in rats.

METHODSThirty six male SD rats (280 +/- 30) g were randomly divided into six groups (n = 6): normal group (N group), balanced perfusion group (BP group), model group (M group), low dose XBJI group (XBJI(L) group), middle dose XBJI group (XBJI(M) group), high dose XBJI group (XBJI(H) group). By Langendorff isolated heart perfusion device to establish the model of myocardial hypoxia/reoxygenation in rats. ELISA was used to detect the concentration of interleukin-1beta (IL-1beta); Western blot was used to detect the expression of nuclear factor kappa B p65 (NF-kappaB p65) protein and toll like receptor 4 (TLR4) protein; and RT-PCR to determine the expression of NF-kappaB p65 mRNA and TLR4 mRNA;To observe microstructure changes of hypoxia/reoxygenation myocardial by light microscopy.

RESULTSCompared with M group, the IL-1beta concentration, NF-kappaB p65 and TLR4 protein,NF-kappaB p65 and TLR4 mRNA of XBJIL group, XBJI(M) group, XBJI(H) group expression decreased in varying degrees,and decreased most obviously all in XBJI(M) group (P < 0.05, P < 0.01); Myocardical structural damage was serious in M group, and improved after treatment XBJI, the most obvious was the XBJI(M).

CONCLUSIONDifferent dose of XBJI can inhibit TLR4--NF-kappaB--IL-1beta signal transduction pathway and reduce several inflammatory reaction after myocardial hypoxia/reoxygenation injury, the 4 ml/100 ml of XBJI is the best.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; Inflammation ; Interleukin-1beta ; metabolism ; Male ; Myocardium ; pathology ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; Signal Transduction ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; metabolism

AMD3100 (Plerixafor) is an antagonist of CXCR4, receptor for stromal cell-derived factor-1 (SDF-1).It disrupts binding of SDF-1 to CXCR4 by competing binding site, thus blocking the physiological function of SDF-1/CXCR4 axis. SDF-1/CXCR4 axis has been shown to play critical roles in stem cell mobilization, migration and homing, and in immunoregulation, inflammatory disease, autoimmune disorder, embryonic development, and tumor cell proliferation, migration and location. AMD3100 has been confined effective for the mobilization of HSC and MSC, inhibition of carcinoma growth and metastasis, suppression of some inflammatory and autoimmune disorder. Therefore, further research on AMD3100 will be helpful to understand the effects of bone marrow microenvironment on the pathogenesis of neoplasm, and to restore the traumatic tissues by mobilizing HSC effectively, that might provide a new idea and measure for the treatment of certain neoplasms. Some research progress of basic research and application on AMD3100 are summarized in this review.
Heterocyclic Compounds ; pharmacology ; Receptors, CXCR4 ; antagonists & inhibitors

OBJECTIVETo investigate the relation of the viral markers in serum and those expressed by hepatocytes to pathological lesions of hepatic tissue in patients with chronic hepatitis B.

METHODSThe relation of viral markers including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb and HBV DNA in serum of 647 patients with chronic hepatitis B and HBsAg, HBcAg expressed by hepatocytes in 418 of these patients to pathological lesions of hepatic tissue was determined.

RESULTSViral markers in serum and those expressed by hepatocytes in patients with chronic hepatitis B were closely correlated with pathological lesions of hepatic tissue.

CONCLUSIONThe degree of inflammation and fibrosis in hepatic tissue is milder in serum HBsAg, HBeAb, HBcAb positive and HBV DNA negative patients but more serious in those with negative hepatocytic expression of HBsAg and HBcAg. HBV DNA is not significantly associated with pathological lesions of hepatic tissue.

Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral ; blood ; genetics ; Female ; Hepatitis B Core Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; physiology ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Liver ; pathology ; virology ; Male ; Middle Aged ; Young Adult

This study was purposed to explore the expression of p57kip2 in the bone marrow of patients with de novo myelodysplastic syndrome (MDS) and its role in MDS pathogenesis, as well as the relationship between the expression of p57kip2 and SDF-1/CXCR4 signal. The expression of p57kip2 and CXCR4 in 67 de novo MDS patients was measured by real-time quantitative PCR. The percentage of CD34(+) cells in the bone marrow from MDS patients was measured by flow cytometry. 18 healthy volunteers were recruited for control. The effect of SDF-1 on p57kip2 expression in bone marrow mononuclear cell (BMMNC) from MDS or normal controls was investigated in vitro, and difference between them was compared. The results showed that low-risk MDS and high-risk MDS displayed a significant reduction of p57kip2 mRNA expression in BMMNC compared with that in control group (P < 0.001) and there was a negative correlation between p57kip2 expression and percentage of CD34(+) (r = -0.458, P < 0.001); the patients with abnormal karyotype showed lower expression of p57kip2 gene, compared to patients with normal karyotype (P = 0.045). Although the expression of CXCR4 had no difference between MDS patients and normal controls, a positive correlation between p57kip2 and CXCR4 in MDS patients was still found (r = 0.609, P < 0.001). Moreover, SDF-1 increased p57kip2 expression in normal BMMNC in dose-dependent manner, but BMMNC from MDS patients showed no response to SDF-1. SDF-1-induced p57 expression was blocked by AMD3100. It is concluded that the low expression of p57 gene in MDS may play a role in the pathogenesis of MDS. Furthermore, SDF-1-induced p57kip2 expression in BMMNC, and the decreasing response of BMMNC to SDF-1 may contribute to the low expression of p57kip2 in MDS patients.
Case-Control Studies ; Chemokine CXCL12 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p57 ; genetics ; metabolism ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; genetics ; metabolism ; Receptors, CXCR4 ; metabolism