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.

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

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 study the methylation status of p73 gene promoter in patients with myelodysplastic syndrome (MDS) and explore its significance with clinical prognosis.

METHODSMethylation of p73 promoter was detected in bone marrow cells from 135 MDS patients and 13 healthy controls by methylation-specific PCR (MSP). The results of MSP were confirmed by bisulfite sequencing. The expression of p73 mRNA was detected by real-time quantitative PCR. Primary bone marrow cells from MDS patients were treated with decitabine, the changes of p73 methylation status and p73 mRNA expression were measured. The role of p73 methylation in the prognosis of MDS and the correlated clinical data were explored.

RESULTSp73 hypermethylation was present in 37.04% of MDS cases and patients with high risk MDS (RAEB-1 and RAEB-2) exhibited a significantly higher frequency of p73 methylation than that of low risk MDS (58.8% vs 29.7%, P = 0.002). The expression of p73 mRNA in the methylated group was decreased compared to that of the unmethylated group (P = 0.032). Decitabine treatment decreased the level of p73 methylation and increased the level of p73 transcripts. Patients with p73 methylation progressed rapidly to AML (P < 0.001) and had shorter survival (P = 0.002) than those who did not have p73 methylation. In the multivariate Cox regression model, BM blast and p73 methylation status emerged as independent prognostic factor for overall survival and leukemia free survival.

CONCLUSIONp73 gene methylation is common in patients with MDS and may indicate poor prognosis. p73 may be a therapeutic target in MDS.

Aged ; Case-Control Studies ; DNA Methylation ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; Nuclear Proteins ; genetics ; Prognosis ; Promoter Regions, Genetic ; Tumor Protein p73 ; Tumor Suppressor Proteins ; genetics

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 observe the effects of integrative therapy on elderly patients with advanced nonsmall cell lung cancer (NSCLC), thus providing clinical evidence for further studies.

METHODSTotally 91 elderly patients with advanced NSCLC were randomly assigned to three groups, i.e., the Chinese medicine (CM) group (Group I, 31 cases), the chemotherapy group (Group II, 30 cases), and the CM and chemotherapy combination group (Group III, 30 cases). Oral administration of CM decoction and intravenous dripping of Chinese patent medicine were given to patients in Group I. Patients in Group II received chemotherapeutic protocol alone. Patients in Group III received chemotherapeutic protocol while taking CM decoction. Twenty-eight days were taken as one therapeutic course, and two courses in total. They were observed for two treatment courses by taking Symptoms Scale of CM to Primary Lung Cancer, bone marrow depression score, and progression-free survival (PFS) as therapeutic efficacy indices. Meanwhile, the Cox's proportional hazards regression model was established to analyze the favorable factors and risk factors that influenced patients' PFS.

RESULTSThe CM symptom integral of Group I and Group III was superior to that before treatment, showing statistical difference (P < 0.01). The occurrence of bone marrow depression in Group III was lower than that in Group II. The degree of bone marrow depression was also milder in Group III than in Group II, but there was no statistical difference in inter-group comparison (P = 0.097, P = 0.299). The PFS was 202 days in Group III, 168 days in Group I, and 129 days in Group II. It was better in Group III than in Group II (P = 0.0157). The Cox regression analysis showed that positive factors to longer PFS included CM + chemotherapy, no surgical management, and PS = 1.

CONCLUSIONSCM therapy could improve the symptoms of elderly patients with advanced NSCLC. It might extend the PFS of the elderly patients by CM therapy combined with chemotherapy.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Integrative Medicine ; Lung Neoplasms ; pathology ; therapy ; Male ; Neoplasm Staging ; Phytotherapy ; Quality of Life