The role of p75 neurotrophin receptor in neurodegenerative diseases / 中国药理学通报

Recently p75 neurotrophin receptor (p75NTR) has been found to play a critical role in the pathology of neurodegen¬erative! diseases including Alzheimer's disease (AD) , Parkin¬son' s disease ( PI)), Huntington's disease ( HI)) , amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS).This arti¬cle reviews the research progress of p75NTR in regulating neuron apoptosis, axon degeneration and cognitive impairment, explo¬ring the application of p75NTR as a potential therapeutic target for the treatment of neurodegenerative diseases.

Effects of ethanol extract of Bombax ceiba leaves and its main constituent mangiferin on diabetic nephropathy in mice / 中国天然药物

The present study was designed to explore the mechanism by which ethanol extract of Bombax ceiba leaves (BCE) and its main constituent mangiferin (MGF) affect diabetic nephropathy by combating oxidative stress. Oral administration of BCE and MGF to normal and streptozotocin (STZ)-induced diabetic mice were carried out. Fasting blood glucose, 24-h urinary albumin, serum creatinine, and blood urea nitrogen were tested, histopathology, and immunohistochemical analysis of kidney tissues were performed. Moreover, mesangial cells were treated with BCE and MGF for 48 h with or without 25 mmol·L of glucose. Immunofluorescence, Western blot and apoptosis analyses were used to investigate their regulation of oxidative stress and mitochondrial function. BCE and MGF ameliorated biochemical parameters and restored STZ-induced renal injury in the model mice. In vitro study showed that high glucose stimulation increased oxidative stress and cell apoptosis in mesangial cells. BCE and MGF limited mitochondrial membrane potential (Δψm) collapse by inhibiting Nox4, mitochondrially bound hexokinase II dissociation, and subsequent ROS production, which effectively reduced oxidative stress, cleaved caspase-3 expression and cell apoptosis. Our work indicated that BCE and MGF had protective effects on diabetic caused kidney injury and prevented oxidative stress in mesangial cells by regulation of hexokinase II binding and Nox4 oxidase signaling.

Antihyperglycemic, antihyperlipidemic and antioxidant effects of standard ethanol extract of Bombax ceiba leaves in high-fat-diet- and streptozotocin-induced Type 2 diabetic rats / 中国天然药物

The present study aimed at exploring the therapeutic potential of standard extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral administration of BCE at doses of 70, 140, and 280 mg·kg, to the normal rats and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out. Effects of BCE on blood glucose, body weight, and a range of serum biochemical parameters were tested, and histopathological observation of pancreatic tissues was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical composition of BCE mainly contained mangiferin, isoorientin, vitexin, isomangiferin, isovitexin, quercetin hexoside, 2'-trans-O-cumaroyl mangiferin, and nigricanside. BCE caused a significant decrease in the concentrations of fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and increases in oral glucose tolerance, high density lipoprotein-cholesterol, and superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic β-cells protection effect and stimulation of insulin secretion from the remaining pancreatic β-cells could be observed after BCE treatment. The results indicated that BCE exhibited an excellent hypoglycemic activity, and alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and protecting pancreatic β-cells are the possible mechanisms involved in anti-diabetic activity of BCE.

Monitoring the source of mesenchymal stem cells in patients after transplantation of mismatched-sex hematopoietic stem cells plus third-party cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In bone marrow transplant patients, the microenvironment in bone marrow is damaged after chemotherapy or radiotherapy. Subsequent to allogenic hematopoietic stem cell transplantation in patients with clinically successful engraftments, the source of mesenchymal stem cells (MSCs) remains controversial. To further verify the stimulatory effect of the simultaneous transplantation of cells from second donors on engraftment success for hematopoietic stem cell transplantation in support of donor MSCs engraftments, the aim of this study is to monitor the dynamics of the engraftment of bone marrow-derived MSCs in patients after transplantation with mismatched-sex hematopoietic stem and third-party cells.</p><p><b>METHODS</b>In this study, the hematopoietic stem cells from 32 clinical donors of different sexes that resulted in successful engraftments were selected for transplantation and were classified into three groups for research purposes: group A consisted of 14 cases of transplantation with bone marrow and recruited peripheral hematopoietic stem cell transplantation, group B contained 8 cases of simultaneous re-transfusion of MSCs from the second donor, and group C contained 10 cases of simultaneous re-transfusion of umbilical blood from the second donor. The bone marrow from 32 patients with successful engraftments of hematopoietic transplantation were selected and sub-cultured with MSCs. Flow cytometry (FCM) was used to measure the expression of surface antigens on MSCs. Denaturing high-performance liquid chromatography (DHPLC) in combination with polymerase chain reaction amplification of short tandem repeats (STRPCR) was used to measure the engraftment status of fifth-generation MSCs in patients. Fluorescence in situ hybridization (FISH) revealed the sex origin of the fifth-generation MSCs in 32 patients. Dynamic examinations were performed on patients receiving donor transplantations.</p><p><b>RESULTS</b>The progenies of fifth-generation MSCs were successfully cultured in 32 cases. The results of FCM demonstrated that the expression levels of CD14+ and CD45+ cells were lower than 0.04% in the fifth-generation MSCs. The analysis using DHPLC and FISH showed similar results. One patient from group B also received a temporary transplantation of MSCs from the donor. The MSCs in the remaining 31 patients all originated from the patients themselves.</p><p><b>CONCLUSIONS</b>After transplantation, the MSCs present in patients originated from the host. In patients transplanted with MSCs from a second donor, the phenomenon of temporary chimerization of MSCs was observed.</p>

Quantitative chimerism kinetics in relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease. Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient. Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally. The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.</p><p><b>RESULTS</b>Twenty-one patients experienced leukemia relapse at a median of 135 days (range, 30 - 720 days) after transplantation. High recipient chimerism in BM was found in all patients at relapse, and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse. With 0.5% recipient DNA as the cut-off, median time between the detection of increased recipient chimerism and relapse was 45 days (range, 0 - 120 days), with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse. Median percentage of recipient DNA in 20 stable remission patients was 0.28%, 0.04%, 0.05%, 0.05%, 0.08%, and 0.05% at 1, 2, 3, 6, 9, and 12 months, respectively, after transplantation. This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination. The recipient chimerisms in BM were significantly higher than those in PB at relapse (P = 0.001).</p><p><b>CONCLUSIONS</b>This SP-based RT-PCR assay is a reliable method for chimerism analysis. Chimerism kinetics in BM can be used as a marker of impending leukemia relapse, especially when no other specific marker is available. Based on our findings, we recommend examining not only PB samples but also BM samples in HSCT patients.</p>

Quantitative assessment of hematopoietic chimerism by quantitative real-time polymerase chain reaction of sequence polymorphism systems after hematopoietic stem cell transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Analysis of changes in recipient and donor hematopoietic cell origin is extremely useful to monitor the effect of hematopoietic stem cell transplantation (HSCT) and sequential adoptive immunotherapy by donor lymphocyte infusions. We developed a sensitive, reliable and rapid real-time PCR method based on sequence polymorphism systems to quantitatively assess the hematopoietic chimerism after HSCT.</p><p><b>METHODS</b>A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time PCR in 101 HSCT patients with leukemia and other hematological diseases. The chimerism kinetics of bone marrow samples of 8 HSCT patients in remission and relapse situations were followed longitudinally.</p><p><b>RESULTS</b>Recipient genotype discrimination was possible in 97.0% (98 of 101) with a mean number of 2.5 (1-7) informative markers per recipient/donor pair. Using serial dilutions of plasmids containing specific SP markers, the linear correlation (r) of 0.99, the slope between -3.2 and -3.7 and the sensitivity of 0.1% were proved reproducible. By this method, it was possible to very accurately detect autologous signals in the range from 0.1% to 30%. The accuracy of the method in the very important range of autologous signals below 5% was extraordinarily high (standard deviation <1.85%), which might significantly improve detection accuracy of changes in autologous signals early in the post-transplantation course of follow-up. The main advantage of the real-time PCR method over short tandem repeat PCR chimerism assays is the absence of PCR competition and plateau biases, with demonstrated greater sensitivity and linearity. Finally, we prospectively analyzed bone marrow samples of 8 patients who received allografts and presented the chimerism kinetics of remission and relapse situations that illustrated the sensitivity level and the promising clinical application of this method.</p><p><b>CONCLUSION</b>This SP-based real-time PCR assay provides a rapid, sensitive, and accurate quantitative assessment of mixed chimerism that can be useful in predicting graft rejection and early relapse.</p>

Chronic hepatic damage in acute promyelocytic leukemia patients treated with tetra-arsenic tetra-sulfide / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the chronic hepatic damage in acute promyelocytic leukemia (APL) patients long-term treated with tetra-arsonic tetra-sulfide (As(4)S(4)).</p><p><b>METHODS</b>The periodical liver biochemical examinations and ultrasonography results and hepatic fibrosis indicators (P III NP and type IV collagen) of patients were analysed.</p><p><b>RESULTS</b>106 APL patients treated with As(4)S(4), the median follow-up time was 36 months (6 - 72). The HCV(-) group includes 84 APL patients. During the first course the abnormal rate of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was 16.7% and 14.5% (higher than the two times of the normal value), the ALT, AST, gamma-glyoxylate aminotransferase (GGT) levels during the first course were statistically higher than As4S4 treatment before (P < 0.05). There were no statistically differences between the ALT, AST, GGT levels after and before treating with As(4)S(4) in half a year, one year, two year, more than three years (P > 0.05). Other biochemical indicators such as ALP, LDH, TBIL, DBIL, TP, ALB, A/G, BUN, CRE, there were no significantly differences before and after As(4)S(4) treatment (P > 0.05). The HCV(+) group includes 22 APL patients, during the first course, the abnormal rate of the ALT, AST were 63.6% and 59.1%, but at the 2 year, more than 3 years there were no significantly differences compared with As(4)S(4) treatment before (P > 0.05). 42 APL patients were treated with As(4)S(4) more than 3 years, in 33 HCV(-) APL patients, two APL patients had splenomegaly, one APL patient's breadth of the portal vein was wider than 1.4 cm, 21 APL patients had fatty liver (63.6%). The hepatic fibrosis indicators of the 16 APL patients were all normal. In 9 HCV(+) APL patients, 4 APL patients had splenomegaly, 2 APL patients, breadth of portal vein were wider than 1.4 cm, 6 APL patients had fatty liver (66.7%). 6 patients were examined with the hepatic fibrosis indicators, 2 patients, were higher than the normal value.</p><p><b>CONCLUSION</b>Long term As(4)S(4) treatment for APL patients had no obvious effects on hepatic function, no obvious hepatic fibrosis and portal hypertension signs at more than 3 years, excepting for the rate of fatty liver was high.</p>

Arsenic absorption and retention in acute promyelocytic leukemia patients treated with tetra-arsenic tetra-sulfide / 中国实验血液学杂志

The objective of this study was to investigate arsenic absorption and retention in acute promyelocytic leukemia (APL) patients treated with tetra-arsenic tetra-sulfide (As(4)S(4)). Arsenic concentrations in samples from APL patients were quantitatively determinated by Hydride Generation Atomic Absorption Spectrometry. The results showed that blood arsenic level was 51.7 +/- 18.7 microg/L (n = 41), urine arsenic level was 2359.1 +/- 1910.6 microg/L (n = 36), and the average daily urinary arsenic excretion was 5.1 +/- 4.06 mg/day (n = 32) on the 7th-9th day after As(4)S(4) administration; blood arsenic level was 61.7 +/- 22.7 microg/L (n = 30), urine arsenic level was 2834.0 +/- 1958.3 microg/L (n = 27), the average daily urinary arsenic excretion was 6.3 +/- 4.98 mg/day (n = 24) on the 10th-12th day after As(4)S(4) administration; blood arsenic level was 62.8 +/- 25.1 microg/L (n = 34), urine arsenic level was 2859.3 +/- 2298.2 microg/L (n = 32) and the average daily urinary arsenic excretion was 6.82 +/- 5.58 mg/day (n = 32) on the 13th-15th day after As(4)S(4) administration. Blood arsenic level was 20.7 +/- 10.9 microg/L (n = 31), urine arsenic level was 525.5 +/- 337.1 microg/L (n = 28), and the average daily urinary arsenic excretion was 1.76 +/- 1.3 mg/day (n = 17) on the 7th-9th day after stop of treatment; blood arsenic level was 16.1 +/- 10.1 microg/L (n = 34), urine arsenic level was 207.1 +/- 164.5 microg/L (n = 28) and the average daily urinary arsenic excretion was 0.42 +/- 0.27 mg/day (n = 22) on the 13th-15th day after stop of treatment. Blood arsenic concentration, urine arsenic concentration and daily urinary arsenic excretion reach a steady state after treatment with As(4)S(4) for 10 days. The average urinary arsenic excretion was 6.82 +/- 5.58 mg/day (n = 32), arsenic absorption level was 9.74 +/- 7.97 mg/day and arsenic absorption efficiency was 0.25 +/- 0.20% during treatment. In conclusion, the majority of absorbed arsenic was excreted from urine and other ways, only a small part of absorbed arsenic was retained in body at the 14th day after therapy was discontinued, blood arsenic concentration, urine arsenic concentration, daily urinary arsenic excretion and hair arsenic concentration could be considered as useful biomarkers for monitoring arsenic absorption and retention in APL patients treated with As(4)S(4).