Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy

Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention. p38 is a unique MAPK family member that contains a PDZ motif at its C-terminus and interacts with a PDZ domain-containing protein tyrosine phosphatase PTPH1. This PDZ-coupled binding is required for both PTPH1 dephosphorylation and inactivation of p38 and for p38 phosphorylation and activation of PTPH1. Moreover, the p38/PTPH1 complex can further regulate their substrates phosphorylation and dephosphorylation, which impacts Ras transformation, malignant growth and progression, and therapeutic response. This review will use the p38/PTPH1 signaling network as an example to discuss the potential of targeting the kinase/phosphatase signaling complex for development of novel targeted cancer therapy.

Structural characterization of Sophora alopecuroides polysaccarides and study on its antitumor activity of CT26 / 中草药

Objective: To study the structure of Sophora alopecuroides polysaccarides (SAP) and its antitumor activity on CT26 transplanted tumor in mice. Methods: The structure was characterized by high-performance gel permeation chromatography (HPGPC), gas chromatography-mass spectrometer (GC-MS), infrared spectroscopy (IR), and nuclear magnetic resonance spectroscopy (NMR). And then the anticancer activity of CT26-bearing mice was investigated in vivo. Results: The results showed that SAP was consisted of D-mannopyranose and D-galactopyranose residues. The main chain of the galactomannan comprises β-(1,4)-linked D-mannopyranose residues, with branches of galactose, linked to the carbohydrate core through α-D-Gal (1,6) linkage. SAP could inhibit the tumor proliferation of CT26-bearing mice in a dose-dependent manner with inhibitory rate of 44.03% at high dose. Conclusion: Structure determination of SAP provides the theoretical basis for structure-activity relationship study. And it is expected to be further developed as a new antitumor drug with high efficiency and low toxicity.

Outcomes of Chimney and/or Periscope Techniques in the Endovascular Management of Complex Aortic Pathologies / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The chimney/periscope technique has been used to address complex aortic pathologies. This study aimed to report the outcomes and experiences of chimney and/or periscope grafts (CPGs) used in the endovascular management of complex aortic pathologies.</p><p><b>METHODS</b>Twenty-two patients with complex aortic pathologies were retrospectively studied from January 2013 to August 2016 in two vascular centers of teaching hospitals. All patients were diagnosed using computed tomography angiography (CTA). The patients were followed up at postoperative 1, 3, 6, and 12 months and yearly thereafter with X-ray, ultrasound, and/or CTA.</p><p><b>RESULTS</b>Twenty-two cases (17 males; mean age 60.7 ± 16.3 years) with complex aortic pathologies were analyzed. Nineteen patients underwent CPGs only, and the other three cases underwent the simultaneous implantation of chimney/periscope and fenestrated/scallop grafts. Twenty-six arteries were managed with forty CPGs during the procedures. Complete angiographies revealed two Type I endoleaks, one Type III endoleak, and one Type IV endoleak. Other intraoperative complications included brachial thrombosis, external iliac artery rupture, and left renal stenosis. The 30-day mortality was 0. The mean follow-up was 26.1 ± 10.1 months with a range of 2-39 months. During the follow-up, two Type I endoleaks and one Type IV endoleak were observed. One right renal stent occlusion occurred in the 5th month and turned patent after reintervention. Three patients died during the follow-up, one due to an aneurysm rupture as a Type I endoleak, and two due to myocardial infarction. The instant technical success was 96%. The primary and secondary patencies were 92% and 96%, respectively. The overall survival rates were 95%, 84%, and 84% at 12, 24, and 36 months, respectively. Stent migration was not observed in any patient.</p><p><b>CONCLUSIONS</b>Chimney/periscope techniques could be used to tackle complex aortic pathologies, but the indications must be strictly controlled, and additional experiences are required.</p>

Nerve Growth Factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion. Nerve growth factor (NGF) has been reported to play an important role in both physiological and pathological angiogenesis. This study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor (VEGF) in angiogenesis.</p><p><b>METHODS</b>Twenty-four mice were randomly allocated to normal control group (n = 6), blank control group (n = 6), VEGF gene transfection group (n = 6), and NGF gene transfection group (n = 6). The model of left hindlimb ischemia model was established by ligating the femoral artery. VEGF165plasmid (125 μg) and NGF plasmid (125 μg) was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, respectively. Left hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia induction. The gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase staining. NGF and VEGF protein expression was detected by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control group. The endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group (P < 0.05). The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group (P < 0.05). Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group (P < 0.05), but there was no significant difference of the NGF protein expression between VEGF group and blank control group (P > 0.05). The type I skeletal muscle fiber proportion in gastrocnemius of NGF group and VEGF group was significantly higher than that of blank control group (P < 0.05).</p><p><b>CONCLUSIONS</b>NGF transfection can promote NGF and VEGF protein expression which not only can induce angiogenesis but also induce type I muscle fiber expression in ischemic limbs.</p>

Human Umbilical Cord Blood CD34+Cells InducedAngiogenesis in Ischemic Limb of Mice / 中国医学科学院学报

Objective To observe the effect of the expanded human umbilical cord blood CD34+cells in ischemic limb of mice and analyse the relationship between the CD34+cells and angiogenesis. Methods Human umbilical cord blood was collected and CD34+cells were separated for expanding. Mice limbs ischemia models were established (n=15) and randomly divided into three groups:expanded CD34+cells group (n=5),fresh CD34+cells group (n=5),and control group(n=5). CD34+cells were detected by DiI dye tracing and antihuman nuclear antigen antibody(HNA) immunohistochemical staining. The improvement of blood reperfusion was evaluated by indicators including limb temperature,CD31 staining,and transforming growth factor-β1 (TGF-β1) mRNA expression. Results On days 14 (t=5.421,P=0.001;t=0.616,P=0.000) and 28(t=10.780,P=0.000; t=12.123,P=0.000),both expanded CD34+cells group and fresh CD34+cells group enjoyed better temperature improvement. Days 28 later,the vascular densities in the expanded CD34+cells group and the fresh CD34+cells group were 592.3±24.6 (t=26.386,P=0.000) and 530.7±25.5 (t=21.502,P=0.000),which were significantly higher than that in control group 219.7±19.9. The TGF-β1 mRNA expression in the expanded CD34+cells group and the fresh CD34+cells group were (0.578±0.050) copies (t=12.376,P=0.000) and (0.504±0.080) copies (t=7.098,P=0.000),both over control group [(0.224±0.040)copies]. Conclusions In vitro culture of cord blood CD34+cells can emigrate to ischemic zone and induce angiogenesis to alleviate ischemia. Thus,it may provide a treatment option for lower limb ischemia.

Effects of 4 Kinds of Antioxidants on the Stability of DHA and EPA / 中国药房

OBJECTIVE: To study the influence factors of the oxidation of DHA and EPA,and to find effective antioxidants.METHODS: The oxidation of DHA and EPA was optimized by orthogonal test with the quality of DHA and EPA as indicators and temperature,light and time as factors.The optimized antioxidants were selected by adding salidroside,BHA,BHT,vitamin E into samples.RESULTS: If there is lower temperature,weaker light and shorter storage,the oxidation of DHA and EPA will be more slowly.Effect of salidroside on the oxidation of DHA and EPA is the strongest.CONCLUSION: The oxidation of DHA and EPA can be reduced by lowering temperature,storing in dark place,reducing storage duration and adding salidroside.

Application of flow cytometry to the evaluation of semen quality / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the role of flow cytometry in semen assessment.</p><p><b>METHODS</b>Semen samples from 104 infertile male patients (as the case group) and 10 fertilized donors (as the control group) were analyzed for the volume of ejaculate and sperm concentration, motility and atypical morphology by computer-assisted semen analysis (CASA), the viability, chromatin structure and mitochondrial membrane potential (MMP) of the sperm stained by SYBR-14/PI, AO and JC-1 respectively, and assessed with flow cytometry. The results were analyzed through SAS software.</p><p><b>RESULTS</b>U tests indicated that the semen from the infertile patients had not only lower concentration (U = 2.51, P = 0.0143), lower motility (U = 3.44, P = 0.001) and higher rate of atypical morphology (U = -5.88, P < 0.0001), but also lower viability (U = 4.72, P < 0.0001), MMP (U = -2.53, P = 0.0309), and chromatin integrity (alpha t: U = -3.82, P = 0.0003; SD alpha t: U = -3.98, P = 0.0001; COMP alpha t: U = -3.57, P = 0.0005). The multiple stepwise regression analysis revealed that sperm motility was positively correlated with sperm membrane integrity (t = 1.66, P = 0.1016), sperm MMP (t = 3.33, P = 0.0014) and sperm acrosome integrity (t = 3.24, P = 0.0019), while sperm MMP was negatively correlated with the rates of sperm neck and tail defects (t = -3.44, P = 0.001).</p><p><b>CONCLUSION</b>Flow cytometry plays a significant role in the evaluation of the quality of human sperm, and can be adopted as a useful tool in the diagnosis and treatment of male infertility.</p>

Tamsulosin in the treatment of benign prostatic hyperplasia patients with acute urinary retention / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of alpha-1 A adrenoceptor antagonist (tamsulosin) in the treatment of benign prostatic hyperplasia (BPH) patients with acute urinary retention.</p><p><b>METHODS</b>Seventy-two BPH patients with acute retention of urine were randomly divided into treatment group and control group of 36 patients each. All the patients were treated with indwelling catheter, oral antibiotics and the patients in treatment group tamsulosin 0.4 mg once a day for 3 days. The catheter was removed after 72 hours of treatment.</p><p><b>RESULTS</b>After removal of the catheter, 44% (32/72) of patients voided successfully. The effect rates were 61% (22/36) in the tamsulosin treatment group and 28% (10/36) in the control group(P < 0.01).</p><p><b>CONCLUSIONS</b>Treatment with tamsulosin was effective in raising the success rate of voiding without catheter after an episode of acute urinary retention. The efficacy of treatment was not influenced by the volume of prostate.</p>

Detection of SEN virus (subtype D/H) infection in Shenzhen / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of newly identified single-chain DNA virus (SENV) infection in Shenzhen.</p><p><b>METHODS</b>Nested polymerase chain reaction (nPCR) was established using primers from ORF1 region of SENV genome. Six hundred and one sera samples from different populations were detected for SENV DNA (D and H subtype) by nPCR. Products of PCR were cloned into T-vector and sequenced.</p><p><b>RESULTS</b>The positive rates of SENV DNA in different populations were as followed: 27.8% in patients with hepatitis B, 22.2% in patients with hepatitis C, 26.9% in hemodialysis patients and 39.3% in IDUs. Among blood donors, the positive rates of SENV DNA were 28.1% in unqualified blood donors, 31.3% in blood donors with an elevated ALT levels and 15.1% in qualified blood donors. The infection rates of SENV in unqualified blood donors and blood donors with an elevated ALT levels were obviously higher than in qualified blood donors (chi(2) = 8.29, P < 0.01 and chi(2) = 6.03, P < 0.01). There was a 6.8% difference of nucleotide between SENV-D standard subtype and 6 isolates with 13.5% difference of nucleotide between SENV-H standard subtype and 4 isolates from Shenzhen.</p><p><b>CONCLUSION</b>Results suggested that SENV infection was common in high-risk groups in Shenzhen.</p>