Tau-mediated Neurodegeneration and Potential Implications in Diagnosis and Treatment of Alzheimer's Disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review recent research advances on tau, a major player in Alzheimer's disease (AD) pathogenesis, a biomarker for AD onset, and potential target for AD therapy.</p><p><b>DATA SOURCES</b>This review was based on a comprehensive search using online literature databases, including PubMed, Web of Science, and Google Scholar.</p><p><b>STUDY SELECTION</b>Literature search was based on the following keywords: Alzheimer's disease, tau protein, biomarker, cerebrospinal fluid (CSF), therapeutics, plasma, imaging, propagation, spreading, seeding, prion, conformational templating, and posttranslational modification. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type.</p><p><b>RESULTS</b>Amyloid plaques enriched with extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks of AD. Although the Aβ hypothesis has dominated AD research for many years, clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset. The research focus in AD has recently shifted to the role of tau in AD. In addition to phosphorylation, tau is acetylated and proteolytically cleaved, which also contribute to its physiological and pathological functions. Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis. Techniques to detect tau at minute levels in CSF and blood have been developed, and improved tracers have facilitated tau imaging in the brain. These advances have potential to accurately determine tau levels at early diagnostic stages in AD. Given that tau is a potential therapeutic target, anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.</p><p><b>CONCLUSION</b>Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.</p>

Amyloid β Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyloid β (Aβ) has been established as a key factor for the pathological changes in the brains of patients with Alzheimer's disease (AD), and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in the AD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type (WT) mice to determine whether senescent neurons are present in the transgenic AD mouse model.</p><p><b>METHODS</b>The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes (DEGs) were screened by quantitative real-time polymerase chain reaction. Cognitive performance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ (oAβ) (1-42) was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence.</p><p><b>RESULTS</b>In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes (labeled as glutamine synthetase), nil expression in activated microglia (labeled as Iba1), and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ (1-42) induced the production of senescence-related protein p16, but not p53 in vitro, which was in line with the in vivo manifestation.</p><p><b>CONCLUSIONS</b>oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.</p>

Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer's Disease Mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated.</p><p><b>METHODS</b>The five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway.</p><p><b>RESULTS</b>Compared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes.</p><p><b>CONCLUSIONS</b>These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.</p>

Molecular diagnosis of children with unexplained intellectual disability/ developmental delay by array-CGH / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze the potential pathogenic genomic imbalance in children with unexplained intellectual disability (ID) and/or developmental delay (DD) and its association with phenotypes, and to investigate the value of array-based comparative genomic hybridization (array-CGH) in clinical molecular genetic diagnosis.</p><p><b>METHODS</b>The whole genome of 16 children with ID/DD was scanned by the array-CGH for detection of genomic copy number variations (CNVs), and the revealed genomic imbalance was confirmed by multiplex ligation-dependent probe amplification.</p><p><b>RESULTS</b>G-band karyotyping of peripheral blood cells showed no abnormalities in the 16 children. The results of the array-CGH revealed that 6 (38%) of the 16 patients had genomic CNVs, and 3 cases of CNVs were normal polymorphic changes; 1 CNV was a microdeletion of 4p16.3, which was the critical region for Wolf-Hirschhorn syndrome, and 1 CNV was a microdeletion of 7q11.23, which was the critical region for Williams-Beuren syndrome. Moreover, a CNV was identified with two duplications at 2q22.2 and 15q21.3 in a boy, which proved to have a clinical significance due to its association with ID, brain DD, unusual facies, cryptorchidism, irregular dentition, etc.</p><p><b>CONCLUSIONS</b>Array-CGH allows for the etiological diagnosis in some of the children with unexplained ID/DD. As a high-throughput and rapid tool, it has a great clinical significance in the etiological diagnosis of ID/DD.</p>

Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Early diagnosis assumes a vital role in an effective treatment of Alzheimer's disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.</p><p><b>METHODS</b>A total of 14 5XFAD mice (at 3 and 6 months old), with 14 age-matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(18F) fluoro-D-glucose ([18F]-FDG) uptake in the hippocampus and cerebral cortex.</p><p><b>RESULTS</b>With the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (18F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (18F)-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared.</p><p><b>CONCLUSIONS</b>The decline of (18F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.</p>

Congenital central hypoventilation syndrome, report of three cases / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate clinical characteristics and PHOX2B gene mutations in congenital central hypoventilation syndrome (CCHS) and to facilitate the early diagnosis and management of CCHS and reduce the misdiagnosis.</p><p><b>METHOD</b>Clinical data of 3 infants with CCHS who had recurrent respiratory failure episodes and dependent on mechanical ventilation support in 3 from March 2008 to April 2012 were analyzed, and blood gas analysis was performed respectively in the awaken and sleeping status. Gene sequencing was used for detection of PHOX2B gene mutation.</p><p><b>RESULT</b>All the three patients had adequate ventilation during awaken time, but they presented with abnormal frequency and shallow breathing associated with alveolar hypoventilation after falling asleep. Blood gas analysis showed hypercapnia and CO2 partial pressure was consistently over 60 mm Hg (1 mm Hg = 0.133 kPa) after falling asleep, which is in accordance with the clinical features of CCHS. The PHOX2B gene sequencing showed that 6 GCN repeats were inserted at exon3 of PHOX2B in case 1, at same position, 5 GCN repeats were inserted in case 2 and 3.</p><p><b>CONCLUSION</b>Normal ventilation in awaken status while shallow slow breathing accompanied with hypercapnia in sleep are the main clinical characteristics of CCHS, which requires mechanical ventilation. Acquired mutation in exon 3 of PHOX2B gene encoding repeated GCN sequence seems to be the molecular etiology of these three patients.</p>

Molecular Analysis of Duchenne muscular dystrophy / 中华实用儿科临床杂志

Objective To detect the mutation type and size variation of the dystrophy gene in Duchenne muscular dystrophy(DMD) patients,and discuss the strategy of molecular genetic diagnosis for DMD.Methods Multiplex ligation-dependent probe amplification(MLPA) and next-generation sequencing(NGS) were applied for genetic detection in patients with clinical suspected DMD.Sanger sequencing was performed to confirm the results.Results Pathogenic mutations were found in 28 cases with DMD.Twenty-two of the 28 cases were found to be positive with MLPA analysis,16 cases with deletion mutations,4 cases with duplication,and 2 cases with both deletion and duplication mutations.Then,NGS technology was performed to detect 5 cases with MLPA positive and 1 case with MLPA negative,which were chosen optionally,and 3 cases showed deletion (exon51 del,chrX:31779857-31795289; exon53 del,chrX:31685440-31747548; exon51-55 del,chrX:31632504-31827732) and 2 cases of duplication (exon45 dup,chrX:31970766-32023816 ; exon55 dup,chrX:31540860-31649750),which were consistent with MLPA analysis.Meanwhile,NGS could determine the location of break point and the size of DNA segments accurately and also detect one point mutation which was MLPA negative.In the end,Sanger sequencing was performed to confirm this point mutation.Conclusions The mutational spectrum of the DMD gene is complex,including deletion/duplication and point mutations,and MLPA is an efficient method for detecting paternal deletion and duplication of DMD,while NGS can not only detect both deletion/duplication and point mutations,but also determine the location of break point and the size of gene segments accurately.Next-generation sequencing may be a powerful technology for early clinical diagnosis,prognostic judgment and prenatal diagnosis of DMD.

Comparative study on application of Duo positive airway pressure and continuous positive airway pressure in preterm neonates with respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To determine whether early application of Duo positive airway pressure (DuoPAP), in comparison with nasal continuous positive airway pressure (NCPAP), can reduce the need for endotracheal intubation and mechanical ventilation and decrease the incidence of bronchopulmonary dysplasia (BPD) in preterm neonates with respiratory distress syndrome (RDS).</p><p><b>METHODS</b>In a single-center, randomized controlled trial, preterm neonates (gestational ages 30-35 weeks) with RDS were randomly assigned to receive DuoPAP (n=34) or NCPAP (n=33) within 6 hours of birth. If the two noninvasive ventilations were not effective, endotracheal intubation and mechanical ventilation were used, and pulmonary surfactant was administered as rescue therapy. The total invasive respiratory support rate and incidence of BPD within 24, 48 and 72 hours of birth were observed. The two groups were compared in terms of PaCO2, PaO2 and oxygenation index (OI) at 1, 12, 24, 48 and 72 hours after using the noninvasive respiratory support.</p><p><b>RESULTS</b>The total invasive respiratory support rates within 48 and 72 hours after birth were significantly lower in the DuoPAP group than in the NCPAP group (P<0.05). There was no difference in the incidence of BPD between the two groups (P>0.05). The OI in the DuoPAP group was significantly higher than in the NCPAP group at 1, 12, 24, 48 and 72 hours after noninlasive respiratory support (P<0.05). The DuoPAP group showed significantly lower PaCO2 than the NCPAP group at 1, 12, and 24 hours after noninvasive respiratory support (P<0.05). PaO2 was significantly higher in the DuoPAP group than in the NCPAP group at 1 and 12 hours after noninvasive respiratory support (P<0.05).</p><p><b>CONCLUSIONS</b>Compared with NCPAP, early application of DuoPAP can decrease the need for endotracheal intubation and mechanical ventilation in preterm neonates with RDS, showing promise for broad use.</p>

Diverse components of voltage-gated calcium channel currents in primary cultured hippocampal neurons / 生理学报

The present study was to record and separate the voltage-gated calcium channel currents (VGCCs) in primary cultured hippocampal neurons. An improved method is described for efficient and stable recording of VGCCs from primary cultured hippocampal neurons. The procedure allows the obtained hippocampal neurons overcome the defects from acutely isolated hippocampal neurons and currents do not rundown apparently after 20 min of membrane rupture. Using whole-cell configurations of patch clamp technique, it is shown that the method does not damage the neuron membrane electrical properties, and successfully records a variety of VGCCs components in hippocampal neurons (such as L, N, P/Q, T, etc.).

Mechanism of the reduction of cerebral ischemic-reperfusion injury through inhibiting the activity of NF-kappaB by propyl gallate / 药学学报

The probable mechanism of the reduction of rat cerebral ischemic-reperfusion injury by propyl gallate was studied. Intraluminal suture middle cerebral artery occlusion model of rat was employed. Propyl gallate was injected immediately after the ischemia was happened. The activity of NF-kappaB, and the expression of COX-2 and HSP70 on the peripheral ischemia were determined by Western blotting. The expression of TNF-alpha was determined by ELISA assay. RT-PCR and immunofluorescence staining were employed to detect the transcription and expression of TLR-4. Results showed that propyl gallate could inhibit the activity of NF-kappaB in the peripheral ischemia, and reduce the expression of COX-2 and TNF-alpha. As the upstream of NF-kappaB, the transcription and expression of TLR-4 decreased, as well as HSP70, the endogenic ligand of TLR-4. As an antioxidant, propyl gallate could reduce the cerebral ischemic-reperfusion injury through inhibiting the activity of NF-kappaB and decreasing the COX-2 and TNF-alpha in the peripheral ischemia. It also could influence HSP70 and TLR-4.

Involvement of Wnt/beta-catenin signaling in tripchlorolide protecting against oligomeric beta-amyloid-(1-42)-induced neuronal apoptosis / 药学学报

This study is to explore whether the Wnt/beta-catenin signaling pathway is involved in the process of tripchlorolide (T4) protecting against oligomeric Abeta(1-42)-induced neuronal apoptosis. Primary cultured cortical neurons were used for the experiments on day 6 or 7. The oligomeric Abeta(1-42) (5 micromol x L(-1) for 24 h) was applied to induce neuronal apoptosis. Prior to treatment with Abeta(1-42) for 24 h, the cultured neurons were pre-incubated with T4 (2.5, 10, and 40 nmol x L(-1)), Wnt3a (Wnt signaling agonists) and Dkk1 (inhibitors) for indicated time. Then the cell viability, neuronal apoptosis, and protein levels of Wnt, glycogen synthase kinase 3beta (GSK3beta), beta-catenin and phospho-beta-catenin were measured by MTT assay, TUNEL staining and Western blotting, respectively. The result demonstrated that oligomeric Abeta(1-42) induced apoptotic neuronal cell death in a time- and dose-dependent manner. Pretreatment with T4 significantly increased the neuronal cell survival and attenuated neuronal apoptosis. Moreover, oligomeric Abeta(1-42)-induced phosphorylation of beta-catenin and GSK3beta was markedly inhibited by T4. Additionally, T4 stabilized cytoplasmic beta-catenin. These results indicate that tripchlorolide protects against the neurotoxicity of Abeta by regulating Wnt/beta-catenin signaling pathway. This may provide insight into the clinical application of tripchlorolide to Alzheimer's disease.

JNK/p38 MAPK involves in ginsenoside Rb1 attenuating beta-amyloid peptide (25-35) -induced tau protein hyperphosphorylation in embryo rat cortical neurons / 药学学报

To explore the effect of ginsenoside Rb1 on JNK/p38 MAPK in the process of beta-amyloid peptide (25-35) -induced tau protein hyperphosphorylation, Western blotting and immunocytochemical stain were performed to observe the tau protein phosphorylation and the expression of JNK/p38 MAPK. The level of tau protein phosphorylation in the sites of Ser396 , Ser199/202 and Thr205 increased after rat cortical neurons exposed to 20 micromol x L(-1) Abeta25-35, meanwhile the level of JNK/p38 MAPK also increased after Abeta25-35 treatment for 12 h. Pretreatment with several doses of ginsenoside Rbl markedly attenuated tau protein hyperphosphorylation and the expression of JNK/p38 MAPK. Ginsenoside Rbl markedly attenuated tau protein hyperphosphorylation through JNK/p38 MAPK pathway.

Vector-mediated shRNA inhibits HIF-1alpha expression in prostate cancer cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To construct a short hairpin RNA (shRNA) vector of the hypoxia inducible factor-1alpha (HIF-1alpha), determine its inhibitory effect on the expression of the HIF-1alpha gene in PC-3M cells, and investigate its application prospects in the treatment of prostate cancer.</p><p><b>METHODS</b>We designed and synthesized the shRNA template sequence specific against HIF-lalpha, inserted it into the vector psilencer 2.1-U6 to generate the plasmid psilencer-HIF, transfected the recombinant plasmid into prostate cancer cell line PC-3M cells and detected the transfection efficiency by cotransfection with the pEGFP vector as well as the expression of HIF-1alpha by RT-PCR and Western blot.</p><p><b>RESULTS</b>The DNA sequencing analysis showed a complete consistency of the recombinant plasmid psilencer-HIF with the design. Twenty-four hours after the transfection, the rate of transfected plasmid was about (89.26 +/- 4.72)% and the vector-mediated shRNA induced RNA interference (RNAi), while 48 hours transfection reduced the HIF-1alpha mRNA and protein levels by 82.09% and 81.61% respectively (P < 0.01) in PC-3M cells.</p><p><b>CONCLUSION</b>The shRNA vector was successfully constructed, which can effectively suppress the expression of HIF-1alpha in prostate cancer cells.</p>

Involvement of protein kinase C in NMDAR-dependent long-term potentiation in rat amygdala / 生理学报

The mechanism of long-term potentiation (LTP) in basolateral amygdala (BLA) was explored using field potential recording in rat brain slice preparation. Field potentials (field excitatory post-synaptic potentials, fEPSPs) in BLA were evoked with sharpened steel bipolar stimulating electrodes placed in the external capsule (EC). Two theta burst stimulations (TBS, interval=10 min) induced LTP in BLA. TBS-induced synaptic potentiation lasted for more than 30 min after the second TBS. LTP in BLA was input-specific and was blocked by N-methyl-D-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid (APV). The effect of protein kinase C (PKC) on LTP was then determined using PKC inhibitor chelerythrine chloride. Bath application of chelerythringe chloride had no effect on basic field potentials and paired-pulse ratio (PPR). However, in the presence of chelerythrine chloride, two TBS failed to induce LTP. In contrast, bath application of chelerythrine chloride 10 min after the second TBS did not affect the maintenance of LTP in BLA. These results indicate that LTP is NMDAR-dependent and PKC is involved in the induction and early maintenance of LTP in BLA.

Advances in the study of immunopharmacological effects and mechanisms of extracts of Tripterygium wilfordii Hook. f. in neuroimmunologic disorders / 药学学报

Extracts of Chinese herb Tripterygium wilfordii Hook. f. (TWHF) have been found to have potent anti-inflammatory and immunosuppressive functions and widely used in China for treatment of rheumatoid arthritis. Also they have been considered to be the potential drugs in the treatment of tumor and acute graft rejections. With the progress of neuroimmunological research on neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson disease (PD) and multiple sclerosis (MS), the neuroprotective strategies to rescue neurons from immunological injury are currently being explored. Recently, studies have indicated that extracts of TWHF such as triptolide, tripchlorolide and (5R)-5-hydroxytriptolide are able to attenuate progression of these neuroimmunologic disorders in vitro and in vivo. Accumulating evidence has shown that they can promote neuronal survival and neurite growth and facilitate functional recovery of brain injury by invoking distinct mechanisms that are related to their neuroprotective roles as inhibitor of neuroinflammatory toxicity of activated-microglia, antioxidants, calcium channel blockers, neurotrophic actions, modulating T cell functions, inhibitor of transcriptional activation of NF-kappaB on genes and signaling. Significant pharmaceutical strategies against neuroimmunologic disorders will hopefully be discovered by understanding the valuable components of TWHF.

Ginsenoside Rb1 attenuates beta-amyloid peptide(25-35) -induced hyperphosphorylation of tau protein through CDK5 signal pathway / 药学学报

This study is to explore the effect of ginsenoside Rb1 on the process of beta-amyloid peptide(25-35) (Abeta(25-35)) -induced hyperphosphorylation of tau protein, and on the level of cyclin-dependent kinase 5 activator, p25/p35. Western blotting and/or immunocytochemical staining were used to detect the levels of phosphorylation of tau protein at the sites of Thr205, Ser396, Ser404 in hippocampal neurons, cdk5 and p25/p35. After exposure to Abeta(25-35) (20 micromol x L(-1)) for 12 h, the levels of tau protein phosphorylation at the sites of Thr205, Ser396, Ser404 were enhanced, the level of p25 was increased, but the level of protein cdk5 was not changed markedly. Pretreatment with ginsenoside Rb1 reduced Abeta(25-35) -induced hyperphosphorylation of tau protein and decreased the lever of p25, but had no effect on cdk5. Ginsenoside Rb1 can attenuate Abeta(25-35) -induced hyperphosphorylation of tau protein through CDK5 signal pathway.

Bone marrow mesenchymal stem cell transplantation aggravates postangioplasty aortic restenosis in rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of bone marrow mesenchymal stem cell transplantation on postangioplasty aortic restenosis in rats.</p><p><b>METHODS</b>48 SD rats were randomly divided into normal control group, balloon injury group, balloon injury and MSCs transplantation group. MSCs were pre-labeled by DAPI (25 microg/ml) and then infused into aorta through the balloon catheter (MSCs 2 x 10(6)/animal). Thoracic aorta were taken for histological examination (frozen and paraffin sections) at 1, 2, 6 weeks post angioplasty, respectively. DAPI labeled MSCs were detected under immunofluorescence microscopy. Expressions of c-kit, proliferating cell nuclear antigen (PCNA), smooth muscle alpha-actin (alpha-SMA) in aorta were determined by immunocytochemistry using related antibodies.</p><p><b>RESULTS</b>The DAPI-labeled MSCs could be detected on impaired intimae and alpha-SMA expression was seen in these cells 1 weeks after MSCs transplantation. Similar weak c-kit expression in neointima was found in both injury and transplantation group at 2 weeks (P > 0.05). Expressions of PCNA and alpha-SMA in the neointima were significantly higher in transplantation group than in injury group at 2 weeks. Intima/tunica media area ratio and luminal stenosis ratio were significantly increased in transplantation group than injury group at 6 weeks (all P < 0.05).</p><p><b>CONCLUSION</b>Bone marrow MSCs transplanted post aortic angioplasty could home to serious wounded aortic intima, differentiate into smooth muscle like cells, promote neointima cellular proliferation and aggravate postangioplasty aortic restenosis in rats.</p>

Application of hyperthermic intraoperative intraperitoneal chemotherapy in patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) on the postoperative metastatic rate and survival rate of advanced gastric cancer (AGC).</p><p><b>METHODS</b>In HIIC group, patients received HIIC (mitomycin C 30 mg and cisplatin 100 mg were added into 2000 ml distilled water, heated to 42 approximately 45 degrees C, perfused to abdominal cavity for 30 min and then sucked) and intravenous chemotherapy after operation (5- FU 10 approximately 15 mg/kg, mitomycin C 0.1 approximately 0.15 mg/kg, adriamycin 0.5 approximately 1 mg/kg i.v drip, once a week for 2 approximately 3 weeks). In control group, patients received intravenous chemotherapy only. The postoperative metastatic rate and survival rate (1- , 3- and 5- year) of patients were compared between 92 cases of AGC undergone HIIC and 120 cases of AGC without HIIC (control group).</p><p><b>RESULTS</b>The peritoneal recurrence rates after operations occurred within two years were 14.1% and 37.5% in HIIC group and control group respectively (P < 0.01). The 1- , 3- , and 5- year survival rates in HIIC group were 98.9%, 68.5%, and 52.2% and in control group 95.0%, 56.7% and 37.5% respectively. The 3- , and 5- year survival rates were significantly different between the two the groups (P < 0.05).</p><p><b>CONCLUSION</b>HIIC can kill isolated intraperitoneal cancer cells, reduce peritoneal recurrence rate after operations, raise significantly survival rate of patient, and improve the prognosis of AGC.</p>

Inhibitory action of propyl gallate on the activation of SAPK/JNK and p38MAPK induced by cerebral ischemia-reperfusion in rats / 药学学报

<p><b>AIM</b>To explore the protective effect of propyl gallate against neuronal injury in the boundary zone of the infarction area in the rat cerebral ischemia-reperfusion model and its possible mechanism.</p><p><b>METHODS</b>Transient focal ischemia induced by middle cerebral artery occlusion in the rats was established by ligation of the left internal carotid artery for 2 h. Rats were treated by propyl gallate with different doses (23.5, 47 and 94 micromol x kg(-1)) for three days before operation. Coronal brain sections were collected after 1 , 2, 4, 6, 12 and 24 h of reperfusion, neuronal injury in the boundary zone of the infarction area was evaluated by TUNEL and Nissl staining. The expression of activated Caspase-3, total SAPK/JNK, p38MAPK and their phosphorylation (Thr183/Tyr185, Thr180/Tyr182) was investigated by immunohistochemistry and Western blotting with corresponding antibodies.</p><p><b>RESULTS</b>Although SAPK/JNK immunoreactivity did not increase at each time point in the boundary zone of the infarction area after reperfusion, p-SAPK/JNK immunoreactivity increased significantly at 1 h and then decreased gradually, and p38MAPK immunoreactivity was enhanced at each time point, peaked at 6 h. Expression of p-p38MAPK peaked at 6 h. Activated Caspase-3 immunoreactivity appeared at 6 h in the boundary zone of the infarction area and peaked at 12 h. TUNEL positive neurons were observed at 12 h and became more abundant at 24 h. The number of Nissl positive neurons decreased gradually and apoptosis ratio of neurons peaked at 24 h. Propyl gallate reduced the immunoreactivity of SAPK/JNK, p-SAPK/JNK, p38MAPK and p-p38MAPK markedly at 1 and 6 h. Propyl gallate with doses of 47 and 94 micromol x kg(-1) were more effective.</p><p><b>CONCLUSION</b>Inhibition on the activation of SAPK/JNK and p38MAPK is the possible protective mechanism of propyl gallate against neuronal injury induced by cerebral ischemia-reperfusion.</p>

Ginsenoside Rbl attenuates beta-amyloid peptide25-35 -induced tau hyperphosphorylation in cortical neurons / 药学学报

<p><b>AIM</b>To explore the effect and the possible mechanism of ginsenoside Rb1 on beta-amyloid peptide (beta-AP)(25-35) -induced tau protein hyperphosphorylation in cortical neurons.</p><p><b>METHODS</b>Western blotting and immunocytochemical staining were used to detect tau phosphorylation level, total tau and glycogen synthase kinase-3beta (GSK-3beta) in cortical neurons.</p><p><b>RESULTS</b>After exposure to beta-AP(25-35) (20 micromol x L(-1)) for 12 h, the levels of tau protein phosphorylation in the sites of Ser 396, Ser 199/202, Thr 231 and total tau were raised. Meanwhile, the expression of GSK-3beta also increased. Pretreatment with ginsenoside Rbl or lithium chloride, a specific inhibitor of GSK-3beta, markedly reduced beta-AP(25-35)-induced tau hyperphosphorylation and the expression of GSK-3beta.</p><p><b>CONCLUSION</b>Ginsenoside Rb1 can attenuate beta AP(25-35)-induced tau protein hyperphosphorylation in cortical neurons by inhibiting the expression of GSK-3beta.</p>