Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes.

OBJECTIVE: To explore whether the regulation of matrix metalloproteinase 9 (MMP-9)/ tissue inhibitors of MMPs (TIMPs) gene expression through histone acetylation is a possible mechanism by which electroacupuncture (EA) protects blood-brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) rat model. METHODS: Male Sprague-Dawley rats were divided into four groups: the sham group, the MCAO group, the MCAO + EA (MEA) group, and the MCAO + EA + HAT inhibitor (HATi) group. The MCAO model was generated by blocking the middle cerebral artery. EA was applied to Baihui (GV20). Samples were collected 1 or 3 d after reperfusion. Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury. The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and chromatin immunoprecipitation (ChIP). RESULTS: Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption. The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression, but HATi reversed these effects of EA. In addition, ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter. CONCLUSION: EA treatment at Baihui (GV20) regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke, which preserves the structural integrity of the BBB in MCAO rats. These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.

Correlation between TEM1 expression and efficacy of neoadjuvant chemotherapy in patients with gastric cancer / 中国肿瘤临床

Objective: To detect the expression of P53, human epidermal growth factor receptor-2 (HER-2), and tumor endothelial marker 1 (TEM1) in gastric cancer tissues, analyze their correlation with clinical efficacy, and explore their potential roles as biomarkers for neoadjuvant chemotherapy. Methods: Sixty-three patients with gastric cancer who underwent fluorouracil-based neoadjuvant che-motherapy in The First Hospital of Lanzhou University from May 2015 to May 2017 were enrolled. Using immunohistochemistry, the expression of P53, Her2, and TEM1 was detected in 63 gastric cancer specimens before neoadjuvant chemotherapy. The efficacy of neoadjuvant chemotherapy was assessed by imaging. The relationship between the expression of P53, HER-2, and TEM1 and the effi-cacy of neoadjuvant chemotherapy was analyzed. Results: The total effective rate of neoadjuvant chemotherapy in 63 patients with advanced gastric cancer was 69.8%, with 2, 7, and 35 patients achieving complete remission, partial remission, and stable disease, re-spectively. Disease progression was noted in 19 patients. Univariate analysis revealed that patients positive for TEM1 and having high T stage had a poor response to neoadjuvant chemotherapy (P<0.05); furthermore, location, differentiation, and size of tumor; P53 posi-tivity (P=0.488); and Her-2 positivity (P=0.106) were not associated with the efficacy of neoadjuvant chemotherapy for gastric cancer. Multivariate analysis revealed that TEM1 positivity and a higher T stage could be factors that predicted the response to neoadjuvant chemotherapy in patients with advanced gastric cancer. Conclusions: TEM1, as a marker of tumor stroma, may be an important molec-ular biological indicator that predicts the poor response to neoadjuvant chemotherapy in patients with gastric cancer.

Comparison of three approaches to establishing Balb/c mouse models of hind-limb ischemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To compared 3 approaches to establishing Balb/c mouse models of hind-limb ischemia suitable for studies of regenerative medicine.</p><p><b>METHODS</b>Thirty eight-week-old male Balb/c mice were randomly divided into 3 groups for establishing models of hind-limb ischemia by both ligating and transecting the femoral artery proximal to the origin of the deep femoral artery branch, ligating the femoral artery proximal to the origin of the deep femoral artery branch, or ligating the femoral artery distal to the femoral artery trunk. The mice were continuously observed for 5 days after the operation, and hind-limb blood perfusion was monitored by laser Doppler imaging on the second postoperative day.</p><p><b>RESULTS</b>All the 3 surgical approaches caused blood flow block in the hind-limbs of the mice. In mice with ligation and transaction of the femoral artery proximal to the origin of the deep femoral artery branch, dry gangrene occurred in the whole hind-limb. Dry gangrene also occurred in the legs and paws of mice with ligation of the femoral artery proximal to the origin of the deep femoral artery branch. In mice with femoral artery ligation distal to the origin of the deep femoral artery branch, the sole of the foot was dry with scaling skin and necrosis of several digits; microscopically examination revealed a large quantity of necrotic muscles accompanied by muscle regeneration.</p><p><b>CONCLUSION</b>Ligating the femoral artery distal to the origin of the deep femoral artery branch can be optimal for establishing Balb/c mouse models of hind-limb ischemia.</p>

Toxicology and tissue distribution of Ruthenium (II) CO-releasing molecules and its interaction with endogenous substances / 药学学报

Carbon monoxide has been proved to be an important signal molecule in body. Transition metal carbonyl compounds are solidified form of carbon monoxide. Numerous studies have shown that Ruthenium carbonyl carbon monoxide releasing molecules have a strong pharmacological activity. In this paper, five Ruthenium (II) carbonyl CORMs 1-5 were synthesized and their toxicology, tissue distribution and interaction with blood endogenous substances were investigated. The results showed CORMs' IC50 to fibroblasts are ranged from 212.9 to 2089.2 micromol x L(-1). Their oral LD50 to mouse is between 800 to 1600 mg x kg(-1). After repeated administration, CORMs 1 and CORMs 5 haven't shown an obvious influence to rats' liver and kidney function, but caused the injury to liver and kidney cells. The in vivo distribution result revealed the majority of CORMs were distributed in blood, liver and kidney, only a small part of CORMs distributed in lung, heart and spleen. They could scarcely cross the blood-brain barrier and distribute to brain. The non-CO ligands in structure have an obvious relevance to their in vivo absorption and distribution. Interestingly, CORMs could enhance the fluorescence of bovine serum albumin, and this enhancement was in direct proportion with the concentration of CORMs. Under different conditions, interaction of CORMs with glutathione got different type of products, one is Ruthenium (II) tricarbonyl complexes, and Ruthenium (II) dicarbonyl complexes.

Clinical value of different imaging techniques in the diagnosis of periampullary carcinoma / 中华消化外科杂志

Periampullary carcinoma is a rare malignant tumor of digestive system,and its accurate diagnosis is still difficult.From January 2007 to July 2012,12 patients with periampullary carcinoma had been admitted to the Southwest Hospital of Third Military Medical University,and the imaging data were retrospectively analyzed.The results of ultrasonography revealed that all tumors were hypoechoic.The tumor displayed hyperenhancement in 3 patients,isoenhancement in 1 patient,hypoenhancement in 8 patients during the arterial phase on contrastenhanced ultrasonography (CEUS),while the tumor displayed hypoenhancement in all patients during the venous phase.Magnetic resonance imaging (MRI) plain scanning showed duodenal papilla enlargement in 1 patient,ampullary tissue mass signal in 2 patients,tissue mass signal at distal common bile duct in 2 patients,the rest 7 patients did not show tissue mass signal.Lower biliary obstruction was the common manifestation of the 12 patients on magnetic resonance cholangiopancreatography (MRCP),intrahepatic and extrahepatic bile vine-like expansion in 4 patients,double duct sign in 2 patients,the bottom of common bile duct with filling defect in 2 patients and it revealed beak-like narrow in 1 patient.CEUS,MRI and MRCP could both play an important role as conventional methods in diagnosing periampullary carcinoma.

A new NK-like cell subset of IL-22 producer:NK-22 cells / 中国免疫学杂志

The mucosal tissues form the interface between the outside world and the sterile environment of the body.Innate immunity plays a critical role in the maintenance of mucosal homeostasis.Recently,a new subset of innate immune cells named NK-22 has been discovered to reside at tonsil and intestine both in human and mice.NK-22 cells share features with both natural killer (NK) cells and lymphoid tissue-inducing (LTi) cells.NK-22 cells express a variety of NK cell receptors and phenotypically resemble that of immature NK cells (iNKs).However,they are quite different from NK cells in function and development.NK-22 cells lack conventional NK cell cytotoxic function and produce IL-22 instead of IFN-?.It is currently considered that NK-22 cells are not a subset of NK cells.They develop from LTi cells and the development process depends on ROR?t and commensal microflora.NK-22 cells are involved in immune protection against the pathogen Citrobacter rodentium.The IL-22 secreted by NK-22 cells contributes to epithelial cell resistance to injury and mucosal tissue repair after microbial infection.