Evaluation of the mechanistic basis for the antibacterial activity of ursolic acid against Staphylococcus aureus.

The antibiotics are generally regarded as the first choice approach to treat dairy mastitis, targeting the public health problems associated with the food safety and the emergence of antibioticresistant bacteria. The objective of the study was to evaluate the antibacterial efficacy of ursolic acid (UA) when used to treat Staphylococcus aureus and other isolates associated with bovine mastitis and to clarify the mechanistic basis for these effects. The bacteriostatic properties of UA extracted from Rosmarinus officinalis L. at four different purity levels were assessed by calculating minimum inhibitory concentration (MIC) values, while the synergistic effects of combining 98% UA with antibiotics were evaluated by measuring the fractional inhibitory concentration index (FICI). Changes in biofilm formation and the growth curves of the clinical isolates were assessed to clarify the bacteriostatic effect of UA. Furthermore, the cell wall integrity, protein synthesis, and reactive oxygen species (ROS) production were assessed to determine the antibacterial mechanism of UA treatment. Ultimately, UA was revealed to exhibit robust activity against Gram-positive bacteria including S. aureus (ATCC 25923), Streptococcus dysgalactiae (ATCC27957), Streptococcus agalactiae (ATCC13813), Enterococcus faecalis (ATCC29212), and Streptococcus mutans (ATCC25175). However, it did not affect Escherichia coli (ATCC 25922). The MIC values of UA preparations that were 98, 50, 30, and 10% pure against S. aureus were 39, 312, 625, and 625 µg/mL, respectively, whereas the corresponding MIC for E. coli was >5,000 µg/mL. The minimum bactericidal concentrations of 98% UA when used to treat three clinical S. aureus isolates (S4, S5, and S6) were 78, 78, and 156 µg/mL, respectively. Levels of biofilm formation for clinical S. aureus isolates decreased with increasing 98% UA concentrations. Above the MIC dose, UA treatment resulted in the dissolution of bacterial cell walls and membranes, with cells becoming irregularly shaped and exhibiting markedly impaired intracellular protein synthesis. S. aureus treated with 98% UA was able to rapidly promote intracellular ROS biogenesis. Together, these data highlight the promising utility of UA as a compound that can be used together with other antibiotics for the treatment of infections caused by S. aureus.

Development and mouse model evaluation of a new phage cocktail intended as an alternative to antibiotics for treatment of Staphylococcus aureus-induced bovine mastitis.

Bovine mastitis (BM) is a prevalent infectious disease in dairy herds worldwide, resulting in substantial economic losses. Staphylococcus aureus is a major cause of mastitis in animals, and its antibiotic resistance poses challenges for treatment. Recently, there has been a renewed interest in the development of alternative methods to antibiotic therapy, including bacteriophages (phages), for controlling bacterial infections. In this study, 2 lytic phages (designated as JDYN for vB_SauM_JDYN and JDF86 for vB_SauM_JDF86) were isolated from the cattle sewage effluent samples collected from dairy farms in Shanghai. The 2 phages have a broad bactericidal spectrum against Staphylococcus of various origins. Genomic and morphological analyses revealed that the 2 phages belonged to the Myoviridae family. Moreover, JDYN and JDF86 remained stable under a wide range of temperatures or pH and were almost unaffected in chloroform. In this study, we prepared a phage cocktail designated "PHC-1" which consisted of a 1:1:1 ratio of JDYN, JDF86 and SLPW (a previously characterized phage). PHC-1 showed the strongest bacteriolytic effect and the lowest frequency of emergence of bacteriophage insensitive mutants compared with monophages. The bovine mammary epithelial cells (MAC-T cells) and lactating mice mastitis model were used to evaluate the effectiveness of PHC-1 in vitro and in vivo, respectively. The results demonstrated that PHC-1 treatment significantly reduced bacterial load, alleviated inflammatory response, and improved mastitis pathology. Altogether, these results suggest that PHC-1 has the potential to treat S. aureus-induced bovine mastitis and that phage cocktails can combat antibiotic-resistant S. aureus infections.

Nerve growth factor (Ngf) gene-driven semaphorin 3a (Sema3a) expression exacerbates thoracic aortic aneurysm dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease and currently there is no pharmacological therapy. Sympathetic nerve overactivity plays an important role in the development of TAAD. Sympathetic innervation is mainly controlled by nerve growth factor (NGF, a key neural chemoattractant) and semaphoring 3A (Sema3A, a key neural chemorepellent), while the roles of these two factors in aortic sympathetic innervation and especially TAAD are unknown. We hypothesized that genetically manipulating the NGF/Sema3A ratio by the Ngf -driven Sema3a expression approach may reduce aortic sympathetic nerve innervation and mitigate TAAD progression. A mouse strain of Ngf gene-driven Sema3a expression (namely NgfSema3a/Sema3a mouse) was established by inserting the 2A-Sema3A expression frame to the Ngf terminating codon using CRISPR/Cas9 technology. TAAD was induced by ß-aminopropionitrile monofumarate (BAPN) both in NgfSema3a/Sema3a mice and wild type (WT) littermates. Contrary to our expectation, the BAPN-induced TAAD was severer in NgfSema3a/Sema3a mice than in wild-type (WT) mice. In addition, NgfSema3a/Sema3a mice showed higher aortic sympathetic innervation, inflammation and extracellular matrix degradation than the WT mice after BAPN treatment. The aortic vascular smooth muscle cells isolated from NgfSema3a/Sema3a mice and pretreated with BAPN in vivo for two weeks showed stronger capabilities of proliferation and migration than that from the WT mice. We conclude that the strategy of Ngf -driven Sema3a expression cannot suppress but worsens the BAPN-induced TAAD. By investigating the aortic phenotype of NgfSema3a/Sema3a mouse strain, we unexpectedly find a path to exacerbate BAPN-induced TAAD which might be useful in future TAAD studies.

Synaptotagmin 1 Suppresses Colorectal Cancer Metastasis by Inhibiting ERK/MAPK Signaling-Mediated Tumor Cell Pseudopodial Formation and Migration.

Although synaptotagmin 1 (SYT1) has been identified participating in a variety of cancers, its role in colorectal cancer (CRC) remains an enigma. This study aimed to demonstrate the effect of SYT1 on CRC metastasis and the underlying mechanism. We first found that SYT1 expressions in CRC tissues were lower than in normal colorectal tissues from the CRC database and collected CRC patients. In addition to this, SYT1 expression was also lower in CRC cell lines than in the normal colorectal cell line. SYT1 expression was downregulated by TGF-ß (an EMT mediator) in CRC cell lines. In vitro, SYT1 overexpression repressed pseudopodial formation and reduced cell migration and invasion of CRC cells. SYT1 overexpression also suppressed CRC metastasis in tumor-bearing nude mice in vivo. Moreover, SYT1 overexpression promoted the dephosphorylation of ERK1/2 and downregulated the expressions of Slug and Vimentin, two proteins tightly associated with EMT in tumor metastasis. In conclusion, SYT1 expression is downregulated in CRC. Overexpression of SYT1 suppresses CRC cell migration, invasion, and metastasis by inhibiting ERK/MAPK signaling-mediated CRC cell pseudopodial formation. The study suggests that SYT1 is a suppressor of CRC and may have the potential to be a therapeutic target for CRC.

Ursolic acid: biological functions and application in animal husbandry.

Ursolic acid (UA) is a plant-derived pentacyclic triterpenoid with 30 carbon atoms. UA has anti-inflammatory, antioxidative, antimicrobial, hepato-protective, anticancer, and other biological activities. Most studies on the biological functions of UA have been performed in mammalian cell (in vitro) and rodent (in vivo) models. UA is used in animal husbandry as an anti-inflammatory and antiviral agent, as well as for enhancing the integrity of the intestinal barrier. Although UA has been shown to have significant in vitro bacteriostatic effects, it is rarely used in animal nutrition. The use of UA as a substitute for oral antibiotics or as a novel feed additive in animal husbandry should be considered. This review summarizes the available data on the biological functions of UA and its applications in animal husbandry.

Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy.

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.

Values of OAS gene family in the expression signature, immune cell infiltration and prognosis of human bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is one of the most common genitourinary malignancies in the world, but its pathogenic genes have not been fully identified and the treatment outcomes are still unsatisfactory. Although the members of 2', 5'-oligoadenylate synthetase (OAS) gene family are known involved in some tumorous biological processes, the roles of the OAS gene family in BLCA are still undetermined. METHODS: By combining vast bioinformatic datasets analyses of BLCA and the experimental verification on clinical BLCA specimen, we identified the expressions and biological functions of OAS gene family members in BLCA with comparison to normal bladder tissues. RESULTS: The expression levels of OAS gene family members were higher in BLCA than in normal bladder tissues. The expression levels of most OAS genes had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells in the microenvironment of BLCA. In addition, high expressions of OAS1, OAS2, OAS3, and OASL predicted better overall survival in BLCA patients. CONCLUSIONS: The highly expressed OAS genes in BLCA can reflect immune cells infiltration in the tumor microenvironment and predict the better overall survival of BLCA, and thus may be considered as a signature of BLCA. The study provides new insights into the diagnosis, treatment, and prognosis of BLCA.

Global profiling of protein lysine malonylation in mouse cardiac hypertrophy.

Lysine malonylation, a novel identified protein posttranslational modification (PTM), is conservative and present in both eukaryotic and prokaryotic cells. Previous studies have reported that malonylation plays an important role in inflammation, angiogenesis, and diabetes. However, its potential role in cardiac remodeling remains unknown. Here, we observed a reduced lysine malonylation in hypertrophic mice hearts created by transverse aortic constriction (TAC) for 8 weeks. We also detected a decreased lysine malonylation in hypertrophic H9C2 cardiomyocytes induced by angiotensin II for 48 h. Using a proteomic method based on affinity purification and LC-MS/MS, we identified total 679 malonylated sites in 330 proteins in the hearts of sham mice and TAC mice. Bioinformatic analysis of the proteomic data revealed enrichment of malonylated proteins involved in cardiac structure and contraction, cGMP-PKG pathway, and metabolism. Specifically, we detected a decreased lysine malonylation in myocardial isocitrate dehydrogenase 2 (IDH2) by immunoprecipitation coupled with Western blotting both in vivo and in vitro. Together, our work suggests an important role and implication of protein lysine malonylation in cardiac hypertrophy, especially the IDH2. SIGNIFICANCE: Heart failure is the terminal stage of cardiac hypertrophy, which imposes an enormous clinical and economic burden worldwide. Despite our knowledge on the pathophysiology of the disease, current therapeutic approaches are still largely limited. Cardiac hypertrophy can be regulated at post-translational modifications (PTMs), and several PTMs have been reported in cardiac hypertrrophy and heart failure. In our study, we first reported a novel PTMs, lysine malonylation, in cardiac hypertophy. we found a reduced lysine malonylation in hypertrophic mice hearts in vivo and H9C2 cardiomyocytes after stimulating with angiotensinII for 48 h in vitro. Using affinity purification and LC-MS/MS, we identified 679 malonylated sites in 330 proteins in the hearts of sham and TAC mice. Compared to the sham group, 5 sites in 2 proteins were quantified as downregulated targets using a 2-fold threshold (downregulation <0.5-fold, P < 0.05). Functional analysis showed a significant enrichment in cardiac structure and contraction, cGMP-PKG pathway and metabolism. Notably, we identified a decreased Kmal level in isocitrate dehydrogenase 2 (IDH2), but the protein level of IDH2 has no changed in cardiac hypertrophy, These results highlight that lysine malonylation is associated with cardiac hypertrophy, and may be a new therapeutic target of the disease.

[Misdiagnosis of Acute Renal Artery Thrombosis as Acute Abdominal Disease:Report of One Case].

Renal artery thrombosis can cause acute occlusion of unilateral or bilateral renal arteries,and kidney failure would be induced if it is not diagnosed and treated in time.Therefore,rapid and correct treatment is especially important for renal artery thrombosis.Due to the lack of specificity of clinical manifestations,this disease in commonly misdiagnosed or missed and thus has a low early diagnosis rate.Here we report a case of acute renal artery thrombosis to improve the diagnosis and treatment.

Glycine Cleavage System and cAMP Receptor Protein Co-Regulate CRISPR/cas3 Expression to Resist Bacteriophage.

The CRISPR/Cas system protects bacteria against bacteriophage and plasmids through a sophisticated mechanism where cas operon plays a crucial role consisting of cse1 and cas3. However, comprehensive studies on the regulation of cas3 operon of the Type I-E CRISPR/Cas system are scarce. Herein, we investigated the regulation of cas3 in Escherichia coli. The mutation in gcvP or crp reduced the CRISPR/Cas system interference ability and increased bacterial susceptibility to phage, when the casA operon of the CRISPR/Cas system was activated. The silence of the glycine cleavage system (GCS) encoded by gcvTHP operon reduced cas3 expression. Adding N5, N10-methylene tetrahydrofolate (N5, N10-mTHF), which is the product of GCS-catalyzed glycine, was able to activate cas3 expression. In addition, a cAMP receptor protein (CRP) encoded by crp activated cas3 expression via binding to the cas3 promoter in response to cAMP concentration. Since N5, N10-mTHF provides one-carbon unit for purine, we assumed GCS regulates cas3 through associating with CRP. It was evident that the mutation of gcvP failed to further reduce the cas3 expression with the crp deletion. These results illustrated a novel regulatory pathway which GCS and CRP co-regulate cas3 of the CRISPR/Cas system and contribute to the defence against invasive genetic elements, where CRP is indispensable for GCS regulation of cas3 expression.

[Correlation of Matrix Metalloproteinases-9 with Microemboli Shedding in Carotid Endarterectomy].

Objective To investigate the change of serum matrix metalloproteinases-9 (MMP-9) expression before,during,and after carotid endarterectomy (CEA) and to investigate the prognostic role of MMP-9. Methods Forty carotid stenosis patients who underwent CEA in the Department of Vascular Surgery,Peking Union Medical College Hospital from February to September 2012 were enrolled in this study. Based on the findings of transcranial doppler monitoring,patients were divided into embolic-positive group and emboli-negative group. Serum samples were obtained from 40 consecutive patients undergoing CEA before operation (pre-op),before de-clamping,30 minutes after de-clamping,and 12 hours after operation (12-h post-op). MMP-9 expression was quantified using enzyme-linked immunosorbent assay and gelatin zymography. Student's t-test and chi-square test were used to compare the differences between these two groups. Results Of these 40 patients,microemboli were detected in 8 patients. The 12-h post-op MMP-9 level was significantly higher than the pre-op level in the emboli-positive group [(904.27±369.47)ng/ml vs. (333.88±126.32) ng/ml,t=4.132,P=0.001].However,there was no difference between pre-op and 12-h post-op MMP-9 levels in the emboli-negative group [(375.83±194.36) ng/ml vs. (472.74±271.21) ng/ml,t=-1.643,P=0.081]. Gelatin zymography also showed higher MMP-9 activity in the emboli-positive group than in the emboli-negative group. Conclusion Serum MMP-9 concentration remarkably increases 12 hours after CEA in patients with microemboli shedding,suggesting MMP-9 may be a potential biomarker for CEA-related cerebral ischemic injury.

The pathogenesis of thoracic aortic aneurysm from hereditary perspective.

Thoracic aortic aneurysm is extremely threatening due to high risk of dissection and rupture. Genetic factors play decisive role in the pathogenesis of thoracic aortic aneurysm. Recent years, several genes are considered to be associated with thoracic aortic aneurysm, among these genes, 11 gene variants identified are responsible for thoracic aortic aneurysm. In this review, we mainly discussed the function of the 11 gene variants in thoracic aortic aneurysm and the histology and cytokine signaling alterations induced by these gene variants.

Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats.

Aims The main objective was to investigate the effects of the transient receptor potential cation channel subfamily V member 1 (TRPV1) on nerve regeneration following sciatic transection injury by functional blockage of TRPV1 using AMG-517, a specific blocker of TRPV1. Methods AMG-517 was injected into the area surrounding ipsilateral lumbar dorsal root ganglia 30 min after unilateral sciatic nerve transection. The number of sciatic axons and the expression of growth-associated protein-43 (GAP-43) and glial fibrillary acidic protein was examined using semithin sections, Western blot, and immunofluorescence analyses. Results Blockage of TRPV1 with AMG-517 markedly promoted axonal regeneration, especially at two weeks after sciatic injury; the number of axons was similar to the uninjured control group. After sciatic nerve transection, expression of glial fibrillary acidic protein was decreased and GAP-43 was increased at the proximal stump. However, the expression of both glial fibrillary acidic protein and GAP-43 increased significantly in AMG-517-treated groups. Conclusions TRPV1 may be an important therapeutic target to promote peripheral nerve regeneration after injury.

Functional characteristics of a novel SMAD4 mutation from thoracic aortic aneurysms (TAA).

SMAD4 is as an essential mediator of the transforming growth factor ß (TGF-ß) signaling pathway, and dysregulated TGF-ß signaling is linked with thoracic aortic aneurysms (TAAs). In this study, we functionally characterized the Smad4 S271N mutation (the mutation c. 812G>A in Smad4 results in the amino acid substitution Ser271Asn) that was isolated from TAA individuals. We first constructed wild-type human Smad4 and Smad4 S271N plasmids. These constructs were then transiently transfected into HEK293T cells, and subsequent real-time PCR and western blotting demonstrated that wild-type Smad4 and Smad4 S271N were successfully expressed in 293T cells. We found that HEK293T cells overexpressing Smad4 S271N showed a strong increase in both cytoplasmic and nuclear Smad4 protein levels in response to TGF-ß1. Although TGF-ß signaling was the same in wild-type Smad4- and Smad4 S271N-transfected cells following TGF-ß1 exposure, interestingly, we observed that transient Smad4 S271N expression in HEK293T cells caused a significant basal activation of TGF-ß signaling. These results indicated that Smad4 may not directly induce TAA; rather it may contribute to TAA in combination with other risk factors.

Coherence transfer of subhertz-linewidth laser light via an optical fiber noise compensated by remote users.

We present a technique for the coherence transfer of laser light through a fiber link, where the optical phase noise induced by environmental perturbation via the fiber link is compensated by remote users. When compensating the fiber noise by remote users, the time base at the remote site independent from that at the local site does not destroy the performance of the fiber output light. Using this technique, we demonstrate the transfer of subhertz-linewidth laser light through a 25-km-long, lab-based spooled fiber. After being compensated, the relative linewidth between the fiber input and output light is 1 mHz, and the relative frequency instability is 4×10-17 at 1 s averaging time and scales down to 2×10-19 at 800 s averaging time. The frequency uncertainty of the light after transferring through the fiber relative to that of the input light is 3.0×10-19. This system is suitable for the simultaneous transfer of an optical signal to a number of end users within a city.

0.26-Hz-linewidth ultrastable lasers at 1557 nm.

Narrow-linewidth ultrastable lasers at 1.5 µm are essential in many applications such as coherent transfer of light through fiber and precision spectroscopy. Those applications all rely on the ultimate performance of the lasers. Here we demonstrate two ultrastable lasers at 1557 nm with a most probable linewidth of 0.26 Hz by independently frequency-stabilizing to the resonance of 10-cm-long ultrastable Fabry-Pérot cavities at room temperature. The fractional frequency instability of each laser system is nearly 8 × 10(-16) at 1-30 s averaging time, approaching the thermal noise limit of the reference cavities. A remarkable frequency instability of 1 × 10(-15) is achieved on the long time scale of 100-4000 s.

ANO1 protein as a potential biomarker for esophageal cancer prognosis and precancerous lesion development prediction.

OBJECTIVES: Anoctamin 1 (ANO1) has been found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous study. Herein we showed the clinical relevance of ANO1 alterations with ESCC and esophageal precancerous lesion progression. RESULTS: ANO1 was detected in 38.1% (109/286) and 25.4% (77/303) of tumors in the two cohorts, but in none of morphologically normal operative margin tissues. ANO1 expression was significantly associated with a shorter overall survival (OS), especially in patients with moderately differentiated and stage IIA tumors. In 499 iodine-unstained biopsies from the endoscopic screening cohort in 2005-2007, all the 72 pathologically normal epithelial mucosa presented negative immunostaining, whereas ANO1 expression was observed in 3/11 tumors and 5/231 intraepithelial lesions. 7/8 ANO1-positive cases had developed unfavorable outcomes revealed by endoscopic follow-up in 2012. Analysis of another independent cohort of 148 intraepithelial lesions further confirmed the correlation between ANO1 expression and progression of precancerous lesions. 3/4 intraepithelial lesions with ANO1 expression had developed ESCC within 4-9 years after the initial endoscopic examination. METHODS: Immunohistochemistry (IHC) was performed to examine ANO1 expression in surgical ESCC specimens and two independent cohorts of esophageal biopsies from endoscopic screening in high-incidence area of ESCC in northern China. Association between ANO1 expression, clinico-pathologic parameters, and the impact on overall survival was analyzed. CONCLUSIONS: Positive ANO1 is a promising biomarker to predict the unfavorable outcome for ESCC patients. More importantly, it can predict disease progression of precancerous lesions.

Deficiency of IL-12p35 improves cardiac repair after myocardial infarction by promoting angiogenesis.

AIMS: IL-12p35 is a pro-inflammatory cytokine that participates in a variety of inflammatory diseases. This study aimed to determine whether IL-12 regulates cardiac injury and repair following acute myocardial infarction (AMI) and investigate the underlying mechanisms. METHODS AND RESULTS: Mice with AMI showed a marked increase in IL-12p35 expression of ischaemic cardiac tissues. IL-12 was mainly produced by CD11b(+) monocytes. Cardiac functions were significantly improved in IL-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to AMI. IL-12p35 deficiency attenuated the infarct scar and hypertrophy compared with WT mice. RNA transcriptome sequencing and quantitative RT-PCR analysis of CD11b(+) monocytes isolated from WT and p35-KO ischaemic hearts revealed a distinct transcriptional profile in p35-KO CD11b(+) monocytes, displaying pro-angiogenesis and anti-inflammation properties. Angiogenesis was enhanced in p35-KO mice with AMI and hindlimb ischaemia. Moreover, tube formation assay and Matrigel plug analysis demonstrated that IL-12 inhibition of angiogenesis was dependent on monocytes. IL-12p35 deficiency inhibited inflammation by reducing chemokine production and monocyte infiltration into the heart. Finally, administration of an IL-12p35-neutralizing antibody limited AMI-induced inflammatory cell infiltration into the heart and improved angiogenesis and cardiac function. CONCLUSIONS: Deficiency of IL-12p35 limited AMI-induced cardiac injury by promoting pro-angiogenesis and anti-inflammatory functions of monocytes.

[Logistic Regression Analysis of Depression in Arteriosclerosis Obliterans Patients and Its Risk Factors].

OBJECTIVE: To investigate the depression in arteriosclerosis obliterans (ASO) patients and its risk factors. METHODS: The self-rating depression scale (SDS) was applied in 228 ASO patients hospitalized in the vascular surgery department of Peking Union Medical College Hospital from March 2010 to October 2011. The risk factors of depression were analyzed by using univariate and multivariate Logistic regression analysis. RESULTS: Of these 228 ASO patients, 133 (58.3%) were found to be depressive. Univariate and multivariate analysis showed that female (OR=0.15,95% CI:0.05-0.45), hypertension (OR=4.63,95% CI:1.90-11.29), coronary heart disease (OR=3.62,95%CI:1.43-9.18), as well as Fontaine 2a (OR=20.76,95% CI:3.21-134.28), 2b (OR=26.34,95% CI:4.20-164.97), 3(OR=192.28,95% CI:25.97-1423.51), and 4(OR=291.41,95% CI:28.67-2962.21) were the risk factors of depression in ASO patients. CONCLUSIONS: ASO patients can easily develop depression. Female, hypertension, coronary heart disease, and Fontaine 2a, 2b,3,and 4 are the risk factors of depression in ASO patients.

[IGHMBP2 overexpression promotes cell migration and invasion in esophageal squamous carcinoma].

Immunoglobulin mu binding protein 2 (IGHMBP2) is located in 11q13.2, which is frequently amplified in esophageal squamous cell carcinoma (ESCC). IGHMBP2 encodes a helicase involved in DNA replication and repair. IGHMBP2 protein also regulates gene transcription. The present study aims to explore the amplification of IGHMBP2 and its potential role in ESCC. A further analysis of our previously reported array-CGH data showed that IGHMBP2 was amplified in 28.9% of primary ESCC tumors. Fluorescence in situ hybridization (FISH) and Western blot showed that IGHMBP2 was amplified and overexpressed in KYSE30, KYSE180, KYSE510 and KYSE150 esophageal cancer cell lines. Transwell assays demonstrated that knockdown of IGHMBP2 in KYSE30 and KYSE150 inhibited cell invasion and migration, and increased the expression levels of E-cadherin. When rescue plasmids expressing IGHMBP2 were introduced, the abilities of cell invasion and migration were restored. These data suggest that IGHMBP2 overexpression may promote invasion and migration of ESCC cells through down-regulation of E-cadherin.