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1.  TSLP Signaling in CD4+ T cells is Required for Th2 Memory 
Thymic stromal lymphopoietin (TSLP) is a key factor in the development of allergic asthma. Th2 memory cells gradually increase in allergic patients with the progression of disease and persist in the lungs during remission although the mechanism is not clear.
To define the role of TSLP in Th2 memory generation and maintenance in vivo.
Adoptive transfer of wild type (WT) and TSLP receptor (TSLPR)-deficient ovalbumin (OVA)-specific CD4+ T cells before Th2 sensitization was used to define T cell specific TSLP effects. Atopic dermatitis and elevated serum TSLP concentration was induced by topical application of the vitamin D3 analog MC903. Memory cells in peripheral blood were monitored weekly with flow cytometry. Memory recall was tested following intranasal OVA challenge.
TSLP signaling in CD4+ T cells is required for the generation/maintenance of memory cells following in vivo priming. TSLPR-deficient CD4+ T cells have no defects in proliferation but fail to survive one week after sensitization, and elevated TSLP expression during sensitization significantly increased the frequency of memory cells. Although in vitro differentiated TSLPR-deficient Th2 cells develop into memory cells with equal efficiency to wild type cells, the recall response to airway antigen challenge is impaired. Moreover, after antigen challenge of mice with established Th2 memory, TSLP signaling in CD4+ T cells significantly affects memory cell generation/maintenance from secondary effector cells.
TSLP signaling in CD4+ T cells is required for not only Th2 memory formation in vivo, but also the recall response of the memory cells to local antigen challenge.
PMCID: PMC4355221  PMID: 25441291
TSLP; Th2 memory; Memory recall; Allergic airway inflammation; Eosinophilia
2.  Precocious leaf senescence by functional loss of PROTEIN S-ACYL TRANSFERASE14 involves the NPR1-dependent salicylic acid signaling 
Scientific Reports  2016;6:20309.
We report here that Arabidopsis PROTEIN S-ACYL TRANSFERASE14 (PAT14), through its palmitate transferase activity, acts at the vacuolar trafficking route to repress salicylic acid (SA) signaling, thus mediating age-dependent but not carbon starvation-induced leaf senescence. Functional loss of PAT14 resulted in precocious leaf senescence and its transcriptomic analysis revealed that senescence was dependent on salicylic acid. Overexpressing PAT14 suppressed the expression of SA responsive genes. Introducing the SA deficient mutants, npr1-5 and NahG, but not other hormonal mutants, completely suppressed the precocious leaf senescence of PAT14 loss-of-function, further supporting the epistatic relation between PAT14 and the SA pathway. By confocal fluorescence microscopy, we showed that PAT14 is localized at the Golgi, the trans-Golg network/early endosome, and prevacuolar compartments, indicating its roles through vacuolar trafficking. By reporter analysis and real time PCRs, we showed that the expression PAT14, unlike most of the senescence associated genes, is not developmentally regulated, suggesting post-transcriptional regulatory mechanisms on its functionality. We further showed that the maize and wheat homologs of PAT14 fully rescued the precocious leaf senescence of pat14-2, demonstrating that the role of PAT14 in suppressing SA signaling during age-dependent leaf senescence is evolutionarily conserved between dicots and monocots.
PMCID: PMC4740857  PMID: 26842807
3.  Estimates and Predictions of Coal Workers’ Pneumoconiosis Cases among Redeployed Coal Workers of the Fuxin Mining Industry Group in China: A Historical Cohort Study 
PLoS ONE  2016;11(2):e0148179.
This research was aimed at estimating possible Coal workers’ pneumoconiosis (CWP) cases as of 2012, and predicting future CWP cases among redeployed coal workers from the Fuxin Mining Industry Group. This study provided the scientific basis for regulations on CWP screening and diagnosis and labor insurance policies for redeployed coal workers of resource-exhausted mines. The study cohort included 19,116 coal workers. The cumulative incidence of CWP was calculated by the life-table method. Possible CWP cases by occupational category were estimated through the average annual incidence rate of CWP and males’ life expectancy. It was estimated that 141 redeployed coal workers might have suffered from CWP as of 2012, and 221 redeployed coal workers could suffer from CWP in the future. It is crucial to establish a set of feasible and affordable regulations on CWP screening and diagnosis as well as labor insurance policies for redeployed coal workers of resource-exhausted coal mines in China.
PMCID: PMC4742233  PMID: 26845337
4.  Prognostic value of high FoxC2 expression in resectable non-small cell lung cancer, alone or in combination with E-cadherin expression 
BMC Cancer  2016;16:16.
FoxC2 is an epithelial–mesenchymal transition (EMT) regulator which induces metastasis. The purpose of this study is to assess the prognostic value of FoxC2 expression in non-small cell lung cancer (NSCLC), alone or in combination with E-cadherin expression.
A retrospective study was conducted using immunohistochemistry to investigate FoxC2 and E-cadherin expression in a cohort of 309 patients with surgically resected NSCLCs. The prognostic value of FoxC2 and E-cadherin on overall survival (OS) and recurrence-free survival (RFS) was determined by Kaplan-Meier analysis and Cox proportional hazard models.
High FoxC2 expression was detected in 26.5 % of tumors, and significantly correlated with tobacco use (p = 0.047), adenocarcinoma (p = 0.008) and nodal involvement (p < 0.001). Univariate analysis revealed its association with OS (p = 0.036) and RFS (p = 0.011). By multivariate analysis, high FoxC2 expression lost its significance as an independent predictor of recurrence (p = 0.077), while TNM stage, nodal status and the presence of high FoxC2 and impaired E-cadherin expression retained independent prognostic significance in relation to both OS and RFS. Subset analyses indicated that high FoxC2 expression was significantly associated with disease outcome in node-positive, but not in node-negative patients.
Evaluation of FoxC2 expression, alone or in combination with E-cadherin expression, may help to stratify NSCLC patients for risk of disease progression, pointing to this EMT regulator as a potential prognostic marker.
PMCID: PMC4711004  PMID: 26758745
Lung cancer; FoxC2; E-cadherin; Prognosis; Immunohistochemistry
5.  Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro 
Journal of Diabetes Research  2016;2016:5671803.
Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation.
PMCID: PMC4736797  PMID: 26881253
6.  A novel method for lymphadenectomy along the left laryngeal recurrent nerve during thoracoscopic esophagectomy for esophageal carcinoma 
Journal of Thoracic Disease  2016;8(1):24-30.
Due to limited space in the left upper mediastinum, complete dissection of lymph nodes (LN) along left recurrent laryngeal nerve (RLN) is difficult. We herein present a novel method for lymphadenectomy along the left RLN during thoracoscopic esophagectomy in the semi-prone position for esophageal carcinoma. The method, suspension the esophagus and push aside trachea, allows en bloc lymphadenectomy along the left RLN from the below aortic arch to the thoracic inlet.
Between September 2014 and September 2015, a total of 110 consecutive patients with esophageal carcinoma were treated with thoraco-laparoscopic esophagectomy with cervical anastomosis in the semi-prone position. Outcomes between those who received surgery with the novel method and conventional surgery were compared.
Fifty patients underwent the novel method and sixty received conventional surgery. The operative field around the left RLN was easier to explore with the novel method. The estimated blood loss was less (23.7±8.2 vs. 34.2±10.3 g, P=0.001), and the number of harvested LNs along the left RLN was greater (6.4±3.2 vs. 4.1±2.8 min, P=0.028) in the novel method group, while the duration of lymphadenectomy along left RLN was longer in the novel method group (28.2±3.9 vs. 20.3±2.8 min, P=0.005). The rate of hoarseness in the novel and conventional groups was 10% and 16.7%, respectively. No significant difference in postoperative morbidity related to the left RLN was noted between the groups.
The novel method during semi-prone esophagectomy for esophageal carcinoma is associated with better surgeon ergonomics and operative exposure.
PMCID: PMC4740152  PMID: 26904208
Semi-prone esophagectomy; lymphadenectomy; left recurrent laryngeal nerve (RLN); esophageal carcinoma; novel method
7.  P25: VATS combined with a subxiphoid incision: a novel approach for large thymoma 
Journal of Thoracic Disease  2015;7(Suppl 3):AB094.
In patients with thymoma larger than 5 cm in diameter, video-assisted thoracoscopic surgery (VATS) remains controversial as an approach for total thymectomy. Aside from the concerns such as possible rupture of tumor capsule, reduced safety margins and increased risk of local recurrence, how to remove specimen of this size from incisions of VATS is another problem that surgeons have to confront. We reported a case of a 47-year-old man who was referred to our department with a huge mass located on the anterior mediastinal and right hemithorax. After careful preoperative evaluation and planning, the tumor was completely removed by VATS and taken out of thoracic cavity through a subxiphoid incision. After resection, histologic analysis confirmed the diagnosis of thymoma B1 type. Postoperative course was uneventful and no adjuvant therapy was offered. The patient has continued to do well with no signs of recurrence at a follow-up of 10 months. We stress that VATS combined with a subxiphoid incision may be a useful surgical option for patients with thymoma larger than 5 cm in size.
PMCID: PMC4700333
Thymoma; video-assisted thoracoscopic surgery (VATS); minimally invasive
8.  Uniportal video-assisted thoracic surgery lobectomy in semiprone position: primary experience of 105 cases 
Journal of Thoracic Disease  2015;7(12):2389-2395.
Uniportal video-assisted thoracic surgery (VATS) is becoming popular, and uniportal lobectomy in semiprone position was reported in 2014. This study aimed to investigate the feasibility and safety of uniportal VATS in semiprone position.
From May 28, 2014 to October 19, 2015, we attempted uniportal VATS lobectomy in semiprone position in 105 cases. Forty-five patients were male, and 60 patients were female. Average age was 57.1±10.6 years (24–76 years). Perioperative parameters were documented.
There were two conversions to three-port lobectomy, one conversion to double-port lobectomy, and three conversions to thoracotomy. Among the patients who received uniportal VATS in semiprone position, mean operation duration was 137.4±47.8 minutes. Mean estimated blood loss was 60.7±102.7 mL. Mean time of drainage was 3.0±2.1 days, and postoperative length of stay averaged 4.9±2.3 days. In the cases of primary lung cancer, the mean number of nodal stations explored was 7.2±1.3, with a mean of 20.8±6.3 lymph nodes resected. As to the mediastinal lymph node specifically, a mean of 4.4±1.0 nodal stations were explored, and the number of resected mediastinal lymph nodes averaged 12.8±5.1. No perioperative death or major complication occurred.
Uniportal VATS lobectomy in semiprone position is feasible and safe.
PMCID: PMC4703695  PMID: 26793366
Video-assisted thoracic surgery (VATS); uniportal; semiprone position
9.  FOXL2 down-regulates vitellogenin expression at mature stage in Eriocheir sinensis 
Bioscience Reports  2015;35(6):e00278.
The present study highlights that forkhead transcription factor (FOXL)2 down-regulates vitellogenin (VTG) synthesis not only through the regulation of follicular cell apoptosis with DEAD-box RNA helicase 20 (DDX20), but also may through the steroidogenic pathway with fushi tarazu factor (FTZ-F)1 at mature stage in Eriocheir sinensis.
Ovarian development in crustaceans is characterized by rapid production of egg yolk protein in a process called vitellogenesis. In the present study, we investigated the involvement of a DEAD (Asp-Glu-Ala-Asp) box RNA helicase 20 (DDX20), forkhead transcription factor (FOXL)2 and fushi tarazu factor (FTZ-F)1 in the regulation of vitellogenesis. Based on ESTs from the testis and accessory gland of Eriocheir sinensis, we cloned the full-length cDNAs of foxl2 and fushitarazu factor 1 (ftz-f1), which include the conserved structural features of the forkhead family and nuclear receptor 5A (NR5A) family respectively. The expression of foxl2 mRNA surged at the mature stage of the ovary, when vtg mRNA swooped, suggesting that foxl2 negatively affects the vitellogenin (VTG) synthesis at this developmental stage. Etoposide (inducing germ cell apoptosis) treatment up-regulated FOXL2 and DDX20 at both the mRNA and the protein levels, primarily in the follicular cells as shown by immunofluorescence analysis. Furthermore, foxl2, ddx20 and ftz-f1 mRNA levels increased significantly with right-eyestalk ablation. Interactions between FOXL2 and DDX20 or FTZ-F1 were confirmed by co-immunoprecipitation and the forkhead domain of FOXL2 was identified as the specific structure interacting with FTZ-F1. In conclusion, FOXL2 down-regulates VTG expression by binding with DDX20 in regulation of follicular cell apoptosis and with FTZ-F1 to repress the synthesis of VTG at the mature stage. This report is the first to describe the molecular mechanism of VTG synthesis in E. sinensis and may shed new light on the regulation of cytochrome P450 enzyme by FOXL2 and FTZ-F1 in vitellogenesis.
PMCID: PMC4708011  PMID: 26430246
DDX20; FOXL2; FTZ-F1; follicular cells; mature stage; vitellogenin (VTG) synthesis
10.  Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury 
Neural Plasticity  2015;2015:249756.
Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.
PMCID: PMC4677233  PMID: 26697232
11.  DC targeting DNA vaccines induce protective and therapeutic antitumor immunity in mice 
Background: Anti-CD11c antibodies target to the CD11c receptor that mediates antigen presentation to T cells by dendritic cells (DCs). To exploit these properties for immunization purposes, we obtained DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from N418 (scFvN418), a monoclonal antibody binding the mouse DC-restricted surface molecule CD11c, and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models. Methods: Induction of humoral and cellular immune responses and antitumoral activity of the DNA vaccines were tested in transplantable HER2/neu-expressing murine tumor models and in transgenic BALB-neuT mice developing spontaneous Neu-driven mammary carcinomas. Results: Upon injection of the breast tumor cell line D2F2/E2 (stably expressing human wild-type HER2), scFvN418-HER2 immunized mice were protected against tumor growth. Even more important for clinical applications, we were able to substantially slow the growth of implanted D2F2/E2 cells by injection of scFvN418-HER2 conjugates into tumor bearing hosts. The existing tumors were eradicated by treatment with scFvN418-HER2 combined with low-dose cyclophosphamide (CTX), which can make a temporary regulatory T cells (Treg) depletion. What’s more, in combination with the low-dose CTX, vaccination with scFvN418-neu significantly retarded the development of spontaneous mammary carcinomas in transgenic BALB-neuT mice. Conclusion: Our results show that DNA vaccine which targeting of dendritic cells in situ by the means of antibody-antigen conjugates may be a novel way to induce long-lasting antitumor immunity.
PMCID: PMC4694247  PMID: 26770347
DNA vaccine; dendritic cell-targeted; HER2/neu; breast cancer; cyclophosphamide
12.  A stubborn anemia caused by ectopic pancreas bleeding in the jejunum revealed by capsule endoscopy 
Ectopic pancreas is extremely rare in clinical setting. Meanwhile, a stubborn anemia without obvious dark bloody stool due to ectopic pancreas diagnosed by capsule endoscopy has not been reported. We reported a case of an ectopic pancreas inducing obscure gastrointestinal bleeding in a 70-year-old woman presenting as stubborn anemia, which was diagnosed by capsule endoscopy. The patient recovered well after resection the lesion. Diagnosis of ectopic pancreas is extremely difficult with conventional techniques. Endoscopists should pay more attention to the ectopic pancreas as a rare differential consideration for occult intestinal bleeding.
PMCID: PMC4671962  PMID: 26682148
Capsule endoscopy; ectopic pancreas; bleeding
13.  A Catalog of Proteins Expressed in the AG Secreted Fluid during the Mature Phase of the Chinese Mitten Crabs (Eriocheir sinensis) 
PLoS ONE  2015;10(8):e0136266.
The accessory gland (AG) is an important component of the male reproductive system of arthropods, its secretions enhance fertility, some AG proteins bind to the spermatozoa and affect its function and properties. Here we report the first comprehensive catalog of the AG secreted fluid during the mature phase of the Chinese mitten crab (Eriocheir sinensis). AG proteins were separated by one-dimensional gel electrophoresis and analyzed by reverse phase high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Altogether, the mass spectra of 1173 peptides were detected (1067 without decoy and contaminants) which allowed for the identification of 486 different proteins annotated upon the NCBI database ( and our transcritptome dataset. The mass spectrometry proteomics data have been deposited at the ProteomeXchange with identifier PXD000700. An extensive description of the AG proteome will help provide the basis for a better understanding of a number of reproductive mechanisms, including potentially spermatophore breakdown, dynamic functional and morphological changes in sperm cells and sperm acrosin enzyme vitality. Thus, the comprehensive catalog of proteins presented here can serve as a valuable reference for future studies of sperm maturation and regulatory mechanisms involved in crustacean reproduction.
PMCID: PMC4549300  PMID: 26305468
14.  Optic radiation mapping reduces the risk of visual field deficits in anterior temporal lobe resection 
Anterior temporal lobe resection (ATLR) is often complicated by superior quadrant visual field deficits (VFDs) because of damage to the anterior portion of the optic radiation (Meyer’s loop). This study reports the evaluation of optic radiation mapping in protecting against VFDs in the ATLR. We retrospectively analyzed 52 patients with medically refractory temporal lobe epilepsy undergoing ATLR between January 2012 and December 2013. The surgical operations in Group I (n=32) were performed with the modified ATLR, and the operations in Group II (n=20) were aided by combining optic radiation mapping by diffusion tensor imaging, microscopic-based neuronavigation and the intraoperative magnetic resonance imaging (iMRI) technique. A t-test was used to compare the size of ATLR, and a chi square test was applied for the postoperative VFD and seizure outcomes. The optic radiation was reconstructed in all patients in Group II. The size of ATLR was 5.11±1.34 cm (3.3-8 cm), and 3.24±0.75 cm (2.2-4.8 cm) in Groups I and II, respectively; the size of ATLR was significantly smaller in Group II (F=9.803; P=0.00). The visual fields assessment by the Humphrey Field Analyser 30-2 test showed 27 patients (84.4%) in Group I suffered VFDs at 3 months post-operation, whereas only eight patients (40.0%) in Group II showed VFDs (Pearson chi square =11.01; P=0.001). The 6-month follow-up survey showed that 90.6% of patients in Group I achieved a good outcome (Engel class I-II), outperforming 85.0% in Group II, however, there was no statistically significant difference (chi square =0.382, P=0.581). This techniques of combining optic radiation mapping, microscopic-based neuronavigation and iMRI aided in precise mapping and hence reduction of the risk of visual field deficits in ATLR. The size of ATLR guided by optic radiation mapping was significantly smaller but the seizure outcome was not significantly affected.
PMCID: PMC4613097  PMID: 26550412
Intraoperative magnetic resonance imaging (iMRI); optic radiation mapping; diffusion tensor imaging (DTI); visual field deficits (VFD); anterior temporal lobe resection (ATLR)
15.  Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma 
Journal of Thoracic Disease  2015;7(8):1398-1405.
Immunohistochemical staining has been widely used in distinguishing lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC), which is of vital importance for the diagnosis and treatment of lung cancer. Due to the lack of a comprehensive analysis of different lung cancer subtypes, there may still be undiscovered markers with higher diagnostic accuracy.
Herein first, we systematically analyzed high-throughput data obtained from The Cancer Genome Atlas (TCGA) database. Combining differently expressed gene screening and receiver operating characteristic (ROC) curve analysis, we attempted to identify the genes which might be suitable as immunohistochemical markers in distinguishing LUAD from LUSC. Then we detected the expression of six of these genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in lung cancer sections using immunohistochemical staining.
A number of genes were identified as candidate immunohistochemical markers with high sensitivity and specificity in distinguishing LUAD from LUSC. Then the staining results confirmed the potentials of the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in distinguishing LUAD from LUSC, and their sensitivity and specificity were not less than many commonly used markers.
The results revealed that the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) might be suitable markers in distinguishing LUAD from LUSC, and also validated the feasibility of our methods for identification of candidate markers from high-throughput data.
PMCID: PMC4561256  PMID: 26380766
Lung cancer; immunohistochemical marker; receiver operating characteristic (ROC) curve analysis; The Cancer Genome Atlas (TCGA)
16.  Extranodal NK/T-cell lymphoma, nasal type: a case report of 7-year natural course and review of literature 
We present our experience a vary case of Extranodal natural killer (NK)/T-cell lymphomas, nasal type (ENKL) who survived for 7 years, and review the recent advances on the differential diagnosis.
PMCID: PMC4583960  PMID: 26464728
Extranodal natural killer/T-cell lymphomas; Epstein-Barr virus; clinical features; prognosis
17.  First report of two rapid-onset fatal infections caused by a newly emerging hypervirulent K. Pneumonia ST86 strain of serotype K2 in China 
Here, we present the first report of one suspected dead case and two confirmed rapid-onset fatal infections caused by a newly emerging hypervirulent Klebsiella pneumoniae ST86 strain of serotype K2. The three cases occurred in a surgery ward during 2013 in Shanghai, China. A combination of multilocus sequence typing, pulsed-field gel electrophoresis, phenotypic and PCR tests for detecting virulence factors (VFs) was used to identify the isolates as K2 ST86 strains with common VFs, including Aerobactin and rmpA. Furthermore, the two K2 ST86 strains additionally harbored a distinct VF kfu (responsible for iron uptake system), which commonly existed in invasive K1 strains only. Thus, the unusual presence of both K1 and K2 VFs in the lethal ST86 strain might further enhance its hypervirulence and cause rapid onset of a life-threatening infection. Nevertheless, despite the administration of a combined antibiotic treatment, these three patients all died within 24 h of acute onset, thereby highlighting that the importance of early diagnosis to determine whether the ST86 strains harbor key K2 VF and unusual K1 kfu and whether patients should receive a timely and targeted antibiotic therapy to prevent ST86 induced fatal pneumonia. Finally, even though these patients are clinically improved, keeping on with oral antibiotic treatment for additional 2–3 weeks will be also vital for successfully preventing hvKP reinfection or relapse.
PMCID: PMC4508851  PMID: 26257712
hypervirulent Klebsiella pneumoniae (hvKP); pyogenic liver abscess (PLA); ST86; virulence factors (VFs); iron-uptake system (kfu)
18.  Inhibition of SREBP Transcriptional Activity by a Boron-Containing Compound Improves Lipid Homeostasis in Diet-Induced Obesity 
Diabetes  2014;63(7):2464-2473.
Dysregulation of lipid homeostasis is intimately associated with obesity, type 2 diabetes, and cardiovascular diseases. Sterol regulatory-element binding proteins (SREBPs) are the master regulators of lipid biosynthesis. Previous studies have shown that the conserved transcriptional cofactor Mediator complex is critically required for the SREBP transcriptional activity, and recruitment of the Mediator complex to the SREBP transactivation domains (TADs) is through the MED15-KIX domain. Recently, we have synthesized several boron-containing small molecules. Among these novel compounds, BF175 can specifically block the binding of MED15-KIX to SREBP1a-TAD in vitro, resulting in an inhibition of the SREBP transcriptional activity and a decrease of SREBP target gene expression in cultured hepatocytes. Furthermore, BF175 can improve lipid homeostasis in the mouse model of diet-induced obesity. Compared with the control, BF175 treatment decreased the expression of SREBP target genes in mouse livers and decreased hepatic and blood levels of lipids. These results suggest that blocking the interaction between SREBP-TADs and the Mediator complex by small molecules may represent a novel approach for treating diseases with aberrant lipid homeostasis.
PMCID: PMC4066337  PMID: 24608444
19.  Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2 
Macrophage survival is believed to be a contributing factor in the development of early atherosclerotic lesions. Dysregulated apoptosis of macrophages is involved in the inflammatory process of atherogenesis. Apigenin is a flavonoid that possesses various clinically relevant properties such as anti-inflammatory, antiplatelet, and antitumor activities. Here we showed that apigenin attenuated atherogenesis in apoE−/− mice in an in vivo test. In vitro experiments suggested that apigenin induced apoptosis of oxidized low density lipoprotein- (OxLDL-) loaded murine peritoneal macrophages (MPMs). Proteomic analysis showed that apigenin reduced the expression of plasminogen activator inhibitor 2 (PAI-2). PAI-2 has antiapoptotic effects in OxLDL-loaded MPMs. Enhancing PAI-2 expression significantly reduced the proapoptosis effects of apigenin. Molecular docking assay with AutoDock software predicted that residue Ser473 of Akt1 is a potential binding site for apigenin. Lentiviral-mediated overexpression of Akt1 wild type weakened the proapoptosis effect of apigenin in OxLDL-loaded MPMs. Collectively, apigenin executes its anti-atherogenic effects through inducing OxLDL-loaded MPMs apoptosis. The proapoptotic effects of apigenin were at least partly attributed to downregulation of PAI-2 through suppressing phosphorylation of AKT at Ser473.
PMCID: PMC4413885  PMID: 25960827
20.  Segmental small bowel necrosis associated with antiphospholipid syndrome: A case report 
Antiphospholipid syndrome is a multi-system disease characterized by the formation of thromboembolic complications and/or pregnancy morbidity, and with persistently increased titers of antiphospholipid antibodies. We report the case of a 50-year-old, previously healthy man who presented with fever and new-onset, dull abdominal pain. A contrast-enhanced computed tomography scan showed segmental small bowel obstruction, for which an emergency laparotomy was performed. Histopathologic examination of resected tissues revealed multiple intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum antiphospholipid (anticardiolipin IgM) and anti-β2-glycoprotein I antibodies were positive. Despite proactive implementation of anticoagulation, steroid, and antibiotic therapies, the patient’s condition rapidly deteriorated, and he died 22 d after admission. This case highlights that antiphospholipid syndrome should be suspected in patients with unexplainable ischemic bowel and intestinal necrosis presenting with insidious clinical features that may be secondary to the disease, as early diagnosis is critical to implement timely treatments in order to ameliorate the disease course.
PMCID: PMC4385561  PMID: 25852299
Anticardiolipin antibodies; Antiphospholipid syndrome; Intestinal necrosis; Mesenteric arteriolar thrombosis; Small bowel obstruction
21.  Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice 
Scientific Reports  2015;5:9488.
Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice, and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus.
PMCID: PMC4377552  PMID: 25820815
22.  The Expression Level and Prognostic Value of Y-Box Binding Protein-1 in Rectal Cancer 
PLoS ONE  2015;10(3):e0119385.
The aims of this study were to simultaneously evaluate the expression of Y-box binding protein-1 (YB-1) in non-neoplastic rectal tissue and rectal cancer tissue, and to collect clinical follow-up data for individual patients. Additionally, we aimed to investigate the developmental functions and prognostic value of YB-1 in rectal cancer. We performed immunohistochemical studies to examine YB-1 expression in tissue samples from 80 patients with rectal cancer, 30 patients with rectal tubular adenoma, and 30 patients with rectitis. The mean YB-1 histological scores for rectal cancer, rectal tubular adenoma, and rectitis tissue specimens were 205.5, 164.3, and 137.7, respectively. Shorter disease-free and overall survival times were found in patients with rectal cancer who had higher YB-1 expression than in those with lower expression (38.2 months vs. 52.4 months, P = 0.013; and 44.4 months vs. 57.3 months, P = 0.008, respectively). Our results indicate that YB-1 expression is higher in rectal cancer tissue than in rectal tubular adenoma and rectitis tissue and that it may be an independent prognostic factor for rectal cancer.
PMCID: PMC4366156  PMID: 25790262
23.  Characterization of Cellulase Secretion and Cre1-Mediated Carbon Source Repression in the Potential Lignocellulose-Degrading Strain Trichoderma asperellum T-1 
PLoS ONE  2015;10(3):e0119237.
Trichoderma asperellum, a traditional bio-control species, was demonstrated to be an excellent candidate for lignocellulose degradation in this work. Comparing to the representatively industrial strain of Trichoderma reeseiQM6a, T. asperellum T-1 showed more robust growth, stronger spore production, faster secretion of lignocellulose-decomposing enzymes and better pH tolerance. The reducing sugar released by strain T-1 on the second day of fermentation was 87% higher than that of strain QM6a, although the maximum reducing sugar yield and the cellulase production persistence of the strain T-1 were lower. Our experiment found that the cellulase secretion was strongly inhibited by glucose, suggesting the existence of carbon source repression pathway in T. asperellum T-1. The inhibiting effect was enhanced with an increase in glucose concentration and was closely related to mycelium growth. SDS-PAGE and secondary mass-spectrum identification confirmed that the expression of endo-1,4-β-xylanase I in T. asperellum T-1 was down-regulated when glucose was added. The factor Cre1, which plays an important role in the down-regulation of the endo-1,4-β-xylanase I gene, was investigated by bioinformatics methods. The protein structure of Cre1, analyzed using multiple protein sequence alignment, indicates the existence of the Zn-fingers domain. Then, the binding sites of Cre1 on the endo-1,4-β-xylanase I gene promoter were further elucidated. This study is the first report about Cre1-mediated carbon repression in the bio-control strain T. asperellum T-1. All of the above results provided good references for better understanding T. asperellum T-1 and improving its application for lignocellulose degradation.
PMCID: PMC4351060  PMID: 25741694
24.  Isoform Switch of Pyruvate Kinase M1 Indeed Occurs but Not to Pyruvate Kinase M2 in Human Tumorigenesis 
PLoS ONE  2015;10(3):e0118663.
Muscle type of pyruvate kinase (PKM) is one of the key mediators of the Warburg effect and tumor metabolism. Due to alternative splicing, there are at least 12 known isoforms of the PKM gene, of which PKM1 and PKM2 are two major isoforms with only a 23 amino acid sequenced difference but quite different characteristics and functions. It was previously thought the isoform switch from PKM1 to PKM2 resulted in high PKM2 expression in tumors, providing a great advantage to tumor cells. However, this traditional view was challenged by two recent studies; one study claimed that this isoform switch does not occur during the Warburg effect; the other study asserted that the isoform switch is tissue-specific. Here, we re-analyzed the RNA sequencing data of 25 types of human tumors from The Cancer Genome Atlas Data Portal, and confirmed that PKM2 was the major isoform in the tumors and was highly elevated in addition to the entire PKM gene. We further demonstrated that the expression level of PKM1 significantly declined even though there was substantially increased expression of the entire PKM gene. The proportion of PKM1 in total transcript variants also significantly declined in tumors but the proportion of PKM2 did not change accordingly. Therefore, we conclude that the isoform switch of PKM1 does indeed occur, but it switches to other isoforms rather than PKM2. Considering the change in the expression levels of PKM1, PKM2 and the entire PKM gene, we propose that the upregulation of PKM2 is primarily due to elevated transcriptional levels of the entire PKM gene, instead of the isoform switch.
PMCID: PMC4349452  PMID: 25738776
25.  Haplotypes of RHO polymorphisms and susceptibility to age-related macular degeneration 
Objective: To investigate whether haplotypes of rhodopsin (RHO) polymorphisms including rs7984, rs2855552, rs2855557 and rs2410 were associated with age-related macular degeneration (AMD) risk in Chinese Han population. Methods: Genotypes of rs7984, rs2855552, rs2855557 and rs2410 were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases and 196 healthy controls. Then, the haplotypes were established with Haploview 4.2 software. And the effects of clinical charactersitics on the frequency of GTTG haplotype were also analyzed. Odds ratios (ORs) with 95% confidence interval (95% CI) were utilized to assess the relationship of haplotypes and genotypes of RHO polymorphisms with susceptibility to AMD. Results: Genotype distribution of all polymorphisms in control group were all in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). In the analysis, we found that mutant alleles of rs7984 and rs2855557 were both associated with increased risk of AMD. For genotype analysis, rs7984 AA and rs2855557AA, rs2410GG genotypes all could increase the risk for AMD (OR=1.905, 95% CI=1.143-3.174; OR=2.226, 95% CI=1.261-3.932; OR=2.073, 95% CI=1.105-3.888). However, rs2855552 showed no effects on the onset of AMD. Compared with GTTA, the haplotypes of GGTG, ATAA and GTTG were all related with AMD susceptibility. Further analysis suggested that age, hypertension and hyperlipidemia history play important roles in the frequency alteration of GTTG haplotype. Conclusion: RHO polymorphisms (rs7984, rs2855557 and rs2410) and haplotypes may confer remarkable susceptibility to AMD. Further investigation showed that gene and environmental factors may work together in the pathogenesis of AMD.
PMCID: PMC4440145  PMID: 26045836
Rhodopsin; age-related macular degeneration; haplotype; polymorphism

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