Zhu L.,Shanghai JiaoTong University |
Ren L.,Shanghai JiaoTong University |
Ren L.,The First Peoples Hospital of Lianyungang |
Chen Y.,Shanghai JiaoTong University |
And 3 more authors.
Journal of Cellular and Molecular Medicine | Year: 2015
During inflammation, high-mobility group box 1 in reduced all-thiol form (at-HMGB1) takes charge of chemoattractant activity, whereas only disulfide-HMGB1 (ds-HMGB1) has cytokine activity. Also as pro-angiogenic inducer, the role of HMGB1 in different redox states has never been defined in tumour angiogenesis. To verify which redox states of HMGB1 induces angiogenesis in colorectal carcinoma. To measure the expression of VEGF-A and angiogenic properties of the endothelial cells (ECs), at-HMGB1 or ds-HMGB1 was added to cell medium, further with their special inhibitors (DPH1.1 mAb and 2G7 mAb) and antibodies of corresponding receptors (RAGE Ab and TLR4 Ab). Also, a co-culture system and conditioned medium from tumour cells were applied to mimic tumour microenvironment. HMGB1 triggered VEGF-A secretion mainly through its disulfide form interacting with TLR4, while co-operation of at-HMGB1 and RAGE mediated migratory capacity of ECs. Functional inhibition of HMGB1 and its receptors abrogated HMGB1-induced angiogenic properties of ECs co-cultured with tumour cells. HMGB1 orchestrates the key events of tumour angiogenesis, migration of ECs and their induction to secrete VEGF-A, by adopting distinct redox states. © 2015 John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
PubMed | The First Peoples Hospital of Lianyungang and Shanghai JiaoTong University
Type: | Journal: Cell death & disease | Year: 2016
Body weight is a component of the mechanical theory of OA (osteoarthritis) pathogenesis. Obesity was also found to be a risk factor for digital OA involving non-weight-bearing joints, which suggested that metabolism influences the occurrence and progression of OA. The metabolic origin of OA has been partially attributed to the involvement of adipokines, such as leptin, the levels of which are significantly and positively correlated with cartilage degeneration in OA patients. However, the mechanisms by which leptin-induced cartilage degeneration occurs are poorly understood. The discovery of chondrogenic progenitor cells (CPCs) opened up new opportunities for investigation. Investigating the effects of leptin on differentiation and proliferation in CPCs would increase our understanding of the roles played by leptin in the aetiology and development of OA. Here, CPCs were harvested using single-cell sorting from rat cartilage tissues to obtain mesenchymal stem-like cells, which possess clonogenicity, proliferation and stemness. High doses of leptin decreased the ability of the CPCs to migrate, inhibited their chondrogenic potential and increased their osteogenic potential, suggesting that leptin changes differentiation fates in CPCs. High doses of leptin induced cell cycle arrest and senescence in CPCs by activating the p53/p21 pathway and inhibiting the Sirt1 pathway. Inhibiting the Sirt1 pathway accelerated cartilage senescence in knockout (KO) mice. Activating the leptin pathway induced higher Ob-Rb expression and was significantly correlated with cartilage degeneration (lower levels of Coll-2) and tissue senescence (higher levels of p53/p21 and lower levels of Sirt1) in OA patients, suggesting that leptin-induced CPCs senescence contributes to the development of OA. Taken together, our results reveal new links between obesity and cartilage damage that are induced by leptin-mediated effects on cell behaviour and senescence.
Yan W.,Soochow University of China |
Yan W.,Taicang Center for Translational Bioinformatics |
Yan W.,The 100th Hospital of PLA |
Xu L.,Soochow University of China |
And 7 more authors.
Oncotarget | Year: 2015
Acute myeloid leukemia (AML) in children is a complex and heterogeneous disease. The identification of reliable and stable molecular biomarkers for diagnosis, especially early diagnosis, remains a significant therapeutic challenge. Aberrant microRNA expression could be used for cancer diagnosis and treatment selection. Here, we describe a novel bioinformatics model for the prediction of microRNA biomarkers for the diagnosis of paediatric AML based on computational functional analysis of the microRNA regulatory network substructure. microRNA-196b, microRNA-155 and microRNA-25 were identified as putative diagnostic biomarkers for pediatric AML. Further systematic analysis confirmed the association of the predicted microRNAs with the leukemogenesis of AML. In vitro q-PCR experiments showed that microRNA-155 is significantly overexpressed in children with AML and microRNA-196b is significantly overexpressed in subgroups M4-M5 of the French-American-British classification system. These results suggest that microRNA-155 is a potential diagnostic biomarker for all subgroups of paediatric AML, whereas microRNA-196b is specific for subgroups M4-M5.
Sun S.,Fudan University |
Liu N.-H.,The First Peoples Hospital Of Lianyungang |
Huang S.-Q.,Fudan University
Journal of Clinical Monitoring and Computing | Year: 2015
To investigate the role of cerebral oxygen saturation (ScO2) for prediction of hypotension after spinal anesthesia for caesarean section. Forty-five parturients undergoing elective caesarean section under spinal anesthesia were selected. Blood pressure, heart rate and pulse oxygen saturation before and after anesthesia were recorded, and the association between changes in ScO2 before and after anesthesia with hypotension after spinal anesthesia was explored. Hypotension occurred in 32 parturients after spinal anesthesia. The decrease in ScO2 after spinal anesthesia in parturients with hypotension was larger than in parturients without hypotension (P < 0.05). The duration from the intrathecal injection to 5 % decrease in ScO2 was shorter than that from the intrathecal injection to the occurrence of hypotension (P < 0.05). The mean time from 5 % decrease in ScO2 to hypotension was 38 s. The area under the receiver operation characteristic curve was 0.83 for decrease in ScO2 for prediction of hypotension (P < 0.05), and the optimal threshold value was 4.5 %. The sensitivity, specificity, positive predictive value and negative predictive value of 4.5 % decrease in ScO2 for prediction of hypotension were 0.75, 0.78, 0.92 and 0.47, respectively. The decrease in ScO2 after spinal anesthesia is associated with hypotension after spinal anesthesia for cesarean section, and may be a clinically useful predictor. © 2015 Springer Science+Business Media New York
Luan H.-F.,The First Peoples Hospital of Lianyungang |
Zhao Z.-B.,The First Peoples Hospital of Lianyungang |
Zhao Q.-H.,Bengbu Medical College |
Zhu P.,The First Peoples Hospital of Lianyungang |
And 2 more authors.
Brazilian Journal of Medical and Biological Research | Year: 2012
The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 μM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dtmax) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.
PubMed | The First Peoples Hospital of Lianyungang, Nanjing University of Technology and Harbin Medical University
Type: Journal Article | Journal: The international journal of biochemistry & cell biology | Year: 2016
Transforming growth factor-beta1 (TGF1) and Phosphatase and Tensin homolog deleted on chromosome ten (PTEN) are involved in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. In previous studies, we have shown that TGF1 and PTEN play an important role in the progression of pulmonary vascular remodeling induced by pulmonary artery smooth muscle cells (PASMCs). However, the mechanisms involved in the activation of PASMCs between TGF1 and PTEN pathways remain unknown. We found that pulmonary vascular walls in hypoxic pulmonary arterial hypertension (PAH) rats were thicker than the vessels from normal rats in vivo. Substantially higher levels of TGF1 and significant loss of PTEN expression were observed in the lungs of PAH rats when compared with normoxia. Meanwhile, AKT, a downstream proliferative signaling protein of the PTEN antagonist PI3K, was markedly activated in the lungs of PAH rats. In vitro studies using PASMCs showed that TGF1 increased cell proliferation in PTEN-dependent manner. Moreover, we found that TGF1 enhanced cell survival, up-regulated the expression of Bcl-2 and procaspase-3, decreased the number of TUNEL-positive cells and caspase-3 expression in PASMCs under serum-deprived (SD) condition via PI3K/AKT pathway. The results further establish that TGF1 promoted PAH by decreasing PTEN expression and increasing PI3K/AKT activation in the lung. In conclusion, TGF1 mediated PTEN inactivation and resistance to apoptosis seems to be key mediators of lung vascular remodeling associated with PAH. These findings further clarify molecular mechanisms that support targeting PTEN/AKT signaling pathway to attenuate pathogenic derangements in PAH.
PubMed | The Affiliated Huaian Hospital of Xuzhou Medical University, Jiangsu Huaian Maternity and Children Hospital, the Fourth Peoples Hospital of Huaian, Nanjing Medical University and 2 more.
Type: | Journal: Molecular therapy. Nucleic acids | Year: 2017
Owing to its easy-to-use and multiplexing nature, the genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease 9) is revolutionizing many areas of medical research and one of the most amazing areas is its gene therapy potentials. Previous explorations into the therapeutic potentials of CRISPR-Cas9 were mainly conducted in vitro or in animal germlines, the translatability of which, however, is either limited (to tissues with adult stem cells amenable to culture and manipulation) or currently impermissible (due to ethic concerns). Recently, important progresses have been made on this regard. Several studies have demonstrated the ability of CRISPR-Cas9 for in vivo gene therapy in adult rodent models of human genetic diseases delivered by methods that are potentially translatable to human use. Although these recent advances represent a significant step forward to the eventual application of CRISPR-Cas9 to the clinic, there are still many hurdles to overcome, such as the off-target effects of CRISPR-Cas9, efficacy of homology-directed repair, fitness of edited cells, immunogenicity of therapeutic CRISPR-Cas9 components, as well as efficiency, specificity, and translatability of in vivo delivery methods. In this article, we introduce the mechanisms and merits of CRISPR-Cas9 in genome editing, briefly retrospect the applications of CRISPR-Cas9 in gene therapy explorations and highlight recent advances, later we discuss in detail the challenges lying ahead in the way of its translatability, propose possible solutions, and future research directions.
PubMed | Jiangsu University, The First Peoples Hospital of Lianyungang and Ningbo Medical Center Lihuili Eastern Hosipital
Type: | Journal: Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy | Year: 2017
The aim of this study is to assess the long-term clinical and radiological outcomes between minimally invasive (MIS) and conventional transforaminal lumbar interbody fusion (TLIF) in treating one-segment lumbar disc herniation (LDH).One-hundred and six patients treated by MIS-TLIF (50 cases) or conventional TLIF (56 cases) were included. Perioperative results were evaluated. Clinical outcomes were compared preoperatively and postoperatively. Radiologic parameters were based on a comparison of preoperative and three-year postoperative lumbar lordosis, segmental lordosis, sacral slope, the cross-sectional area of the paraspinal muscle and fusion rates.MIS TILF had significantly less blood, shorter operation time, mean return to work time and lower intramuscular pressure compared with the conventional group during the operation. VAS scores for lower back pain and ODI in MIS-TLIF were significantly decreased. The mean cross-sectional area of the paraspinal muscle was significantly decreased after surgery in the conventional TLIF group and no significant intragroup differences were established in the MIS-TLIF group. No significant differences were found in fusion rate, lumbar lordosis, segmental lordosis and sacral slope.Both MIS and conventional TLIF were beneficial for patients with LDH. However, MIS-TLIF manifests a great improvement in perioperative outcomes, low back pain, disability and preventing paraspinal muscle atrophy during the follow-up period observation.
Zhang L.,Jiangsu University |
Zhang L.,the First Peoples Hospital of Lianyungang
Oncogene | Year: 2014
SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein levels in human gastric cancer tissues, and SALL4 level was highly correlated with lymph node metastasis. Enforced expression of SALL4 enhanced the proliferation and migration of human gastric cancer cells, whereas knockdown of SALL4 by siRNA led to the opposite effects. In addition, SALL4 overexpression promoted the growth and metastasis of gastric xenograft tumor in vivo. SALL4 overexpression induced epithelial-mesenchymal transition (EMT) in gastric cancer cells, with increased expression of Twist1, N-cadherin and decreased expression of E-cadherin. Moreover, SALL4 promoted the acquirement of stemness in gastric cancer cells through the induction of Bmi-1 and Lin28B. Taken together, our findings indicate that SALL4 has oncogenic roles in gastric cancer through the modulation of EMT and cell stemness, suggesting SALL4 as a novel target for human gastric cancer diagnosis and therapy.