Publications by authors named "Yi-Xin Chen"

71 Publications

Schisandrol B promotes liver enlargement via activation of PXR and YAP pathways in mice.

Phytomedicine 2021 Apr 17;84:153520. Epub 2021 Feb 17.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Background: Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown.

Purpose: This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly.

Methods: Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence.

Results: SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice.

Conclusion: These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153520DOI Listing
April 2021

Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer.

Acta Pharmacol Sin 2021 Feb 15. Epub 2021 Feb 15.

Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.

PARP inhibitors are a group of inhibitors targeting poly(ADP-ribose) polymerases (PARP1 or PARP2) involved in DNA repair and transcriptional regulation, which may induce synthetic lethality in BRCAness tumors. Systematic analyzes of genomic sequencing in prostate cancer show that ~10%-19% of patients with primary prostate cancer have inactivated DNA repair genes, with a notably higher proportion of 23%-27% in patients with metastatic castration-resistant prostate cancer (mCRPC). These characteristic genomic alterations confer possible vulnerability to PARP inhibitors in patients with mCRPC who benefit only modestly from other therapies. However, only a small proportion of patients with mCRPC shows sensitivity to PARP inhibitors, and these sensitive patients cannot be fully identified by existing response prediction biomarkers. In this review, we provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.
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http://dx.doi.org/10.1038/s41401-020-00604-1DOI Listing
February 2021

A novel model of constrictive pericarditis associated with myocardial fibrosis in rats.

Clin Exp Pharmacol Physiol 2021 Apr 21;48(4):563-574. Epub 2020 Dec 21.

Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.

An efficient animal model is fundamental for studies on the underlying mechanisms of constrictive pericarditis (CP). A novel CP rat model was established by pericardial injection composing of lipopolysaccharides (LPS) and talcum powder without thoracotomy. Pathological changes were confirmed by histological staining. E-flow Doppler of mitral valve, tissue Doppler E' in the medial mitral annular (E' ) and the lateral mitral annular (E' ) were measured to assess ventricular filling function. Circumferential, longitudinal, and radial strains (SC, SL and SR) and the respective strain rates (SrC, SrL and SrR) were analyzed in interventricular septum (IVS) and left ventricular free wall (LVFW). Rat cardiac fibroblasts (CFs) were treated with LPS. The activation of transforming growth factor β1 (TGF-β1) was confirmed by Q-PCR and western blot assays. Thickening of pericardium and fibrosis in pericardium and subepicardial myocardium were showed in the model group. Diastolic dysfunction in the CP group was indicated by decreased E' and E' /E' , increased E/E' , decreased E of SrC and SrL, increased A and decreased E/A of SrC, SrL and SrR. Systolic dysfunction was indicated by decreased SC and SL in CP rats. The levels of TGF-β1, p-Smad2/3, α-smooth muscle actin (α-SMA), and collagen-I/III (COL-I/III) were increased in the CP group. The increased TGF-β1 that induced by LPS activated and phosphorylated Smad2/3 resulting in the secretion of α-SMA and COL-I/III. This model is of vital importance in studying the pathogenesis of CP.
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http://dx.doi.org/10.1111/1440-1681.13449DOI Listing
April 2021

Plasma Fibrinogen as a Diagnostic Marker of Infection in Patients with Nonunions.

Infect Drug Resist 2020 4;13:4003-4008. Epub 2020 Nov 4.

Department of Orthopedics, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.

Background: The timely and accurate diagnosis of infected nonunion is challenging, and there is a need for more efficient biomarkers. Previous studies have shown that fibrinogen plays an important role in mediating inflammation in bacterial infections and, therefore, could be a valuable biomarker for infected nonunion. The purpose of this study was to evaluate and compare the performance of plasma fibrinogen and other traditional blood markers for the diagnosis of infected nonunion.

Materials And Methods: We retrospectively studied 146 patients who underwent surgery for primary nonunion between January 2018 and January 2020. The patients were divided into those with infected nonunion (n = 55) and those with aseptic nonunion (n = 91). The preoperatively analyzed parameters were plasma fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood cell (WBC) count. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of the biomarkers, and Youden's index was calculated to determine their optimal cut-off values.

Results: The plasma fibrinogen values were significantly higher (p < 0.001) in the patients with infected nonunion than in those with aseptic nonunion. ROC curve analysis showed that plasma fibrinogen had a high value of area under the curve (0.816), which indicated that it had good diagnostic ability. Further, at the optimal threshold value of 2.75 g/L, plasma fibrinogen had the highest sensitivity (78.2%; 95% CI = 64.6-87.8) and good specificity (82.4%; 95% CI, 72.7-89.3).

Conclusion: In comparison to the traditional markers of infection, plasma fibrinogen showed good diagnostic ability for the detection of infected nonunion. It may have potential as a practical and cost-efficient biomarker for the diagnosis of infected nonunion.
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http://dx.doi.org/10.2147/IDR.S269719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649214PMC
November 2020

Outcomes of Femoral Neck Fractures Treated with Cannulated Internal Fixation in Elderly Patients: A Long-Term Follow-Up Study.

Orthop Surg 2020 Jun 28;12(3):809-818. Epub 2020 May 28.

Orthopedics Department, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Objectives: To evaluate the long-term efficacy of cannulated internal fixation in patients who sustain femoral neck fracture (FNF) and risk factors influencing the outcomes.

Methods: This retrospective study analyzed data from 73 elderly patients aged ≥60 years old, hospitalized for FNF and treated with cannulated internal fixation between August 2008 and July 2016. The inclusion criteria were: (i) patients aged ≥60 years; (ii) patients with recent femoral neck fracture, with times of injury ranging from 12-72 h; and (iii) patients who underwent Garden II-IV closed reduction and internal fixation. Patients were classified based on the Garden fracture type and Pauwels angle. Clinical data and radiographs before and after the surgery were collected. Subsequently, surgery was performed with the patient in supine position, under general or lumbar epidural anesthesia. Closed reduction was performed until satisfactory fracture reduction quality was achieved. The weight of all included patients were <75 kg, and thus, minimal internal fixation was performed. The ischemic necrosis of the femoral head was diagnosed by considering the symptoms, signs, and radiological findings. Harris hip scores were used to evaluate postoperative recovery of hip function. Furthermore, relationships between Garden fracture type and necrosis rate of the femoral head, Pauwels angle and necrosis rate of the femoral head, Garden fracture type and Harris hip score, and age and Harris hip score were analyzed.

Results: The mean duration of surgery was 1 ± 0.17 h and blood loss for all the patients was approximately 15 mL. The included patients were followed up for 13-128 months, with an average follow-up of 61 months. Among the included 73 patients, 65 (89.0%) exhibited satisfactory union, seven (9.6%) had femoral head necrosis, and one (1.4%) had nonunion. For seven patients with femoral head necrosis, there were two, two, and three patients classified as Garden IV, Garden III, and Garden II, respectively, and two and five patients classified as Pauwels II and Pauwels III, respectively. Among the seven cases, four underwent hip replacement. Garden fracture type was not significantly associated with femoral head necrosis (χ = 0.44, P > 0.05) or Harris score (χ = 1.43, P > 0.05). Patients with Pauwels I (0%) and II (4.3%) fractures exhibited a significantly lower necrosis rate than those with Pauwels III fractures (41.7%) (P < 0.05).

Conclusions: Cannulated internal fixation was more suitable for older Chinese patients with Pauwels I/II fractures than those with Pauwels III fractures.
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http://dx.doi.org/10.1111/os.12683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307235PMC
June 2020

Targeted bile acids and gut microbiome profiles reveal the hepato-protective effect of WZ tablet (Schisandra sphenanthera extract) against LCA-induced cholestasis.

Chin J Nat Med 2020 Mar;18(3):211-218

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510000, China. Electronic address:

Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera (Wuzhi tablet, WZ) can significantly protect against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice, partially due to the activation of PXR pathway and promotion of liver regeneration. However, the effect of WZ on the bile acids profile and gut microbiome in cholestastic mice remain unknown. In this study, the effect of WZ against LCA-induced liver injury was evaluated and its effect on the bile acids metabolome and gut microbiome profiles in cholestastic mice was further investigated. Targeted metabolomics analysis was performed to examine the change of bile acids in the serum, liver, intestine and feces. The change of intestinal flora were detected by the genomics method. Targeted metabolomics analysis revealed that WZ enhanced the excretion of bile acids from serum and liver to intestine and feces. Genomics analysis of gut microbiome showed that WZ can reverse LCA-induced gut microbiome disorder to the normal level. In conclusion, WZ protects against LCA-induced cholestastic liver injury by reversing abnormal bile acids profiles and alteration of gut microbiome.
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http://dx.doi.org/10.1016/S1875-5364(20)30023-6DOI Listing
March 2020

What Is the Most Reliable Classification System to Assess Tibial Pilon Fractures?

J Foot Ankle Surg 2020 Jan - Feb;59(1):48-52

Surgeon, Department of Orthopaedics, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

The aim of this study was to assess inter- and intraobserver agreement of the traditional systems (Ruedi-Allgower, AO [Arbeitsgemeinschaft für Osteosynthesefragen], and Topliss) and the newly proposed Leonetti classification system of pilon fractures. We studied all patients at our center who underwent pilon fracture surgery over a 2-year period: 68 patients (70 legs) were included. Four observers independently classified each pilon fracture according to the Ruedi-Allgower, AO, Topliss, and Leonetti systems by evaluating radiographs and computed tomography images on 2 occasions. The inter- and intraobserver agreements were calculated using the Fleiss kappa test. Interobserver reliability was good for AO types (A, B, and C) and Ruedi-Allgower (κ = 0.71 and 0.61, respectively), whereas the interobserver reliability was moderate for AO groups (A1, A2, A3, B1, B2, B3, C1, C2, and C3), Topliss families, Topliss subfamilies, Leonetti types, and Leonetti subtypes. Intraobserver reproducibility was excellent for the Ruedi-Allgower classification, AO types, and Topliss families and good for AO groups, Topliss subfamilies, and Leonetti types and subtypes. Ruedi-Allgower and AO classification systems are the most reliable among those currently used for pilon fractures, but with lower agreement at the AO group level. The use of Topliss and Leonetti classification systems is not recommended because of less favorable results.
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http://dx.doi.org/10.1053/j.jfas.2019.07.002DOI Listing
July 2020

Pulsed electromagnetic field (PEMF): A potential adjuvant treatment for infected nonunion.

Med Hypotheses 2020 Mar 18;136:109506. Epub 2019 Nov 18.

Department of Orthopaedics, Drum Tower Hospital, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, China. Electronic address:

Infected nonunion is still a challenge for orthopaedic surgeons. The goal of treatment is to eliminate infection and achieve bone union. Surgery is the only effective method currently. However, it is invasive and the results are still unsatisfactory. Therefore, seeking a noninvasive and effective method to resolve infected nonunion is necessary. Pulsed electromagnetic field (PEMF) has been used for the treatment of nonunion for more than 40 years. PEMF could promote bone formation at tissue, cell and subcellular levels. Furthermore, our study showed that PEMF had bactericidal effect. The hypothesis we proposed herein is that PEMF may be an adjuvant treatment for infected nonunion by controlling infection and inducing bone formation.
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http://dx.doi.org/10.1016/j.mehy.2019.109506DOI Listing
March 2020

Effect of Induced Membrane Formation Followed by Polymethylmethacrylate Implantation on Diabetic Foot Ulcer Healing When Revascularization Is Not Feasible.

J Diabetes Res 2019 19;2019:2429136. Epub 2019 Nov 19.

Department of Endocrinology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, #3 E. Qingchun Rd, Hangzhou 310016, China.

No study has investigated the role of induced membrane (IM) formation in treating diabetic foot ulcer (DFU). This retrospective study was aimed (1) at evaluating the potential role of a two-staged surgical approach, comprising polymethylmethacrylate (PMMA) implantation and IM formation, in the treatment of DFU and (2) at comparing the results of those with routine wound debridement in patients with DFUs and nonrevascularized peripheral arterial disease (PAD). Fifty patients with infected DFUs who were not candidates for vascular interventions were enrolled between February 2016 and April 2018 and assigned to the PMMA group ( = 28) and conventional group ( = 22). The healing rate, major amputation rate, duration of healing, frequency of debridement procedures, patient survival rate, and reulceration of DFUs were determined. The Mann-Whitney test, independent sample -test, and or Fisher exact test were used in statistical analysis. Overall clinical outcomes were statistically different between the groups ( = -2.495, = 0.013). In the PMMA group, 16 patients (57.1%) with intact IM formation achieved ulceration healing at 13.1 ± 3.7 weeks with a mean number of debridements of 1.3 ± 0.4, which were significantly different compared to those values in 5 patients of the conventional group (22.7%, = 0.014; healing duration: 26.4 ± 7.8 weeks, = 0.016; mean number of debridements: 3.6 ± 0.5, ≤ 0.001). At a mean 16.8 ± 4.3-month follow-up, patient survival rates were 92.9% and 68.2% in the PMMA and conventional groups, respectively ( = 0.032). The major amputation rate and reulceration of DFUs were similar between the groups. The two-staged surgical approach is an available, effective modality for improving healing of DFUs. This study provides preliminary information of IM formation followed by PMMA implantation in the management of DFUs in PAD when revascularization is not feasible.
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http://dx.doi.org/10.1155/2019/2429136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885796PMC
June 2020

Validation of Single Centre Pre-Mobile Atrial Fibrillation Apps for Continuous Monitoring of Atrial Fibrillation in a Real-World Setting: Pilot Cohort Study.

J Med Internet Res 2019 12 3;21(12):e14909. Epub 2019 Dec 3.

Department of Cardiology, Chinese PLA General Hospital, Beijing, China.

Background: Atrial fibrillation is the most common recurrent arrhythmia in clinical practice, with most clinical events occurring outside the hospital. Low detection and nonadherence to guidelines are the primary obstacles to atrial fibrillation management. Photoplethysmography is a novel technology developed for atrial fibrillation screening. However, there has been limited validation of photoplethysmography-based smart devices for the detection of atrial fibrillation and its underlying clinical factors impacting detection.

Objective: This study aimed to explore the feasibility of photoplethysmography-based smart devices for the detection of atrial fibrillation in real-world settings.

Methods: Subjects aged ≥18 years (n=361) were recruited from September 14 to October 16, 2018, for screening of atrial fibrillation with active measurement, initiated by the users, using photoplethysmography-based smart wearable devices (ie, a smart band or smart watches). Of these, 200 subjects were also automatically and periodically monitored for 14 days with a smart band. The baseline diagnosis of "suspected" atrial fibrillation was confirmed by electrocardiogram and physical examination. The sensitivity and accuracy of photoplethysmography-based smart devices for monitoring atrial fibrillation were evaluated.

Results: A total of 2353 active measurement signals and 23,864 periodic measurement signals were recorded. Eleven subjects were confirmed to have persistent atrial fibrillation, and 20 were confirmed to have paroxysmal atrial fibrillation. Smart devices demonstrated >91% predictive ability for atrial fibrillation. The sensitivity and specificity of devices in detecting atrial fibrillation among active recording of the 361 subjects were 100% and about 99%, respectively. For subjects with persistent atrial fibrillation, 127 (97.0%) active measurements and 2240 (99.2%) periodic measurements were identified as atrial fibrillation by the algorithm. For subjects with paroxysmal atrial fibrillation, 36 (17%) active measurements and 717 (19.8%) periodic measurements were identified as atrial fibrillation by the algorithm. All persistent atrial fibrillation cases could be detected as "atrial fibrillation episodes" by the photoplethysmography algorithm on the first monitoring day, while 14 (70%) patients with paroxysmal atrial fibrillation demonstrated "atrial fibrillation episodes" within the first 6 days. The average time to detect paroxysmal atrial fibrillation was 2 days (interquartile range: 1.25-5.75) by active measurement and 1 day (interquartile range: 1.00-2.00) by periodic measurement (P=.10). The first detection time of atrial fibrillation burden of <50% per 24 hours was 4 days by active measurement and 2 days by periodic measurementThe first detection time of atrial fibrillation burden of >50% per 24 hours was 1 day for both active and periodic measurements (active measurement: P=.02, periodic measurement: P=.03).

Conclusions: Photoplethysmography-based smart devices demonstrated good atrial fibrillation predictive ability in both active and periodic measurements. However, atrial fibrillation type could impact detection, resulting in increased monitoring time.

Trial Registration: Chinese Clinical Trial Registry of the International Clinical Trials Registry Platform of the World Health Organization ChiCTR-OOC-17014138; http://www.chictr.org.cn/showprojen.aspx?proj=24191.
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http://dx.doi.org/10.2196/14909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918204PMC
December 2019

Microwaves increase the effectiveness of systemic antibiotic treatment in acute bone infection: experimental study in a rat model.

J Orthop Surg Res 2019 Sep 6;14(1):286. Epub 2019 Sep 6.

Department of Orthopaedics, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, China.

Background: Osteomyelitis is a challenge for orthopedic surgeons due to its protracted treatment process. Microwaves (MWs) can increase blood perfusion due to their thermal effect. Furthermore, MWs demonstrated significant bactericidal effects in vitro. In the present study, we assumed that the application of a 2450-MHz-frequency MW together with systemic antibiotic treatment would provide synergy for the treatment of acute osteomyelitis.

Methods: The medullary cavity of the right tibia was inoculated with 10 CFU of methicillin-sensitive Staphylococcus aureus (MSSA-ATCC 29213) in 40 rats, and the rats were randomly divided into four groups according to treatment: group I, saline (control); group II, saline + MW therapy; group III, systemic cefuroxime; and group IV, systemic cefuroxime + MW therapy. MWs were applied for 20 min per day to the infected limbs, and all rats were sacrificed on the 7th day. The severity of tibial osteomyelitis was assessed by quantitative culture analysis.

Results: Bacterial counts in groups III and IV were significantly reduced compared with those in the control (p = 0.001 and < 0.001, respectively). Furthermore, significant differences were detected between groups III and IV (p = 0.033). However, the difference between groups I and II was nonsignificant (p = 0.287).

Conclusion: Our experimental model suggests that MW therapy provides a significant synergy for systemic antibiotic treatment. However, further clinical trials are required to safely use this treatment modality in patients.
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http://dx.doi.org/10.1186/s13018-019-1342-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729059PMC
September 2019

Circular RNA screening from EIF3a in lung cancer.

Cancer Med 2019 08 13;8(9):4159-4168. Epub 2019 Jun 13.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China.

Eukaryotic initiation factor 3 (EIF3) is one of the largest and most complex translation initiation factors, which consists of 13 subunits named eukaryotic translation initiation factor 3 subunit A (EIF3a) to EIF3m. EIF3a is the largest subunit of EIF3. Previous studies suggested that EIF3a is a housekeeping gene, recent results have found that EIF3a is closely related to the tumorigenesis and drug resistance. Circular RNAs (circRNAs) derived from biologically important gene can play an important role in gene regulation. However, the mechanism underlying circRNAs' biological functions is not well understood yet. In this work, we screened 31 EIF3a-derived circRNAs, in which two circEIF3as were identified to be correlated with cisplatin drug sensitivity in lung cancer. Two circEIF3as were found involved in RNA-binding proteins-mediated biological processes and may be related to translational regulation according to bioinformatics analyses. CircEIF3as, the transcriptional initiation factor EIF3a transcribed circRNAs, are associated with both drug sensitivity and translation regulation. These findings mean that they may have a functional synergy effect with EIF3a or be valuable therapeutic targets for treatment like EIF3a. This is the first study that exploits circRNAs screening from EIF3a in lung cancer, our findings provide a novel perspective on the function of EIF3a and circEIF3as in lung cancer.
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http://dx.doi.org/10.1002/cam4.2338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675731PMC
August 2019

A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice.

Gut 2020 02 29;69(2):343-354. Epub 2019 Mar 29.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health & School of Life Science, Xiamen University, Xiamen, China.

Objective: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.

Methods: A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.

Results: Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.

Conclusions: The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.
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http://dx.doi.org/10.1136/gutjnl-2018-317725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984059PMC
February 2020

Thermodynamics in the Universe Described by the Emergence of Space and the Energy Balance Relation.

Entropy (Basel) 2019 Feb 11;21(2). Epub 2019 Feb 11.

School of Physics and Electronic Science, Zunyi Normal University, Zunyi 563006, China.

It has previously been shown that it is more common to describe the evolution of the universe based on the emergence of space and the energy balance relation. Here we investigate the thermodynamic properties of the universe described by such a model. We show that the first law of thermodynamics and the generalized second law of thermodynamics (GSLT) are both satisfied and the weak energy condition are also fulfilled for two typical examples. Finally, we examine the physical consistency for the present model. The results show that there exists a good thermodynamic description for such a universe.
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http://dx.doi.org/10.3390/e21020167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514649PMC
February 2019

Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-κB pathway.

Cancer Lett 2019 04 23;447:33-40. Epub 2019 Jan 23.

Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, China. Electronic address:

Based on analysis of Epstein-Barr virus (EBV) BART microRNA expression profiles, we previously reported that EBV-encoded miR-BART13 is upregulated in nasopharyngeal carcinoma (NPC) plasma specimens. However, the effects and molecular mechanisms of miR-BART13 in NPC remain largely unknown. We found that miR-BART13 was significantly upregulated in NPC tissue specimens. Ectopic expression of miR-BART13 promoted NPC cell proliferation, epithelial mesenchymal transition, and metastasis in vitro, and facilitated xenograft tumor growth and lung metastasis in vivo. Molecularly, NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), a negative regulator of the NF-κB signaling, was identified to be a direct target of miR-BART13 in NPC cells, and NKIRAS2 mRNA and protein expression was inversely correlated with miR-BART13 in NPC tissues, respecitvely. Furthermore, the NF-κB signaling pathway was activated by miR-BART13. By rescued experiments, reconstitution of NKIRAS2 expression abrogated all the phenotypes upregulated by miR-BART13, and attenuated activity of NF-κB signaling pathway activated by miR-BART13 in NPC cells. Our findings indicated the newly identified miR-BART13/NKIRAS2/NF-κB signaling axis may provide further insights into better understanding of NPC initiation and development, and targeting of this pathway could be further studied as a therapeutic strategy for NPC patients.
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http://dx.doi.org/10.1016/j.canlet.2019.01.022DOI Listing
April 2019

Coating the plate with antibiotic cement to treat early infection after fracture fixation with retention of the implants: a technical note.

BMC Musculoskelet Disord 2018 Oct 10;19(1):360. Epub 2018 Oct 10.

Department of Orthopaedics, The First People's Hospital of Zhangjiagang, No. 68 Jiyangxi Road, Zhangjiagang, China.

Background: Local antibiotic therapy has gained increasing attraction in the prevention and treatment of fracture infection. However, no reports have used local antibiotic therapy in the management of early infection after fracture fixation with retention of implants.

Methods: The present surgical technique report the use of antibiotic impregnated bone cement in the management of early infection after fracture fixation. Initially, the fractures were fixed with plates. The average time from initial procedure to debridement was15 days (range 9 to 25 days). The infections were treated with irrigation, debridement, and retention of the implant. The lateral surface of the plates was coated with antibiotic cement and the bone defect was filled with antibiotic cement spacer after thorough debridement.

Results: Ten patients underwent this technique. The mean follow-up was 2.0 years (range 6 months to 4 years). The bone union rate was 100%, and the average time to bone healing was5.5 months.There was recurrence of infection in one patient before bone healing, but the implants were left in place until bone healed, and the infection was eradicated after implant removal.

Conclusion: Coating the plate with antibiotic cement is a simple technique which may play a role in the management of early infection after fracture fixation.
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http://dx.doi.org/10.1186/s12891-018-2285-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178260PMC
October 2018

Social functions of relaxed open-mouth display in golden snub-nosed monkeys ().

Zool Res 2019 Mar 13;40(2):113-120. Epub 2018 Aug 13.

College of Life Science and Technology, Central South University of Forestry and Technology, Changsha Hunan 410004, China.

Relaxed open-mouth display serves important social functions in relation to submission, reconciliation, affiliation and reassurance among non-human primate societies; however, quantitative evidence on this behavior remains insufficient among multi-level social groups. From July to November 2016, we examined four potential functions of the relaxed open-mouth display during pairwise, intra-unit social interactions among 18 free-ranging adult and sub-adult golden snub-nosed monkeys () who belonged to three one-male, multi-female units (OMU) at Dalongtan, Shennongjia National Park, China. Results showed that: compared with no relaxed open-mouth display, (1) the occurrence of displacement by a dominant individual approaching a subordinate was lower and the distance of the subordinate to the approaching dominant was shorter when the subordinate showed open-mouth display; (2) relaxed open-mouth display reduced the probability of continued attack for victims of aggression and allowed victims to achieve closer proximity to the aggressor during post-conflict periods; (3) relaxed open-mouth display by dominant individuals allowed them to achieve closer proximity to subordinates; and (4) the exchange of relaxed open-mouth display had a greater impact on the outcome of interactions than one individual alone giving this signal. These findings suggest that relaxed open-mouth display serves important functions regarding submission, reconciliation, affiliation and reassurance in coordinating social interactions within OMUs in golden snub-nosed monkeys.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2018.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378559PMC
March 2019

Functional miRNA variants affect lung cancer susceptibility and platinum-based chemotherapy response.

J Thorac Dis 2018 Jun;10(6):3329-3340

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China.

Background: Platinum-based chemotherapy is widely used as the first-line treatment of lung cancer. MicroRNAs have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in miRNA involved in miRNA biogenesis and structural alteration may affect miRNA expression. In this study, we aimed to investigate the association of functional miRNA variants with the lung cancer susceptibility and platinum-based chemotherapy response.

Methods: Nine genetic polymorphisms in miR-605, 146a, 149, 196a-2, 27a, 499, 30c-1, 5197 and let-7a-2 were selected with comprehensive collection strategy and genotyped by MALDI-TOF mass spectrometry in a total of 215 health control and 507 lung cancer patients (386 patients received at least two consecutive cycles of platinum-based chemotherapy).

Results: We found that an allele carriers of miR-146a rs2910164 (P=0.022, OR=1.315) and C allele carriers of miR-149 rs71428439 (P=0.042, OR=1.372) performance a high risk of lung cancer. Mir-30c-1 rs928508 (P=0.005, in recessive model) and let-7a-2 rs629367 (P=0.030 and P=0.021, in additive and dominant models, respectively) showed strong relationship with lung cancer risk in age under 57 years. The rs11614913 (miR-196a-2) C allele or rs9280508 (miR-30c-1) G allele carriers shown more sensitive to platinum both in additive (P=0.010, P=0.022, respectively) and dominant models (P=0.001, P=0.018, respectively).

Conclusions: These findings suggested that SNPs rs71428439 (miR-149), rs2910164 (miR-146a), rs928508 (mir-30c-1) and rs629367 (let-7a-2) were associated with the lung cancer prevalence, polymorphisms of rs11614913 (miR-196a-2) and rs9280508 (miR-30c-1) significantly influenced the patients' response to platinum-based chemotherapy, which may serve as potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.
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http://dx.doi.org/10.21037/jtd.2018.05.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051820PMC
June 2018

Effects of spirodiclofen on life history traits and population growth of a spider mite predator Oligota flavicornis (Coleoptera: Staphyllinidae) based on the age-stage two-sex life table theory.

Pest Manag Sci 2019 Mar 15;75(3):639-647. Epub 2018 Sep 15.

Institute of Plant Protection, Fujian Academy of Agriculture Sciences, Fuzhou, China.

Background: Knowledge of the compatibility between spirodiclofen and the predator Oligota flavicornis is an important aspect for the management of spider mites.

Results: We used the age-stage, two-sex life table to assess the effects of spirodiclofen on the life history traits and population growth of O. flavicornis. At the maximum recommended concentration (60 mg a.i. L ) and also at twice the maximum recommended dosage (120 mg a.i. L ), the preadult stages of O. flavicornis were significantly lengthened, while the adult longevity and fecundity decreased significantly. The finite rate (λ), intrinsic rate of increase (r), and net reproduction rate (R ) decreased, while the mean generation time (T) was longer after both the 60 and 120 mg a.i. L treatments than it was in the control and 30 mg a.i. L treatments. Life expectancy and reproductive value were higher in the control and 30 mg a.i. L treatment than in the 60 and 120 mg a.i. L treatments; the two higher concentrations were detrimental to the development of O. flavicornis.

Conclusion: A proper combination of the O. flavicornis and spirodiclofen to control the spider mite, while avoiding the side effect of spirodiclofen, could be achieved based on the knowledge of life tables. © 2018 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5158DOI Listing
March 2019

Long noncoding RNA promoted apoptosis and increased cisplatin chemosensitivity via regulating the hnRNP-U-GADD45A axis in lung squamous cell carcinoma.

Oncotarget 2017 Nov 27;8(57):97476-97489. Epub 2017 Oct 27.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.

Chemotherapeutic insensitivity remains one of the major obstacles in clinical treatment of lung squamous cell carcinoma (LSCC). Recently, increasing evidence has suggested that long non-coding RNAs (lncRNAs) promote tumorigenesis in many cancer types. However, the potential biological roles and regulatory mechanisms of lncRNAs in response to cisplatin treatment are poorly understood. Here, we found that lncRNA (surfactant associated 1, pseudogene), highly expressed in lung, was down-regulated in LSCC tissues and could be induced upon cisplatin treatment in LSCC cells. Elevated induced apoptosis and enhanced the sensitivity to cisplatin of LSCC cells. We further identified that hnRNP-U (heterogeneous nuclear ribonucleoprotein U) was down-regulated in LSCCs and positively correlated with patients' poor prognosis as well as SFTA1P. Mechanistic studies revealed that could up-regulate hnRNP-U expression. In addition, we identified that hnRNP-U enhanced cisplatin-induced apoptosis through up-regulation of GADD45A, high expression of which was correlated with good prognosis in LSCC patients. Our findings demonstrated that might serve as a useful biomarker for LSCC diagnosis and a predictor for cisplatin chemotherapy response in patients with LSCC.
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http://dx.doi.org/10.18632/oncotarget.22138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722577PMC
November 2017

Temperature-Dependent Development of Oligota flavicornis (Coleoptera: Staphylinidae) Preying on Tetranychus cinnabarinus (Acarina: Tetranychidae).

J Econ Entomol 2017 12;110(6):2334-2341

Institute of Plant Protection, Fujian Academy of Agriculture Sciences, China.

The effect of nine constant temperatures on developmental time of Oligota flavicornis (Boisduval and Lacordaire) preying on Tetranychus cinnabarinus (Boisduval) (Acari: Tetranychidae) eggs was determined under laboratory conditions of 75 ± 5% RH and a 16:8 (L:D) h photoperiod. O. flavicornis survival rates were highest between 18 and 30°C, although O. flavicornis eggs developed successfully to adults at 12-32°C, and the developmental durations to adult at the seven temperatures (12, 15, 18, 20, 25, 30, and 32°C) were 114.41, 51.66, 33.45, 23.21, 13.43, 11.54, and 17.18 d, respectively. Two linear and seven nonlinear models (Logan-6 and Logan-10, Taylor, Lactin-1 and Lactin-2, and Brière-1 and Brière-2) were fit to the developmental rates of the immature predatory stages to estimate the thermal constant (K) and critical temperatures. The lower temperature threshold (T0) and K for the immature stages using the common linear model were 9.96°C and 225.73 degree-days and Ikemoto-Takai linear model were 11.01°C and 167.14 degree-days, respectively. The upper temperature threshold values estimated by the Logan-6 and Lactin-1 models were both 34.86°C. The T0 values estimated by the Brière-1 and Brière-2 models were 10.67 and 9.32°C for all immature stages, respectively, and the estimated optimal temperature according to the Brière-2 model was 29.59°C. Therefore, the two linear models and Brière-2 model estimates approximated the actual relationship between the temperature and developmental rate of immature O. flavicornis.
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http://dx.doi.org/10.1093/jee/tox259DOI Listing
December 2017

Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice.

Sci Rep 2017 10 31;7(1):14707. Epub 2017 Oct 31.

Multidisciplinary Research Center, Shantou University, Shantou, 515063, Guangdong, China.

The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee's index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, β-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more β-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.
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http://dx.doi.org/10.1038/s41598-017-14408-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666019PMC
October 2017

Metastasis-associated in colon cancer 1: A promising biomarker for the metastasis and prognosis of colorectal cancer.

Oncol Lett 2017 Oct 26;14(4):3899-3908. Epub 2017 Jul 26.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Colorectal cancer (CRC) is the fourth most frequent type of malignancy in the world. Metastasis accounts for >90% mortalities in patients with CRC. The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as a novel biomarker for the prediction of metastasis and disease prognosis, particularly for patients with early-stage disease. Previous clinical studies demonstrated that MACC1 expression and polymorphisms in CRC tissues were indicators of metastasis, and that circulating transcripts in plasma were also significantly associated with the survival of patients. The present review describes the use of MACC1 beyond its utility in the clinic. By elucidating the upstream and downstream signal pathways of MACC1, the well-known mechanisms of MACC1-mediated cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) are summarized, as well as the potential signaling pathways. Furthermore, the underlying mechanisms by which the overexpression of MACC1 causes cisplatin resistance are emphasized.
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http://dx.doi.org/10.3892/ol.2017.6670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605967PMC
October 2017

Outcomes of cement beads and cement spacers in the treatment of bone defects associated with post-traumatic osteomyelitis.

BMC Musculoskelet Disord 2017 Jun 12;18(1):256. Epub 2017 Jun 12.

Department of Orthopaedics, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, No. 321 Zhongshan Road, Nanjing, China.

Background: Cement spacers (Masquelet technique) have traditionally been used for the treatment of segmental bone defects. However, no reports have used cement spacers for the treatment of small/partial segmental bone defects associated with osteomyelitis and compared the outcomes with cement beads.

Methods: We retrospectively analysed 40 patients with post-traumatic osteomyelitis of the tibia who underwent treatment, which was performed in two stages. In the first stage, thorough debridement was performed, and bone defects were filled with either antibiotic-impregnated cement beads (bead group, 18 patients) or spacers (spacer group, 22 patients). In the second stage, the cement beads or spacers were removed (for the spacer group, the induced membrane formed by the spacer was preserved) and the bone defects were filled with cancellous autografts.

Results: All patients in the bead group had small/partial segmental bone defects after debridement, while 3 patients in the spacer group had large/segmental bone defects. The mean volume of bone defects of the spacer group (40.4 cm) was significantly larger than that of the bead group (32.4 cm). The infection control rate (88.9%,16/18 vs 90.9%, 20/22), bone healing time (8.5 months vs 7.5 months) and complication rates (22.2%, 4/18 vs 27.2%, 6/22) were comparable between bead group and spacer group.

Conclusion: The results of this study suggest that cement spacers may have an infection control rate comparable to cement beads in the treatment of bone defects associated with post-traumatic osteomyelitis. Furthermore, cement spacers could be used for the reconstruction of small/partial segmental bone defects as well as for large/segmental bone defects, whereas cement beads were not suitable for the reconstruction of large/segmental bone defects.
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http://dx.doi.org/10.1186/s12891-017-1614-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468979PMC
June 2017

Comparison of the direct and indirect reduction techniques during the surgical management of posterior malleolar fractures.

BMC Musculoskelet Disord 2017 03 14;18(1):109. Epub 2017 Mar 14.

Department of Orthopaedics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, China.

Background: The optimal method for the reduction and fixation of posterior malleolar fracture (PMF) remains inconclusive. Currently, both of the indirect and direct reduction techniques are widely used. We aimed to compare the reduction quality and clinical outcome of posterior malleolar fracture managed with the direct reduction technique through posterolateral approach or the indirect reduction technique using ligamentotaxis.

Methods: Patients with a PMF involving over 25% of the articular surface were recruited and assigned to the direct reduction (DR) group or the indirect reduction (IR) group. Following reduction and fixation of the fracture, the quality of fracture reduction was evaluated in post-operative CT images. Clinical and radiological follow-ups were performed at 6 weeks, 3 months, 6 months, 12 months, and then at 6 month-intervals postoperatively. Functional outcome (AOFAS score), ankle range of motion, and Visual Analog Scale (VAS) were evaluated at the last follow-up. Statistical differences were compared between the DR and IR groups considering the patient demographics, quality of fracture reduction, AOFAS score, and VAS.

Results: Totally 116 patients were included, wherein 64 cases were assigned to the DR group and 52 cases were assigned to the IR group. The quality of fracture reduction was significant higher in the DR group (P = 0.038). In the patients who completed a minimum of 12 months' follow-up, a median AOFAS score of 87 was recorded in the DR group, which was significantly higher than that recorded in the IR group (a median score of 80). The ankle range of motion was slightly better in the DR group, with the mean dorsiflexion restriction recorded to be 5.2° and 6.1° in the DR and IR group respectively (P = 0.331). Similar VAS score was observed in the two groups (P = 0.419).

Conclusions: The direct reduction technique through a posterolateral approach provide better quality of fracture reduction and functional outcome in the management of PMF over 25% of articular surface, as compared with the indirect reduction technique using ligamentotaxis.

Trial Registration: NCT02801474 (retrospectively registered, June 2016, ClinicalTrails.gov).
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http://dx.doi.org/10.1186/s12891-017-1475-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351253PMC
March 2017

Association between well-characterized lung cancer lncRNA polymorphisms and platinum-based chemotherapy toxicity in Chinese patients with lung cancer.

Acta Pharmacol Sin 2017 Apr 6;38(4):581-590. Epub 2017 Mar 6.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.

Platinum-based chemotherapy is the standard first-line treatment for most lung cancer patients. However, the toxicity induced by platinum-based chemotherapy greatly impedes its clinical use. Previous studies showed that long non-coding RNAs (lncRNAs) with over 200 nucleotides in length affect drug response and toxicity. In the present study, we investigated the association of well-characterized lung cancer lncRNA polymorphisms with platinum-based chemotherapy toxicity in Chinese patients with lung cancer. A total of 467 lung cancer patients treated with platinum-based chemotherapy for at least two cycles were recruited. We primarily focused on gastrointestinal and hematological toxicities. A total of 14 potentially functional polymorphisms within 8 lncRNAs (HOTTIP, HOTAIT, H19, ANRIL, CCAT2, MALAT1, MEG3, and POLR2E) were genotyped. Unconditional logistical regression analysis was conducted to assess the associations. Gene-gene and gene-environment interactions were identified using the software generalized multifactor dimensionality reduction (GMDR). ANRIL rs1333049 was associated with severe overall toxicity in an additive model (adjusted OR=0.723, 95% CI=0.541-0.965, P=0.028). ANRIL rs1333049 was also associated with severe gastrointestinal toxicity in both the additive (adjusted OR=0.690, 95% CI=0.489-0.974, P=0.035) and dominant (adjusted OR=0.558, 95% CI=0.335-0.931, P=0.025) models. MEG3 rs116907618 was associated with severe gastrointestinal toxicity in an additive model (adjusted OR=1.717, 95% CI=1.007-2.927, P=0.047). GMDR identified the three-factor interaction model of POLR2E rs3787016-HOTTIP rs3807598-chemotherapy regimen as the best predictive model for hematological toxicity. In conclusion, ANRIL and MEG3 genetic polymorphisms are associated with severe platinum toxicity and could be considered as biomarkers for pretreatment evaluation in Chinese patients with lung cancer.
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http://dx.doi.org/10.1038/aps.2016.164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386317PMC
April 2017

Genome-scale analysis identifies GJB2 and ERO1LB as prognosis markers in patients with pancreatic cancer.

Oncotarget 2017 Mar;8(13):21281-21289

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.

Pancreatic cancer is a complex and heterogeneous disease with the etiology largely unknown. The deadly nature of pancreatic cancer, with an extremely low 5-year survival rate, renders urgent a better understanding of the molecular events underlying it. The aim of this study is to investigate the gene expression module of pancreatic adenocarcinoma and to identify differentially expressed genes (DEGs) with prognostic potentials. Transcriptome microarray data of five GEO datasets (GSE15471, GSE16515, GSE18670, GSE32676, GSE71989), including 117 primary tumor samples and 73 normal pancreatic tissue samples, were utilized to identify DEGs. The five sets of DEGs had an overlapping subset consisting of 98 genes (90 up-regulated and 8 down-regulated), which were probably common to pancreatic cancer. Gene ontology (GO) analysis of the 98 DEGs showed that cell cycle and cell adhesion were the major enriched processes, and extracellular matrix (ECM)-receptor interaction and p53 signaling pathway were the most enriched pathways according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Elevated expression of gap junction protein beta 2 (GJB2) and reduced endoplasmic reticulum oxidoreductase 1-like beta (ERO1LB) expression were validated in an independent cohort. Kaplan-Meier survival analysis revealed that GJB2 and ERO1LB levels were significantly associated with the overall survival of pancreatic cancer patients. GJB2 and ERO1LB are implicated in pancreatic cancer progression and can be used to predict patient survival. Therapeutic strategies targeting GJB2 and facilitating ERO1LB expression may deserve evaluation to improve prognosis of pancreatic cancer patients.
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http://dx.doi.org/10.18632/oncotarget.15068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400583PMC
March 2017

Circulating Betatrophin Levels and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

PLoS One 2017 12;12(1):e0169941. Epub 2017 Jan 12.

Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Objective: The association between circulating betatrophin levels and gestational diabetes mellitus (GDM) is controversial. The aim of our study was to systematically review available literature linking betatrophin to GDM for a comprehensive understanding of the relationship between circulating betatrophin levels and GDM in human.

Methods: PubMed, The Cochrane Library, Medline and CNKI were searched for studies published up to August 2016. Manual searches of references of the relevant original studies were conducted. Pooled estimates were measured using the fixed or random effect model. Overall effect was reported in a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0.

Results: Of 25 references reviewed, 8 studies met our inclusion criteria and contributed to meta-analysis. All the studies were used to evaluate the relationship between betatrophin levels in blood and GDM. Betatrophin levels were significantly elevated in women with GDM compared with those without GDM (SMD = 1.05; 95% CI: 0.41-1.68, P = 0.001). This evidence was more consistent among women with betatrophin blood draw during the third trimester (SMD = 1.3, 95% CI: 1-1.61, P < 0.001) and for women BMI ≥ 28 kg/m2 (SMD = 1.53, 95% CI: 1.30-1.75, P < 0.001).

Conclusions: The evidences from this meta-analysis indicated that the levels of circulating betatrophin were significantly elevated among women with GDM compared with women with normal glucose tolerance, especially with BMI ≥ 28 kg/m2 and in the third trimester.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169941PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231180PMC
August 2017

MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway.

Sci Rep 2017 01 11;7:40384. Epub 2017 Jan 11.

Departments of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.

Our previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3'UTR of eIF3a. In addition, the overexpression of miRNA-488 inhibited cell migration and invasion in A549 cells, and also inhibited cell proliferation, cell cycle progression by elevated P27 expression. Compared to the parental cell line, A549/cisplatin (DDP) resistant cells exhibited a higher level of miRNA-488. Moreover, we found that miRNA-488 was associated with cisplatin resistance in three NSCLC cells (A549, H1299 and SK-MES-1). The mechanism of miRNA-488 induced cisplatin resistance was that miRNA-488 activated nucleotide excision repair (NER) by increasing the expression of Replication Protein A (RPA) 14 and Xeroderma pigmentosum group C (XPC). In conclusion, our results demonstrated that miRNA-488 is a tumor suppressor miRNA that acts by targeting eIF3a. Moreover, miRNA-488 also participates in eIF3a mediated cisplatin resistance in NSCLC cells.
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http://dx.doi.org/10.1038/srep40384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225486PMC
January 2017

Prognostic and predictive values of CDK1 and MAD2L1 in lung adenocarcinoma.

Oncotarget 2016 Dec;7(51):85235-85243

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.

Lung cancer remains as the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. This study aims to investigate biomarkers associated with cancer progression and prognosis of LUAD. We integrated expression profiles of 668 lung cancer patients in five datasets from the Gene Expression Omnibus (GEO) and identified a panel of differentially expressed genes (DEGs). Function enrichment analysis highlighted that these genes were closely associated with the carcinogenesis of LUAD, such as cell cycle, ECM-receptor interaction and p53 signaling pathway. Cyclin-dependent kinase 1 (CDK1) and MAD2 mitotic arrest deficient-like 1 (MAD2L1), two critical mitotic checkpoint genes, were selected for further study. Elevated expression of CDK1 and MAD2L1 was validated in an independent LUAD cohort. Kaplan-Meier analysis revealed that CDK1 and MAD2L1 expression was negatively correlated with both overall survival (OS) and relapse-free survival (RFS). In conclusion, CDK1 and MAD2L1 were adverse prognostic biomarkers for LUAD whose increased expression could render patients with LUAD a high risk of cancer recurrence and poor survival, suggesting that they might be applied as potential targets for LUAD treatment.
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http://dx.doi.org/10.18632/oncotarget.13252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356732PMC
December 2016