Publications by authors named "Zhen-Zhen Zhang"

50 Publications

Clinical features of Chinese children with COVID-19 and other viral respiratory infections.

Pediatr Pulmonol 2021 Sep 24. Epub 2021 Sep 24.

Department of Infectious Diseases, National Clinical Research Center for Child Health and Disorders, The Children's Hospital of Chongqing Medical University, Chongqing, China.

Objective: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI).

Methods: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed.

Results: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1β, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups.

Conclusion: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.
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http://dx.doi.org/10.1002/ppul.25700DOI Listing
September 2021

SIRT7 restricts HBV transcription and replication through catalyzing desuccinylation of histone H3 associated with cccDNA minichromosome.

Clin Sci (Lond) 2021 Jun;135(12):1505-1522

The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.

Chronic hepatitis B virus (HBV) infection is a significant public health burden worldwide. HBV covalently closed circular DNA (cccDNA) organized as a minichromosome in nucleus is responsible for viral persistence and is the key obstacle for a cure of chronic hepatitis B (CHB). Recent studies suggest cccDNA transcription is epigenetically regulated by histone modifications, especially histone acetylation and methylation. In the present study, we identified transcriptionally active histone succinylation (H3K122succ) as a new histone modification on cccDNA minichromosome by using cccDNA ChIP-Seq approach. Silent mating type information regulation 2 homolog 7 (SIRT7), as an NAD+-dependent histone desuccinylase, could bind to cccDNA through interaction with HBV core protein where it catalyzed histone 3 lysine 122 (H3K122) desuccinylation. Moreover, SIRT7 acts cooperatively with histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1) and SET domain containing 2 (SETD2) to induce silencing of HBV transcription through modulation of chromatin structure. Our data improved the understanding of histone modifications of the cccDNA minichromosome, thus transcriptional silencing of cccDNA may represent a novel antiviral strategy for the prevention or treatment of HBV infection.
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http://dx.doi.org/10.1042/CS20210392DOI Listing
June 2021

Destination Joint Spacers: A Similar Infection-Relief Rate But Higher Complication Rate Compared with Two-Stage Revision.

Orthop Surg 2021 May 25;13(3):884-891. Epub 2021 Mar 25.

Department of Orthopaedic Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Objective: To evaluated the clinical outcomes of periprosthetic joint infection (PJI) patients with destination joint spacer compared with that of two-stage revision.

Methods: From January 2006 to December 2017, data of PJI patients who underwent implantation with antibiotic-impregnated cement spacers in our center due to chronic PJI were collected retrospectively. The diagnosis of PJI was based on the American Society for Musculoskeletal Infection (MSIS) criteria for PJI. One of the following must be met for diagnosis of PJI: a sinus tract communicating with the prosthesis; a pathogenis isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; four of the following six criteria exist: (i) elevated ESR and CRP; (ii) elevate dsynovial fluid white blood cell (WBC) count; (iii) elevated synovial fluid neutrophil percentage (PMN%); (iv) presence of purulence in the affected joint; (v) isolation of a microorganism in one periprosthetic tissue or fluid culture; (vi) more than five neutrophilsper high-power fields in five high-power fields observed from histological analysis of periprosthetic tissue at ×400 magnification. Age, sex, body mass index (BMI), and laboratory test results were recorded. All patients were followed up regularly after surgery, the infection-relief rates were recorded, Harris hip score (HHS) and knee society score (KSS) were used for functional evaluation, a Doppler ultrasonography of the lower limb veins was performed for complication evaluation. The infection-relief rates and complications were compared between destination joint spacer group and two-stage revision group.

Results: A total of 62 patients who were diagnosed with chronic PJI were enrolled, with an age of 65.13 ± 9.94 (39-88) years. There were 21 cases in the destination joint spacer group and 41 cases in the temporary spacer group, namely, two-stage revision group (reimplantation of prosthesis after infection relief). The Charlson comorbidity index (CCI) in the destination joint spacer group was higher than that in the temporary spacer group, and this might be the primary reason for joint spacer retainment. As for infection-relief rate, there were three cases of recurrent infection (14.29%) in the destination joint spacer group and four cases of recurrent infection (9.76%) in the two-stage revision group, there were no significant differences with regard to infection-relief rate. Moreover, there two patients who suffered from spacer fractures, three cases of dislocation, one case of a periarticular fracture, and three cases of deep venous thrombosis in destination joint spacer group, while there was only one case of periprosthetic hip joint fracture, one case of dislocation, and one patient suffered from deep venous thrombosis of the lower extremity in two-stage revision. The incidence of complications in the destination joint spacer group was higher than that of two-stage revision.

Conclusions: In summary, the present work showed that a destination joint spacer might be provided as a last resort for certain PJI patients due to similar infection-relief rate compared with two-stage revision.
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http://dx.doi.org/10.1111/os.12996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126900PMC
May 2021

[Effect of pertussis vaccination on clinical manifestations of infants and young children with pertussis].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Feb;23(2):138-142

Department of Infection, Children's Hospital, Chongqing Medical University/Ministry of Education Key Laboratory of Child Development and Disorders/National Clinical Research Center for Child Health and Disorders(Chongqing)/China International Science and Technology Cooperation Base of Child Development and Critical Disorders/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.

Objective: To study the effect of pertussis vaccination on the clinical manifestations of infants and young children with pertussis.

Methods: A retrospective analysis was performed to investigate the differences in clinical manifestations and peripheral blood cell levels between pertussis children with different pertussis vaccination status.

Results: A total of 1 083 children with pertussisat at age of < 3 years were enrolled, with 551 children in the unvaccinated group and 532 in the vaccinated group. Of all the children, 392 had an age of onset of < 3 months (372 were unvaccinated and 20 were vaccinated) and 691 children had an age of onset of ≥ 3 months (179 were unvaccinated and 512 were vaccinated). Compared with the vaccinated group, the unvaccinated group had a longer length of hospital stay and a higher incidence rate of respiratory failure ( < 0.05). Among the children ≥ 3 months of age, the incidence of severe pneumonia in the unvaccinated group was higher than that in the vaccinated group ( < 0.05), and the incidence of severe pneumonia was the highest in the unvaccinated group (10.6%) and the lowest in the 4-dose vaccination group (1.2%). Among the 101 patients with severe pneumonia, 80 (79.2%) were observed in the unvaccinated group and only 21 (20.8%) in the four different doses vaccination groups. For the children with an age of onset of ≥ 3 months, the unvaccinated group had higher white blood cell count, absolute value of lymphocytes, and platelet count than the vaccinated group ( < 0.05).

Conclusions: Pertussis vaccination can reduce the incidence of severe pneumonia and respiratory failure and alleviate the severity of respiratory complications in infants and young children with pertussis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921537PMC
February 2021

Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx.

J Hepatol 2021 03 25;74(3):522-534. Epub 2020 Sep 25.

The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China. Electronic address:

Background & Aims: Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional silencing of cccDNA is a crucial curative strategy that may be achieved by targeting the viral protein HBx.

Methods: We screened 2,000 small-molecule compounds for their ability to inhibit HiBiT-tagged HBx (HiBiT-HBx) expression by using a HiBiT lytic detection system. The antiviral activity of a candidate compound and underlying mechanism of its effect on cccDNA transcription were evaluated in HBV-infected cells and a humanised liver mouse model.

Results: Dicoumarol, an inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1), significantly reduced HBx expression. Moreover, dicoumarol showed potent antiviral activity against HBV RNAs, HBV DNA, HBsAg and HBc protein in HBV-infected cells and a humanised liver mouse model. Mechanistic studies demonstrated that endogenous NQO1 binds to and protects HBx protein from 20S proteasome-mediated degradation. NQO1 knockdown or dicoumarol treatment significantly reduced the recruitment of HBx to cccDNA and inhibited the transcriptional activity of cccDNA, which was associated with the establishment of a repressive chromatin state. The absence of HBx markedly blocked the antiviral effect induced by NQO1 knockdown or dicoumarol treatment in HBV-infected cells.

Conclusions: Herein, we report on a novel small molecule that targets HBx to combat chronic HBV infection; we also reveal that NQO1 has a role in HBV replication through the regulation of HBx protein stability.

Lay Summary: Current antiviral therapies for hepatitis B are not curative because of their inability to eliminate covalently closed circular DNA (cccDNA), which persists in the nuclei of infected cells. HBV X (HBx) protein has an important role in regulating cccDNA transcription. Thus, targeting HBx to silence cccDNA transcription could be an important curative strategy. We identified that the small molecule dicoumarol could block cccDNA transcription by promoting HBx degradation; this is a promising therapeutic strategy for the treatment of chronic hepatitis B.
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http://dx.doi.org/10.1016/j.jhep.2020.09.019DOI Listing
March 2021

-Symmetric 1,2-Diphenylethane-1,2-diamine-Derived Primary-Tertiary Diamine-Catalyzed Asymmetric Mannich Addition of Cyclic -Sulfonyl Trifluoromethylated Ketimines.

J Org Chem 2020 09 25;85(17):11331-11339. Epub 2020 Aug 25.

Provincial Key Laboratory of Natural Medicine and Immuno-Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, P. R. China.

A simple chiral primary-tertiary diamine derived from -symmetric 1,2-diphenylethane-1,2-diamine as the organocatalyst in combination with the trifluoroacetic acid additive for the asymmetric Mannich reaction of cyclic sulfonyl trifluoromethylated ketimines and methyl ketones afforded the desired product with high enantioselectivity (73-96% ee). The reactions proceeded well for a variety of different substituted cyclic -sulfonyl trifluoromethyl ketimines and various alkyl methyl ketones, providing access to diverse enantioenriched benzo-fused cyclic sulfamidate -heterocycles bearing a trifluoromethylated α-tetrasubstituted carbon stereocenter. This study also investigated the diastereoselective reduction of the carbonyl group and ring cleavage reduction of the sulfamidate group of the corresponding Mannich product.
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http://dx.doi.org/10.1021/acs.joc.0c01446DOI Listing
September 2020

The clinical and immunological features of pediatric COVID-19 patients in China.

Genes Dis 2020 Dec 14;7(4):535-541. Epub 2020 Apr 14.

The Key Laboratory of Molecular Biology of Infectious Diseases Designated By the Chinese Ministry of Education, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults ( < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3-4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.
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http://dx.doi.org/10.1016/j.gendis.2020.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194810PMC
December 2020

Overexpression of ubiquitin-conjugating enzyme E2 L3 in hepatocellular carcinoma potentiates apoptosis evasion by inhibiting the GSK3β/p65 pathway.

Cancer Lett 2020 07 5;481:1-14. Epub 2020 Apr 5.

Department of Infectious Disease, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

UBE2L3 is a ubiquitin-conjugating protein belonging to the E2 family that consists of 153 amino acid residues. In this study, we found that UBE2L3 was generally upregulated in clinical HCC samples compared to non-tumour samples and that there was a strong association between high UBE2L3 expression and tumour size, clinical grade and prognosis in HCC patients. UBE2L3 depletion inhibited the proliferation and induced the apoptosis of HCC cells. At the molecular level, we observed that UBE2L3 depletion enhanced the protein stability of GSK3β, thus promoting the expression and activation of GSK3β. Subsequently, activated GSK3β phosphorylated p65 and promoted its nuclear translocation to increase the expression of target genes, including PUMA, Bax, Bim, Bad, and Bid. In vivo, knockout of UBE2L3 in HCC cells inhibited tumour growth in orthotopic liver injection nude mouse models. Moreover, inhibition of p65 or GSK3β significantly restored the effects induced by UBE2L3 knockout in HCC. Together, this study reveals the stimulatory effect of UBE2L3 on HCC cell proliferation, suggesting that UBE2L3 may be an important pro-tumorigenic factor in liver carcinogenesis and a potential therapeutic target of HCC.
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http://dx.doi.org/10.1016/j.canlet.2020.03.028DOI Listing
July 2020

Enantioselective (3+2) cycloaddition via N-heterocyclic carbene-catalyzed addition of homoenolates to cyclic N-sulfonyl trifluoromethylated ketimines: synthesis of fused N-heterocycle γ-lactams.

Chem Commun (Camb) 2020 Feb;56(10):1553-1556

Henan Key Laboratory of Polyoxometalate Chemistry, Provincial Key Laboratory of Natural Medicine and Immuno-Engineering, and College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, P. R. China.

An enantioselective (3+2) cycloaddition of enals and cyclic N-sulfonyl trifluoromethyl ketimines via N-heterocyclic carbene-catalyzed homoenolate addition is described. This reaction can efficiently construct fused N-heterocycle γ-lactams bearing two adjacent chiral centers with >20 : 1 dr and 94-99% ee, with one chiral center as a trifluoromethylated α-tetrasubstituted carbon stereocenter.
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http://dx.doi.org/10.1039/c9cc09269bDOI Listing
February 2020

PIN1 Inhibition Sensitizes Chemotherapy in Gastric Cancer Cells by Targeting Stem Cell-like Traits and Multiple Biomarkers.

Mol Cancer Ther 2020 03 26;19(3):906-919. Epub 2019 Dec 26.

Division of Translational Therapeutics, Department of Medicine and Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Gastric cancer is the third leading cause of cancer-related death worldwide. Diffuse type gastric cancer has the worst prognosis due to notorious resistance to chemotherapy and enrichment of cancer stem-like cells (CSC) associated with the epithelial-to-mesenchymal transition (EMT). The unique proline isomerase PIN1 is a common regulator of oncogenic signaling networks and is important for gastric cancer development. However, little is known about its roles in CSCs and drug resistance in gastric cancer. In this article, we demonstrate that PIN1 overexpression is closely correlated with advanced tumor stages, poor chemo-response and shorter recurrence-free survival in diffuse type gastric cancer in human patients. Furthermore, shRNA-mediated genetic or all- retinoic acid-mediated pharmaceutical inhibition of PIN1 in multiple human gastric cancer cells potently suppresses the EMT, cell migration and invasion, and lung metastasis. Moreover, PIN1 genetic or pharmaceutical inhibition potently eliminates gastric CSCs and suppresses their self-renewal and tumorigenicity and Consistent with these phenotypes, are that PIN1 biochemically targets multiple signaling molecules and biomarkers in EMT and CSCs and that genetic and pharmaceutical PIN1 inhibition functionally and drastically enhances the sensitivity of gastric cancer to multiple chemotherapy drugs and These results demonstrate that PIN1 inhibition sensitizes chemotherapy in gastric cancer cells by targeting CSCs, and suggest that PIN1 inhibitors may be used to overcome drug resistance in gastric cancer.
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http://dx.doi.org/10.1158/1535-7163.MCT-19-0656DOI Listing
March 2020

Somatic gene mutation signatures predict cancer type and prognosis in multiple cancers with pan-cancer 1000 gene panel.

Cancer Lett 2020 02 23;470:181-190. Epub 2019 Nov 23.

Department of Hepatobiliary Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Electronic address:

Most cancers are caused by somatic mutations. Some common mutations in the same cancer type can form a "signature" to specifically predict the prognosis or to distinguish it from other cancers. In this study, 710 somatic cell mutations were identified in 142 cases, including digestive, lung and urogenital cancers, and the digestive cancers were further divided into liver, stomach, intestinal, esophageal and cardia cancer. The above mutations were located in 166 genes. In addition, a group of high-frequency mutation genes with specific characteristics were screened to form predictive signatures for each cancer. Verification using TCGA suggested that the signatures could predict the stages, progression-free survival, and overall survival of digestive, intestinal, and liver cancers (P < 0.05). The validation cases further confirmed the predictive role of digestive and liver cancers signatures in diagnosis and prognosis. Overall, this study established predictive signatures for different cancer systems and their subtypes. These findings enable a better understanding in cancer genome, and contribute to the personalized diagnosis and treatment.
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http://dx.doi.org/10.1016/j.canlet.2019.11.022DOI Listing
February 2020

Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy.

Exp Eye Res 2020 01 21;190:107886. Epub 2019 Nov 21.

Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, PR China. Electronic address:

Diabetic retinopathy (DR) is a microvascular complication of diabetes and one of the most common causes of blindness in active stage. This study is performed to explore the effects of microRNA-21 (miR-21) on retinal vascular endothelial cell (RVEC) viability and angiogenesis in rats with DR via the phosphatidylinositiol 3-kinase/protein kinase B (PI3K/Akt)/vascular endothelial growth factor (VEGF) signaling pathway by binding to phosphatase and tensin homolog (PTEN). Sprague Dawley (SD) rats were used for establishment of DR models. Target relationship between miR-21 and PTEN was assessed by bioinformatics prediction in combination with dual-luciferase reporter gene assay. Identification of expression of miR-21, PTEN and PI3K/Akt/VEGF signaling pathway-related genes in the retinal tissues was then conducted. In order to assess the contributory role of miR-21 in DR, the RVECs were transfected with mimic or inhibitor of miR-21, or siRNA-PTEN, followed by the detection of expression of PTEN and PI3K/Akt/VEGF-related genes, as well as the measurement of cell viability, cell cycle and apoptosis. Increased expression of miR-21 and PI3K/Akt/VEGF related genes, along with a reduced expression of PTEN was observed in the retinal tissues of DR rats. PTEN was targeted and negatively regulated by miR-21, while the PI3K/Akt/VEGF signaling pathway was activated by miR-21. RVECs transfected with miR-21 inhibitor exhibited promoted viability and angiogenesis, and inhibited apoptosis. To conclude, our results indicated that miR-21 overexpression could potentially stimulate RVEC viability and angiogenesis in rats with DR through activation of the PI3K/Akt/VEGF signaling pathway via repressing PTEN expression, highlighting the potential of miR-21 as a target for DR treatment.
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http://dx.doi.org/10.1016/j.exer.2019.107886DOI Listing
January 2020

Decreased RIPK1 expression in chondrocytes alleviates osteoarthritis via the TRIF/MyD88-RIPK1-TRAF2 negative feedback loop.

Aging (Albany NY) 2019 10 11;11(19):8664-8680. Epub 2019 Oct 11.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Osteoarthritis (OA) is the most common degenerative joint disease and involves the loss of articular cartilage integrity, formation of articular osteophytes, remodeling of subchondral bone, and synovitis. Knockdown of receptor interacting serine/threonine kinase (RIPK) 1 leads to anti-inflammatory and anti-apoptotic effects. However, the involvement of RIPK1 in the pathogenesis of OA is unclear. Here, we evaluated the effect of RIPK1 on chondrocytes and elaborated the underlying molecular mechanism. Knockdown of RIPK1 protected chondrocytes against inflammation and apoptosis induced by interleukin (IL)-1β and . RIPK1 was required for myeloid differentiation primary response 88 (MyD88)- and TIR-domain-containing adapter-inducing interferon b (TRIF)-mediated production of matrix metalloproteinases (MMPs) in OA. Moreover, overexpression of RIPK1 promoted the expression of tumor necrosis factor receptor-associated factor 2 (TRAF2), which blocked the expression and phosphorylation of RIPK1. Upregulation of TRAF2 decreased the expression of TRIF, MyD88, and MMPs in chondrocytes. Furthermore, knockdown of RIPK1 blocked activation of the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling pathways. In summary, knockdown of RIPK1 alleviated OA in a manner mediated by the TRIF/MyD88-RIPK1-TRAF2 negative feedback loop and activation of the NF-κB and JNK signaling pathways.
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http://dx.doi.org/10.18632/aging.102354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814603PMC
October 2019

Association of hemoglobin with arterial stiffness evaluated by carotid-femoral pulse wave velocity among Chinese adults.

Chronic Dis Transl Med 2019 Jun 13;5(2):122-128. Epub 2018 Jul 13.

Department of Nephrology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, China.

Objective: Increased hemoglobin (Hb) levels are known to be associated with increased cardiovascular events and mortalities. Therefore, we assumed that high Hb levels were associated with arterial stiffness. Pulse wave velocity (PWV) is a simple and noninvasive method for measuring arterial stiffness to assess cardiovascular disease in general populations. Accordingly, we conducted a cross-sectional study to explore the association of Hb with PWV.

Methods: A total of 6642 adults aged 54.5 ± 11.2 years undergoing physical examinations were enrolled, 71.7% of whom were males. Arterial stiffness was evaluated by carotid-femoral PWV (cfPWV). Multivariable regression analyses were performed to determine the relationship between Hb and increased cfPWV.

Results: In this study, the mean Hb (per 10 g/L increase) was 144.7 ± 13.9 g/L, and the mean cfPWV was 15.1 ± 3.1 m/s. cfPWV was significantly higher in high hemoglobin groups ≥15.4 g/L (Quartile 4) than in the lowest hemoglobin group (Quartile 1 ≤ 13.6 g/L;  < 0.001). Multiple linear regression analysis revealed that Hb positively correlated with cfPWV ( = 0.16,  < 0.01). Univariate Logistic regression analysis revealed that Hb was associated with increased cfPWV, with an odd ratio () of 1.46 (95% confidence interval [], 1.39-1.54). After adjusting for potential confounders, Hb and the highest Hb quartile group were also independently associated with increased cfPWV, with a fully adjusted of 1.11 (95% , 1.02-1.20) and 1.45 (95% , 1.01-2.08), respectively.

Conclusion: This study demonstrated that Hb levels significantly correlate with increased cfPWV.
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http://dx.doi.org/10.1016/j.cdtm.2018.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656875PMC
June 2019

Cynanchum bungei Decne and its two related species for "Baishouwu": A review on traditional uses, phytochemistry, and pharmacological activities.

J Ethnopharmacol 2019 Oct 24;243:112110. Epub 2019 Jul 24.

Department of Pharmacognosy, School of Pharmacy, Navy Medical University, 325 Guohe Road, Shanghai, 200433, China. Electronic address:

Ethnopharmacological Relevance: Cynanchum bungei Decne. (CB) (Asclepiadaceae) and its two related species Cynanchum auriculatum Royle ex Wight. (CA) and Cynanchum wilfordii (Maxim.) Hemsl. (CW) are well known Chinese herbal medicines known by the name Baishouwu. Among them, CB has long been used for nourishing the kidney and liver, strengthening the bones and muscles, and regulating stomachache. However, to date, no comprehensive review on Baishouwu has been published.

Aim Of The Review: This review aims to provide a comprehensive summary on traditional uses, phytochemistry, pharmacology, and toxicology of the three herbal components of Baishouwu with the ultimate objective of providing a guide for future scientific and therapeutic potential use of Baishouwu.

Material And Methods: A literature search was undertaken on CB, CA and CW by analyzing the information from scientific databases (SciFinder, Pubmed, Elsevier, Google Scholar, Web of Science, and Baidu Scholar). Information was also gathered from local classic herbal literatures and conference papers on ethnopharmacology and the information provided in this review has been obtained from peer-reviewed papers.

Results: Comparative analysis of literature search indicate that ethnopharmacological use of CB was recorded in China, however, CA and CW have been used in China, Korea and Japan. To date, 151 chemical compounds have been isolated from these species, and the major chemical constituents have been revealed to be acetophenones, C-steroids, terpenoids, and alkaloids. These compounds and extracts have been proven to exhibit significant pharmacological activities, including anti-tumor, anti-inflammatory, immunomodulatory, hypolipidemic, anti-obesity, hepatoprotective, antifungal, antiviral, anti-depressant, vasodilating and estrogenic activities.

Conclusions: CB, CA and CW collectively known as Baishouwu are valuable medicinal herbs with multiple pharmacological activities. The traditional use for nourishing liver is closely associated with the hepatoprotective activity. The available literature performs that various of the activity of Baishouwu can be attributed to acetophenones and C-steroids. It is high time that more efforts should be focused on the underlying mechanisms of their beneficial bioactivities and the structure activity relationship of the constituents, as well as their potential synergistic and antagonistic effects. The proper toxicology evaluation is crucial to guarantee the safety, efficacy, and eligibility for medical use. Further research on the comprehensive evaluation of medicinal quality and the understanding of multi-target network pharmacology of Baishouwu is in great request.
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http://dx.doi.org/10.1016/j.jep.2019.112110DOI Listing
October 2019

MicroRNA-183 inhibition exerts suppressive effects on diabetic retinopathy by inactivating -mediated PI3K/Akt/VEGF signaling pathway.

Am J Physiol Endocrinol Metab 2019 06 5;316(6):E1050-E1060. Epub 2019 Mar 5.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , People's Republic of China.

Diabetic retinopathy (DR) is a serious diabetic complication caused by both environmental and genetic factors. Molecular mechanisms of DR may lead to the discovery of reliable prognostic indicators. The current study aimed to clarify the mechanism of microRNA-183 (miR-183) in DR in relation to the PI3K/Akt/VEGF signaling pathway. Microarray-based gene expression profiling of DR was used to identify the differentially expressed genes. Sprague-Dawley rats were used for the establishment of DR models, and then miR-183 was altered by mimic or inhibitor or was downregulated by siRNA to explore the regulatory mechanism of miR-183 in DR. Furthermore, the expression of miR-183, CD34, endothelial nitric oxide synthase (eNOS), and the PI3K/Akt/VEGF signaling pathway-related genes as well as reactive oxygen species (ROS) level was determined, and the relationship between miR-183 and was also verified. Cell growth, cell apoptosis, and angiogenesis were determined. Microarray analysis revealed the involvement of miR-183 in DR via the PI3K/Akt/VEGF signaling pathway by targeting . Upregulated miR-183 and downregulated were observed in retinal tissues of DR rats. miR-183 overexpression activated the PI3K/Akt/VEGF signaling pathway, upregulated CD34, eNOS, and ROS, and inhibited was confirmed as a target gene of miR-183. miR-183 overexpression or knockdown promoted cell growth and tube formation while it suppressed cell apoptosis of vascular endothelial cells in DR rats. In this study, we demonstrated that miR-183 silencing inhibiting cell growth and tube formation in vascular endothelial cells of DR rats via the PI3K/Akt/VEGF signaling pathway by upregulating .
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http://dx.doi.org/10.1152/ajpendo.00444.2018DOI Listing
June 2019

IL-17 produced by Th17 cells alleviates the severity of fungal keratitis by suppressing CX43 expression in corneal peripheral vascular endothelial cells.

Cell Cycle 2019 02 20;18(3):274-287. Epub 2019 Jan 20.

a Department of Ophthalmology , The First Affiliated Hospital of Dalian Medical University , Dalian , P. R. China.

Fungal keratitis is a relatively common ocular disease requiring positive medical management combined with surgical intervention. Interleukin-17 (IL-17) was reported to promote the activation and mobilization of neutrophile granulocyte to foci of inflammation. This study investigated the effect of IL-17 production from Th17 cells on the progression of fungal keratitis. A mouse model of fungal keratitis induced by Candida albicans was successfully constructed to detect infiltration of inflammatory cells in corneal tissues by hematoxylin-eosin (HE) staining and immunohistochemistry. Fungal load capacity of mouse cornea was also detected. The regulatory role of IL-17 in fungal keratitis with the involvement of CX43 was investigated with the relevant expression of inflammatory factors detected and activation of vascular endothelial cells assessed. Furthermore, in vivo experiment was also performed to confirm the role of CX43 in keratitis. Mice with fungal keratitis showed increased level of inflammatory cytokines and infiltration of inflammatory cells. Silencing IL-17 in Th17 cells and overexpressing CX43 could inhibit the activation of vascular endothelial cells. Besides, CX43 knockdown in vivo alleviated fungal keratitis in mice. The possible mechanism of the above findings could be IL-17 inhibiting the level of CX43 through the AKT signaling pathway. Taken together, IL-17 could inhibit the occurrence and development of fungal keratitis by suppressing CX43 expression through the AKT signaling pathway. Therefore, this study provides a potential target for the treatment of fungal keratitis.
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http://dx.doi.org/10.1080/15384101.2018.1556059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380429PMC
February 2019

Secondary metabolites from Antarctic marine-derived fungus Penicillium crustosum HDN153086.

Nat Prod Res 2019 Feb 30;33(3):414-419. Epub 2018 Mar 30.

a Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China , Qingdao , P. R. China.

A new polyene compound (1) and a new diketopiperazine (2), as well as three known compounds (3-5), were isolated from the Antarctic marine-derived fungus Penicillium crustosum HDN153086. The structures of 1-5 were deduced based on MS, NMR and TD-DFT calculations of specific ECD spectra. These compounds were evaluated for their cytotoxic activities against K562 cell line and only compound 2 exhibited cytotoxicity against K562 cell, with IC value of 12.7 μM.
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http://dx.doi.org/10.1080/14786419.2018.1455045DOI Listing
February 2019

Farnesol inhibits development of caries by augmenting oxygen sensitivity and suppressing virulence-associated gene expression inStreptococcus mutans.

J Biomed Res 2017 Jul;31(4):333-343

Jiangsu Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Streptococcus mutans is a primary etiological agent of dental caries. Farnesol, as a potential antimicrobial agent, inhibits the development ofS. mutans biofilm. In this study, we hypothesized that farnesol inhibits caries development in vitro and interferes with biofilm formation by regulating virulence-associated gene expression. The inhibitory effects of farnesol to S. mutans biofilms on enamel surfaces were investigated by determining micro-hardness and calcium measurements. Additionally, the morphological changes ofS. mutans biofilms were compared using field emission scanning electron microscopy and confocal laser scanning microscopy, and the vitality and oxygen sensitivity ofS. mutans biofilms were compared using MTT assays. To investigate the molecular mechanisms of farnesol's effects, expressions of possible target genesluxS, brpA, ffh, recA, nth, and smx were analyzed using reverse-transcription polymerase chain reaction (PCR) and quantitative PCR. Farnesol-treated groups exhibited significantly higher micro-hardness on the enamel surface and lower calcium concentration of the supernatants as compared to the-untreated control. Microscopy revealed that a thinner film with less extracellular matrix formed in the farnesol-treated groups. As compared to the-untreated control, farnesol inhibited biofilm formation by 26.4% with 500 µmol/L and by 37.1% with 1,000 µmol/L (P<0.05). Last, decreased transcription levels of luxS, brpA, ffh, recA, nth, and smx genes were expressed in farnesol-treated biofilms. In vitrofarnesol inhibits caries development and S. mutans biofilm formation. The regulation of luxS, brpA, ffh, recA, nth, and smx genes may contribute to the inhibitory effects of farnesol.
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http://dx.doi.org/10.7555/JBR.31.20150151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548994PMC
July 2017

LncRNA H19 regulates ID2 expression through competitive binding to hsa-miR-19a/b in acute myelocytic leukemia.

Mol Med Rep 2017 Sep 18;16(3):3687-3693. Epub 2017 Jul 18.

Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University‑The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, P.R. China.

Acute myelocytic leukemia (AML) is the most common type of acute leukemia. Long non‑coding RNAs (lncRNAs) serve an important role in regulating gene expression through chromatin modification, transcription and post‑transcriptional processing. LncRNA H19 was considered as an independent prognostic marker for patients with tumors. The expression of lncRNA H19 was identified to be significantly upregulated in bone marrow samples from patients with AML‑M2. Furthermore, it was demonstrated that the knockdown of lncRNA H19 resulted in increased expression of hsa‑microRNA (miR)‑19a/b and decreased expression of inhibitor of DNA binding 2 (ID2) in AML cells. The knockdown of lncRNA H19 inhibited the proliferation of AML cells in vitro, which could be partially reversed by ID2 overexpression. Furthermore, the results of the bioinformatic analysis revealed potential hsa‑miR‑19a/b‑3p binding sites in lncRNA H19 and ID2. Altogether, the results of the present study suggest that lncRNA H19 regulates the expression of ID2 through competitive binding to hsa‑miR‑19a and hsa‑miR‑19b, which may serve a role in AML cell proliferation.
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http://dx.doi.org/10.3892/mmr.2017.7029DOI Listing
September 2017

MicroRNA-200c plays an oncogenic role in nasopharyngeal carcinoma by targeting PTEN.

Tumour Biol 2017 May;39(5):1010428317703655

1 Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.

Recent studies suggested that microRNA-200 family microRNAs play critical roles in cancer initiation and metastasis. The underlying mechanism remained elusive. In this study, we show that microRNA-200c is upregulated in nasopharyngeal carcinoma cells. Manipulation of microRNA-200c levels affected cell growth, migration, and invasion in nasopharyngeal carcinoma cell lines. Furthermore, PTEN was identified as a direct target of microRNA-200c. Overexpression of PTEN resulted in similar effects to those of anti-microRNA-200c transfection. In vivo suppression of microRNA-200c level reduced tumor growth in mice. Overall, our data suggest that microRNA-200c plays an oncogenic role in nasopharyngeal carcinoma by targeting PTEN.
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http://dx.doi.org/10.1177/1010428317703655DOI Listing
May 2017

Circulating thyroid stimulating hormone receptor messenger RNA and differentiated thyroid cancer: A diagnostic meta-analysis.

Oncotarget 2017 Jan;8(4):6623-6629

Institute of Biomedical Sciences, Minhang Hospital, Fudan University, Shanghai, P.R. China.

Thyroid stimulating hormone receptor messenger RNA (TSHR-mRNA) is over-expressed in thyroid cancer patients, which indicates that TSHR-mRNA is a potential biomarker of thyroid cancer. However, system evaluation for TSHR-mRNA as a diagnostic biomarker of thyroid cancer is deficient. The performance of TSHR-mRNA for thyroid cancer diagnosis was evaluated in this study. Three common international databases as well as a Chinese database were applied for literature researching. Quality assessment of the included literatures was conducted by the QUADAS-2 tool. Totally, 1027 patients from nine studies eligible for the meta-analysis were included in this study. Global sensitivity and specificity for the positivity of TSHR-mRNA in the thyroid cancer diagnosis is 72% and 82%. The value of AUC for this test performance was 0.84. Our meta-analysis suggests that TSHR-mRNA might be a potential biomarker to complete present diagnostic methods for early and precision diagnosis of thyroid cancer. Notably, this findings need validation thorough large-scale clinical studies.
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http://dx.doi.org/10.18632/oncotarget.14251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351657PMC
January 2017

Reactive Oxygen Species-mediated Loss of Phenotype of Parvalbumin Interneurons Contributes to Long-term Cognitive Impairments After Repeated Neonatal Ketamine Exposures.

Neurotox Res 2016 11 21;30(4):593-605. Epub 2016 Jul 21.

Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, China.

Ketamine, a common anesthetic used for pediatric patients, has been shown to induce neurotoxicity and alter adolescent behaviors in rats when administered during neonatal period. However, the mechanisms underlying this kind of neurotoxicity remain largely to be determined. Herein, we studied whether the reactive oxygen species (ROS) due to the increased NOX2 mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Sprague-Dawley male rat pups received a daily administration of ketamine intraperitoneally (75 mg/kg) from postnatal day 6 (P6) to P8 for three consecutive days. For the interventional study, pups were treated with a NADPH oxidase inhibitor, apocynin (Apo). Learning and memory abilities were tested by the open field, fear conditioning, and Morris water maze on P40, P42-44, and P50-56, respectively. For histological and biochemical assays, a separate cohort of rats was killed on P9 or P60, and the brain tissues were harvested. Our results showed the upregulation of 8-OHdG and gp91/NOX2 and downregulation of PV and glutamic acid decarboxylase 67 (GAD67) after repeated ketamine exposures, which co-occurred with the long-term cognitive impairments as evidenced by the decreased freezing time to context. However, Apo treatment attenuated these abnormalities. Our results suggest that oxidative damage, probably due to the increased NOX2, mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Moreover, the inhibition of NADPH oxidase may protect against cognitive dysfunction.
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http://dx.doi.org/10.1007/s12640-016-9653-1DOI Listing
November 2016

An overall and dose-response meta-analysis for thyrotropin and thyroid cancer risk by histological type.

Oncotarget 2016 07;7(30):47750-47759

Institute of Biomedical Sciences, Minhang Hospital, Fudan University, Shanghai, P.R. China.

Thyrotropin (TSH) is thought as a risk factor for thyroid cancer. However, the effect of serum TSH might depend on histological types of thyroid cancer. We searched for related studies including serum TSH as an exposure and thyroid cancer as a result in PUBMED, EMBASE and Chinese National Knowledge Infrastructure up to April 21, 2016. This meta-analysis included 22 articles with 53,538 participants. When comparing all histological thyroid cancer, the pooled odds ratios of thyroid cancer in patients with nodules was found to increase significantly with higher serum TSH concentrations for differentiated thyroid carcinoma (1.88 vs .1.48, P = 0.0000) and papillary thyroid carcinoma (2.08 vs. 1.48, P = 0.0006). Each 1 mU/L increase of serum TSH was associated with 14% greater risk of thyroid cancer for all histological thyroid cancer, 16% for differentiated thyroid carcinoma and 22% for papillary thyroid carcinoma. In addition, high serum TSH was associated with a reduced risk for follicular thyroid carcinoma (OR = 0.73, 95% CI: 0.52, 1.02). This meta-analysis suggested high serum TSH concentration is risky for papillary thyroid carcinoma but not for follicular thyroid carcinoma.
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http://dx.doi.org/10.18632/oncotarget.10282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216976PMC
July 2016

Effects of Intraoperative Hemodynamics on Incidence of Postoperative Delirium in Elderly Patients: A Retrospective Study.

Med Sci Monit 2016 Apr 3;22:1093-100. Epub 2016 Apr 3.

Department of Anesthesiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China (mainland).

Background: Postoperative delirium (POD) is a common complication in the elderly. This retrospective study investigated the effect of intraoperative hemodynamics on the incidence of POD in elderly patients after major surgery to explore ways to reduce the incidence of POD.

Material/methods: Based on the incidence of POD, elderly patients (81±6 y) were assigned to a POD (n=137) or non-POD group (n=343) after elective surgery with total intravenous anesthesia. POD was diagnosed based on the guidelines of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the confusion assessment method. The hemodynamic parameters, such as mean arterial pressure, were monitored 10 min before anesthesia (baseline) and intraoperatively. The incidence of intraoperative hypertension, hypotension, tachycardia, and bradycardia were calculated.

Results: At 30 min and 60 min after the initiation of anesthesia and at the conclusion of surgery, the monitored hemodynamic parameter values of the POD group, but not those of the non-POD group, were significantly higher than at baseline. Multivariate logistic regression analysis showed that intraoperative hypertension and tachycardia were significantly associated with POD.

Conclusions: Intraoperative hypertension and tachycardia were significantly associated with POD. Maintaining intraoperative stable hemodynamics may reduce the incidence of POD in elderly patients undergoing surgery.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822944PMC
http://dx.doi.org/10.12659/msm.895520DOI Listing
April 2016

SIRT6 Overexpression Potentiates Apoptosis Evasion in Hepatocellular Carcinoma via BCL2-Associated X Protein-Dependent Apoptotic Pathway.

Clin Cancer Res 2016 07 9;22(13):3372-82. Epub 2016 Feb 9.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Purpose: To characterize the functional role of SIRT6 in hepatocellular carcinoma (HCC).

Experimental Design: The expression of SIRT6 in 60 paired paraffin-embedded HCC tissues and adjacent nontumoral liver tissues was examined by immunohistochemistry. The expression of SIRT6 in 101 paired frozen HCC tissues and adjacent nontumoral liver tissues was analyzed by Western blotting analysis and qPCR. The biologic consequences of overexpression and knockdown of SIRT6 in HCC cell lines were studied in vitro and in vivo

Results: SIRT6 expression was frequently upregulated in clinical HCC samples, and its expression was highly associated with tumor grade (P = 0.02), tumor size (P = 0.02), vascular invasion (P = 0.004), and shorter survival (P = 0.024). Depletion of SIRT6 from multiple liver cancer cell lines inhibited their growth and induced apoptosis in vitro At the molecular level, we observed that the activation of the BCL2-associated X protein (Bax) signaling pathway, a major pathway that determines cancer cell apoptosis, is regulated by SIRT6 via its deacetylase activity. SIRT6 was recruited to the promoter of Bax, where it deacetylated histone 3 lysine 9 and suppressed its promoter activity. Binding of transcription factors (p53 and E2F-1) to Bax promoter was also generally increased in SIRT6-depleted cells. In mouse xenografts, SIRT6 suppression inhibited tumor growth and induced apoptosis. Finally, there is a negative correlation between SIRT6 and Bax mRNA expressions in human HCC samples.

Conclusions: SIRT6 is an important protumorigenic factor in liver carcinogenesis. Thus, the therapeutic targeting of SIRT6 may offer options for HCC treatment. Clin Cancer Res; 22(13); 3372-82. ©2016 AACR.
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http://dx.doi.org/10.1158/1078-0432.CCR-15-1638DOI Listing
July 2016

Spectral properties of the temporal evolution of brain network structure.

Chaos 2015 Dec;25(12):123112

State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace, Xi'an Jiaotong University, Xi'an 710049, China.

The temporal evolution properties of the brain network are crucial for complex brain processes. In this paper, we investigate the differences in the dynamic brain network during resting and visual stimulation states in a task-positive subnetwork, task-negative subnetwork, and whole-brain network. The dynamic brain network is first constructed from human functional magnetic resonance imaging data based on the sliding window method, and then the eigenvalues corresponding to the network are calculated. We use eigenvalue analysis to analyze the global properties of eigenvalues and the random matrix theory (RMT) method to measure the local properties. For global properties, the shifting of the eigenvalue distribution and the decrease in the largest eigenvalue are linked to visual stimulation in all networks. For local properties, the short-range correlation in eigenvalues as measured by the nearest neighbor spacing distribution is not always sensitive to visual stimulation. However, the long-range correlation in eigenvalues as evaluated by spectral rigidity and number variance not only predicts the universal behavior of the dynamic brain network but also suggests non-consistent changes in different networks. These results demonstrate that the dynamic brain network is more random for the task-positive subnetwork and whole-brain network under visual stimulation but is more regular for the task-negative subnetwork. Our findings provide deeper insight into the importance of spectral properties in the functional brain network, especially the incomparable role of RMT in revealing the intrinsic properties of complex systems.
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http://dx.doi.org/10.1063/1.4937451DOI Listing
December 2015

Clinical and Etiological Characteristics of Atypical Hand-Foot-and-Mouth Disease in Children from Chongqing, China: A Retrospective Study.

Biomed Res Int 2015 26;2015:802046. Epub 2015 Nov 26.

Department of Infectious Disease, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.

Background: Hand-foot-and-mouth disease (HFMD) is a disease that had similar manifestations to chickenpox, impetigo, and measles, which is easy to misdiagnose and subsequently causes delayed therapy and subsequent epidemic. To date, no study has been conducted to report the clinical and epidemiological characteristics of atypical HFMD.

Methods: 64 children with atypical HFMD out of 887 HFMD children were recruited, stool was collected, and viral VP1 was detected.

Results: The atypical HFMD accounted for 7.2% of total HFMD in the same period (64/887) and there were two peaks in its prevalence in nonepidemic seasons. Ten children (15.6%) had manifestations of neurologic involvement, of whom 4 (6.3%) were diagnosed with severe HFMD and 1 with critically severe HFMD, but all recovered smoothly. Onychomadesis and desquamation were found in 14 patients (21.9%) and 15 patients (23.4%), respectively. The most common pathogen was coxsackievirus A6 (CV-A6) which accounted for 67.2%, followed by nontypable enterovirus (26.6%), enterovirus 71 (EV-A71) (4.7%), and coxsackievirus A16 (A16) (1.5%).

Conclusions: Atypical HFMD has seasonal prevalence. The manifestations of neurologic involvement in atypical HFMD are mild and usually have a good prognosis. CV-A6 is a major pathogen causing atypical HFMD, but not a major pathogen in Chongqing, China.
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http://dx.doi.org/10.1155/2015/802046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674665PMC
September 2016

[Study on anti-inflammation effect and involved mechanism of Guizhi Fuling capsule and its active complex].

Zhongguo Zhong Yao Za Zhi 2015 Mar;40(6):993-8

The aim of this study was to investigate the anti-inflammatory effect of Guizhi Fuling capsule and its active complex (consistent of 15 active compounds) on LPS-induced RAW264. 7 cells. The effect of Guizhi Fuling capsule and its active complex on cell viability in RAW264. 7 cells were determined by MTT assay. The inhibitory effect of Guizhi Fuling capsule and active complex on the releasing of IL-1β, TNF-α and PGE2 induced by LPS in RAW264. 7 cells was detected by ELISA assay. The expression of IL-1β and mPGES-1 in Guizhi Fuling capsule or active complex treated RAW264. 7 cells was examined by Western blot assay. Guizhi Fuling capsule and active complex showed no significant effect on the cell viability in RAW264. 7 cells at doses range from 12.5 to 400 mg x L(-1). Compared with LPS treated group, Guizhi Fuling capsule and active complex dose dependently reduced the releasing of IL-1β, TNF-α and PGE2 induced by LPS in RAW264. 7 cells. Moreover, the expression of IL-1β and mPGES-1 was decreased after Guizhi Fuling capsule and active complex treatment, which might contribute to the inhibitory effect of Guizhi Fuling capsule in the releasing of IL-1β, TNF-α and PGE2. This study provided the evidence that Guizhi Fuling capsule and active complex remarkably inhibited the releasing of IL-1β, TNF-α and PGE2induced by LPS in RAW264. 7 cells by reducing the expression IL-1β and mPGES-1. This study provided an experimental basis of Guizhi Fuling capsule for the treatment of inflammation and a theoretical basis for the development of effective compounds of Guizhi Fuling capsule.
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March 2015

ANAC005 is a membrane-associated transcription factor and regulates vascular development in Arabidopsis.

J Integr Plant Biol 2016 May 25;58(5):442-51. Epub 2015 Sep 25.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

Vascular tissues are very important for providing both mechanical strength and long-distance transport. The molecular mechanisms of regulation of vascular tissue development are still not fully understood. In this study we identified ANAC005 as a membrane-associated NAC family transcription factor that regulates vascular tissue development. Reporter gene assays showed that ANAC005 was expressed mainly in the vascular tissues. Increased expression of ANAC005 protein in transgenic Arabidopsis caused dwarf phenotype, reduced xylem differentiation, decreased lignin content, repression of a lignin biosynthetic gene and genes related to cambium and primary wall, but activation of genes related to the secondary wall. Expression of a dominant repressor fusion of ANAC005 had overall the opposite effects on vascular tissue differentiation and lignin synthetic gene expression. The ANAC005-GFP fusion protein was localized at the plasma membrane, whereas deletion of the last 20 amino acids, which are mostly basic, caused its nuclear localization. These results indicate that ANAC005 is a cell membrane-associated transcription factor that inhibits xylem tissue development in Arabidopsis.
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http://dx.doi.org/10.1111/jipb.12379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054944PMC
May 2016
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