Publications by authors named "Xuefang Zhang"

25 Publications

  • Page 1 of 1

Pain location is associated with fracture type in acute osteoporotic thoracolumbar vertebral fracture: a prospective observation study.

Pain Med 2021 Jul 28. Epub 2021 Jul 28.

Department of Spine Surgery, Honghui Hospital of Xi'an Jiaotong University Health Science Center.

Objective: This study investigated the relationship between pain location and fracture type in the patients with acute osteoporotic vertebral fracture (OVF).

Design: A prospective observation study.

Subject: A total of 306 patients with acute OVF were included.

Methods: The site of pain of each patient was recorded, and the patients were divided into pain at fracture site group (group 1) and pain at non-fracture site group (group 2). The fracture type was classified into four types: type I, upper endplate type; type II, central type; type III, lower endplate type; type IV, burst type.

Results: There were 146 patients in the group 1, of which 20.55% (30/146) were type I, 33.56% (49/146) were type II, 15.75% (23/146) were type III, and 30.14% (44/146) were type IV. There were 227 patients in the group 2, of which 57.27% (130/227) were type I, 5.29% (12/227) were type II, 35.24% (80/227) were type III, and 2.20% (5/227) were type IV. There was a statistical difference in the fracture type distribution between the two groups (P < 0.05). The VAS in the group 1 was higher than that in the group 2 at the initial diagnosis (P < 0.05).

Conclusions: For patients with acute OVF, the site of pain is related to the type of fracture. The pain at the fracture site is more often observed in the central type and burst type of fractures, while pain at the non-fracture site is more often observed in the upper and lower endplate type of fractures. Additionally, when OVF are suspected, radiological assessment of thoracic and lumbar spine is recommended to better detect fractures that could cause pain distal to the site of the fracture.
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http://dx.doi.org/10.1093/pm/pnab229DOI Listing
July 2021

OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair.

Cell Death Dis 2021 06 16;12(7):622. Epub 2021 Jun 16.

School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei Province, 071002, China.

Accumulated evidence shows that OGT-mediated O-GlcNAcylation plays an important role in response to DNA damage repair. However, it is unclear if the "eraser" O-GlcNAcase (OGA) participates in this cellular process. Here, we examined the molecular mechanisms and biological functions of OGA in DNA damage repair, and found that OGA was recruited to the sites of DNA damage and mediated deglycosylation following DNA damage. The recruitment of OGA to DNA lesions is mediated by O-GlcNAcylation events. Moreover, we have dissected OGA using deletion mutants and found that C-terminal truncated OGA including the pseudo HAT domain was required for the recruitment of OGA to DNA lesions. Using unbiased protein affinity purification, we found that the pseudo HAT domain was associated with DNA repair factors including NONO and the Ku70/80 complex. Following DNA damage, both NONO and the Ku70/80 complex were O-GlcNAcylated by OGT. The pseudo HAT domain was required to recognize NONO and the Ku70/80 complex for their deglycosylation. Suppression of the deglycosylation prolonged the retention of NONO at DNA lesions and delayed NONO degradation on the chromatin, which impaired non-homologus end joining (NHEJ). Collectively, our study reveals that OGA-mediated deglycosylation plays a key role in DNA damage repair.
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http://dx.doi.org/10.1038/s41419-021-03910-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209095PMC
June 2021

[Risk factors analysis of adjacent fractures after percutaneous vertebroplasty for osteoporotic vertebral compression fracture].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jan;35(1):20-25

Department of Spine Surgery, Honghui Hospital Affiliated to Medical School of Xi'an Jiaotong University, Xi'an Shaanxi, 710054, P.R.China.

Objective: To investigate the risk factors of adjacent fractures after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).

Methods: A total of 2 216 patients who received PVP due to symptomatic OVCF between January 2014 and January 2017 and met the selection criteria were selected as study subjects. The clinical data was collected, including gender, age, height, body mass, history of smoking and drinking, whether the combination of hypertension, diabetes, coronary arteriosclerosis, chronic obstructive pulmonary disease (COPD), bone mineral density, the number of fractured vertebrae, the amount of cement injected into single vertebra, the cement leakage, and whether regular exercise after operation, whether regular anti-osteoporosis treatment after operation. Firstly, single factor analysis was performed on the observed indicators to preliminarily screen the influencing factors of adjacent fractures after PVP. Then, logistic regression analysis was carried out for relevant indicators with statistical significance to screen risk factors.

Results: All patients were followed up 12-24 months, with an average of 15.8 months. Among them, 227 patients (10.24%) had adjacent fractures. The univariate analysis showed that there were significant differences between the fracture group and non-fracture group in age, gender, preoperative bone density, history of smoking and drinking, COPD, the number of fractured vertebrae and the amount of bone cement injected into the single vertebra, as well as regular exercise after operation, regular anti-osteoporosis treatment after operation ( <0.05). Further multivariate logistic regression analysis showed that the elderly and female, history of smoking, irregular exercise after operation, irregular anti-osteoporosis treatment after operation, low preoperative bone density, large number of fractured vertebrae, and small amount of bone cement injected into the single vertebra were risk factors for adjacent fractures after PVP in OVCF patients ( <0.05).

Conclusion: The risk of adjacent fractures after PVP increases in elderly, female patients with low preoperative bone mineral density, large number of fractured vertebrae, and insufficient bone cement injection. The patients need to quit smoking, regular exercise, and anti-osteoporosis treatment after PVP.
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http://dx.doi.org/10.7507/1002-1892.202008044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171608PMC
January 2021

Clinicopathological features and prognostic analysis of 77 patients with multiple primary cancers.

J BUON 2020 Jul-Aug;25(4):2110-2116

Department of Oncology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523000, China.

Purpose: The purpose of this study was to analyze the characteristics, diagnosis and treatment principles and prognosis of multiple primary cancers (MPC).

Methods: A total of 77 patients with MPC admitted in the Central Hospital of Changsha from December 2013 to December 2018 were enrolled in this retrospective analysis. The survival of these 77 patients with complete follow-up data was calculated.

Results: There were 77 patients with multiple primary cancers, including 70 patients with double primary cancers, 6 patients with three primary cancers, and 1 patient with four primary cancers. Among the 77 MPC patients, there were 4 synchronous carcinomas (SC), 58 metachronous carcinomas (MC), and 15 unknown cases. The 3, 5, and 10-year overall survival rates of 77 patients with follow-up data were 86.5%, 18.2%, and 12.9%, respectively. The median survival time of 4 SC and 58 MC patients was 12 months and 108 months, respectively. The median survival time was 48.5 months in 23 patients with an interval of less than 5 years, and 108 months in 29 patients with first and second primary cancers whose interval was more than 5 years. The median survival time of 26 patients with second primary lung cancer was 84 months, and that of 23 patients with second primary non-lung cancer was 156 months.

Conclusions: MPCs are more likely to occur in the colorectum, and the prognosis of patients with metachronous cancer is better than that of patients with synchronous cancer. The longer the interval between two cancers, the better the prognosis will be. The prognosis of the second primary non-lung cancer patients is better than that of the lung cancer patients.
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July 2021

Blockade of IL-6 alleviates bone loss induced by modeled microgravity in mice.

Can J Physiol Pharmacol 2020 Oct 13;98(10):678-683. Epub 2020 Aug 13.

Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.

This study investigated the effects of blockade of IL-6 on bone loss induced by modeled microgravity (MG). Adult male mice were exposed to hind-limb suspension (HLS) and treated with IL-6-neutralizing antibody (IL-6 nAb) for 4 weeks. HLS in mice led to upregulation of IL-6 expression in both sera and femurs. IL-6 nAb treatment in HLS mice significantly alleviated bone loss, evidenced by increased bone mineral density of whole tibia, trabecular thickness and number, bone volume fraction of proximal tibiae, and ultimate load and stiffness of femoral diaphysis. IL-6 nAb treatment in HLS mice significantly enhanced levels of osteocalcin in sera and reduced levels of deoxypyridinoline. In MC3T3-E1 cells exposed to MG in vitro, IL-6 nAb treatment increased mRNA expression and activity of alkaline phosphatase, mRNA expression of osteopontin and runt-related transcription factor 2, and protein levels of osteoprotegerin and decreased protein levels of receptor activator of the NF-κB ligand. In RAW254.7 cells exposed to MG, IL-6 nAb treatment downregulated mRNA expression of cathepsin K and tartrate-resistant acid phosphatase (TRAP) and reduced numbers of TRAP-positive multinucleated osteoclasts. In conclusion, blockade of IL-6 alleviated the bone loss induced by MG.
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http://dx.doi.org/10.1139/cjpp-2019-0632DOI Listing
October 2020

PD-1 mRNA expression in peripheral blood mononuclear cells as a biomarker for different stages of primary gouty arthritis.

J Cell Mol Med 2020 08 8;24(16):9323-9331. Epub 2020 Jul 8.

Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

There is currently a lack of biomarkers to assist the diagnosis and prediction of primary gouty arthritis (PG). Therefore, we evaluated the clinical value of programmed cell death protein 1 (PD-1) mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with PG. This study included 36 patients with acute phase PG (APPG), 48 with non-acute phase PG (NAPPG), 42 with asymptomatic hyperuricemia (AH) and 79 normal controls (NCs). PD-1 mRNA expression levels were detected by qRT-PCR. PD-1 mRNA expression was statistically analysed by ANOVA or t tests, while correlations between PD-1 mRNA and clinical variables were assessed using Pearson correlation tests. Receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic value of PD-1 in different PG stages. PD-1 mRNA expression was significantly lower in patients with APPG than that in NAPPG, AH and NCs (P < 0.01). Correlation analysis revealed that PD-1 mRNA levels correlated negatively with T-score (r = -0.209, P < 0.01). ROC curve analysis showed that serum uric acid (SUA), PD-1 mRNA and both combined displayed higher diagnostic value in patients with PG, NAPPG and APPG compared to that in NCs and patients with non-PG arthritis (NPG). Moreover, ROC curve analysis showed that SUA and PD-1 mRNA had good diagnostic value in APPG, with the greatest diagnostic power when combined. PD-1 mRNA could be a clinical auxiliary diagnostic biomarker for APPG, and the combined use of PD-1 mRNA and SUA is better than that of SUA alone.
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http://dx.doi.org/10.1111/jcmm.15582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417685PMC
August 2020

miR-331-3p Inhibits Proliferation and Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Targeting elf4B-PI3K-AKT Pathway.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033819892251

Department of Radiotherapy, Dongguan People' Hospital, Dongguan, China.

Background: The incidence of nasopharyngeal carcinoma is increasing gradually, but the pathogenesis is not completely clear. MicroRNA, a highly conserved endogenous noncoding small molecule RNA, plays an essential role in the regulation of gene expression and is a hotspot in cancer research worldwide.

Objectives: Although previous studies have confirmed that the abnormal expression of microRNAs is closely related to the progression of nasopharyngeal carcinoma, the role of miRNA-331-3p in nasopharyngeal carcinoma has not been studied. The purpose of this study was to explore the role and mechanism of miRNA-331-3p in the progression of nasopharyngeal carcinoma.

Materials And Methods: Real-time quantitative reverse transcription polymerase chain reaction was performed to detect the expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cell lines (CNE-1 and 5-8F cells). After overexpression of miRNA-331-3p in CNE-1 cells, cell proliferation was measured by Cell Counting Kit-8 assay, cell invasion was detected by Transwell assay, and apoptosis was tested by flow cytometry. In addition, the dual-luciferase reporter assay was used to identify the target gene of miRNA-331-3p and Western blotting was performed to measure the relative protein expression.

Results: The expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cells was decreased significantly. Overexpression of miRNA-331-3p markedly inhibited the proliferation and invasion of CNE-1 cells and promoted cell apoptosis. Moreover, overexpression of miRNA-331-3p reduced the expression of target gene elF4B, leading to inhibition of the phosphorylation of Phosphoinositide 3-kinase (PI3K) and Serine/ threonine kinase (AKT).

Conclusion: miRNA-331-3p inhibited cell proliferation and induced cell apoptosis in nasopharyngeal carcinoma by targeting gene and then blocked the PI3K-AKT signaling pathway.

Significance: The role of miRNA-331-3p in the development of NPC and its mechanism provide new ideas for the treatment of nasopharyngeal carcinoma.
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http://dx.doi.org/10.1177/1533033819892251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985969PMC
September 2020

Long Non-coding RNA JHDM1D-AS1 Interacts with DHX15 Protein to Enhance Non-Small-Cell Lung Cancer Growth and Metastasis.

Mol Ther Nucleic Acids 2019 Dec 10;18:831-840. Epub 2019 Oct 10.

Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China. Electronic address:

JHDM1D antisense 1 (JHDM1D-AS1), a long non-coding RNA (lncRNA), has been shown to promote pancreatic cancer growth by inducing an angiogenic response. However, its biological and clinical significance in non-small-cell lung cancer (NSCLC) is still unclear. In this study, we examined the expression and prognostic significance of JHDM1D-AS1 in NSCLC. The effects of JHDM1D-AS1 knockdown or overexpression on NSCLC growth and metastasis were investigated. We show that JHDM1D-AS1 is upregulated in NSCLC relative to adjacent normal lung tissues. High JHDM1D-AS1 expression is significantly correlated with advanced tumor, node, and metastasis (TNM) stage and lymph node metastasis. JHDM1D-AS1 expression serves as an independent prognostic factor for overall survival of patients with NSCLC. Functionally, JHDM1D-AS1 knockdown inhibits NSCLC cell aggressiveness both in vitro and in vivo, which is rescued by ectopic expression of JHDM1D-AS1. JHDM1D-AS1 binding stabilizes DHX15 protein in NSCLC cells. DHX15 overexpression enhances NSCLC cell proliferation and invasion, whereas knockdown of DHX15 exerts opposite effects. JHDM1D-AS1-mediated aggressive phenotype is impaired when DHX15 is silenced. Ectopic expression of DHX15 restores the defects in proliferation and invasion of JHDM1D-AS1-depleted NSCLC cells. Collectively, the interaction between JHDM1D-AS1 and DHX15 accounts for NSCLC growth and metastasis. This work provides potential additional therapeutic targets for treatment of NSCLC.
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http://dx.doi.org/10.1016/j.omtn.2019.09.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861564PMC
December 2019

Interleukin‑12 exacerbates Sjögren's syndrome through induction of myeloid‑derived suppressor cells.

Mol Med Rep 2019 Aug 6;20(2):1131-1138. Epub 2019 Jun 6.

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, Jiangsu 210093, P.R. China.

Interleukin (IL)‑12 modulates the generation and function of various immune cells and plays a vital role in the pathogenesis of Sjögren's syndrome (SS). Myeloid‑derived suppressor cells (MDSCs) are involved in autoimmune diseases by regulating various immune responses. However, it has not been confirmed whether inflammatory IL‑12 participates in the progression of SS via regulating MSDCs. In the present study, the plasma levels of IL‑12 were detected by ELISA in SS‑like non‑obese diabetic (NOD) mice. The mice were treated by intraperitoneal injection of IL‑12 and anti‑IL‑12 antibody, respectively, and then the salivary flow rate was detected. The pathology of submandibular glands was evaluated in tissue sections stained with hematoxylin and eosin. The proportion of MDSCs was assessed by flow cytometry. The results showed that plasma IL‑12 was significantly increased in the SS‑like NOD mice comparing with that noted in the control mice. The exogenous IL‑12 exacerbated SS‑like symptoms of NOD mice and promoted the generation of both bone marrow (BM) and splenic MDSCs in the SS‑like NOD mice. Of note, anti‑IL‑12 alleviated SS‑like symptoms of NOD mice and inhibited the generation of BM and splenic MDSCs. Moreover, the generation of MDSCs was crippled in the IL‑12‑deficient C57BL/6 (Il‑12‑/‑ B6) mice. Our findings suggest that aggravation of SS‑like symptoms by IL‑12 in NOD mice may be attributed to its promotion of MDSC development.
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http://dx.doi.org/10.3892/mmr.2019.10352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625410PMC
August 2019

Long-term Antibody Persistence After Hepatitis E Virus Infection and Vaccination in Dongtai, China.

Open Forum Infect Dis 2019 Apr 28;6(4):ofz144. Epub 2019 Mar 28.

Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Background: Hepatitis E virus (HEV) is of global significance. HEV is a common cause of acute hepatitis in China. One of the major unanswered questions about HEV is the persistence of antibodies after infection and vaccination.

Methods: We examined antibody persistence 6.5 years after HEV exposures through natural infection and vaccination. Ninety-seven vaccine recipients and 70 individuals asymptomatically infected with HEV enrolled in the phase III HEV239 vaccine trial in Dongtai, China, were revisited.

Results: Antibody loss was 23.4% (95% confidence interval [CI], 17.1%-30.5%), with a nonsignificantly higher percentage of loss among those naturally infected (30.0%; 95% CI, 19.6%-42.1%) than those vaccinated (18.6%; 95% CI, 11.4%-27.7%; = .085). Age and gender were not associated with antibody persistence. Only 2 people (1.2%) self-reported medically diagnosed jaundice or hepatitis-like illness in the last 10 years, both of whom had persistent antibodies. Contact with a jaundice patient and injectable contraceptive use were marginally associated with loss of detectable anti-HEV antibodies ( = .047 and .082, respectively), whereas transfusion was marginally associated with antibody persistence ( = .075).

Conclusions: Antibody loss was more common among those naturally infected compared with those vaccinated. However, none of the characteristics examined were strongly associated with antibody loss, suggesting that factors not yet identified may play a more important role in antibody loss. Long-term postvaccination antibody persistence is currently unknown and will be an important consideration in the development of policies for the use of the highly efficacious HEV vaccine. NCT01014845.
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http://dx.doi.org/10.1093/ofid/ofz144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475590PMC
April 2019

Treatment with hydrogen sulfide donor attenuates bone loss induced by modeled microgravity.

Can J Physiol Pharmacol 2019 Jul 14;97(7):655-660. Epub 2019 Mar 14.

Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.

The present study was undertaken to explore the therapeutic potential of hydrogen sulfide against bone loss induced by modeled microgravity. Hindlimb suspension (HLS) and rotary wall vessel bioreactor were applied to model microgravity in vivo and in vitro, respectively. Treatment of rats with GYY4137 (a water soluble donor of hydrogen sulfide, 25 mg/kg per day, i.p.) attenuated HLS-induced reduction of bone mineral density in tibiae, and preserved bone structure in tibiae and mechanical strength in femurs. In HLS group, GYY4137 treatment significantly increased levels of osteocalcin in sera. Interestingly, treatment of HLS rats with GYY4137 enhanced osteoblast surface, but had no significant effect on osteoclast surface of proximal tibiae. In MC3T3-E1 cells exposed to modeled microgravity, GYY4137 stimulated transcriptional levels of runt-related transcription factor 2 and enhanced osteoblastic differentiation, as evidenced by increased mRNA expression and activity of alkaline phosphatase. HLS in rats led to enhanced levels of interleukin 6 in sera, skeletal muscle, and tibiae, which could be attenuated by GYY4137 treatment. Our study showed that GYY4137 preserved bone structure in rats exposed to HLS and promoted osteoblastic differentiation in MC3T3-E1 cells under modeled microgravity.
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http://dx.doi.org/10.1139/cjpp-2018-0521DOI Listing
July 2019

[Comparison of accuracy between robot-assisted and fluoroscopy-guided percutaneous pedicle screw placement for treatment of lumbar spondylolisthesis].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2018 11;32(11):1371-1376

Department of Spine Surgery, Honghui Hospital Affiliated to Medical College of Xi'an Jiaotong University, Xi'an Shaanxi, 710054, P.R.China.

Objective: To explore the clinical application value of the spinal robot-assisted surgical system in mild to moderate lumbar spondylolisthesis and evaluate the accuracy of its implantation.

Methods: The clinical data of 56 patients with Meyerding grade Ⅰ or Ⅱ lumbar spondylolisthesis who underwent minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) between January 2017 and December 2017 were retrospectively analysed. Among them, 28 cases were preoperatively planned with robotic arm and percutaneous pedicle screw placement according to preoperative planning (group A); the other 28 cases underwent fluoroscopy-guided percutaneous pedicle screw placement (group B). There was no significant difference in gender, age, body mass index, slippage type, Meyerding grade, and surgical segmental distribution between the two groups ( >0.05). The screw insertion angle was measured by CT, the accuracy of screw implantation was evaluated by Neo's criteria, and the invasion of superior articular process was evaluated by Babu's method.

Results: One hundred and twelve screws were implanted in the two groups respectively, 5 screws (4.5%) in group A and 26 screws (23.2%) in group B penetrated the lateral wall of pedicle, and the difference was significant ( =9.157, =0.002); the accuracy of nail implantation was assessed according to Neo's criteria, the results were 107 screws of degree 0, 3 of degree 1, 2 of degree 2 in group A, and 86 screws of degree 0, 16 of degree 1, 6 of degree 2, 4 of degree 3 in group B, showing significant difference between the two groups ( =4.915, =0.031). In group B, 20 (17.9%) screws penetrated the superior articular process, while in group A, 80 screws were removed from the decompression side, and only 3 (3.8%) screws penetrated the superior articular process. According to Babu's method, the degree of screw penetration into the facet joint was assessed. The results were 77 screws of grade 0, 2 of grade 1, 1 of grade 2 in group A, and 92 screws of grade 0, 13 of grade 1, 4 of grade 2, 3 of grade 3 in group B, showing significant difference between the two groups ( =7.814, =0.029). The screw insertion angles of groups A and B were (23.5±6.6)° and (18.1±7.5)° respectively, showing significant difference ( =3.100, =0.003).

Conclusion: Compared to fluoroscopy-guided percutaneous pedicle screw placement, robot-assisted percutaneous pedicle screw placement has the advantages such as greater accuracy, lower incidence of screw penetration of the pedicle wall and invasion of the facet joints, and has a better screw insertion angle. Combined with MIS-TLIF, robot-assisted percutaneous pedicle screw placement is an effective minimally invasive treatment for lumbar spondylolisthesis.
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http://dx.doi.org/10.7507/1002-1892.201804049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414108PMC
November 2018

Inexpensive Weight-Reducing Aid (L-Carnitine) as An Efficient Catalyst for Synthesis of Benzimidazoles.

Comb Chem High Throughput Screen 2018 ;21(8):567-570

School of Chemical & Environmental Engineering, Wuyi University, Jiangmen 529020, China.

Aim And Objective: The benzimidazole derivatives have been obtained via weightreducing aid (L-Carnitine) as a cheap catalyst. A wide range of aromatic aldehydes easily undergo condensations with substituted o-phenylendiamine under mild condition to afford the target molecular in excellent yields.

Materials And Methods: Melting points were measured on an Electrothemal X6 microscopy digital melting point apparatus. 1H NMR and 13C NMR spectra were recorded in DMSO-d6 on a Bruker AVANCE 400 (400 MHz) instrument with the TMS at d 0.00 ppm as an internal standard. C, H and N analysis were performed by a Perkin-Elmer 2400 CHN elemental analyzer. Chemicals used were of commercial grade without further purification. An equimloar (1.0 mmol) mixture of o-phenylenediamine 1, aromatic aldehyde 2, and L-Carnitine (10 mol%) was vigorously stirred at 60°C in EtOH (3 mL) for the specific time indicated by TLC (petroleum: ethyl acetate ether = 4:1). After completion of the reaction, the mixture was quenched by adding H2O (20 mL), extracted with EtOAc (3 x 10 mL), and the combined extracts were dried by anhydrous MgSO4. The filtrate was evaporated and the corresponding benzimidazole was obtained as the only product. The products 3a-3r were obtained in 82-95% yields. The structures of the products 3 were identified by their IR, 1H NMR, 13C NMR and elemental analysis spectra.

Results: The products were obtained in 82-95% yields in 30-80 min. The method has several advantages such as simple, clean and environmentally process, excellent yield and avoiding use of inconvenient preparation of catalyst. Meanwhile, the catalyst L-Carnitine is a kind of weightreducing aid, which might be applied to broad green catalyzed system.

Conclusion: A facile synthesis of benzimidazoles comprising the reaction of various aldehydes with substituted o-phenylendiamine in good to excellent yield is provided using L-Carnitine as an efficient catalyst. The protocol overcomes the earlier disadvantages like harsh reaction conditions, tedious work-up, expensive process, wastes generation and the use of metallic oxide, which might be applied to the synthesis of benzimidazoles pharmaceticals in order to meet friendly environmental demands.
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http://dx.doi.org/10.2174/1386207321666181018163940DOI Listing
August 2019

Wet cupping for hypertension: a systematic review and meta-analysis.

Clin Exp Hypertens 2019 5;41(5):474-480. Epub 2018 Sep 5.

e Department of Nursing , Nanjing City Hospital of Traditional Chinese Medicine , Nanjing , China.

To assess the efficacy and safety of wet cupping in adults with hypertension, we conducted a systematic review and meta-analysis using 13 databases. Wet cupping alone or in combination with antihypertensive medication or acupuncture was used. Seven randomized trials were included, most not of high methodological quality. A few small studies suggested that wet cupping alone versus antihypertensive medication significantly reduced blood pressure and Traditional Chinese Medicine syndrome (hypertension-related symptoms). However based on current evidence, no firm conclusions can be drawn and no clinical recommendations made. Research projects included need validation. Studies indicate that wet cupping is a safe therapy.
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http://dx.doi.org/10.1080/10641963.2018.1510939DOI Listing
July 2019

mTOR regulates NLRP3 inflammasome activation via reactive oxygen species in murine lupus.

Acta Biochim Biophys Sin (Shanghai) 2018 Sep;50(9):888-896

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.

Inflammasomes are protein complexes responsible for the release of IL-1 family cytokines, and they play critical roles in immunity and inflammation. The best-characterized inflammasome, the NOD-like receptor protein 3 (NLRP3) inflammasome, is involved in the development of multiple autoimmune diseases. However, the underlying mechanisms of abnormal NLRP3 inflammasome activation in systemic lupus erythematosus (SLE) remain elusive. Here, western blot analysis was used to detect the level of NLRP3 components and mTORC1/2 substrate in the kidney tissues from B6.MRL-FASlpr/J lupus mice and C57BL/6 mice, and the results showed that mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) and the NLRP3 inflammasome were hyperactivated in B6.MRL-FASlpr/J lupus mice. The inhibition of mTOR by INK128, a novel mTORC1/2 inhibitor, suppressed LPS/ATP and LPS/nigericin-induced NLRP3 inflammasome activation in bone marrow-derived macrophages (BMDMs) in vitro. INK128 decreased both the mRNA and protein levels of NLRP3 in an NF-κB-independent manner. Moreover, we reported for the first time that the inhibition of mTOR suppressed mitochondrial reactive oxygen species (ROS) production in BMDMs stimulated by an NLRP3 agonist. Furthermore, N-acetyl-L-cysteine, a ROS inhibitor, decreased NLRP3 expression, and rotenone, a robust ROS inducer, partially reversed the inhibitory effect of INK128 on NLRP3. These results demonstrated that mTOR regulated the activation of the NLRP3 inflammasome at least partially via ROS-induced NLRP3 expression. Importantly, in vivo data demonstrated that INK128 treatment prominently attenuated lupus nephritis and suppressed NLRP3 inflammasome activation in B6.MRL-FASlpr/J lupus mice. Taken together, our results suggest that activation of mTOR/ROS/NLRP3 signaling may contribute to the development of SLE.
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http://dx.doi.org/10.1093/abbs/gmy088DOI Listing
September 2018

Myeloid-derived suppressor cells exacerbate Sjögren's syndrome by inhibiting Th2 immune responses.

Mol Immunol 2018 09 18;101:251-258. Epub 2018 Jul 18.

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, PR China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing, PR China. Electronic address:

Myeloid-derived suppressor cells (MDSCs) can regulate various aspects of immune responses based on their potent immune-suppressive activity. Studies reported that MDSCs participated in many autoimmune diseases. However, the role of MDSCs in Sjögren's syndrome (SS) is unknown. In this study, we determined the frequencies and function of MDSCs in non-obese diabetic (NOD) mice and SS patients. The NOD mice were adoptively transferred with MDSCs or treated with anti-Gr1 antibody. Results showed that peripheral MDSCs increased significantly with the development of SS-like syndrome in NOD mice and the percentage of MDSCs was higher in SS patients than healthy controls. The SS-like syndrome aggravated after transfer of MDSCs in NOD mice. The deletion of MDSCs in NOD mice alleviated SS-like syndrome. Mechanistically, MDSCs down-regulated the percentages of Th2 cells in NOD mice and SS patients. In summary, our findings suggested that MDSCs exacerbated Sjögren's syndrome by inhibiting Th2 cells.
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http://dx.doi.org/10.1016/j.molimm.2018.07.016DOI Listing
September 2018

Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine.

Cell Physiol Biochem 2017 21;43(2):589-601. Epub 2017 Sep 21.

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.

Background/aim: Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur).

Methods: Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay. The cell cycle and apoptosis of SKOV3 cells were monitored by flow cytometry. The mRNA and protein expression levels of target genes were respectively examined by qRT-PCR and western blot. The biological effects of miR-124 on midkine (MK) were verified by a luciferase activity analysis.

Results: Combined treatment of DHA and Cur synergistically decreased cell viability, arrested cell cycle, and promoted apoptosis in SKOV3 cells. Moreover, it significantly attenuated the expression of oncogene MK and synergistically upregulated the expression of miR-124. Furthermore, miR-124 was verified to bind directly to the 3'-untranslated region of MK mRNA, resulting in mRNA degradation and reduced MK protein levels. The combination of DHA with Cur significantly inhibited tumor growth in xenograft nude mice without obvious toxicity.

Conclusion: Co-treatment with DHA and Cur exhibited a synergistic anti-tumor effect on SKOV3 cells both in vitro and in vivo.
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http://dx.doi.org/10.1159/000480531DOI Listing
October 2017

Notch-Hes-1 axis controls TLR7-mediated autophagic death of macrophage via induction of P62 in mice with lupus.

Cell Death Dis 2016 08 18;7(8):e2341. Epub 2016 Aug 18.

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China.

The increased death of macrophages has been considered as a pathogenic factor for systemic lupus erythematosus (SLE), and dysfunction of autophagy may contribute to improper cell death. However, the effect of autophagy on macrophage during the pathogenesis of SLE is still unclear. Here we found that the death rate and autophagy level of macrophages significantly increased in MRL/lpr lupus-prone mice. Activation of toll-like receptor 7 (TLR7) triggered macrophage death in an autophagy-dependent but caspase-independent way in vitro. Moreover, P62/SQSTM1 is thought to have an essential role in selective autophagy. We also demonstrated that P62/SQSTM1 was required for TLR7-induced autophagy, and knockdown of P62 suppressed R848-induced cell death and LC3II protein accumulation. As an important mediator for cell-cell communication, Notch signaling is responsible for cell-fate decisions. Our results showed that activation of TLR7 also upregulated the expression of Notch1, especially its downstream target gene Hairy and enhancer of split 1 (Hes-1) in macrophages. Of note, we found that Hes-1, as a transcriptional factor, controlled TLR7-induced autophagy by regulating P62 expression. Furthermore, to confirm the above results in vivo, TLR7 agonist imiquimod (IMQ)-induced lupus mouse model was prepared. Splenic macrophages from IMQ-treated mice exhibited increased autophagy and cell death as well as enhanced expressions of Notch1 and Hes-1. Our results indicate that Notch1-Hes-1 signaling controls TLR7-induced autophagic death of macrophage via regulation of P62 in mice with lupus.
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http://dx.doi.org/10.1038/cddis.2016.244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108329PMC
August 2016

Identification of potential therapeutic target genes, key miRNAs and mechanisms in acute myeloid leukemia based on bioinformatics analysis.

Med Oncol 2015 May 2;32(5):152. Epub 2015 Apr 2.

Department of Hematology, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin, 150001, China,

The study was aimed to explore the underlying mechanisms and identify the potential target genes and key miRNAs for acute myeloid leukemia (AML) treatment by bioinformatics analysis. The microarray data of GSE9476 were downloaded from Gene Expression Omnibus database. A total of 64 samples, including 26 AML and 38 normal samples, were used to identify differentially expressed genes (DEGs) between AML and normal samples. The functional enrichment analysis was performed, and protein-protein interaction (PPI) network of the DEGs was constructed by Cytoscape software. Besides, the target miRNAs for DEGs were identified. Totally, 323 DEGs were identified, including 87 up-regulated and 236 down-regulated genes. Not only up-regulated genes but also down-regulated genes were related to hematopoietic-related functions. Besides, down-regulated genes were also enriched in primary immunodeficiency pathway. Tumor necrosis factor (TNF), interleukin 7 receptor (IL7R), lymphocyte-specific protein tyrosine kinase (LCK), CD79a molecule and immunoglobulin-associated alpha (CD79A) were identified in these functions. TNF and LCK were hub nodes in PPI networks. miR-124 and miR-181 were important miRNAs in this study. The hematopoietic-related functions and primary immunodeficiency pathway may be associated with AML development. Genes, such as TNF, IL7R, LCK and CD79A, may be potential therapeutic target genes for AML, and miR-124 and miR-181 may be key miRNAs in AML development.
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http://dx.doi.org/10.1007/s12032-015-0572-4DOI Listing
May 2015

Streptomyces yaanensis sp. nov., isolated from soil.

Int J Syst Evol Microbiol 2013 Dec 19;63(Pt 12):4719-4723. Epub 2013 Aug 19.

School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.

A novel actinomycete, designated Z4(T), was isolated from soil in Yaan, Sichuan Province, south China. The taxonomic status of this strain was established using a polyphasic approach. The morphological and chemotaxonomic characteristics of the organism are typical of the members of the genus Streptomyces. Phylogenetic analysis based on the almost complete 16S rRNA gene sequence indicated that strain Z4(T) belonged to the genus Streptomyces, branching off next to Streptomyces durhamensis ATCC 23194(T) (98.7 %), Streptomyces puniciscabiei KACC 20253(T) (98.7 %) and Streptomyces filipinensis ATCC 23905(T) (98.6 %). However, DNA-DNA hybridization studies and phenotypic differences between strain Z4(T) and closely related species of the genus Streptomyces suggested that strain Z4(T) represented a different genomic species. It is therefore proposed that Z4(T) ( = CGMCC 4.7035(T) = KCTC 29111(T)) represents the type strain of a novel species of the genus Streptomyces, for which the name Streptomyces yaanensis sp. nov. is proposed.
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http://dx.doi.org/10.1099/ijs.0.054734-0DOI Listing
December 2013

Streptomyces wuyuanensis sp. nov., an actinomycete from soil.

Int J Syst Evol Microbiol 2013 Aug 25;63(Pt 8):2945-2950. Epub 2013 Jan 25.

Institute of Agri-resources and Regional Planning, CAAS, Beijing 100081, PR China.

A novel actinomycete, strain FX61(T), was isolated from a saline sample collected from the Inner Mongolian Autonomous Region in China and subjected to a taxonomic study using a polyphasic approach. The predominant menaquinones were MK-9(H6), MK-9(H8) and MK-9(H4). The major fatty acids were iso-C16 : 0, anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 1 H, C16 : 0, iso-C14 : 0 and anteiso-C17 : 0. The phospholipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, two phosphatidylinositol mannosides and an unidentified phospholipid. The G+C content of the genomic DNA was 72 mol%. The 16S rRNA gene sequence of the isolate had greater than 98 % similarity with those of Streptomyces griseoincarnatus ATCC 23623(T) (98.2 %), Streptomyces labedae DSM 41446(T) (98.2 %), Streptomyces variabilis ATCC 19815(T) (98.2 %), Streptomyces erythrogriseus ATCC 27427(T) (98.2 %), Streptomyces matensis ATCC 23935(T) (98.2 %), Streptomyces althioticus ATCC 19724(T) (98.2 %) and Streptomyces luteosporeus ATCC 33049(T) (98.0 %), showing that the novel strain should be assigned to the genus Streptomyces. DNA-DNA hybridizations with the seven above-mentioned members of the genus Streptomyces showed 29.8, 28.5, 27.0, 25.5, 25.0, 23.5 and 22.0 % relatedness, respectively. On the basis of the phenotypic characteristics and genotypic distinctiveness, strain FX61(T) should be classified as a novel species of the genus Streptomyces, for which the name Streptomyces wuyuanensis sp. nov. is proposed. The type strain is FX61(T) (= CGMCC 4.7042(T) = KCTC 29112(T)).
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http://dx.doi.org/10.1099/ijs.0.047050-0DOI Listing
August 2013

Friedmanniella flava sp. nov., a soil actinomycete.

Int J Syst Evol Microbiol 2013 May 31;63(Pt 5):1771-1775. Epub 2012 Aug 31.

National Engineering Research Center for Vegetables, Beijing 100097, PR China.

A novel actinomycete, strain W6(T), was isolated from a soil sample of Yunnan Province, China. The bacterium was aerobic, non-motile, non-spore-forming and Gram-stain-positive. Genetic, phenotypic and chemical properties of the isolate were studied. 16S rRNA gene sequence data suggested that the novel isolate belonged to the genus Friedmanniella and shared 98.6% sequence similarity with Friedmanniella antarctica DSM 11053(T) and Friedmanniella okinawensis DSM 21744(T), the most closely related species. The cell-wall peptidoglycan contained ll-diaminopimelic acid, and mycolic acids were absent. The main menaquinone was MK-9(H4) and the predominant fatty acids were anteiso-C15:0 and iso-C15:0. The phospholipid profile contained phosphatidylglycerol, phosphatidylinositol, phosphatidylcholine and diphosphatidylglycerol. The DNA G+C content of strain W6(T) was 72 mol%. Strain W6(T) showed 30.0% and 28.5% DNA-DNA relatedness, respectively, to F. antarctica DSM 11053(T) and F. okinawensis DSM 21744(T). The combined genotypic and phenotypic data showed that strain W6(T) should be assigned to the genus Friedmanniella as a representative of a novel species, for which the name Friedmanniella flava sp. nov. is proposed. The type strain is W6(T) ( = CGMCC 4.6856(T) =JCM 17701(T)).
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http://dx.doi.org/10.1099/ijs.0.043984-0DOI Listing
May 2013

Characterization of photosystem I from spinach: effect of solution pH.

Photosynth Res 2012 Apr 4;112(1):63-70. Epub 2012 Apr 4.

Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266555, People's Republic of China.

Our previous work has demonstrated the isolation of photosystem I (PSI) from spinach using ultrafiltration with a final purity of 84%. In order to get a higher purity of PSI and more importantly to develop a practical bioseparation process, key physiochemical properties of PSI and their dependence on operational parameters must be assessed. In this study, the effect of solution pH, one of the most important operating parameters for membrane process, on the property of PSI was examined. Following the isolation of crude PSI from spinach using n-dodecyl-beta-D: -maltoside as detergent, the isoelectric point, aggregation size, zeta potential, low-temperature fluorescence, atomic force microscopy imaging, secondary structure, and thermal stability were determined. Solution pH was found to have a significant effect on the activity, aggregation size and thermal stability of PSI. The results also suggested that the activity of PSI was related to its aggregation size.
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http://dx.doi.org/10.1007/s11120-012-9737-6DOI Listing
April 2012

Actinoplanes atraurantiacus sp. nov., isolated from soil.

Int J Syst Evol Microbiol 2012 Oct 16;62(Pt 10):2533-2537. Epub 2011 Dec 16.

School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.

A Gram-positive-staining bacterium, designated Y16(T), was isolated from a soil sample from Yunnan Province, China. The isolate grew optimally at 25-30 °C, grew at pH 6.0-9.0 and could grow with 3 % NaCl. Strain Y16(T) had cell-wall peptidoglycan based on meso-diaminopimelic acid. The predominant menaquinones were MK-9(H(4)) and MK-9(H(2)). The major fatty acid methyl esters were anteiso-C(15 : 0), iso-C(15 : 0), anteiso-C(17 : 0) and C(16 : 0). These chemotaxonomic characteristics suggested that the organism belonged to the genus Actinoplanes. Strain Y16(T) shared 98.7, 98.3 and 97.9 % 16S rRNA gene sequence similarity with Actinoplanes deccanensis IFO 13994(T), A. abujensis A4029(T) and A. brasiliensis DSM 43805(T), respectively. The DNA G+C content of the isolate was 70.8 mol%. DNA-DNA relatedness between the novel isolate and the type strains of A. deccanensis, A. abujensis and A. brasiliensis was 35.2, 32.0 and 22.3 %, respectively. In addition, the pattern of phenotypic properties distinguished strain Y16(T) from its closest phylogenetic neighbours. It is therefore concluded that strain Y16(T) ( = CGMCC 4.6857(T) = JCM 17700(T)) represents a novel species of the genus Actinoplanes, for which the name Actinoplanes atraurantiacus sp. nov. is proposed.
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http://dx.doi.org/10.1099/ijs.0.037226-0DOI Listing
October 2012

A novel membrane based process to isolate photosystem-I membrane complex from spinach.

Photosynth Res 2011 Feb 28;107(2):187-93. Epub 2011 Jan 28.

Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266555, People's Republic of China.

The isolation of photosystem-I (PS-I) from spinach has been conducted using ultrafiltration with 300 kDa molecular weight cut-off polyethersulfone membranes. The effects of ultrafiltration operating conditions on PS-I activity were optimized using parameter scanning ultrafiltration. These conditions included solution pH, ionic strength, stirring speed, and permeate flux. The effects of detergent (Triton X-100 and n-dodecyl-beta-D-maltoside) concentration on time dependent activity of PS-I were also studied using an O(2) electrode. Under optimized conditions, the PS-I purity obtained in the retentate was about 84% and the activity recovery was greater than 94% after ultrafiltration. To our knowledge, this is the first report of the isolation of a membrane protein using ultrafiltration alone.
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http://dx.doi.org/10.1007/s11120-011-9625-5DOI Listing
February 2011
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