Publications by authors named "Cui-Cui Liu"

49 Publications

The epigenetic mechanisms involved in chronic pain in rodents: A mini-review.

Curr Neuropharmacol 2021 Sep 23. Epub 2021 Sep 23.

Guangdong Province Key Laboratory of Brain Function and Disease, Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.

Chronic pain, as a common distressing neurological disorder, about 30% of the global population suffers from it. In addition to being highly prevalent, chronic pain causes heavy economic and social burden. Although substantial progress has been achieved to dissect the underlying mechanism of chronic pain in the past few decades, the incidence and treatment of this neurological illness is yet not properly managed in clinical practice. While nerve injury-, chemotherapy- or inflammation-induced functional regulation of gene expression in the dorsal root ganglion and spinal cord are extensively reported to be involved in the pathogenic process of chronic pain, the specific mechanism of these altered transcriptional profile still remains unclear. Recent studies have shown that epigenetic mechanisms, including DNA/RNA methylation, histone modification and circular RNAs regulation, are involved in the occurrence and development of chronic pain. In this review, we provide a description of research on the role of epigenetic mechanism in chronic pain, summarize the latest clinical and preclinical advance in this field, and propose the potential directions for further research to elucidate the molecular mechanism underlying the pathogenesis of chronic pain.
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http://dx.doi.org/10.2174/1570159X19666210924104757DOI Listing
September 2021

Primary central nervous system lymphoma initially manifesting as cerebral white matter lesions followed by isolated extracerebral relapse: a case report.

Neurol Sci 2021 Nov 12;42(11):4825-4828. Epub 2021 Aug 12.

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, People's Republic of China.

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http://dx.doi.org/10.1007/s10072-021-05532-4DOI Listing
November 2021

The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling.

Front Oncol 2021 11;11:616445. Epub 2021 Mar 11.

Department of Anesthesia, Jinan People's Hospital, Jinan, China.

Non-small cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. Bupivacaine serves as a widely used local anesthetic and presents potential anti-tumor activity. Nevertheless, the function of bupivacaine in the NSCLC development remains elusive. Here, we tried to investigate the impact of bupivacaine on the NSCLC progression. Significantly, we revealed that bupivacaine was able to reduce the proliferation and induce the apoptosis of NSCLC cells. Bupivacaine could attenuate the invasion and migration in the cells. Mechanically, the treatment of bupivacaine increased the expression ratio of light chain 3B-II (LC3B-II)/LC3B-I and the expression of Beclin-1 in the NSCLC cells. Meanwhile, the expression of the autophagic adaptor protein p62 was decreased by bupivacaine treatment in the cells. The treatment of bupivacaine attenuated the phosphorylation of AKT and mTOR in the NSCLC cells. The AKT activator SC79 and autophagy inhibitor 3-methyladenine (3-MA) reversed the bupivacaine-inhibited phosphorylation of AKT and mTOR and bupivacaine-induced autophagy, as well as the bupivacaine-attenuated NSCLC progression in the cells. Bupivacaine could inhibit the tumor growth . In conclusion, we discovered that the local anesthetic bupivacaine inhibited the progression of NSCLC by inducing autophagy through Akt/mTOR signaling. Our finding provides new insights into the mechanism by which bupivacaine attenuates the development of NSCLC. Bupivacaine may serve as a potential anti-tumor candidate for the therapeutic strategy of NSCLC.
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http://dx.doi.org/10.3389/fonc.2021.616445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991299PMC
March 2021

Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.

Cancer Sci 2021 Jun 1;112(6):2349-2360. Epub 2021 May 1.

Department of Lung Cancer, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.
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http://dx.doi.org/10.1111/cas.14845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177790PMC
June 2021

STIM1 mediates IAV-induced inflammation of lung epithelial cells by regulating NLRP3 and inflammasome activation via targeting miR-223.

Life Sci 2021 Feb 2;266:118845. Epub 2020 Dec 2.

Department of Respiratory and Critical Care Medicine, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi, China. Electronic address:

Aims: Influenza A virus (IAV) infection accelerates the inflammatory injury of lung epithelial cells that contributes to pulmonary lesion. Recently, stromal interaction molecule 1 (STIM1) was found to mediate cellular immune response and participated in lung tumorigenesis. Our study aimed to illustrate the function and mechanism of STIM1 in IAV-induced inflammation injury and oxidative stress of lung epithelial cells.

Main Methods: We evaluated the levels of STIM1 in IAV-infected patients' serum and BEAS-2B cells using RT-qPCR, Elisa and western blotting methods. MTT and Elisa were performed to measure cell viability and cytokine contents. Besides, ROS intensity, SOD contents and cell apoptosis were detected based on DCFH-DA probe, colorimetry and cell death kits. A luciferase assay and Pearson's correlation analysis evaluated the associations between target genes.

Key Findings: STIM1 was dramatically up-regulated in IAV-infected patients' serum and BEAS-2B cells. Silencing STIM1 in vitro inhibited oxidative stress and inflammatory responses induced by IAV, and reversed cell viability and suppressed apoptosis. Moreover, miR-223 and NLRP3 were negatively and positively correlated with STIM1. STIM1 was found to regulate NLRP3 expression by binding the AACUGAC motif in miR-223. STIM1/miR-223/NLRP3 axis modulated IAV-induced inflammation injury of lung epithelial cells.

Significance: Our evidence indicated that silencing STIM1 alleviated IAV-induced inflammation injury of lung epithelial cells by inactivating NLRP3 and inflammasome via promoting miR-223 expression. These findings may contribute to understand the mechanism of IAV-induced lung injury and help for therapy of IAV infection.
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http://dx.doi.org/10.1016/j.lfs.2020.118845DOI Listing
February 2021

Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation.

J Alzheimers Dis 2020 ;74(2):521-534

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.

Hyperphosphorylated tau is one of the key characteristics of Alzheimer's disease (AD), and tau pathology correlates with cognitive impairment in AD better than amyloid-β (Aβ) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOEɛ4, the strongest genetic risk factor for AD, was found to be involved in tau pathology in frontotemporal dementia. This result indicated that apolipoprotein E (ApoE) may also participate in tau phosphorylation in AD. In the present study, we injected Aβ oligomer (AβO) into the lateral ventricles of wild-type (WT) mice and apoE-/- mice to test the process of tau phosphorylation in the acute phase. We found that the phosphorylated tau and phosphokinase levels were higher in WT mice than in apoE-/- mice. These phenomena were also confirmed in vitro. ApoE ɛ4-treated apoE-/- neurons exhibited more phosphorylated tau than ApoE ɛ2- and ApoE ɛ3-treated neurons. We also found that AβO induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by AβOs in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by AβO via inflammation.
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http://dx.doi.org/10.3233/JAD-190711DOI Listing
August 2021

Genome wide survey, evolution and expression analysis of PHD finger genes reveal their diverse roles during the development and abiotic stress responses in Brassica rapa L.

BMC Genomics 2019 Oct 24;20(1):773. Epub 2019 Oct 24.

Key Laboratory of Ministry of Education for Genetics, Breeding and Multiple Utilization of Crops, College of Crop Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Background: Plant homeodomain (PHD) finger proteins are widely present in all eukaryotes and play important roles in chromatin remodeling and transcriptional regulation. The PHD finger can specifically bind a number of histone modifications as an "epigenome reader", and mediate the activation or repression of underlying genes. Many PHD finger genes have been characterized in animals, but only few studies were conducted on plant PHD finger genes to this day. Brassica rapa (AA, 2n = 20) is an economically important vegetal, oilseed and fodder crop, and also a good model crop for functional and evolutionary studies of important gene families among Brassica species due to its close relationship to Arabidopsis thaliana.

Results: We identified a total of 145 putative PHD finger proteins containing 233 PHD domains from the current version of B. rapa genome database. Gene ontology analysis showed that 67.7% of them were predicted to be located in nucleus, and 91.3% were predicted to be involved in protein binding activity. Phylogenetic, gene structure, and additional domain analyses clustered them into different groups and subgroups, reflecting their diverse functional roles during plant growth and development. Chromosomal location analysis showed that they were unevenly distributed on the 10 B. rapa chromosomes. Expression analysis from RNA-Seq data showed that 55.7% of them were constitutively expressed in all the tested tissues or organs with relatively higher expression levels reflecting their important housekeeping roles in plant growth and development, while several other members were identified as preferentially expressed in specific tissues or organs. Expression analysis of a subset of 18 B. rapa PHD finger genes under drought and salt stresses showed that all these tested members were responsive to the two abiotic stress treatments.

Conclusions: Our results reveal that the PHD finger genes play diverse roles in plant growth and development, and can serve as a source of candidate genes for genetic engineering and improvement of Brassica crops against abiotic stresses. This study provides valuable information and lays the foundation for further functional determination of PHD finger genes across the Brassica species.
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http://dx.doi.org/10.1186/s12864-019-6080-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814106PMC
October 2019

CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain.

Nat Commun 2019 09 11;10(1):4119. Epub 2019 Sep 11.

Guangdong Province Key Laboratory of Brain Function and Disease, Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.

Circular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus. Downregulation of circAnks1a by siRNA attenuates pain-like behaviour induced by nerve injury. In the cytoplasm, we show that circAnks1a promotes the interaction between transcription factor YBX1 and transportin-1, thus facilitating the nucleus translocation of YBX1. In the nucleus, circAnks1a binds directly to the Vegfb promoter, increases YBX1 recruitment to the Vegfb promoter, thereby facilitating transcription. Furthermore, cytoplasmic circAnks1a acts as a miRNA sponge in miR-324-3p-mediated posttranscriptional regulation of VEGFB expression. The upregulation of VEGFB contributes to increased excitability of dorsal horn neurons and pain behaviour induced by nerve injury. We propose that circAnks1a and VEGFB are regulators of neuropathic pain.
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http://dx.doi.org/10.1038/s41467-019-12049-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739334PMC
September 2019

Randomized Trial on Comparison of the Efficacy of Extracorporeal Shock Wave Therapy and Dry Needling in Myofascial Trigger Points.

Am J Phys Med Rehabil 2019 08;98(8):677-684

From the Department of Rehabilitation Medicine, Guangdong Second Provincial General Hospital, Southern Medical University, Guangzhou, People's Republic of China (SL); Department of Rehabilitation Medicine, Lianjiang People's Hospital, Guangdong, People's Republic of China (ZZ); Department of Rehabilitation, Sun Yat-Sen Memorial Hospital, Guangzhou, People's Republic of China (SL, C. Lin, SK, C. Liu, SW, CM); Department of Ultrasonic, Sun Yat-Sen Memorial Hospital, Guangzhou, People's Republic of China (JR); and Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China (WX).

Objective: The aim of the study was to compare the efficacy of radial extracorporeal shock wave therapy and dry needling in the treatment of myofascial trigger points in the upper trapezius muscle.

Design: A total of 65 patients with myofascial trigger points were randomly divided into extracorporeal shock wave therapy group (n = 32) and dry needling group (n = 33). Patients received 3 wks of treatment at 1-wk intervals (in both groups). Visual analog scale, pressure pain threshold, Neck Disability Index, and shear modulus were evaluated before treatment, immediately after the first therapy, 1 mo, and 3 mos after the completion of the third therapy.

Results: Significant improvements of visual analog scale, pressure pain threshold, and Neck Disability Index scores were observed at all time points after treatment (P < 0.01) in both treatment groups. The shear modulus of myofascial trigger points was reduced in both dry needling group (P < 0.05) and extracorporeal shock wave therapy group (P < 0.01) immediately after the first treatment. Significant reductions in shear modulus were maintained up to 3-mo posttreatment in both groups (P < 0.01). There were no significant differences between the radial extracorporeal shock wave therapy group and dry needling group.

Conclusions: The extracorporeal shock wave therapy is as effective as dry needling for relieving pain, improving function, and reducing shear modulus for patients with myofascial trigger points after a series of three treatments.
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http://dx.doi.org/10.1097/PHM.0000000000001173DOI Listing
August 2019

Reduction of SIRT1 epigenetically upregulates NALP1 expression and contributes to neuropathic pain induced by chemotherapeutic drug bortezomib.

J Neuroinflammation 2018 Oct 20;15(1):292. Epub 2018 Oct 20.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.

Background: Bortezomib is a frequently used chemotherapeutic drug for the treatment of multiple myeloma and other nonsolid malignancies. Accumulating evidence has demonstrated that bortezomib-induced persistent pain serves as the most frequent reason for treatment discontinuation.

Methods: The von Frey test was performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, chromatin immunoprecipitation, western blot, immunohistochemistry, and small interfering RNA were performed to explore the molecular mechanisms in adult male Sprague-Dawley rats.

Results: We found that application of bortezomib significantly increased the expression of NALP1 protein and mRNA levels in spinal dorsal horn neurons, and intrathecal application of NALP1 siRNA attenuated the bortezomib-induced mechanical allodynia. In addition, bortezomib also decreased the SIRT1 expression, and treatment with SIRT1 activator resveratrol ameliorated the NALP1 upregulation and mechanical allodynia induced by bortezomib. Meanwhile, knockdown of SIRT1 using the SIRT1 siRNA induced the NALP1 upregulation in dorsal horn and mechanical allodynia in normal animal. These results suggested that reduction of SIRT1 induced the NALP1 upregulation in dorsal horn neurons, and participated in bortezomib-induced mechanical allodynia. Importantly, we found that the binding of SIRT1 and NALP1 promoter region did not change before and after bortezomib treatment, but SIRT1 downregulation increased p-STAT3 expression. Furthermore, the activation of STAT3 enhanced the recruitment of p-STAT3 to the Nalp1 gene promoter, which increased the acetylation of histone H3 and H4 in NALP1 promoter regions and epigenetically upregulated NALP1 expression in the rodents with bortezomib treatment.

Conclusion: These findings suggested a new epigenetic mechanism for NALP1 upregulation involving SIRT1 reduction and subsequent STAT3-mediated histone hyperacetylation in NALP1 promoter region in dorsal horn neurons, which contributed to the bortezomib-induced mechanical allodynia.
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http://dx.doi.org/10.1186/s12974-018-1327-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195754PMC
October 2018

flavonoid extraction for spinal cord injury in a rat model.

Neural Regen Res 2018 Dec;13(12):2200-2208

Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Flavonoids from Huangqin (dried roots of Scutellaria baicalensis Georgi) have anti-inflammatory effects, and are considered useful for treatment of spinal cord injury. To verify this hypothesis, the T9-10 spinal cord segments of rats were damaged using Allen's method to establish a rat spinal cord injury model. Before model establishment, Huangqin flavonoid extraction (12.5 g/kg) was administered intragastrically for 1 week until 28 days after model establishment. Methylprednisolone (30 mg/kg) was injected into the tail vein at 30 minutes after model establishment as a positive control. Basso, Beattie, and Bresnahan locomotor scale scores were used to assess hind limb motor function. Hematoxylin-eosin staining was used to detect pathological changes in the injured spinal cord. Immunofluorescence and western blot assays were performed to measure immunoreactivity and expression levels of brain-derived neurotrophic factor, neuronal marker neurofilament protein, microglial marker CD11b and astrocyte marker glial fibrillary acidic protein in the injured spinal cord. Huangqin flavonoid extraction markedly reduced spinal cord hematoma, inflammatory cell infiltration and cavities and scars, and increased the Basso, Beattie, and Bresnahan locomotor scale scores; these effects were identical to those of methylprednisolone. Huangqin flavonoid extraction also increased immunoreactivity and expression levels of brain-derived neurotrophic factor and neurofilament protein, and reduced immunoreactivity and expression levels of CD11b and glial fibrillary acidic protein, in the injured spinal cord. Overall, these data suggest that Huangqin flavonoid extraction can promote recovery of spinal cord injury by inducing brain-derived neurotrophic factor and neurofilament protein expression, reducing microglia activation and regulating reactive astrocytes.
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http://dx.doi.org/10.4103/1673-5374.241472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199921PMC
December 2018

[Residue Levels and Health Risk Assessment of Organochlorine Pesticides in Rice from Shanghai].

Huan Jing Ke Xue 2018 Feb;39(2):927-934

Key Laboratory of Yangtze River Water Environment(Ministry of Education), College of Environment Science and Engineering, Tongji University, Shanghai 200092, China.

As one of the main producers and consumers of pesticides in the world, China has historically used large quantities of organochlorine pesticides, such as DDT and HCH. Rice is a staple food crop in Shanghai, where the Qingpu and Chongming districts are two important rice planting areas. This study detected the residue levels of 24 organochlorine pesticides (OCPs) in rice samples collected from Qingpu and Chongming in Shanghai. The composition and health risk of OCPs in rice samples were investigated. The results revealed that DDTs and HCHs were the main OCPs in rice from the study area. The mean levels of 24 OCPs residues in rice from Qingpu and Chongming were 6.53 ng·g and 4.70 ng·g, respectively. The analyses of all the target compounds met the China National Food Safety Standard. The concentrations of 4,4-DDE and -HCH were the highest in rice from Qingpu, while 2,4-DDT and -HCH were the main components in rice from Chongming. Source analysis showed that dicofol and lindane might be still used recently in some areas of Shanghai. The health risk assessment results indicated that there was no obvious risk to human health by eating rice from Shanghai based on the OCPs studied.
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http://dx.doi.org/10.13227/j.hjkx.201706080DOI Listing
February 2018

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na1.6 in sensory neurons to promote neuropathic pain.

Sci Signal 2018 03 27;11(523). Epub 2018 Mar 27.

Neuroscience Program, Zhongshan School of Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou 510080, China.

Palmitoylation of δ-catenin is critical to synapse plasticity and memory formation. We found that δ-catenin palmitoylation is also instrumental in the development of neuropathic pain. The abundances of palmitoylated δ-catenin and the palmitoyl acyltransferase DHHC3 were increased in dorsal root ganglion (DRG) sensory neurons in rat models of neuropathic pain. Inhibiting palmitoyl acyltransferases or decreasing δ-catenin abundance in the DRG by intrathecal injection of 2-bromopalmitate or shRNA, respectively, alleviated oxaliplatin or nerve injury-induced neuropathic pain in the rats. The palmitoylation of δ-catenin, which was induced by the inflammatory cytokine TNF-α, facilitated its interaction with the voltage-gated sodium channel Na1.6 and the kinesin motor protein KIF3A, which promoted the trafficking of Na1.6 to the plasma membrane in DRG neurons and contributed to mechanical hypersensitivity and allodynia in rats. These findings suggest that a palmitoylation-mediated KIF3A/δ-catenin/Na1.6 complex enhances the transmission of mechanical and nociceptive signals; thus, blocking this mechanism may be therapeutic in patients with neuropathic pain.
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http://dx.doi.org/10.1126/scisignal.aar4394DOI Listing
March 2018

Upregulation of NLRP3 via STAT3-dependent histone acetylation contributes to painful neuropathy induced by bortezomib.

Exp Neurol 2018 04 12;302:104-111. Epub 2018 Jan 12.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address:

Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats. Furthermore, the expressions of p-STAT3 were colocalized with NLRP3-positive cells in DRG neurons, and inhibition of STAT3 by intrathecal injection of AAV-Cre-GFP into STAT3 mice or inhibitor S3I-201 suppressed the upregulation of NLRP3 and mechanical allodynia induced by bortezomib treatment. Chromatin immunoprecipitation further found that bortezomib increased the recruitment of STAT3, as well as the acetylation of histone H3 and H4, in the NLRP3 promoter region in DRG neurons. Importantly, inhibition of the STAT3 activity by using S3I-201 or DRG local deficiency of STAT3 also significantly prevented the upregulated H3 and H4 acetylation in the NLRP3 promoter region following bortezomib treatment. Altogether, our results suggest that the upregulation of NLRP3 in DRG via STAT3-dependent histone acetylation is critically involved in bortezomib-induced mechanical allodynia.
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http://dx.doi.org/10.1016/j.expneurol.2018.01.011DOI Listing
April 2018

Predicting Parametrial Invasion in Cervical Carcinoma (Stages IB1, IB2, and IIA): Diagnostic Accuracy of T2-Weighted Imaging Combined With DWI at 3 T.

AJR Am J Roentgenol 2018 Mar 11;210(3):677-684. Epub 2018 Jan 11.

1 Department of Radiology, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Rd, Zhengzhou 45008, China.

Objective: The objective of our study was to retrospectively evaluate the efficacy of combined analysis of T2-weighted imaging and DWI in the diagnosis of parametrial invasion (PMI) in cervical carcinoma.

Materials And Methods: The clinical records of 192 patients with cervical carcinoma who met the study requirements were reviewed for this retrospective study. The signal intensities of suspicious PMI tissue were assessed on T2-weighted images, DW images, and apparent diffusion coefficient maps independently by two experienced radiologists. The radiologist observers predicted the presence of PMI by scoring T2-weighted imaging alone and then by scoring T2-weighted imaging and DWI combined. The results were compared with histopathologic findings.

Results: Histopathologic findings revealed PMI in 24 of 192 study subjects. In positively predicting the presence of PMI, T2-weighted imaging and DWI combined scored significantly better than T2-weighted imaging alone, as proven by high sensitivity (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 75.0% vs 83.3% [p = 0.477]; observer 2, 66.7% vs 91.7% [p < 0.05]), high specificity (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 84.5% vs 98.8% [p < 0.001]; observer 2, 85.7% vs 98.8% [p < 0.001]), and high accuracy (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 83.3% vs 96.9% [p < 0.001]; observer 2, 83.3% vs 97.9% [p < 0.001]). The area under the ROC curve was also significantly higher for T2-weighted imaging and DWI combined (observer 1, 0.911; observer 2, 0.952) than for T2-weighted imaging alone (observer 1, 0.798; observer 2, 0.762). Although the interobserver agreement was good for T2-weighted imaging (κ = 0.695) and excellent for T2-weighted imaging and DWI combined (κ = 0.753), the improvement failed to achieve statistical significance (p = 0.28).

Conclusion: Combined analysis of T2-weighted imaging and DWI enhances the accuracy of diagnosing PMI in patients with cervical cancer compared with T2-weighted imaging alone.
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http://dx.doi.org/10.2214/AJR.17.18104DOI Listing
March 2018

Multifunctionalization of graphene and graphene oxide for controlled release and targeted delivery of anticancer drugs.

Am J Transl Res 2017 15;9(12):5197-5219. Epub 2017 Dec 15.

Translational Medicine Center, Hong-Hui Hospital, Xi'an Jiaotong University College of MedicineXi'an 710054, China.

Among various nanomaterials, graphene and its derivatives have attracted considerable research interest in diverse application areas-including nanomedicine-because of their extraordinary physical, chemical, and optical properties. Intensive research is underway to investigate the biomedical application of graphene and graphene-based nanosystems as drug-delivery vehicles for cancer therapy, and this is considered as one of the novel therapeutic approaches for performing on-demand chemotherapy coupled with photothermal therapy or photodynamic therapy. Here, we systematically summarize recent progress in the synthesis and functionalization of graphene by using a vast range of materials, including small molecules, polymers, and biomolecules, in order to overcome the inherent drawbacks of graphene oxide (GO) nanocarriers and thereby make these nanocarriers suitable for delivering chemotherapeutic agents, genes, and short interfering RNAs. Moreover, we address the opportunities and challenges associated with future clinical application of GO for cancer therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752875PMC
December 2017

A distinct clinicopathological variant of focal cortical dysplasia IIId characterized by loss of layer 4 in the occipital lobe in 12 children with remote hypoxic-ischemic injury.

Epilepsia 2017 10 23;58(10):1697-1705. Epub 2017 Aug 23.

Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: In 2011, the International League Against Epilepsy (ILAE) proposed a consensus classification system of focal cortical dysplasia (FCD) to distinguish clinicopathological subtypes, for example, "isolated" FCD type Ia-c and IIa-b, versus "associated" FCD type IIIa-d. The histopathological differentiation of FCD type I and III variants remains, however, a challenging issue in everyday practice. We present a unique histopathological pattern in patients with difficult-to-diagnose FCD, which highlights this dilemma, but also helps to refine the current ILAE classification scheme of FCD.

Methods: We present a retrospective series of 11 male and one female patient with early onset pharmacoresistant epilepsy of the posterior quadrant (mean age at seizure onset = 4.6 years). All surgical specimens were reviewed. Clinical histories were retrieved and extracted from archival patient files.

Results: Microscopic inspection revealed abnormalities in cortical architecture with complete loss of layer 4 in all surgical samples of the occipital lobe, as confirmed by semiquantitative measurements (p < 0.01). Clinical history reported early transient hypoxic condition in nine patients (75%). Magnetic resonance imaging (MRI) revealed abnormal signals in the occipital lobe in all patients, and signal changes suggestive of subcortical encephalomalacia were found in seven patients. Surgical treatment achieved favorable seizure control (Engel class I and II) in seven patients with an available follow-up period of 6.1 years.

Significance: Prominent disorganization of cortical layering and lack of any other microscopically visible principle lesion in the surgical specimen would result in this neuropathological pattern hitherto being classified as FCD ILAE type Ib. However, perinatal hypoxia with distinctive MRI changes suggested primarily a hypoxemic lesion and acquired pathomechanism of neuronal cell loss in the occipital lobe of our patient series. We propose, therefore, classifying this distinctive clinicopathological pattern as a separate variant of FCD ILAE type IIId.
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http://dx.doi.org/10.1111/epi.13855DOI Listing
October 2017

Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib.

Exp Neurol 2017 10 18;296:74-82. Epub 2017 Jul 18.

Zhongshan School of Medicine, Guangdong Province Key Laboratory of Brain Function and Disease, Faculty of Forensic Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats. Spinal local application of methylglyoxal also induced mechanical allodynia and central sensitization in normal rats. Moreover, administration of bortezomib upregulated the expression of receptors for advanced glycation end products (RAGE) and phosphorylated STAT3 (p-STAT3) in dorsal horn. Importantly, intrathecal injection of metformin, a known scavenger of methylglyoxal, significantly attenuated the upregulation of methylglyoxal and RAGE in dorsal horn, central sensitization and mechanical allodynia induced by bortezomib treatment, and blockage of RAGE also prevented the upregulation of p-STAT3, central sensitization and mechanical allodynia induced by bortezomib treatment. In addition, inhibition of STAT3 activity by S3I-201 attenuated bortezomib-induced mechanical allodynia and central sensitization. Local knockdown of STAT3 also ameliorated the mechanical allodynia induced by bortezomib administration. Our results suggest that accumulation of methylglyoxal may activate the RAGE/STAT3 signaling pathway in dorsal horn, and contributes to the spinal central sensitization and persistent pain induced by bortezomib treatment.
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http://dx.doi.org/10.1016/j.expneurol.2017.07.010DOI Listing
October 2017

Activation of the RAGE/STAT3 Pathway in the Dorsal Root Ganglion Contributes to the Persistent Pain Hypersensitivity Induced by Lumbar Disc Herniation.

Pain Physician 2017 07;20(5):419-427

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

Background: Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy.

Objective: The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH.

Study Design: Controlled animal study.

Setting: University laboratory.

Methods: After LDH induced by implantation of autologous nucleus pulposus (NP, harvested from animal tail) on the left L5 nerve root was established, mechanical thresholds and electrophysiological tests were conducted at relevant time points during an observation period of 28 days. Protein levels and localization of RAGE and p-STAT3 were performed by using Western blotting and immunohistochemistry, respectively.

Results: LDH induced persistent pain hypersensitivity, increased excitability of DRG neurons, and upregulated the expression of RAGE and p-STAT3 in the DRG. Consecutive injection of both RAGE antagonist FPS-ZM1 (i.t.) and STAT3 activity inhibitor S3I-201 (i.t.) inhibited the enhanced excitability of DRG neurons and mechanical allodynia induced by NP implantation. Furthermore, local knockdown of STAT3 by intrathecal injection of AAV-Cre-GFP into STAT3flox/flox mice markedly alleviated NP implantation-induced mechanical allodynia in mice. Importantly, the expression of p-STAT3 was colocalized with that of RAGE in the DRG and inhibition of RAGE with FPS-ZM1 prevented NP implantation-induced STAT3 activation.

Limitations: More underlying mechanism(s) of the role of the RAGE/STAT3 pathway on the formation and development of persistent pain hypersensitivity induced by LDH will be needed to be explored in future research.

Conclusions: These findings suggest activation of the RAGE/STAT3 pathway plays a critical role in persistent pain induced by LDH, and this pathway may represent novel therapeutic targets for the treatment of LDH-induced persistent pain.

Key Words: Lumbar disc herniation, persistent pain, RAGE, STAT3, DRG.
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July 2017

Heterologous Expression and Characterization of a Novel Chitinase (ChiEn1) from Coprinopsis cinerea and its Synergism in the Degradation of Chitin.

J Agric Food Chem 2017 Aug 1;65(32):6943-6956. Epub 2017 Aug 1.

Jiangsu Key Laboratory for Microbes and Microbial Functional Genomics, Jiangsu Engineering and Technology Research Center for Industrialization of Microbial Resources, College of Life Science, Nanjing Normal University , Nanjing, PR China 210023.

Chitinase ChiEn1 did not hydrolyze insoluble chitin but showed hydrolysis and transglycosylation activities toward chitin-oligosaccharides. Interestingly, the addition of ChiEn1 increased the amount of reducing sugars released from chitin powder by endochitinase ChiIII by 105.0%, and among the released reducing sugars the amount of (GlcNAc) was increased by 149.5%, whereas the amount of GlcNAc was decreased by 10.3%. The percentage of GlcNAc in the products of chitin powder with the combined ChiIII and ChiEn1 was close to that in the products of chitin-oligosaccharides with ChiEn1, rather than that with ChiIII. These results indicate that chitin polymers are first degraded into chitin oligosaccharides by ChiIII and the latter are further degraded to monomers and dimers by ChiEn1, and the synergistic action of ChiEn1 and ChiIII is involved in the efficient degradation of chitin in cell walls during pileus autolysis. The structure modeling explores the molecular base of ChiEn1 action.
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http://dx.doi.org/10.1021/acs.jafc.7b02278DOI Listing
August 2017

[DMSO Promotes Hematopoietic Differentiation of Human Embryonic Stem Cells in vitro].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2017 Jun;25(3):644-649

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. E-mail:

Objective: To explore the role of dimethyl sulfoxide (DMSO) in the hematopoietic differentiation of human embryonic stem cells (hESCs).

Methods: The role of DMSO in hematopoietic differentiation of hESC was investigated by using a established stepwise hematopoietic differentiation system from hESC, immunofluorescouse assay and flow cytometry. Furthermore, the window phase of DMSO action was explored by adding it to the different stage of hematopoietic differentiation.

Results: Immunofluorescence and flow cytometry analysis showed that DMSO significantly promoted the generation of CD43 hematopoietic progenitor cells (HPC). The flow cytometry demonstrated that DMSO profoundly promoted the generation of APLNR lateral plate mesoderm cells and CD31CD34 hemogenic endothelium progenitors (HEP). The addition of DMSO in the window phase of lateral plate mesoderm cell generation could markedly improve the generation of hematopoietic progenitor cells.

Conclusion: DMSO promotes hematopoietic differentiation of hESC through enhancing the generation of APLNR positive lateral plate mesoderm cells. The addition of DMSO in the window phase of lateral plate mesoderm cell generation can significantly improve the generation of hematopoietic progenitor cells.
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http://dx.doi.org/10.7534/j.issn.1009-2137.2017.03.002DOI Listing
June 2017

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

J Neurophysiol 2017 08 14;118(2):1321-1328. Epub 2017 Jun 14.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; and

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain. Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain.
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http://dx.doi.org/10.1152/jn.00745.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558033PMC
August 2017

Chlorogenic acid prevents inflammatory responses in IL‑1β‑stimulated human SW‑1353 chondrocytes, a model for osteoarthritis.

Mol Med Rep 2017 Aug 6;16(2):1369-1375. Epub 2017 Jun 6.

Translational Medicine Center, Hong‑Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710054, P.R. China.

Chlorogenic acid (CGA), which is a natural compound found in various plants, has been reported to exert notable anti‑inflammatory activities. The present study investigated the effects and underlying mechanism of CGA on interleukin (IL)‑1β‑induced osteoarthritis (OA) chondrocytes. An in vitro OA‑like chondrocyte model was established using IL‑1β‑stimulated human SW‑1353 chondrocytes. Cell viability was assessed using an MTT assay. Nitric oxide (NO) and IL‑6 production were evaluated by Griess reaction and ELISA, respectively. The expression levels of inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX‑2), collagen II, matrix metalloproteinase (MMP)‑13, p65 nuclear factor (NF)‑κB and inhibitor‑κBα were detected by western blot analysis. The results indicated that CGA reversed IL‑1β‑induced increases in iNOS/NO, IL‑6, MMP‑13 and COX‑2/PGE2 production, and reversed the IL‑1β‑mediated downregulation of collagen II. In addition, the data suggested that CGA was capable of inhibiting the IL‑1β‑induced inflammatory response, at least partially via the NF‑κB signaling pathway. In conclusion, CGA may be considered a suitable candidate agent in the treatment of OA.
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http://dx.doi.org/10.3892/mmr.2017.6698DOI Listing
August 2017

Epigenetic upregulation of CXCL12 expression mediates antitubulin chemotherapeutics-induced neuropathic pain.

Pain 2017 04;158(4):637-648

Department of Forensic Medicine, Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou, China.

Clinically, Microtubule-targeted agents-induced neuropathic pain hampers chemotherapeutics for patients with cancer. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12 and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 using the transgenic mice (CXCL12) or neutralizing antibody or siRNA ameliorated the mEPSC's enhancement and mechanical allodynia. In addition, paclitaxel and vincristine both could increase the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the acetylation of histone H4 in the CXCL12-expressing neurons. Immunoprecipitation and chromatin immunoprecipitation assays demonstrated that antitubulin chemotherapeutics increased the binding of STAT3 to the CXCL12 gene promoter and the interaction between STAT3 and p300, and contributed to the enhanced transcription of CXCL12 by increasing the acetylation of histone H4 in CXCL12 gene promoter. Inhibition of STAT3 by intrathecal injection of adeno-associated virus encoding Cre and green fluorescent protein into STAT3 mice or inhibitor S3I-201 into rats suppressed the CXCL12 upsurge by decreasing the acetylation of histone H4. Finally, blockade of CXCR4 but not CXCR7 ameliorated the paclitaxel- or vincristine-induced mechanical allodynia. Together, these results suggested that enhanced interaction between STAT3 and p300 mediated the epigenetic upregulation of CXCL12 in dorsal horn neurons, which contributed to the antitubulin chemotherapeutics-induced persistent pain.
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http://dx.doi.org/10.1097/j.pain.0000000000000805DOI Listing
April 2017

The inhibition of spinal synaptic plasticity mediated by activation of AMP-activated protein kinase signaling alleviates the acute pain induced by oxaliplatin.

Exp Neurol 2017 Feb 14;288:85-93. Epub 2016 Nov 14.

Zhongshan School of Medicine, Guangdong Province Key Laboratory of Brain Function and Disease, Faculty of Forensic Medicine, Sun Yat-Sen University, Guangzhou 510080, China.

Our recent findings demonstrated that oxaliplatin entering CNS may directly induce spinal central sensitization, and contribute to the rapid development of CNS-related side effects including acute pain during chemotherapy. However, the mechanism is largely unclear. In the current study, we found that the amplitude of C-fiber-evoked field potentials was significantly increased and the expression of phosphorylated mammalian AMP-activated protein kinase α (AMPKα) was markedly decreased following high frequency stimulation (HFS) or single intraperitoneal injection of oxaliplatin (4mg/kg). Spinal local application of AMPK agonist metformin (25μg) prevented the long term potentiation (LTP) induction and the activation of mTOR/p70S6K signal pathway, and significantly attenuated the acute thermal hyperalgesia and mechanical allodynia following single oxaliplatin treatment. Importantly, we found that incubation of low concentration oxaliplatin at dose of 6.6nM (the detected concentration in CSF following a single intraperitoneal injection of oxaliplatin) also significantly inhibited the AMPKα activation and increased the amplitude of sEPSCs, the number of action potential, and the expression of p-mTOR and p-p70S6K in spinal cord slices. Metformin (25μg) or rapamycin (2μg) inhibited the increased excitability of dorsal horn neurons and the decrease of p-AMPKα expression induced by low concentration oxaliplatin incubation. Furthermore, spinal application of AMPK inhibitor compound C (5μg) induced the spinal LTP, thermal hyperalgesia and mechanical allodynia, and rapamycin attenuated the spinal LTP, the thermal hyperalgesia and mechanical allodynia following oxaliplatin treatment (i.p.). Local application of metformin significantly decreased the mTOR and p70S6K activation induced by tetanus stimulation or oxaliplatin (i.p.). These results suggested that the decreased AMPKα activity via negatively regulating mTOR/p70S6K signal pathway enhanced the synaptic plasticity and contributed to acute pain induced by low concentration of oxaliplatin entering CNS.
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http://dx.doi.org/10.1016/j.expneurol.2016.11.009DOI Listing
February 2017

Progress on the autophagic regulators and receptors in plants.

Yi Chuan 2016 07;38(7):644-650

Institute of Genetics, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.

Autophagy is an evolutionarily highly conserved catabolic pathway among eukaryotic cells that protects the organisms against environmental stress. Normally, autophagy is mainly involved with autophagy-related proteins(ATGs) and autophagic regulators including a series of cytoplasmic proteins and small molecules. Besides, the selective autophagy, which targets damaged organalles or protein aggregates, is mediated by the additional receptors to help the ATGs recognize different substrates. In this review, we summarize recent advances in autophagic regulators like ROS(Reactive oxygen species), TOR(Target of rapamycin) and receptors like NBR1(Neighbor of BRCA1 gene protein), RPN10(Regulatory particle non-ATPase 10) as well as their functional mechanisms mainly in Arabidopsis thaliana.
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http://dx.doi.org/10.16288/j.yczz.15-525DOI Listing
July 2016

Application of bee venom and its main constituent melittin for cancer treatment.

Cancer Chemother Pharmacol 2016 Dec 27;78(6):1113-1130. Epub 2016 Sep 27.

Translational Medicine Center, Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, 710054, China.

Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles. In this review, we summarize the current knowledge regarding anticancer effects of bee venom and its main compound MEL on different kinds of tumor cells as well as elucidate their possible anticancer mechanisms. It could be concluded that MEL exerts multiple effects on cellular functions of cancerous cells such as proliferation, apoptosis, metastasis, angiogenesis as well as cell cycle, and the anticancer processes involve diverse signal molecules and regulatory pathways. We also highlight the recent research progress for efficient delivery of MEL peptide, thus providing new ideas and hopeful strategies for the in vivo application of MEL.
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http://dx.doi.org/10.1007/s00280-016-3160-1DOI Listing
December 2016

[Inhibitory effect of KyoT2 overexpression on proliferation and migration of airway smooth muscle cells in mice with asthma].

Zhongguo Dang Dai Er Ke Za Zhi 2016 Sep;18(9):885-890

Department of Asthma, Children's Hospital of Xi'an, Xi'an 710003, China.

Objective: To investigate the effect of KyoT2 on the proliferation and migration of airway smooth muscle cells (ASMCs) in mice with asthma.

Methods: Ovalbumin (OVA) was used to establish the asthmatic model of airway remodeling in BALB/c mice. ASMCs were isolated and cultured, and primarily cultured ASMCs were used as the control group. The expression of KyoT2 in ASMCs was measured in the control and asthma groups. After the ASMCs from asthmatic mice were transfected with pCMV-Myc (empty vector group) or pCMV-Myc-KyoT2 plasmid with overexpressed KyoT2 (KyoT2 expression group) for 48 hours, RT-PCR and Western blot were used to measure the mRNA and protein expression of KyoT2, the MTT assay and BrdU assay were used to measure the proliferation of ASMCs, and Transwell assay was used to measure the migration of ASMCs. Western blot was used to determine the effect of KyoT2 overexpression on the protein expression of RBP-Jκ, PTEN, and AKT.

Results: Compared with the control group, the asthma group had significantly downregulated expression of KyoT2 in ASMCs, and the KyoT2 expression group had significantly upregulated expression of KyoT2 in ASMCs (P<0.05). Compared with the empty vector group, overexpressed KyoT2 significantly inhibited cell proliferation and migration, downregulated the expression of RBP-Jκ and AKT, and upregulated the expression of PTEN.

Conclusions: Overexpressed KyoT2 can inhibit the proliferation and migration of ASMCs through the negative regulation of RBP-Jκ/PTEN/AKT signaling pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389975PMC
September 2016

The Modes of Action of ChiIII, a Chitinase from Mushroom Coprinopsis cinerea, Shift with Changes in the Length of GlcNAc Oligomers.

J Agric Food Chem 2016 Sep 8;64(37):6958-68. Epub 2016 Sep 8.

Jiangsu Key Laboratory for Microbes and Microbial Functional Genomics, Jiangsu Engineering and Technology Research Center for Industrialization of Microbial Resources, College of Life Science, Nanjing Normal University , Nanjing 210023, People's Republic of China.

A putative class III endochitinase (ChiIII) was reported previously to be expressed dominantly in fruiting bodies of Coprinopsis cinerea, and its expression levels increased with the maturation of the fruiting bodies. This paper further reports that ChiIII is a novel chitinase with exo- and endoactivities. When the substrate was (GlcNAc)3-5, ChiIII exhibited exoactivity, releasing GlcNAc processively from the reducing end of (GlcNAc)3-5; when the substrate was (GlcNAc)6-7, the activity of ChiIII shifted to an endoacting enzyme, randomly splitting chitin oligosaccharides to various shorter oligosaccharides. This shift in the mode of action of ChiIII may be related to its stronger hydrolytic capacity to degrade chitin in fungal cell walls. The predicted structure of ChiIII shows that it lacks the α+β domain insertion; however, its substrate binding cleft seems to be deeper than that of common endochitinases but shallower and more open than that of common exochitinases, which may be related to its exo- and endohydrolytic activities.
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http://dx.doi.org/10.1021/acs.jafc.6b03086DOI Listing
September 2016

mir-500-Mediated GAD67 Downregulation Contributes to Neuropathic Pain.

J Neurosci 2016 06;36(23):6321-31

Zhongshan Medical School, Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-Sen University, Guangzhou 510080, China,

Unlabelled: Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the interactions between synaptic dysfunction and the genes that are involved in persistent pain remain elusive. In the present study, we found that neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection significantly impaired the function of GABAergic synapses of spinal dorsal horn neurons via the reduction of the GAD67 expression. We also found that mir-500 expression was significantly increased and involved in the modulation of GAD67 expression via targeting the specific site of Gad1 gene in the dorsal horn. In addition, knock-out of mir-500 or using mir-500 antagomir rescued the GABAergic synapses in the spinal dorsal horn neurons and attenuated the sensitized pain behavior in the rats with neuropathic pain. To our knowledge, this is the first study to investigate the function significance and the underlying molecular mechanisms of mir-500 in the process of neuropathic pain, which sheds light on the development of novel therapeutic options for neuropathic pain.

Significance Statement: Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the underlying molecular mechanisms remain elusive. The present study illustrates for the first time a mir-500-mediated mechanism underlying spinal GABAergic dysfunction and sensitized pain behavior in neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection, which sheds light on the development of novel therapeutic options for neuropathic pain.
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http://dx.doi.org/10.1523/JNEUROSCI.0646-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604885PMC
June 2016
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