1.Chemical constituents from stems of Hedyotis hedyotidea and their immunosuppressive activity.
Tian-tian ZHANG ; Sha-sha GAO ; Jun-jie HOU ; Yong-qin ZHOU ; Jie-wen ZHOU ; Xiao-gang WANG ; Nan QIN ; Jia-chun CHEN ; Hong-quan DUAN ; Jin-bo FANG
China Journal of Chinese Materia Medica 2015;40(12):2357-2362
Hedyotis hedyotidea has been traditionally used for the treatment of arthritis, cold, cough, gastro-enteritis, headstroke, etc. But few studies have screened the active compounds from extracts of H. hedyotidea. In this study, the structure of the chemical constituents from stems of H. hedyotidea were determined and the immunosuppressive activity of the compounds was evaluated. The compounds were separated and purified with silica gel, gel column chromatographies and preparative HPLC, and their structures were identified by spectral methods such as MS and NMR. Eleven compounds were obtained and identified as(6S,9S) -vomifoliol (1), betulonic acid (2), betulinic acid (3), betulin(4), 3-epi-betulinic acid (5), ursolic acid (6), β-sitosterol (7), stigmast-4-en-3-one (8), 7β-hydroxysitosterol (9), (3β,7β) -7-methoxystigmast-5-en-3-ol (10) and morindacin (11). This is the first report of compounds 1, 2, 4, 8, 9, 10 and 11 from H. hedyotidea. Compounds 1, 2 and 8-11 were firstly isolated from the genus Hedyotis, and compounds 9 and 10 were isolated from the family Rubiaceae for the first time. The immunosuppressive activity of these compounds was tested using the lymphocyte transsormationtest. Compounds 4, 6 and 9 showed significant immunosuppressive activity.
Animals
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Drugs, Chinese Herbal
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chemistry
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isolation & purification
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pharmacology
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Hedyotis
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chemistry
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Immunosuppressive Agents
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chemistry
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isolation & purification
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pharmacology
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Lymphocytes
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drug effects
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immunology
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Male
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Mass Spectrometry
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Mice
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Mice, Inbred C57BL
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Molecular Structure
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Plant Stems
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chemistry
2.Effect of high glucose, angiotensin II and receptor antagonist Losartan on the expression of connective tissue growth factor in cultured mesangial cells.
Songmin HUANG ; Fang LIU ; Zhaohui SHA ; Ping FU ; Yifan YANG ; Yong XU ; Haiyan ZHOU
Chinese Medical Journal 2003;116(4):554-557
OBJECTIVETo observe the effect of high glucose, angiotensin II (AngII) and Losartan on the expression of connective tissue growth factor (CTGF) mRNA in cultured mesangial cells (MCs).
METHODSMCs of SD rats were isolated and cultured. High glucose (30 mmol/L) and AngII (10(-9), 10(-7), and 10(-5) mol/L) were added to the medium for 72 hours to observe the influence on CTGF mRNA expression. Losartan of 10(-5) mol/L and AngII of 10(-5) mol/L were added to the medium to observe the effects of Losartan on CTGF mRNA expression stimulated by AngII. The expressions of CTGF mRNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR).
RESULTSRT-PCR showed that high glucose and AngII up-regulated the expression of CTGF mRNA, and AngII stimulated the expression in a dose-dependent manner. Expression of CTGF mRNA induced by AngIIwas partially suppressed by 10(-5) mol/L Losartan (P < 0.05).
CONCLUSIONSHigh glucose and AngII can enhance the expression of CTGF mRNA and thus be involved in the process of renal fibrosis. Losartan can have a partial fibrogenesis-inhibiting effect, with implications for the treatment of renal fibrosis.
Angiotensin II ; pharmacology ; Animals ; Cells, Cultured ; Connective Tissue Growth Factor ; Gene Expression ; drug effects ; Glomerular Mesangium ; metabolism ; Glucose ; pharmacology ; Immediate-Early Proteins ; genetics ; Intercellular Signaling Peptides and Proteins ; genetics ; Losartan ; pharmacology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley
3.Preparation, characterization of paclitaxel-loaded Pluronic P105 polymeric micelles and in vitro reversal of multidrug resistant tumor.
Yong-Zhong WANG ; Xiao-Ling FANG ; Ya-Juan LI ; Zhi-Wen ZHANG ; Li-Mei HAN ; Xian-Yi SHA
Acta Pharmaceutica Sinica 2008;43(6):640-646
Drug delivery system (DDS) is a novel approach to overcome multidrug resistance (MDR) in tumors nowadays. This work was designed to investigate a new micellar delivery system for in vitro reversal of resistant ovarian tumor cells, based on a nonionic triblock copolymer Pluronic P105 and paclitaxel (PTX). The PTX-loaded polymeric micelles (P105/PTX) were prepared by thin film-hydration methods. Based on the results of single factor experiments, the P105/PTX micelle formulation was optimized by employing the central composite design-response surface methodology. The physico-chemical properties of the P105/PTX micelles were characterized, including micelle size, drug loading coefficient, in vitro release behavior, etc. The cytotoxicity of the P105/PTX micelles was assessed against human ovarian tumor cell line, SKOV-3/PTX, by a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. In order to understand the possible mechanism of Pluronic effects in resistant tumor cells, cellular uptake study of micellar PTX or Rhodamine-123 (R-123) was also carried out. The results showed that the micelle size was about 24 nm with drug loading coefficient of 1.1% and PTX concentration of 700 microg x mL(-1). The cumulative release amount of PTX from the P105/PTX micelles was only 45.4% in 6 h (P < 0.05) and 79.6% in 24 h, whereas Taxol injection in 6 h released 95.2% PTX. The IC50 values of the P105/PTX micelles and Taxol injection against SKOV-3/PTX were 1.14 and 5.11 microg x mL(-1), and resistance reversion index (RRI) was 9.65 and 2.15, respectively. The micellar PTX or R-123 exhibited a significant increase in cellular uptake in resistant SKOV-3/PTX cells compared with free PTX or R-123. These results indicated that PTX could effectively be solubilized by Pluronic P105 block copolymers via thin film-hydration process and formulation optimization, producing nano-scale polymeric micelles with sustained release property in vitro. The P105/PTX micelles were effectively able to reverse resistance to PTX in SKOV-3/PTX tumor cells compared with Taxol injection or free PTX solution, and the enhanced cytotoxicity in the resistant SKOV-3/PTX cell was related to the improved cellular uptake of PTX by Pluronic P105 copolymers.
Antineoplastic Agents, Phytogenic
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administration & dosage
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chemistry
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pharmacology
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Cell Line, Tumor
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Drug Carriers
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Drug Delivery Systems
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Drug Resistance, Multiple
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drug effects
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Drug Resistance, Neoplasm
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drug effects
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Excipients
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chemistry
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Female
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Humans
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Inhibitory Concentration 50
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Micelles
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Ovarian Neoplasms
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metabolism
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pathology
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Paclitaxel
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administration & dosage
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chemistry
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metabolism
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pharmacology
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Particle Size
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Poloxamer
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chemistry
4.Relationship between mutations of epidermal growth factor receptor gene and clinicopathologic features of non-small cell lung cancers.
Fang WANG ; Sha FU ; Tao TANG ; Ling DENG ; Xiao ZHANG ; Yin-zhen LI ; Jian-yong SHAO
Chinese Journal of Pathology 2011;40(10):664-666
OBJECTIVETo explore the relationship between the mutations of epidermal growth factor receptor (EGFR) gene and clinicopathological characteristics in patients with non-small cell lung cancers (NSCLC).
METHODSParaffin-embedded tissue specimens were obtained from 1444 patients with NSCLC. The genomic DNA was extracted. Mutations of EGFR gene (exons 19 and 21) were detected by real-time PCR.
RESULTSDNA was available in 1410 cases. Somatic mutations of the EGFR gene were identified in 401 cases (27.8%). Among patients with EGFR mutations, 41.4% (n=166) had del E746-A750 of exon19, 6.7% (n=27) had del L747-P753insS of exon 19, 50.3% (n=201) had L858R of exon 21, and 1.5% (n=6) had L861Q of exon 21. Woman, non-smoker and adenocarcinoma showed a higher percentage of EGFR mutation (43.2%, 37.6%, and 33.5%, respectively). However, there was no association among age, grades, lymph node metastasis, and TNM stages (P>0.05). The mutation rate of BAC subtype (61.3%, 19/31) and adenocarcinoma with BAC features (48.0%, 12/25) was significantly higher than that of conventional adenocarcinoma (32.4%, 336/1038). A further assess of the smoking status found a trend that the more increased smoking exposure, the lower the incidence of EGFR mutations. A multivariable analysis revealed that adenocarcinoma, never smoking, and female were independently associated with EGFR mutations (odds rations=3.381, 2.393, and 1.727, respectively).
CONCLUSIONSThe detection rate of EGFR mutation is higher in Chinese patients, especially in non-smoking female patients with adenocarcinoma. Real-time PCR is a sensitive and accurate method to detect the mutations of EGFR gene and can therefore provide useful information for clinical treatment.
Adenocarcinoma ; genetics ; Adenocarcinoma, Bronchiolo-Alveolar ; genetics ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Exons ; Female ; Genes, erbB-1 ; genetics ; Humans ; Lung Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Mutation Rate ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking ; Young Adult
5.COX-2 inhibitor celecoxib can suppress the proliferation of FLT3-ITD positive acute myeloid leukemia cells with prominent down regulation of MEK/MCL-1 expression in vitro.
Li-Xia DU ; Yong-Qian JIA ; Wen-Tong MENG ; Fang-Fang SHI ; Xu-Shu ZHONG ; Ling-Ling MA ; Jin YUAN ; Ji-Sha ZENG
Journal of Experimental Hematology 2013;21(5):1157-1161
The purpose of this study was to investigate the effects of Celecoxib on the proliferation of the FLT3-ITD positive and negative acute myeloid leukemia cells and its mechanism. The proliferation inhibition effect of Celecoxib with different doses on the FLT3-ITD positive cells MV4-11 and the FLT3-ITD negative K562 cells was detected by CCK-8 method, the cell apoptosis was determined by flow cytometry, and the MEK, Mcl-1, pAKT expression was tested by Western blot. The results showed that Celecoxib inhibited the proliferation of both MV4-11 and K562 cells, but the IC50 for MV4-11 was (29.14 ± 2.4) µmol/L, which was significantly lower than that of K562 cells (39.84 ± 1.0) µmol/L (P < 0.05); The induced apoptosis rate of Celecoxib at 20-80 µmol/L on MV4-11 was not observed, but there was apparent influence on K562 at the same concentration. Western blot showed that Celecoxib down-regulated the expression of MEK and Mcl-1 but did not change the expression of pAKT obviously on MV4-11 cells, while the expression of Mcl-1 was reduced a little, but no obvious change were found in the expression of MEK and pAKT on K562 cells. It is concluded that the Celecoxib can inhibit the proliferation of FLT3-ITD positive AML cells distinctly, and the potential mechanism may be related to the inhibition of the MEK/Mcl-1 signaling pathway.
Apoptosis
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drug effects
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Celecoxib
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Cell Proliferation
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drug effects
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Cyclooxygenase 2 Inhibitors
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pharmacology
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Gene Expression Regulation, Leukemic
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Humans
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K562 Cells
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Leukemia, Myeloid, Acute
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drug therapy
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metabolism
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pathology
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MAP Kinase Kinase 1
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genetics
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Myeloid Cell Leukemia Sequence 1 Protein
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genetics
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Proto-Oncogene Proteins c-akt
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genetics
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Pyrazoles
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pharmacology
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Signal Transduction
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Sulfonamides
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pharmacology
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fms-Like Tyrosine Kinase 3
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genetics
6. Research progress of gut-skin axis in three inflammatory skin diseases
Yi CHEN ; Yong-Fang WANG ; Sha-Sha SONG ; Li-Li WU ; Xin-Yu LU
Chinese Pharmacological Bulletin 2022;38(7):979-982
Cut and skin have many similarities that all colonized with a large number of mierobiota.Among them,gut mierobiota has an important impact on health.Gut microbiota disturbance may trigger an inflammatory response .which in turn leads to tis¬sue damage or autoimmune reactions.A large number of studies have shown that gut microbiota is closely related to skin health and the theory of gut-skin axis has also been proposed.This arti¬ cle explores the effect of gut microbiota on three common inflam¬matory skin diseases, including psoriasis, atopic dermatitis and acne vulgaris.The important role of gut microbiota in the treat¬ment of inflammatory skin diseases is also reviewed.
7.Inhibitory effect of total saponins of Panax notoginseng on rat bone marrow mesenchymal stem cell apoptosis.
Yong-Fang OU ; Xue-Kun FU ; Xing-Sha MEI ; Hui-Zhen ZHENG
Acta Physiologica Sinica 2016;68(3):285-292
The study was aimed to investigate the effects of total saponins of Panax notoginseng (tPNS) on cobalt chloride (CoCl2)-induced apoptosis of rat bone marrow mesenchymal stem cells (rBMSCs) and the underlying mechanism. rBMSCs were isolated by density gradient centrifugation from Sprague Dawley (SD) rats. After being incubated with different concentrations of tPNS (1, 10, 100 μg/mL) for 48 h, the rBMSCs were stained with EdU and PI for proliferation and cell cycle assay, respectively. CoCl2 group was treated with 300 μmol CoCl2 for 24 h, and different concentrations tPNS groups were treated with 300 μmol CoCl2 plus 1, 10 or 100 μg/mL tPNS. After Annexin V-FITC/PI staining, flow cytometry was applied to measure the cell apoptosis. For mitochondrial membrane potential assay, rhodamine123 and Hoechst33342 staining were used. qRT-PCR was applied to analyze gene expression of Bcl-2 family. The results showed that the proliferation rates of the three concentrations tPNS groups were all higher than that of the control group (all P < 0.05). Compared with control group, only 100 μg/mL tPNS group exhibited increased cell percentage of S and G2 phase. Compared with that in control group (without CoCl2), the apoptotic rate was increased by 14.2% in CoCl2 group. And the apoptotic rates were reduced by 14.4%, 12.8% and 13.9% in three concentrations tPNS groups, compared with that in CoCl2 group (all P < 0.01). CoCl2 could decrease the mitochondrial membrane potential, while different concentrations of tPNS reversed the inhibitory effect of CoCl2. Bcl-2 and Bcl-xl mRNA expressions in all tPNS groups were higher than those in CoCl2 group (all P < 0.05). Moreover, 10 and 100 μg/mL tPNS groups showed lower ratios of Bax/Bcl-2, compared with CoCl2 group. The results suggest that tPNS protects the rBMSCs against CoCl2-induced apoptosis through improving the cell mitochondrial membrane potential, up-regulating the expressions of anti-apoptosis genes Bcl-2 and Bcl-xl, and reducing the Bax/Bcl-2 gene expression ratio.
Animals
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Apoptosis
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Bone Marrow Cells
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Membrane Potential, Mitochondrial
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Mesenchymal Stromal Cells
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Mitochondria
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Panax notoginseng
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Rats
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Rats, Sprague-Dawley
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Saponins
8.Randomized controlled trials of acupuncture at Tiaokou (ST 38) for treatment of periarthritis of shoulder.
Chang-qing GUO ; Fo-ming ZHANG ; Yan SHA ; Guang-hao MA ; Yun-xia LIU ; Yan-gang LIU ; Ji-ping ZHAO ; Bi-fa FAN ; Hui-fang MA ; Guang YANG ; Shi-liang LI ; Yong-wang ZHANG ; Bo HU ; Rui-hua SUN ; Li LIANG ; Li-xin QIN
Chinese Acupuncture & Moxibustion 2006;26(8):544-546
OBJECTIVETo study the basic therapeutic function of Tiaokou (ST 38).
METHODSAccording to clinically multi-central randomized controlled and single-blind test principle, 257 cases of periarthritis of shoulder were divided into two groups, a test group (n = 124) treated with oral anti-inflammatory analgesic medicine combined with acupuncture at Tiaokou (ST 38), and a control group (n = 133) treated with oral anti-inflammatory analgesic medicine. Their therapeutic effects were compared.
RESULTSThe total effective rate for stopping pain was 96.0% in the test group and 91.7% in the control group with a very significant difference between the two groups (P< 0.01). And the total effective rate for improvement of shoulder activity was 86.3% in the test group and 59.4% in the control group with a very significant difference between the two groups (P<0.01).
CONCLUSIONOral anti-inflammatory analgesic medicine combined with acupuncture has obvious therapeutic effect on periarthritis of shoulder, which is better than that of simple oral anti-inflammatory analgesic medicine.
Humans ; Periarthritis ; therapy ; Shoulder ; Shoulder Pain ; therapy ; Single-Blind Method
10. CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice
Yan-Fang KONG ; Wei-Lin SHA ; Xiao-Bo WU ; Lin-Xia ZHAO ; Ling-Jie MA ; Yong-Jing GAO ; Yong-Jing GAO
Neuroscience Bulletin 2021;37(3):339-352
Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal root ganglion (DRG) neurons, and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia. SNL also increased the mRNA levels of CXCL9, CXCL10, and CXCL11, whereas only CXCL10 increased the number of action potentials (APs) in DRG neurons. Furthermore, in Cxcr3