1.Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis.
Hui XUE ; Dike TAO ; Yuteng WENG ; Qiqi FAN ; Shuang ZHOU ; Ruilin ZHANG ; Han ZHANG ; Rui YUE ; Xiaogang WANG ; Zuolin WANG ; Yao SUN
Frontiers of Medicine 2019;13(5):575-589
Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.
2.Study on serum Let-7b in patients with prostate cancer
Xiaogang GUO ; Tao HAN ; Pingping HU ; Changming ZHU ; Youbao WANG
Chinese Journal of Postgraduates of Medicine 2018;41(9):810-813
Objective To investigate the significance of serum Let-7b in prostate cancer (PCa). Methods From July 2015 to September 2016, 72 patients with PCa (PCa group) and 34 healthy people (control group) were selected. The Let- 7b was detected by Western blot and fluorescence quantitative polymerase chain reaction (PCR), and the Let-7b was compared between 2 groups. Results The Let-7b in PCa group was significantly lower than that of control group (0.81 ±0.38 vs.1.31 ±0.34), and there was statistical difference (P<0.01). In PCa group, the Let- 7b in patients with TNM T3 and T4 stage was significantly lower than that in patients with TNM T1 and T2 stage (0.74 ± 0.39 vs. 0.88 ± 0.38), and there was statistical difference (P<0.05); the Let-7b in patients with hormone dependence was significantly higher than that in patients with hormone resistance (1.03 ± 0.40 vs. 0.64 ± 0.27), and there was statistical difference (P<0.05). Receiver operating characteristics curve analysis result showed that Let-7b sensitivity and specificity were 72.2% and 88.2% in the diagnosis of PCa. Conclusions Let-7b can indicate the degree of malignancy of the tumor and the hormone resistance. For patients with the high risk of early diagnosis of refractory PCa, the patients′ individualized treatment plan could be adjusted.
3.Regulatory effect of a Chinese medicine Wuji Pill ( WJW) on brain-gut peptides in the rats of post-inflammatory irritable bowel syndrome
Hefei HUANG ; Weijie QIANG ; Qing YANG ; Yujie LI ; Xiaogang WENG ; Yajie WANG ; Qi LI ; Weiyan CAI ; Tao CHEN ; Xiaoxin ZHU ; Ying CHEN
Acta Laboratorium Animalis Scientia Sinica 2018;26(3):265-271
Objective To explore the biological indicators of diagnosis and treatment of irritable bowel syndrome (IBS), and to explore the mechanism of action of a Chinese medicine Wuji Pill (WJW) on irritable bowel syndrome (IBS). Methods (1) Postinflammatory irritable bowel syndrome (PI-IBS) rat model was established by acetic acid plus restraint stress method . (2) The colonic motor ability of rats was evaluated by colon motility index (MI), the number of fecal particles discharged within 2 h, and the time of glass pellet discharge. (3) The formation of PI-IBS model rats and the therapeutic effect of WJW were observed. (4) The levels of calcitonin gene-related peptide (CGRP), motilin (MTL), neuropeptide Y (NPY), substance P (SP), somatostatin (SS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) in the brain and colon tissues of PI-IBS rats were measured by ELISA. Results (1) The rat PI-IBS model was successfully established. Compared with the normal group, the body weight of the model rats was decreased, the food intake decreased, the amount of feces increased, loose stools and amorphous soft stools appeared, voluntary movements decreased, colon motility index ( MI) significantly increased ( P < 0. 05 ), the number of fecal particles discharged significantly increased ( P< 0. 05), and the glass pellet discharge time was significantly shortened ( P < 0. 05). (2) WJW treatment for 7 days significantly improved a variety of symptoms. Compared with the normal control, the levels of CGRP, SS and VIP in the brain tissue of PI-IBS rats were significantly increased (P< 0. 05), and the NPY concentration was significantly decreased ( P < 0. 05). However, the treatment with WJW significantly reduced CGRP, SS and VIP levels (P< 0. 05), and significantly increased the NPY concentration level (P < 0. 05). (3) Compared with the normal control group, the levels of CCK, NPY, MTL, SS and VIP in colonic tissues of PI-IBS rats were significantly decreased (P< 0. 05), while WJW significantly increased the CCK and VIP levels. Conclusions WJW can be used to treat IBS by regulating the levels of various brain-gut peptides in the brain and colon tissues of IBS rats. These anomalous and adjustable brain-gut peptides may become a potential biomarker for the diagnosis and treatment of IBS.
4.Relationship bewteen gastric pH and hospital-acquired pneumonia in neurological intensive care unit patients
Chen MA ; Jingya WEI ; Bo HUI ; Jiwen ZHU ; Xin ZHENG ; Tao KANG ; Xiaogang KANG ; Fang YANG ; Wen JIANG
Chinese Journal of Neurology 2016;49(11):864-868
Objective To explore the relationship between gastric juice pH and hospital-acquired pneumonia ( HAP) , the gastric bacterial colonization and etiology of HAP in neurologic intensive care unit patients by monitoring gastric juice pH value.Methods From October 2014 to May 2015, consecutive seventy-two tube feeding patients admitted in the Department of Neurology Intensive Care Unit in Xijing Hospital were enrolled in this research.The type and concentration of pathogens from gastric contents were collected, while samples from upper respiratory tract and pharynx were detected dynamically at the same time.Results (1)The group with new onset HAP was higher in gastric juice pH (6.4(5.4,6.4) vs 5.4 (2.5, 6.4), Z=-2.37, P=0.01); (2) The isolation rate of colonized bacteria in gastric cavity was associated with the pH of gastric juice , achieving 60.8% ( 42/69 ) in HAP group; ( 3 ) When the gastric juice pH was >4, the isolation rate of Gram-negative bacilli in gastric cavity obviously increased (63.6%(28/44) vs 35.7%(10/28),χ2 =5.323, P=0.021); (4)The same pathogens were found in stomach-pharynx-upper respiratory tract in 7 cases ( 17.5%) of the total 40 HAP patients.Conclusion Increased gastric juice pH was associated with gastric colonization , especially Gram-negative bacilli , and may lead to a higher incidence of new onset HAP in patients on enteral feeding.
5.Effects of minocycline on cerebral blood flow and endothelin-1 protein expression in ischemic penumbra of rats with focal cerebral ischemia reperfusion
Tao TAO ; Linwang GAN ; Jie FU ; Zuoxiao LI ; Xiaogang LI
Chongqing Medicine 2016;(1):27-29
Objective To investigate the effects of minocycline on regional cerebral blood flow and the expression of endothe-lin-1(ET-1) in ischemic penumbra of rats after focal cerebral ischemia reperfusion injury .Methods Middle cerebral artery occlusion (MCAO) with nylon suture was used to be established as focal cerebral ischemia reperfusion mode (I/R) ,a total of 35 male Spra-geue-Dawley rats were randomly divided into 3 groups :sham-operated group(n= 10) ,model group(n= 15) and minocycline group (n= 15) .After 24 hours of I/R ,The neurobehavioral function of rats was evaluated by Longa′s test ,the regional cerebral blood flow in ischemic penumbra was assessed with laser-Doppler flowmetry .After 6 and 24 hours of I/R ,the expression of ET-1 in peri-in-farct region was measured by both immunohistochemistry and radioimmunoassay .Results Compared with sham-group ,the Longa′s test scales ,ET-1 protein expression increased and the rCBF decreased in ischemic penumbra in model group(P< 0 .05) .the Longa′s test scales ,ET-1 protein expression decreased and the rCBF decreased in ischemic penumbra in minocycline group when compared to the model group(P< 0 .05) .Conclusion Minocycline could promote neurological functional recovery of rats after MCAO ,which might be attributed to increase the cerebral blood flow and regulate the endothelin-1 expression in ischemic penumbra .
6.Comparison of T2 FLAIR and GRE-T2* WI in detection of traumatic extra-axial hemorrhage
Chunxue WU ; Jun MA ; He JIN ; Baiyun LIU ; Xiaogang TAO ; Runfa TIAN
Journal of Practical Radiology 2016;32(3):331-334
Objective To explore the value of fluid-attenuated inversion recovery (FLAIR)sequence and gradient echo T2 ?weighted image (GRE-T2 ? WI)in diagnosis of acute traumatic extra-axial hemorrhage.Methods 50 patients who were diagnosed as acute traumatic extra-axial hemorrhage by plain CT underwent FLAIR and GRE-T2 ? WI in acute stage.The diagnosis consistency (Kappa ),detection rate of subarachnoid hemorrhage(SAH),epidural hemorrhage(EDH)and subdural hemorrhage(SDH)were compared.The detection rates of SAH in 8 locations among FLAIR,GRE-T2 ? WI and combination of two sequences were analyzed by Chi-square test.Results 48 patients were enrolled in the study.The diagnosis consistency of SAH between FLAIR and GRE-T2 ? WI was high (k =1.0).The detection rate of SAH was 100% for both FLAIR and GRE-T2 ? WI.Comparing with GRE-T2 ? WI and combi-nation of two sequences,FLAIR tended to misdiagnose SAH in perimesencephalic cistern (P <0.05).The diagnosis consistency of EDH between FLAIR and GRE-T2 ? WI was high (k =1.0).3 patients with EDH were all detected by FLAIR and GRE-T2 ? WI. The diagnosis consistency of SDH between FLAIR and GRE-T2 ? WI was high (k =0.943).The detection rate of 12 patients with SDH was 100% in FLAIR,and 1 patient with SDH was missed by GRE-T2 ? WI.Conclusion The detection rate of acute traumatic extra-axial hemorrhage is high for both FLAIR and GRE-T2 ? WI.Combination of two sequences can improve the accuracy of acute traumatic extra-axial hemorrhage in clinic.
7.Effects of minocycline on neurite outgrowth of PC12 cells following oxygen glucose deprivation
Tao TAO ; Xinyue QIN ; Jinzhou FENG ; Hua LUO ; Xiaogang LI
Chongqing Medicine 2015;(5):605-607
Objective To investigate the effects of minocycline on cell viability and neurite outgrowth of pheochromocytoma cells (PC12) after oxygen‐glucose deprivation(OGD) injury .Methods PC12 cells were exposed to OGD insult for 2 ,4 ,6 ,8 h to estab‐lish a cerebral ischemia model in vitro .High‐differentiated PC12 cells were cultivated and randomly divided into three groups :con‐trol group ,OGD group and various doses of minocycline(0 .1 ,1 .0 ,10 .0 μM) treated group .24 h after OGD‐reperfusion ,PC12 cells viability was assessed by CCK‐8 assay ,the neurite was labeled with MAP‐2 by immunofluorescence and neurite length was meas‐ured by the Image‐Pro Plus 7 .0 software ,GAP‐43 protein expression was determined by Western blotting .Results Compared to the OGD groups ,minocycline induced a concentration‐dependent increase in cells viability [(46 .1 ± 2 .9)% vs .(77 .0 ± 2 .5)% ,P<0.01],improvedneuriteoutgrowthandincreasedtheexpressionofGAP‐43proteininPC12cellsafterOGDinjury([(0.34±0.04) vs .(2 .11 ± 0 .10) ,P<0 .01] .Conclusion Minocycline could protect against oxygen glucose deprivation injury and promote neurite outgrowth .This finding suggests minocycline may be a novel therapy for cerebral ischemia .
8.Bacterial distribution of cerebrospinal fluid cultures and its effect on therapeutic efficacy in patients with severe intracranial infection after open craniotomy
Yiming FAN ; Baiyun LIU ; Xiaogang TAO ; Gang WANG ; Zhao XU ; Hetao WU
Chinese Journal of Trauma 2014;30(12):1165-1171
Objective To investigate the distribution characteristics of pathogens isolated fromcerebrospinal fluid of neurosurgical patients with intracranial infection following open craniotomy and thetherapeutic effect influenced by these pathogens,in order to give a reference to the clinical treatmentmeasures.Methods A retrospective analysis was made on the pathogen distribution and therapeuticeffect of 43 patients with intracranial infection and positive cerebrospinal fluid cultures after open cranioto-my from May 2007 to May 2013.Cerebrospinal fluid was cleared using the intraventricular catheter orlumbar catheter combined with intraventricular (ventricular irrigation) or intraspinal (intrathecalirrigation) injection of antibacterial agents.Results To test bacteria in cerebrospinal fluid pathogencultures,34 cases were infected with single strain (26 Gram-positive bacteria and 8 Gram-negativebacteria) and 9 cases had mixed infection with multiple strains.Fifty-two pathogen strains were isolated,including 32 (62%) Gram-positive bacteria,18 (35%) Gram-negative bacteria,2 (4%) fungi.A totalof 29 cases were cured (67%),7 improved (16%),and 7 ineffective (16%).Conclusions Cere-brospinal fluid pathogen infection is primarily Gram-positive bacterial infection,usually staphylococcusepidermidis and staphylococcus aureus.Gram-negative pathogens are acinetobacter,klebsiella,andpseudomonas aeruginosa.Ventriculoperitoneal shunting surgery and craniocerebral surgery are often asso-ciated with mixed infection of pathogens.Ventricular irrigation allows better results than intrathecal irriga-tion.Indications of intrathecal irrigation treatment used to control intracranial infection after ventriculoper-itoneal shunting surgery and craniocerebral surgery should be strictly performed.
9.Effect of PARP inhibitor PJ34 on blood-brain barrier permeability and MMP-9 expression following traumatic brain injury in mice
Xiaogang TAO ; Baiyun LIU ; Xuetao CHEN ; Shuyu HAO ; Runfa TIAN
Chinese Journal of Trauma 2014;30(12):1230-1235
Objective To investigate the role of poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 in regulating blood-brain barrier (BBB) permeability and matrix metalloproteinases-9 (MMP-9) expression in a mouse model of traumatic brain injury (TBI).Methods A total of 136 adult male BALB/c mice were randomly divided into sham-operated group,injured group and PJ34-treated group according to the random number table.Controlled cortical impact in mice was established.At 6 and 24hours postinjury,neurological deficit was evaluated,including motor,sensory,reflex and beam balance tests ; BBB permeability and brain water content were detected using Evans blue test and gravimetric technique; brain contusion volume was measured using HE staining; levels of MMP-9 in cytosolic fractions were detected using Western blotting.Results At 6 and 24 hours postinjury,neurological severity score in PJ34-treated group (8.00 ± 0.26,7.50 ±0.25) were lower than those in injured group (12.50 ±0.39,11.80 ± 0.32) ; brain contusion volume in PJ34-treated group [(11.25 ± 0.91) mm3,(13.55 ±1.06) mm3] was lower than those in injured group [(25.37 ± 1.75) mm3,(28.24 ± 1.51) mm3] ; BBB permeability in PJ34-treated group [(440.08 ± 3.10) μg/mg,(860.46 ± 3.86) μg/mg] was lower than those in injured group [(936.96 ± 4.71) μg/mg,(1 302.23 ± 5.89) μg/mg] (all P < 0.01).Brain water content lowered significantly in PJ34-treated group than in injured group at 6 hours postinjury [(80.77 ± 0.76) % vs (82.55 ± 0.73) %,P < 0.0l],but between-group difference was not significant at 24 hours postinjury.Lower levels in MMP-9 were also observed in PJ34-treated group compared with injured group at 6 and 24 hours postinjury(P < 0.05 or 0.01).Conclusion PARP inhibitor PJ34 can attenuate MMP-9 up-regulation,inhibit BBB injury and hence protect the brain against TBI in mice.
10.Dendritic cells phagocytized apoptotic lymphocytes induce the development of regulatory B cells with high secretion of interleukin-10
Yuxiang WEI ; Xiaogang WANG ; Li XIAO ; Wenqiang ZHOU ; Dehua ZHENG ; Tao YU ; Bingyi SHI
Organ Transplantation 2014;(4):237-241
Objective To investigate the feasibility of immature dendritic cells (imDC)phagocytized psoralen ultraviolet A (PUVA)-treated splenic lymphocytes (PUVA-SP DC)in mice inducing B lymphocytes to be regulatory B cells (Breg)with high secretion of interleukin (IL)-10 (IL-10 +Breg). Methods Bone marrow-derived DC of mice was cultured. Spleen lymphocytes of mice were isolated and treated by PUVA,and turned to be PUVA-SP. The bone marrow-derived imDC was co-cultured with PUVA-SP in vitro to obtain PUVA-SP DC. Splenic B lymphocytes of mice were separated by anti-CD19 magnetic beads and co-cultured with different kinds of DC for 48 hours. The levels of interferon (IFN )-γ,transforming growth factor (TGF)-β,IL-12p70,and IL-10 in the culture supernatant of B lymphocytes,imDC,imDC+B lymphocytes, PUVA-SP DC and PUVA-SP DC +B lymphocytes were measured by enzyme-linked immune absorbent assay (ELISA). The accounts of IL-10 +Breg in B lymphocytes,imDC+B lymphocytes,mDC+B lymphocytes and PUVA-SP DC+B lymphocytes were detected by flow cytometry. Results Compared with the other 4 groups, the level of IL-10 in cell culture supernatant of PUVA-SP DC+B lymphocytes was significantly higher (all in P<0.05). Compared with the other groups,the account of IL-10 +Breg in PUVA-SP DC+B lymphocytes was significantly higher. Conclusions PUVA-SP DC can induce splenic B lymphocytes to differentiate into IL-10 +Breg.

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