1.Suppression of HMGB1 inhibits neuronal autophagy and apoptosis to improve neurological deficits in rats following intracerebral hemorrhage.
Lie ZHANG ; Shu Chuan MIAO ; Zhong Xin YANG ; Zong Xi LI ; Ying Jun FAN ; Kai YU ; Ke Yang HUANG ; Qing Xi HUANG ; Xun XIA
Journal of Southern Medical University 2022;42(7):1050-1056
OBJECTIVE:
To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats.
METHODS:
Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA.
RESULTS:
The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05).
CONCLUSION
Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.
Animals
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Apoptosis
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Apoptosis Regulatory Proteins/metabolism*
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Autophagy
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Beclin-1
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Caspase 3/metabolism*
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Cerebral Hemorrhage/therapy*
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Proto-Oncogene Proteins c-bcl-2/metabolism*
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Rats
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Rats, Sprague-Dawley
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bcl-2-Associated X Protein/metabolism*
2.Long-term trend of viral hepatitis mortality and potential years of life lost in Jing’an District of Shanghai, 1976-2015
Qui-ping WAN ; Jun-ling ZHU ; Jin HUANG ; Jian-jing XIONG ; Xiao-lie YIN ; Xiao-ming YANG ; Ling-li SHI ; Yun-hui WANG ; Xiao-ting CHU
Shanghai Journal of Preventive Medicine 2021;33(7):593-598
Objective:To analyze the long-term trend of viral hepatitis mortality in Jing’an District of Shanghai, and to provide a reference for viral hepatitis prevention and control. Methods:Mortality rate, standard mortality rate, PYLL and potential years of life lost rate (PYLL‰) of viral hepatitis in Jing’an district of Shanghai from 1976 to 2015 were calculated. The annual percent change (APC) of the mortality and PYLL‰ were analyzed by Joinpoint regression analysis. Results:From 1976 to 2015, there were 1 342 viral hepatitis death cases, including 832 males and 510 females. The average crude mortality rate was 8.31/100 000, and the average age-standardized mortality rate was 5.45/100 000. Among the deaths of viral hepatitis, men had a higher mortality rate, age-standardized mortality rate and PYLL% than women (
3.Electroacupuncture Delays Cartilage Degeneration by Modulating Nuclear Factor-κB Signaling Pathway.
Guang-Wen WU ; Jun CHEN ; Yun-Mei HUANG ; Cai-Bin PAN ; Wen-Lie CHEN ; Shi-Mao ZHANG ; Wei LIN ; Xian-Xiang LIU ; Ming-Xia WU
Chinese journal of integrative medicine 2019;25(9):677-683
OBJECTIVE:
To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA).
METHODS:
Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β (IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis.
RESULTS:
EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01).
CONCLUSION
EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.
4.Effect of safflower yellow on atherosclerosis in rabbits with hyperlipidemia
Shu-Ling LIU ; Hai-Rong CAI ; Xin-Gui CAI ; Lie-Yuan ZHANG ; Wei-Zhang ZHANG ; Qiu-Ping HUANG ; Bo-Jun CHEN
Journal of International Pharmaceutical Research 2018;45(8):603-610
Objective To investigate the effect of safflower yellow injection on atherosclerosis in rabbits with hyperlipidemia.Methods Ninety-six New Zealand rabbits were randomly divided into four groups:the control group, model group, safflower yellowtest group (10.9, 5.45 and 2.725 mg/kg) and the positive control (atorvastatin) group. The control group was fed with normal feed, while the other three groups were fed with high fat diet for 8 weeks, combined with intraperitoneal injection of vitamin D3, to establish hyperlipidemia model. Then, the three-dosage safflower yellow-test groups were given intraperitoneal injection of safflower yellow (10.9, 5.45 and 2.725 mg/kg), respectively, the positive control group was given atorvastatin calcium[2 mg/ (kg·d) ]by intragastric administration, and the control and model groups were orally given an equal volume of normal saline, all once a day every day for 8weeks. After 16 h fasting following the last administration, the body weight, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), oxidized low density lipoprotein (OX-LDL), matrix metalloproteinases 9 (MMP-9), tissue inhibitors of metalloproteinase 1 (TIMP-1), apolipoprotein E (ApoE), low density lipoprotein receptor (LDL-R), and scavenger receptor class B type1 (SR-B1) levels were measured. The morphological changes of thoracic aortas were examined by HE staining. Results At the 16 th week, compared with the control group, the body weight as well as the TC, TG, LDL-C, OX-LDL, MMP-9, HIF-1α, VEGF, VCAM-1 and PF4 level were all increased significantly (P<0.05), while the level of HDL-C, ApoE, LDL-R, and SR-B1 decreased significantly (P<0.05), accompanied with the atherosclerotic changes in the thoracic aortas indicated by the HE staining in the model group. Compared with the model group, the body weight as well as the TC, LDL-C, OX-LDL, MMP-9, HIF-1α, VEGF, VCAM-1 and PF4 level were decreased significantly (P<0.05), and the TIMP-1 level increased (P<0.05) in all of the three-dosage safflower yellow-test groups. Meanwhile, compared with the model group, in the 10.9 and 5.45 mg/kg safflower yellow groups, the TG level were decreased and the ApoE and SR-B1 levels were increased significantly (P<0.05). On the other hand, the LDL-R level significantly increased only in the safflower yellow 10.9 mg/kg group (P<0.05). HE staining showed a significant reduction in atherosclerorotic changes of the thoracic aorta in the safflower yellow-test groups. Conclusion Safflower yellow may inhibit the progression of atherosclerosis by regulating the lipid metabolism and MMP-9/TIMP-1 balance and also by inhibiting the HIF-1α, VEGF, VCAM-1 and PF4 expression.
5.Impact of KIT D816 mutation on salvage therapy in relapsed acute myeloid leukemia with t(8;21) translocation.
Ben Fa GONG ; Ye Hui TAN ; Ai Jun LIAO ; Jian LI ; Yue Ying MAO ; Ning LU ; Yi DING ; Er Lie JIANG ; Tie Jun GONG ; Zhi Lin JIA ; Yu SUN ; Bing Zong LI ; Shu Chuan LIU ; Juan DU ; Wen Rong HUANG ; Hui WEI ; Jian Xiang WANG
Chinese Journal of Hematology 2018;39(6):460-464
Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.
Antineoplastic Combined Chemotherapy Protocols
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Cytarabine
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Humans
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Leukemia, Myeloid, Acute/therapy*
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Prognosis
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Retrospective Studies
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Salvage Therapy
6.Study on chemical constituents of Inula cappa.
Li-hua ZHENG ; Xiao-jiang HAO ; Chun-mao YUAN ; Lie-jun HUANG ; Jian-xin ZHANG ; Fen DONG ; Tian-yun FAN ; Gui-hui WU ; Yan CHEN ; Yuan MA ; Yi-min FAN ; Wei GU
China Journal of Chinese Materia Medica 2015;40(4):672-678
Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, and MCI, and semi-preparative HPLC were used for separation and purification of constituents from Inula cappa. The 22 compounds were obtained and their strutures were determined by NMR and MS spectra data as nine flavonoids: luteolin (1), apigenin (2), chrysoeriol (3), artemetin (4), 2', 5-di- hydroxy-3, 6, 7, 4', 5'-pentamethoxyflavone (5), chrysosplenol C (6), apigenin-5-0-β-D-glucopyranoside (7), luteolin-3-methyl, luteolin-3-methylether-4'-0-β-D-glucopyranoside (8), luteolin-4'-0-β-D-glucopyranoside (9); four triterpenes: darma-20, 24-dien- 3β-0-acetate (10), darma-20, 24-dien-3β-ol (11), epirfiedelanol (12), friedelin (13); three coumarins: scopoletin (14) , isosco- poletin (15) , scopolin(16) , and other types of compounds stigmasta-5, 22-dien-3β-0-7-one (17), stigmasterol (18), palmitic acid (19), linoleic acid (20), linoleic acid methyl ester (21), (E) -9, 12, 13-trihydroxyoetadee-10-enoie acid (22). Compound 5 is a new natural product. Compounds 3-9, 15, 17, 21, and 22 were isolated from this genus for the first time.
Drugs, Chinese Herbal
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chemistry
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isolation & purification
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Inula
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chemistry
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Molecular Structure
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Spectrometry, Mass, Electrospray Ionization
7.Combination of transrectal 125I seeds implantation brachytherapy and intermittent hormonal therapy for locally advanced prostate cancer.
Hao-Ming WU ; Jun LÜ ; Wei-Lie HU ; Jin-He ZHANG ; Wei WANG ; Yuan-Song XIAO ; Nan-Xiong WANG ; Jun-Wu RAN ; Xiao-Dong HUANG
National Journal of Andrology 2013;19(7):617-621
OBJECTIVETo evaluate the clinical efficacy of transrectal 125 I seeds implantation brachytherapy (BT) combined with intermittent hormonal therapy (IHT) in the treatment of locally advanced prostate cancer.
METHODSWe treated 27 patients with locally advanced prostate cancer by transrectal 125I seeds implantation BT combined with IHT, and dynamically observed the changes in the PSA level, prostate volume, maximum urinary flow rate (Qmax) and International Prostate Symptoms Score (IPSS).
RESULTSAll the implantation procedures were completed smoothly, lasting 20 to 35 minutes, with 40 to 58 seeds implanted. At 6 months after implantation, the PSA level was < 0.2 microg/L in all the patients (< 0.1 microg/L in 19 cases), the prostate volume was significantly reduced (P < 0.05), and Qmax and IPSS remarkably improved (P < 0.05). At 3 years after implantation, 19 cases were in the first cycle and the other 8 in the third cycle of IHT, of which 2 progressed to androgen-independent prostate cancer, and another 2 developed early bone metastasis. The rates of 3-year biochemically and clinically progression-free survival were 70.3% and 85.2%, respectively, and the rate of therapeutic effectiveness was 92.6%. No severe complications occurred in any of the cases.
CONCLUSIONTransrectal 125I seeds implantation BT combined with IHT is a safe and minimally invasive procedure for locally advanced prostate cancer, which can effectively retard its clinical progression with no such complications as severe urethral, rectal or erectile dysfunction.
Aged ; Brachytherapy ; Combined Modality Therapy ; Hormones ; therapeutic use ; Humans ; Iodine Radioisotopes ; administration & dosage ; therapeutic use ; Male ; Prostatic Neoplasms ; radiotherapy ; therapy ; Treatment Outcome
8.Expressions of somatomedins in anoxic prostate epithelial cells.
Wen SHEN ; Jun LÜ ; Ping LI ; Cheng HUANG ; Wei WANG ; Chen-Hui ZHU ; Wei-Lie HU
National Journal of Andrology 2013;19(1):24-28
OBJECTIVETo observe the changes in the expressions of somatomedins in the prostate epithelial cells in anoxic condition.
METHODSWe cultured prostate epithelial cell line RWPE-1 in vitro. At 4, 8, 12, 24, 48 hours after seeding of the cells, we determined the gene and protein expressions of the epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in the prostate epithelial cells by RT-PCR and ELISA, respectively.
RESULTSWith the increase of time, the expressions of the EGF, bFGF, TGF-beta, IGF-1 and VEGF genes were obviously up-regulated, more significantly in the anoxic than in the normoxic prostate epithelial cells. Take FGF mRNA, its expression level was 0.14 +/- 0.01 in the anoxic and 0. 12 +/- 0.01 in the normoxic prostate epithelial cells at 8 hours (P = 0.01), but increased to 0.29 +/- 0.01 and 0.14 +/- 0.01, respectively, at 48 hours (P < 0.001). The expression of the TGF-beta protein was also more significantly increased in the anoxic than in the normoxic prostate epithelial cells, 0.32 +/- 0.01 versus 0.26 +/- 0.01 at 4 hours (P = 0.017) and 1.56 +/- 0.13 versus 0.87 +/- 0.06 at 48 hours (P < 0.001). The other 4 somatomedins showed no significant differences in their protein expressions between anoxic and normoxic conditions.
CONCLUSIONAnoxia can up-regulate the gene expressions of somatomedins and increase the secretion of TGF-beta in prostate epithelial cells.
Cell Hypoxia ; Cell Line ; Epithelial Cells ; metabolism ; Gene Expression Regulation ; Humans ; Male ; Prostate ; cytology ; Somatomedins ; metabolism ; Transforming Growth Factor beta ; metabolism ; Up-Regulation
9.Effect of botulinum toxin type A injection into the masseter muscle on mandibular development in rats.
Jin-Jun HUANG ; Da-Lie LIU ; Bing CHEN ; Jin-Huang WANG
Chinese Journal of Plastic Surgery 2010;26(4):280-285
OBJECTIVETo investigate the effect of Botulinum toxin type A (Botox) injection into the masseter muscle on mandibular development in rats.
METHODS12 28-day-old Wistar rats were divided into two groups as Botox group (n= 6) and control group (n = 6) which received anesthesia only. In Botox group, Botox was injected into the right masseter muscle, while only sterile saline into the left muscle. When the rats were 75-day-old, CT scan and 3D reconstruction were performed for cephalometry. The masseter muscles at both sides were weighed. Histologic study of masseter muscle and mandible was also performed.
RESULTSThe weight of right masseter muscle was (0.4575 +/- 0.0940) g in Botox group, and (0.8899 +/- 0.1030) g in control group (< 0.05). The mandibular height II and III was (10.8 +/- 0.8) mm and (9.5 +/- 0.6) mm in Botox group and (12.5 +/- 0.6) mm and (10.7 +/- 0.4) mm in control group, respectively (P < 0.05). The intergonial distance was (11.6 +/- 0.6) mm and (12.4 +/- 0. 6) mm in Botox and control group, respectively (P > 0.05).
CONCLUSIONSWhen the rats receive Botox injection into the masseter muscle at young age, the grown-up rats have a decreased mandibular height, but the mandibular length and intergonial distance are not affected.
Animals ; Botulinum Toxins, Type A ; administration & dosage ; pharmacology ; Injections, Intramuscular ; Male ; Mandible ; drug effects ; growth & development ; Masseter Muscle ; Rats ; Rats, Wistar
10.Effect of denervation of masseter muscle on the development of mandible
Jin-Jun HUANG ; Lei SHAN ; Da-Lie LIU ; Jin-Huang WANG
Chinese Journal of Neuromedicine 2010;9(3):262-265
Objective To evaluate the effect of denervation of masseter muscle on the development of mandible.Methods Twenty-four 28-day-old Wistar rats were randomly divided into operative(n=9),sham-operative(n=9)and control(n=6)groups.The main trunk and initial branches of the masseter nerve on the right side were resected in the operative group.The nerve was exposed,but not resected in the sham-oporative group.The control group was only anaesthetised.CT scan and 3D reconstruction were performed when the rats were 75 d old.Seven cephaiometric points were selected and digitized and selected 7 linear distances were measured.The rots were killed with an overdose of 10% chloral hydrate after the CT scan.Masseter muscles on each side were obtained and weighted immediately.Results The mass of the mandible of the operative side was significantly lighter than that of the non-operative side in the operative group(P<0.05).No significant variances on length of the mandible Ⅰ,Ⅱ and Ⅲ,and height of the mandible Ⅰ were found among the 3 groups(P>0.05).Compared with the control group,the operative group showed shorter height of the mandible Ⅱ and width of the mandible,and the operative and sham-operative groups showed shorter height of the mandible Ⅲ(P<0.05).Conclusion Changes on mandibular height Ⅱ and bilateral width after denervation of masseter muscle are noted and no influence on mandibular length is found.

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