1.Mechanism of vanillic acid against cardiac fibrosis induced by isoproterenol in mice based on Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways.
Hai-Bo HE ; Mian WU ; Jie XU ; Qian-Qian XU ; Fang-Zhu WAN ; Hua-Qiao ZHONG ; Ji-Hong ZHANG ; Gang ZHOU ; Hui-Lin QIN ; Hao-Ran LI ; Hai-Ming TANG
China Journal of Chinese Materia Medica 2025;50(8):2193-2208
This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals
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Isoproterenol/adverse effects*
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Male
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Mice
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Signal Transduction/drug effects*
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Vanillic Acid/administration & dosage*
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Dynamins/genetics*
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Mice, Inbred C57BL
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Fibrosis/genetics*
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Apoptosis/drug effects*
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Mitochondria/metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Myocardium/metabolism*
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Humans
2.Effect mechanism of dihydromyricetin on the tumor biological characteristics of endometrial cancer cells
Wei-Hua CUI ; Jing-Ying SONG ; Shu-Xin QIAO ; Shu-Zhong DUAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1039-1043
Objective To explore the effects of dihydromyricetin on the proliferation,apoptosis,and invasion of endometrial cancer(EC)cells and its possible mechanisms.Methods Ishikawa cells in the logarithmic growth phase were taken and divided into the control group,20 μmol/L dihydromyricetin intervention group,40 μmol/L dihydromyricetin intervention group,and 80 μmol/L dihydromyricetin intervention group,which were treated with different final concentrations of dihydromyricetin(0 μmol/L,20 μmol/L,40 μmol/L,80 μmol/L).Then,CCK-8 assay and flow cytometry were used to detect the effects of dihydromyricetin on the cell proliferation and apoptosis.Transwell experiment was used to detect the effect of dihydromyricetin on the cell invasion.qRT-PCR and Western blot were used to detect the effects of dihydromyricetin on the cell expression of miR-21 and PTEN.Results Compared with the control group,the cell proliferation inhibition rate and apoptosis rate in the dihydromyricetin intervention group were significantly increased(P<0.05),and gradually increased with the increase of dihydromyricetin concentration(P<0.05).Compared with the control group,the numbers of migration and invasion cells in the dihydromyricetin intervention group were significantly decreased(P<0.05),and gradually decreased with the increase of dihydromyricetin concentration(P<0.05).Compared with the control group,the cell expression of miR-21 in the dihydromyricetin intervention group was significantly decreased(P<0.05),and gradually decreased with the increase of dihydromyricetin concentration(P<0.05),the expression levels of PTEN mRNA and protein were significantly increased(P<0.05),and gradually increased with the increase of dihydromyricetin concentration(P<0.05).Conclusion Dihydromyricetin can inhibit the growth and metastasis of EC cells,and the inhibitory effect is positively correlated with its concentration.The mechanism may be related to the effect of dihydromyricetin on the miR-21/PTEN signaling pathway of EC cells.
4.Surveillance of cockroach population and evaluation of control effects in households from 2017 to 2019 in Jiading District of Shanghai
Shao-hua WANG ; Zheng-rong WU ; Teng-fei DONG ; Qiao-yan WANG ; Wei FANG ; Pei-song ZHONG ; Pei-en LENG ; Ming-qiu FAN ; Hong-xia LIU
Shanghai Journal of Preventive Medicine 2020;32(12):1001-
Objective To learn the population and infestation rates of cockroaches from 2017 to 2019 in Jiading District of Shanghai, to evaluate the effect of cockroach termination in household, and to provide information for cockroach control. Methods Cockroaches were controlled by dinotefuran baits and clean-up in households.Sticky trap and visual method were employed for density monitoring in farmers markets, supermarkets, hotels, restaurants, hospitals, and residential areas.Visual method was used in households before and after using the insecticide. Results Sticky trap result showed the room infestation rate was 3.24%, mean adhesion rate was 3.29%, the density was 0.06 per board, and the density peak appeared in May.Rate of invasion and density decreased year by year.
5.Effect of thunder-fire moxibustion combined with vibration training on low back pain of primary osteoporosis.
Lu ZHU ; Dao-Ming XU ; Wen-Zhong WU ; Hua-Ning XU ; Jing LIU ; Lan-Ying LIU ; Qiao-Ling FAN ; Hai-Ying GUO ; Wen SHI ; Han-Jun LI ; Ya-Na CAO
Chinese Acupuncture & Moxibustion 2020;40(1):17-20
OBJECTIVE:
To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by 's modulus of ultrasonic wave, and seek an objective evaluating method.
METHODS:
A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone ('s modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment.
RESULTS:
Compared before treatment, the VAS scores, 's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all <0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both <0.05). In the observation group, the VAS scores, 's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all <0.05).
CONCLUSION
The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.
Acupuncture Points
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Humans
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Low Back Pain
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etiology
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therapy
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Moxibustion
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Osteoporosis
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complications
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Quality of Life
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Treatment Outcome
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Vibration
6.Treatment of Recalcitrant Plantar Warts with 5-aminolevulinic Acid Photodynamic Therapy(ALA-PDT)after Preconditioning with Superpulse Carbon Dioxide Laser
Hai-Rong DAI ; Hui ZHOU ; Qiao-Fei LI ; Hong-Zhong LING ; Ji-Huang XIE ; Yu-Hua LI ; Guang-Ling CAO
Journal of Sun Yat-sen University(Medical Sciences) 2018;39(1):152-156
[Objective]To investigate the efficacy and safety of ALA-PDT following CO2laser preconditioning for recal-citrant plantar warts.[Methods]Patients with recalcitrant plantar warts were enrolled in this study,and received ALA-PDT treatment following CO2laser preconditioning. Cure rate and side effects were observed.[Results]Twenty patients were en-rolled and 85%(17/20)showed complete clearance of plantar warts after one to three times of ALA-PDT. PDT treatment time was once in two patients(10%),twice in five patients(25%)while three times in 10 patients(50%).No infection or scar tissue was observed.Five(25%)patients were infected with one type of HPV,while 15(75%)patients with two or mul-tiple types of HPV. No difference was observed in complete clearance rate between patients with single or multiple HPV gen-otypes infection.[Conclusions]Superpulse carbon dioxide laser pretreatment enhanced the efficacy of ALA-PDT treatment on recalcitrant plantar warts.Further study is needed to determine the association of HPV genotype with outcome of recalci-trant plantar warts.
7.Effects of Crude Toxins from Colletotrichum gloeosporioides on Growth of Dendrobium officinale Kimura et Migo
Qiao Xiao YAN ; Hua Kai LIANG ; Fan Yi LI ; Min Zhi ZHONG ; Wen Guan XIE ; Ping Xiao LAI ; Fang Gui ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2018;35(1):155-162
To explore the effects of crude toxins from Colletotrichum gloeosporioides(C. gloeosporioides)on the growth of Dendrobium officinale Kimura et Migo(D. officinale),and to provide early basis for thescreening and cultivation of the resistant variants of C. gloeosporioides. Methods Seedlings of D. officinal werecultivated in MS medium added with different concentrations of the crude toxins from C. gloeosporioides. Theeffects of the crude toxin on the growth of seedlings were observed, and the optimum resistance -selectionthreshold was preliminarily screened. Results In the concentration range of 5% - 15%(volume fraction),crudetoxins from C. gloeosporioides increased the plant height,stem diameter,number of new bud,root number,and fresh mass of D. officinale,among which the effect of 5%(volume fraction)of crude toxins was the moststrongest. In the concentration range of 35% - 40%(volume fraction),crude toxins suppressed the plant height,leaf number,number of new bud,root number,and the fresh mass of D. officinale. When cultured with 20%(volume fraction)crude toxins, D. officinale was blooming, and the flowers appeared variation phenomenon.Conclusion The crude toxins from C. gloeosporioides have biological activity and certain toxicity,which can beconsidered as a selection agent instead of pathogenin in vitro to screen the resistant variant of D. officinale,butthe optimum resistance-selection threshold still needs further research.
8.Finding of a NDM-1 carbapenems-producing Leclercia adcarboxglata
Feng YU ; Lin-Qiang DENG ; Qiao-Shi ZHONG ; Ya-Ping HANG ; Yan-Ling LIU ; Hui DING ; Yan-Hui CHEN ; Long-Hua HU
Chinese Journal of Clinical Laboratory Science 2018;36(1):25-28
Objective To investigate the resistance mechanism of a carbapenems-resistant Leclercia adcarboxglata.Methods The species was identified by the automatic microbial analyzer,matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA sequence analysis.The conventional drug susceptibility test was detected with automatic microbial analyzer,and the minimum inhibitory concentration (MIC) for imipenem was examined by E-test.The phenotypes of carbapenemase were detected by modified carbapenem inactivation method (mCIM) and the genotypes of resistance genes were detected by polymerase chain reaction (PCR) and DNA sequencing.The characteristics of the carried plasmid were analyzed by conjugation test and S1pulsed-field gel electrophoresis (S1-PFGE).Results The clinical isolates of Leclercia adcarboxglata were resistant to imipenem,other beta-lactam antibiotics(except aztreonam) and aminoglycosides,but sensitive to quinolones and sulfonamides.The conjugation test resulted in a drug-resistance spectrum of the receptor strain E.coli J53 similar to Leclercia adcarboxglata bacteria.The phenotype of carbapenemase was positive.PCR amplification and sequencing analysis showed that blaNDM-1,blaTEM and aac (6')-Ib were detectable in the isolates simultaneously,while the conjugon only carried blaNDM-1.S1-PFGE revealed that Leclercia adcarboxglata carried 3 plasmids.Conclusion The carbapenems resistance of Leclercia adcarboxglata may contribute to carrying blaNDM-1 gene which may exist in an around 100 kb plasmid transmitted with conjugation.
9.Death caused by ST19 Klebsiella oxytoca with wcaG virulence gene in leukemic patient
Hui DING ; Long-Hua HU ; Qiao-Shi ZHONG ; Ya-Ping HANG ; Yan-Ling LIU ; Feng YU ; Yan-Hui CHEN ; Xiao-Yan HU ; Li-Ming ZHANG ; Bai-Ling ZHANG ; Nan ZHANG ; Xiao-Zhong WANG
Chinese Journal of Zoonoses 2017;33(8):753-756
We investigated the cause of a leukemia patient induced by infect in a strain of Klebsiella oxytoca with hypermucoviscosity (HMV) phenotype.Identification and drug susceptibility of the isolate were carried out with VITEK-2 compact system.HMV phenotype was detected by string-test.The major high virulence capsular serotypes (K1,K2,K5,K20,K54 and K57) and virulence factors (rmpA,wcaG,allS,kfu,aerobactin,fimH,uge,wabG and cf29a) were detected by polymerase chain reaction and DNA sequencing.Molecular typing was performed by multilocus sequence typing (MLST).Results showed that the isolates of blood and lung tissue were Klebsiella oxytoca belonged to ST 19,which were sensitive to the antibiotics used in test,expressing the HMV phenotype.The virulence gene wcaG was found,while other virulence genes and the major high virulence capsular serotypes were negative.It indicates that ST19 Klebsiella oxytoca with wcaG virulence gene is the main reason causing leukemic patient death.
10.The role of glutamate and peptidoglycan in nanotubes formation between adjacent bacteria
shi Qiao ZHONG ; ping Ya HANG ; lin Yan LIU ; Hui DING ; Feng YU ; hui Yan CHEN ; hua Long HU
Chinese Journal of Zoonoses 2017;33(10):893-896
We investigated the formation mechanism and immediate constituents of nanotubes between adjacent bacteria,pre venting rapid increase of drug-resistant bacteria provide potential targets.We used scanning electron microscopy(SEM) to observe formation of nanotubes;glutamic was determined by surface desorption atmospheric pressure chemical ionization mass spectrometry(SDAPCI-MS)and peptidoglycan was determined by enzyme linked immunosorbent assay(ELISA) in the forma tion of nanotubes before and after.The results showed that Staphylococcus aureus and Escherichia coli consumed more glutamic after formation of nanotubes;at the same time,the concentration of peptidoglycan in nanotubes formation of S.aureus and E.coli increased significantly.This study illuminated the glutamic and peptidoglycanin role mechanism of nanotubes form.We found that peptidoglycan is constituents of nanotubes and glutamic is the main energy source for the formation of nanotubes.

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