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GPER and IGF-1R mediate the anti-inflammatory effect of genistein against lipopolysaccharide-induced nigrostriatal injury

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GPER and IGF-1R mediate the anti-inflammatory effect of geni...

2019中国生理学会学术年会暨张锡钧基金第十五届全国青年优秀生理学学术论文交流会及第十三届全国青年生理学工作者学术会议

作者：张梅 Zhong-Rui Du wen-fang chen Department of Physiology and Pathophysiology Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological DisordersSchool of Basic MedicineQingdao University

Objective Neuroinflammation plays an important role in the pathogenesis of Parkinson’s disease(PD).The present study was designed to investigate the anti-inflammatory and neuroprotective mechanism of genistein in LPS-induced PD rat *** LPS was injected into the substantia nigra to establish a rat inflammatory model of *** dopamine(DA) content in the striatum was studied by *** numbers of TH-ir neurons and the activation of microglia in the SNpc were detected by *** inflammatory factors protein expressions were detected by western blot and *** Genistein pretreatment could ameliorate the apomorphine-induced rotational behavior in LPS-induced inflammatory PD rat *** attenuated LPS-induced decrease of the contents of DA and its metabolites in striatum as well as the loss of TH-IR neurons in the lesioned side of *** GPER antagonist G15 or IGF-1 R antagonist JB-1 blocked the neuroprotective effects of ***, genistein significantly inhibited LPS-induced microglial activation and production of TNF-α, IL-1β, iNOS and *** of GPER or IGF-1 R by G15 or JB1 could attenuate the anti-inflammatory effects of ***, genistein treatment could inhibit the LPS-induced activation of NF-κB and MAPKs signaling pathways in the lesioned side of SN, which could also be blocked by G15 or *** Genistein inhibits microglial inflammatory responses and protects nigral dopaminergic neurons via GPER and IGF-1 R signaling pathways.

关键词： genistein G protein-coupled estrogen receptor insulin-like growth factor 1 receptor neuroinflammation Parkinson’s disease

Impact of imipenem treatment on colonic mycobiota in rats with double-hit sepsis

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Chinese Medical Journal 2013年第10期126卷 1850-1854页

作者： GUAN Jun LIUShao-ze LIN Zhao-fen LI wen-fang LIUXue-feng chen De-chang Department of Critical Care and Emergency Medicine ShanghaiChangzheng Hospital Second Military Medical University Shanghai200003 China

Background Broad-spectrum antibiotic administration promotes intestinal colonization of exogenous fungal pathogens in healthy animals and has been recognized as one of the risk factors of invasive fungal infection in clinical settings. It is unclear whether broad-spectrum antibiotic treatment would change the intestinal mycobiota without exogenous fungal challenge in the context of sepsis. Methods We established a rat model of double-hit sepsis using burn injury and endotoxin challenge. Rats with burn injury or double-hit sepsis received imipenem treatment for 3 days or 9 days, and their colon contents were sampled for selective fungal culture and isolation counts. Results Imipenem treatment promoted the overgrowth of the commensal fungus Geotrichum capitatum in rats with burn injury. Imipenem treatment also promoted colon colonization by exogenous fungi in rats with burn injury and double-hit sepsis, including Trichosporon cutaneum, Candida albicans, Candida krusei, and Candida glabrata. A longer duration of imipenem treatment had a stronger impact on colon colonization by exogenous fungi. Conclusion Imipenem treatment facilitates the overgrowth of commensal fungi and colonization by exogenous, potentially pathogenic fungi in the colons of rats with burn injury or double-hit sepsis.

关键词： sepsis, imipenem mycobiota burn, endotoxin

Prognosis of BK polyomavirus nephropathy: 10-year analysis of 133 renal transplant recipients at a single center

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Chinese Medical Journal 2019年第4期132卷 388-394页

作者： Xu-Tao chen Shi-Cong Yang Jun Li Rong-Hai Deng wen-fang chen Jiang Qiu Li-Zhong chen Chang-Xi Wang Gang Huang Department of Organ Transplantation The First Affiliated Hospital of Sun Yat Sen UniversityGuangzhouGuangdong 510080China Department of Pathology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China.

Background: BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN. Methods: We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up. Results: After a mean follow-up period of 14.4 (range, 0.3–109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow- up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min^-1·1.73 m^-2, t= 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min^-1·1.73 m^-2, t= 3.034, P= 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min^-1·1.73 m^-2), urine viral loads (median, 1.3 × 105vs. 1.4 × 107 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ^2= 6.341, P= 0.042). Conclusion: Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.

关键词： Kidney transplantation BK virus Pathology Rejection Prognosis

GPER is involved in the anti-inflammatory effects of genistein in BV2 microglial cells

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GPER is involved in the anti-inflammatory effects of geniste...

中国神经科学学会第十二届全国学术会议

作者： Zhong-Rui DU Liang-Jie YUAN wen-fang chen Department of Physiology Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders Medical College of Qingdao University

Objective Genistein is an isoflavonoid phytoestrogen extracted from leguminous plants exerting both estrogen agonist and antagonist activities. The present study hypothesized that the anti-inflammatory effects of genistein against lipopolysaccharide（LPS）-induced BV2 microglial activation might be mediated by membrane estrogen receptor（G-protein coupled estrogen receptor, GPER）. Methods The anti-inflammatory effects of genistein were investigated in LPS-induced microglial activation in murine BV2 cells. G1, the specific agonist of GPER, was used as a positive control. The pharmacological blockade and lentivirus-mediated si RNA knockdown of GPER were used to study the underlying mechanism. Results Genistein mimicked the effects of G1 treatment by inhibiting the LPS-induced gene expressions of inflammatory cytokines, including TNF-a, IL-1b, COX-2 and iNOS in BV2 microglial cells. Pretreatment with GPER antagonist G15 or si RNA knockdown of GPER could significantly block the anti-inflammatory effects of genistein and G1. Furthermore, pretreatment with G15 could also block the inhibitory effects of genistein on LPS-induced phosphorylation of JNK, p38, ERK and IkB. Conclusion Genistein exerts antin-inflammatory effects in BV2 microglial cells possibly by the activating GPER.

关键词： genistein G protein-coupled estrogen receptor insulin-like growth factor 1 receptor microglia

Combined detection of urine specific gravity and BK viruria on prediction of BK polyomavirus nephropathy in kidney transplant recipients

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Chinese Medical Journal 2020年第1期133卷 33-40页

作者： Xu-Tao chen Ze-Yuan Wang Yang Huang Jin-Yuan Wang Shi-Cong Yang wen-fang chen Pei-Song chen Jun Li Rong-Hai Deng Gang Huang Department of Organ Transplantation.The First Affiliated Hospital of Sun Yat-Sen University Guangzhou.Guangdong 510080China Zhongshan School of Medicine.Sun Yat-Sen University Guangzhou.Guangdong 510080.China Department of Pathology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China Department of Clinical Laboratory The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080Chin

Background:BK polyomavirus(BKPyV)-associated nephropathy(BKPyVAN)is an important cause of dysfunction and failure of renal *** study aimed to assess the diagnostic performance of morning urine specific gravity(MUSG)in diagnosing BKPyVAN in kidney transplant ***:A total of 87 patients,including 27 with BKPyVAN,22 with isolated BKPyV viruria,18 with T cell-mediated rejection(TCMR),and 20 with stable graft function,were enrolled in the First Affiliated Hospital of Sun Yat-Sen University from March 2015 to February *** at biopsy and during a follow-up period of 24 months after biopsy was collected and *** operating characteristic(ROC)curve analysis was used to determine the ability of MUSG to discriminate ***:At biopsy,the MUSG of BKPyVAN group(1.008±0.003)was significantly lower than that of isolated BK viruria group(1.013±0.004,P<0.001),TCMR group(1.011±0.003,P=0.027),and control group(1.014±0.006,P<0.001).There was no significant difference in MUSG among the isolated BK viruria group,TCMR group,and control group(P=0.253).In BKPyVAN group,the timing and trend of MUSG elevate were consistent with the timing and trend of the decline of viral load in urine and plasma,reaching a statistical difference at 3 months after treatment(1.012±0.003,P<0.001)compared with values at *** analysis indicated that the optimal cut-off value of MUSG for diagnosis of BKPyVAN was 1.009,with an area under the ROC curve(AUC)of 0.803(95%confidence interval[CI]:0.721–0.937).For differentiating BKPyVAN and TCMR,the optimal MUSG cut-off value was 1.010,with an AUC of 0.811(95%CI:0.687–0.934).Conclusion:Combined detection of MUSG and BKPyV viruria is valuable for predicting BKPyVAN and distinguishing BKPyVAN from TCMR in renal transplant recipients.

关键词： BK polyomavirus Kidney transplantation Nephropathy Rejection Urinalysis

Engineered Cancer Nanovaccines:A New Frontier in Cancer Therapy

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Nano-Micro Letters 2025年第2期17卷 134-168页

作者： Yijie Wang Congrui Liu Chao fang Qiuxia Peng wen Qin Xuebing Yan Kun Zhang Central Laboratory and Department of Medical Ultrasound Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo.32West Second SectionFirst Ring RoadChengdu 610072People’s Republic of China Department of Stomatology and Central Laboratory School of MedicineShanghai Tenth People’s HospitalTongji UniversityNO.301 Yan‑Chang‑Zhong RoadShanghai 200072People’s Republic of China Jiangsu Provincial Innovation and Practice Base for Postdoctors Suining People’s HospitalAffiliated Hospital of Xuzhou Medical UniversityNo.2Bayi West RoadSuiningXu Zhou 221000Jiangsu ProvincePeople’s Republic of China

Vaccinations are essential for preventing and treating disease,especially cancer nanovaccines,which have gained considerable interest recently for their strong anti-tumor immune *** can prompt the immune system to generate antibodies and activate various immune cells,leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and *** enhance the flexibility and targeting of vaccines,nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level,enabling more controlled and precise drug delivery to enhance immune *** nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within *** small size of these nanomaterials allows for precise targeting of T cells,dendritic cells,or cancer cells,thereby eliciting a more potent anti-tumor *** this paper,we focus on the classification of carriers for cancer nanovaccines,the roles of different target cells,and clinically tested cancer nanovaccines,discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation,while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

关键词： Cancer nanovaccines Immunotherapy Nanobiotechnology Immune targets Signaling pathway

PI3K/Akt signaling pathway is involved in the neuroprotective effects of icariin on dopaminergic neurons in the mice model of Parkinson’s disease

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PI3K/Akt signaling pathway is involved in the neuroprotectiv...

中国神经科学学会第十届全国学术会议

作者： Xian-Chang SUN Xian-Qi GAO Lin WU wen-fang chen Department of Physiology Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:PhysiologyMedical College of Qingdao University

Objective Icariin is the major active compound of Herba epimedii,a commonly used Chinese herb for the management of some age-related *** present study aims to delineate the neuroprotective effects of icariin on dopaminergic neurons and the possible mechanisms in a mice model of Parkinson’s disease（PD） induced by l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine（MPTP）.Methods The DA content in the striatum was studied by *** blot was used to determine the protein expressions of Bcl-2,Bax,and Caspase 3 in the *** numbers of tyrosine hydroxylase-immunoreactive（TH-IR） neurons in the substantial nigra were assessed by *** Icariin treatment could ameliorate the decreased DA content in the striatum induced by *** effect could be completely blocked by *** sigmficantly decreased the TH-IR neurons in the substantia *** with icariin could reverse the decrease of TH-IR induced by *** effect also could be blocked by ***,MPTP-challenge with icariin treatment demonstrated reduced neurotoxicity with Bcl-2,Bax,caspase 3 protein levels in the *** These data demonstrated that icariin has neuroprotective effects on dopaminergic neurons in the MPTP-induced PD mice and its actions might involve activation of PI3K signaling pathway.

关键词： icariin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Parkinson’s disease phosphatidylinositol 3-kinase

Wave effect of gravitational waves intersected with a microlens field Ⅱ:An adaptive hierarchical tree algorithm and population study

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 241-254页

作者： Xikai Shan Guoliang Li Xuechun chen wen Zhao Bin Hu Shude Mao Department of Astronomy Tsinghua University Purple Mountain Observatory Chinese Academy of Sciences Institute for Frontier in Astronomy and Astrophysics Beijing Normal University School of Physics and Astronomy Beijing Normal University School of Astronomy and Space Science University of Science and Technology of China CAS Key Laboratory for Researches in Galaxies and Cosmology Department of Astronomy University of Science and Technology of ChinaChinese Academy of Sciences

The gravitational lensing wave effect generated by a microlensing field embedded in a lens galaxy is an inevitable phenomenon in strong lensed gravitational waves （SLGWs）.This effect presents both challenges and opportunities for the detection and application of ***,investigating this wave effect requires computing a complete diffraction integral over each microlens in the *** is extremely time-consuming due to the large number of microlenses （10～3-10～6）.Therefore,simply adding all the microlenses is ***,the complexity of the time delay surface makes the lens plane resolution a crucial factor in controlling numerical *** this paper,we propose a trapezoid approximation-based adaptive hierarchical tree algorithm to meet the challenges of calculation speed and *** find that this algorithm accelerates the calculation by four orders of magnitude compared to the simple adding method and is one order of magnitude faster than the fixed hierarchical tree algorithm proposed for electromagnetic *** importantly,our algorithm ensures controllable numerical errors,increasing confidence in the *** with our previous work （***.66,239511,2023）,this paper addresses all numerical issues,including integral convergence,precision,and computational time1).Finally,we conducted a population study on the microlensing wave effect of SLGWs using this algorithm and found that the microlensing wave effect cannot be ignored,especially for Type II SLGWs （from saddle position of the time delay surface） due to their intrinsic geometric structures and their typical intersection with a denser microlensing ***,more than 33%（11%） of SLGWs have a mismatch larger than 1%（3%） compared to the unlensed ***,we found that the mismatch between signal pairs in a doubly imaged GW is generally larger than 10-3,and 61%（25%） of signal pairs have a mismatch larger than 1%（3%）.Therefo

关键词： gravitational lensing diffractional integral algorithm gravitational wave

Neuroprotective effects of genistein against 6-OHDA-induced neurotoxicity in SK-N-SH cells

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Neuroprotective effects of genistein against 6-OHDA-induced ...

中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Quan-Gui GAO,wen-fang chen Department of Physiology,Medical College of Qingdao University,Qingdao,266071 China

＜正＞Genistein,a natural isoflavone phytoestrogen present in soybean,has a chemical structure similar to steroidal *** genistein exposure may act similarly to estradiol in augmenting amphetamine-stimulated striatal dopamine release in male and female *** vitro study has revealed that genistein can protect the primary neurons of ventral mesencephalon against 1-methyl-4-phenylpyridinium（MPP+） induced dopaminergic neuronal *** previous studies have demonstrated that genistein mimics the action of estradiol in stimulation of MCF-7 cell growth by the crosstalk between estrogen receptor（ER）-dependent pathway and insulin-like growth factor I receptor（IGF-IR）-dependent pathway. The present study aims to investigate the neuroprotective effects of genistein against 6-OHDA-induced neurotoxicity in SK-N-SH cells and the possible ***-N-SH cells were cultured in phenol-red free DMEM supplemented with 10%sFBS and treated with genistein for 24 h before exposure to *** viability was determined by MTT assay. Apoptosis was assessed by the gene expressions of Bcl-2 and Bax,and changes in mitochondrial membrane potential. Genistein had obvious concentration-dependent neuroprotective effects on cell viability against 6-OHDA-induced *** with genistein could reverse the decrease of Bcl-2 and the increase of Bax gene expressions induced by *** could attenuated 6-OHDA-induced the decrease in mitochondrial membrane potential. These effects could be completely blocked by ER antagonist ICI182,780 or IGF-IR antagonist *** results clearly show that genistein may attenuate 6-OHDA-induced apoptosis through the crosstalk between the ER-dependent pathway and IGF-IR-dependent pathway.

关键词： genistein neuroprotection apoptosis estrogen receptor insulin-like growth factor I receptor