1.Gastrodin inhibits microglia-mediated inflammatory response in isch-emic hypoxic neonatal mice via CCR5/JAK1/STAT1 signaling pathway
Jinsha SHI ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Xinglin ZHANG ; Ha-Onan ZHANG ; Jinghui LI ; Juanjuan LI
Chinese Journal of Pathophysiology 2024;40(2):309-316
AIM:To investigate the effect of gastrodin(GAS)on microglia-mediated inflammatory response after hypoxic-ischemic brain damage(HIBD)neonatal mice by regulating the expression of JAK1/STAT1 pathway through C-C chemokine recepeor 5(CCR5).METHODS:Forty-eight C57BL/6J mice at about 10 days after birth were randomly divided into sham group,HIBD model group and HIBD+GAS group.BV-2 microglia were divided into control(Con)group,oxygen glucose deprivation(OGD)group,oxygen glucose deprivation with gastrodin intervention(OGD+GAS)group,GAS group,Maraviroc(MVC)group,OGD+MVC group,and OGD+MVC+GAS group.The mRNA expression of CCL4 and CCR5 were detected by RT-qPCR.The protein expression of CCR5,p-JAK1,p-STAT1,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by Western blot.The expression of CCR5,p-JAK1 and p-STAT1 in cells were observed by immunofluorescence staining.RESULTS:(1)Compared with sham group,the expression levels of CCL4 and CCR5 mRNA,and CCR5,p-JAK1 and p-STAT1 proteins were significantly higher in the ischemic side of the corpus callosum in HIBD group(P<0.05).(2)Compared with Con group,the protein levels of CCR5,p-JAK1 and p-STAT1 significantly increased in BV-2 cells of OGD group(P<0.05).The protein levels of CCR5,p-JAK1 and p-STAT1 in BV-2 cells of OGD+GAS group were significantly lower than those of OGD group(P<0.05).(3)Maraviroc did not cause significant BV-2 cell death in the 0~80 μmol/L range.The p-JAK1 and p-STAT1 protein levels in MVC+OGD group were significantly lowered compared with OGD group(P<0.05),but no significant difference was found between MVC+ OGD and OGD+MVC+GAS groups.CONCLUSION:Gastrodin can exert neuroprotective effects via CCR5/JAK1/STAT1 signaling pathway.
2.Gastrodin alleviates microglia-mediated inflammatory responses in neonatal mice with hypoxic-ischemic brain damage by regulating CCR5/AKT signaling
Jinsha SHI ; Haonan ZHANG ; Xinglin ZHANG ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Zhao WANG ; Hang YU ; Juanjuan LI
Journal of Southern Medical University 2024;44(10):1850-1857
Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.
3.Protective effect and mechanism of Scutellariae Radix on fibrosis in diabetic cardio-myopathy based on network pharmacology and cytology experiments
Kaijia SHI ; Cai LUO ; Yangyang ZHAO ; Xinglin ZHU ; Jinxuan CHAI ; Junli GUO ; Wei JIE
Chinese Journal of Arteriosclerosis 2024;32(5):386-394
Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy(DCM).Methods The technology platform of Chinese medicine system pharmacology(TCMSP)and the small molecule drug target prediction(Swiss Target Prediction)platform were used to excavate the active components of Scutellariae Radix and the target of its response.DCM related disease gene targets were screened using GeneCards,Disgene,UniPort and OMIM databases,and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram.Cytoscape 3.9.1 software was a-dopted to visualize the key target network.Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM,and draw pathway maps through the KEGG database.H9c2 and AC16 cardio-myocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group,35 mmol/L D-glucose as the high glucose group,and 10 μmol/L Baicalin was used for intervention.The levels of TGF-β1,collagen Ⅰ(COL Ⅰ)and collagen Ⅲ(CO LⅢ)mRNA were detected by RT-qPCR,and the expression of Smad2/3,p-Smad2/3,COL Ⅰ and COL Ⅲprotein were detected by Western blot,TGF-β1 level in supernatant was assessed by ELISA.Results Through the a-bove platform,a total of 33 effective ingredients including Baicalin,441 core targets,and 1 884 DCM disease genes were retrieved,150 core genes for treating DCM with Scutellariae Radix were obtained.The drug-disease interacted genes such as TGF-β1,TP53,MMP-9 and IL-6 were obtained through String PPI,KEGG signaling pathways such as MAPK and PI3K/Akt were enriched.In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1,COL Ⅰ and COL Ⅲ mRNA levels,p-Smad2/3,COL Ⅰ and COL Ⅲ protein levels,and signifi-cantly increased the content of TGF-β1 in the supernatant,while Baicalin weakened its expression.Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets,among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.
4.Gastrodin alleviates microglia-mediated inflammatory responses in neonatal mice with hypoxic-ischemic brain damage by regulating CCR5/AKT signaling
Jinsha SHI ; Haonan ZHANG ; Xinglin ZHANG ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Zhao WANG ; Hang YU ; Juanjuan LI
Journal of Southern Medical University 2024;44(10):1850-1857
Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.
5.Gastrodin inhibits the lipopolysaccharide-induced microglia activation through the SOX2/β-catenin signaling pathway
Xinglin ZHANG ; Jinsha SHI ; Hongming FU ; Yurui HUANG ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Juanjuan LI
Chinese Journal of Neuroanatomy 2024;40(3):365-372
Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0~40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P<0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P<0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P<0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.
6.Integrated Traditional Chinese and Western Medicine Treatment for Acute Lymphoblastic Leukemia Complicated with Severe COVID-19 in Recovery Stage: A Case Report
Xinglin GUO ; Jianzhu SHAO ; Jing JING ; Mingzhong XIAO ; Chongxiang XUE ; Qingwei LI ; Yanjiao ZHANG ; Chensi YAO ; Xuefei ZHAO ; Keyu CHEN ; Yingying YANG ; Xiuyang LI ; Yusheng BAI
Journal of Traditional Chinese Medicine 2023;64(23):2466-2470
This paper reported a case of severe COVID-19 in the recovery stage with acute lymphoblastic leukemia treated by integrated traditional Chinese and western medicine, with the intention of shedding light on the clinical diagnosis and treatment of similar conditions. The patient, who had acute lymphoblastic leukemia, developed COVID-19 infection during the bone marrow suppression period after chemotherapy. Treatment with western medicine was mainly anti-infection, symptomatic management, and supportive care. During the recovery stage, considering the patient's chemotherapy history and disease progression, the overall syndrome was identified as deficiency of both qi and yin and binding of phlegm and blood. Based on the “state-target” combined treatment strategy, herbal prescriptions were selected and modified to address the “deficiency state”, “disease target”, and “symptom target”. In addition to western medicine, the patient was administered with Shengmai Powder (生脉散) and Compound Zhebei Granules (复方浙贝颗粒) in its modifications to boost qi, nourish yin, and reinforce healthy qi, nourish and cool the blood, ultimately achieving satisfactory therapeutic effects.
7.China' s process and challenges in achieving the United Nations Millennium Development Goal 5
Xinglin FENG ; Qing YANG ; Ling XU ; Yan WANG ; Yan GUO
Journal of Peking University(Health Sciences) 2011;43(3):391-396
Objective:China was categorized as one of the 68 countdown countries to achieve the United Nations Millennium Development Goals (MDG) 5. This paper aimed to analyze the situation of maternal survival, and coverage of proven cost effective interventions in China, where specific attention was paid to disparities. Methods: National maternal and child mortality surveillance data were used to estimate maternal mortality ratio (MMR). Coverage for proven interventions was analyzed based on National Health Services Survey, where experts' consultations were made for complementation. Results: There had been a significant reduction of MMR in China, however great disparities existed, with rural Ⅱ to Ⅳ areas experiencing 2 to 5 times higher maternal mortality risks than urban areas and accounting for over 70% maternal mortality burdens. Postpartum hemorrhage, pregnancy associated hypertension, embolism and sepsis were the leading causes, and over 75% of the maternal mortality was caused by preventable or curable causes. Maternal health services utilization decreased in accordance with region' s development level. Socioeconomic factors like financial difficulties were the main obstacles hindering access of care.Even those who made deliveries in hospitals faced different probabilities in receiving qualified care according to their socioeconomic standings. Conclusion: China is on track to achieve MDG 5, however great disparities exist. It is necessary to specifically target rural types Ⅱ to Ⅳ areas. Major causes of maternal mortality which can be prevented or averted through the provision of essential obstetrical care. Yet as compared with maternity health needs, insufficient coverage of maternal and child health (MCH) care services and poor service quality are the leading predisposing factors contributing to maternal mortality in China.
8.Effect of Passive Exercise on Neural Functional Recovery in Rabbits after Peripheral Nerve Crushed Injury
Lining ZHANG ; Xinglin WANG ; Ziyang LIU ; Zhengmao WEI ; Yizhu GUO ; Yiqiong ZHENG ; Xiaoming ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2007;13(3):243-244
Objective To investigate the effect of passive exercise on neural functional recovery after peripheral nerve crushed injury.MethodsThe effect of passive exercise on early peripheral nerve regeneration and recovery of motor function were observed with electrophysiological and histological indexes compared with that of the splinting group.ResultsThe nerve conduction of training group was faster than that in the splinting group,and the latency of compound muscle action potentials(CMAP)was shorter(P<0.05).The thickness of myelin sheath,average numbers of myelinated nerve fibera per area and diameter of regenerating axon in training group were larger than those in the splinting group(P<0.05).The wet weight of sural triceps of training group were bigger than that of the splinting group(P<0.01).ConclusionThe passive exercise can improve the early recovery of motor function and neural regeneration after peripheral nerve crushed injury.
9.Clinical Analysis on Brachial Plexus Injury with 41 Cases
Ziyang LIU ; Xinglin WANG ; Yizhu GUO
Chinese Journal of Rehabilitation Theory and Practice 2007;13(4):393-395
Objective To observe the long-term result of brachial plexus injury.Methods41 cases of brachial plexus injury were divided into the non-operation group (n=11), neurolysis group (n=17), never repair group (n=13). Retrospective analysis of the charts and follow-up survey of the functional recovery of shoulder joint and elbow joint were carried out. Gilbert score and Mallett score were adopted at the follow-up.ResultsIn the non-operation group, 9 cases were graded as excellent, 1 case as good, 1 case as bad. In the neurolysis group, 2 cases were graded as excellent and good. In the never repair group, 2 cases of shoulder joint obtained excellent, 4 cases of elbow joint were grade as good.ConclusionThe simple surgical result of brachial plexus injury is not satisfactory, it should be combined with postoperative rehabilitation.
10.Research on the social determinants of child health inequalities
Xinglin FENG ; Juan SHEN ; Yan GUO
Journal of Peking University(Health Sciences) 2004;0(03):-
Objective:To investigate the impact of social determinants of health on the inequality of child health and health care utilization.Methods:Information of 1 118 children aged 0 to 16 is extracted from the Chinese Family Panel Studies(CFPS)year 2008 cross sectional survey data for the analysis.Age standardized concentration curves and concentration indices are employed to assess the inequalities for incidence of low birth weight,self reported good health,adequate timing of breast feeding,health insurance coverage and incidence of catastrophic health expenditures for these children.Concentration indices are decomposed to four levels of social determinants of health(community,family,mother and individual level)to understand their contributions to health inequality respectively.Results:There are health inequalities existing in the investigated children,among which social factors at mother and family level have the largest contribution.Conclusion:To respond to the call by the WHO to achieve health equity through action on the social determinants of health in a generation,the inequalities of health and health care utilization amongst Chinese children should be put on the policy agenda,and social policies should intervene from multiple social dimensions,especially from family and mother levels.


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