1.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.
2.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.
3.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.
4.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.
5.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.
6.Treating Adult-onset Still's Disease Based on the Theory of Latent Pathogens in Yin (阴)Level
Guishu OUYANG ; Guangyu LI ; Xianping TANG ; Shenyi LIU ; Lianlian LIU ; Yinqi HU
Journal of Traditional Chinese Medicine 2025;66(15):1604-1609
Guided by the theory of latent pathogens, it is believed that the basic pathogenesis of adult-onset Still's disease is the latent pathogens in the deep yin level. The onset of the disease is fundamentally characterized by the deficiency of both qi and yin as the root, with dampness, heat, phlegm, and blood stasis as the branch, which triggered by intruding pathogens activate the latent pathogens in yin level. The treatment focuses on nourishing yin and dispersing heat as the key therapeutic method. It is proposed that clearing and resolving dampness-heat, expelling pathogens outward, dispersing the latent pathogens, reinforcing healthy qi and consolidating the root, boosting qi and nourishing yin as treatment idea. In clinic, Qinghao Biejia Decoction (青蒿鳖甲汤) could be used as the basic formula, and modified with characteristic herb pairs such as Qinghao (Artemisia annua) - Digupi (Lycium chinense) to enrich yin and clear heat, and enforce the power of clearing deficient heat; Biejia (Lawsonia inermis) - Xuchangqing (Vincetoxicum mukdenense) to enrich yin and activate blood, unblock the collaterals and dissipate masses; Duhuo (Angelica biserrata) - Mudanpi (Paeonia × suffruticosa) to dispel wind and activate blood, resolve dampness and unblock the collaterals, so as to clear and warm simultaneously, and regulate qi and blood at the same time; and Chuanshanlong (Dioscorea nipponica) - Difuzi (Bassia scoparia) to dissolve stasis and dispel phlegm, explore and dispel latent pathogens.
7.Effect of bluetongue virusinfection on type Ⅰ interferon response in BHK-21 cells
Shimei LUO ; Yunyi CHEN ; Qisha LI ; Yanmei ZHOU ; Yifei WANG ; Xinyu LIAO ; Xuer-Ou HU ; Yuanjian WEI ; Mengqin LI ; Meng ZHU ; Xun ZHANG ; Beirui CHEN ; Xianping MA ; Jiarui XIE ; Meiling KOU ; Haisheng MIAO ; Fang LI ; Huashan YI
Chinese Journal of Veterinary Science 2024;44(8):1639-1644,1690
Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.
8.Molecular study of a case with variant of RHCE*ce allele in haplotype dce resulting in weakened e antigen
Yongkui KONG ; Hecai YANG ; Ming SHAO ; Yinghui CHEN-LI ; Wanjin ZHANG ; Xiaoyan ZHANG ; Jing WANG ; Xianping LYU ; Qiankun YANG
Chinese Journal of Medical Genetics 2024;41(9):1039-1044
Objective:To explore the RH genotype for a female with RhD(-) blood type and its molecular basis. Methods:A 26-year-old female who had attended the outpatient clinic of the First Affiliated Hospital of Zhengzhou University in August 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents for Rh phenotyping with gel card method. PCR-sequence-based typing (PCR-SBT) and DNA sequencing were used to determine the RHD zygosity and RH genotype of the proband and her parents. Homology modeling of Rh proteins was performed with bioinformatic software, and protein structural alterations caused by the variant was simulated by molecular dynamics. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-0870-003). Results:Serological tests showed that the proband and her father both had weakened e antigen of the Rh phenotype. PCR-SBT and DNA sequencing showed that the genotypes of the proband and her parents were dce/ dCE, dce/ DcE and dCE/ DcE, respectively. And the genotypes of the RHD and RHCE of the proband were RHD*01N.01/ RHD*01N.16, RHCE*01.01/RHCE*04, respectively. Protein simulation and molecular dynamics analysis revealed that the ce_16C variant resulted from RHCE* ce (c.48G>C) may alter the structure of intracellular and extracellular loops, mainly affecting the mobility of extracellular loops 2, 6 and intracellular loops 3, 4. Conclusion:Variant of the RHCE* ce allele c. 48G>C probably underlay the weakened e antigen in this proband.
9.Clinical value of serum PKN1,TNFRSF4 and DDIT4 in predicting lymph node metastasis and prognosis of patients with endometrial cancer
Xinyu LI ; Yingjie LIU ; Jia GUO ; Nan XU ; Xiaojie YANG ; Xianping DONG
International Journal of Laboratory Medicine 2024;45(16):1931-1935,1940
Objective To explore the clinical value of serum protein kinase N1(PKN1),tumor necrosis factor receptor superfamily member 4(TNFRSF4),and DNA damage-inducible transcription factor 4(DDIT4)in predicting lymph node metastasis and prognosis of patients with endometrial cancer.Methods A total of 180 cases of endometrial cancer patients treated in Tangshan Maternal and Child Health Hospital from October 2019 to October 2021 were selected as endometrial cancer group.In addition,180 patients with benign uterine diseases treated in this hospital during the same period were selected as the benign disease group,and 180 healthy patients who underwent physical examination in this hospital were selected as the healthy group.The endometrial cancer group was divided into 42 cases with lymph node metastasis and 138 cases without lymph node metastasis according to whether lymph node metastasis occurred.The patients were divided into poor prognosis group and good prognosis group according to the follow-up results.The levels of serum PKN1,TNFRSF4 and DD1T4 in each group were compared,the influencing factors of patient prognosis were analyzed by Logistic model,and the predictive value of serum PKN1,TNFRSF4 and DDIT4 on prognosis of patients was analyzed by drawing the receiver operating characteristic curve.Results Compared with the healthy group,the levels of serum PKN1 and DDIT4 in endometrial cancer group and benign disease group were in-creased,and the levels of serum TNFRSF4 were decreased,with statistical significance(P<0.05).The serum levels of PKN1 and DDIT4 in lymph node metastasis group were higher than those in no lymph node metasta-sis group,and the levels of TNFRSF4 were lower than those in no lymph node metastasis group,with statisti-cal significance(P<0.05).The proportion of poor prognosis group with low differentiation degree,positive lymphovascular space invasion and myometrial infiltration≥1/2 was higher than that of good prognosis group,and the difference was statistically significant(P<0.05).The levels of serum PKN1 and DDIT4 in the poor prognosis group were higher than those in the good prognosis group,and the levels of TNFRSF4 were lower than those in the good prognosis group,with statistical significance(P<0.05).Serum PKN1,DDIT4,LVSI and myometrial infiltration were risk factors for the prognosis of endometrial cancer,and serum TN-FRSF4 was protective factor for the prognosis of endometrial cancer(P<0.05).Serum PKN1,TNFRSF4 and DDIT4 combined predicted the prognosis of patients with endometrial cancer more effectively than each serum index alone(P<0.05).Conclusion Serum PKN1,TNFRSF4 and DDIT4 are related to lymph node metasta-sis and prognosis of patients with endometrial cancer,and have high predictive efficacy for patient prognosis.
10.Clinical study on the treatment of OSAHS in children with different surgical approaches based on H-uvu-lopalatopharyngoplasty
Zhitai CHEN ; Shengguo WANG ; Benzhong ZHOU ; Xianping SHI ; Feifeng WU ; Longqiao LI ; Zesheng ZHANG ; Guangjie ZHOU ; Yang LIU
Journal of Practical Stomatology 2024;40(5):687-690
Objective:To study the clinical effects of modified surgical method with H-uvulopalatopharyngoplasty(H-UPPP)and traditional surgical method in the treatment of obstructive sleep apnea hypopnea syndrome(OSAHS)in children.Methods:The clini-cal data of 364 pediatric patients with OSAHS were retrospectively analyzed.The patients were divided into 2 groups and treated by low-temperature plasma knife radio frequency ablation for bilateral tonsil removal combined with H-UPPP(group A,n=204)and low-temperature plasma knife radio frequency ablation only(group B,n=160)respectively.The operative time,intraoperative bleed-ing,postoperative secondary bleeding,VAS of pain following operation,postoperative traumatic white film shedding time,OAH1,LSaO2,ESS scores and complications of the 2 groups were compared.Results:In group A the operative time,intraoperative bleed-ing,VAS,OAHI and ESS scores were lower than those in group B(P<0.05),wile postoperative traumatic white film detachment time and LSaO2 were higher(P<0.05).No statistically significant difference in terms of the number of cases of postoperative seconda-ry bleeding and complications was observed between the 2 groups(P>0.05).Conclusion:The combination of low-temperature plas-ma radio frequency ablation and H-UPPP for the treatment of OSAHS may provide clear intraoperative view,and may improve the treatment effects.

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