المؤلفون: Fan, Shuangbo, Xu, Qian, Wang, Liang, Wan, Yulin, Qiu, Sheng

المصدر: Pharmacology ; volume 105, issue 3-4, page 164-172 ; ISSN 0031-7012 1423-0313

الوصف: SMBA1 (small-molecule Bax agonists 1), a small molecular activator of Bax, is a potential anti-tumour agent. In the present study, we investigated the biological effects of SMBA1 on glioblastoma (GBM) cells. SMBA1 reduced the viabilities of U87MG, U251 and T98G cells in a time- and dose-dependent manner. Moreover, treatment with SMBA1 induced cell cycle arrest at the G2/M phase transition, accompanied by the downregulation of Cdc25c and cyclin B1 and the upregulation of p21. SMBA1 also induced apoptosis of GBM cells in a dose-dependent manner. Mechanistically, SMBA1 induced apoptosis via the intrinsic pathway. Silencing of Bax or ectopic expression of Bcl-2 significantly inhibited SMBA1-induced apoptosis. Moreover, SMBA1 inhibited the growth of U87MG xenograft tumours in vivo. Overall, SMBA1 shows anti-proliferative effects against GBM cells through activation of the intrinsic apoptosis pathway.

الإتاحة: https://doi.org/10.1159/000500292Test
https://www.karger.com/Article/Pdf/500292Test

المؤلفون: Wang, Liang¹ (AUTHOR), Fan, Shuangbo¹ (AUTHOR), Zhao, Zhenping¹ (AUTHOR), Xu, Qian¹ (AUTHOR)

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM). 10/27/2021, p1-6. 6p. 4 Charts.

مصطلحات موضوعية: *NERVE growth factor, *HYDROCEPHALUS, *ARGININE, *VASOPRESSIN, *DECOMPRESSIVE craniectomy, *ADRENOCORTICOTROPIC hormone, *HEAD injuries

مستخلص: In recent years, the incidence of craniocerebral trauma has increased, making it one of the important causes of death and disability in neurosurgery patients. The decompressive craniectomy (DC) after severe craniocerebral injury has become the preferred treatment for patients with severe craniocerebral injury, but the incidence of postoperative hydrocephalus has become a difficult problem in clinical treatment. This study observed the changes of nerve growth factor (NGF), adrenocorticotropic hormone (ACTH), and arginine vasopressin (AVP) levels in the CSF after DC in patients with craniocerebral injury and analyzed the relationship between the three indicators and communicating hydrocephalus. The results showed that the levels of NGF, ACTH, and AVP in patients with cranial injury after DC were significantly higher than those in healthy subjects, and subdural effusion, traumatic subarachnoid hemorrhage (tSAH), and the levels of NGF, ACTH, and AVP in the CSF were independent risk factors for communicating hydrocephalus. Monitoring the levels of NGF, ACTH, and AVP is of great significance for clinicians to judge the occurrence of traffic hydrocephalus, evaluate the prognosis of patients with craniocerebral injury after DC, and guide clinical treatment. [ABSTRACT FROM AUTHOR]

المؤلفون: Gao, Liansheng, Xu, Weilin, Fan, Shuangbo, Li, Tao, Zhao, Tengfei, Ying, Guangyu, Zheng, Jingwei, Li, Jianru, Zhang, Zhongyuan, Yan, Feng, Zhu, Yongjian, Chen, Gao

المساهمون: National Natural Science Foundation of China, Natural Science Foundation of Zhejiang Province

المصدر: BioFactors ; volume 44, issue 4, page 369-386 ; ISSN 0951-6433 1872-8081

الوصف: The aim of this study was to investigate the potential effect and mechanism of action of MANF in attenuating neuronal apoptosis following t‐SCI. A clip compressive model was used to induce a crush injury of the spinal cord in a total of 230 rats. The Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content, and blood spinal cord barrier (BSCB) permeability were evaluated. The expression levels of MANF and its downstream proteins were examined by western blotting. Immunofluorescence staining of MANF, NeuN, GFAP, Iba‐1, cleaved caspase‐3, and TUNEL staining were also performed. Cells were counted in six randomly selected fields in the gray matter regions of the sections from two spinal cord sites (2 mm rostral and caudal to the epicenter of the injury) per sample. A cell‐based mechanical injury model was also conducted using SH‐SY5Y cells. Cell apoptosis and viability were assessed by flow cytometry, an MTT assay, and trypan blue staining. Subcellular structures were observed by transmission electron microscopy. MANF was mainly expressed in neurons. The expression levels of MANF, and its downstream target, p‐Akt, were gradually increased and after t‐SCI. Treatment with MANF increased Bcl‐2 and decreased Bax and CC‐3 levels; these effects were reversed on treatment with MK2206. The BBB score, spinal cord water content, and BSCB destruction were also ameliorated by MANF treatment. MANF decreases neuronal apoptosis and improves neurological function through Akt/MDM‐2/p53 pathway after t‐SCI. Therefore, MANF might be a potential treatment for patients with t‐SCI. © 2018 BioFactors, 44(4):369–386, 2018

الإتاحة: https://doi.org/10.1002/biof.1433Test

المؤلفون: Fan, Shuangbo¹ (AUTHOR), Xu, Qian¹ (AUTHOR), Wang, Liang¹ (AUTHOR), Wan, Yulin¹ (AUTHOR), Qiu, Sheng² (AUTHOR) qius2001@163.com

المصدر: Pharmacology. Mar2020, Vol. 105 Issue 3/4, p164-172. 9p. 1 Color Photograph, 3 Black and White Photographs, 1 Graph.

مصطلحات موضوعية: *GLIOMAS, *APOPTOSIS, *CELLS, *GLIOBLASTOMA multiforme

مستخلص: SMBA1 (small-molecule Bax agonists 1), a small molecular activator of Bax, is a potential anti-tumour agent. In the present study, we investigated the biological effects of SMBA1 on glioblastoma (GBM) cells. SMBA1 reduced the viabilities of U87MG, U251 and T98G cells in a time- and dose-dependent manner. Moreover, treatment with SMBA1 induced cell cycle arrest at the G2/M phase transition, accompanied by the downregulation of Cdc25c and cyclin B1 and the upregulation of p21. SMBA1 also induced apoptosis of GBM cells in a dose-dependent manner. Mechanistically, SMBA1 induced apoptosis via the intrinsic pathway. Silencing of Bax or ectopic expression of Bcl-2 significantly inhibited SMBA1-induced apoptosis. Moreover, SMBA1 inhibited the growth of U87MG xenograft tumours in vivo. Overall, SMBA1 shows anti-proliferative effects against GBM cells through activation of the intrinsic apoptosis pathway. [ABSTRACT FROM AUTHOR]