1.Protective effect of active ingredients of Kang Fu Ling on PC12 cells oxidative injury induced by microwave irradiation
Junjun CHEN ; Hongying BAI ; Ruiyun PENG ; Li ZHAO ; Yunliang WANG ; Shaohua HU ; Xueyan ZHANG ; Zhixiu XU ; Yanhui HAO
Military Medical Sciences 2016;40(4):281-284
Objective To observe the effect of the three active ingredients of a Chinese traditional medicine compound named Kang Fu Ling( KFL) against PC12 cells oxidative damage induced by microwave radiation.Methods PC12 cells were differentiated into neuros induced by nerve growth factor ( NGF ) .PC12 cells were incubated for 48 hours after astragalosides,total paeony glycoside and tanshinones were added at different concentrations (1, 3, or 9 μg/ml) .The cells in the control group were cultivated with the only medium of the same volume.Then, cells were irradiated with 30 mW/cm2 microwave for 6 minutes.The morphology of PC12 cells was observed under an inverted microscope soon before and after irradiation and the cell viability was measured by methylthiazolyl tetrazolium ( MTT) colorimetry.Reactive oxygen species ( ROS ) was determined using active oxygen probe 2′, 7′-dichlorodihyarofluolescen diacetde ( DCFH-DA ) while malonyldialdehyde(MDA) was measured in the homogenate of PC12 cells through thiobarbituric acid ( TBA) reactive substance assay.Results The cell morphology of each group showed no obvious difference.6 h after irradiation, the viability of irradiation control group measured by MTT declined apparently(P<0.01)compared with the normal control group.The 3 μg/ml astragalosides treatment group increased the viability of PC12 cells after microwave exposure ( P <0.01).The contents of ROS and MDA were increased after irradiation(P<0.01).However, in the three active ingredients of Kang Fu Ling treatment groups, both ROS and MDA were much lower than in irradiation control group.Conclusion Astragalosides, total paeony glycoside and tanshinones, which are the three active ingredients of Kang Fu Ling, all have protective effect against PC12 cell injury caused by microwave radiation,possibly by scavenging free radicals and reducing oxidative stress injury.
2.Efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma
Gongai WANG ; Yanyan LIANG ; Yongtian ZHANG ; Yuanyuan ZHANG ; Shasha DONG ; Yunliang HAO
Journal of Leukemia & Lymphoma 2024;33(3):152-155
Objective:To explore the clinical efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. The clinical data of 38 patients with RRMM in Jining NO.1 People's Hospital from Janunary 2020 to December 2022 were retrospectively analyzed. All patients were treated with daratumumab-based combined regimens. The Dd regimen (12 cases) was treated with daratumumab and dexamethasone, the DPD regimen (20 cases) was treated with pomalodomide based on the Dd regimen, the DVD regimen (6 cases) was treated with bortezomib based on the Dd regimen. The therapeutic efficacy and adverse reactions of all groups were analyzed. Kaplan-Meier method was used for survival analysis.Results:The median follow-up time was 9.5 months (1.0 months, 32.5 months) and the median treatmemt time was 6.2 months (3.2 months, 25.6 months). Among 38 patients, 7 cases (18.7%) achieved complete remission, 9 cases (23.6%) achieved very good partial remission, 10 cases (26.3%) achieved partial remission, 4 cases (10.5%) achieved minimal remission, 5 cases (13.1%) achieved stable disease, 3 cases (7.9%) had the progression of the disease. The overall response rate (ORR) was 78.9% (30/38). The ORR was 66.7%(8/12), 83.3%(5/6), 85.0%(17/20), respectively in the Dd group, DVD group and DPD group. There was no statistically significant difference in the ORR between the DVD group and DPD group ( χ2 = 0.01, P>0.05); there was no statistically significant difference in the ORR between the DVD group and Dd group ( χ2 = 0.55, P>0.05); there was no statistically significant difference in the ORR between the DPD group and Dd group ( χ2 = 1.47, P>0.05). The median progression-free survival (PFS) time was 12.5 months (95% CI: 8.5-24.2 months),the median overall survival (OS) time was not reached, and the 1-year OS rate was 89.4%. Among 38 patients, the main adverse reactions during treatment were infusion-related adverse reactions in 5 cases, grade 3 neutropenia in 7 cases, grade 3 thrombocytopenia in 9 cases, severe anemia in 12 cases; no one had drug discontinuation or drug reduction due to the intolerance of adverse reactions. Conclusions:Daratumumab-based combined regimens in the treatment of RRMM show a favorable efficacy and safety.
3.Effects of regulation of the PI3K/AKT signaling pathway by TYROBP on neuroinflammation and autophagy
Xiangrong XIAO ; Li GONG ; Yunliang ZHU ; Xinyu YANG ; Yanlei HAO ; Ruolin LI
Chinese Journal of Geriatrics 2023;42(11):1330-1336
Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.
4.Analysis of clinical effect of azacitidine combined with CAG regimen on treatment of relapsed/refractory acute myeloid leukemia
Gongai WANG ; Kewei XUE ; Shumei LI ; Yunliang HAO ; Shasha DONG
Journal of Leukemia & Lymphoma 2020;29(3):157-159
Objective:To explore the clinical effect of azacitidine combined with CAG regimen on the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The data of 50 patients with relapsed/refractory AML (non-acute promyelocytic leukemia) in Jining No. 1 People's Hospital from September 2018 to September 2019 was retrospectively analyzed, and the patients were divided into the control group and the test group according to the different treatment drugs. The control group (28 cases) was treated with CAG regimen alone, and the test group (22 cases) was treated with azacitidine combined with CAG regimen. The total effective rate and adverse reactions of the two groups were observed after 1 course of treatment.Results:After one course of treatment, the total clinical effective rate in the test group was 86% (19/22), and the rate in the control group was 71% (20/28), there was a statistically significant difference between the two groups (χ 2 = 5.273, P < 0.05). There were no significant differences in the incidence of adverse reactions such as fever, pulmonary infection, vomiting, and thrombocytopenia between the two groups (all P > 0.05). Conclusion:Azacitidine combined with CAG regimen in the treatment of relapsed/refractory AML can improve the clinical efficacy without increasing the adverse reactions.
5.Effect of chidamide combined with arsenic acid on the proliferation of T cell lymphoma Hut-78 cells and its mechanism
Gongai WANG ; Qing LI ; Yunliang HAO ; Shasha DONG
Journal of Leukemia & Lymphoma 2020;29(5):257-260
Objective:To investigate the effect of chidamide combined with arsenic acid on the proliferation inhibitory of T cell lymphoma Hut-78 cells and its mechanism.Methods:Low concentration group included 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide + 4.0 μmol/L arsenic trioxide). High concentration group included 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide + 6.0 μmol/L arsenic trioxide). Both groups were used to treat Hut-78 cells for 24 h and 48 h, respectively. Cell proliferation of Hut-78 cells in all drug treatment groups was tested by using methyl thiazolyl tetrazolium (MTT) method, and the proliferation inhibitory rate was also calculated. The expressions of vascular endothelial growth factor (VEGR) and bcl-2 protein of Hut-78 cells in different drug treatment groups by using Western blotting.Results:The cell proliferation inhibitory rate of Hut-78 cells treated for 24 h of 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) was (8.8±0.1)%, (9.2±0.5)% and (11.0±0.1)%, respectively ( F = 12.45, P < 0.05); The cell proliferation inhibitory rate of Hut-78 cells treated for 48 h was (19.1±0.5)%, (18.3±0.9)%, (23.1±1.3)%, respectively ( F = 9.86, P < 0.05). The cell proliferation inhibitory rate of Hut-78 cells treated for 24 h of 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) was (15.4±0.9)%, (13.2±0.9)% and (18.2±1.1)%, respectively ( F = 7.06, P < 0.05); The cell proliferation inhibitory rate of Hut-78 cells treated for 48 h was (28.5±1.2)%, (31.3±0.8)%, (45.2±2.1)%, respectively ( F = 14.32, P < 0.05). When Hut-78 cells were treated with 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) for 24 h, the relative expression level of bcl-2 protein was (58.4±2.9)%, (55.9±3.8)%, (53.2±2.1)%, respectively ( F = 17.52, P < 0.05); the relative expression level of VEGF protein was (60.5±4.2)%, (57.5±2.8)%, (50.9±3.5)%, respectively ( F = 7.36, P < 0.05). When Hut-78 cells were treated with 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) for 48 h, the relative expression level of bcl-2 protein was (48.2±1.8)%, (40.1±2.2)%, (32.3±3.1)%, respectively ( F = 10.38, P < 0.05); the relative expression level of VEGF protein was (51.4±4.1)%, (48.9±2.9)%, (40.8±3.8)%, respectively ( F = 8.96, P < 0.05). When Hut-78 cells were treated with 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) for 24 h, the relative expression level of bcl-2 protein was (55.4±3.1)%, (42.5±2.8)%, (37.8±4.2)%, respectively ( F= 10.35, P < 0.05); the relative expression level of VEGF protein was (49.2±3.4)%, (42.1±4.9)%, (34.3±5.1)%, respectively ( F= 17.82, P <0.05). When Hut-78 cells were treated with 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) for 48 h, the relative expression level of bcl-2 protein was (40.1±0.9)%, (35.3±1.6)%, (27.8±2.4)%, respectively ( F = 15.36, P < 0.05); the relative expression level of VEGF protein was (40.3±3.8)%, (35.9±4.6)%, (20.1±2.9)%, respectively ( F = 9.78, P < 0.05). Conclusion:Chidamide and arsenic trioxide have synergistic inhibitory effects on T cell lymphoma Hut-78 cells, which may be related to the down-regulated expressions of bcl-2 and VEGR.
6.Progress of myeloid-derived suppressor cells in hematological tumors
Yejing ZHU ; Yunliang HAO ; Yun GUAN
Journal of Leukemia & Lymphoma 2020;29(11):698-701
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that can regulate the immune response. They play an important role in the formation and progression of tumors and can suppress immune response in infections and inflammatory diseases. In recent years, MDSC have attracted a lot of attention in the field of tumor immunology, especially in solid tumors, but little is known about the role in hematological tumors. In this paper, the characteristics, functions and related clinical researches of MDSC in hematological tumors including multiple myeloma (MM), lymphoma, leukemia, and myelodysplastic syndrome (MDS) will be summarized to provide new ideas for the treatment of hematologic system tumors.
7.Up-regulation effect of neureglin1β on extracellular signal-regulated kinase 5 signaling pathway in rats with cerebral ischemia reperfusion injury
Hongyun LI ; Ning GU ; Yaqing JI ; Rui ZHANG ; Cui HAO ; Yunliang GUO
Chinese Journal of Neuromedicine 2016;15(11):1105-1110
Objective To explore the regulating mechanism ofneuregulin1β (NRG1β) on extracellular signal-regulated kinase 5 (ERK5) signaling pathway in rats with cerebral ischemia reperfusion injury.Methods Fifty male Wistar rats were divided randomly into sham-operated group,model group,treatment group,inhibitor group,and inhibitor combined with treatment group (n=10).Focal cerebral ischemic models were established by inserting a monofilament thread to achieve middle cerebral artery occlusion (MCAO).The rats were injected 5 μL (2 μg/kg) NRGlβ to the internal carotid artery.This inhibitor BIX02189 was injected into the internal carotid artery before ischemia.The neurobehavioral functions were evaluated by modified neurological severity scale (mNSS).The apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick-end labeling,and the expressions of phosphorylated (p-) mitogen activated proteins kinase kinase 5 (MEKK5),ERK5 and myocyte enhancer-binding factor 2C (MEF2C) were determined by immunohistochemical assay and Western blotting.Results The rats in the model group appeared neurobehavioral dysfunction,the number of apoptotic cells in the cortex was increased,and the expressions of p-MEKK5,p-ERK5 and p-MEF2C showed compensable enhancement,which were significantly different as compared with those in the sham-operated group (P<0.05).As compared with those in the model group and inhibitor combined with treatment group,the expressions of p-MEKK5,p-ERK5 and p-MEF2C were further significantly enhanced,the number of apoptotic cells was significantly decreased and the neurobehavioral functions were significantly improved in treatment group (P<0.05).As compared with those in the model group and inhibitor combined with treatment group,the number of apoptotic cells was significantly increased,and the expressions ofp-MEKK5,p-ERK5 and p-MEF2C were significantly decreased in the inhibitor group (P<0.05).Conclusion NRG1β could play a neuroprotective role by activating the MEKK5-ERK5-MEF2C signaling pathway and further up-regulating the expressions of p-MEKK5,p-ERK5 and p-MEF2C to inhibit the inflammation induced by cerebral ischemia reperfusion injury in rats.