ABSTRACT
Aim To determine the effect of histamine H
ABSTRACT
OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.
Subject(s)
Humans , Apoptosis , Bortezomib/pharmacology , Cell Line, Tumor , Cell Proliferation , Interleukin-1 Receptor-Associated Kinases , Multiple Myeloma , Pentacyclic Triterpenes , Signal TransductionABSTRACT
Objective To study the effect of electroacupuncture on repair of spinal cord injury and its effect on somatosensory evoked potential ( SEP) in dog models of intervertebral disc prolapse. Methods Nine Beagle dogs were randomly divided into three groups. In the model group and electroacupuncture group, the dog disc prolapse models were made by balloon compression, and in the electroacupuncture group, electroacupuncture was used every day for 14 days after operation. The model group was not treated after surgery. Sham operation was performed in the control group. Each dog was scored according to the Texas Spinal Cord Injury Scale for Dogs (TSCIS) scores before surgery (day 0) and on days 1, 4, 7, 14 after surgery. At the same time, SEP wave was measured using an EMG Evoked Potential Measuring Systerm and its latency and amplitude were analyzed. Results There was a significant difference in TSCIS scores between the model group, electroacupuncture group and control group at 1 day after operation. There was a significant difference between the electroacupuncture and model groups at 14 days after surgery. The amplitude of SEP in the model and electroacupuncture groups was significantly different from that in the control group at 1 day after operation, and there was a significant differ-ence between the electroacupuncture and model groups at 14 days after operation. There was a significant difference in the latency of SEP between the model and electroacupuncture groups at 4 days after operation, and between the electroacupunc-ture and model groups after at 14 days after operation. Conclusions Electroacupuncture can effectively promote healing of spinal cord injury in dogs with intervertebral disc prolapse, improve the TSCIS scores, restore SEP waveform, shorten the latency and enhance the amplitude. SEP can reflect the degree of spinal cord injury to a certain extent, and can be used to evaluate the effect of electroacupuncture treatment in these dogs.
ABSTRACT
Objective To study the effect of electroacupuncture on repair of spinal cord injury and its effect on somatosensory evoked potential ( SEP) in dog models of intervertebral disc prolapse. Methods Nine Beagle dogs were randomly divided into three groups. In the model group and electroacupuncture group, the dog disc prolapse models were made by balloon compression, and in the electroacupuncture group, electroacupuncture was used every day for 14 days after operation. The model group was not treated after surgery. Sham operation was performed in the control group. Each dog was scored according to the Texas Spinal Cord Injury Scale for Dogs (TSCIS) scores before surgery (day 0) and on days 1, 4, 7, 14 after surgery. At the same time, SEP wave was measured using an EMG Evoked Potential Measuring Systerm and its latency and amplitude were analyzed. Results There was a significant difference in TSCIS scores between the model group, electroacupuncture group and control group at 1 day after operation. There was a significant difference between the electroacupuncture and model groups at 14 days after surgery. The amplitude of SEP in the model and electroacupuncture groups was significantly different from that in the control group at 1 day after operation, and there was a significant differ-ence between the electroacupuncture and model groups at 14 days after operation. There was a significant difference in the latency of SEP between the model and electroacupuncture groups at 4 days after operation, and between the electroacupunc-ture and model groups after at 14 days after operation. Conclusions Electroacupuncture can effectively promote healing of spinal cord injury in dogs with intervertebral disc prolapse, improve the TSCIS scores, restore SEP waveform, shorten the latency and enhance the amplitude. SEP can reflect the degree of spinal cord injury to a certain extent, and can be used to evaluate the effect of electroacupuncture treatment in these dogs.
ABSTRACT
<p><b>OBJECTIVE</b>To study and compare the effect of neutrophil elastase inhibitors (GW311616A and sivelestat) on the proliferation and apoptosis of U937 cells.</p><p><b>METHODS</b>Inhibitory effects of GW311616A and sivelestat on the proliferation of U937 cells were assayed by MTT assay. The morphologic changes of U937 cells were detected by transmission electron microscope, and apoptosis was observed by AnnexinV-FITC/PI staining. The changes of cell cycle and apoptosis were detected by flow cytometry. The expression of NE in U937 cells was observed by indirect immunofluorescence, the variations of content and activity of NE in U937 cells were measured through ELISA assay and colorimetric method.</p><p><b>RESULTS</b>MTT showed that both NE inhibitors could inhibit the proliferation of U937 cells in a dose dependent manner. The IC50 of GW311616A and sivelestat were 150 and 214 μmol/L respectively. The inhibition effect of GW311616A was significantly higher than of sivelestat (P<0.01). Typical apoptosis morphological changes of U937 cells was observed through electron microscope. AnnexinV-FITC/PI staining showed that U937 cells could be induced to undergo apoptosis by the two inhibitors, the apoptosis ratio of 150μmol/L GW311616A group (13.60%) was significantly higher than that of 150μmol/L sivelestat group (3.69%)(P<0.01). The result of flow cytometry indicated that the apoptosis ratio of 150 μmol/L GW311616A group was 14.61%, U937 cell cycle was mainly blocked in G2/M phase; meanwhile 150 μmol/L sivelestat group as 4.25% with cell cycle in S phase. The fluorescence intensity of GW311616A group obviously decreased than of sivelestat group. And the two inhibitors could reduce the content and activity of NE in U937 cells, but the effect of GW311616A was significantly higher than of sivelestat (P<0.01).</p><p><b>CONCLUSION</b>GW311616A and sivelestat could inhibit the proliferation and cause apoptosis of U937 cells. Furthermore, GW311616A was more effective and harmful to cells than sivelestat.</p>