ABSTRACT
AIM: To investigate the role and possible mechanism of gastrodin combined with dexamethasone in myocardial cell injury induced by oxygen-glucose deprivation. METHODS: Oxygen-glucose deprivation (OGD) model was established. The cells were divided into 5 groups: normal control group, OGD group, DEX group, GAS group and DEX+GAS group. The activity of myocardial cells was detected by CCK-8 test in each group. The activity of LDH was detected by colorimetry in each group. The apoptosis of myocardial cells was detected by TUNEL method in each group. The ELISA assay was used to detect the inflammatory factors in culture medium of myocardial cells in each group. Western blot was used to detect the expression of Notch1, Bax, Bcl-2 and Beclin1 in myocardial cells in each group.RESULTS: The results showed that GAS combined with DEX could significantly increase the activity of myocardial cells and decrease the apoptosis, reduce production of TNF-α, IL-6, IL-1β and promote production of IL-10, decrease the release of LDH significantly of myocardial cells induced by OGD. The results of Western blot showed that GAS combined with DEX increased the expression of Notch1, Bcl-2 and autophagy-related gene Beclin1, but decreased the expression of Bax of myocardial cells induced by OGD. CONCLUSION: The combination of GAS and DEX may promote autophagy and increase cell activity, inhibit apoptosis and inflammatory reaction by activating Notch signaling pathway, thereby reducing OGD-induced myocardial cells damage.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the changes of relative telomere length (RTL) of peripheral blood (PB) CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺T lymphocytes, CD19⁺B lymphocytes and bone marrow (BM) CD34⁺ cells and its association with disease severity in untreated patients with immuno-related pancytopenia (IRP).</p><p><b>METHODS</b>The PB CD3⁺ , CD3⁺ CD4⁺ , CD3⁺ CD8⁺ T lymphocytes, CD19⁺ B lymphocytes, and BM CD34⁺ cells were purified by magnetic activated cell sorting (MACS), and RTL were measured with flow-fluorescence in situ hybridization (FLOW-FISH).</p><p><b>RESULTS</b>The RTL of CD3⁺, CD3⁺CD4⁺ , and CD3⁺CD8⁺T lymphocytes in untreated IRP patients were (27.754 ± 16.323)%, (7.526 ± 3.745)% and (25.854 ± 14.789)%, respectivly, which were significantly shorter than those in healthy-controls (54.555 ± 19.782)%, (12.096 ± 2.805)%, and (38.367 ± 4.626)% (P<0.05). The RTL of CD19⁺ lymphocytes in untreated IRP patients was (22.136 ± 16.142)%, which was significantly shorter than that in healthy controls (42.846 ± 16.353)% (P<0.01). There was no significant difference of BM CD34⁺ cells RTL between the untreated IRP patients (22.528 ± 21.601)% and the healthy controls (23.936 ± 19.822)% (P>0.05). There were significantly positive correlations between the RTL of B lymphocytes and the count of white blood cell (r=0.706, P=0.015). There were negative correlations between RTL of B lymphocytes and the clinical symptoms (r=-0.613, P=0.045) and positive correlations with therapeutic effect (r=0.775, P=0.005).</p><p><b>CONCLUSION</b>The shorter RTL of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD19⁺ lymphocytes, and the normal RTL of BM CD34⁺ cells in untreated IRP patients were identified, which might imply that IRP is a type of acquired autoimmune diseases.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , B-Lymphocyte Subsets , Allergy and Immunology , Lymphocytes , Pancytopenia , Allergy and Immunology , Pathology , T-Lymphocyte Subsets , Allergy and Immunology , TelomereABSTRACT
<p><b>OBJECTIVE</b>To detect memory B lymphocyte (Bm) in peripheral blood (PB) of immune-related pancytopenia (IRP).</p><p><b>METHODS</b>86 patients with IRP and 11 health volunteers were enrolled in this study. Bm (CD5⁺ CD19⁺ CD27⁺) and bone marrow mononucleated cell antibodies (BMMNC-Ab) were determined via fluorescence-activated cell sorting, and clinical outcomes of these patients were analyzed.</p><p><b>RESULTS</b>(1)43 initial patients achieved obvious remission in all 52 initial cases after conventional immunosuppression therapy. 16 relapsed patients with IRP received Rituximab (RTX) and 14 cases achieved obvious remission, among which 7 cases were refractory to conventional immunosuppression therapy, 5 cases exhibited obvious remission, and 2 cases did not respond. Other 18 relapsed cases received conventional immunosuppression therapy and 13 cases achieved obvious remission. (1)The level of Bm in PB in 52 initial patients with IRP was(1.81 ± 0.97)%, and no significant difference was observed between the initial patients and health volunteers (1.75 ± 0.55)% (P>0.05). The level of Bm in PB in 34 relapsed patients with IRP was obviously higher than that in the initial IRP patients and health volunteers (P<0.05). Significant difference was observed in the level of Bm in PB in 16 relapsed IRP patients between pre-therapy and post-therapy with RTX (P<0.05). No statistical difference was found between the remission and no-response groups in relapsed patients treated with RTX. RTX regimen produced more effective outcome than conventional immunosuppression therapy, which better eliminated Bm than the latter (P<0.05). Initial patients with IRP who relapsed within a two-year follow-up period had a lower level of Bm in PB compared with un-relapsed patients (P<0.05). Majority of BMMNC- Ab antibodies in relapsed patients were IgG (82.4%) and IgM (69.2%) autoantibodies in patients with initial IRP.</p><p><b>CONCLUSION</b>The level of Bm in PB was associated with relapsed patients with IRP. Bm did not respond to conventional immunosuppression therapy,but responded to RTX.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Monoclonal, Murine-Derived , Therapeutic Uses , B-Lymphocyte Subsets , Allergy and Immunology , Immunologic Memory , Immunosuppression Therapy , Pancytopenia , Allergy and Immunology , Therapeutics , Recurrence , Rituximab , Treatment OutcomeABSTRACT
Aim: To search for novel α_1-adrenoceptor(α_1-AR) antagonists. Methods: On the basis of hybridization principle with silodosin as the lead compound, twelve 5-[2-[4-[ ( substituted phenoxy) alkyl] piperazin-1-yl] propyl] indoline compounds were designed and synthesized by maintaining indoline while incorporating the 1-[(substituted phenoxy) alkyl] piperazine group. Results: The structures of synthesized target compounds were confirmed by the elemental analysis, IR, ESI-MS and ~1H NMR. Preliminary pharmacological test showed that pA_2 values of six target compounds were greater than 7. 50, which suggested that the compounds possessed considerable α_1-AR antagonic activity. Conclusion: 5-[2-[4-[ ( substituted phenoxy) alkyl] piperazin-1-yl] propyl] indoline compounds is potentially a new candidate for α_1-AR antagonist.