Objective To investigate the correlation mechanism between miR-153-3p and Nrf2 expression in human nucleus pulposus cells and intervertebral disc degeneration(IDD).Methods The oxidative damage model of nucleus pulposus cells was duplicated induced by H2O2.MiR-153-3p inhibitor-NC,si-NRF2-NC,miR-153-3p inhibitor,and si-NRF2 were transfected into nucleus pulposus cells according to the grouping require.The transfection efficiency was detected by RT-qPCR and Western blot.The cell viability was determined by the CCK-8 assay,when the intracellular reactive oxygen species(ROS)levels and the ratio of mitochondrial membrane potential decline were measured by flow cytometry,RT-qPCR was used to detect the expression levels of Nrf2,MMP-3,Col II,PINK1,Parkin,P62,and p38 MAPK.And dual luciferase reporter assay was used to measure luciferase activity.Results(1)HNPCs treated with H2O2 showed a decrease in HNPCs cell viability,a reduction in mitochondrial membrane potential,an increase in ROS levels,and a decrease in Col II expression(P<0.05).And the expression of MMP-3,P62,and p38 MAPK increased,while the expression of PINK1 and Parkin decreased.There was no significant change in Nrf2(P>0.05).(2)Inhibition of miR-153-3p expression in nucleus pulposus cells treated with H2O2 led to increased cell viability,elevated mitochondrial membrane potential,reduced ROS levels,and enhanced Col-II expression,accompanied by decreased expression of MMP-3,P62,and p38 MAPK,while simultaneously increasing the expression of PINK1,Parkin,and Nrf2(P<0.05).(3)When miR-153-3p expression was inhibited and Nrf2 expression was silenced in nucleus pulposus cells treated with H2O2,a notable decline in cell viability and mitochondrial membrane potential was observed,along with a marked increase in ROS levels.Additionally,Col-II expression decreased,whereas the expression of MMP-3,P62,and p38 MAPK increased.However,the expression of Nrf2,PINK1,and Parkin decreased(P<0.05).(4)Dual-luciferase assay analysis revealed binding sites and a binding relationship between miR-153-3p and Nrf2,indicating a negative correlation between miR-153-3p and Nrf2(P<0.05).Conclusion Inhibition of miR-153-3p expression can alleviate H2O2 induced degeneration and fibrosis of nucleus pulposus cells,activate autophagy of damaged nucleus pulposus cells,and delay apoptosis of nucleus pulposus cells.This effect is related to the PINK1/Parkin pathway and p38 MAPK inflammatory response pathway regulated by Nrf2.

OBJECTIVE To study the pharmacodynamics and pharmacokinetics of semaglutide(Sem)capsules in type 2 diabetic model rats.METHODS Male SD rats were divided into the normal control group,type 2 diabetic model group and model+Sem capsules(0.839,1.678 and 2.517 mg·kg-1)groups.A type 2 diabetic rat model was induced by high sugar and high fat diet feeding combined with ip given streptozotocin(STZ)injection.Seven days after modeling,the model+Sem capsules group was ig given Sem capsules at the corresponding dose in a fasting state,once a day,for 14 d.Body mass,fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)levels were regularly mea-sured in each group of rats.Plasma from rats in the model+Sem capsules 0.839,1.678 and 2.517 mg·kg-1 groups at different time points was collected at the end of the continuous administration of Sem capsules,and the content of Sem in the plasma of rats was determined by liquid chromatography-tandem mass spectrometry.Concentration-time curves were plotted,and the main pharmacokinetic parameters were fitted by the WinNonlin non-atrial model method.RESULTS Compared with the model group,the body mass of rats in model+Sem capsules dosing groups decreased significantly after 7 and 14 d of Sem capsules intervention(P<0.05,P<0.01),so did FBG(P<0.01)and the HbA1c level(P<0.01).Meanwhile,FBG and HbA1c levels of rats in model+Sem capsules 1.678 and 2.517 mg·kg-1 groups were not significantly different from those of the normal control group after 14 d of Sem capsules intervention,suggesting that FBG and HbA1c levels were basically restored to normal.Phar-macokinetic results showed that the elimination half-life(t1/2)of Sem in plasma after ig administration of Sem capsules 0.839,1.678,and 2.517 mg·kg-1 for 14 d in rats was 7.40±1.34,7.48±0.33 and(8.23±0.90)h,respectively,the peak concentration(Cmax)was 18±9,81±23 and(256±53)μg·L-1,time to peak(Tmax)was 0.06±0.13,1.56±0.88,(1.50±1.00)h,respectively,the area under the curve(AUC0-t)was 158±76 μg·h·L-1,858±310 and(3795±1539)μg·h·L-1,and the accumulation index was 1.12±0.05,1.12±0.01 and 1.15±0.04,respectively.CONCLUSION Sem capsules ig administrated can effectively reduce body mass,FBG and HbA1c levels in type 2 diabetic model rats,and lead to glucose reduction and by mass loss.After 14 d of continuous administration of Sem capsules,there is no accu-mulation of semaglutide in rats in the dose range of 0.839-2.517 mg·kg-1,and the exposure increases with the dose.

BACKGROUNDThe prognostic values of interim and post-therapy fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) scanning have been confirmed in several subtypes of lymphoma. However, its prognostic value in Burkitt's lymphoma has not been clearly defined. The aim of the present study was to assess the prognostic value of PET/CT scanning during different treatment processes of Burkitt's lymphoma.

METHODSA total of 29 adult patients with newly diagnosed Burkitt's lymphoma were retrospectively involved in this study; of them, 23 patients underwent baseline PET/CT, 15 patients underwent mid-therapy PET/CT after 1-4 cycles of chemotherapy, and 17 patients underwent post-therapy PET/CT after all planned first-line chemotherapy cycles. Mid-therapy and post-therapy PET/CT results (positive vs. negative) were visually interpreted according to the criteria of the International Harmonization Project. The reduction in the maximum standardizes uptake values (∆SUVmax) of 25%, 50%, and 75% were regarded as cutoff points. Overall survival (OS) and progression-free survival (PFS) were regarded as the major endpoints.

RESULTSThe median OS and PFS were 27.6 months (range 6.5-78.3 months) and 27.2 months (range 3.0-78.3 months), respectively. The median SUVmax of the baseline PET/CT was 18.3 (range 1.6-35.9), whereas the median SUVmax of the mid-therapy and post-therapy PET/CT decreased to 4.0 (range 0-17.6) and 3.0 (range 0-14.5), respectively. The patients' Eastern Cooperative Oncology Group (ECOG) scores (<2 vs. ≥2) were significantly associated with the baseline PET/CT SUVmax. The mid-therapy and post-therapy PET/CT results (positive vs. negative) showed no significant association with OS or PFS. The optimal cutoff ∆SUVmax from the baseline to the post-therapy PET/CT that could predict a change in OS in patients with Burkitt's lymphoma was 50% (P = 0.019).

CONCLUSIONS(18)F-FDG uptake was intense in Burkitt's lymphoma, and there was a significant reduction in SUVmax during the interim and post-therapy PET/CT procedures. A ∆SUVmax of greater than 50% was a favorable cutoff point to predict the OS of Burkitt's lymphoma patients.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Burkitt Lymphoma ; diagnostic imaging ; drug therapy ; Female ; Fluorodeoxyglucose F18 ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; methods ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Treatment Outcome