Objective To investigate the effect and possible mechanism of microRNA-26a(miR-26a)on the syn-thesis of extracellular matrix(ECM)induced by high glucose(HG)in renal tubular epithelial cells(RTECs).Methods A model of diabetic kidney disease(DKD)was constructed by inducing RTECs with HG.MiR-26a was overexpressed in HG-induced RTECs,and RT-qPCR and Western blot were used to assess the effects of miR-26a on ECM synthesis and ferroptosis-related markers in HG-treated RTECs.Ferrostatin(Fer-1)was used to inhibit ferroptosis in the DKD model,and its impact on ECM synthesis was evaluated.RT-qPCR and Western blot were performed to measure ferroptosis-related markers,and fluorescence microscopy was used to observe the intensity of reactive oxygen species(ROS).Results Compared with the control group,the expression of miR-26a decreased in HG-treated cells,while the expression levels of ECM synthesis-related indexes fibronectin and collagen Ⅰ in-creased.After overexpressing miR-26a,the HG+miR-26a group showed a significant increase in miR-26a expres-sion and a decrease in fibronectin and collagen Ⅰ expression compared to the HG group.In terms of ferroptosis,the protein and mRNA expression of SLC7A11 and GPX4 significantly decreased,the expression of TFR-1 and AC-SL4 significantly increased,and the fluorescence intensity of ROS was significantly enhanced in the HG group com-pared with the control group.Inhibition of ferroptosis in the HG+Fer-1 group resulted in significant changes in fer-roptosis and ECM synthesis-related indicators expression levels compared to the HG group.Furthermore,re-expres-sion of miR-26a in the HG+miR-26a led to significant changes in ferroptosis-related indicators expression levels and decreased ROS fluorescence intensity compared to the HG group.Conclusions In HG-induced RTECs,miR-26a inhibits the occurrence of ferroptosis,thus reducing ECM synthesis.

Objective:To observe the characteristics of resting-state brain activity in Parkinson disease (PD) patients with peak-dose dyskinesia, and to explore its pathogenesis.Methods:From March 2017 to November 2019, totally 27 PD patients with peak-dose dyskinesia (dyskinetic group), and 29 PD patients without dyskinesia (non-dyskinetic group) treated in the First Affiliated Hospital of Nanjing Medical University and 27 healthy controls from the community were recruited.Resting-state functional magnetic resonance imaging (rs-fMRI) and clinical scale data were collected.SPSS 26.0 software and REST software were used for data analysis.The whole brain amplitude of low-frequency fluctuation (ALFF) values were compared among the three groups.Correlation analysis was performed between ALFF values of the significant brain regions and the scale scores.Finally, receiver operating characteristic (ROC) curve was used to evaluate the efficacy of ALFF values of significant brain regions in identifying three groups of subjects.Results:The peak-dose dyskinetic group showed decreased ALFF in right inferior frontal gyrus(MNI: x=36, y=21, z=30; x=36, y=18, z=30)and increased ALFF in right supplementary motor area (MNI: x=9, y=0, z=69; x=6, y=-3, z=72)(all P<0.05, Alphasim correction) compared with non-dyskinetic group and healthy controls.ALFF value in right inferior frontal gyrus was negatively correlated with unified dyskinesia rating scale (UDysRS) scores ( r=-0.47, P=0.018). The ALFF value of the right inferior frontal gyrus was more effective in identifying peak-dose dyskinetic patients from non-dyskinetic patients and healthy controls, and the area under the curve of right inferior frontal gyrus were 0.881 and 0.787 (both P<0.01), respectively. Conclusion:Abnormal spontaneous brain activity in right inferior frontal gyrus and right supplementary motor area can be the neurobiological basis of peak-dose dyskinesia in PD patients.The severity of peak-dose dyskinesia is associated with abnormal brain activity of right inferior frontal gyrus.The ALFF value of right inferior frontal gyrus is a potential imaging marker for identifying peak-dose dyskinetic patient.

Objective:To investigate the characteristics of regional brain functional centrality(DC)in patients with levodopa-induced dyskinesia(LID)and to explore the pathogenesis of LID.Methods:A total of 33 PD patients with LID(PD-LID), 41 PD patients without LID(PD-nLID)and 37 healthy controls from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study.Differences in DC among the three groups were compared and the correlation between Z-DC values of the brain regions with differences and the scores of the involuntary movement scale(items 1-7)was analyzed.Results:Compared with Controls, PD-LID patients showed increased DC in the right amygdala(extending to the right globus pallidus)(MNI: x=30, y=-3, z=-18, t=4.00, P<0.05 after AlphaSim correction)and in the right postcentral gyrus(MNI: x=57, y=-9, z=39, t=-3.59; MNI: x=42, y=-33, z=57, t=-4.23, P<0.05 after AlphaSim correction)and reduced DC in the right superior parietal lobule(MNI: x=24, y=-51, z=72, t=-3.95, P<0.05 after AlphaSim correction).Compared with the PD-nLID group, the PD-LID group showed increased DC in the right globus pallidus(MNI: x=30, y=-12, z=-3, t=3.09, P<0.05 after AlphaSim correction).DC changes in the right globus pallidus were positively correlated with AIMS score( r=0.482, P=0.004). Conclusions:The enhancement of DC function in the right globus pallidus may be closely related to the onset and severity of LID.

Hydrogen sulfide (H2S) is recognized as one of three gasotransmitters together with nitric oxide (NO) and carbon monoxide (CO). As a signaling molecule, H2S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H2S prodrugs for various reasons. In this review, we summarize different H2S prodrugs, their chemical properties, and some of their potential therapeutic applications.