1.The efficacy and safety of hydroxychloroquine sulfate on pregnancy outcomes in patients with systemic lupus erythematosus
Li ZHOU ; Xiafei XIN ; Yudong CHU
Chinese Journal of Rheumatology 2017;21(1):10-14
Objective To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) on pregnancy outcomes in patients with systemic lupus erythematosus (SLE). Methods One hundred and sixty-six pregnant patients with SLE from Janurary 2010 to December 2015 were studied retrospectively . Fifty-two patients were excluded due to new-onset during pregnancy, active disease or termination of pregnancy as a result of continuous intaking of immunosuppressant. The remaining 114 SLE patients in stable condition before pregnancy were divided into the following two groups: prednisone combined with HCQ and prednisone alone. The effects of HCQ on disease activity and pregnancy outcome were analyzed. Differences between groups were analyzed by chi-square test. Results A total of 90 patients (78.9%) had successful pregnancy. Among 71 patients treated with prednisone combined with HCQ, 60 patients (84.5%) had no disease flare and 62 cases (87.3%) had successful pregnancy. Among 43 patients treated with prednisone alone, 28 patients (65.1%) had no disease flare and 28 cases (65.1%) had successful pregnancy. No abnormality of neither visual field nor fundus was observed among patients treated with HCQ. No congenital abnormalities were found among new born infants. Conclusion HCQ intake during pregnancy in SLE patients can reduce disease flare and improve the pregnancy outcome, indicating that HCQ is safe for SLE patients during pregnancy.
2.Effects of intermedin preconditioning on cyclin expression after renal ischemia-reperfusion in rats
Yudong CHU ; Rongshan LI ; Xi QIAO ; Xiuli SUN
Chinese Journal of Rheumatology 2011;15(8):541-545
Objective To observe the effect of intermedin (IMD) preconditioning on cyclin D1, cyclin E and CDKs expression, and explore its role in.promoting kidney tissue regeneration after renal ischemiareperfusion injury. Methods One hundred and forty-four healthy male Wistar rats were randomly divided into four groups: sham operation (S) group, ischemia-reperfusion injury (IR) group, empty plasmid (EP) group and IMD group. In the IR group, after the right kidney was excised, the aorta abdominalis and left renal artery were bluntly dissected in EP and IMD group, empty plasmid and IMD plasmid were transfected into the left kidney using ultrasound-micro-bubble (SonoVue) mediated system, respectively. One week later, renal IRI model was made by clasping the left renal artery for 45 min. After 1, 2, 3, 4, 7 and 14 day of reperfusion, the kidney in each group was collected to detect the expression of cyclin D1, cyclin E, CDK4 and CDK2 by western blot analysis or enzyme-linked immunosorbent assay (ELISA). Results Compared with S group, the expression of cyclin D1, cyclin E, CDK4 and CDK2 was significantly up-regulated in day 1, 2,3, 4, 7 and 14 in IR group. And the above index increased gradually after reperfusion, and reached the peak at day 7 (F=54.92, 69.60, 61.28, 77.38, P<0.05). While in IMD group, these indexes reached the peak at day 1, then progressively declined, and could not be detected at day 14 (compared with the IR group, F=54.92, 69.60, 61.28, 77.38, P<0.05). Conclusion IMD preconditioning can up-regulate the expression of cyclin D1, cyclin E, CDK2 and CDK4 in the early phase of renal ischemia-reperfusion injury that may accelerate repair of renal tissue, at least by part, by enhancinge cell proliferation.
3. Aspirin intervenes in hyperlipidemia kidney damage by blocking endoplasmic reticulum stress in podocytes
Yudong CHU ; Rongshan LI ; Yuan TIAN ; Pengjie XU ; Jiang LIU ; Xiaohui QIU ; Shizhong BU
Chinese Journal of Nephrology 2020;36(2):139-144
Objective:
To investigate the effects and underlying mechanisms of aspirin on endoplasmic reticulum stress in podocytes induced by hyperlipemia.
Methods:
Cultured podocytes were divided into four groups: control group, aspirin (100 μg/ml) group, oxidized low density lipoprotein (ox-LDL, 100 μg/ml) group, aspirin+ox-LDL group. The expression of protein kinase R-1ike endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor-4 (ATF4) and CAAT/enhancer binding protein homologous protein (CHOP) at 6 h, 12 h, 24 h, 48 h were evaluated by real-time PCR. The related proteins of p-PERK and p-eIF2α at 24 h and ATF4 at 12 h were evaluated by Western blotting, respectively.
Results:
The expressions of PERK, eIF2α peaked at 24 h, while ATF4 and CHOP peaked at 12 h in ox-LDL group and aspirin+ox-LDL group. Compared with control group, the expressions of PERK, eIF2α, ATF4 and CHOP were significantly higher in ox-LDL group at each times (all
4.Mechanisms of Fufang Biejia Ruangan Pills Against Alcoholic Liver Disease via Regulating Liver-brain Dialogue Mediated by HMGB1-BDNF Axis
Yudong LIU ; Xiangying YAN ; Tao LI ; Chu ZHANG ; Bingbing CAI ; Zhaochen MA ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):214-223
ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills (FBRP) in the intervention of alcoholic liver disease (ALD) using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group, model group, and FBRP low-, medium-, and high-dose groups (9.6, 19.2, 38.4 mg·kg-1). Except for the normal group, the remaining groups were given 56° white wine by gavage to establish the acute ALD model, with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group, model group, and FBRP medium-dose group (19.2 mg·kg-1). The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin (HE), Sirius Red, oil red O staining, and enzyme-linked immunosorbent assay (ELISA). Intoxication behaviors of each group were objectively evaluated through sobering-up time, net-catching, and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue, with experimental validation by ELISA, Western blot, and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in liver tissues of mice in the acute and chronic ALD model groups were significantly increased (P<0.05). Compared with the model group, the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased (P<0.05). Compared with the normal group, the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks (P<0.01). Compared with the model group, the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks (P<0.05). Compared with the normal group, the expression of high mobility group protein B1 (HMGB1) protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased (P<0.01). Compared with the model group, the expression of HMGB1 protein in FBRP medium dose group was significantly decreased (P<0.05,P<0.01). Compared with the normal group, the expression of brain-derived neurotrophic factor (BDNF) protein and the release of γ-aminobutyric acid (GABA) in the prefrontal cortex of the model group were significantly decreased (P<0.01). Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased (P<0.05). ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.