Refractory autoimmune hemolytic anemia in a patient with systemic lupus erythematosus and ulcerative colitis: A case report.

BACKGROUND: Ulcerative colitis (UC) and systemic lupus erythematosus (SLE) are both systemic immunoreactive diseases, and their pathogenesis depends on the interaction between genes and environmental factors. There are no reports of UC with SLE in China, but six cases of SLE with UC have been reported in China. The combination of these two diseases has distinct effects on the pathogenesis of both diseases. CASE SUMMARY: A female patient (30 years old) came to our hospital due to dull umbilical pain, diarrhea and mucous bloody stool in August 2018 and was diagnosed with UC. The symptoms were relieved after oral administration of mesalazine (1 g po tid) or folic acid (5 mg po qd), and the patient were fed a control diet. On June 24, 2019, the patient was admitted for treatment due to anemia and tinnitus. During hospitalization, the patient had repeated low-grade fever and a progressively decreased Hb level. Blood tests revealed positive antinuclear antibody test, positive anti-dsDNA antibody, 0.24 g/L C3 (0.9-1.8 g/L), 0.04 g/L C4 (0.1-0.4 g/L), 32.37 g/L immunoglobulin (8-17 g/L), and 31568.1 mg/24 h total 24-h urine protein (0-150 mg/24 h). The patient was diagnosed with SLE involving the joints, kidneys and blood system. Previously reported cases of SLE were retrieved from PubMed to characterize clinicopathological features and identify prognostic factors for SLE. CONCLUSION: The patient was discharged in remission after a series of treatments, such as intravenous methylprednisolone sodium succinate, intravenous human immunoglobulin, cyclophosphamide injection, and plasma exchange. After discharge, the patient took oral prednisone acetate tablets, cyclosporine capsules, hydroxychloroquine sulfate tablets and other treatments for symptoms and was followed up regularly for 1 month, after which the patient's condition continued to improve and stabilize.

Effects of Changyu Daotan Decoction on Depression via Restoration of Mice Hippocampus and Alteration of Expression of Relevant Neurotrophic Factors.

Depression, a sort of common psychological disorder, is a serious hazard to people's health and social progress. Conventional clinical means for this disorder nowadays are mostly chemical medicine treatments accompanied by psychological counseling. Chinese application of using TCM to treat mental diseases like depression could be traced from hundreds of years ago, in comparison to the long-term depression course and the chemical medicine administration demerits like side effects and resistance, traditional Chinese medicines are milder, more lasting, stable and are the optimal choice for perennial depression treatment. This study was committed to making a comprehensive investigation of Changyu Daotan Decoction's efficacy in the depression mice model, and it turned out that the Changyu Daotan Decoction was capable of restoring the hippocampus of the depression mice and altering the expressions of neurotrophic factors (the expressions of ß-Catenin, cyclin D1 and in GSK-3ß BDNF, GFAP, NGF, and Wnt signaling pathways). Results of metabonomics analysis showed that the contents of GABA, His, Tyr, Trp, PA, and 5-HIAA in the mice of the Changyu Daotan Decoction group were restored after administration and showed a conspicuous relevance with the metabolic.

Local anesthetic levobupivacaine inhibits stemness of osteosarcoma cells by epigenetically repressing MAFB though reducing KAT5 expression.

Osteosarcoma is the most prevalent bone cancer and accounts for over half of sarcomas. In this study, we identified that the treatment of levobupivacaine suppressed proliferation of osteosarcoma cells in vitro. The tumor xenograft analysis showed that levobupivacaine significantly repressed the osteosarcoma cell growth in the nude mice. The treatment of levobupivacaine improved the apoptosis rate and attenuated invasion and migration abilities of osteosarcoma cells. The sphere formation capabilities of osteosarcoma cells were repressed by levobupivacaine. The protein levels of Sox-2, Oct3/4, and Nanog were inhibited by the treatment of levobupivacaine in osteosarcoma cells. Regarding mechanism, we identified that levobupivacaine inhibited MAFB and KAT5 expression in osteosarcoma cells. We observed that lysine acetyltransferase 5 could enriched in the promoter region of MAF BZIP transcription factor B, while levobupivacaine treatment could repressed the enrichment. The suppression of KAT5 by siRNA repressed the enrichment of histone H3 acetylation at lysine 27 and RNA polymerase II on promoter of MAFB. The expression of MAFB was decreased by KAT5 knockdown in osteosarcoma cells. The expression of MAFB was repressed by levobupivacaine, while the overexpression of KAT5 could reverse the repression of MAFB. KAT5 contributes to the cell proliferation and stemness of osteosarcoma cells. The overexpression of KAT5 or MAFB could reverse levobupivacaine-attenuated cell proliferation and stemness of osteosarcoma cells. Therefore, we concluded that local anesthetic levobupivacaine inhibited stemness of osteosarcoma cells by epigenetically repressing MAFB though reducing KAT5 expression. Levobupivacaine may act as a potential therapeutic candidate for osteosarcoma by targeting cancer stem cells.

Long Noncoding RNA GAS5 Inhibits Osteogenic Differentiation through MicroRNA 382-3p/TAF1 Signaling.

Long noncoding RNAs (lncRNAs) have been confirmed as important regulators during osteogenic differentiation. Previous research has disclosed that growth arrest-specific transcript 5 (GAS5) can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), but the underlying regulatory mechanism of GAS5 during the osteogenic differentiation of hBMSCs is unclear. Osteogenic differentiation was induced in hBMSCs by using osteogenic medium (OM). Gene expression was assessed by quantitative real-time PCR (RT-qPCR) or Western blot assays as needed. Alkaline phosphatase (ALP) activity, ALP staining, and alizarin red S (ARS) staining assays were performed to evaluate the impact of GAS5, microRNA 382-3p (miR-382-3p), and TATA box binding protein-associated factor 1 (TAF1) on osteogenic differentiation in vitro. The interaction among GAS5, miR-382-3p, and TAF1 was determined by RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and luciferase reporter assays. Expression of GAS5 (transcript variant 2) was downregulated during the osteogenic differentiation of hBMSCs, and its overexpression retarded the osteogenic differentiation of hBMSCs. GAS5 inhibited miR-382-3p by targeting RNA-directed microRNA degradation (TDMD). miR-382-3p downregulation partially offset the promoted osteogenic differentiation of hBMSCs upon GAS5 silencing. TAF1 negatively modulated osteogenic differentiation, and it activated GAS5 transcription so as to form a positive GAS5-miR-382-3p-TAF1 feedback loop in hBMSCs. This research was the first to reveal that the GAS5-miR-382-3p-TAF1 feedback loop inhibited the osteogenic differentiation of hBMSCs, which provided new clues for exploring the mechanism of osteogenic differentiation and disclosed the potential of GAS5 as a promising target during osteogenic differentiation.

1,4-Dihydropyridine (DHP) suppresses against oxidative stress in nucleus pulposus via activating sirtuin-1.

Intervertebral disc degeneration (IVDD) is a major cause of many spinal diseases characterized mainly by nucleus pulposus degradation. 1,4-dihydropyridine (DHP), a new activator of sirtuin-1 (sirt1), has been reported to have anti-oxidative effects. The aim of this study is to investigate the effect of DHP on nucleus pulposus (NP) cells in vitro. NP cells were pretreated with IL-1ß to establish a degenerated model, and then treated with DHP alone or DHP combined with selisistat (an inhibitor of sirt1). ROS level was analyzed by flow cytometry. Production of IL-6 and TNF-α were evaluated by the enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and sirt1. We found that DHP inhibited IL-1ß-induced upregulation of ROS, TNF-α, IL-6, MMP-3, ADAMTS-5. Besides, DHP remarkably increased the sirt1 and anti-oxidative protein SOD-1 level. Furthermore, DHP significantly protected the IL-1ß-induced degradation of collagen-II and aggrecan. However, the inhibitory effect of DHP was obvious abolished by selisistat, suggesting that DHP exerts these effects in NP cells through activating sirt1. Taken together, we found that DHP inhibited the ROS, inflammatory response and ECM degradation through activating Sirt1 in human NP cells.