INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

OBJECTIVE: To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines. METHODS: Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8. RESULTS: ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC CONCLUSION ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.
Apoptosis ; Autophagy ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Hydroxychloroquine/analogs & derivatives* ; Multiple Myeloma

OBJECTIVETo observe effect of prescriptions replenishing vital essence, tonifying Qi and activating blood on expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-IP (IL-1beta) in serum and submaxillary gland of non-obese diabetic (NOD) mice with Sjogren's syndrome.

METHODThirty-two NOD mice were divided into four groups at random: the model group, the traditional Chinese medicine (TCM) group, the hydroxychloroquine group, the TCM and western medicine (WM) group, with 8 mice in each group. Eight Balb/C mice were taken as the normal normal control group. The TCM group was orally administered with 0.4 mL decoction replenishing vital essence, tonifying Qi and activating blood (100 g x kg(-1)) everyday; the hydroxychloroquine group were given 0.4 mL hydroxychloroquine (60 mg x kg(-1)) everyday; the TCM WM group were given 0.4 mL decoction, replenishing vital essence tonifying Qi and activating blood (50 g x kg(-1)) and hydroxychloroquine (60 mg x kg(-1)) everyday. Mice were sacrificed after eight weeks, and their arterial blood and tissues of submaxillary gland were collected. The levels of TNF-alpha, IL-1beta in serum were detected by ELISA. Expressions of TNF-alpha, IL-1beta protein in submaxillary gland were detected by immunohisto-chemistry.

RESULTCompared with other groups, TNF-alpha, IL-1beta in serum and submaxillary gland in the model group were higher (P < 0.05). The normal group showed lower serum TNF-alpha level than other groups (P < 0.05), but without statistical significance compared with the TCM group. IL-1beta in serum in the TCM group and the TCM WM group were lower than that of the hydroxychloroquine group (P < 0.05), but without statistical significance compared with the normal group. TNF-alpha protein expression in the TCM group and the TCM WM group showed no significant difference compared with the normal group, whereas the TCM WM group were notably lower than that of the hydroxychloroquine group (P < 0.05). IL-1beta expression in the TCM WM group showed no significant difference compared with the normal group.

CONCLUSIONThe decoction replenishing vital essence, tonifying Qi and activating blood can decrease the levels of TNF-alpha, IL-1beta in serum and submaxillary gland of NOD mice with Sjogren's syndrome. It may improve pathological damage of submaxillary gland by regulating Th1/Th2 cell factors, in order to achieve the therapeutic effect on SS.

Animals ; Antirheumatic Agents ; pharmacology ; Drug Administration Schedule ; Drug Therapy, Combination ; Enzyme-Linked Immunosorbent Assay ; Hydroxychloroquine ; pharmacology ; Immunohistochemistry ; Interleukin-1beta ; analysis ; blood ; Medicine, Chinese Traditional ; methods ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Random Allocation ; Sjogren's Syndrome ; blood ; drug therapy ; metabolism ; Submandibular Gland ; metabolism ; Tumor Necrosis Factor-alpha ; analysis ; blood