Case report: Complex paraneoplastic syndromes in thymoma with nephrotic syndrome, cutaneous amyloidosis, myasthenia gravis, and Morvan's syndrome.

Background: Apart from myasthenia gravis (MG), thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes (PNSs). Here, we report on a rare case presenting with four different PNSs, namely, MG, membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome associated with thymoma. Case presentation: A middle-aged man was frequently hospitalized because of nephrotic syndrome (stage I membranous nephropathy), cutaneous amyloidosis, and MG with acetylcholine receptor (AChR) antibody and titin antibody positivity. Chest CT showed a thymic mass in the left anterior mediastinum, and he received intravenous immunoglobulin (IVIG), methylprednisolone pulse therapy, thoracoscopic thymoma resection, and radiotherapy. Postoperative pathological examination revealed a type B2 thymoma. During the perioperative stage, his electrocardiogram (ECG) showed myocardial infarction-like ECG changes; however, his levels of cardiac enzymes and troponin were normal, and he had no symptoms of precardiac discomfort. Six months after thymectomy, his nephrotic syndrome and MG symptoms were relieved; however, he presented with typical manifestations of Morvan's syndrome, including neuromyotonia, severe insomnia, abnormal ECG activity, and antibodies against leucine-rich glioma-inactivated 1 (LGI1) and γ-amino-butyric acid-B receptor (GABABR). His symptoms did not improve after repeated IVIG and steroid therapies. Finally, he received low-dose rituximab, and his symptoms gradually resolved. Conclusion: This case serves to remind us that apart from MG, thymoma is also associated with other autoimmune PNSs such as membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome. Autoimmune PNSs can present concurrently with or after surgical or medical therapy for thymoma. For Morvan's syndrome post-thymectomy with LGI1 antibody positivity, B-cell depletion therapy such as intravenous rituximab is an effective treatment.

[Influence of long non-coding RNA Gm15645 on the podocyte injury in diabetic nephropathy].

OBJECTIVE: To explore the influence of long non-coding (lnc) RNA Gm15645 on the podocyte injury in mice with diabetic nephropathy. METHODS: Male db/db mice (with Type 2 diabetes) with a genetic background of C57BLKs/J and db/m mice (healthy) born in littermates were randomly divided into three groups. db/db group was injected with lncRNAGm15645 shRNA lentivirus with a podocyte-specific marker NPHS2; db/db blank group was injected with saline, and db/db control group was injected withnon-sense lentivirus. The results of PAS staining, pathological changes of renal tissue, relative expression of GSK-3beta, and podocin expression were compared. RESULTS: lncRNAGm15 645 was overexpressed and podocin was down-regulated in the lentivirus overexpressed group. Mesangial cell proliferation, mesangial matrix hyperplasia, thickened basement membrane, widely fused foot process, and podocyte injury were observed by PAS staining. The expression of Gm15645 in the db/db group was significantly lower than that of the db/db blank group and db/db control group (P< 0.05), while the expression of podocin was higher (P< 0.05). Gm15645 was co-stained with podocin in renal tissue, and the target gene was GSK-3beta. CONCLUSION: lncRNAGm15645 may provide an early biomarker for the occurrence of podocyte injury in diabetic nephropathy. The mechanism may be related to the feedback regulation of GSK-3beta gene.

MicroRNA-10a-3p mediates Th17/Treg cell balance and improves renal injury by inhibiting REG3A in lupus nephritis.

BACKGROUND: The therapeutic approaches guided toward microRNAs (miRNAs) have been extensively explored in lupus nephritis (LN), but the precise position of miR-10a-3p posted in disease is not translated thoroughly. Therein, this work pivoting on miR-10a-3p was launched with the involvement of regenerating islet-derived 3 α (REG3A). METHODS: Peripheral blood samples from LN patients and healthy controls (n = 132) were collected. miR-10a-3p and REG3A expression in peripheral blood mononuclear cells were tested. Mice were injected with miR-10a-3p agomir, miR-10a-3p antagomir and/or REG3A low expression vector for presentation of their roles in renal function, T helper cell 17 (Th17)/regulatory cell (Treg) balance, renal pathological damage, JAK2/STAT3 pathway activation and renal injury in LN. The relation between miR-10a-3p and REG3A was tested. RESULTS: MiR-10a-3p was down-regulated while REG3A was up-regulated in LN. Restoring miR-10a-3p or silencing REG3A decreased Th17/Treg ratio in CD4+ T cells, inhibited JAK2/STAT3 pathway activation, ameliorated renal function, improved renal pathological damage and alleviated renal injury in LN. REG3A depletion negated the effects of down-regulated miR-10a-3p on LN. MiR-10a-3p targeted REG3A. CONCLUSION: The work elucidates that miR-10a-3p restoration decreases Th17/Treg ratio and attenuates renal injury in LN via inhibiting REG3A and the activation of JAK2/STAT3 pathway, which renews the therapeutic reference for LN management.

[Effects of piperazine ferulate on TGF-beta1-induced renal interstitial fibroblast activation].

OBJECTIVE: To investigate the effects of piperazine ferulate (PF) on TGF-beta1-induced renal interstitial fibroblast activation, and to explore the mechanism of PF in the prevention of renal tubulointerstitial fibrosis. METHODS: In cultured normal rat renal kidney fibroblast (NRK-49F), the effect of PF on the TGF-beta1-induced cell vitality was observed by MTT. The protein expression levels of a-smooth muscle actin (alpha-SMA), connective tissue growth factor (CTGF) induced by TGF-beta1 were evaluated by immunocytochemistry. The levels of a-SMA, CTGF mRNA expression induced by TGF-beta1, were determined by quantitative real time fluroscent polymerase chain reaction. The levels of collagen type I (Col I) and fibronectin (FN) protein expression were examined by Enzyme Linked Immunosorbent Assay(ELISA). RESULTS: TGF-beta1 may markedly increase the cell vitality, alpha-SMA and CTGF expression, FN and Col I protein expression (P < 0.05). Compared with TGF-beta1-induced group, PF can partly decrease the cell vitality, level of alpha-SMA and CTGF expression and extracellular matrix(ECM) synthesis induced by TGF-beta1 (P < 0.05). CONCLUSION: PF may inhibit TGF-beta1-induced fibrosis in the renal fibroblast to a certain extent.