Glyoxylic Acid Monohydrate-Promoted Formation of the C-SO2 Bond Starting from Maleimides/Quinones and Sodium Sulfinates.

By using glyoxylic acid monohydrate as a promoter, a wide range of substances containing a C-SO2 bond could be obtained from N-substituted maleimides or quinones and sodium sulfinates. The protocol features mild reaction conditions, short reaction time, and good atomic economics, which provides an alternative protocol for the α-sulfonylation of α,ß-unsaturated ketones.

Calcineurin inhibitors or cyclophosphamide in the treatment of membranous nephropathy superimposed with FSGS lesions: a retrospective study from China.

BACKGROUND: Cyclophosphamide (CTX) and calcineurin inhibitors (CNIs) based regimens are recommended as immunosuppressive therapies for patients with idiopathic membranous nephropathy (IMN). Focal and segmental glomerular sclerosis (FSGS) lesions, which are common in membranous nephropathy (MN), are poor predictors of outcome. This study compared the differences of prognosis between two regimens in patients with IMN combined with FSGS lesions. METHODS: This retrospective study enrolled 108 patients with biopsy-proven IMN, accompanied with FSGS lesions, nephrotic syndrome and an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2 who were treated with CTX or CNIs. We used propensity score matching (PSM) for balancing the confounding variables. RESULTS: During follow-up, 10 patients (10/55 [18.2%]; nine males) in the CNIs group showed a 50% decline in eGFR; eight had a not otherwise specified variant. Patients initially treated with CNIs had a significantly higher risk of progression to the primary outcome and a lower probability of complete or total remission. The relapse rate was higher in patients who initially received CNIs- than in those who received CTX-based treatment. Before PSM, age and 24-h urine protein level differed significantly between the groups. The PSM model included data from 72 patients. Worse outcomes were also noted among patients who initially received CNIs than those who received CTX-based treatments after matching. CONCLUSIONS: Patients with MN combined with FSGS lesions have a higher risk of renal functional decline and a higher rate of relapse after CNIs than after CTX therapy.

RP1, a RAGE antagonist peptide, can improve memory impairment and reduce Aß plaque load in the APP/PS1 mouse model of Alzheimer's disease.

Amyloid-ß (Aß) accumulation is a pathological hallmark of Alzheimer's disease (AD). The receptor for advanced glycation end products (RAGE) is involved in the production and accumulation of Aß. RP1, a peptide antagonist of RAGE, was screened by phage display technology in our previous studies, and its neuroprotective effects on an AD cell model have been confirmed. However, its efficacy in vivo remains unclear. Here, the intranasal delivery of RP1 to APPSwe/PS1dE9 (APP/PS1) mice significantly improved memory impairment and relieved the Aß burden by decreasing the expression of amyloid precursor protein and ß-secretase. RNA-sequencing (RNA-seq) was utilized to identify differentially expressed genes (DEGs) in APP/PS1 mice after RP1 administration. Several DEGs in RAGE downstream signalling pathways were downregulated. Some transcription factors (such as Fos) and the pathways enriched in the remarkable modules may also be related to the efficacy of RP1. In conclusion, RP1 significantly improves the AD symptoms of APP/PS1 mice, and the RNA-seq results provide new ideas for elucidating the possible mechanisms of RP1 treatment.

Norcantharidin Enhances High Concentrations of Fetal Bovine Serum-Induced Apoptosis in Human Mesangial Cells by Regulating the Mitogen-Activated Protein Kinase Signaling Pathway.

AIM: This study aimed to investigate the effect of norcantharidin (NCTD) on human mesangial cells (HMCs) apoptosis in vitro and further examine its molecular mechanism. METHODS: HMCs were divided into 5 groups: control group, 25% fetal bovine serum (FBS)-treated group, and NCTD groups (NCTD [2.5, 5 and 10 µg/mL] + 25% FBS, respectively). Cell proliferation was determined by MTT assay, while apoptosis was evaluated by Hoechest 33258 staining, the level of cytochrome c, immunohistochemistry, and apoptotic-related proteins/gene expression. RESULTS: Cell viability was inhibited in NCTD-treated HMCs in a dose-dependent manner. The number of apoptotic cells and the content of cytochrome c were significantly increased by NCTD treatment but that of mitochondrial membrane was decreased. Moreover, the expression of bcl-2 and caspase-3 was prompted by NCTD, but the expression of bax, MMP-2, and MMP-9 in 25% FBS-treated HMCs was inhibited. In addition, NCTD markedly unregulated the expression of apoptosis-related gene/protein, including p-Erk1/2, phosphorylated-Jun N-terminal kinase (JNK), p-p38, and p53. CONCLUSION: NCTD enhances 25% FBS-treated HMC apoptosis in vitro, and this effect may be attributed to the modulation of the ERK, JNK, and p38 mitogen-activated protein kinase signaling pathways.

Focal segmental glomerulosclerosis, excluding atypical lesion, is a predictor of renal outcome in patients with membranous nephropathy: a retrospective analysis of 716 cases.

BACKGROUND: Focal segmental lesions (FSLs) are not uncommon in idiopathic membranous nephropathy (IMN). The reported percentage of IMN patients with focal segmental glomerulosclerosis (FSGS) lesions varies widely between studies. The objective of this study was to differentiate atypical FSL (aFSL) from typical FSGS in IMN and to analyse the clinicopathological predictors of primary outcome of IMN patients. METHODS: A total of 716 patients with biopsy-proven IMN between January 1, 2007 and December 31, 2017 were enrolled in the study. An atypical focal segmental lesion was defined as pure synechia, segmental hyperplasia of podocytes or thickening of the GBM accompanied by proliferation of the mesangial matrix, and absence of typical FSGS. The patients were divided into three groups: patients without FSL (FSL-), patients with typical FSGS (FSGS+), and patients with aFSL (aFSL+).The primary outcome was a 50% decline in the initial estimated glomerular filtration rate or end-stage renal disease (ESRD) incidence. Secondary outcomes included all-cause death and ESRD. RESULTS: FSGS was present in 174 patients, while aFSL was noted in 161 patients. Systolic blood pressure was higher in both aFSL+ group and FSGS+ groups compared with the FSL- group. IMN patients without FSL and with aFSL had lower serum creatinine levels than IMN patients with FSGS. Both the FSGS+ and aFSL+ groups had higher levels of proteinuria and lower albumin levels than the FSL- group. Renal tissue lesions, including tubulointerstitial fibrosis, glomerular obsolescence, and vascular sclerosis were significantly more severe in the FSGS+ group. Cox multivariate analysis showed that older age ≥ 60 years, eGFR< 60 ml/(min·1.73m2), tubulointerstitial fibrosis area ≥ 15% and FSGS at biopsy were independent risk factors for the primary outcome. CONCLUSIONS: No significant difference in outcome was found between the FSL- and aFSL+ groups, although the patients with aFSL had lower levels of serum albumin and eGFR, higher level of urinary protein, more severe renal lesions with proliferation of the mesangial area,tubulointerstitial fibrosis and vascular sclerosis. FSGS, excluding atypical lesions, was an independent predictor of the primary outcome.