ABSTRACT
OBJECTIVE: To detect the relationship between CTGF in the bone marrow of MM patients and osteolytic lesion of myeloma, moreover, to investigate the clinical significance of CTGF in MM. METHODS: Fifity-four MM patients treated in our hospital from March 2019 to April 2020 were enrolled, and 28 healthy volunteers were selected as the control group. The plasma in bone marrow of the patients was collected, and the ELISA was used to detect the level of CTGF in bone marrow plasma and the relationship between its and clinical characteristics were statistically analyzed. RESULTS: The CTGF level of MM patients was significantly higher than those in the healthy control group (P<0.001); the CTGF level in male patients was higher than that in female patients (P=0.007); the CTGF level in MM patients with osteolytic lesions was significantly higher than patients without osteolytic lesions and controls (P=0.007, P=0.001). The CTGF level in MM patients was positively correlated with the number of bone lesions (P<0.001, r=0.52). CTGF levels in patients with ≥3 bone lesions were significantly higher than those with <3 bone lesions and without bone lesions (P=0.014, P=0.002). ROC curve result showed that CTGF expression level shows a significant diagnostic value for MM bone disease (P<0.001). CONCLUSION: The abnormally high expression of CTGF level in MM patients is related to the degree of myelomas osteolytic lesions and can reflect the progress of MM.
Subject(s)
Multiple Myeloma , Osteolysis , Bone Marrow , Connective Tissue Growth Factor , Female , Humans , Male , ROC CurveABSTRACT
Alzheimer's disease is pathologically defined by accumulation of extracellular amyloid-ß (Aß). Approximately 25 mutations in ß-amyloid precursor protein (APP) are pathogenic and cause autosomal dominant Alzheimer's disease. To date, the mechanism underlying the effect of APP mutation on Aß generation is unclear. Therefore, investigating the mechanism of APP mutation on Alzheimer's disease may help understanding of disease pathogenesis. Thus, APP mutations (A673T, A673V, E682K, E693G, and E693Q) were transiently co-transfected into human embryonic kidney cells. Western blot assay was used to detect expression levels of APP, beta-secretase 1, and presenilin 1 in cells. Enzyme-linked immunosorbent assay was performed to determine Aß1-40 and Aß1-42 levels. Liquid chromatography-tandem mass chromatography was used to examine VVIAT, FLF, ITL, VIV, IAT, VIT, TVI, and VVIA peptide levels. Immunofluorescence staining was performed to measure APP and early endosome antigen 1 immunoreactivity. Our results show that the protective A673T mutation decreases Aß42/Aß40 rate by downregulating IAT and upregulating VVIA levels. Pathogenic A673V, E682K, and E693Q mutations promote Aß42/Aß40 rate by increasing levels of CTF99, Aß42, Aß40, and IAT, and decreasing VVIA levels. Pathogenic E693G mutation shows no significant change in Aß42/Aß40 ratio because of inhibition of γ-secretase activity. APP mutations can change location from the cell surface to early endosomes. Our findings confirm that certain APP mutations accelerate Aß generation by affecting the long Aß cleavage pathway and increasing Aß42/40 rate, thereby resulting in Alzheimer's disease.
ABSTRACT
Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3',4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain.
