The lysine acetyltransferase 6A (KAT6A, MOZ, MYST3) is a member of the MYST family of protein acetyltransferases, which are essential for different biological processes such as craniofacial, embryonic, stem cell development, and hematopoiesis. KAT6A is an oncogene in human acute myeloid leukemia (AML), and KAT6A overexpression in AML is associated with metastases and poor prognoses. Furthermore, KAT6A mutations play an important role in cancer formation and progression and result in therapeutic resistance in both hematopoietic malignancies and solid tumors.
View Article and Find Full Text PDFNeuronal damage in the hippocampus induced by high glucose has been shown to promote the onset and development of cognitive impairment in diabetes, but the underlying molecular mechanism remains unclear. Guided by single-cell RNA sequencing, we here report that high glucose increases O-GlcNAcylation of Bmal1 in hippocampal neurons. This glycosylation promotes the binding of Clock to Bmal1, resulting in the expression of transcription factor Bhlhe41 and its target Dnajb4.
View Article and Find Full Text PDFCombination therapy proven to be an effective therapeutic approach for estrogen receptor (ER)-positive breast cancer. Currently, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are combined with aromatase inhibitors (AIs) or selective estrogen receptor degraders (SERDs) as first-line therapy for advanced ER-positive breast cancer. Herein, a new family of quinoline scaffold SERDs was synthesized and evaluated in MCF-7 cells.
View Article and Find Full Text PDFHigh glucose has been proved to impair cognitive function in type 2 diabetes, but the underlying mechanisms remain elusive. Here, we found that high glucose increased transcription factors' SP1 O-GlcNAcylation in regulatory T (Treg) cells. Glycosylated SP1 further enhanced HDAC2 recruitment and histone deacetylation on Na/Ca/Li exchanger (NCLX) promoter, which downregulated NCLX expression and led to mitochondrial calcium overload and oxidative damage, thereby promoting Treg cell dysfunction, M1 microglia polarization, and diabetes-associated cognitive impairment.
View Article and Find Full Text PDFDPP4 has been shown to induce diabetes-associated mitochondrial dysfunction and cognitive impairment through its non-canonical function. Here, we report that enhanced DPP4 expression in diabetes contributes to IP3R2-mediated mitochondria-associated ER membrane (MAM) formation, mitochondria calcium overload, and cognitive impairment, and its knockdown showed opposite effects. Mechanistically, DPP4 binds to PAR2 in hippocampal neurons and activates ERK1/2/CEBPB signaling, which upregulates ERp29 expression and promotes its binding to IP3R2, thereby inhibiting IP3R2 degradation and promoting MAM formation, mitochondria calcium overload, and cognitive impairment.
View Article and Find Full Text PDFBackground: Impairment of regulatory T (Treg) cells function is implicated in the pathogenesis of immune imbalance-mediated cognitive impairment. A complete understanding of whether and how this imbalance affect cognitive function in type 2 diabetes is lacking, and the driver affecting this imbalance remains unknown.
Methods: We examined the impact of enzymatic and non-enzymatic function of DPP4 on Treg cell impairment, microglia polarization and diabetes-associated cognitive defects and identified its underlying mechanism in type 2 diabetic patients with cognitive impairment and in db/db mice.
Coxsackievirus B group 5 (CVB5) represents one of the major pathogens that cause diseases such as hand, foot and mouth disease (HFMD) and aseptic meningitis et al. Currently, no specific drugs and vaccines are available, and a safe and effective CVB5 vaccine is of great value for control of the diseases. In this study, CVB5 P1 precursor and 3CD protease were co-expressed in Sf9 cells by using a baculovirus expression system.
View Article and Find Full Text PDFDipeptidyl peptidase-4 (DPP4) has been proven to exert its functions by both enzymatic and nonenzymatic pathways. The nonenzymatic function of DPP4 in diabetes-associated cognitive impairment remains unexplored. We determined DPP4 protein concentrations or its enzymatic activity in type 2 diabetic patients and db/db mice and tested the impact of the non-enzymatic function of DPP4 on mitochondrial dysfunction and cognitive impairment both in vivo and in vitro.
View Article and Find Full Text PDFObjective: The objective of this study was to assess the association of plasma dipeptidyl peptidase-4 (DPP4) activity, brain-derived neurotrophic factor (BDNF), and the DPP4/BDNF ratio (DBR) with moderate to severe depressive symptoms in patients with type 2 diabetes mellitus. Increased DPP4 activity and decreased BDNF in peripheral circulation have been implicated in the pathophysiology of depression.
Methods: We performed a cross-sectional study using data from 1535 patients with type 2 diabetes mellitus.
Attenuation of brain-derived neurotrophic factor (BDNF) availability and increased dipeptidyl peptidase-4 (DPP4) activity have both been reported to link to the pathogenesis of depression. The aim of this study was to test the correlation between depressive symptoms and plasma DPP4 activity to BDNF ratio (DBR). We evaluated DPP4 activity, BDNF, oxidative stress parameters and inflammatory markers and calculated DBR in a cross-sectional sample of 1640 non-diabetic participants.
View Article and Find Full Text PDFSince decreased brain-derived neurotrophic factor (BDNF) and increased dipeptidyl peptidase-4 (DPP4) activity have both been implicated in the pathogenesis of mild cognitive impairment (MCI), the aim of our study was to evaluate the association of MCI with plasma DPP4 activity to BDNF ratio (DBR) in an elderly population with normal glucose tolerance. We cross-sectionally measured C-reactive protein, interleukin-6, nitrotyrosine, 8-iso-PGF2a, DPP4 activity BDNF and calculated the DBR in a total of 1,066 elderly participants in China. MCI was determined by the Montreal Cognitive Assessment and finally confirmed by neurologists.
View Article and Find Full Text PDFUnlabelled: Hyperglycemia, insulin resistance and hypertriglyceridesmia are risk factors for albuminuria in type 2 diabetes. Angiopoietin-like Protein 8(ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the relationship between ANGPTL8 and albuminuria in type 2 diabetes.
View Article and Find Full Text PDFBackground: Hypertriglyceridemia, insulin resistance and hyperglycemia are risk factors for atherosclerosis in type 2 diabetes. Angiopoietin-like protein 8 (ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the correlations between serum levels of ANGPTL8 and subclinical atherosclerosis in type 2 diabetes.
View Article and Find Full Text PDFAim: To examine whether the baseline 25-hydroxyvitamin D [25(OH)D] level was predictive of the onset of prediabetes or type 2 diabetes (T2DM) in the Chinese population.
Methods: This was a 4-year follow-up study that was conducted in the Chengdu region of China as part of the China National Diabetes and Metabolic Disorders Study. The study included 490 participants that were free of prediabetes and type 2 diabetes mellitus (T2DM) at baseline and had complete data by follow-up examinations.
Objective: Increased dipeptidyl peptidase-4 (DPP4) activity and reduced brain-derived neurotrophic factor (BDNF) in peripheral circulation are both associated with a high risk of mild cognitive impairment (MCI) in the elderly. Hence, we aimed to investigate the association between plasma DPP4 activity to BDNF ratio (DBR) and MCI in elderly patients with type 2 diabetes.
Design And Methods: We measured plasma DPP4 activity, BDNF levels, oxidative stress parameters, inflammatory markers and calculated DBR in 1833 elderly type 2 diabetic patients aged 60 years or older.
Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT).
View Article and Find Full Text PDFObjective: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is attributed to a "multi-hits hypothesis" involving insulin resistance, oxidative stress and inflammation. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing the"multi-hits". Hence, we investigated the association between plasma DPP4 activity and NAFLD in nondiabetic Chinese population.
View Article and Find Full Text PDFObjective: Obesity, inflammation, and decreased neuropeptide Y (NPY) are risk factors for depression. Dipeptidyl peptidase-4 (DPP4), a newly identified adipokine, has been proved to promote inflammation and NPY degradation. Hence, we aimed to investigate the association between plasma DPP4 activity and depression symptoms in middle-aged and older adults.
View Article and Find Full Text PDFBMC Cardiovasc Disord
September 2016
Background: The prevalence of hypertension in adults is increasing each year and has become a main public health issue worldwide. We must consider the impact of both individual factors and interactions among these factors on hypertension in adults. This study was designed to elucidate the clinical and metabolic characteristics of the prevalence of hypertension in adults and to explore the risk factors and interactions among these factors in adults with hypertension.
View Article and Find Full Text PDFObjective: Hyperglycemia, inflammation, and oxidative stress are thought to be involved in the pathogenesis of cognitive decline. Dipeptidyl peptidase-4 (DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes.
View Article and Find Full Text PDFObjective: To investigate the association between plasma Dipeptidyl peptidase-4 (DPP4) activities and diabetic nephropathy in type 2 diabetes.
Research Design And Methods: A total of 1193 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4 activity, mannose 6-phosphate receptor, inflammatory markers and oxidative stress parameters were measured in all participants.
J Clin Endocrinol Metab
October 2015
Context: Inflammation, insulin resistance, dyslipidemia, and glucagon-like peptide-1 (GLP-1) are risk factors for osteoporosis. Dipeptidyl peptidase-4 (DPP4) is a newly identified adipokine related to these risk factors.
Objective: To investigate the association between plasma DPP4 activities and osteoporosis.
This prospective cohort study aimed to analyze the association between serum ferritin levels and the risk of abnormal glucose metabolism (AGM) in Southwestern Chinese population. The 383 subjects who are aged ≥20 years and free of AGM at baseline between in 2007 and in 2008 were included in Southwestern China, and their baseline serum ferritin levels were measured. Among these subjects, 140 subjects were developed into AGM during the follow-up (2008-2012).
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