Biomedical subjects

Jihong Chen

Publications and source records attributed to Jihong Chen.

7 recordsLinked to original sources

PubMed2026

Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.

End-stage renal disease (ESRD) remains a major clinical challenge with high morbidity and mortality, and its molecular mechanisms, particularly those shared among diverse primary kidney diseases during progression to ESRD, have not been studied. Here we conduct a large-scale two-stage epigenome-wide association study of ESRD in two independent cohorts consisting of 704 controls and 1031 ESRD cases. We identify 52 ESRD-associated differentially methylated CpG positions (ESRD DMPs) showing consistent association between the two cohorts and across diverse kidney diseases, implicating 144 candidate genes enriched in inflammatory and immune pathways. Five of the 52 DMPs are associated with ESRD complications, and seven with renal function decline in early-stage chronic kidney disease, demonstrating their potential as prognostic biomarkers for ESRD and its complications. Our findings highlight inflammation, immune dysregulation, and renal fibrosis as shared epigenetic drivers of ESRD progression, and identify biomarkers with potential utility for risk stratification and therapeutic intervention.

Humans↗

PubMed2006

Valproic acid and butyrate induce apoptosis in human cancer cells through inhibition of gene expression of Akt/protein kinase B.

BACKGROUND: In eukaryotic cells, the genomic DNA is packed with histones to form the nucleosome and chromatin structure. Reversible acetylation of the histone tails plays an important role in the control of specific gene expression. Mounting evidence has established that histone deacetylase inhibitors selectively induce cellular differentiation, growth arrest and apoptosis in variety of cancer cells, making them a promising class of anticancer drugs. However, the molecular mechanisms of the anti-cancer effects of these inhibitors have yet to be understood. RESULTS: Here, we report that a key determinant for the susceptibility of cancer cells to histone deacetylase inhibitors is their ability to maintain cellular Akt activity in response to the treatment. Also known as protein kinase B, Akt is an essential pro-survival factor in cell proliferation and is often deregulated during tumorigenesis. We show that histone deacetylase inhibitors, such as valproic acid and butyrate, impede Akt1 and Akt2 expression, which leads to Akt deactivation and apoptotic cell death. In addition, valproic acid and butyrate induce apoptosis through the caspase-dependent pathway. The activity of caspase-9 is robustly activated upon valproic acid or butyrate treatment. Constitutively active Akt is able to block the caspase activation and rescues cells from butyrate-induced apoptotic cell death. CONCLUSION: Our study demonstrates that although the primary target of histone deacetylase inhibitors is transcription, it is the capacity of cells to maintain cellular survival networks that determines their fate of survival.

Apoptosis↗

PubMed2005

JBEAM: multiscale curve coding via beamlets.

A multiscale coder for curves and boundaries is presented. It utilizes a multiscale structure--beamlets--that is designed primarily for linear and curvilinear features. The coder is composed of three main components: 1) a rate-distortion optimized beamlet-based representation, 2) a tree-based coding from a beamlet representation to a symbol stream, and 3) an entropy coder. This coder is named "JBEAM." Taking advantage of its multiscale property, we utilized tree-based coding to make it progressive. The derived coder has a low order of computational complexity. Simulations demonstrate an advantage over the state-of-the-art industrial standard: JBIG 2. A software package, which includes an implementation of JBEAM, is made available. Variations and potential improvements of this method will be discussed. This work may inspire more activities in this line of research, improving curve coding.

Algorithms↗

PubMed2005

B56 regulatory subunit of protein phosphatase 2A mediates valproic acid-induced p300 degradation.

Transcriptional coactivator p300 is required for embryonic development and cell proliferation. Valproic acid, a histone deacetylase inhibitor, is widely used in the therapy of epilepsy and bipolar disorder. However, it has intrinsic teratogenic activity through unidentified mechanisms. We report that valproic acid stimulates proteasome-dependent p300 degradation through augmentation of gene expression of the B56gamma regulatory subunits of protein phosphatase 2A. The B56gamma3 regulatory and catalytic subunits of protein phosphatase 2A interact with p300. Overexpression of the B56gamma3 subunit leads to proteasome-mediated p300 degradation and represses p300-dependent transcriptional activation, which requires the B56gamma3 interaction domain of p300. Conversely, silencing of the B56gamma subunit expression by RNA interference increases the stability and transcriptional activity of the coactivator. Our study establishes the functional interaction between protein phosphatase 2A and p300 activity and provides direct evidence for signal-dependent control of p300 function.

Enzyme Inhibitors↗

PubMed2004

Building a cascade detector and its applications in automatic target detection.

A hierarchical classifier (cascade) is proposed for target detection. In building an optimal cascade we considered three heuristics: (1) use of a frontier-following approximation, (2) controlling error rates, and (3) weighting. Simulations of synthetic data with various underlying distributions were carried out. We found that a weighting heuristic is optimal in terms of both computational complexity and error rates. We initiate a systematic comparison of several potential heuristics that can be utilized in building a hierarchical model. A range of discussions regarding the implications and the promises of cascade architecture as well as of techniques that can be integrated into this framework is provided. The optimum heuristic--weighting algorithms--was applied to an IR data set. It was found that these algorithms outperform some state-of-the-art approaches that utilize the same type of simple classifier.

Journal Article↗

PubMed2002

Impact of domain interchange on conformational stability and equilibrium folding of chimeric class micro glutathione transferases.

Rat micro class glutathione transferases M1-1 and M2-2 are homodimers that share a 78% sequence identity but display differences in stability. M1-1 is more stable at the secondary and tertiary structural levels, whereas its quaternary structure is less stable. Each subunit in these proteins consists of two structurally distinct domains with intersubunit contacts occurring between domain 1 of one subunit and domain 2 of the other subunit. The chimeric subunit variants M(12), which has domain 1 of M1 and domain 2 of M2, and its complement M(21), were used to investigate the conformational stability of the chimeric homodimers M(12)-(12) and M(21)-(21) to determine the contribution of each domain toward stability. Exchanging entire domains between class micro GSTs is accommodated by the GST fold. Urea-induced equilibrium unfolding data indicate that whereas the class micro equilibrium unfolding mechanism (i.e., N(2) <--> 2I <--> 2U) is not altered, domain exchanges impact significantly on the conformational stability of the native dimers and monomeric folding intermediates. Data for the wild-type and chimeric proteins indicate that the order of stability for the native dimer (N(2)) is M2-2 > M(12)-(12) M1-1 approximately M(21)-(21), and that the order of stability of the monomeric intermediate (I) is M1 > M2 approximately M(12) > M(21). Interactions involving Arg 77, which is topologically conserved in GSTs, appear to play an important role in the stability of both the native dimeric and folding monomeric structures.

Amino Acid Sequence↗

PubMed2002

Attenuation of glucocorticoid signaling through targeted degradation of p300 via the 26S proteasome pathway.

The effects of acetylation on gene expression are complex, with changes in chromatin accessibility intermingled with direct effects on transcriptional regulators. For the nuclear receptors, both positive and negative effects of acetylation on specific gene transcription have been observed. We report that p300 and steroid receptor coactivator 1 interact transiently with the glucocorticoid receptor and that the acetyltransferase activity of p300 makes an important contribution to glucocorticoid receptor-mediated transcription. Treatment of cells with the deacetylase inhibitor, sodium butyrate, inhibited steroid-induced transcription and altered the transient association of glucocorticoid receptor with p300 and steroid receptor coactivator 1. Additionally, sustained sodium butyrate treatment induced the degradation of p300 through the 26S proteasome pathway. Treatment with the proteasome inhibitor MG132 restored both the level of p300 protein and the transcriptional response to steroid over 20 h of treatment. These results reveal new levels for the regulatory control of gene expression by acetylation and suggest feedback control on p300 activity.

Acetylation↗