Biomedical subjects

Kejun Liu

Publications and source records attributed to Kejun Liu.

8 recordsLinked to original sources

PubMed2026

CARS1 as a Prognostic Biomarker and Candidate Therapeutic Vulnerability in Hepatocellular Carcinoma: Insights Into Tumor Progression and the Immune Microenvironment.

BACKGROUND: Cysteinyl-tRNA synthetase 1 (CARS1) has been included in ferroptosis-related prognostic signatures, but its clinicopathological relevance, cellular functions, and relationship with the immune microenvironment in hepatocellular carcinoma (HCC) remain incompletely characterized. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were integrated with corresponding data from an institutional HCC tissue cohort of 60 patients. CARS1 expression was evaluated by immunohistochemistry, and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA) and multiplex immunofluorescence, as well as by analyzing public single-cell datasets. The effects of CARS1 depletion were evaluated in MHCC97H and Hep3B cells using Cell Counting Kit-8 (CCK-8) assays, cell-cycle profiling, wound-healing assays, Transwell migration assays, western blotting, and erlotinib-sensitivity assays. RESULTS: CARS1 expression was elevated in HCC and was associated with adverse clinicopathological features and poor overall survival. Quantitative immunohistochemistry confirmed elevated CARS1 protein expression in tumor tissues. CARS1 depletion inhibited cell proliferation, altered cell-cycle distribution, impaired migration, and enhanced in vitro sensitivity to erlotinib. High CARS1 expression was also associated with increased infiltration of Th2-like immune cells. CONCLUSIONS: Elevated CARS1 expression is associated with an adverse biological and immune phenotype in HCC. These clinical, histopathological, and loss-of-function findings support further investigation of CARS1 as a prognostic marker and candidate therapeutic target in HCC, although additional mechanistic and in vivo validation is required.

Humans↗

PubMed2006

Gene expression profiling of androgen receptor antagonists in the rat fetal testis reveals few common gene targets.

The androgen receptor (AR) is expressed in the fetal testis; however, the role of AR in fetal testicular development is poorly understood. Disrupted AR activity and subsequent gene expression alterations may disturb developmental programming of the fetal testis and result in testicular abnormalities later in life. The present study was performed to examine global gene expression patterns in rat fetal testis following in utero exposure to various AR antagonists. Pregnant Sprague-Dawley rats were treated with flutamide (50 mg/kg/day), linuron (50 mg/kg/day), vinclozolin (200 mg/kg/day), p,p'-DDE (100 mg/kg/day) or corn oil vehicle by gavage daily from gestation day (GD) 12-19. Testes were isolated on GD 19, and AR immunostaining, histology, and global changes in gene expression were determined. There were no alterations in the pattern or expression level of AR and no apparent histological changes in the fetal testes in any treatment group. Microarray analysis using Dunnett's test with multiple testing correction revealed no significant gene expression alterations following exposure to flutamide, linuron, vinclozolin, and p,p'-DDE. A less stringent analysis yielded some chemical specific effects on gene expression, and these effects were further evaluated by real-time RT-PCR. Vinclozolin treatment reduced the expression of several genes involved in cholesterol biosynthesis, though the testosterone levels were unchanged in the fetal testes in any treatment group. In flutamide, linuron, and p,p'-DDE treatment groups, the expression of hemoglobin Y, beta-like embryonic chain (Hbb-y) was reduced. Myomesin 2 (Myom2) expression was increased following linuron treatment. Given the lack of a common set of genes and the absence of overt histopathology, we conclude that the fetal testis is not a major target for AR activity at this stage of development although some cell-type specific gene expression changes cannot be ruled out.

Androgen Antagonists↗

PubMed2005

Differential steroidogenic gene expression in the fetal adrenal gland versus the testis and rapid and dynamic response of the fetal testis to di(n-butyl) phthalate.

The phthalate ester di(n-butyl) phthalate (DBP) causes feminization of male rats upon in utero exposure by repressing expression of genes required for testicular steroidogenesis. Previous work in our laboratory has shown that repression of gene expression and steroidogenesis in the fetal testis is apparent within a few hours of DBP exposure. The purpose of this study was to determine the precise timing of DBP-associated gene expression changes in the fetal testis using transcriptional profiling and to determine whether DBP exerts similar effects on steroidogenesis in the fetal adrenal. A DBP time-course experiment showed that testicular steroidogenesis was decreased within 1 h of DBP exposure and that this decrease preceded the repressed transcription of Star (steroidogenic acute regulatory protein); Scarb1 (scavenger receptor class B, member 1; also know as Sr-b1); Cyp11a1 (cytochrome P450, family 11, subfamily a, polypeptide 1; also known as P450SCC); and Cyp17a1 (cytochrome P450 family 17, subfamily a, polypeptide 1; also known as Cyp17). Gene expression profiling demonstrated rapid (within 1 to 3 h) and transient induction of immediate early genes in the fetal testis after administration of DBP to the pregnant dam. There was a statistically insignificant decrease in corticosterone production by the fetal adrenal after in utero exposure to DBP from Gestation Day 12 to Gestation Day 19. The extent of steroidogenesis diminution was much less in the adrenal than in the testis (approximately 45% decrease in the adrenal versus 87% decrease in the testis) and expression of genes required for steroidogenesis in the adrenal was unaffected by DBP. Together, these studies demonstrate that DBP initiates a rapid and dynamic change in gene expression in the fetal testis that likely plays a role in the reduction in steroidogenesis that is unique to the fetal testis relative to the steroidogenically active fetal adrenal.

Adrenal Glands↗

PubMed2005

Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis.

Male reproductive tract abnormalities associated with testicular dysgenesis in humans also occur in male rats exposed gestationally to some phthalate esters. We examined global gene expression in the fetal testis of the rat following in utero exposure to a panel of phthalate esters. Pregnant Sprague-Dawley rats were treated by gavage daily from Gestational Days 12 through 19 with corn oil vehicle (1 ml/kg) or diethyl phthalate (DEP), dimethyl phthalate (DMP), dioctyl tere-phthalate (DOTP), dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP), dipentyl phthalate (DPP), or benzyl butyl phthalate (BBP) at 500 mg/kg per day. Testes were isolated on Gestational Day 19, and global changes in gene expression were determined. Of the approximately 30 000 genes queried, expression of 391 genes was significantly altered following exposure to the developmentally toxic phthalates (DBP, BBP, DPP, and DEHP) relative to the control. The developmentally toxic phthalates were indistinguishable in their effects on global gene expression. No significant changes in gene expression were detected in the nondevelopmentally toxic phthalate group (DMP, DEP, and DOTP). Gene pathways disrupted include those previously identified as targets for DBP, including cholesterol transport and steroidogenesis, as well as newly identified pathways involved in intracellular lipid and cholesterol homeostasis, insulin signaling, transcriptional regulation, and oxidative stress. Additional gene targets include alpha inhibin, which is essential for normal Sertoli cell development, and genes involved with communication between Sertoli cells and gonocytes. The common targeting of these genes by a select group of phthalates indicates a role for their associated molecular pathways in testicular development and offers new insight into the molecular mechanisms of testicular dysgenesis.

Animals↗

PubMed2005

PowerMarker: an integrated analysis environment for genetic marker analysis.

SUMMARY: PowerMarker delivers a data-driven, integrated analysis environment (IAE) for genetic data. The IAE integrates data management, analysis and visualization in a user-friendly graphical user interface. It accelerates the analysis lifecycle and enables users to maintain data integrity throughout the process. An ever-growing list of more than 50 different statistical analyses for genetic markers has been implemented in PowerMarker. AVAILABILITY: www.powermarker.net

Algorithms↗

PubMed2005

Genetic diversity and population structure of teosinte.

The teosintes, the closest wild relatives of maize, are important resources for the study of maize genetics and evolution and for plant breeding. We genotyped 237 individual teosinte plants for 93 microsatellites. Phylogenetic relationships among species and subspecific taxa were largely consistent with prior analyses for other types of molecular markers. Plants of all species formed monophyletic clades, although relationships among species were not fully resolved. Phylogenetic analysis indicated that the Mexican annual teosintes divide into two clusters that largely correspond to the previously defined subspecies, Z. mays ssp. parviglumis and ssp. mexicana, although there are a few samples that represent either evolutionary intermediates or hybrids between these two subspecies. The Mexican annual teosintes show genetic substructuring along geographic lines. Hybridization or introgression between some teosintes and maize occurs at a low level and appears most common with Z. mays ssp. mexicana. Phylogeographic and phylogenetic analyses of the Mexican annual teosintes indicated that ssp. parviglumis diversified in the eastern part of its distribution and spread from east to west and that ssp. mexicana diversified in the Central Plateau of Mexico and spread along multiple paths to the north and east. We defined core sets of collections of Z. mays ssp. mexicana and ssp. parviglumis that attempt to capture the maximum number of microsatellite alleles for given sample sizes.

Alleles↗

PubMed2003

Genetic structure and diversity among maize inbred lines as inferred from DNA microsatellites.

Two hundred and sixty maize inbred lines, representative of the genetic diversity among essentially all public lines of importance to temperate breeding and many important tropical and subtropical lines, were assayed for polymorphism at 94 microsatellite loci. The 2039 alleles identified served as raw data for estimating genetic structure and diversity. A model-based clustering analysis placed the inbred lines in five clusters that correspond to major breeding groups plus a set of lines showing evidence of mixed origins. A "phylogenetic" tree was constructed to further assess the genetic structure of maize inbreds, showing good agreement with the pedigree information and the cluster analysis. Tropical and subtropical inbreds possess a greater number of alleles and greater gene diversity than their temperate counterparts. The temperate Stiff Stalk lines are on average the most divergent from all other inbred groups. Comparison of diversity in equivalent samples of inbreds and open-pollinated landraces revealed that maize inbreds capture <80% of the alleles in the landraces, suggesting that landraces can provide additional genetic diversity for maize breeding. The contributions of four different segments of the landrace gene pool to each inbred group's gene pool were estimated using a novel likelihood-based model. The estimates are largely consistent with known histories of the inbreds and indicate that tropical highland germplasm is poorly represented in maize inbreds. Core sets of inbreds that capture maximal allelic richness were defined. These or similar core sets can be used for a variety of genetic applications in maize.

Alleles↗

PubMedDate not supplied

PowerMV: a software environment for molecular viewing, descriptor generation, data analysis and hit evaluation.

Ideally, a team of biologists, medicinal chemists and information specialists will evaluate the hits from high throughput screening. In practice, it often falls to nonmedicinal chemists to make the initial evaluation of HTS hits. Chemical genetics and high content screening both rely on screening in cells or animals where the biological target may not be known. There is a need to place active compounds into a context to suggest potential biological mechanisms. Our idea is to build an operating environment to help the biologist make the initial evaluation of HTS data. To this end the operating environment provides viewing of compound structure files, computation of basic biologically relevant chemical properties and searching against biologically annotated chemical structure databases. The benefit is to help the nonmedicinal chemist, biologist and statistician put compounds into a potentially informative biological context. Although there are several similar public and private programs used in the pharmaceutical industry to help evaluate hits, these programs are often built for computational chemists. Our program is designed for use by biologists and statisticians.

Computer Simulation↗