Biomedical subjects

Yan Hu

Publications and source records attributed to Yan Hu.

At least 19 recordsLinked to original sources

PubMed2026

Effects of domestication on the body morphology and genetic diversity of the yellowfin seabream (Acanthopagrus latus).

The yellowfin seabream (Acanthopagrus latus) is a significant economic fish along the southeast coast of China. Recently, the drastic decline in the wild populations, exacerbated by overfishing and climate change, has heightened our reliance on aquaculture. However, the current lack of research on its domestication hinders effective conservation of wild populations and balanced management alongside the aquaculture industry. Studies on body characteristics have shown that wild yellowfin seabream possess a higher body, while cultured ones exhibit a wider body. Whole-genome SNP analysis revealed moderate genetic differentiation between cultured and wild populations. Further analyses of linkage disequilibrium, heterozygosity, and genetic diversity revealed that the degree of SNP linkage was lower in the wild population compared to the cultured population. In contrast, heterozygosity and nucleotide polymorphisms were significantly higher in the wild population (P < 0.001 and P < 0.05, respectively). Additionally, over 300 candidate genes were identified in each cultured population through genomic selection signature analysis, with 67 key genes shared among all three, which were linked to growth and development (ghrb, ghsra, and cfl1), immune response (aire, cd36, and igbp1), and salinity adaptation (abcc3, clic4, and kcnk15). Enrichment analysis indicated that the key candidate genes were significantly enriched in pathways related to protein kinase activity, ion binding and growth hormone synthesis, secretion and action (FDR < 0.05). The findings provide valuable insights into the variation in body size of yellowfin seabream under domestication selection and offer an important theoretical basis for the genetic improvement of yellowfin seabream.

Animals↗

PubMed2025

Refining sequence-to-activity models by increasing model resolution.

Decoding the cis-regulatory syntax that controls gene expression is essential for improving our understanding of cell differentiation and disease. To identify regulatory motifs and their regulatory syntax, deep learning based sequence-to-activity (S2A) models learn transcription factor binding motifs and their combinations from DNA sequence by modeling measured chromatin accessibility. Previously, we developed AI-TAC, a S2A model that predicts chromatin accessibility across various immune cell types in multi-task fashion, effectively decoding the regulatory syntax underlying immune cell differentiation. While ATAC-seq is commonly used to measure regional accessibility, it also provides high-resolution profiles, the distribution of Tn5 insertion sites, that offer additional insights into the precise location and strength of TF binding sites. Here we demonstrate that modeling ATAC-seq profiles alongside accessibility consistently improves predictions of differential chromatin accessibility across cell types. Moreover, we also find that multi-task learning across related immune cell types consistently outperforms single-task models. To understand what additional information bpAITAC learns from ATAC-seq profiles, we systematically compare sequence attributions from models trained with and without ATAC-seq profiles. We identify novel motifs with strong effect sizes that emerge only when profile data is included. Our findings suggest that modeling ATAC-seq at base-pair resolution enables the model to learn a more nuanced and sensitive representation of the cis-regulatory syntax driving immune cell-specific chromatin landscapes.

ATAC-seq↗

PubMed2006

Effect of anthocyanin-rich extract from black rice (Oryza sativa L. indica) on hyperlipidemia and insulin resistance in fructose-fed rats.

This study was designed to evaluate the effect of an anthocyanin-rich extract from black rice on hyperlipidemia and insulin resistance in fructose-fed rats. Rats fed fructose diet for 4 weeks exhibited significantly higher plasma insulin levels and lower insulin sensitivity than the control rats fed AIN-93G diet. Dietary supplementation with the anthocyanin-rich extract (5 g/kg of high-fructose diet) prevented the development of fructose-induced insulin resistance. After fructose-induced insulin resistance had been established, 4-week treatment with the anthocyanin-rich extract (5 g/kg of high-fructose diet) or pioglitazone (270 mg/kg of high-fructose diet) ameliorated the glucose intolerance and hyperlipidemia, but the extract failed to reverse the fructose-induced hyperinsulinemia as pioglitazone did. In addition, rats supplemented by the extract exhibited lower oxidative stress than the fructose-fed controls, as indicated by the lower concentrations of plasma thiobarbituric acid reactive substances and blood oxidized glutathione. Overall, these results suggest that the anthocyanin-rich extract from black rice improves certain metabolic abnormalities associated with diets high in fructose.

Animals↗

PubMed2006

Effector function of leucocytes from susceptible and resistant mice against distinct isolates of Candida albicans.

Neutrophils and macrophages were generated in vitro from mice that display either high or low tissue susceptibilities to Candida albicans infection and their ability to phagocytose and kill three isolates of the yeast with different virulence characteristics was evaluated. In the absence of opsonization, phagocytosis by BALB/c and CBA/CaH neutrophils was comparable, but the killing was very poor. Opsonization with normal serum slightly decreased phagocytosis, but it had markedly different effects on killing, either enhancing or inhibiting candidacidal activity, depending on the combination of yeast isolate and mouse strain. In contrast, BALB/c macrophages showed high levels of phagocytosis and killing of both unopsonized yeasts and opsonized yeasts; whereas killing of unopsonized yeasts by CBA/CaH macrophages was poor, it was markedly enhanced by opsonization.

Animals↗

PubMed2006

Papillomavirus E2 protein interacts with and stimulates human topoisomerase I.

The papillomavirus (PV) E2 protein plays a role in recruiting viral and cellular DNA replication factors, such as PV E1 or RPA to PV genomes. Using both purified proteins and through co-precipitation, it was determined that HPV-11 E2 binds human topoisomerase I. E2 can stimulate topoisomerase I DNA relaxation activity 3- to 4-fold. Conversely, topoisomerase I is unable to stimulate E2 DNA binding. These findings suggest that stimulation of topoisomerase I by E2 may help promote efficient relaxation of the torsional stress induced by PV DNA replication.

DNA Topoisomerases, Type I↗

PubMed2006

Different effects of capsaicin on I(A) and I(K) in pain-conduct neurons of rats.

The different effects of capsaicin on I(A) and I(K) currents in pain-conduct neurons of trigeminal ganglia (TG) were investigated. In cultured TG neurons of rats, whole-cell patch clamp techniques were used to record the I(A) and I(K) before and after capsaicin perfused. Results revealed that 1 micromol/L capsaicin could inhibit the amplitude of I(A) by 48.2% (n = 10, P < 0.05), but had no inhibitory effect on I(K) (n = 7, P > 0.05). Ten micromol/L capsaicin could significantly inhibit the amplitude of I(A) by 93.2% (n = 8, P < 0.01), but only slightly inhibit the amplitude of I(K) by 13.2% (n = 7, P < 0.05). Neither 1 micromol/L nor 10 micromol/L capsaicin had effects on the active curve of I(A) and I(K). It was concluded that capsaicin could selectively inhibit the I(A) current, and this effect might involve in the analgesic mechanisms of capsaicin.

Animals↗

PubMed2006

Cellular topoisomerase I modulates origin binding by bovine papillomavirus type 1 E1.

In addition to viral proteins E1 and E2, bovine papillomavirus type 1 (BPV1) depends heavily on host replication machinery for genome duplication. It was previously shown that E1 binds to and recruits cellular replication proteins to the BPV1 origin of replication, including DNA polymerase alpha-primase, replication protein A (RPA), and more recently, human topoisomerase I (Topo I). Here, we show that Topo I specifically stimulates the origin binding of E1 severalfold but has no effect on nonorigin DNA binding. This is highly specific, as binding to nonorigin DNA is not stimulated, and other cellular proteins that bind E1, such as RPA and polymerase alpha-primase, show no such effect. The stimulation of E1's origin binding by Topo I is not synergistic with the stimulation by E2. Although the enhanced origin binding of E1 by Topo I requires ATP and Mg2+ for optimal efficiency, ATP hydrolysis is not required. Using an enzyme-linked immunosorbent assay, we showed that the interaction between E1 and Topo I is decreased in the presence of DNA. Our results suggest that Topo I participates in the initiation of papillomavirus DNA replication by enhancing E1 binding to the BPV1 origin.

Adenosine Triphosphate↗

PubMed2006

[Preliminary study on determination of specific cellular immunity of patients with hepatitis B].

BACKGROUND: To evaluate an enzyme linked immunospot (ELISPOT) method for testing the specific cellular immunity of patients with hepatitis B and preliminarily investigate into the difference of cellular immunity in patients with various types of hepatitis B. METHODS: The patients with acute hepatitis B, chronic hepatitis B liver cirrhosis, healthy persons with HBV vaccine immunization, healthy persons with past HBV infection and HBV naive persons were enrolled in this study. Their peripheral blood mononuclear cells were tested by ELISPOT to determine the number of gamma-interferon secreting cells. RESULTS: The number of gamma-interferon secreting cells was significantly different between the patients with acute hepatitis B and those with chronic hepatitis B, and between the patients with acute hepatitis B and those with liver cirrhosis (P=0.0209 and P=0.0211). CONCLUSION: The specific cellular immunity in the patients with hepatitis B could be evaluated by determining the number of gamma-interferon secreting cells with the method of testing their peripheral blood mononuclear cells by ELISPOT. The specific cellular immunity was stronger in the patients with acute hepatitis B than in those with chronic hepatitis B and liver cirrhosis.

Enzyme-Linked Immunosorbent Assay↗

PubMed2006

[Identification and typing of human enteroviruses using an RT-PCR assay].

BACKGROUND: To establish a molecular detection and typing assay for identification and typing of human enteroviruses (HEV) which is suitable for clinical detection and epidemiologic research. METHODS: Using both primers specific for HEV genus and HEV typing primers and reverse transcription polymerase chain reaction (RT-PCR) the authors detected preliminarily HEV by agarose gel electrophoresis and then identified serotype through nucleotide sequence analysis of RT-PCR amplicons. The monospecific antisera neutralization was applied to validate the typing results. RESULTS: The serotype of 18 suspicious HEV samples was identified: 4 Coxsackievirus type A24 (CVA24), 3 CVB3, 1 CVB2, 1 CVA9, 1 CVA15, 1 Echovirus type 3 (E3), 1 E6, 1 E9, 1 E11, 1 E14, 1 E33 and 1 Rhinovirus type 9. The result was validated by monospecitive antisera neutralization. CONCLUSION: This RT-PCR assay for HEV detection and typing may be suitable for clinical detection and epidemic research since this method is sensitive and specific for direct identification and typing of HEV.

DNA Primers↗

PubMed2006

[Follow up study on viruses associated with SARS among the SARS patients].

BACKGROUND: To study the existence status of the SARS-CoV, retrovirus, and the poliovirus in the bodies of the patients with SARS and the possible relationship between the three viruses and SARS. METHODS: The clinical specimens of the nasopharyngeal swabs, sputum (or saliva), urine, fecal specimens were collected on three consecutive days from 8 patients with SARS 2 years after the recovery from SARS. SARS-CoV, reovirus and poliovirus RNA was detected by using reverse transcription (RT)-PCR; IgG antibody to the poliovirus type 1 and 3 and the antibody to SARS-CoV were determined using enzyme linked immunosorbent assay (ELISA). RESULTS: All the specimens were negative for SARS-CoV and reovirus by RT-PCR, but the fecal specimens from 4 persons were positive for poliovirus. The sequences of these poliovirus were highly homologous to that of human poliovirus type 1 strain sabin 1 genome at nucleotide level, but back mutations have occurred in the primary attenuating mutation sites at nucleotide position 480 (G --> A) in the 5' UTR and the nucleotide position 2795 (A --> G). No SARS-CoV, reovirus, and poliovirus were found in the normal controls. Three serum specimens were positive for the antibody to SARS-CoV. The IgG antibody to poliovirus were detected in 4 SARS patients and 23 healthy persons. No positive results for antibody to SARS-CoV were detected in the 25 healthy persons. CONCLUSION: The positive rate of the poliovirus antibody in the serum of SARS patients 2 years after recovery was significantly different from that of the normal controls, and the positive rate of poliovirus in the fecal specimens was still very high, and more importantly back mutations have occurred in the attenuating mutation sites at nucleotide position which plays an important role in the poliomyelitis.

Adult↗

PubMed2006

[Determination of total flavonoids in Abrus cantoniensis and its dynamic changes].

OBJECTIVE: To develop a method for ultrasonic extraction and determination of total flavonoids in Abrus cantoniensis, and to analyze its dynamic changes. METHOD: The optimized condition of extraction of total flavonoids was studied with orthogonal design. The contents of total flavonoids in different organs and of different growth stages were determined by UV-visible spectrophotometer. RESULT: The ethanol volume and extraction times were the main factors impacting the effects of ultrasonic extraction. The content of total flavonoids in stems were higher than in roots and the lowest in leaves. The dynamic changes of total flavonoids contents in roots and stems of A. cantoniensis were in similar trends. Its total flavonoids content in the two parts of plant increased gradually with the growth and reached the maximum in October, and the content decreased significantly in Feburay of next year. The content of total flavonoids in leaves reached also to the highest value before leaves fell off. CONCLUSION: The optimized extraction method of total flavonoids in Abrus contoniensis was obtained with three times with 80% ethanol at 20 times of volume for 30 min. The results implied that the best yield and quality may be obtained before leaves fall.

Abrus↗

PubMed2005

A new molecularly imprinted polymer for selective extraction of cotinine from urine samples by solid-phase extraction.

Cotinine, the main metabolite of nicotine in human body, is widely used as a biomarker for assessment of direct or passive exposure to tobacco smoke. A method for molecularly imprinted solid-phase extraction (MISPE) of cotinine from human urine has been investigated. The molecularly imprinted polymer (MIP) with good selectivity and affinity for cotinine was synthesized using cotinine as the template molecule, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker. The imprinted polymer was evaluated for use as a SPE sorbent, in tests with aqueous standards, by comparing recovery data obtained using the imprinted form of the polymer and a non-imprinted form (NIP). Extraction from the aqueous solutions resulted in more than 80% recovery. A range of linearity for cotinine between 0.05 and 5 microg mL-1 was obtained by loading 1 mL blank urine samples spiked with cotinine at different concentrations in acetate buffer of pH 9.0, and by using double basic washing and acidic elution. The intra-day coefficient of variation (CV) was below 7% and inter-day CV was below 10%. This investigation has provided a reliable MISPE-HPLC method for determination of cotinine in human urine from both active smokers and passive smokers.

Chromatography, High Pressure Liquid↗

PubMed2005

Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice.

To identify the genes and signal pathways responsible for mechanical loading-induced bone formation, we evaluated differential gene expression on a global basis in the tibias of C57BL/6J (B6) mice after four days of four-point bending. We applied mechanical loads to the right tibias of the B6 mice at 9 N, 2 Hz for 36 cycles per day, with the left tibias used as unloaded controls. RNA from the tibias was harvested 24 h after last stimulation and subjected to microarray. Of the 20,280 transcripts hybridized to the array, 346 were differentially expressed in the loaded bones compared to the controls. The validity of the microarray data was established with the increased expression of bone-related genes such as pleiotrophin, osteoglycin, and legumain upon four-point bending and confirmation of increased expression of selected genes by real-time PCR. The list of differentially expressed genes includes genes involved in cell growth, differentiation, adhesion, proteolysis, as well as signaling molecules of receptors for growth factors, integrin, Ephrin B2, endothelin, and adhesion G protein coupled receptor. Pathway analyses suggested that 28 out of the 346 genes exhibited a direct biological association. Among the biological network, fibronectin and pleitrophin function as important signaling molecules in regulating periosteal bone formation and resorption in response to four-point bending. Furthermore, some expressed sequence tags (ESTs) with no prior known function have been identified as potential mediators of mechanotransduction signaling pathways. Further studies on these previously unknown genes will improve our understanding of the molecular pathways and mechanisms involved in bone's response to mechanical stress.

Anabolic Agents↗

PubMed2005

Comparative proteomic analysis of intra- and interindividual variation in human cerebrospinal fluid.

Cerebrospinal fluid (CSF) is a potential source of biomarkers for many disorders of the central nervous system, including Alzheimer disease (AD). Prior to comparing CSF samples between individuals to identify patterns of disease-associated proteins, it is important to examine variation within individuals over a short period of time so that one can better interpret potential changes in CSF between individuals as well as changes within a given individual over a longer time span. In this study, we analyzed 12 CSF samples, composed of pairs of samples from six individuals, obtained 2 weeks apart. Multiaffinity depletion, two-dimensional DIGE, and tandem mass spectrometry were used. A number of proteins whose abundance varied between the two time points was identified for each individual. Some of these proteins were commonly identified in multiple individuals. More importantly, despite the intraindividual variations, hierarchical clustering and multidimensional scaling analysis of the proteomic profiles revealed that two CSF samples from the same individual cluster the closest together and that the between-subject variability is much larger than the within-subject variability. Among the six subjects, comparison between the four cognitively normal and the two very mildly demented subjects also yielded some proteins that have been identified in previous AD biomarker studies. These results validate our method of identifying differences in proteomic profiles of CSF samples and have important implications for the design of CSF biomarker studies for AD and other central nervous system disorders.

Cerebrospinal Fluid Proteins↗

PubMed2005

A microfluidic device using a green organic light emitting diode as an integrated excitation source.

A simply fabricated microfluidic device using a green organic light emitting diode (OLED) and thin film interference filter as integrated excitation source is presented and applied to fluorescence detection of proteins. A layer-by-layer compact system consisting of glass/PDMS microchip, pinhole, excitation filter and OLED is designed and equipped with a coaxial optical fiber and for fluorescence detection a 300 microm thick excitation filter is employed for eliminating nearly 80% of the unwanted light emitted by OLEDs which has overlaped with the fluorescence spectrum of the dyes. The distance between OLED illuminant and microchannels is limited to approximately 1 mm for sensitive detection. The achieved fluorescence signal of 300 microM Rhodamine 6G is about 13 times as high as that without the excitation filter and 3.5 times the result of a perpendicular detection structure. This system has been used for fluorescence detection of Rhodamine 6G, Alexa 532 and BSA conjugates in 4% linear polyacrymide (LPA) buffer (in 1 x TBE, pH 8.3) and 1.4 fmol and 35 fmol mass detection limits at 0.7 nl injection volume for Alexa and Rhodamine dye have been obtained, respectively.

Acrylic Resins↗

PubMed2005

A novel inflammation-induced ubiquitin E3 ligase in alveolar type II cells.

LINCR was identified as a glucocorticoid-attenuated response gene induced in the lung during endotoxemia. The LINCR protein has structural similarities to Drosophila Neuralized, which regulates the developmentally important Notch signaling pathway. Endotoxemia-induced LINCR expression in vivo was localized by in situ hybridization to alveolar epithelial type II cells, and shown to be induced by LPS and inflammatory cytokines in the T7 alveolar epithelial type II cell line. RING domain-dependent ubiquitin E3 ligase activity of LINCR was demonstrated using full-length FLAG-LINCR or a deletion mutant lacking the RING domain expressed in 293T cells, and using a GST-LINCR RING fusion protein expressed in Escherichia coli. LINCR preferentially interacted with the ubiquitin-conjugating enzyme UbcH6 and preferentially generated polyubiquitin chains linked via non-canonical lysine residues. We conclude that LINCR is a novel inflammation-induced ubiquitin E3 ligase expressed in alveolar epithelial type II cells, and discuss its potential role in the lung response to inflammation.

Animals↗

PubMed2005

Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation.

Hutchinson-Gilford progeria syndrome (HGPS), a progeroid syndrome in children, is caused by mutations in LMNA (the gene for prelamin A and lamin C) that result in the deletion of 50 aa within prelamin A. In normal cells, prelamin A is a "CAAX protein" that is farnesylated and then processed further to generate mature lamin A, which is a structural protein of the nuclear lamina. The mutant prelamin A in HGPS, which is commonly called progerin, retains the CAAX motif that triggers farnesylation, but the 50-aa deletion prevents the subsequent processing to mature lamin A. The presence of progerin adversely affects the integrity of the nuclear lamina, resulting in misshapen nuclei and nuclear blebs. We hypothesized that interfering with protein farnesylation would block the targeting of progerin to the nuclear envelope, and we further hypothesized that the mislocalization of progerin away from the nuclear envelope would improve the nuclear blebbing phenotype. To approach this hypothesis, we created a gene-targeted mouse model of HGPS, generated genetically identical primary mouse embryonic fibroblasts, and we then examined the effect of a farnesyltransferase inhibitor on nuclear blebbing. The farnesyltransferase inhibitor mislocalized progerin away from the nuclear envelope to the nucleoplasm, as determined by immunofluoresence microscopy, and resulted in a striking improvement in nuclear blebbing (P < 0.0001 by chi2 statistic). These studies suggest a possible treatment strategy for HGPS.

Alkyl and Aryl Transferases↗

PubMed2005

The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells.

IMP-3, a member of the insulin-like growth factor-II (IGF-II) mRNA-binding protein (IMP) family, is expressed mainly during embryonic development and in some tumors. Thus, IMP-3 is considered to be an oncofetal protein. The functional significance of IMP-3 is not clear. To identify the functions of IMP-3 in target gene expression and cell proliferation, RNA interference was employed to knock down IMP-3 expression. Using human K562 leukemia cells as a model, we show that IMP-3 protein associates with IGF-II leader-3 and leader-4 mRNAs and H19 RNA but not c-myc and beta-actin mRNAs in vivo by messenger ribonucleoprotein immunoprecipitation analyses. IMP-3 knock down significantly decreased levels of intracellular and secreted IGF-II without affecting IGF-II leader-3, leader-4, c-myc, or beta-actin mRNA levels and H19 RNA levels compared with the negative control siRNA treatment. Moreover, IMP-3 knock down specifically suppressed translation of chimeric IGF-II leader-3/luciferase mRNA without altering reporter mRNA levels. Together, these results suggest that IMP-3 knock down reduced IGF-II expression by inhibiting translation of IGF-II mRNA. IMP-3 knock down also markedly inhibited cell proliferation. The addition of recombinant human IGF-II peptide to these cells restored cell proliferation rates to normal. IMP-3 and IMP-1, two members of the IMP family with significant structural similarity, appear to have some distinct RNA targets and functions in K562 cells. Thus, we have identified IMP-3 as a translational activator of IGF-II leader-3 mRNA. IMP-3 plays a critical role in regulation of cell proliferation via an IGF-II-dependent pathway in K562 leukemia cells.

5' Untranslated Regions↗