Biomedical subjects

Y L Liu

Publications and source records attributed to Y L Liu.

At least 19 recordsLinked to original sources

PubMed2026

ARID1A Mediates ROS-Induced Osteoclast Activation in TMJ Osteoarthritis.

Excessive osteoclast activation drives rapid subchondral bone destruction, serving as a critical early-stage event precipitating temporomandibular joint osteoarthritis (TMJ-OA). Although epigenetic remodeling is widely recognized as an important interface between pathological environmental signals and genomic response, the specific epigenetic mechanisms translating TMJ-OA-associated stimulation into pathological osteoclast activation remain to be elucidated. Here, using a mechanically induced TMJ-OA mouse model, we identify aberrant reactive oxygen species (ROS) accumulation as a critical upstream driver initiating excessive osteoclast activation and subsequent joint deterioration. By integrating transcriptomic and epigenomic analyses, we delineate the chromatin remodeler AT-rich interaction domain 1A (ARID1A) as an essential oxidative stress sensor within the osteoclast lineage. Mechanistically, ROS accumulation induces ARID1A upregulation and recruitment to the Src enhancer, transcriptionally activating Src and amplifying PI3K-AKT signaling to drive pathological osteoclastogenesis. Conditional knockout of Arid1a in myeloid cells effectively abrogates subchondral bone loss and cartilage destruction in TMJ-OA. Translating these mechanistic insights, we engineered an ROS-responsive, osteoclast-targeting hydrogel for the on-demand delivery of an ARID1A-dependent canonical BRG1/BRM-associated factor complex inhibitor, which successfully alleviates TMJ-OA progression. Our findings establish the epigenetic response to ROS accumulation as a key pathogenic mechanism in TMJ-OA and highlight ARID1A as a promising therapeutic target for early disease intervention.

biomaterial(s)↗

PubMed1992

Characterization and purification of a novel transcriptional repressor from HeLa cell nuclear extracts recognizing the negative regulatory element region of human immunodeficiency virus-1 long terminal repeat.

Cellular transcription factors play critical roles in regulating human immunodeficiency virus (HIV) gene transcription, although the precise mechanism(s) defining their roles are not well established. Primarily it has been suggested that sequence-specific interaction of trans-activating proteins with cis-acting DNA elements plays a crucial role in regulating the target genes. The negative regulatory element (NRE) of HIV-1 long terminal repeat (LTR) is one such defined region that has been reported to down-regulate LTR-directed HIV gene expression. Information regarding the role of this region in the regulation of HIV expression is lacking. Here we describe an attempt to further characterize the role of NRE cis-elements and define any sequence-specific interaction with cellular factors. Using gel mobility shift DNA-binding and Southwestern blot assays, we have mapped a distinct region of NRE (-290 to -260, a 30-base pair (bp) domain of NRE-A) sequences of HIV-1 LTR, which recognizes a specific DNA-binding protein from HeLa cell nuclear extracts. This factor is a 38-kDa polypeptide which can be affinity-purified to near homogeneity by this 30-bp specific oligonucleotide in affinity chromatography. The cellular factor from HeLa cell nuclear extract exhibits specific interaction only with the 30-bp NRE-A domain of HIV-1 LTR and acts as a strong transcriptional repressor/inhibitor molecule in the DNA-protein gel binding, as well as in vitro transcriptional studies with the nuclear extracts from cells with productive HIV-1 infection. To our knowledge, this is the first report of a factor recognizing a distinct segment within NRE that has been shown to exert an inhibitory effect on transcriptionally active DNA-protein "pre-initiation" complex formation, suggesting a possible role in HIV-1 gene regulation.

Base Sequence↗

PubMed1992

Mechanisms regulating cardiac fuel selection in hyperthyroidism.

Starvation (48 h) decreases fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations and the ratio of free to acylated carnitine in hearts of euthyroid rats. These decreases, which are indicative of increased lipid fuel oxidation, are accompanied by decreased rates of glucose uptake and phosphorylation, assessed by using radioactive 2-deoxyglucose. Cardiac concentrations of acylated carnitines were increased at the expense of free carnitine even in the fed state in response to experimental hyperthyroidism, but neither Fru-2,6-P2 concentrations nor rates of glucose utilization were suppressed. Starvation (48 h) did not further increase the proportion of acylated carnitine in the heart in hyperthyroidism, and suppression of Fru-2,6-P2 concentrations and glucose utilization rates by starvation was attenuated. Although glucose utilization rates were decreased, starvation did not decrease immunoreactive GLUT 4 protein concentrations. Furthermore, although hyperthyroidism was associated with a statistically significant (30-40%) increase in relative abundance of GLUT 4 mRNA, the amount of GLUT 4 protein was not increased by hyperthyroidism in either the fed or the starved state. The results demonstrate a significant effect of hyperthyroidism to enhance cardiac glucose utilization in starvation by a mechanism which does not involve changes in GLUT 4 expression but may be secondary to changes in glucose-lipid interactions at the tissue level.

Animals↗

PubMed1992

Isolation of potential cancer chemopreventive agents from Eriodictyon californicum.

Activity-based fractionation of Eriodictyon californicum resulted in the isolation of 12 flavonoids that inhibit the metabolism of the carcinogen benzo[a]pyrene by hamster embryo cells in tissue culture. One was identified as a new flavanone, 3'-methyl-4'-isobutyryleriodictoyol [1], on the basis of spectroscopic analysis and alkaline hydrolysis. The seven other active flavanones were identified as eriodictyol [2], homoeriodictyol [3], 5,4'-dihydroxy-6,7-dimethoxyflavanone [4], pinocembrin [5], sakuranetin [6], 5,7,4'-trihydroxy-6,3'-dimethoxyflavanone [7], and naringenin 4'-methyl ether [8]. Four active flavones were also isolated: cirsimaritin [9], chrysoeriol [10], hispidulin [11], and chrysin [12]. The high inhibition of benzo[a]pyrene metabolism and the activation of benzo[a]pyrene to ultimate carcinogenic DNA-binding metabolites by cirsimaritin and chrysoeriol at a concentration of only 10 micrograms/ml indicates that these flavones warrant further investigation in vivo as potential chemopreventive agents.

Animals↗

PubMed1992

New tetrasaccharide flavonol glycoside from Epimedium acuminatum.

A new tetrasaccharide flavonol glycoside was isolated from the aerial parts of Epimedium acuminatum, along with three known flavonoids. The structure of the new compound, named acuminatoside [1], was established to be anhydroicaritin-3-O-alpha-L-rhamnopyranosyl(1----2)-alpha-L-rhamno pyranoside-7- O-beta-D-glucopyranosyl-(1----2)-beta-D-glucopyranoside by means of spectroscopic techniques (uv, eims, fdms, fabms, 1H nmr, 1H-1H COSY, 2D-J, 13C nmr, APT, and 1H-13C HETCOR) and chemical methods (acid hydrolysis, enzymatic hydrolysis, and tlc-densitometry). The known compounds were identified as icariin, epimedoside A, and kaempferitrin.

Carbohydrate Sequence↗

PubMed1992

Ras mediates translation initiation factor 4E-induced malignant transformation.

Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7 GpppN, where N is any nucleotide). eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras.

3T3 Cells↗

PubMed1992

Calcium calmodulin dependent kinase II in cat visual cortex and its development.

A monoclonal antibody against the alpha-subunit of calcium/calmodulin-dependent protein kinase II (CAM-K II) was used to visualize the kinase in developing kitten visual cortex. CAM-K II was first expressed in neurons of the deep cortical layers (V and VI) at postnatal day 1-4 and appeared in the remaining cortical layers within the first 2 weeks. The level of immunoreactivity declined in cells of layer V and upper layer VI at about 30-40 days of age. By postnatal day 90, the most densely labelled neurons were concentrated in cortical layers II, III, lower layer IV and in layer VI. This laminar pattern remained constant into adulthood. EM studies showed that the kinase was found in both pre- and postsynaptic locations. About twice as many immunopositive neurons were found in cortical layers II-IV and VI in young adult cats when geniculate input was removed by an unilateral thalamic lesion performed early in life. These results indicate that expression of CAM-K II is developmentally regulated in visual cortical neurons; the alteration of immunoreactivity after early LGN lesions suggests that the level of the kinase (or its alpha-subunit) is also regulated by cortical input.

Animals↗

PubMed1992

[Value and mechanism of abnormal postexercise systolic blood pressure response for detection of coronary artery disease].

The value of an abnormal ratio of recovery systolic blood pressure to peak exercise SBP for detecting coronary artery diseases (CAD) is controversial. We evaluated the ratio in 39 patients with angiographically documented CAD and 52 patients with normal coronary artery undergoing treadmill exercise. If a response with the ratio higher than 1.0 and 0.8 at 1 and 3 min. of recovery was considered as abnormal, the sensitivity for detecting CAD was 66.7%, the specificity 73.1% and the accuracy 70.3%. If ST segment depression is combined into the criteria, the specificity and accuracy reach 94.2% and 76.9%. In CAD, the ratio at 3 min. of recovery showed significant negative correlation with resting left ventricular ejection fraction (LVEF) (r = -0.461, P < 0.01). It is suggested that low resting LVEF may be one of the mechanism of this abnormal ratio in CAD.

Adult↗

PubMed1992

[Acuminatin from the aerial part of Epimedium acuminatum].

A new flavonol glycoside, C27H28O10, mp 151-152 degrees C (MeOH), named acuminatin (I), was isolated from the aerial part of Epimedium acuminatum Franch in addition to four known compounds. By means of UV, FAB-MS, EI-MS, 1HNMR, 13CNMR and chemical evidences, the structure of acuminatin was established as 6", 6"-dimethylpyrano (2", 3": 7, 8) 4'-methyl kaempferol-3-O-alpha-L-rhamnopyranoside. The known compounds were identified as kaempferol-3-O-alpha-L-rhamnopyranoside (II), quercitrin (III), hyperin (IV) and daucosterol (V).

Drugs, Chinese Herbal↗

PubMed1992

[Structure of swertiapuniside from Swertia punicea Hemsl].

A new xanthone glycoside, swertiapuniside (V), has been isolated from the whole plant of Swertia punicea Hemsl. The structure was elucidated as 1,5,8-trihydroxy-3-methoxyxanthone-8-O-beta-D-glucopyranosyl (1-6)-O-beta-D-glucopyranoside by means of chemical and spectroscopic data. Four other known xanthones mangiferin (I), bellidifodin (II), 1,3,5,8-tetrahydroxyxanthone (III) and swertinolin (IV) were also identified.

Drugs, Chinese Herbal↗

PubMed1991

Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry.

Previous studies have demonstrated that dietary administration of the schistosomicidal drug 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) ameliorates the hepatotoxicity of aflatoxin B1 (AFB1). Notably, mortality, altered hepatic function, hepatic AFB1-DNA adduct levels, and expression of hepatic enzyme-altered foci were markedly reduced in the rat by concurrent feeding of oltipraz during exposures to AFB1. Collectively, these studies prompted us to evaluate the chemoprotective properties of oltipraz against AFB1-induced liver cancer. In addition, preliminary molecular dosimetry studies were undertaken to determine the utility of measurements of urinary aflatoxin-N7-guanine excretion as a marker of relative risk for hepatocarcinogenesis in AFB1-exposed rats. For the carcinogenesis studies, 5-wk-old male F344 rats were randomly divided into two groups. One group (55 rats) received the AIN-76A diet, and the other group (56 rats) received the AIN-76A diet supplemented with 0.075% oltipraz. The oltipraz-supplemented diet was fed for 4 wk. Beginning 1 wk after starting the experimental diets, all rats in both groups received 25 micrograms of AFB1/rat/day by gavage for 5 days per wk over the next 2 wk. One wk following cessation of dosing with AFB1, oltipraz was removed from the diet, and all rats were fed the AIN-76A diet for the remainder of the experiment. At 3 mo after dosing, livers of ten sentinel rats from each group were analyzed for the burden of gamma-glutamyltranspeptidase-positive foci. In accord with previous findings, rats fed the oltipraz-supplemented diet exhibited substantial reductions in the focal burden (97% reduction; P less than 0.05) of these AFB1-induced lesions. The remaining rats were maintained for the cancer study until they became moribund or the termination of the experiment at 23 mo. Gross liver lesions were identified at autopsy and confirmed by microscopic evaluation. An 11% incidence of hepatocellular carcinoma was observed in the AFB1-treated, control diet-fed rats. An additional 9% of this group had hepatocellular adenomas. Oltipraz afforded complete protection against both AFB1-induced hepatocellular neoplasms. Using Kaplan-Meier survival analyses, rats in the oltipraz group had a significantly (P less than 0.02) longer life span and an increased survival free of liver tumors (P less than 0.0002). Molecular dosimetry studies used rats fed either the oltipraz-supplemented or control diet for 1 wk and then challenged with a single dose of AFB1 to examine the initial rates of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 excreted in the urine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗

PubMed1991

Glucose utilization by interscapular brown adipose tissue in vivo during nutritional transitions in the rat.

Glucose utilization indices (GUI) of interscapular brown adipose tissue (IBAT) declined by 84% after 48 h starvation. Two-thirds of the overall response was observed within 6 h, correlating with decreased insulin concentrations. Re-feeding 48 h-starved rats restored insulin concentrations and evoked a rapid 15-fold increase in IBAT GUI. GUI values after re-feeding were markedly higher than those observed at equivalent insulin concentrations in control post-absorptive rats.

Adipose Tissue, Brown↗

PubMed1991

In vitro immunopharmacological profile of the plant flavonoid baohuoside-1.

A novel flavonoid compound baohuoside-1 (3,5,7-trihydroxy-4'-methoxyl-8-prenylflavone-3-O-alpha-L-rhamnopy ranoside) was investigated for immunopharmacological properties in vitro. The results show that baohuoside-1 has significant suppressive effects on neutrophil chemotaxis, mitogen-induced lymphocyte transformation, mixed-lymphocyte culture, NK-cell cytotoxicity and IL-2 production. These dose-dependent inhibitory effects were found to be significant at concentrations of less than 1 microgram/ml, compared with greater than 94% cell viability at concentrations of 10 micrograms/ml. These results suggest that baohuoside-1 may have potential as an anti-inflammatory/immunosuppressive agent.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

[Effect of Polyporus umbellatus polysaccharide on function of macrophages in the peritoneal cavities of mice with liver lesions].

The cells in peritoneal cavities of mice were taken out and cultured in vitro. The amount to release H2O2 of the macrophages was assayed by fluorimetry. Polyporus umbellatus polysaccharide (PUP) could not only increase the number of macrophages and the amount of H2O2 release in the peritoneal cavities of normal mice, but also raise the lowered number of macrophages and the ability to release H2O2 in the peritoneal cavities of the mice with liver lesions caused by CCl4 significantly. So PUP could improve the cellular immunity of normal mice and the mice with liver lesions.

Animals↗

PubMed1991

Case-control study on pathogenesis of pneumonia in children aged 0-2 years.

In order to know the incidence of risk factors predisposing children to pneumonia, case control study was carried out in six MCH Model Counties in 1986. Single factor analysis showed 29 factors were responsible for the increasing incidence of pneumonia. 13 of 29 factors were major pneumonia risk factors by the standard of means greater than 15 and OR greater than 3. They were malnutrition, anemia, riskets, pneumonia history, repeated colds, chronic diarrhoea, congenital malformation, asphyxia neonatorum, amniotic fluid aspiration, artificial feeding, too much clothing, family member with acute respiratory illness (ARI) and contact with ARI patients. Among them 7 factors were related to individual health condition. Therefore, it is important to improve general health of children so as to reduce the incidence of pneumonia.

Case-Control Studies↗

PubMed1991

Modulation of the mitogenic activity of eukaryotic translation initiation factor-4E by protein kinase C.

Eukaryotic initiation factor-4E (eIF-4E) binds to the cap structure of eukaryotic mRNAs and is a component of the cap-binding protein complex eIF-4F. eIF-4E is present in cells in limiting concentrations and is phosphorylated both in vivo and in vitro by protein kinase C (PKC). Recently, eIF-4E has been implicated as an intracellular transducer of extracellular growth signals; microinjection of recombinant eIF-4E into quiescent NIH 3T3 cells induced DNA synthesis. In the present report, the mitogenic activity of eIF-4E was examined after coinjection with PKC. Recombinant eIF-4E was phosphorylated by PKC at the same amino acid that is phosphorylated in cultured cells and reticulocytes in response to phorbol ester. At limiting concentrations of eIF-4E, coinjection with PKC induced a fivefold increase in the mitogenic activity of eIF-4E. Injection of PKC alone or coinjection of eIF-4E with cAMP-dependent protein kinase (PKA) or the Raf protein had no effect. These results suggest that the mitogenic activity of eIF-4E is enhanced by PKC-specific phosphorylation and that phosphate addition is a rate-limiting step in eIF-4E activity.

Animals↗

PubMed1990

Glucose utilization and disposal in cardiothoracic and skeletal muscles during the starved-to-fed transition in the rat.

Glucose utilization indices (GUI) increased to fed values in diaphragm and oxidative skeletal muscles and exceeded fed values in non-oxidative muscles within 2 h of re-feeding chow to 48 h-starved rats. Cardiac GUI reached fed values only after 7 h. Glycogen deposition accounted for most of the glucose phosphorylated in skeletal muscle over the first 2 h in oxidative muscles and over the first 4 h in non-oxidative muscles. In oxidative muscles, the contribution of glycogen deposition to total glucose 6-phosphate disposal diminished as re-feeding was extended from 2 to 6 h.

Animals↗

PubMed1990

Glucose utilization by skeletal muscles in vivo in experimental hyperthyroidism in the rat.

In the fed state, hyperthyroidism increased glucose utilization indices (GUIs) of skeletal muscles containing a lower proportion of oxidative fibres. Glycogen concentrations were unchanged, but active pyruvate dehydrogenase (PDHa) activities were decreased. Hyperthyroidism attenuated the effects of 48 h of starvation to decrease muscle GUI. Glycogen concentrations and PDHa activities after 48 h of starvation were low and similar in euthyroid and hyperthyroid rats. The increase in glucose uptake and phosphorylation relative to oxidation and storage in skeletal muscle induced by hyperthyroidism may contribute to increased glucose re-cycling in the fed hyperthyroid state and to glucose turnover in the starved hyperthyroid state.

Animals↗