Biomedical subjects

Sang Hyun Park

Publications and source records attributed to Sang Hyun Park.

16 recordsLinked to original sources

PubMed2026

Biallelic loss of RB1 in hepatocellular carcinoma as synthetic lethal target for artificial intelligence-guided therapy.

The retinoblastoma (RB1) gene is a critical tumor suppressor that regulates cell cycle progression and genomic stability. Although RB1 alterations have been reported in hepatocellular carcinoma (HCC), the biological and clinical consequences of biallelic RB1 inactivation (RB1-Bi) remain poorly defined. We performed a comprehensive allele-specific genomic analysis of HCC patients from the TCGA-LIHC (n = 355) and in-house AMC (n = 206) cohorts, collectively comprising the AMC-TCGA discovery cohort. In this combined cohort, RB1-Bi was identified in 14.6% of tumors, was enriched in poorly differentiated HCCs and was independently associated with significantly reduced overall survival (adjusted hazard ratio 3.32, 95% CI 1.93-5.72, p < 0.001). Additionally, a deep learning-based histopathology model using hematoxylin and eosin-stained slides (i.e., FR-MIL model) accurately predicted RB1-Bi status (F1 score 84.39% [95% CI, ±0.02]), making it readily identifiable in routine clinical practice. The prevalence and prognostic impact of RB1-Bi, as well as FR-MIL model performance, were consistent across independent validation cohorts, including advanced-stage tumors and external institutions. High-throughput drug screening in isogenic HCC models revealed that RB1-Bi HCC cells were particularly sensitive to inhibitors targeting mitotic regulators (e.g., AURKA, PLK1, KSP) and DNA damage response pathways (e.g., PARP inhibitors). Synthetic lethal interactions between RB1-Bi and these compounds were demonstrated in vitro and in vivo, and combination treatment with mitotic and PARP inhibitors had synergistic effects with acceptable tolerability. We conclude that RB1-Bi represents a clinically actionable biomarker that identifies a high-risk HCC subtype with specific therapeutic vulnerabilities, offering new opportunities for precision medicine.

Humans↗

PubMed2006

Identification, culture, and characterization of germline stem cell-like cells in chicken testes.

We recently succeeded in inducing germline transmission by transferring chicken testicular cells into heterologous testes. This study was designed subsequently to identify pluripotent cells in the testicular cells, which would induce the germline transmission. Testicular cells retrieved from juvenile (4-wk-old) or adult (24-wk-old) White Leghorn (WL) chickens were stained with germ cell-specific markers anti-SSEA1, anti-SSEA3, anti-SSEA4, anti-EMA1, anti-ITGA6, and anti-ITGB1 antibodies; 2C9; and lectin-Solanum tuberosum agglutinin (STA). The percentages of the cells that were positive for each marker were within the ranges of 0.33% -0.44% and 0.029%-0.072% of the total testicular cell population in the juvenile and adult, respectively, and significant (P < 0.0002) differences were detected between the ages. When 1 x 10(6) testicular cells were cultured in Dulbecco minimum essential medium-based medium supplemented with leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF2), and/or insulinlike growth factor 1 (IGF1), colony formation was detected only in LIF++FGF2-containing or LIF+FGF2+IGF1-containing medium during primary culture, and the supplementation of LIF+FGF2+IGF1 was the most efficient for maintaining the colony-forming cells through subculture. The established cells retrieved at the end of the primary culture or the 20th subpassage were positive for chicken germ cell-specific periodic acid-Schiff (PAS), EMA1, 2C9, SSEA1, SSEA3, SSEA4, ITGA6, and ITGB1; and lectin-STA markers (evaluated after 11th subpassage). Double staining of lectin-STA with anti-SSEA1, anti-SSEA3, anti-SSEA4, anti-ITGA6, and anti-ITGB1 also was possible. They differentiated spontaneously into embryoid bodies after being cultured in LIF-free medium. We conclude that germline stem cell-like cells are present in chicken testicular cells retrieved from both juvenile and adult testes, which can be identified with the specific markers for primordial germ cells or embryonic germ cells.

Animals↗

PubMed2006

Salicornia herbacea prevents high fat diet-induced hyperglycemia and hyperlipidemia in ICR mice.

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.

Adipose Tissue↗

PubMed2006

Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob mice.

Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.

Animals↗

PubMed2005

Complexation of ferrocene derivatives by the cucurbit[7]uril host: a comparative study of the cucurbituril and cyclodextrin host families.

The formation of inclusion complexes between cucurbit[7]uril (CB[7]) and ferrocene and its derivatives has been investigated. The X-ray crystal structure of the 1:1 inclusion complex between ferrocene and CB[7] revealed that the guest molecule resides in the host cavity with two different orientations. Inclusion of a set of five water-soluble ferrocene derivatives in CB[7] was investigated by 1H NMR spectroscopy and calorimetric and voltammetric techniques. Our data indicate that all neutral and cationic guests form highly stable inclusion complexes with CB[7], with binding constants in the 10(9)-10(10) M(-)(1) and 10(12)-10(13) M(-1) ranges, respectively. However, the anionic ferrocenecarboxylate, the only negatively charged guest among those surveyed, was not bound by CB[7] at all. These results are in sharp contrast to the known binding behavior of the same guests to beta-cyclodextrin (beta-CD), since all the guests form stable inclusion complexes with beta-CD, with binding constants in the range 10(3)-10(4) M(-1). The electrostatic surface potentials of CB[6], CB[7], and CB[8] and their size-equivalent CDs were calculated and compared. The CD portals and cavities exhibit low surface potential values, whereas the regions around the carbonyl oxygens in CBs are significantly negative, which explains the strong affinity of CBs for positively charged guests and also provides a rationalization for the rejection of anionic guests. Taken together, our data suggest that cucurbiturils may form very stable complexes. However, the host-guest interactions are very sensitive to some structural features, such as a negatively charged carboxylate group attached to the ferrocene residue, which may completely disrupt the stability of the complexes.

Bridged-Ring Compounds↗

PubMed2005

Euonymus alatus prevents the hyperglycemia and hyperlipidemia induced by high-fat diet in ICR mice.

Euonymus alatus (EA), known as a Gui Jeon Wu in China, has been used as a folk medicine for regulating blood circulation, relieving pain, eliminating blood clot, and treating dysmenorrhea in Asian countries. Although EA has anecdotally ascertained to show the anti-hyperglycemic activity by enhancing insulin secretion, there is no sufficient experimental evidence for anti-hyperglycemic activity of EA. The purpose of this study was to investigate the preventive effect of 50% ethanol extract of EA in high-fat diet-induced hyperglycemic and hyperlipidemic ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice was to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high-fat diet with either 350, 700 mg/kg of EA (EA350 and EA700) or 250 mg/kg of metformin (MET250) for a 10-week period. EA not only reduced body weight in a dose dependent manner, but also corrected associated hyperinsulinemia and hyperlipidemia. EA exerted beneficial effects on glucose and lipid homeostasis in diabetes that are not secondary to its ability to decrease food intake but its specific effects on hepatic lipogenesis related genes (SREBPla, FAS, GAPT) and PPAR-gamma gene expression in periepididymal fat. Taken together, the combined effect of EA to reduce plasma glucose and lipid levels, and reduce the deposition of triglyceride in the liver are indicative of a marked improvement in obesity-related diabetes and non-alcoholic fatty liver disease.

Adipose Tissue↗

PubMed2005

Antidiabetic stilbene and anthraquinone derivatives from Rheum undulatum.

The antidiabetic-activity-guided fractionation and isolation of the 80% EtOH extracts obtained from cultivated Korean Rhubarb rhizomes (Rheum undulatum, Polygonaceae) led to the isolation and characterization of one stilbene, desoxyrhapontigenin (1) and two anthraquinones, emodin (2) and chrysophanol (3). Their structures were established by chemical and spectroscopic methods. Compounds 1, 2, and 3 inhibited postprandial hyperglycemia by 35.8, 29.5, 42.3%, respectively.

Animals↗

PubMed2005

Repair of steps and gaps in articular fracture models.

To examine the healing of surface defects in articular fractures, gaps measuring 0.5 mm wide and 2 mm deep were created in 0.5-mm coronal step-offs on the medial femoral condyles of 16 rabbits, and identical gaps without step-offs were created in another set of 13 rabbits. Evaluation of repair was done 6, 12, and 24 weeks postoperatively. Histologically, subchondral bone restoration of gaps in step-offs was complete by 24 weeks, whereas restoration was incomplete in most gap-only lesions. Bone density measured by peripheral quantitative computed tomography was normal in gaps in step-offs by 24 weeks, but values were less than in controls in the gap-only group. A moderate degree of degeneration was detected only at the high sides of step-off + gap lesions. The joint surface was restored by fibrous cartilage that showed gradually improving maturity in all defects, however, real integration with adjacent original cartilage did not occur. Immunohistologic examination showed decreasing collagen Type I and increasing Type II staining intensity in repair tissue of both types of lesions. These observations suggest that minor surface gaps and steps of articular fractures may regenerate without inducing severe early joint degeneration. However, certain repair features make the long-term outcome of these defects uncertain.

Animals↗

PubMed2004

Antidiabetic coumarin and cyclitol compounds from Peucedanum japonicum.

The antidiabetic activity-guided fractionation and isolation of the 80% EtOH extracts from Peucedani Radix (Peucedanum japonicum, Umbelliferae) led to the isolation and characterization of a coumarin and a cyclitol as active principles, that is, peucedanol 7-O-beta-D-glucopyranoside (1) and myo-inositol (2). Their structures were identified by spectroscopic methods. Compound 1 showed 39% inhibition of postprandial hyperglycemia at 5.8 mg/kg dose, and compound 2 also significantly inhibited postprandial hyperglycemia by 34% (P<0.05).

Animals↗

PubMed2004

Metal-on-metal surface arthroplasty with a cemented femoral component: a 7-10 year follow-up study.

Forty-two McMinn metal-on-metal surface arthroplasties were implanted in 23 males and 16 females, average age 47.5 years old. The overall survivorship at 7 years was 79%; with any reoperation surgery as endpoint, 80%; and 93%; with aseptic loosening of the socket and femoral component, respectively. The average Surface Arthroplasty Risk Index of patients who had failed or were at risk of failing on the femoral side was significantly greater than for the rest of the cohort, 3.9 versus 1.9. The overall survivorship of the McMinn component was unacceptably low, with the majority of failures occurring with the cemented acetabular components. The recent reintroduction of surface arthroplasty of the hip using metal-on-metal bearings and cementless acetabular components may benefit young patients with hip arthritis with appropriate patient selection.

Adult↗

PubMed2003

Lanthanum indium oxide from X-ray powder diffraction.

LaInO(3), a promising ion conductor for a holistic solid oxide fuel cell, was synthesized by a solid-state reaction method. The structure was refined by the Rietveld method using X-ray powder diffraction data. The structure of LaInO(3) is distorted by the in-phase and antiphase tilting of oxygen octahedra in the a(+)b(-)b(-) system of the InO(6) polyhedra. In the Pmna space group, the In atom lies on an inversion centre and the La atom and one of the O atoms lie on a mirror plane.

Journal Article↗

PubMed2003

A stable cis-stilbene derivative encapsulated in cucurbit[7]uril.

cis-Diaminostilbene dihydrochloride encapsulated in cucurbit[7]uril does not spontaneously isomerize to the trans isomer at room temperature as a result of the strong host-guest interactions including strong hydrogen bonds between the two protonated amine termini of the C-shaped guest and the portal oxygen atoms of the host.

Journal Article↗

PubMed2003

Expression of early development-related genes in bovine nuclear transferred and fertilized embryos.

Cloning efficiency following somatic cell nuclear transfer is very low. In order to obtain insights into this problem, mRNA expression patterns of early development-related genes in nuclear transferred embryos were compared with those obtained from in vivo and in vitro fertilization. Semiquantitative reverse-transcription polymerase chain reaction assay was used to compare the gene expression of, the cell adhesion protein E-cadherin, interleukin-6, heat-shock protein 70.1 and bos taurus apoptosis regulator box-a (Bax). The relative abundances of glucose transporter-1, E-cadherin and interleukin-6 were significantly (P < 0.05) higher in in vitro fertilized morulae than in vivo derived morulae. Transcription of the gene encoding octamer-binding transcription factor 4 was higher in blastocysts obtained from in vivo fertilization than in those from in vivo blastocysts. The transcript for Bax was markedly upregulated in blastocysts derived from in vitro production and nuclear transfer procedures compared with in vivo fertilization. These results suggest that alterations in mRNA expression of early development genes are more associated with in vitro culture condition than the nuclear transfer procedure itself.

Animals↗

PubMed2003

Surface damage on open box posterior-stabilized polyethylene tibial inserts.

Twenty retrieved Scorpio posterior-stabilized implants were available for analysis. The mean implantation time was 22 months (range, 2 days-42 months). Favorable types and amounts of surface damage were seen on the tibiofemoral and backsides of these modular PE liners that had been packaged in an inert environment and then sterilized by gamma irradiation. Delamination represented only 0.1% of the total surface damage. Off-axis loading (varus malalignment) was associated with tibial component loosening but there was no evidence of peripheral damage of PE caused by edge loading. With this open-box design, hyperextension marks on the anterior aspect of the posterior-stabilized post from femoral component impingement occurred in 11 of 20 cases and was related to sagittal component positioning: excess tibial slope or increased tibial slope combined with a flexed femoral component. Unique coarse abrasions occurred in 16 of 20 cases and were the result of cement extrusion into the open box, especially with varus malalignment. These observations provide guidance for optimizing the surgical technique and the design of posterior-stabilized total knee components.

Adult↗

PubMed2002

Tuning and dissecting electronic and steric effects in ammonium receptors: nonactin vs artificial receptors.

Ion selective electrodes (ISE) based on three different tripodal receptors (5, 6, and 7) have been investigated for sensing ammonium ion. Each receptor is based on three pyrazole groups that can accept three H-bonds from the bound ammonium ion. The receptor based on 4-bromo-3,5-dimethylpyrazole (6) is the most sensitive with a detection limit for ammonium ion of 2.5 x 10(-5) M at pH 8. The detection limits for the receptors based on 2,3-dimethylpyrazole (5) and unsubstitued pyrazole (7) are 1.0 x 10(-4) and 2.0 x 10(-4) M, respectively. The selectivities of the receptors 5, 6, and 7 for sensing ammonium ion over potassium ion (logK(NH)4+(/K)+) are -2.8, -2.3, and -1.7, respectively. In contrast, the detection limit and the selectivity of a nonactin-based ISE are 2.2 x 10(-5) M and -1.3, respectively. Crystallographic studies reveal that 6 accepts three H-bonds from the bound ammonium and singly protonated receptor 5 forms three H-bonds with the bound water molecule.

Anti-Bacterial Agents↗

PubMedDate not supplied

Novel and efficient preparation of precursor [188Re(OH2)3(CO)3]+ for the labeling of biomolecules.

A novel and efficient method for preparing 188Re(I) tricarbonyl precursor [188Re(OH2)3(CO)3]+ has been developed by reacting [188Re]perrhenate with Schibli's kit in the presence of borohydride exchange resin (BER) as a reducing agent and an anion scavenger. The precursor was produced in more than 97% yield by reacting a solution of tetrahydroborate exchange resin (BER, 3 mg), borane-ammonia (BH3.NH3, 3 mg), and potassium boranocarbonate (K2[H3BCO2], 3 mg) in 0.9% saline with a solution of sodium perrhenate (Na188ReO4) with up to 50 MBq and concentrated phosphoric acid (85%, 7 microL) at 60 degrees C for 15 min. HPLC and TLC revealed 0% unreacted [188Re]perrhenate ion and <3% of colloidal 188ReO2. Since the precursor is produced with high radiochemical purity and labeling efficiency under the milder conditions than those required for the conventional reducing agents, the latter can be replaced.

Borohydrides↗