Won-Il Jeong

Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-κB pathway in lipopolysaccharide-stimulated macrophage

Quercetin is a flavonoid molecule ubiquitous in nature and functions as an anti-oxidant and anti-inflammatory agent with little toxicity in vivo and in vitro. Dose- and time-dependent effect of quercetin has been investigated on proinflammatory cytokine expression and NO production, focusing on its effects on the MAP kinases and the NF-κB signal transduction pathways in LPS-stimulated RAW 264.7 cells by using RT-PCR and immunoblotting. Quercetin strongly reduced activation of phosphorylated ERK kinase and p38 MAP kinase but not JNK MAP kinase by LPS treatment. In addition, quercetin treatment inhibited NF-κB activation through stabilization of the NF-κB/IκB complex and IκB degradation and proinflammatory cytokines and NO/iNOS expression. Quercetin may exert its anti-inflammatory and immunomodulatory properties in the effect molecules such as proinflammatory cytokines and NO/iNOS by suppressing the activation of ERK and p38 MAP kinase, and NF-κB/IκB signal transduction pathways.

Canine renal failure syndrome in three dogs

Three dead dogs were brought to the College of Veterinary Medicine, Kyungpook National University for study. Clinically, all the dogs showed emaciation, anorexia, depression, hemorrhagic vomiting and diarrhea for 7~10 days before death. All the clinical signs were first noted for about one month after feeding the dogs with commercial diets. At necropsy, all 3 dogs had severe renal damage with the same green-yellowish colored nephroliths in the renal pelvis. They also showed systemic hemorrhage and calcification of several organs, which might have been induced by uremia. Microscopically, necrosis, calcification and calculi were detected in the renal tubules, and especially in the proximal convoluted tubules and collecting ducts of the kidney. These findings were supportive of a mycotoxic effect, and especially on their kidneys. However, the precise cause of the toxic effect in these cases of canine renal failure could not be determined.

p53 and cell-cycle-regulated protein expression in small intestinal cells after fast-neutron irradiation in mice.

The involvement of the p53 gene in apoptosis of many cell types towards γ-radiation is well established. However, little information is available on the relationship between p53 status and cells’ ability to undergo apoptosis following exposure to fast neutrons. The aim of this study was to characterize the apoptotic pathway traveled by neutrons in mouse intestinal crypt cells. Each mouse received whole body doses of 0.25–8 Gy fast neutrons and were sacrificed 0, 4, 6, 12, 24, 48, and 72 h, respectively, after irradiation. Apoptosis of crypt cells and expression of p53, cyclin A, cyclin B, cyclin D, and cyclin E were measured. The apoptosis in crypt cells was maximal at 4 and 6 h after irradiation, showing a gradual decline at 24 h. The highest frequency of apoptosis was seen at a 1 Gy dose and then declined gradually beyond a 2 Gy dose with high levels of damage. In immunoblot analysis, apoptosis was confirmed to be dependent on p53 function after fast-neutron irradiation. In addition, cyclin B1, cyclin D, and cyclin E were overexpressed in intestinal cells after fast-neutron irradiation and their immunoreactivities were increased strongly in round and oval cells of laminar propria in villi core and crypts. The results of the current study suggest that apoptosis in crypt cells shows a time- and dose-dependent increase after fast-neutron irradiation. In addition, fast-neutron-induced apoptosis in mouse intestinal crypt cells appears to be related to the increase in functional p53 proteins to a level sufficient to initiate apoptosis and up-regulation of cell-cycle-regulated proteins, which may lead to resistance to DNA damage through cell cycle arrest, is involved deeply in protection of gastrointestinal cells after low doses of fast-neutron irradiation. (Mol Cell Biochem 270: 21–28, 2005)

Multiple Congenital Malformation in a Holstein Calf

A 10-day-old male Holstein dairy calf with orthopaedic abnormalities was unable to stand but was alert with a suckle reflex. At necropsy, the calf showed multiple defects, including partial agenesis of the left rib plate, deformed left scapula, shortened left humerus, agenesis of the left kidney, atresia ani and scoliosis. The cause of these anomalies could not be determined. This report is the first to describe partial agenesis of ribs in a calf.

Macrophages, myofibroblasts and mast cells in a rat liver infected with Capillaria hepatica

We trapped a rat (Rattus norvegicus) infected with Capillaria hepatica. At necropsy, grossly yellowish-white nodules (2-3 mm in diameter) were noted to be scattered on the livers surface. Microscopically, granulomatous and fibrotic nodules that contained the eggs and/or adult worms of Capillaria hepatica were detected in the liver. Septal fibrosis was diffusely formed throughout the liver. There were a number of ED1-positive macrophages located in the sinusoids of the pseudolobules. On the double staining, myofibroblasts and mast cells were generally observed within the fibrous septa with the mast cells in close proximity to the myofibroblasts. We suggest that the interactions between macrophages, myofibroblasts and mast cells play a role in the septal fibrosis observed in rats infected by Capillaria hepatica.

Measurement of Estrogen Effect on Bone Turnover by 2H2O Labeling

Estrogen loss has been known to increase bone turnover through accelerated bone resorption coupled by increased bone formation. In the present study, we measured estrogen effect on bone turnover by incorporation of 2H from 2H2O into amino acids. At 6 weeks of age, rats were either sham-operated (sham) or ovariectomized (ovx). Two weeks after surgery, 17β-estradiol (est) was implanted subcutaneously to ovx rats. At 9 weeks of age, 2H2O labeling started by administration of 4% 2H2O to rats for 4 or 7 weeks in drinking water after a single intraperitonial bolus injection with 99.9% 2H2O. Body 2H2O enrichments were stable at approximately 3.0% over labeling period. Fractional replacements (f) of the midshaft femur were higher in the sham group (40.36 ± 4.89% vs 42.47 ± 11.22%) than the ovx (28.57 ± 9.67% vs 37.47 ± 8.34%) and est (26.57 ± 4.00% vs 30.35 ± 5.34%) groups 4 and 7 weeks after labeling, respectively. Ovariectomy-induced bone loss was observed in the trabecular bone along with a significantly increased number of osteoclasts, all of which were normalized after estradiol treatment. Taken together, our results indicate that estrogen deficiency significantly reduces the proportion of newly synthesized bone matrix as well as the total amount of bone matrix. The reduced portion of new matrix in ovx rats, presumably caused by activated osteoclastic degradation, was compensated rapidly with time. In addition, estradiol treatment protected the bone matrix by decreasing bone turnover rate.

ENA Actimineral Resource A restores bone loss and bone quality in ovariectomized rats

The purpose of this study was to examine the effects of ENA Actimineral Resource A (ENA-A), seaweed origin alkaline water, on postmenopausal osteoporosis in ovariectomized (OVX) rats. The 12-week old Wistar rats were divided randomly into 4 groups: ovariectomized (OVX), OVX plus 0.5% ENA-A, OVX plus 5% ENA-A and OVX plus 10% ENA-A. A histopathological analysis indicated that ENA-A could prevent OVX-induced bone loss by increasing femur trabecular bone area in a dose-dependent manner. ENA-A significantly (p < 0.05) increased serum estradiol levels, decreased serum osteocalcin activity and suppressed serum pyridinoline (PYD) levels. The in vitro effects of ENA-A were also studied using MC3T3-E1 cells. ENA-A significantly stimulated cell proliferation and increased both ALP activity and calcium deposition in a dose-dependent manner. These results suggest that the treatment of ovariectomized rats with ENA-A not only prevents bone resorption but also appears to maintain the cancellous bone structure of postmeopausal osteoporosis.

Effects of bio-active ceramic resources in cutaneous wound healing and the role of TGF-β signaling

The wound healing process is a highly orchestrated process, which includes inflammation, re-epithelialization, granulation tissue formation, matrix formation and re-modeling. In this paper, we attempt to determine if bio-active ceramic resource powder particles had an effect on cutaneous wound healing. Furthermore, we investigated its related mechanism and the expression of Smads of cutaneous wound healing, which can be accelerated by bio-active ceramic ointment. Topically applied lesions of 5%, 10% and 15% bio-active ceramic ointment (AO) showed accelerated wound closure, re-epithelialization, and the related immediate down stream of TGF-β (p-Smad2/3 and Smad3) was suppressed. In particular, 10% and 15% AO lesions became closed faster at Days 3 and 4 of post-wound and p-Smad2/3 was also suppressed. All AO lesions showed accelerated mild wound closure at Day 6, but there were no significant difference. Several papers reported that Smad3 may mediate the signaling pathways that is inhibitory to wound healing, as the deletion of Smad3 leads to enhanced re-epithelialization and contraction of the wound area. This study showed that topical, bio-active ceramic ointment applications accelerated wound closure, re-epithelialization and the suppression of Smad proteins (p-Smad2/3, Smad3). The data revealed that the suppression of Smad3, which was induced by bio-active ceramic resources powder particles affected re-epithelialization and cutaneous wound closure. At the end of this paper, we concluded that bio-active ceramic resources affect cutaneous wound healing by accelerating the re-epithelialization of keratinocytes and that is mediated by the suppression of related protein, Smad3.

Alcohol-induced bone degradation and its early detection in the alcohol-fed castrated rats

The objective of this study was to examine alcohol-induced changes of bone in hormone-deficient males using the developed method. In the process of bone resorption, type I collagen crosslinking molecules, pyridinoline (PYD), are released into the circulation and cleared by the kidneys. 2H2O as a tracer has been applied to measure the synthesis rates of slow-turnover proteins and successfully applied to bone collagen synthesis in our hormone deficiency rats. This study demonstrated for the first time, the early changes of the femur bone degradation in hormone-deficient male individuals, more influenced by alcohol through histopathological study, serum PYD assay, and 2H2O labeling. We also observed that serum PYD was a sensitive pathological marker of bone degradation in castrated osteoporosis males and the unique features of 2H2O labeling to measure the bone turnover collagen synthesis rates were excellent markers of bone degradation and aging.

The Ossifying Epulis Accompanying Multi-Nucleated Giant Cells in a Dog

An epulis was occurred on gingiva of 11-year old female dog, Yorkshire terrier. Our case had feature of ossifying epulis but there were a few multi-nucleated giant cells (MGCs). MGCs had osteoclast-like appearance and giant cell epulis usually appears at the site of tooth extraction. Therefore, we suggest that appearance of MGCs in our case may be due to phagocytosis pre-formed osteoid/bone or our case may be mixed epulides of ossifying and giant cell epulis by mixed stimulation of chronic gingivitis and trauma and in flammation by tooth extraction. Thus, MGCs have possibility enough to appear in ossifying epulis, but ossifying epulis accompanying MGCs has not been reported. Therefore, our case may deserves an attention as an unique case and will be helpful to study pathogenesis of giant cell containing lesion of the jaw.