Hun-Mo Yang

Acute exercise induces FGF21 expression in mice and in healthy humans.

Fibroblast growth factor 21 (FGF21) plays an important role in the regulation of energy homeostasis during starvation and has an excellent therapeutic potential for the treatment of type 2 diabetes in rodents and monkeys. Acute exercise affects glucose and lipid metabolism by increasing glucose uptake and lipolysis. However, it is not known whether acute exercise affects FGF21 expression. Here, we showed that serum FGF21 level is increased in mice after a single bout of acute exercise, and that this is accompanied by increased serum levels of free fatty acid, glycerol and ketone body. FGF21 gene expression was induced in the liver but not in skeletal muscle and white adipose tissue of mice after acute exercise, and further, the gene expression levels of hepatic peroxisome proliferator-activated receptor α (PPARα) and activating transcription factor 4 (ATF4) were also increased. In addition, we observed increased FGF21 level in serum of healthy male volunteers performing a treadmill run at 50 or 80% VO2max. These results suggest that FGF21 may also be associated with exercise-induced lipolysis in addition to increased catecholamines and reduced insulin.

Fabrication and biocompatibility of novel bilayer scaffold for skin tissue engineering applications

In this study, a novel bilayer scaffold composed of electrospun polycaprolactone and poly(lacto-co-glycolic acid) (PCL/PLGA) membrane and glutaraldehyde (3.5% v/v) cross-linked chitosan/gelatin hydrogel was fabricated using two methods: electrospinning of the membrane onto the lyophilized hydrogel (BS-1) and membrane underlaying and casting method (BS-2). The morphology of the fabricated scaffolds was examined by scanning electron microscope (SEM). Mechanical strength, porosity, swelling capacity, and biodegradation rates of the scaffolds were also characterized. The in vitro biocompatibility of the materials was investigated by assessing cytotoxicity and cell proliferation on the material was measured using MTT assay. In addition, cell adhesion on the material was investigated by SEM. The BS-2 was grafted in Sprague-Dawley rats to determine its in vivo behavior and biocompatibility. The experimental results showed that the addition of the membrane layer to the hydrogel decreased swelling and degradation rates and provided ease of handling during implantation. Grafted BS-2 showed normal wound healing and no major inflammatory reaction was observed.

On stabilization of PVPA/PVA electrospun nanofiber membrane and its effect on material properties and biocompatibility

A novel nanofiber membrane was fabricated by electrospinning composed of polyvinyl phosphonic acid (PVPA) and polyvinyl alcohol (PVA). Stabilization was done due to the high dissolvability of the membrane when in contact with water. Physical treatment was done by exposure to heat at 150°C in a vacuum environment at different periods of time. Chemical crosslinking was done by immersion inmethanol and methanol/ glutaraldehyde. A heat-exposed membrane was also further crosslinked chemically. All conditions were compared with regards to its effect on the material properties of the membranes and its biological response in vitro with MG-63 osteoblast-like cell line. Visual examination and dimensional analyses showed that heat treatment produced discoloration on the membrane surface and chemical crosslinking reduced membrane dimensions. Tensile strength and strain improved in crosslinked membranes compared to noncrosslinked counterpart. Swelling and degradation was also investigated and was seen to vary depending on the crosslinking condition. Biocompatibility was observed to be more favorable in heat-treated membranes.

The effects of running a 308 km ultra-marathon on cardiac markers.

Abstract The aim of this study was to investigate the expression of cardiac strain and damage in 18 male marathoners with average age of 52.8±5.0 years running at a 308 km ultra-marathon. Blood samples were collected at pre-race, 100 km, 200 km and 308 km check points for the analysis of cardiac muscle injury markers, creatine kinase (CK), creatine kinase–myocardial band (CK–MB), cardiac troponin I (cTnI) and cardiac muscle strain marker, N-terminal pro-brain natriuretic peptide (NT-proBNP). The CK levels increased 1127.2±507.9 IU/L, 5133.8±2492.7 IU/L and 4958.4±2087.9 IU/L at 100 km, 200 km and 308 km, respectively, compared to the pre-race levels. The CK–MB levels increased 20.2±11.2 ng/mL, 73.3±35.6 ng/mL and 68.6±42.6 ng/mL at 100, 200 and 308 km, respectively, compared to the pre-race levels. The CK–MB/CK ratio showed that the CK–MB mass index was within the normal range (<2.5%) at 100 km, 200 km and 308 km. The cTnI levels showed no significant difference in all check points. The NT-proBNP levels increased 146.55±92.7 pg/mL, 167.95±111.9 pg/mL and 241.23±121.2 pg/mL at 100, 200 and 308 km, respectively, compared to the pre-race levels. The normal CK–MB mass index (<5.0 ng/mL) and the absence of an increase in the cTnI levels during the 308 km ultra-marathon suggested that no myocardial injury despite an elevation in CK–MB. The increase in NT-proBNP levels probably resulted from continuous hemodynamic cardiac stress and represents a transient physiological myocardial protective response.

The effect of Oligonol intake on cortisol and related cytokines in healthy young men

This study investigated the effects of Oligonol intake on cortisol, interleukin (IL)-1β, and IL-6 concentrations in the serum at rest and after physical exercise loading. Nineteen healthy sedentary male volunteers participated in this study. The physical characteristics of the subjects were: a mean height of 174.2 ± 2.7 cm, a mean weight of 74.8 ± 3.6 kg and a mean age of 22.8 ± 1.3 years. Each subject received 0.5 L water with Oligonol (100 mg/day) (n = 10) or a placebo (n = 9) daily for four weeks. The body composition, the white blood cell (WBC) and differential counts as well as the serum cortisol, IL-1β, and IL-6 concentrations were measured before and after Oligonol intake. The cortisol concentration and serum levels of IL-1β and IL-6 after Oligonol intake were significantly decreased compared to before treatment (P < 0.01, respectively). In addition, the rate of increase of these factors after exercise was decreased compared to the placebo group. There was no change in the WBC and differential cell counts. These results suggest that oral Oligonol intake for four weeks had a significant effect on inhibition of inflammatory markers in healthy young men.

Caffeine Increases Sweating Sensitivity via Changes in Sudomotor Activity During Physical Loading

We assessed the effect of caffeine on sudomotor activity and sweating sensitivity during physical loading. Both physiological responses could occur due to energy expenditure. Subjects were 13 athletically trained males (22.1 ± 3.7 years old, 174.2 ± 5.4 cm tall, and weighing 70.9 ± 4.6 kg, with maximal oxygen consumption [VO(2)max] of 53.6 ± 4.4 mL/kg/minute). The study involved a within-subject, random, crossover design. Tests were performed following the ingestion of 3 mg/kg caffeine. The physical loading involved running for 30 minutes at 60% VO(2)max (24.0 ± 0.5°C, 40 ± 3.0% relative humidity). Tympanic temperature (TYMP) was significantly higher in the caffeine-consuming group (Caffe-I) at pre-exercise (40 minutes after caffeine intake and immediately before running) (P<.05). Mean body temperature (mT(b)) was significantly higher in the Caffe-I group at pre- and post-exercise (30 min after start of running) (P<.05). Onset time of localized sweating was significantly shorter in the Caffe-I group (P<.01), but localized sweat volume and active sweat gland output (per single gland) was significantly higher in the Caffe-I group (P<.001). Activated sweat gland density was significantly increased in the Caffe-I group on the abdomen and thigh (P<.01). In conclusion, caffeine ingestion caused not only increases in TYMP and mT(b) through thermogenesis, but also an increased sweating sensitivity via changes in sudomotor activity.

Effects of Macrophage on Biodegradation of β-tricalcium Phosphate Bone Graft Substitute

Various calcium phosphate bioceramics are distinguished by their excellent biocompatibility and osteoconductivity. Especially, the exceptional biodegradability of β-TCP makes it a bone graft substitute of choice in many clinical applications. The activation of osteoclasts, differentiated from macrophage precursor cells, trigger a cell-mediated resorption mechanism that renders β-TCP biodegradable. Based on this evidence, we studied the biodegradation process of granular-type β-TCP bone graft substitute through in vitro and in vivo studies. Raw 264.7 cells treated with RANKL and M-CSF differentiated into osteoclasts with macrophage-like properties, as observed with TRAP stain. These osteoclasts were cultured with β-TCP nano powders synthesized by microwaveassisted process. We confirmed the phagocytosis of osteoclasts by observing β-TCP particles in their phagosomes via electron microscopy. No damage to the osteoclasts during phagocytosis was observed, nor did the β-TCP powders show any sign of cytotoxicity. We also observed the histological changes in subcutaneous tissues of rats implanted with granule-type β-TCP synthesized by fibrous monolithic process. The β-TCP bone graft substitute was well surrounded with fibrous tissue, and 4 months after implantation, 60% of its mass had been biodegraded. Also, histological findings via H&E stain showed a higher level of infiltration of lymphocytes as well as macrophages around the granule-type β-TCP. From the results, we have concluded that macrophages play an important role in the biodegradation process of β-TCP bone graft substitutes.

The Role of RANTES in a Murine Model of Food Allergy

Food allergy is an important and common health issue, and there is a need to identify and characterize the sensitizing mechanisms. One of the common causes of food allergy is ovalbumin (OVA), a dietary antigen from eggs. We hypothesized that OVA‐induced food allergy in the gut involves the activation of the chemokine regulated on activation, normal T cell expressed and secreted (RANTES), which then recruits eosinophils to lesioned tissue. The purpose of this study was to clarify whether RANTES expression correlates with eosinophil infiltration in the gut of OVA‐sensitized BALB/c mice in response to oral OVA challenge. BALB/c mice were immunized with OVA 1 µg and sensitized after 2 weeks by intragastric administration of OVA. Sensitization to the oral OVA challenge was analyzed by examining eosinophil infiltration into the gut tissue (immunohistochemistry), mucosal eosinophil cationic protein (ECP) concentration, and RANTES mRNA expression (reverse‐transcriptase polymerase chain reaction and Southern blotting) at 3, 6, 12, and 24 h after the challenge. There was marked edema of the intestinal villi, and eosinophil infiltration to the lamina propria peaked at 6 h in OVA‐sensitized mice. RANTES mRNA expression peaked at 3 h and 6 h and declined thereafter. The expression of RANTES mRNA in the allergic mice was much higher than in the nonallergic, normal, or unsensitized control mice. Tissue eosinophilia and intestinal ECP levels were significantly correlated with the RANTES mRNA level. We conclude that RANTES may play a central role in the pathogenesis of food‐mediated gastrointestinal allergy.

Relationships Between IgG, IgM, IgE and Resistance to Reinfection During the Early Phase of Infection with Clonorchis sinensis in Rats

An enzyme linked immunosorbent assay (ELISA) was used to study the correlation between the levels of IgG, IgM and IgE immunoglobulin isotypes and resistance to re‐infection in rats during the first month of infection with Clonorchis sinensis. Rats were infected with Clonorchis sinensis (primary infection), and then treated with praziquantel on the 1st, 3rd, 7th, 14th and 28th day post infection (p.i.). To measure resistance, rats were re‐infected with C. sinensis (secondary infection), 2 weeks after the treatment and worms were recovered 4 weeks later. During the primary infection, significantly increased levels of IgG isotype were observed on days 14 and 28 p.i. (P < 0.001) and IgM levels were significantly increased on 3rd and 28th day (P < 0.001). During the secondary infection, significantly increased levels of IgG isotype were found from 3rd to 28th day and IgE isotype on 7th and 14th day (P < 0.01) while significant levels of IgM were found on the 3rd and 28th day (P < 0.05). Furthermore, significant differences of worm numbers between infected and control group was found on the 14th and 28th day (P < 0.001). An inverse correlation between the IgG levels and the resistance to re‐infection was also observed (r = − 0.948, P = 0.004), indicating that the resistance to reinfection is highly associated with the levels of IgG during the early phase of infection, and then with the IgM and IgE.

The Influence of Alpha-fetoprotein on Natural Suppressor Cell Activity and Ehrlich Carcinoma Growth.

The influence of alpha-fetoprotein (AFP) on the bone marrow (BM) natural suppressor (NS) cells of intact Ehrlich carcinoma -bearing CBA mice was studied. Bone marrow NS cells were fractionated into three fractions by isopycnic centrifugation on percoll gradients: NS1 (rho=1.080 g/ml), NS2 (rho=1.090 g/ml) and NS3 (1.100>rho>1.090 g/ml). These fractions were highly different in their sensitivity to known NS cell inductors (interleukin (IL)-2, IL-3 or histamine). None of the NS fractions isolated from the intact mice spontaneously produced antiproliferative activity, however, they showed a high level of NS (antiproliferative and natural killer cell inhibitory) activity under the influence of AFP. A single injection of AFP to intact mice led to an increase of spontaneous NS activity and the inhibition of natural killer cell activity. NS activity, especially NS2, was increased in when tumor cells were subcutaneously inoculated three days after AFP injection. In the AFP-treated mice, the tumor mass at 14 days was 60% larger than that in the untreated mice. Our data confirmed that AFP is a tumor marker that can inhibit cancer immunity and plays a role in cancer pathogenesis.