UNLABELLEDOBJECTIVE To investigate the effect of Guanxinkang (GXK) on ATP-sensitive potassium channel in myocardial cells of rat with ischemic/reperfusion injury and its possible mechanism for cardiac vascular protection and anti-myocardial ischemia.

METHODSWistar rats were established into I/R injured models by 10 min perfusion--30 min no-flow ischemia--45 min reperfusion, and divided into 5 groups: the I/R model group and 4 treatment groups treated respectively with glibenclamide, pinacidil, GXK and GXK+glibenclamide. Rats' heart were isolated for detecting Ca(2+)-Mg(2+)-ATPase, Na(+)-K(+)-ATPase activity in myocardial cells, and the changes of current in ATP-sensive potassium channel (K(ATP)) was recorded by whole patch clamp technique. Data were controlled by those taken from normal rats in a control group.

RESULTSK(ATP) in the GXK treated group were higher than that in the I/R model group; and similar to that in the pinacidil treated group (P > 0.05). As compared with the model group, activities of Ca(2+)-Mg(2+)-ATPase and Na(+)-K(+)-ATPase in the GXK treated group were increased significantly (P < 0.05).

CONCLUSIONGXK shows definite intervention effect on myocardial I/R injury; which is possibly by way of furthering the opening of K(ATP) channel, decreasing Ca2+ influx, and inhibiting Ca2+ overload.

Animals ; Calcium ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardial Ischemia ; metabolism ; physiopathology ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Wistar

SINE-VNTR-Alu (SVA) elements are present in hominoid primates and are divided into 6 subfamilies (SVA-A to SVA-F) and active in the human population. Using a bioinformatic tool, 22 SVA element-associated genes are identified in the human genome. In an analysis of genomic structure, SVA elements are detected in the 5' untranslated region (UTR) of HGSNAT (SVA-B), MRGPRX3 (SVA-D), HYAL1 (SVA-F), TCHH (SVA-F), and ATXN2L (SVA-F) genes, while some elements are observed in the 3'UTR of SPICE1 (SVA-B), TDRKH (SVA-C), GOSR1 (SVA-D), BBS5 (SVA-D), NEK5 (SVA-D), ABHD2 (SVA-F), C1QTNF7 (SVA-F), ORC6L (SVA-F), TMEM69 (SVA-F), and CCDC137 (SVA-F) genes. They could contribute to exon extension or supplying poly A signals. LEPR (SVA-C), ALOX5 (SVA-D), PDS5B (SVA-D), and ABCA10 (SVA-F) genes also showed alternative transcripts by SVA exonization events. Dominant expression of HYAL1_SVA appeared in lung tissues, while HYAL1_noSVA showed ubiquitous expression in various human tissues. Expression of both transcripts (TDRKH_SVA and TDRKH_noSVA) of the TDRKH gene appeared to be ubiquitous. Taken together, these data suggest that SVA elements cause transcript isoforms that contribute to modulation of gene regulation in various human tissues.
3' Untranslated Regions ; 5' Untranslated Regions ; Exons ; Gene Expression Profiling ; Genome, Human ; Genomics ; Humans ; Lung ; Organ Specificity ; Poly A ; Primates ; Protein Isoforms

Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration- (>50 μM) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to 500 μM. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at 25 μM. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.
Acetylcysteine ; Cell Line ; Cytoplasm ; Fibroblasts ; GTP-Binding Proteins ; Hepatocytes ; Humans ; Hyperglycemia ; Hypoglycemia ; Larva ; Liver ; Mortality ; Reactive Oxygen Species* ; RNA, Small Interfering ; Weight Gain ; Zebrafish

This study was performed to develop a children's dietary life safety index required by the Special Act on Safety Management of Children's Dietary Life enacted in 2009. An analytical hierarchy process was used to obtain initial weights of dietary life safety evaluation indicators. The Delphi method was applied to develop the weights along with 98 food and nutrition professionals. Three representative policy indicators, nine strategy indicators, 11 main evaluation indicators, and 20 detailed evaluation indicators were selected for the children's dietary life safety assessment. Three policy indicators and nine strategy indicators were the following: children's food safety indicator (support level of children' safety, safety management level of children's favorite foods, and safety management level of institutional food service), children's nutrition safety indicator (management level of missing meals and obesity, nutrition management level of children's favorite foods, and nutrition management level of institutional food service), and children's perception and practice level indicator ("Dietary Life Law" perception level, perception, and practice level for dietary life safety management, perception, and practice level for nutrition management). Weights of 40%, 40%, and 20% were given for the three representative policy indicators. The relative importance of nine strategic indicators, which were determined by the Delphi method is as follows: For children's food safety, support level of children's safety, safety management level of children's favorite foods, and safety management level of institutional food service were given weights of 12%, 9%, and 19%, respectively. For children's nutrition safety, the missing meals and obesity management level, nutrition management level of children's favorite foods, and the nutrition management level of institutional food service were given weights of 13%, 11%, and 16%, respectively. The "Dietary Life Law" perception level, perception and practice level of dietary life safety management, and perception and practice level of nutrition management were given weights of 4%, 7%, and 9%, respectively.
Food Safety ; Food Services ; Korea ; Meals ; Obesity ; Safety Management ; Weights and Measures

BACKGROUND: Adipose-derived stem cells (ADSCs) exert immunomodulatory effects in the treatment of transplant rejection. This study aimed to evaluate the effects of ADSCs on the skin graft survival in a human-to-rat xenograft transplantation model and to compare single and multiple injections of ADSCs. METHODS: Full-thickness human skin xenografts were transplanted into the backs of Sprague–Dawley rats. The rats were injected subcutaneously on postoperative days 0, 3, and 5. The injections were as follows: triple injections of phosphate-buffered saline (PBS group), a single injection of ADSCs and double injections of PBS (ADSC 9 1 group), and triple injections of ADSCs (ADSC 9 3 group). The immunomodulatory effects of ADSCs on human skin xenografts were assessed. RESULTS: Triple injections of ADSCs considerably delayed cell-mediated xenograft rejection compared with the PBS and ADSC 9 1 groups. The vascularization and collagen type 1–3 ratios in the ADSC 9 3 group were significantly higher than those in the other groups. In addition, intragraft infiltration of CD3-, CD4-, CD8-, and CD68-positive cells was reduced in the ADSC 9 3 group. Furthermore, in the ADSC 9 3 group, the expression levels of proinflammatory cytokine interferon-gamma (IFN-c) were decreased and immunosuppressive prostaglandin E synthase (PGES) was increased in the xenograft and lymph node samples. CONCLUSION This study presented that triple injections of ADSCs appeared to be superior to a single injection in suppressing cell-mediated xenograft rejection. The immunomodulatory effects of ADSCs are associated with the downregulation of IFN-c and upregulation of PGES in skin xenografts and lymph nodes.

Increased fat intake is known to be a major cause of prostate cancer. In this study, we investigated the effect of dietary high fat on prostate intraepithelial neoplasia using transgenic adenocarcinoma mouse prostate (TRAMP) mice. Six-week-old male TRAMP mice were fed AIN93G (control group, 4.0 kcal/kg, n=6) and AIN93G-HFD (experimental group, 4.8 kcal/kg, n=7) for 10 weeks. Prostate histopathology, urogenital tract (UGT) weight, epididymal white adipose tissue weight, argyrophilic nucleolar organizer regions (AgNORs) counts, and serum leptin levels were examined. AIN93G-HFD fed group showed progressed neoplastic lesions in the prostate (P<0.05) compared to AIN93G fed group. AIN93G-HFD intake resulted in a increase in the weight of UGT (P<0.05) and epididymal white adipose tissue. The number of Ag-NOR positive dots significantly increased in each prostate lobe and final serum leptin levels in AIN93G-HFD fed group were about twice those of AIN93G fed group (P<0.05). Dietary high fat was related to the prostate cancer progression in the early stage of TRAMP mice and increased serum leptin levels, suggesting that the regulation of dietary components could delay the progression of prostate cancer.
Adenocarcinoma ; Adipose Tissue, White ; Animals ; Humans ; Leptin ; Male ; Mice ; Nucleolus Organizer Region ; Prostate ; Prostatic Neoplasms

Severe acute respiratory syndrome (SARS) is a life-threatening disease for which accurate diagnosis is essential. Although many tools have been developed for the diagnosis of SARS, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. We have raised polyclonal and monoclonal antibodies (Abs) using a recombinant form of the SARS virus nucleocapsid protein. Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.
Antibodies, Viral/*immunology ; Blotting, Western ; Coronavirus 229E, Human/*immunology ; Coronavirus OC43, Human/*immunology ; Cross Reactions ; Humans ; Nucleocapsid Proteins/genetics/*immunology ; Recombinant Proteins/immunology ; SARS Virus/genetics/*immunology ; Severe Acute Respiratory Syndrome/diagnosis/*immunology

Sarcoidosis is a granulomatous disease that can involve any organ, although it primarily involves the lungs, intrathoracic lymph nodes, skin, and eyes. We present a case of sarcoidosis with pancytopenia, resulting from bone marrow involvement. A 35-year-old man was admitted to hospital for chronic cough and blurred vision. On chest computed tomography, there were multiple pulmonary nodules and mediastinal lymph nodes enlargement. As the patient also showed pancytopenia, we performed a bone marrow biopsy, as well as a transbronchial lung biopsy. Both biopsies showed non-caseating granulomas. We diagnosed the patient with sarcoidosis with pulmonary, bone marrow, uvea, liver and spleen involvement. After oral steroid therapy, the patient's symptoms as well as his pancytopenia improved. We present this case to demonstrate the significance of bone marrow biopsy in cases of sarcoidosis with pancytopenia, as well the possibility of clinical improvement with steroid treatment.
Adult ; Biopsy ; Bone Marrow ; Cough ; Eye ; Granuloma ; Humans ; Liver ; Lung ; Lymph Nodes ; Multiple Pulmonary Nodules ; Pancytopenia ; Sarcoidosis ; Skin ; Spleen ; Thorax ; Uvea ; Vision, Ocular

The effect of NaCl plus 3% chitosan on the systolic blood pressure of spontaneously hypertensive rats (SHR) were evaluated and compared with NaCl plus KCl (NaCl, 49.36% + KCl 49.36%) and chitosan or NaCl treatment alone. In SHR, administration of NaCl plus chitosan (44 mM Na/day) for two months significantly decreased the systolic blood pressure greater than of NaCl plus KCl and NaCl alone. NaCl plus chitosan resulted, though not statistically significant, in decreased urinary Na+ excretion and decreased blood urea nitrogen levels. Urinary creatinine of NaCl plus chitosan was slightly decreased compared to 3 treated groups. Serum electrolytes levels, however, remained unchanged. The combination of NaCl and chitosan may be superior to the conventional use of NaCl plus KCl or NaCl alone in the prevention of hypertension. Even though these supplementary diets have demonstrated potential anti-hypertensive effects in the experimental animal model, further research is needed before any recommendations can be made.
Angiotensin I/blood ; Angiotensin II/biosynthesis ; Animals ; Blood Pressure/*drug effects/physiology ; Blood Urea Nitrogen ; Body Weight/drug effects ; Chitosan/*administration & dosage ; Chlorides/blood/urine ; Creatinine/urine ; Heart/physiology ; Histocytochemistry ; Hypertension/*prevention & control ; Kidney/physiology ; Male ; Potassium/blood/urine ; Potassium Chloride/administration & dosage ; Random Allocation ; Rats ; Rats, Inbred SHR ; Sodium/blood/urine ; Sodium Chloride, Dietary/*administration & dosage ; Systole/drug effects/physiology

Although rodents have previously been used in ecotoxicological studies, they are expensive, time-consuming, and are limited by strict legal restrictions. The present study used a zebrafish (Danio rerio) model and generated data that was useful for extrapolating toxicant effects in this system to that of humans. Here we treated embryos of the naive-type as well as a transiently transfected zebrafish liver cell line carrying a plasmid (phAhREEGFP), for comparing toxicity levels with the well-known aryl hydrocarbon receptor (AhR)-binding toxicants: 3,3',4,4',5-pentachlorobiphenyl (PCB126), 2,3,7,8-tetrachlorodibenzo-p-dioxin, and 3-methylcholanthrene. These toxicants induced a concentration-dependent increase in morphological disruption, indicating toxicity at early life-stages. The transient transgenic zebrafish liver cell line was sensitive enough to these toxicants to express the CYP1A1 regulated enhanced green fluorescent protein. The findings of this study demonstrated that the zebrafish in vivo model might allow for extremely rapid and reproducible toxicological profiling of early life-stage embryo development. We have also shown that the transient transgenic zebrafish liver cell line can be used for research on AhR mechanism studies.
Animals ; Benz(a)Anthracenes/toxicity ; Cell Line ; Green Fluorescent Proteins ; Hepatocytes/cytology/physiology ; Larva/drug effects/growth & development ; Lethal Dose 50 ; Polychlorinated Biphenyls/toxicity ; Tetrachlorodibenzodioxin/toxicity ; Water Pollutants, Chemical/*adverse effects ; Zebrafish/*physiology