UG0712 is a new ginsenoside extract processed from ginseng leaves. A subchronic toxicity study of UG0712 was conducted in male and female SD rats. Rats were treated with UG0712 at doses of 100, 400 and 1,600 mg/kg/day for 13 weeks, and observed followed by 4-week recovery period at a highest dose. No-treatment-related effects were observed regarding the mortality, ophthalmic examination, urinalysis and histopathology. Although the changes in clinical sign, body weight, organ weight, hematology, and serum biochemistry were observed, they were temporal and pharmacological effects. Based on the present experiment conditions, the no observed adverse effect level was considered to be more than 1,600 mg/kg/day in both sexes of rats.
Animals ; Biochemistry ; Body Weight ; Female ; Hematology ; Humans ; Male ; Mortality ; No-Observed-Adverse-Effect Level ; Organ Size ; Panax* ; Rats* ; Urinalysis

Although ginseng (genus Panax) leaf extract contains high concentrations of bioactive constituents, its effects have been reported in few preclinical studies, and information regarding its toxicity is not sufficient to allow for its clinical use. We evaluated the genotoxicity of UG0712, which is a powdered extract of ginseng leaves. UG0712 did not increase the number of revertant colonies in 4 histidine auxotrophic strains of Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) or in a tryptophan auxotrophic strain of Escherichia coli (WP2uvrA(pKM101)) at any concentration evaluated, either in the absence or presence of the metabolic activation system. There was no significant increase in the number of metaphase cells with structural or numerical aberrations in the UG0712-treated groups compared to the concurrent vehicle control at any dose, regardless of the presence of the metabolic activation system. Oral administration of the extract at doses up to 2,000 mg/kg in male mice did not increase the frequency of micronucleated polychromatic erythrocytes in the bone marrow, and did not result in any significant clinical signs, body weight loss, gross findings, or mortality. These results suggest that UG0712 does not act as a mutagenic or genotoxic material at the concentrations evaluated.
Administration, Oral ; Animals ; Biotransformation ; Body Weight ; Bone Marrow ; Chromosome Aberrations ; Erythrocytes ; Escherichia coli ; Histidine ; Humans ; Male ; Metaphase ; Mice ; Mortality ; Panax* ; Salmonella typhimurium ; Tryptophan

New supplements with preventive effects against skin photodamage are receiving increasing attention. This study evaluated the anti-photoaging effects of salmon nasal cartilage proteoglycan (SPG), acting as a functional material for skin health. We administered SPG to in vitro and in vivo models exposed to ultraviolet B (UVB) radiation and assessed its moisturizing and anti-wrinkle effects on dorsal mouse skin and keratinocytes and dermal fibroblasts cell lines. These results showed that SPG restored the levels of filaggrin, involucrin, and AQP3 in the epidermis of UVB-irradiated dorsal skin and keratinocytes, thereby enhancing the keratinization process and water flow. Additionally, SPG treatment increased the levels of hyaluronan and skin ceramide, the major components of intercellular lipids in the epidermis. Furthermore, SPG treatment significantly increased the levels of collagen and procollagen type 1 by down-regulating matrix metalloproteinase 1, which play a crucial role in skin fibroblasts, in both in vitro and in vivo models. In addition, SPG strongly inhibited mitogen-activated protein kinase (MAPKs) signaling, the including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. These findings suggest that dietary SPG may be an attractive functional food for preventing UVB-induced photoaging. And this SPG product may provide its best benefit when treating several signs of skin photoaging.

OBJECTIVE: To define the molecular basis of TGF-beta1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-beta1, TGF-beta1 receptors, and Smads, the regulators of the TGF-beta1 signaling pathway, in human cervical cancers. METHODS: Expression of TGF-beta1, TGF-beta1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-beta1, TGF-beta1 receptors and Smads was also measured by quantitative genomic PCR. RESULTS: Abnormal overexpression of TGF-beta1 and abnormal reduction of type II TGF-beta1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis. CONCLUSION: Our study demonstrates that disruption of TGF-beta/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-beta/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-beta1 1's tumor suppression function.
Humans ; Polymerase Chain Reaction ; RNA, Messenger ; Transforming Growth Factor beta1 ; Uterine Cervical Neoplasms

PURPOSE: Occult papillary thyroid carcinomas (OPC) are defined as tumors measuring <15 mm. These tumors are believed to be a less aggressive subset of papillary cancers. They generally behave more like benign lesions and are often more conservatively treated. However, it is unclear if a cancer 1.0 to 1.5 cm in diameter will have a similar favorable clinical behavior as tumors <1.0 cm (micropapillary thyroid carcinoma). Therefore, a retrospective chart review study of patients with OPC in order was carried out in order to answer this question and characterize the biology and optimal treatment for OPCs. METHODS: From October 2001 to January 2007, Among the impalpable thyroid nodules detected incidentally during screening examinations, 260 patients underwent surgery for occult papillary thyroid cancer (OPC) at Kangnam Cha University hospital. The data from these patients was analyzed retrospectively. The mean follow up period was 25.6 +/- 14.5 (max: 63, min: 1) months. RESULTS: The mean age of these patients was 42.8 years, and 233 (89.5%) were female. 46.2% of patients underwent a total or neartotal thyroidectomy, and 54.6% underwent a central lymph node dissection. Of the 260 patients, 55 (21.2%) had lymph node metastases. The OPC presented with signs of aggressiveness including multifocality (34.2%), bilaterality (17.7%), capsular invasion (52.7%), and lymph node metastases (21.2%). A progressively increasing frequency of the signs of tumor aggressiveness was observed with increasing tumor size at presentation. LN metastases were associated with the tumor size (P=0.0063), extracapsular invasion (P=0.0015) and multfocallity (P=0.0020). However, there was no association with age and gender. With a follow-up of up to 63 months, 3 patients had a local recurrence (0.014%). No patients currently have active disease and no patients with OPC died during this period. CONCLUSION: In OPC patients, there is a progressively increasing frequency of the signs of tumor aggressiveness with increasing tumor size. Moreover, a small size itself cannot guarantee low risk and low recurrence rate. The prevalence of LN metastases and extracapsular invasion were higher in those with a tumor size >0.5 cm. A near-total or total thyroidectomy with a central lymph node dissection is the preferred treatment. The early detection and treatment of OPC might be warranted through the routine use of thyroid USG and USG-guided FNA.
Biology ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; Mass Screening ; Neoplasm Metastasis ; Prevalence ; Recurrence ; Retrospective Studies ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroid Nodule ; Thyroidectomy

BACKGROUND: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. METHODS: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. RESULTS: Aloe QDM complex down-regulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1beta and -6) and HIF1alpha mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-kappaB p65 from the cytosol in the WAT. CONCLUSION: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.
Adipogenesis ; Adipose Tissue ; Adipose Tissue, White ; Aloe ; AMP-Activated Protein Kinases ; Animals ; Blotting, Western ; Cytokines ; Cytosol ; Developed Countries ; Diabetes Mellitus, Type 2 ; Diet ; Diet, High-Fat ; Humans ; Inflammation ; Macrophages ; Male ; Mice ; Mice, Obese ; Muscles ; NF-kappa B ; Obesity ; Receptors, Scavenger ; RNA, Messenger ; Thiazolidinediones

BACKGROUND: Obesity is a major health problem and leads to metabolic diseases such as type 2 diabetes, insulin resistance and hyperlipidemia. Recently, it was reported that aloe QDM complex, composed of processed aloe vera gel, aloesin and chromiun could improve insulin sensitivity by enhancing 5' adenosine monophosphate-activated protein (AMPK) activity and has an anti-inflammatory effect by reducing the level of pro-inflammatory cytokines. It is also known that aloe QDM complex can reduce body weight, body fat mass and insulin resistance in type 2 diabetes patients. The purpose of this study was to assess for possible synergistic effects of weight-bearing circuit training and aloe QDM complex supplementation on body composition, physical fitness, blood profile and diabetes risk factors. METHODS: Study subjects included 19 participants randomly assigned to the Exercise group (Ex, n=9) and to the Exercise with aloe QDM complex group (Q-Ex, n=10). Both groups participated in weight-bearing circuit training 3 times a week for 4 weeks and took a capsule composed of either aloe (aloe QDM complex) or soy bean (placebo), 1100 mg/day for 4 weeks. Body composition was measured by dual-energy x-ray absorptiometry. Grip strength, flexibility, curl-up, balance, agility, Sargent jump and VO2max were measured, as well as fasting blood samples taken. RESULTS: After 4 weeks of weight-bearing circuit training and aloe QDM complex supplementation, the significant interactions (time x intervention) between the groups regarding body fat percentage (F=7.024, P=0.017) and body fat mass (F=5.243, P=0.035) were calculated. There were significant differences in body fat percentage (P=0.029) and body fat mass (P=0.039). No significant interaction was observed in physical fitness, blood profile and diabetes risk factors. CONCLUSIONS: In this study, the combination of weight-bearing circuit training and aloe QDM complex supplementation showed a positive effect for reducing body fat mass, and could be an effective intervention for managing obesity.
Absorptiometry, Photon ; Adenosine ; Adipose Tissue ; Aloe* ; Body Composition ; Body Weight ; Cytokines ; Fasting ; Female ; Hand Strength ; Humans ; Hyperlipidemias ; Insulin Resistance ; Metabolic Diseases ; Middle Aged* ; Obesity ; Physical Fitness ; Pliability ; Risk Factors ; Soybeans ; Weight-Bearing*

BACKGROUND: Obesity is a major health problem and leads to metabolic diseases such as type 2 diabetes, insulin resistance and hyperlipidemia. Recently, it was reported that aloe QDM complex, composed of processed aloe vera gel, aloesin and chromiun could improve insulin sensitivity by enhancing 5' adenosine monophosphate-activated protein (AMPK) activity and has an anti-inflammatory effect by reducing the level of pro-inflammatory cytokines. It is also known that aloe QDM complex can reduce body weight, body fat mass and insulin resistance in type 2 diabetes patients. The purpose of this study was to assess for possible synergistic effects of weight-bearing circuit training and aloe QDM complex supplementation on body composition, physical fitness, blood profile and diabetes risk factors. METHODS: Study subjects included 19 participants randomly assigned to the Exercise group (Ex, n=9) and to the Exercise with aloe QDM complex group (Q-Ex, n=10). Both groups participated in weight-bearing circuit training 3 times a week for 4 weeks and took a capsule composed of either aloe (aloe QDM complex) or soy bean (placebo), 1100 mg/day for 4 weeks. Body composition was measured by dual-energy x-ray absorptiometry. Grip strength, flexibility, curl-up, balance, agility, Sargent jump and VO2max were measured, as well as fasting blood samples taken. RESULTS: After 4 weeks of weight-bearing circuit training and aloe QDM complex supplementation, the significant interactions (time x intervention) between the groups regarding body fat percentage (F=7.024, P=0.017) and body fat mass (F=5.243, P=0.035) were calculated. There were significant differences in body fat percentage (P=0.029) and body fat mass (P=0.039). No significant interaction was observed in physical fitness, blood profile and diabetes risk factors. CONCLUSIONS: In this study, the combination of weight-bearing circuit training and aloe QDM complex supplementation showed a positive effect for reducing body fat mass, and could be an effective intervention for managing obesity.
Absorptiometry, Photon ; Adenosine ; Adipose Tissue ; Aloe* ; Body Composition ; Body Weight ; Cytokines ; Fasting ; Female ; Hand Strength ; Humans ; Hyperlipidemias ; Insulin Resistance ; Metabolic Diseases ; Middle Aged* ; Obesity ; Physical Fitness ; Pliability ; Risk Factors ; Soybeans ; Weight-Bearing*

OBJECTIVE: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that transcriptional inactivation of FHIT, as a consequence of aberrant 5'-CpG island methylation, plays an important role in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5'-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer. METHODS: To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR and bisulfite DNA sequencing. RESULTS: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological characteristics. CONCLUSION: In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5'-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of FHIT expression and the prognostic factors of cervical cancer in our Korean cohort.
Cohort Studies ; Female ; Histidine ; Humans ; Methylation ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sulfites ; Uterine Cervical Neoplasms