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1.
Infect Control Hosp Epidemiol ; 44(5): 827-829, 2023 05.
Article in English | MEDLINE | ID: mdl-35225184

ABSTRACT

The risk factors of environmental contamination by SARS-CoV-2 are largely unknown. We analyzed 1,320 environmental samples obtained from COVID-19 patients over 1 year. The risk factors for contamination of COVID-19 patients' surrounding environment were higher viral load in the respiratory tract and shorter duration from symptom onset to sample collection.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , RNA , Environmental Pollution , Risk Factors
2.
Viruses ; 14(5)2022 04 23.
Article in English | MEDLINE | ID: mdl-35632623

ABSTRACT

The clinical characteristics and the effect of viral RNA loads on fatality in 56 patients with severe fever with thrombocytopenia syndrome (SFTS) were analyzed. The non-survival group (12 patients) demonstrated a significantly higher mean age (77 years) than the survival group (44 patients, 65 years) (p = 0.003). The survival rates were 91.7% and 8.3% in patients with Ct values ≥30 and differed significantly (p = 0.001) in the survival and non-survival groups, respectively. The survival rates were 52.4% and 47.6% in patients with viral copy numbers ≥10,000 and 94.3% and 5.7% in patients with viral copy numbers <10,000 in the survival and non-survival groups, respectively (p = 0.001). In a multivariate analysis, viral copy numbers and initial Acute Psychologic Assessment and Chronic Health Evaluation II (APACHE II) scores were identified as the factors affecting fatality (p = 0.015 and 0.011, respectively). SFTS viral RNA loads can be useful markers for the clinical prediction of mortality and survival.


Subject(s)
Bunyaviridae Infections , Phlebovirus , Severe Fever with Thrombocytopenia Syndrome , Aged , Humans , RNA, Viral/genetics , Viral Load
3.
Microbiol Spectr ; 9(3): e0067221, 2021 12 22.
Article in English | MEDLINE | ID: mdl-34817278

ABSTRACT

Here, we aimed to investigate the diagnostic value of a serological assay using the nucleocapsid protein developed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection and evaluated its performance using three commercial enzyme-linked immunosorbent assays (ELISAs), namely, Standard E 2019 novel coronavirus disease (COVID-19) total antibody (Ab) ELISA (SD Biosensor), and EDI novel coronavirus COVID-19 IgG and IgM ELISA. A recombinant nucleocapsid protein (rNP) was expressed from plants and Escherichia coli for the detection of serum total Ab. We prospectively collected 141 serum samples from 32 patients with reverse transcription-PCR (RT-PCR)-confirmed COVID-19 and determined the sensitivity and dynamics of their total Ab response. Specificity was evaluated using 158 prepandemic samples. To validate the assays, we evaluated the performance using two different cutoff values. The sensitivity and specificity for each assay were as follows: 92.91% and 94.30% (plant-rNP), 83.69% and 98.73% (SD Biosensor), 75.89% and 98.10% (E. coli-rNP), 76.47% and 100% (EDI-IgG), and 80.39% and 80% (EDI-IgM). The plant-based rNP showed the highest sensitivity and area under the receiver operating characteristic (ROC) curve (0.980) among all the assays (P < 0.05). The seroconversion rate for total Ab increased sequentially with disease progression, with a sensitivity of 100% after 10 to 12 days of post-symptom onset (PSO) for both rNP-plant-based and SD Biosensor ELISAs. After 2 weeks of PSO, the seroconversion rates were >80% and 100% for EDI-IgM and EDI-IgG ELISA, respectively. Seroconversion occurred earlier with rNP plant-based ELISA (5 days PSO) compared with E. coli-based (7 days PSO) and SD Biosensor (8 days PSO) ELISA. We determined that rNP produced in plants enables the robust detection of SARS-CoV-2 total Abs. The assay can be used for serosurvey and complementary diagnosis of COVID-19. IMPORTANCE At present, the principal diagnostic methods for COVID-19 comprise the identification of viral nucleic acid by genetic approaches, including PCR-based techniques or next-generation sequencing. However, there is an urgent need for validated serological assays which are crucial for the understanding of immune responses against SARS-CoV-2. In this study, a highly sensitive and specific serological antibody assay was developed for the detection of SARS-CoV-2 with an overall accuracy of 93.56% using a recombinant nucleoprotein expressed from plants.


Subject(s)
Antibodies, Viral/blood , COVID-19 Testing/methods , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Nucleocapsid Proteins/immunology , Plant Proteins/immunology , Escherichia coli/genetics , Humans , Immunoglobulin G , Immunoglobulin M , Nucleocapsid , Plant Proteins/genetics , Recombinant Proteins/genetics , Recombinant Proteins/immunology , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Seroconversion , Nicotiana/genetics
4.
Sci Rep ; 11(1): 16764, 2021 08 18.
Article in English | MEDLINE | ID: mdl-34408188

ABSTRACT

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients' blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.


Subject(s)
Phlebovirus , RNA, Viral , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Severe Fever with Thrombocytopenia Syndrome , Female , Follow-Up Studies , Humans , Male , Phlebovirus/genetics , Phlebovirus/metabolism , Prospective Studies , RNA, Viral/blood , RNA, Viral/genetics , Severe Fever with Thrombocytopenia Syndrome/blood , Severe Fever with Thrombocytopenia Syndrome/diagnosis , Severe Fever with Thrombocytopenia Syndrome/genetics
5.
Arch Pharm Res ; 42(4): 319-325, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30599056

ABSTRACT

Folate is the generic term for both naturally occurring food folate and folic acid, the fully oxidized monoglutamate form of the vitamin that is used in dietary supplements and fortified foods. It is a water-soluble vitamin B9 and is important for health, growth, and development. As a precursor of various cofactors, folate is required for one-carbon donors in the synthesis of DNA bases and other essential biomolecules. A lack of dietary folate can lead to folate deficiency and can therefore result in several health problems, including macrocytic anemia, elevated plasma homocysteine, cardiovascular disease, birth defects, carcinogenesis, muscle weakness, and difficulty in walking. Several studies have implied that folate might exert a positive effect on skeletal muscle development. However, the precise effects of folate in skeletal muscle development are still poorly understood. Thus, this review provides an updated discussion of the roles of folate in skeletal muscle cell development and the effects of folic acid supplementation on the functions of skeletal muscle cells.


Subject(s)
Folic Acid/pharmacology , Muscle Development/drug effects , Muscle, Skeletal/drug effects , Animals , Humans , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism
6.
Oncol Rep ; 38(3): 1783-1789, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28731136

ABSTRACT

Colorectal cancer (CRC) is the third most frequently diagnosed cancer and cause of cancer-related deaths. Despite advancements in conventional therapeutic approaches to CRC, most patients with CRC die of their disease. There is a need to develop novel therapeutic agents for this malignancy. Therefore, the present study aimed to examine the anticancer effects and elucidate the underlying mechanism of MHY451 in HCT116 human colorectal cancer cells. Treatment with MHY451 inhibited cell growth in a time- and concentration-dependent manner. MHY451 increased the accumulation of cell cycle progression at the G2/M phase. This agent decreased the protein level of cyclin B1 and its activating partners, Cdc25c and Cdc2, whereas it increased the cell cycle inhibitor p21WAF/CIP. The induction of apoptosis was observed by decreased viability, cleavage of poly(ADP-ribose) polymerase (PARP), alteration in the ratio of Bax/Bcl-2 protein expression and reduction of procaspase-8 and -9. Pretreatment with Z-VAD-FMK, a pan-caspase inhibitor, inhibited MHY451-induced apoptosis, indicating that apoptotic cell death by MHY451 was mediated through caspases. Moreover, the apoptotic effect of MHY451 was reactive oxygen species (ROS)-dependent, evidenced by the inhibition of MHY451-induced PARP cleavage and ROS generation by N-acetylcysteine-induced ROS scavenging. Taken together, these results demonstrate that MHY451 exerts anticancer effects by regulating the cell cycle, inducing apoptosis through caspase activation and generating ROS. These results suggest that MHY451 has considerable potential for chemoprevention or treatment of CRC or both.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Colorectal Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Acetylcysteine/metabolism , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Colorectal Neoplasms/metabolism , Cyclin B1/metabolism , G2 Phase Cell Cycle Checkpoints/drug effects , HCT116 Cells , Humans , Poly(ADP-ribose) Polymerases/metabolism , bcl-2-Associated X Protein/metabolism
7.
Int J Oncol ; 51(2): 715-723, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28656256

ABSTRACT

A synthetic analogue of resveratrol, 4-(6-hydroxy-2-naphtyl)-1,3-benzenediol (HS-1793), with improved photosensitivity and stability profiles, has been recently reported to exert anticancer activity on various cancer cells. However, the molecular mechanism of action and in vivo efficacy of HS-1793 in breast cancer cells have not been fully investigated. In the present study, we evaluated the effect of HS-1793 on hypoxia-inducible factor-1α (HIF-1α), which drives angiogenesis and the growth of solid tumors, in addition to the in vivo therapeutic effects of HS-1793 on breast cancer cells. HS-1793 was found to inhibit hypoxia (1.0% oxygen)-induced HIF-1α expression at the protein level, and its inhibitory effect was more potent than that of resveratrol in MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, HS-1793 reduced the secretion and mRNA expression of vascular endothelial growth factor (VEGF), a key mediator of HIF-1-driven angiogenesis, without affecting cell viability. To evaluate the anticancer effects of HS-1793 in vivo, triple-negative MDA-MB-231 breast cancer xenografts were established in nude mice. HS-1793 significantly suppressed the growth of breast cancer tumor xenografts, without any apparent toxicity. Additionally, decreases in Ki-67, a proliferation index marker, and CD31, a biomarker of microvessel density, were observed in the tumor tissue. Expression of HIF-1 and VEGF was also downregulated in xenograft tumors treated with HS-1793. These in vivo results reinforce the improved anticancer activity of HS-1793 when compared with that of resveratrol. Overall, the present study suggests that the synthetic resveratrol analogue HS-1793 is a potent antitumor agent that inhibits tumor growth via the regulation of HIF-1, and demonstrates significant therapeutic potential for solid cancers.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Naphthols/administration & dosage , Resorcinols/administration & dosage , Triple Negative Breast Neoplasms/drug therapy , Vascular Endothelial Growth Factor A/genetics , Animals , Cell Proliferation/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , MCF-7 Cells , Mice , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Xenograft Model Antitumor Assays
8.
Int J Oncol ; 47(6): 2226-32, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26498863

ABSTRACT

The effects of sulforaphane (a natural product commonly found in broccoli) was investigated on hypoxia inducible factor-1α (HIF-1α) expression in HCT116 human colon cancer cells and AGS human gastric cancer cells. We found that hypoxia-induced HIF-1α protein expression in HCT116 and AGS cells, while treatment with sulforaphane markedly and concentration-dependently inhibited HIF-1α expression in both cell lines. Treatment with sulforaphane inhibited hypoxia-induced vascular endothelial growth factor (VEGF) expression in HCT116 cells. Treatment with sulforaphane modulated the effect of hypoxia on HIF-1α stability. However, degradation of HIF-1α by sulforaphane was not mediated through the 26S proteasome pathway. We also found that the inhibition of HIF-1α by sulforaphane was not mediated through AKT and extracellular signal-regulated kinase phosphorylation under hypoxic conditions. Finally, hypoxia-induced HCT116 cell migration was inhibited by sulforaphane. These data suggest that sulforaphane may inhibit human colon cancer progression and cancer cell angiogenesis by inhibiting HIF-1α and VEGF expression. Taken together, these results indicate that sulforaphane is a new and potent chemopreventive drug candidate for treating patients with human colon cancer.


Subject(s)
Anticarcinogenic Agents/pharmacology , Colonic Neoplasms/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Isothiocyanates/pharmacology , Vascular Endothelial Growth Factor A/biosynthesis , Blotting, Western , Cell Hypoxia/drug effects , Cell Hypoxia/physiology , Cell Movement/drug effects , Colonic Neoplasms/metabolism , Enzyme-Linked Immunosorbent Assay , HCT116 Cells , Humans , Sulfoxides
9.
Int J Mol Med ; 36(4): 1073-80, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26310574

ABSTRACT

Folic acid is a water-soluble vitamin in the B-complex group, and an exogenous intake is required for health, growth and development. As a precursor to co-factors, folic acid is required for one-carbon donors in the synthesis of DNA bases and other essential biomolecules. A lack of dietary folic acid can lead to folic acid deficiency and can therefore result in several health problems, including macrocytic anemia, elevated plasma homocysteine levels, cardiovascular disease, birth defects, carcinogenesis, muscle weakness and difficulty in walking. Previous studies have indicated that folic acid exerts a positive effect on skeletal muscle functions. However, the precise role of folic acid in skeletal muscle cell differentiation remains poorly understood. Thus, in the present study, we examined the effects of folic acid on neo-myotube maturation and differentiation using C2C12 murine myoblasts. We found that folic acid promoted the formation of multinucleated myotubes, and increased the fusion index and creatine kinase (CK) activity in a concentration-dependent manner. In addition, western blot analysis revealed that the expression levels of the muscle-specific marker, myosin heavy chain (MyHC), as well as those of the myogenic regulatory factors (MRFs), MyoD and myogenin, were increased in the folic acid-treated myotubes during myogenic differentiation. Folic acid also promoted the activation of the Akt pathway, and this effect was inhibited by treatment of the C2C12 cells with LY294002 (Akt inhibitor). Blocking of the Akt pathway with a specific inhibitor revealed that it was necessary for mediating the stimulatory effects of folic acid on muscle cell differentiation and fusion. Taken together, our data suggest that folic acid promotes the differentiation of C2C12 cells through the activation of the Akt pathway.


Subject(s)
Cell Differentiation/drug effects , Folic Acid/pharmacology , Muscle Development/drug effects , Myoblasts/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Animals , Cell Line , Mice , Myoblasts/cytology
10.
Int J Mol Med ; 36(3): 792-800, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26178971

ABSTRACT

A main characteristic of aging is the debilitating, progressive and generalized impairment of biological functions, resulting in an increased vulnerability to disease and death. Skeletal muscle comprises approximately 40% of the human body; thus, it is the most abundant tissue. At the age of 30 onwards, 0.5­1% of human muscle mass is lost each year, with a marked acceleration in the rate of decline after the age of 65. Thus, novel strategies that effectively attenuate skeletal muscle loss and enhance muscle function are required to improve the quality of life of older subjects. The aim of the present study was to determine whether loquat (Eriobotrya japonica) leaf extract (LE) can prevent the loss of skeletal muscle function in aged rats. Young (5-month-old) and aged (18­19-month-old) rats were fed LE (50 mg/kg/day) for 35 days and the changes in muscle mass and strength were evaluated. The age­associated loss of grip strength was attenuated, and muscle mass and muscle creatine kinase (CK) activity were enhanced following the administration of LE. Histochemical analysis also revealed that LE abrogated the age­associated decrease in cross­sectional area (CSA) and decreased the amount of connective tissue in the muscle of aged rats. To investigate the mode of action of LE, C2C12 murine myoblasts were used to evaluate the myogenic potential of LE. The expression levels of myogenic proteins (MyoD and myogenin) and functional myosin heavy chain (MyHC) were measured by western blot analysis. LE enhanced MyoD, myogenin and MyHC expression. The changes in the expression of myogenic genes corresponded with an increase in the activity of CK, a myogenic differentiation marker. Finally, LE activated the Akt/mammalian target of rapamycin (mTOR) signaling pathway, which is involved in muscle protein synthesis during myogenesis. These findings suggest that LE attenuates sarcopenia by promoting myogenic differentiation and subsequently promoting muscle protein synthesis.


Subject(s)
Aging/drug effects , Eriobotrya/chemistry , Muscle Development/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiology , Plant Extracts/pharmacology , Animals , Cell Line , Creatine Kinase/metabolism , Muscular Atrophy/prevention & control , MyoD Protein/metabolism , Myoblasts/drug effects , Myoblasts/metabolism , Myogenin/metabolism , Myosin Heavy Chains/metabolism , Plant Extracts/chemistry , Plant Leaves/chemistry , Rats , Rats, Sprague-Dawley
11.
J Transl Med ; 13: 203, 2015 Jun 27.
Article in English | MEDLINE | ID: mdl-26116070

ABSTRACT

BACKGROUND: Anthocyanins are major constituents of food colours and have been reported to possess anti-diabetic activities for potential medicinal use. The precise role of anthocyanins in diabetic nephropathy is poorly understood. We investigated whether anthocyanin-rich Seoritae extract (SE) can potentially prevent oxidative stress and lipotoxicity, which are the main causes of renal damage in diabetic nephropathy, via activation of AMP-activated protein kinase (AMPK) and the consequent effects on its target molecules. METHODS: Four groups of male C57BLKS/J db/m and db/db mice were used. Diabetic and non-diabetic mice were orally administered 10 mg/kg body weight SE daily for 12 weeks, starting at 8 weeks of age. RESULTS: db/db mice treated with anthocyanins showed decreased albuminuria. Anthocyanins ameliorated intra-renal lipid concentrations in db/db mice with improvement of glomerular matrix expansion and inflammation, which was related to increased phosphorylation of AMPK and activation of peroxisome proliferator-activated receptor (PPAR) α and PPARγ, and inhibited the activity of acetyl-CoA carboxylase and sterol regulatory element-binding protein 1. Anthocyanins reversed diabetes-induced increases in renal apoptosis and oxidative stress. In cultured human glomerular endothelial cells, anthocyanins prevented high glucose-induced oxidative stress and apoptosis through activation of AMPK in the same manner. CONCLUSIONS: The results revealed that anthocyanins ameliorated diabetic nephropathy in db/db mice via phosphorylation of AMPK, the major energy-sensing enzyme, and the consequent effects on its target molecules, which appeared to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Anthocyanins/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Kidney Diseases/drug therapy , Kidney/pathology , Lipids/toxicity , Plant Extracts/therapeutic use , Animals , Anthocyanins/pharmacology , Apoptosis/drug effects , Cholesterol/metabolism , Collagen Type IV/metabolism , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/pathology , Dinoprost/analogs & derivatives , Dinoprost/urine , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelial Cells/pathology , Enzyme Activation/drug effects , Fatty Acids/metabolism , Humans , Kidney/drug effects , Kidney/enzymology , Kidney Diseases/enzymology , Kidney Diseases/pathology , Male , Mice, Inbred C57BL , Oxidative Stress/drug effects , Phenotype , Phosphorylation/drug effects , Plant Extracts/pharmacology , Glycine max/chemistry , Transforming Growth Factor beta/metabolism , Triglycerides/metabolism , bcl-2-Associated X Protein/metabolism
12.
Exp Ther Med ; 9(4): 1421-1428, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25780445

ABSTRACT

Herbal extracts and dietary supplements may be extracted from the medicinal plants used in traditional Chinese medicine, and are used increasingly commonly worldwide for their benefits to health and quality of life. Thus, ensuring that they are safe for human consumption is a critical issue for the preparation of plant extracts as dietary supplements. The present study investigated extracts of Salvia miltiorrhiza Bunge (S. miltiorrhiza), traditionally used in Asian countries to treat a variety of conditions, as a dietary supplement or as an ingredient in functional foods. Dried S. miltiorrhiza root was extracted with various solvents and under varying extraction conditions, and the effects of the extracts on the viability of five human cancer cell lines were compared. Extracts obtained using 100% ethanol and 100% acetone as solvents exhibited more potent effects compared with extracts obtained using 70 and 30% aqueous ethanol. Furthermore, the active components of S. miltiorrhiza ethanol extracts, known as tanshinones, were investigated. Dihydrotanshinone I was observed to exhibit a higher cytotoxic potential compared with the other tanshinones in the majority of the examined cell lines. Conversely, cryptotanshinone exhibited weak anti-cancer activity. In summary, the results of the present study suggest that the active components obtained from an ethanol extract of S. miltiorrhiza possess the potential to be used as ingredients in functional and health care foods that may be used to improve the effectiveness of chemotherapeutics in the prevention and/or treatment of cancer.

13.
Int J Mol Med ; 35(3): 755-62, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25529824

ABSTRACT

Aging causes phenotypic changes in skeletal muscle progenitor cells that lead to the progressive loss of myogenic differentiation and thus a decrease in muscle mass. The naturally occurring triterpene, ursolic acid, has been reported to be an effective agent for the prevention of muscle loss by suppressing degenerative muscular dystrophy. Leucine, a branched-chain amino acid, and its metabolite, ß-hydroxy-ß-methylbutyric acid, have been reported to enhance protein synthesis in skeletal muscle. Therefore, the aim of the present study was to investigate whether the combination of ursolic acid and leucine promotes greater myogenic differentiation compared to either agent alone in C2C12 murine myoblasts. Morphological changes were observed and creatine kinase (CK) activity analysis was performed to determine the conditions through which the combination of ursolic acid and leucine would exert the most prominent effects on muscle cell differentiation. The effect of the combination of ursolic acid and leucine on the expression of myogenic differentiation marker genes was examined by RT-PCR and western blot analysis. The combination of ursolic acid (0.5 µM) and leucine (10 µM) proved to be the most effective in promoting myogenic differentiation. The combination of ursolic acid and leucine significantly increased CK activity than treatment with either agent alone. The level of myosin heavy chain, a myogenic differentiation marker protein, was also enhanced by the combination of ursolic acid and leucine. The combination of ursolic acid and leucine significantly induced the expression of myogenic differentiation marker genes, such as myogenic differentiation 1 (MyoD) and myogenin, at both the mRNA and protein level. In addition, the number of myotubes and the fusion index were increased. These findings indicate that the combination of ursolic acid and leucine promotes muscle cell differentiation, thus suggesting that this combination of agents may prove to be beneficial in increasing muscle mass.


Subject(s)
Cell Differentiation/drug effects , Leucine/pharmacology , Myoblasts/cytology , Myoblasts/drug effects , Triterpenes/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Creatine Kinase/metabolism , Gene Expression , Histocompatibility Antigens/genetics , Histocompatibility Antigens/metabolism , Mice , Muscle Fibers, Skeletal/metabolism , MyoD Protein/genetics , MyoD Protein/metabolism , Myoblasts/metabolism , Myogenin/genetics , Myogenin/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Ursolic Acid
14.
Int J Oncol ; 45(3): 1250-6, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24969167

ABSTRACT

Betaine is an important human nutrient obtained from various foods and studies in animals and humans have provided results suggesting their pathogenesis of various chronic diseases and points to a role in risk assessment and disease prevention. However, the molecular mechanisms of its activity remain poorly understood and warrant further investigation. This study was performed to investigate the anti-inflammation and tumor preventing capacity of betaine on colitis-associated cancer in mice. In in vivo experiments, we induced colon tumors in mice by azoxymethane (AOM) and dextran sulfate sodium (DSS) and evaluated the effects of betaine on tumor growth. Administration with betaine significantly decreased the incidence of tumor formation with downregulation of inflammation. Treatment with betaine inhibited ROS generation and GSSG concentration in colonic mucosa. Based on the qPCR data, administration of betaine inhibited inflammatory cytokines such TNF-α, IL-6, iNOS and COX-2. In in vitro experiments, LPS-induced NF-κB and inflammatory-related cytokines were inhibited by betaine treatment in RAW 264.7 murine macrophage cells. Our findings suggest that betaine is one of the candidates for the prevention of inflammation-associated colon carcinogenesis.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Betaine/administration & dosage , Colitis/chemically induced , Colitis/drug therapy , Colonic Neoplasms/chemically induced , Colonic Neoplasms/pathology , Animals , Azoxymethane , Cell Line , Dextran Sulfate , Gene Expression Regulation, Neoplastic/drug effects , Glutathione/metabolism , Humans , Macrophages/metabolism , Male , Mice , Mice, Inbred ICR , Reactive Oxygen Species/metabolism
15.
Article in English | MEDLINE | ID: mdl-24701239

ABSTRACT

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.

16.
Int J Oncol ; 44(5): 1599-606, 2014 May.
Article in English | MEDLINE | ID: mdl-24626522

ABSTRACT

Apigenin (4',5,7-trihydroxyflavone) is a natural flavonoid, shown to have chemopreventive and/or anticancer properties in a variety of human cancer cells. The involvement of autophagy in apigenin-induced apoptotic cell death of HCT116 human colon cancer cells was investigated. Apigenin induced suppression of cell growth in a concentration-dependent manner in HCT116 cells. Flow cytometric analyses indicated that apigenin resulted in G2/M phase arrest. This flavone also suppressed the expression of both cyclin B1 and its activating partners, Cdc2 and Cdc25c, whereas the expression of cell cycle inhibitors, such as p53 and p53-dependent p21(CIP1/WAF1), was increased after apigenin treatment. Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles by flow cytometry. Furthermore, the results of the western blot analysis revealed that the levels of LC3-II, the processed form of LC3-I, was increased by apigenin. Treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the levels of PARP cleavage. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in HCT116 colon cancer cells. Autophagy plays a cytoprotective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for colon cancer control.


Subject(s)
Antineoplastic Agents/pharmacology , Apigenin/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Colorectal Neoplasms/pathology , Adenine/analogs & derivatives , Adenine/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Cyclin B1/metabolism , Humans , Signal Transduction/drug effects
17.
Int J Mol Med ; 33(4): 943-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24481288

ABSTRACT

Corosolic acid (CA), a pentacyclic triterpene isolated from Lagerstroemia speciosa L. (also known as Banaba), has been shown to exhibit anticancer properties in various cancer cell lines. However, the anticancer activity of CA on human colorectal cancer cells and the underlying mechanisms remain to be elucidated. In this study, we investigated the effects of CA on cell viability and apoptosis in HCT116 human colon cancer cells. CA dose-dependently inhibited the viability of HCT116 cells. The typical hallmarks of apoptosis, such as chromatin condensation, a sub-G1 peak and phosphatidylserine externalization were detected by Hoechst 33342 staining, flow cytometry and Annexin V staining following treatment with CA. Western blot analysis revealed that CA induced a decrease in the levels of procaspase-8, -9 and -3 and the cleavage of poly(ADP-ribose) polymerase (PARP). The apoptotic cell death induced by CA was accompanied by the activation of caspase-8, -9 and -3, which was completely abrogated by the pan-caspase inhibitor, z-VAD­FMK. Furthermore, CA upregulated the levels of pro-apoptotic proteins, such as Bax, Fas and FasL and downregulated the levels of anti-apoptotic proteins, such as Bcl-2 and survivin. Taken together, our data provide insight into the molecular mechanisms of CA-induced apoptosis in colorectal cancer (CRC), rendering this compound a potential anticancer agent for the treatment of CRC.


Subject(s)
Apoptosis/drug effects , Caspases/metabolism , Colonic Neoplasms/enzymology , Colonic Neoplasms/pathology , Signal Transduction/drug effects , Triterpenes/pharmacology , Cell Cycle Proteins/metabolism , Cell Shape/drug effects , Cell Survival/drug effects , Chromatin/metabolism , Enzyme Activation/drug effects , G1 Phase/drug effects , HCT116 Cells , Humans , Triterpenes/chemistry
18.
Reprod Fertil Dev ; 24(5): 649-55, 2012.
Article in English | MEDLINE | ID: mdl-22697115

ABSTRACT

Varicocele is the most common cause of primary male infertility and is associated with oxidative stress. The aim of the present study was to investigate the effects of anthocyanin on a rat model of varicocele. Twenty-four male rats were divided into four experimental groups: a normal control group, a varicocele-induced control group and two varicocele-induced groups treated with either 40 or 80mgkg(-1), p.o., anthocyanin for 4 weeks. Varicocele was induced by the partial obstruction of the left renal vein. After 8 weeks, the testes and epididymides from rats in all groups were removed, weighed and subjected to histological examination and semen analysis. Apoptosis in the testes was determined by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) and oxidative stress was assessed by measuring 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Although no significant differences in sperm counts were observed among the groups, anthocyanin treatment of the varicocele-induced groups resulted in significantly increased testes weight, sperm motility and spermatogenic cell density (P<0.05). Anthocyanin treatment also significantly decreased apoptotic body count and 8-OHdG concentrations (P<0.05). We suggest that the antioxidant effect of anthocyanin prevented the damage caused by varicocele-induced reactive oxygen species.


Subject(s)
Anthocyanins/pharmacology , Glycine max/chemistry , Seeds/chemistry , Spermatogenesis/drug effects , Varicocele/pathology , Animals , Color , Disease Models, Animal , Drug Evaluation, Preclinical , Male , Organ Size , Rats , Rats, Sprague-Dawley , Seeds/ultrastructure , Sperm Count , Spermatogenesis/physiology , Testis/drug effects , Testis/growth & development , Varicocele/physiopathology
19.
Urol Int ; 88(4): 470-6, 2012.
Article in English | MEDLINE | ID: mdl-22433441

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the effect of cyanidin-3-O-ß-D-glucopyranoside (C3G) concentrated materials from mulberry fruit on improvement and protection of erectile function. MATERIALS AND METHODS: Sprague-Dawley rats (12 weeks old) were divided into three groups (n = 12 in each): normal control, diabetes mellitus (DM), and DM with C3G concentrated material treatment (DM + C3G). DM and DM + C3G group rats received a single injection of streptozotocin (50 mg/kg), and 4 weeks after induction of diabetes, the DM + C3G group rats were treated with daily concentrated material treatment (10 mg/kg) dissolved in water for 8 weeks. After 12 weeks of streptozotocin injections, the rats in each group underwent intracavernosal pressure measurement and then the corporal tissues were sampled. RESULTS: The DM group rats showed markedly lower erectile parameters than those in the control group, whereas rats in the DM + C3G group showed improved erectile function by minimizing corporal apoptosis and increasing the expression of endothelial nitric oxide synthase (NOS) and neuronal NOS protein. A significant increase in 8-hydroxy-2-deoxyguanosine (8-OHdG) was shown in the DM group compared with the normal group. However, in the DM + C3G group, 8-OHdG was statistically significantly reduced compared with the DM group. CONCLUSIONS: The current study is the first to suggest that C3G concentrated materials may have a potency to improve and protect erectile function under conditions of diabetes-induced oxidative stress.


Subject(s)
Anthocyanins/pharmacology , Antioxidants/pharmacology , Diabetes Complications/prevention & control , Diabetes Mellitus, Experimental/drug therapy , Erectile Dysfunction/prevention & control , Morus , Oxidative Stress/drug effects , Penile Erection/drug effects , Penis/drug effects , 8-Hydroxy-2'-Deoxyguanosine , Animals , Anthocyanins/isolation & purification , Antioxidants/isolation & purification , Apoptosis/drug effects , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Diabetes Complications/etiology , Diabetes Complications/metabolism , Diabetes Complications/pathology , Diabetes Complications/physiopathology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Erectile Dysfunction/etiology , Erectile Dysfunction/metabolism , Erectile Dysfunction/pathology , Erectile Dysfunction/physiopathology , Fruit , In Situ Nick-End Labeling , Male , Morus/chemistry , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide Synthase Type III/metabolism , Penis/metabolism , Penis/pathology , Penis/physiopathology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism
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