Antihyperlipidemic and Antioxidant Effects of C-phycocyanin in Golden Syrian Hamsters Fed with a Hypercholesterolemic Diet.

Hyperlipidemia and oxidation play major roles upon cardiovascular diseases (CVDs). C-phycocyanin (CPC), the major component in blue-green algae, possesses antiinflammatory and radical scavenging properties. Herein we aimed to investigate the effect of CPC upon lipid metabolism and its antioxidant effects. Golden Syrian hamsters were randomly assigned to five groups: (1) control; (2) 0.2% cholesterol; (3) 0.2% cholesterol+ 1% lopid; (4) 0.2% cholesterol+ 0.25% CPC; and (5) 0.2% cholesterol+ 1.25% CPC. All animals were sacrificed after 8-week feeding. Serum cholesterol, triglyceride (TG), low-density lipoprotein (LDL), glutamate-oxaloacetate transaminase (GOT), and glutamate-pyruvate transaminase (GPT) were examined. The diene conjugation in the Cu(2+)-mediated oxidation of LDL was measured. The protein levels of several antioxidative enzymes including catalase (CAT), superoxide dismutases (SOD), and glutathione peroxidase (GPx) of liver were assayed. HepG2 cells were cultured in medium containing various concentrations of CPC (0, 1, 15, and 30 µM). The mRNA concentrations of LDL receptor, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase, SOD-1 and GPx of HepG2 cells in each group were analyzed. CPC was effective in lowering serum cholesterol, total cholesterol (TC), TG, LDL, GOT, and GPT. CPC was found to decrease the malondialdehyde (MDA) equivalents and delay the diene conjugation in the Cu(2+)-mediated oxidation of LDL. CPC increase the enzyme expressions of CAT, SOD, and GPx. CPC concentrations were positively correlated with the mRNA level of LDL receptor while the mRNA levels of HMG CoA reductase, SOD-1, and GPx in HepG2 cells were not affected. The lipid-lowering and antioxidation effects of CPC suggest its roles in prevention of CVD and atherosclerotic formation.

Chromosome 15q21-22-related polymorphisms and haplotypes are associated with susceptibility to type-2 diabetic nonproliferative retinopathy.

OBJECTIVE: Diabetic retinopathy (DR) is a microvascular complication of diabetes with a complex multifactorial pathogenesis. We aimed to investigate whether chromosome 15q21-22-related gene polymorphisms could be used as markers of DR susceptibility in type 2 diabetic (T2D) individuals. METHODS: Individuals were divided into three groups: (1) T2D with nonproliferative DR (NPDR; n=102); (2) T2D with proliferative DR (PDR; n=72); (3) T2D without DR (n=573). Six single-nucleotide polymorphisms (SNPs) (rs7174997, rs3751624, rs8025011, rs17818837, rs2922220, and rs2414520) lying within chromosome 15q21-22 region were genotyped by using Illumina HumanHap550-Duo BeadChips. Genotypes/allelic frequencies and haplotypes for these polymorphisms in each group were compared. RESULTS: The MYO5C related SNP (rs3751624)*A related genotype and allele are associated with higher susceptibilities to DR, including PDR and NPDR. The rs3751624*GG/AA+AG percentages in each group are (1) 75.5%/24.5%, (2) 73.6%/26.4%, and (3) 82.5%/17.5%. In contrast, the other five SNPs in each group were not significantly different. One haplotype (G-A-G-G-T-G) appears significantly different between T2D individuals with and without DR. Other haplotype distributions were not significantly different between each group. CONCLUSION: The MYO5C related SNP (rs3751624)*A related genotype/allele and haplotype (G-A-G-G-T-G) might be associated with susceptibility for retinopathy in T2D individuals. Some chromosome 15q21-22* related genetic variations might contribute to the pathogenesis of DR.

XRCC1 399 Arg-related genotype and allele, but not XRCC1 His107Arg, XRCC1 Trp194Arg, KCNQ2, AT1R, and hOGG1 polymorphisms, are associated with higher susceptibility of endometriosis.

X-ray repair cross-complementing group 1 (XRCC1) and human 8-oxoguanine glycosylase 1 (hOGG1) play important roles in base excision repair. KCNQ genes comprising voltage-gated ion-channels related with cell stability. Angiotensin II type 1 receptor (AT1R) is related with angiogenesis, which influence endometriosis growth, invasion and regression. We aimed to investigate whether these polymorphisms were associated with endometriosis susceptibility. Women were divided [ 1 ]: endometriosis (n = 136 [ 2 ]); non-endometriosis groups (n = 112). XRCC1 (codon 107, 194, 399), hOGG1, KCNQ2, AT1R polymorphisms were amplified by PCR and detected by electrophoresis after restriction enzyme (RsaI, HpaII, MspI, Fnu4HI, Ava II, Dde I) digestions. Genotypes and allelic frequencies in both groups were compared. Proportions of XRCC1 Arg399Gln*GG/GA/AA and G/A allele between both groups were [ 1 ]: 41.9/53.7/4.4% and 68.8/31.2% [ 2 ]; 30.4/54.5/15.1% and 57.6/42.4% (p < 0.05). Other 5 polymorphisms (XRCC1 codon 107 and 194, hOGG1, KCNQ2, and AT1R) between both groups were non-significantly different. Proportions of XRCC1 107*AA/AG/GG and XRCC1 194*TT/TC/CC between both groups were [ 1 ]: 3.7/27.2/69.1% and 5.8/34.6/59.6% [ 2 ]; 2.6/21.4/75.8% and 11.6/37.5/50.9%. HOGG1*CC/CG/GG, KCNQ2*AA/AC/CCC and AT1R*AA/AC/CC were [ 1 ]: 14.8/42.6/42.6, 14/41.9/44.1 and 92.6/7.4/0% [ 2 ]; 11.6/50/38.4, 17/50/33 and 100/0/0%. We concluded that XRCC1 399 Arg-related genotype and allele are correlated with higher susceptibility to endometriosis, which suggested its association with endometriosis pathogenesis. XRCC1 107 and 194, hOGG1, KCNQ2, and AT1R are not associated with endometriosis susceptibility.

Effects of diosgenin on myometrial matrix metalloproteinase-2 and -9 activity and expression in ovariectomized rats.

Diosgenin, a traditional Yam extraction, has been used in hormone replacement for menopausal women. We aimed to investigate the influences of diosgenin administration upon the MMP-2 and -9 activity and expression and reproductive hormones of ovariectomized (OVX) rats, a model of menopausal status. Seven-week old female Wistar rats with bilateral OVX or sham operation (controls) were divided and administered different dosages of diosgenin (0, 10, 50, or 100 mg/kg/day) for 8 weeks. Serum was then sampled for progesterone (P4) and estradiol (E2) assay and uterine horns harvested. Myometrial MMP-2 and -9 activity and expression were surveyed and myometrial collagen expression was also assayed. The results show higher body weight in OVX rats across the 8 weeks post surgery and no significant differences were noted among OVX or Sham rats with diosgenin supplements. There were lower P4 and E2 concentrations in OVX rats compared to Sham rats, and higher P4 concentration of Sham rats post diosgenin supplement. MMP-2 and -9 mRNA expression and activity was lower in OVX rats, although higher MMP-2 and lower MMP-9 activity/mRNA expression was observed in OVX rats post diosgenin supplementation. Collagen mRNA expression was higher in OVX rats compared to Sham controls, and diosgenin administration decreased collagen mRNA expression in OVX rats. In conclusion, diosgenin is associated with gelatinase expression and collagen metabolism in OVX rats. Diosgenin administration can partially reverse the effects of OVX upon MMP functions and hormone status. Adequate diosgenin supplement might modulate myometrial gelatinase expression and collagen metabolism in menopausal subjects.

JAK-1 rs2780895 C-related genotype and allele but not JAK-1 rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277 are associated with higher susceptibility to asthma.

BACKGROUND: Asthma, one major respiratory consequence, might be caused by a complex interaction between multiple candidate genes and environmental factors. Herein, we aimed to investigate whether Janus kinase (JAK)-1 gene polymorphisms are associated with asthma susceptibility. MATERIALS AND METHODS: Patients were divided into two groups: (1) asthma (n=117) and (2) nonasthma (n=60). The JAK-1 polymorphisms (rs2780895, rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277) were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme (HpyCH4IV, Tsp45I, HpaII, XmnI, MspI, and HpaII) digestions. Genotypes, allelic frequencies, and association of haplotypes in both groups were compared. RESULTS: JAK-1 rs2780895 gene polymorphism is associated with susceptibility to asthma. Distributions of JAK-1 rs2780895*CC/CT/TT and C/T allele in both groups are: (1) 80/4/16% and 82/18%; (2) 48/45/7% and 71/29%. Other 5 JAK-1 SNPs (rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277) are not associated with asthma susceptibilities. Distributions of JAK-1 rs10789166*AA/AG/GG, rs4916008*CC/CT/TT, rs2780885*CC/CT/TT, rs17127114*AA/AG/GG, rs3806277*AA/AG/GG in both groups are: (1) 50/40/10%, 42/49/9%, 50/40/10%, 9/37/54%, 8/35/57%; (2) 43/50/7%, 40/50/10%, 50/43/7%, 7/48/45%, 6/42/52%. Haplotype analyses for JAK-1 gene polymorphisms (rs2780895-rs10789166-rs4916008-rs2780885-rs17127114-rs3806277) revealed that JAK-1 haplotypes are not associated with asthma susceptibilities. CONCLUSIONS: JAK-1 rs2780895 C-related genotype and allele are associated with higher susceptibility to asthma. JAK-1 rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277 single-nucleotide polymorphisms are not associated with asthma development. Some JAK-related genetic variations might be associated with asthma pathogenesis, which deserve further surveys.

Major histocompatibility complex class I chain-related gene polymorphisms: associated with susceptibility to Kawasaki disease and coronary artery aneurysms.

BACKGROUND: Kawasaki disease (KD) involves a complex interaction of immunoinflammatory process, cytokine activation, and genetic factors. We aimed to investigate whether genetic variations in a major histocompatibility complex (MHC) class could be used as markers of susceptibility in KD and coronary artery aneurysm lesions (CALs). METHODS: Individuals were divided into following groups: (1) normal controls; (2) KD with CAL; (3) KD without CAL. Polymorphisms for MHC class I chain-related genes A (MICA) (rs2301747, rs2256184, rs2848716), MICB (rs2855804, rs3132464, rs2516400), BAT3 (rs750332), MSH5 (rs1150793), and chromosome 6 open reading frame 27 (C6orf27, rs707928) were genotyped with polymerase chain reaction and the TaqMan(®) allelic discrimination assay. Genotypes, alleles, and haplotype in each group were compared. RESULTS: Genotype and allele frequency of MICB*rs2516400 polymorphisms in each group were significantly different. MICB (rs2516400)*C-related genotypes/alleles are correlated with development of KD and CAL. Proportions of rs2516400*TT/TC/CC were (1) 1/39/60%, (2) 0/0/100%, and (3) 0/0/100%. Other single-nucleotide polymorphisms were not associated with KD susceptibilities. Haplotypes (rs2301747-rs2256184-rs2848716-rs2855804-rs3132464-rs2516400-rs750332-rs1150793-rs707928) G-G-G-C-T-C-T-A-A, C-A-G-T-T-C-T-A-A, and G-G-G-C-C-C-T-A-A were associated with higher susceptibilities for KD. The G-G-G-T-T-T-T-G-G and C-G-G-T-T-T-T-A-A haplotypes were associated with lower susceptibilities. CONCLUSION: MICB*rs2516400 polymorphisms and some MHC class I-related haplotypes are associated with KD susceptibility. MICB and MHC class I genetic variations might contribute to the pathogenesis of KD and CAL.

Association of STAT4 polymorphisms with susceptibility to primary membranous glomerulonephritis and renal failure.

BACKGROUND: Membranous glomerulonephritis (MGN) is one of common causes of idiopathic nephrotic syndrome in adults, and 25% of MGN patients proceed to end-stage renal disease. STAT4 gene polymorphisms have been reported to be associated with many inflammatory diseases. The objective of this study was to clarify the relationship between STAT4 gene polymorphisms and the pathogenesis of MGN. METHODS: We investigated the association of three STAT4 gene polymorphisms (rs3024912, rs3024908, and rs3024877) with the susceptibility to MGN in 403 Taiwanese populations (138 MGN patients and 265 controls). RESULTS: The results indicated that the statistically significant difference in genotype frequency distribution was found at rs3024908 SNP in MGN patients and control groups (p=0.014). In addition, the individuals with the GG genotype at rs3024912 SNP may have a higher risk in kidney failure of MGN patients (adjusted odds ratio [OR]=3.255; 95% confidence interval [CI]=1.155-9.176, p=0.026). CONCLUSIONS: Our data provide a new information that the STAT4 (rs3024912 and rs3024908) polymorphisms may be the underlying cause of MGN, and these polymorphisms revealed by this study warrant further investigation.

Effects of gonadotropins (Gonal-F and Puregon) on human endometrial cell proliferation in vitro.

CONDENSATION: Both Gonal-F and Puregon, especially in their high-dosage administration, might inhibit the endometrial cell proliferation in the initial 48-hour culture. After 72-hour culture, Gonal-F persisted the inhibition of the endometrial growth, whereas Puregon reversed its effect to enhance endometrial growth. OBJECTIVES: Endometrial proliferation or regeneration during menstrual cycle is regulated by sexual hormones. However, the effect of gonadotropins on the endometrial cell growth remains obscure. Herein, we aimed to investigate the effects of recombinant follicle-stimulating hormones (r-FSHs) (Gonal-F and Puregon) on the proliferation of human endometrial cells in vitro. MATERIALS AND METHODS: Human endometrial cells (RL95-2 cells) were obtained commercially and cultured in the serum-containing media in the presence of r-FSHs (Gonal-F and Puregon at concentrations of 0mIU/mL, 200mIU/mL, 400mIU/mL, and 600mIU/mL) up to 72 hours. According to the gonadotropin concentrations, all cultured endometrial cells were divided into four groups: (1) 0mIU/mL (control); (2) 200mIU/mL; (3) 400mIU/mL; and (4) 600mIU/mL. After 72-hour culture, endometrial cell proliferations were assessed overnight by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The influences of different r-FSH agents and dosages on endometrial cell proliferation in each group were evaluated and compared. RESULTS: In the four Gonal-F groups, the cell absorption (control and 200mIU/mL, 400mIU/mL, and 600mIU/mL Gonal-F) after 24/48/72-hour cultures were as follows: (1) 0.57/0.7/0.82; (2) 0.56/0.66/0.78; (3) 0.55/0.64/0.77; and (4) 0.51/0.61/0.78. After 48 hours, higher dosage of Gonal-F appeared to significantly inhibit the endometrial cell proliferation. After 72-hour culture, all three dosages of Gonal-F appeared to inhibit the endometrial cell proliferation similarly. In Puregon groups, the cell absorptions were as follows: (1) 0.62/0.53/0.62; (2) 0.61/0.5/0.66; (3) 0.61/0.49/0.66; and (4) 0.64/0.49/0.66. Puregon administration displayed initial inhibition and subsequent stimulation effects on the endometrial cells. CONCLUSIONS: Both Gonal-F and Puregon, especially in their high-dosage administration, appeared to inhibit the endometrial cell proliferation in the initial 48-hour culture. After 72-hour culture, Gonal-F persisted the inhibition of the endometrium, whereas Puregon reversed its effect by enhancing the endometrial growth. The differences might be because of the different formulations or molecular structures existing between alpha and beta follitropins.

Effects of α and ß recombinant FSH (Gonal-F, Puregon) and progesterone upon human endometrial cell proliferation in-vitro: a preliminary study.

Endometrial proliferation or regeneration during menstrual cycle is regulated by sexual hormones. However, the effect of gonadotrophins on the endometrial cell growth remains obscure. Herein, we aimed to investigate the effects of r-FSH (Gonal-F, Puregon) and progesterone on the proliferation of human endometrial cells in-vitro. According as gonadotrophin concentrations, the follicular-phase endometrial cells were divided into six groups: (1) 0 (controls), (2) 1; (3) 10; (4) 100; (5) 1000; (6) 100,000 µIU/ml. The cell countings with microscopy and cell proliferation kit assay were used to assess the endometrial cell proliferations. In Gonal-F groups, the cell absorptions (%) after 24/48 h culture were: (1) 100/100; (2) 103.8/102.3; (3) 104.8/102.8; (4) 102.3/101.3; (5) 96.3/94.2; (6) 86.8/84.3. In Puregon groups, the cell absorptions were: (1) 100/100; (2) 102.8/101.9; (3) 103/102.3; (4) 103.9/103.5; (5) 102.9/102.4; (6) 103.7/103.2 (non-different). In progesterone groups, the cell absorptions were: (1) 100/100; (2) 99.1/101.9; (3) 83.5/80.4; (4) 80.7/82.4. Higher dosage of Gonal-F (100,000 µIU/ml) and progesterone (10, 100 µg/ml) appeared the significant inhibition upon endometrium. We conclude that lower dosages of Gonal-F, Puregon, and progesterone appear the non-significant influence upon endometrium. Higher dosage of Gonal-F (10,000 µIU/ml) and progesterone (10, 100 µg/ml), but not Puregon, might interfere with the endometrial proliferation during follicular phase.

Leiomyoma and vascular endothelial growth factor gene polymorphisms: a systematic review.

Leiomyomas (myoma or fibroid) are the most common gynecologic tumors that occur in women of reproductive age, but their molecular pathogenesis is still unknown. Since the growth of leiomyomas involve numerous vascular factors, an association between the leiomyoma and growth factors is suspected. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors. VEGF regulates angiogenesis and mediates sex steroid-induced cell growth and differentiation. VEGF-mediated activities seem to contribute to the pathogenesis of leiomyoma. Genetic variations, including polymorphisms, in VEGF might also be associated with the complex pathogenesis of leiomyomas. Here, we performed a systematic review of the roles of VEGF and its polymorphisms in the pathogenesis of leiomyoma.

Insulin-like growth factors II exon 9 and E-cadherin-Pml I but not myeloperoxidase promoter-463, urokinase-ApaL I nor xeroderma pigmentosum polymorphisms are associated with higher susceptibility to leiomyoma.

OBJECTIVES: To investigate the roles of insulin-like growth factor II (IGF2), myeloperoxidase (MPO), E-cadherin (CDH1), urokinase and xeroderma pigmentosum group A and D (XPA, XPD) polymorphisms upon leiomyoma susceptibility. STUDY DESIGN: Women were divided into: group 1, leiomyoma (n=158); group 2, non-leiomyoma (n=156). Polymorphisms (IGF2 exon 9*A/G, MPO-463*A/G, CDH1-Pml I, urokinase-ApaL, XPA*A-23G, XPD*Lys751Gln) were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme digestion. Genotype and allelic frequencies were compared between both groups. RESULTS: Associations between leiomyoma with IGF2 and CDH1 polymorphism exist. Proportions of IGF2 exon 9*AA/AG/GG in and CDH1* CC/CT/TT in the groups were: group 1, 38/39.2/22.8% and 27.8/66.5/5.7%; group 2, 22.4/53.9/23.7% and 21.2/64.1/14.7. MPO, urokinase, XPA and XPD in both groups were non-significantly different. Proportions of MPO*AA/AG/GG, urokinase*CC/CT/TT, XPA*AA/AG/GG and XPD*AA/AC/CC were: group 1: 1.9/23.4/74.7%, 0.6/7/92.4%, 20.9/55.1/24%, 85.4/14.6/0%; group 2: 3.8/24.4/71.8%, 1.3/4.5/94.2%, 22.4/53.9/23.7%, 84.6/15.4/0%. CONCLUSION: IGF2*A allele and CDH1*C allele were correlated with leiomyoma susceptibility, which may be associated with leiomyoma development. MPO, urokinase, XPA and XPD polymorphisms are not related to leiomyoma susceptibilities.

Human lymphocyte antigen B-associated transcript 2, 3, and 5 polymorphisms and haplotypes are associated with susceptibility of Kawasaki disease and coronary artery aneurysm.

CAPSULE: HLA-B associated transcript (BAT) 2, 3, and 5 polymorphisms and haplotypes are associated with Kawasaki disease (KD) and coronary artery aneurysm (CAA) formations. OBJECTIVE: KD, an acute vasculitis with unknown etiology, involves a complex interaction of immuno-inflammatory process, cytokines activation, and genetic factors. We aimed to investigate if genetic variants of human lymphocyte antigen (HLA)-BAT2, 3, and 5 (BAT2, 3, and 5) could be used as markers of susceptibility in KD and CAA. METHODS: Individuals were divided into three groups: (1) normal controls; (2) KD with CAA; and (3) KD without CAA. Polymorphisms for BAT2 (-8671, 16483), BAT3 (8854, 2-24), and BAT5 (22655, 9569) were genotyped by PCR system with TaqMan allelic discrimination assay. Genotype/allelic frequencies and haplotypes (BAT2(-8671)-BAT2(16483)-BAT3(8854)-BAT3(2-24)-BAT5(22655)-BAT5(9569)) in each group were compared. RESULTS: Genotype distribution and allele frequency of BAT2 -8671, BAT3 8854, and BAT5 22655, 9569 polymorphisms in each group were significantly different. BAT2 -8671*G, BAT3 8854*C, BAT5 22655*C, and 9569*A-related genotypes and alleles are correlated with the developments of KD and CAA. BAT haplotypes of ATTGTG and ATCATG are associated with higher susceptibilities of KD with CAA susceptibility. CONCLUSION: BAT2 -8671, BAT3 8854, and BAT5 22655, 9569 polymorphisms as well as BAT haplotypes (ATTGTG and ATCATG) might be associated with higher KD susceptibility and CAA formation. HLA-B region polymorphisms might contribute to the pathogenesis of KD and CAA.

Deleterious effects of arsenic, benomyl and carbendazim on human endometrial cell proliferation in vitro.

OBJECTIVE: We aimed to investigate the effects of arsenic (As), benomyl (Ben), and carbendazim (Carb) on endometrial cells. MATERIALS AND METHODS: Human endometrial cells were obtained during diagnostic curettage. All cultured endometrial cells were divided into four groups: (1) 0 M (controls), (2) 10(-6) M, (3) 10(-5) M, (4) 10(-4) M for As, Ben and Carb. After 24 and 48 hours in culture, endometrial cell proliferations were assessed by diphenyltetrazolium bromide assay. The influences of different concentrations of As, Ben and Carb upon the endometrium were compared. RESULTS: During the first 24 hours, As, Ben and Carb appeared to have insignificant influences upon endometrial growth. After 48 hours in culture, all three agents significantly inhibited endometrial growth. In As groups, cell absorption after 48 hours culture were 100% (group 1), 82.1% (group 2), 43.6% (group 3) and 35.3% (group 4). In Ben groups, cell absorption was 100% (1), 75.9% (2), 66.4% (3) and 49. 6% (4). In the Carb groups, cell absorption was 100% (1), 70.4% (2), 73.0% (3) and 76.7% (4). CONCLUSION: The agents As, Ben and Carb appear to have inhibitory effects upon endometrial cells after 48 hours in culture.

Mitochondria DNA deletion and copy numbers of cumulus cells associated with in vitro fertilization outcomes.

OBJECTIVE: Mitochondria are important organelles in cell biology. We aimed to study the effects of mitochondrial DNA variations in cumulus cells (CCs) upon in vitro fertilization and embryo transfer (IVF-ET) outcomes. STUDY DESIGN: A total of 51 women undergoing IVF-ET were recruited for the study. The CCs were collected during oocyte retrievals. Mitochondria DNA 4977-bp deletion (dmtDNA-delta5Kb) and copy numbers (MCN) of CCs were analyzed by polymerase chain reaction. The relationships of dmtDNA-delta5Kb and MCN with patients' age, embryo qualities and pregnancy rates (PRs) were detected and compared. RESULTS: PRs were positively correlated with younger age, better transferred embryo qualities and lower dmtDNA-delta5Kb ratios in CCs. The dmtDNA-delta5Kb status was positively associated with older age and higher MCN but was not associated with embryo morphologic scoring. The dmtDNA-delta5Kb ratios of transferred embryos in pregnancy and nonpregnancy groups were 0% and 10.4%, respectively. The dmtDNA-delta5Kb in > or = 34-year-old and <34-year-old groups were 6.9% and 3.2%, respectively. CONCLUSION: The dmtDNA-delta5Kb and MCN statuses of CCs are negatively associated with PRs, which might be potential tools for oocyte evaluation and embryo selections during IVF-ET.

Identification of novel peptides specifically binding to endometriosis by screening phage-displaying peptide libraries.

OBJECTIVE: To search for novel peptides and common binding motif that specifically bind to endometriosis. DESIGN: Prospective study. SETTING: Department of Biological Science and Technology in national university. PATIENT(S): Specimens were divided into [1] ectopic endometrium (n = 10); [2] eutopic endometrium (n = 10). INTERVENTION(S): Peptides specifically binding to endometriosis are screened from a phage-displaying peptide library (Ph.D.-12) by using whole-cell screening technique after an adsorption elution amplification procedure. MAIN OUTCOME MEASURE(S): Combinatorial peptide libraries were used to identify small molecules that bind with high affinity to receptor molecules and mimic the interaction with natural ligands. Few pans of positive phage clones with significantly positive signals were identified by ELISA and analyzed by DNA sequencing. RESULT(S): During the biopanning processes, the recovered phage number (10(6) pfu/mL) in parts 1, 2, 3, 4, and 5 of the study were 9, 33, 82, 142, and 169. Nine phages consistently had residue Arg, whereas six clones had a consensus motif of Arg-X-Arg-X-X-X-X-Arg. The biotin-labeled peptide bound to endometriosis cells in a dose-dependent manner, yet the control peptide revealed lesser binding activity. CONCLUSION(S): The novel motif is associated with higher affinity of endometriosis, which might be useful in endometriosis targeting and as potential antiendometriosis therapies. We provide one potential approach for novel therapies toward endometriosis.

STAT2*C related genotypes and allele but not TLR4 and CD40 gene polymorphisms are associated with higher susceptibility for asthma.

OBJECTIVE: Asthma is caused by a complex interaction between multiple genes and environmental factors. Herein we aimed to investigate whether signal transducer and activator of transcription (STAT2), toll-like receptors 4 (TLRs4) and CD40-related polymorphisms are associated with asthma susceptibility. DESIGN: Children were divided: (1) asthma (n=117); (2) normal controls (n=60). The polymorphisms of STAT2, TLR4 and CD40 polymorphism were analyzed by PCR-RFLP genotyping. Genotypes, allelic frequencies and association of haplotypes in both groups were compared. RESULTS: STAT2*C related genotypes, but not TLR4 and CD40 polymorphism, are associated with higher susceptibility for asthma. Distributions of STAT2*CC/CG/GG and C/G allele in both groups are: (1) 0/11.1/88.9 % and 5.6/94.4%; (2) 0/1.7/98.3% and 0.8/99.2% (p<0.05). Proportions of TLR4*rs10983755 AA/AG/GG and rs1927914 CC/CT/TT homozygote are: (1) 35.1/8.5/56.4% and 9.4/56.4/34.2%; (2) 35/8.3/56.7% and 16.7/48.3/35% (non-difference). Proportions of CD40*rs1883832 CC/CT/TT, rs3765459 AA/AG/GG, and rs4810485 TT/GT/GG are: (1) 29.9/53/17.1%, 6.8/47.9/45.3 and 18.8/62.4/18.8%; (2) 36.7/41.7/21.6%, 1.6/46.7/ 51.7 and 15/51.7/33.3% (non-difference). Haplotype analyses for TLR4 and CD40 genes revealed their non-association and non-additional effect upon asthma susceptibilities. CONCLUSION: STAT2*C related genotypes and alleles are associated with asthma susceptibilities and pathogenesis. There were non-association and non-additional effects of TLR4/CD40 gene polymorphisms and haplotypes upon asthma risk.

The p21 codon 31*C- and DRD2 codon 313*T-related genotypes/alleles, but not XRCC1 codon 399, hOGG1 codon 326, and DRD1-48 polymorphisms, are correlated with the presence of leiomyoma.

OBJECTIVE: To investigate whether the gene polymorphisms for p21, X-ray repair cross-complementing group 1 (XRCC1), human 8-oxoguanine glycosylase 1 (hOGG1), and dopamine D1 and D2 receptors (DRD1, -2) are associated with leiomyoma susceptibility. DESIGN: Prospective study. SETTING: Departments of gynecology and genetics in a medical center. PATIENT(S): Women were divided into two groups: leiomyoma (n = 120) and nonleiomyoma (n = 112). INTERVENTION(S): The p21 codon 31, XRCC1 codon 399, hOGG1 codon 326, DRD1-48, and DRD2 codon 313 polymorphisms were genotyped by polymerase chain reaction with restriction enzyme digestions (Blp I, MspI, Fnu4HI, Dde I, and NcoI, respectively). MAIN OUTCOME MEASURE(S): Genotypes and allelic frequencies. RESULT(S): The p21 codon 31(*)C- and DRD2 codon 313(*)T-related genotypes/alleles were associated with the presence of leiomyomas. The proportions of p21(*)CC/CA/AA and DRD2(*)CC/CT/TT in both groups were 27.5/68.3/4.2% and 12.5/51.7/35.8% (leiomyoma); and 14.3/51.8/33.9% and 33.9/40.2/25.9% (nonleiomyoma). XRCC1, hOGG1, and DRD1 were not correlated with the presence of leiomyomas. XRCC1(*)GG/GA/AA, hOGG1(*)TT/TA/AA, and DRD1(*)GG/GA/AA were 54.2/37.5/8.3%, 36.7/44.2/19.1%, and 3.3/25.8/70.8% (leiomyoma); and 48.2/47.3/4.5%, 43.6/41/15.4%, and 3.6/25/71.4% (nonleiomyoma). CONCLUSION(S): The p21 codon 31(*)C- and DRD2 codon 313(*)T-related genotypes/alleles were associated with the presence of leiomyoma. XRCC1, hOGG1, and DRD1 were not correlated with leiomyoma development.

Effect of exercise training on calpain systems in lean and obese Zucker rats.

Exercise training plays a major role in the improving physiology of diabetes. Herein we aimed to investigate the influence of exercise upon the calcium-dependent calpain-isoform expressions of lean or obese Zucker rats, a model of obesity and type II diabetes (NIDDM). Five-month-old rats were divided: (1) obese sedentary (OS, n=7); (2) obese exercise (OE, n=7); (3) lean sedentary (LS, n=7); (4) lean exercise (LE, n=7). After 2-month exercise (treadmill running), the body weight (BW) and expression of calpain 10, mu-calpain, and m-calpain in skeletal muscles were determined by RT-PCR, using beta-actin as internal standard. We found exercise is useful for BW lossing, especially in the obese rats. The BW difference between OS and OE rats (69 g vs. 18.2 g) was more significantly than that between LS and LE rats (41.8 g vs. 28.7 g). The calpain 10 expression of LS rats (0.965) was lower than that of LE rats (1.006), whereas those of OS and OE were comparable. The mu- or m-calpain expressions of sedentary groups (OS, LS) was significantly higher than those of exercise groups (OE, LE). The mu-calpain expression (1.13/0.92) and m-calpain expression (1.01/0.99) of OS/LS rats was significantly higher than those of OE/LE rats [1.07/0.9 (micro-calpain); 0.97/0.95 (m-calpain)]. We concluded that the micro- or m-calpains in skeletal muscle are regulated by exercise in both lean and obese Zucker rats. Exercise and BW controlling might improve the physiopathology of obesity and diabetes. Both micro- or m-calpains might become useful markers for prognoses of diabetes.

Effects of yam and diosgenin on calpain systems in skeletal muscle of ovariectomized rats.

OBJECTIVE: Yam or diosgenin (extracted from the root of wild yam) is traditionally used for hormone replacement in menopausal women. Calpains are crucially related to the degradation of myofibrillar proteins in skeletal muscle. This study aimed to investigate the effects of yam and diosgenin on the calpain isoform expression in ovariectomized rats, a model of menopausal status. MATERIALS AND METHODS: Female rats were divided into: (1) controls; (2) ovariectomized rats; (3) ovariectomized rats receiving yam (250, 750, 1,500 mg/kg/day); (4) ovariectomized rats receiving diosgenin (10, 50, 100 mg/kg/day). Yam and diosgenin were administered for 8 weeks. The expression of mu- and m-calpain in skeletal muscles was determined by reverse transcriptase-polymerase chain reaction. RESULTS: The mu-calpain/beta-actin and m-calpain/beta-actin ratios in the control group (0.9 and 1.09, respectively) were significantly higher than those in the ovariectomized group (0.58 and 0.72, respectively). In the yam group, the expression of mu- and m-calpain was lowest in the ovariectomized group receiving no supplementation and lower in the 250 mg group compared with the 750 and 1,500 mg groups (for 0, 250, 750 and 1,500 mg dosage groups, mu-calpain, 0.58, 0.88, 1.24 and 1.13, respectively; m-calpain, 0.72, 1.02, 1.38 and 1.47, respectively). In contrast, there were no significant differences in the expression of mu- and m-calpain mRNAs among the different diosgenin dosage groups (for 0, 10, 50 and 100 mg of diosgenin, mu-calpain, 0.58, 0.56, 0.62 and 0.58, respectively; m-calpain, 0.72, 0.58, 0.71 and 0.54, respectively). Decreased expression of mu- or m-calpain was observed in the ovariectomized group compared with the normal controls. CONCLUSION: Yam, but not its extract (diosgenin), is associated with the regulation of calpain isoforms in ovariectomized rats. Adequate yam supplements might improve the muscular calpain-related physiopathology associated with menopausal status.