Purinergic receptor P2X7 activates NOX2/JNK signaling to participate in granulosa cell inflammation and apoptosis in polycystic ovary syndrome.

Increasing evidence shows that polycystic ovary syndrome (PCOS) is often accompanied by an inflammatory response, hence, appropriately managing granulosa cell inflammation is critical to regaining ovarian function in PCOS. In this study, the differential levels of purinergic receptor P2X7 between the control and PCOS samples in the dataset GSE34526 were assessed, then PCOS mouse models were established. Following evaluating the fluctuations in hormone levels, inflammatory cytokines, and P2X7, mice received treatment with the P2X7 antagonist A740003. Its effects on hormones, inflammation, apoptosis, and NOX2 signaling in mice were examined. Afterward, primary mouse granulosa cells were isolated, and the mediating role of NOX2 signaling in the P2X7 regulatory pathway was confirmed by transfection of NOX2 overexpression plasmids. The results demonstrated that P2X7 was significantly elevated in the PCOS samples in the dataset. Compared with the control group, PCOS mice had significant differences in the follicle-stimulating hormone, luteinizing hormone, testosterone, anti-Müllerian hormone, inflammatory factors, and P2X7. Treatment with A740003 partially restored these parameter levels, including NOX2 signaling. Based on in vitro experiments on primary mouse granulosa cells, the above findings were re-verified, and the overexpression of NOX2 could reverse the regulatory function of P2X7. The present study highlights that P2X7 level increases in PCOS, and inhibition of P2X7 can reduce disease symptoms. It is involved in inflammation and apoptosis in granulosa cells through NOX2/JNK signaling.

SIRT6 reduces the symptoms of premature ovarian failure and alleviates oxidative stress and apoptosis in granulosa cells by degrading p66SHC via H3K9AC.

CONTEXT: Substantial evidence suggests that ovarian oxidative stress can result in severe ovarian dysfunction. OBJECTIVE: The purpose of this article is to investigate the potential of SIRT6 in alleviating premature ovarian failure (POF) by inhibiting oxidative stress. METHODS: To mimic POF, mice were administered daily subcutaneous injections of d-galactose. The levels of E2, FSH, LH, AMH, and progesterone in serum were measured, along with changes in follicles and SIRT6 levels. Mice were treated with the SIRT6 agonist MDL-800, SIRT6 levels, follicles, and aforementioned hormones were reassessed. The effects of MDL-800 on oxidative stress and apoptosis were subsequently identified. Primary granulosa cells were isolated from mice, and the effects of H2O2 and MDL-800 on cell viability, oxidative stress, SIRT6 level, and apoptosis were evaluated. In addition, the regulation of SIRT6 on H3K9AC/p66SHC was verified by examining changes in protein levels, promoter activity, and the reversal effects of p66SHC overexpression. RESULTS: MDL-800 mitigated hormone fluctuations, reduced follicle depletion in ovarian tissue, and attenuated oxidative stress and apoptosis in mice. In vitro experiments demonstrated that MDL-800 enhanced the resilience of primary granulosa cells against H2O2, as evidenced by increased cell viability and reduced oxidative stress and apoptosis. Furthermore, SIRT6 was found to decrease H3K9AC and p66SHC levels, as well as attenuate p66SHC promoter activity. The protective effects of MDL-800 on cells were reversed upon p66SHC overexpression. CONCLUSION: In summary, this study highlights that activation of SIRT6 can alleviate POF and reduce oxidative stress by degrading H3K9AC and suppressing p66Shc levels in granulosa cells.

Post-Traumatic Stress Disorder Is Associated with Elevated Plasma Cholesterol in Female TT Homozygotes of LDLR rs5925.

To explore the mechanism of inconsistent relationships between plasma lipid profiles and post-traumatic stress disorder (PTSD) reported before, we hypothesized that interplays might exist between PTSD and a variation of rs5925 at low-density lipoprotein receptor (LDLR) gene on plasma lipid profiles. To test our hypothesis, we analyzed the plasma lipid profiles of 709 high school pupils with various genotypes of LDLR rs5925 and with or without PTSD. The results demonstrated that PTSD prevalence in the C allele carriers was higher than that in the TT homozygotes regardless of gender. The C allele carriers had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ratios of TC to high-density lipoprotein cholesterol (TC/HDL-C) and LDL-C/HDL-C than the TT homozygotes in the male controls, and only higher TC in the female controls, but no differences in the male or female PTSD subjects. PTSD increased TC in the female TT homozygotes but not in the female C allele carriers. PTSD increased TC/HDL-C in the male TT homozygotes but not in the C allele carriers. These results suggest interactions between PTSD and LDLR rs5925 on plasma lipid profiles, which may be among the explanations for previously reported inconsistent relationships between LDLR rs5925 or PTSD and plasma lipid profiles, and facilitate the development of precision medicine interferences in hypercholesterolemia in individuals with different genetic backgrounds and psychiatric status. Psychiatric care or drug supplement may particularly be needed by female hypercholesterolemic subjects with the TT genotype of LDLR rs5925 in Chinese adolescents.

Predictive factors of depression symptoms among adolescents in the 18-month follow-up after Wenchuan earthquake in China.

BACKGROUND: It is unclear about the change and risk factors of depression among adolescent survivors after earthquake. AIMS: This study aimed to explore the change of depression, and identify the predictive factors of depression among adolescent survivors after the 2008 Wenchuan earthquake in China. METHODS: The depression among high school students at 6, 12 and 18 months after the Wenchuan earthquake were investigated. The Beck Depression Inventory (BDI) was used in this study to assess the severity of depression. RESULTS: Subjects included 548 student survivors in an affected high school. The rates of depression among the adolescent survivors at 6-, 12- and 18-month after the earthquake were 27.3%, 42.9% and 33.3%, respectively, for males, and 42.9%, 61.9% and 53.4%, respectively, for females. Depression symptoms, trauma-related self-injury, suicidal ideation and PTSD symptoms at the 6-month follow-up were significant predictive factors for depression at the 18-month time interval following the earthquake. CONCLUSIONS: This study highlights the need for considering disaster-related psychological sequela and risk factors of depression symptoms in the planning and implementation of mental health services. Long-term mental and psychological supports for victims of natural disasters are imperative.

Association of Leptin Receptor Gene Polymorphisms with Genetic Susceptibility to Ischemic Stroke.

BACKGROUND: Ischemic stroke is a multifactorial disease that is influenced by both genetic and environmental factors. Identification of the genetic factors that are underlining this disease is important. Leptin receptor (LEPR) mediates the leptin-regulated human energy homeostasis, and mutations of LEPR can increase cardiovascular risks and may predispose an individual to ischemic stroke. METHODS: We analyzed distribution of 3 single nucleotide polymorphisms (SNPs) of LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) in 101 patients with ischemic stroke and 105 controls by polymerase chain reaction-restriction fragment length polymorphism strategy. RESULTS: Our results showed that there were significant differences in the genotype and allele distribution of Lys109Arg and Gln223Arg polymorphisms of the LEPR gene between case and control. The 109GG and 223GG genotype were associated with a significantly increased risk of ischemic stroke (odds ratio [OR], 3.23; P = .001 and OR, 2.87; P = .008, respectively). The 109G and 223G alleles carriers were correlated with an increased incidence of ischemic stroke (OR, 2.72; P = .001; OR, 2.94; P = .004). By haplotype analyses, we found that 109A/223G/656G haplotype was associated with an increased risk of ischemic stroke although this was not observed in the control group (OR, 3.86; P = .029). CONCLUSIONS: LEPR 109GG and 223GG genotypes and the 109G and 223G alleles are associated with the risk of ischemic stroke. Our data suggest that LEPR Lys109Arg and Gln223Arg polymorphisms could be used as genetic predictive factor for ischemic stroke.

[Effects of APOC3 polymorphisms on the plasma lipids in healthy adolescents with different body mass index].

OBJECTIVE: To investigate the possible effects of apolipoprotein C I gene (APOC3) polymorphisms on plasma lipids in healthy adolescents with different body mass index (BMI). METHODS: Seven hundred and twenty three adolescents were divided into four groups according to BMI: group 1 CBMI= (17.80 +/- 0.75) kg/m2,n=180], group 2 [BMI = (19.39 +/- 0.32) kg/m2, n=182), group 3 [BMI= (20.68 +/- 0.43) kg/m2, n=1813 and group 4 [BMI= (23.40 +/- 2.05) kg/m2 ,n=180J. Fasting venous blood samples were collected, plasma lipids were determined and genome DNA was extracted for determining the genotypes of the APOC3 Sst I and -482C>T polymorphisms by PCR-RFLP. RESULTS: With the elevation of BMI, height and plasma high-density lipoprotein cholesterol decreased significantly (P<0.001 for both), body mass, waist circumference, hip circumference, waist/hip ratio, plasma triglycerides (TG), total cholesterol and low-density lipoprotein cholesterol levels increased significantly (P<0.001 for all). No significant differences in TG levels among Sst I genotypes were observed in group 1, group 2 and group 3; but in group 4, significant differences in TG levels among Sst I genotypes were observed, S2 carriers had higher TG levels than the adolescents with S1S1 genotype. No significant differences in plasma lipids among -482C>T genotypes were observed in all groups. CONCLUSION: The elevation of plasma TG levels by the S2 allele of APOC3 Sst I polymorphism is associated with BMI. It is possible that the reduction of body mass could favorably modulate the elevation of TG levels by S2 allele in healthy adolescents.

[Effects of apolipoprotein A1 gene rs670 and rs5069 polymorphisms on the plasma lipid profiles in healthy adolescents with different body mass index].

OBJECTIVE: To investigate the possible effects of apolipoprotein A1 gene (APOA1) rs670 and rs5069 polymorphisms on plasma lipid profiles in healthy adolescents with different body mass index (BMI). METHODS: Totally 723 adolescents were divided into four groups according to their BMI: group 1[BMI =(17.80 ± 0.75)kg/m2], group 2[BMI = (19.39 ± 0.32) kg/m²], group 3[BMI = (20.68 ± 0.43) kg/m²], and group 4[BMI=(23.40 ± 2.05) kg/m²]. Height, weight, waist circumference, hip circumference, blood pressure, heart rate, plasma lipids, and blood glucose were determined, BMI and waist to hip ratio (W/H ratio) were calculated,and genome DNA was extracted for analyzing the genotypes of the APOA1 rs670 and rs5069 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No significant differences in height, weight, BMI, waist circumference, hip circumference, W/H ratio, blood pressure, heart rate, plasma lipids, and blood glucose between APOA1 rs670 or rs5069 genotypes were observed among group 1, group 2, and group 3. In group 4, A carriers of the rs670 polymorphism had significantly higher systolic blood pressure (P=0.017) and blood glucose levels (P=0.009) than the adolescents with the GG genotype. T carriers of the rs5069 polymorphism had significantly higher height (P=0.013), weight (P=0.011), and hip circumference (P=0.026) than the adolescents with the CC genotype. CONCLUSIONS: In healthy adolescents with higher BMI, APOA1 rs670 polymorphism is associated with systolic blood pressure and blood glucose levels. The elevation of systolic blood pressure and blood glucose levels in A carriers of APOA1 rs670 polymorphism may be favorably modulated by weight loss.

METTL3 silencing inhibits ferroptosis to suppress ovarian fibrosis in PCOS by upregulating m6A modification of GPX4.

Methyltransferase-like 3 (METTL3) is extensively reported to be involved in organ fibrosis. Ovarian fibrosis is a main characteristic of polycystic ovary syndrome (PCOS). However, the reaction mechanism of METTL3 in PCOS is poorly investigated. This paper was intended to reveal the role and the mechanism of METTL3 in PCOS. Animal and cell models of PCOS were induced by dehydroepiandrosterone (DHEA). H&E staining was performed to detect the pathological alterations in ovary tissues. Masson staining, immunofluorescence, along with western blot measured fibrosis both in vitro and in vivo. To evaluate estrous cycle, vaginal smear was performed. Lipid peroxidation and ferroptosis were evaluated by MDA assay kits, GSH assay kits, immunohistochemistry, Prussian blue staining and western blot. qRT-PCR and western blot were adopted to estimate METTL3 and GPX4 expression. The m6A and hormone secretion levels were respectively assessed by m6A RNA Methylation Quantitative Kit and corresponding kits. The interaction between METTL3 and GPX4 was testified by immunoprecipitation. The fibrosis and ferroptosis were aggravated and m6A and METTL3 expression were increased in ovarian tissues of DHEA-induced PCOS mice. METTL3 silencing alleviated pathological changes, affected hormone secretion level, and repressed fibrosis, lipid peroxidation and ferroptosis in the ovarian tissues of PCOS mice. In vitro, DHEA stimulation increased m6A and METTL3 expression and induced ferroptosis and fibrosis. METTL3 knockdown promoted GPX4 expression in DHEA-induced granulosa cells by m6A modification and restrained DHEA-induced fibrosis, lipid peroxidation and ferroptosis in granulosa cells via elevating GPX4. METTL3 silence inhibited ovarian fibrosis in PCOS, which was mediated through suppressing ferroptosis by upregulating GPX4 in m6A-dependent manner.

[The association study of the LIPC -250g/A polymorphism and high-carbohydrate/low-fat diet induced serum lipid and apolipoprotein concentration changes in healthy youth].

OBJECTIVE: To investigate the role of the - 250G/A polymorphism in the promoter region of hepatic lipase gene (LIPC) on serum lipid profile and its interactions with a high-carbohydrate/low-fat (HC/LF) diet on serum lipid profiles in a young healthy Chinese population. METHODS: After a stabilization diet for seven days, fifty-six young healthy subjects (27 males, 29 females) were given the HC/LF diet for six days. The serum lipid profiles were analyzed of the twelve-hour fasting venous blood samples collected in the mornings of the first, the eighth and the fourteenth days. The concentrations of serum apolipoproteins were measured. The LIPC -250G/A polymorphism were analyzed. RESULTS: At baseline, the female subjects with the GG genotype had significantly higher high-density lipoprotein cholesterol (HDL-C) (P= 0. 041) and apolipoprotein A- I (Apo A- I ) (P= 0. 020) than the male subjects with the same genotype. After the stabilization diet, the females had significantly higher HDL-C (GG genotype: P=0. 021, A carriers: P=0. 014) and Apo A-I (GG genotype: P= 0. 035, A carriers: P= 0. 006) than the males in all genotypes. After the HC/LF diet, the female A carriers had significantly higher total cholesterol (TC) (P= 0. 042) than the male A carriers, and the females had significantly higher Apo A- I than the males in all genotypes (GG genotype: P=0. 010, A carriers: P=0. 009). Compared with thosebefore the HC / LF diet , TC ( males with GG genotype : P = 0. 013 , male A carriers: P = 0. 000 ; females with GG genotype: P=0. 025, female A carriers: P=0. 048) and low-density lipoprotein cholesterol (LDL-C) (males with GG genotype: P = 0. 028, male A carriers: P = 0. 000; females with GG genotype: P= 0. 004, female A carriers: P=0. 001) significantly decreased after the diet in all the subjects. Triglycerides (TAG) (GG genotype: P=0. 006, A carriers: P= 0. 001) significantly increased in the females regardless of the genotype. However, only in the male A carriers, HDL-C (P= 0. 011) and Apo A- I (P= 0. 041) significantly increased after the diet. CONCLUSION: The A allele at the LIPC -250G/A polymorphism is associated with the HC/LF diet induced HDL-C and Apo A-I concentration changes in the males.

[Effects of an insertion/deletion polymorphism of angiotensin converting enzyme gene on the changes of serum lipid ratios and blood pressure induced by a high-carbohydrate and low-fat diet].

OBJECTIVE: To investigate the effects of an insertion/deletion (I/D) polymorphism at the intron 16 of the gene of angiotensin converting enzyme (ACE) on the changes of serum lipid ratios and blood pressure induced by a high-carbohydrate and low-fat (HC/LF) diet in healthy Chinese Han youth. METHODS: Fifty six healthy Chinese Han young volunteers were enrolled. A washout diet was given for seven days followed by the HC/LF diet for six days. Serum lipids and blood pressure were measured on the 1st, 8th, and 14th days. Serum lipid ratios were calculated. The ACE I/D polymorphism was detected by PCR. RESULTS: There were no significant differences of serum lipid ratios and blood pressure at baseline and before and after the HC/LF diet between the II genotype and the D carriers (ID and DD genotypes) in the whole study population, the males or the females separately. When compared with those before the HC/LF diet, all the subjects regardless of the genotype experienced statistical decreases of low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-C/HDL-C) and total cholesterol (TC)/HDL-C, but significant decrease of systolic blood pressure (SBP) was only found in the subjects with the II genotype. After taking into account gender, triglyceride (TG)/HDL-C and Log (TG/HDL-C) decreased in the males with theII genotype and increased in the female counterparts. The decreases of TC/HDL-C and LDL-C/HDIL-C were observed in all the males and the female D carriers. SBP decreased only in the male D carriers. CONCLUSION: The interaction of the HC/LF diet with the I allele of the intron 16 I/D polymorphism at the ACE gene decreases TG/HDL-C and log (TG/HDL-C) in males, but increases TG/HDL-C and log (TG/HDL-C) in females in the Chinese young population. The interplay with the D allele lowers SBP in males, and TC/HDL-C and LDL-C/ HDL-C in females.

[Effects of a high-carbohydrate diet on the serum lipid and apolipoprotein ratios in healthy young adults with different genotypes of APOA1 -75 G/A polymorphism].

OBJECTIVE: To investigate the effects of a high-carbohydrate diet on the lipid and apolipoprotein ratios in healthy young adults with different genotypes of the polymorphism at -75 site in the promoter region of the gene of apolipoprotein AI (APOA1). METHODS: Fifty-six subjects aged (22.89 +/- 1.80) years were given a wash-out diet for 7 days, followed by a high-carbohydrate diet for 6 days. The wash-out diet contained 15% protein, 31% fat, and 54% carbohydrate. The high-carbohydrate diet contained 15% protein, 15% fat, and 70% carbohydrate. Twelve-hour fasting serum lipids and apolipoproteins B100 and AI were measured on the mornings of the 1st, the 8th, and the 14th days from the beginning of the wash-out diet. The ratios of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C, and apolipoprotein B100 (APOB100)/apolipoprotein AI (APOAI) were calculated. The genome DNA was extracted and the polymorphism of APOA1 -75 G/A was determined by polymerase chain reaction followed by restriction fragment length polymorphism assay. RESULTS: At baseline, the lipid and apolipoprotein ratios showed no significant differences between the GG genotype and the A carriers in males (P > 0.05), whereas the female A carriers had a significantly higher ratio of LDL-C/ HDL-C compared with the female subjects with the GG genotype (P < 0.05). Following the high-carbohydrate diet, significant decreases of TC/HDL-C were found in all the groups, regardless of sex and genotype (P < 0.01). LDL-C/HDL-C experienced significant decreases in both the genotypes in males (P < 0.05), while in females, significant decrease of LDL-C/HDL-C was only observed in A carriers (P < 0.01). CONCLUSION: The A allele of the -75 G/A polymorphism in APOA1 may have specific effects on the LDL-C/HDL-C ratio in females.

[The role of CD14 promoter - 159 C-> T polymorphism on changes of serum lipid ratios induced by high-carbohydrate/low-fat diets in healthy Chinese Han youth].

OBJECTIVE: To investigate the role of CD14 promoter - 159 C-> T polymorphism on ratios of serum lipids and its interaction on the ratios with a high-carbohydrate/low-fat (HC/LF) diet in a young and healthy Chinese Han population. METHODS: After a washout diet for seven days, fifty six healthy young subjects (22.89 +/- 1.80 years) were given the HC/LF diet for six days. Twelve-hour fasting venous blood samples were collected in the mornings of the first, the eighth and the fourteenth days. The serum lipid profiles and the CD14 -159 C->T polymorphism were analyzed. The ratios of triglyceride/high density lipoprotein-cholesterol (TG/HDL-c), log (TG/HDL-c), total cholesterol/high density lipoprotein-cholesterol (TC/HDL-c) and low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-c/HDL-c) were calculated. RESULTS: The male carriers of the C allele had significantly higher TG/HDL-c and log (TG/HDL-c) than the female carriers at baseline, after the washout diet and after the HC/LF diet, higher TC/HDL-c at baseline and after the washout diet, and higher LDL-c/HDL-c only after the washout diet. The female subjects with the TT genotype had higher TG/HDL-c and log (TG/HDL-c) than the female carriers of the C allele at baseline, after the washout diet and after the HC/LF diet, higher LDL-c/HDL-c at baseline and after the HC/LF diet, and higher TC/HDL-c only after the washout diet. Compared with that before the HC/LF diet, TC/HDL-c was significantly decreased after the HC/LF diet regardless of gender and the genotype of the CD14 -159 polymorphism. LDL-c/HDL-c was significantly decreased in both the male and female carriers of the C allele. TG/HDL-c and log (TG/HDL-c) were significantly increased only in the female carriers of the C allele. CONCLUSION: In the subjects with C allele, the HC/LF diet is a minor factor and its effects on the lipid ratios can be masked by the effects of the C allele at CD14 -159. The interaction between the HC/LF diet and the C allele at CD14 -159 can decrease LDL-c/HDL-c in both males and females and increase TG/ HDL-c and log (TG/HDL-c) in the females.

[Effects of a low-fat and high-carbohydrate diet on the physiological and biochemical indices in healthy youth with different body mass index].

OBJECTIVE: To investigate the effects of a low-fat and high-carbohydrate (LF-HC) diet on the physiological and biochemical indexes in healthy youth with different body mass index (BMI). METHODS: Seven overweight participants [BMI=(27.82 +/- 1.64) kg/m2] and 49 age-matched controls [BMI = (20.06 +/- 2.41) kg/ m2] were given a washout diet for 7 d, followed by a LF-HC diet for 6 d. The washout diet contained 31.1% fat and 54.1% carbohydrate, and the LF-HC diet contained 14.8% fat and 70.1% carbohydrate of total energy. Anthropometric measurements were conducted on the mornings of the first, eighth and fourteenth days. Serum samples were prepared from twelve-hour fasting venous blood. Biochemical indexes including lipids; glucose and insulin were measured with routine methods. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS: At baseline, the control group had lower levels of body mass (P = 0.000), BMI (P = 0.000), waist-hip ratio (P = 0.000), systolic blood pressure (P = 0.001), diagnostic blood pressure (P = 0.016) and triglycerides (P = 0.006), and a higher level of HDL cholesterol (P = 0.005) than the overweight group. When compared with those before the ILF-HC diet, total cholesterol (P < 0.05) and LDL cholesterol (P < 0.05) decreased, and insulin (P < 0.05) and HOMA-IR (P < 0.05) increased in both the control group and the overweight group after the LF-HC diet. Increased triglycerides (P = 0.000) were observed only in the control subjects, and HDL cholesterol (P = 0.018) increased only in the overweight subjects after the LF-HC diet. CONCLUSION: The responses of serum TG and HDL-C to the LF-HC diet are related to BMI in healthy youth.

[Effects of the LIPE C-60G polymorphism on changes of plasma lipids and glucose induced by a high-carbohydrate diet in healthy youth].

OBJECTIVE: To investigate the interaction of the C-60G polymorphism of hormone sensitive lipase gene (LIPE) with a high carbohydrate (high-CHO) diet on plasma lipids and glucose in a young and healthy Chinese Han population. METHODS: 27 males and 29 females were given a washout diets of 31% fat, 54% carbohydrate and 15% protein for 7 days, followed by the high-CHO diet of 15% fat, 70% carbohydrate and 15% protein for 6 days, without total energy restriction. Plasma lipid profiles, glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI) at baseline, before and after the high-CHO diets as well as the LIPE C-60G polymorphism were analyzed. RESULTS: The females with the CC genotype had significantly higher levels of high-density lipoprotein cholesterol (HDL-C) (P < 0.01, P < 0.05) and apolipoprotein A-I (apo A-I ) (P < 0.01, P < 0.01) than the males with the same genotype both before and after the high-CHO diet. After the high-CHO diet, only the females with the CC genotype had significantly higher levels of total cholesterol (TC) (P < 0.01) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05) than their male counterparts. Compared with those before the high-CHO diet, the males with the CC genotype had significantly lower levels of BMI (P < 0.05), TC (P < 0.01) and LDL-C (P < 0.01), but significantly higher levels of HDL-C (P < 0.01) and apo A-I (P < 0.05) after the high-CHO diet. The males with the CG genotype experienced significant decreases of BMI (P < 0.05) and TC (P < 0.01). The females with the CC genotype experienced significant decreases of TC (P < 0.01) and LDL-C (P < 0.01) but significant increases of triglyceride (TG) (P < 0.01) and insulin (P < 0.05). The females with the CG genotype experienced a significant decrease of TC (P < 0.05) but a significant increase of TG (P < 0.05). CONCLUSION: LIPE C-60G variation can inhibit the decrease of LDL-C and the increases of HDL-C and apo A-I in young healthy males induced by the high-CHO diet, and can inhibit the decrease of LDL-C and the increase of insulin in young healthy females induced by the same diet.

[Effects of the +83C/T polymorphism in apolipoprotein AI gene on the changes of serum biochemical traits of gluocse and lipid metabolism induced by high-carbohydrate diets].

OBJECTIVE: The aim of the present study was to investigate the possible effects of the +83C/T polymorphism in apolipoprotein AI gene (apoA1) on the changes of serum lipids, glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) induced by a high-carbohydrate diet in healthy youth. METHODS: Fifty-six participants were given a washout diet for 7 d, followed by a high-carbohydrate diet for 6 d. The washout diet contained 15% protein, 31% fat and 54% carbohydrate. The high-carbohydrate diet contained 15% protein, 15% fat and 70% carbohydrate. Twelve hour fasting venous blood was drawn on the mornings of the first, eighth and fourteenth days. Blood lipids, glucose and insulin were measured, and HOMA-IR was calculated. The genome DNA was extracted and the apoA1 + 83C/T polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism. RESULTS: Triglyceride and insulin were found significantly increased in the subjects with the CC genotype, but not in the T carriers after the high-carbohydrate diet. Significant decreases of total cholesterol and LDL-C and a significant increase of HDL-C were observed after the dietary intervention of the high-carbohydrate diet. CONCLUSION: The triglyceride and insulin changes after the high-carbohydrate diet can be modulated by the apoA1 +83C/T polymorphism, and the T allele may eliminate the increase in triglyceride and insulin induced by the high-carbohydrate diet.

[Effects of the beta2-adrenergic receptor Gln27Glu variation on changes of serum lipid and apolipoprotein ratios induced by a high-carbohydrate/low-fat diet in healthy youth].

OBJECTIVE: To investigate the effects of the Gln27Glu polymorphism of beta2-adrenergic receptor (beta2AR) on serum lipid and apolipoprotein ratios and its interaction with high-carbohydrate/low-fat (HC/LF) diet on the ratios in healthy youth. METHODS: After on a washout diet for seven days, fifty six healthy young subjects were given the HC/LF diet for six days. The 12 hour-fasting serum lipids and apolipoproteins (apo) AI and B100 were measured on the 1st, the 8th and the 14th days. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoAI/apoB100 were calculated. The polymorphism of Gln27Glu was analyzed by PCR-RFLP method. RESULTS: No significant differences were found of the lipid and apolipoprotein ratios at baseline and before the HC/LF diet between the subjects with the CC genotype (wide type) and the G carriers (mutation carriers) in the whole study sample or the males and the females separately. The G carriers had a significantly higher level of log (TG/HDL-C) (P=0.038) than the subjects with the CC genotype did after the HC/LF diet in the whole study sample but not in the males and the females separately. Significant decreases of LDL-C/HDL-C and TC/HDL-C were observed in all the subjects after the HC/LF diet when compared with those before the HC/LF diet (P<0.05), but a significant increase of apoAI/apoB100 (P=0.021) only in the subjects with the CC genotype. When gender was taken into account, significant decreases of LDL-C/HDL-C and TC/HDL-C were found after the HC/ LF diet in the male subjects regardless of genotypes (P<0.05). Significant increases of TG/HDL-C and log (TG/ HDL-C) and a significant decrease of TC/HDL-C were found in all the female subjects (P<0.05), while a significant decrease of LDL-C/HDL-C (P=0.037) was only observed in the female subjects with the CC genotype. CONCLUSION: The G allele of beta2AR Gln27Glu variation can inhibit the decrease of LDL-C/HDL-C in females after HC/LF diet intervention.

Anti-hepatitis B virus activities of cinobufacini and its active components bufalin and cinobufagin in HepG2.2.15 cells.

Cinobufacini (Huachansu) is a Chinese medicine prepared from the skin of Bufo bufo gargarizans Cantor (Bufonidae), which has long been used in traditional Chinese medicine (TCM). The aim of present study was to examine the anti-hepatitis B virus (HBV) activities of cinobufacini and its active components bufalin and cinobufagin in the human HBV-transfected cell line HepG2.2.15. The hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core-related antigen (HBcrAg) concentrations in cell culture medium were determined by chemiluminescent enzyme immunoassay after HepG2.2.15 cells were respectively treated with different concentrations of cinobufacini, bufalin, and cinobufagin for 3 or 6 d. HBV DNA and mRNA were determined using transcription-mediated amplification and real-time polymerase chain reaction (PCR), respectively. On d 3, cinobufacini at a concentration of 1 µg/ml had no activity against HBV virological markers. However, on d 6, cinobufacini at 1 µg/ml effectively inhibited the secretion of HBsAg, HBeAg, and HBcrAg by 29.58, 32.87, and 42.52%. It was more potent than the positive control lamivudine (100 µg/ml). Bufalin and cinobufagin slightly inhibited HBV antigen secretion. Treatment with cinobufacini, bufalin, or cinobufagin had no anti-HBV effect on DNA in cell culture medium. Consistent with the HBV antigen reduction, HBV mRNA expression was markedly inhibited in comparison to the control when HepG2.2.15 cells were treated with cinobufacini, bufalin, or cinobufagin. Results suggested that cinobufacini had more potent activity against HBV antigen secretion than its components bufalin and cinobufagin and this inhibitory role was attributed to the specific inhibition of HBV mRNA expression.

[Effects of the 54G/C polymorphism of sterol regulatory element-binding protein-1c on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy youth].

OBJECTIVE: To investigate the effects of 54G/C polymorphism of sterol regulatory element-binding protein-1c gene (SREBP-1c) on serum lipid ratios and their response to high-carbohydrate/low-fat (HC/LF) diet in healthy youth. METHODS: After a regular diet for 7 days of wash-out, 56 healthy youth (22.89 +/- 1.80 yrs) were given HC/LF diet for 6 days. The regular diet contained 54% carbohydrate, 15% protein, and 31% fat of the total energy. The HC/LF diet contained 70% carbohydrate, 15% protein, and 15% fat of the total energy. The serum lipids and glucose were measured on the 1st, 8th and 14th days. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. The 54G/C polymorphism of SREBP-1c gene was analyzed by PCR-RFLP method. RESULTS: No significant difference was found in lipid ratios and glucose at baseline and after regular diet in subjects with different genotypes in either the whole studied population or in males or females only. However, after HC/LF diet, LDL-C/HDL-C was significantly lower in females carrying the C allele than those of GG homozygotes (P< 0.05). Compared with those before HC/LF diet, TC/HDL-C and LDL-C/HDL-C were significantly decreased in all the subjects (P< 0.05). When gender was taken into account, significant increase of TG/HDL-C and log(TG/HDL-C) was found only in females with GG genotype (P< 0.05). All the subjects experienced significant decrease of TC/HDL-C and LDL-C/HDL-C regardless of their genders and genotypes (P< 0.05). CONCLUSION: The 54G/C polymorphism of SREBP-1c gene can influence the response of TG/HDL-C and log(TG/HDL-C) to HC/LF diet in females. The C allele may be a protective factor to prevent the increase of TG induced by HC/LF diet in females.

[Effects of adiponectin gene SNP45T/G on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy Chinese youth].

OBJECTIVE: To investigate the effects of adiponectin gene (APM1) SNP45T/G on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy young Chinese. METHODS: Fifty-six healthy young subjects were given two consecutive diets. The first was control diet (54% carbohydrate, 15% protein, and 31% fat) for 7 days, and the second was HC/LF diet (70% carbohydrate, 15% protein, and 15% fat) for 6 days. Before and after each diet, serum lipids and SNP45T/G were analyzed. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. RESULTS: There was no significant difference of baseline lipid ratios between subjects with TT genotype and subjects carrying G allele (G carriers) in the whole population or in the males and females separately. The G allele was associated with significantly higher TC/HDL-C after HC/LF diet in the males (P < 0.05); and the males with TT genotype had significant decreases of LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.05) after HC/LF diet compared with those before the diet, while G carriers only experienced significant decrease of TC/HDL-C (P < 0.01). In the females, TT genotype was associated with significantly higher TG/HDL-C (P < 0.05) and log (TG/HDL-C) (P < 0.05) both before and after the HC/LF diet. When compared with those before HC/LF diet, elevated TG/HDL-C (P < 0.05) and log (TG/ HDL-C) (P < 0.05) and declined TC/HDL-C (P < 0.01) were observed in the subjects with TT genotype after the diet. In the female subjects of G carriers, LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.01) decreased significantly after the HC/LF diet. CONCLUSION: G allele of APM1 45T/G could inhibit increase of TG/HDL-C and log (TG/HDL-C) and promote the decrease of LDL-C/HDL-C induced by HC/LF diet in healthy young females. But in the healthy young males, it might eliminate the decline of LDL-C/HDL-C induced by HC/LF diet and increase TC/HDL-C.