Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.

PURPOSE: To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. METHODS AND RESULTS: TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. CONCLUSION: The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. METHODS: We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT. RESULTS: After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. CONCLUSIONS: NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.

Effects of genetic variants in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, ORM1 on PK/PD of telmisartan in Chinese patients with mild to moderate essential hypertension
.

PURPOSE: This study aimed to understand the effects of single nucleotide polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the pharmacokinetics (PK) (plasma concentration) and pharmacodynamics (PD) (blood pressure) of telmisartan in Chinese patients. METHODS: 58 Han Chinese patients (aged 45 - 72 years) with mild to moderate essential hypertension were included and received 80 mg/day telmisartan for 4 weeks. The plasma concentration and genetic variants were determined by LC/MS/MS and MALDI-TOF mass spectrometry, respectively. Multivariable linear analysis was used to examine the relationships between PK/PD and genetic variants. RESULTS: Females showed a significantly higher AUClast than males (n = 22, 4,879.48 ± 3,449.33 h×ng/mL vs. n = 36, 2,715.59 ± 2,223.77 h×ng/mL, p = 0.047). Amongst all genetic variants investigated, the patients with UGT1A1 rs4124874 AA (n = 11, 1,730.51 ± 1,325.79 h×ng/mL) had a significantly lower AUClast compared with patients with UGT1A1 rs4124874 CC+AC (n = 19 + 28, 4,177.44 ± 3,222.11 h×ng/mL and 3,810.82 ± 2,960.43 h×ng/mL, p = 0.027). None of the SNPs investigated was associated with the PD responses to telmisartan. CONCLUSION: Variation of UGT1A1 (rs4124874) affects PK of telmisartan in Chinese patients, highlighting the value of genetic testing in precision medicine as the telmisartan dose could be adjusted based on UGT1A1 genetic variations.
.

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.

Anti-apoptosis effect of polysaccharide isolated from the seeds of Cuscuta chinensis Lam on cardiomyocytes in aging rats.

To investigate the mechanism of apoptosis in myocardial cells of aging rats induced by D-galactose and to study the effect of the Polysaccharide isolated from the seeds of Cuscuta chinensis Lam (PCCL) on apoptosis of cardiomyocytes and its corresponding machinasim in aging rat model. Fifty male SD rats were randomly divided into 5 groups. Normal control group (NC). D-galactose (100 mg · kg(-1)d(-1) for 56 day) indued aging group (MC), D-galactose plus 100 mg kg(-1) d(-1) PCCL group (ML), D-galactose plus 200 mg kg(-1) d(-1) PCCL group (MM), and D-galactose plus 400 mg kg(-1) d(-1) PCCL group (MH). Same volume of solution (water, or PCCL aqueous solution) was given by gavage for 56 days. Then the hearts were collected and apoptosis parameters were evaluated. Caspase-3 and Cyt c were determined by fluorescence spectrometer, the apoptosis rate was assessed by AnnexinV-FITC method by Flow-Cytometry, [Ca(2+)]i and [Ca(2+)]i overloaded by KCL were observed by laser scanning confocal microscopy (LSCM); Bcl-2 and Bax were examined by immunohistochemistry. The content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3, Bax expression level in D-galactose induced aging group were higher than NC (p < 0.05). The ratio of Bcl-2/Bax was decreased in D-galactose induced aging group compared to NC. On the other hand, the content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3 and apoptosis rate, as well as Bax expression level in all three PCCL groups were decreased compared to galactose induced group (p < 0.05). Bcl-2/Bax ratio was increased in all PCCL groups compared to galactose induced aging group. PCCL could decrease the apoptosis of cardiomyocytes by the mitochondria apoptosis pathway.

Heating tumors with tumor cell-derived nanoparticles to enhance chemoimmunotherapy for colorectal cancer.

Aim: To investigate the mechanism of doxorubicin (DOX)-induced immunogenic cell death (ICD) and to improve immunotherapy efficacy. Materials & methods: In this study, hybrid vesicles containing DOX (HV-DOX) were prepared by thin-film hydration with extrusion, and the formulated nanoparticles were characterized physically. Furthermore, in vitro experiments and animal models were used to investigate the efficacy and new mechanisms of chemotherapy combined with immunotherapy. Results: DOX improved tumor immunogenicity by alkalinizing lysosomes, inhibiting tumor cell autophagy and inducing ICD. HVs could activate dendritic cell maturation, synergistically enhancing chemotherapeutic immunity. Conclusion: The mechanism of DOX-induced ICD was explored, and antitumor immunity was synergistically activated by HV-DOX to improve chemotherapeutic drug loading and provide relevant antigenic information.

[The effect of eukaryotic expression plasmid ARHI on gastric cancer].

OBJECTIVE: To study the effect of expressed aplasia ras homolog member I (ARHI) on the malignant biological behaviors of gastric cancer including the proliferation, migration and invasion of the cell. METHODS: The eukaryotic expression plasmid of ARHI was constructed and transfected into MKN-28 cell with lipofectamine 2000 as pEGFP-ARHI group, transfected with pEGFP-N1 as pEGFP-N1 group, and untreated MKN-28 as control group. The expression of ARHI was detected by Western blotting and fluorescence microscope. CCK-8 assay was used to analyze the cell proliferation, the wound-healing assay and transwell assay were performed to investigate the effects on migration and invasion. RESULTS: Compared with the pEGFP-N1 group and control group, proliferation, invasion and migration of the pEGFP-ARHI group were depressed (P < 0.05). CONCLUSION: Recombination eukaryotic expression pEGFP-ARHI could partially reverse the malignant phenotypes of gastric cancer cell MKN-28.

Novel Self-Assembled Multifunctional Nanoprobes for Second-Near-Infrared-Fluorescence-Image-Guided Breast Cancer Surgery and Enhanced Radiotherapy Efficacy.

Breast-conserving surgery (BCS) is the predominant treatment approach for initial breast cancer. However, due to a lack of effective methods evaluating BCS margins, local recurrence caused by positive margins remains an issue. Accordingly, radiation therapy (RT) is a common modality in patients with advanced breast cancer. However, while RT also protects normal tissue and enhances tumor bed doses to improve therapeutic effects, current radiosensitizers cannot meet these urgent clinical needs. To address this, a novel self-assembled multifunctional nanoprobe (NP) gadolinium (Gd)-diethylenetriaminepentaacetic acid-human serum albumin (HSA)@indocyanine green-Bevacizumab (NPs-Bev) is synthesized to improve the efficacy of fluorescence-image-guided BCS and RT. Fluorescence image guidance of the second near infrared NP improves complete resection in tumor-bearing mice and accurately discriminates between benign and malignant mammary tissue in transgenic mice. Moreover, targeting tumors with NPs induces more reactive oxygen species under X-ray radiation therapy, which not only increases RT sensitivity, but also reduces tumor progression in mice. Interestingly, self-assembled NPs-Bev using HSA, the magnetic resonance contrast agent and Bevacizumab-targeting vascular growth factor A, which are clinically safe reagents, are safe in vitro and in vivo. Therefore, the novel self-assembled NPs provide a solid precision therapy platform to treat breast cancer.

[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.

Application of molecular imaging in immune checkpoints therapy: From response assessment to prognosis prediction.

Recently, immune checkpoint therapy (ICT) represented by programmed cell death1 (PD-1) and its major ligands, programmed death ligand 1 (PD-L1), has achieved significant success. Detection of PD-L1 by immunohistochemistry (IHC) is a classic method to guide the treatment of ICT patients. However, PD-L1 expression in the tumor microenvironment is highly complex. Thus, PD-L1 IHC is inadequate to fully understand the relevance of PD-L1 levels in the whole body and their dynamics to improve therapeutic outcomes. Intriguingly, numerous studies have revealed that molecular imaging technologies could potentially meet this need. Therefore, the purpose of this narrative review is to summarize the preclinical and clinical application of ICT guided by molecular imaging technology, and to explore the future opportunities and practical difficulties of these innovations.

[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.

Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN.

Notch receptors (Notch1-4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

[Effects of lipoprotein lipase gene Ser447stop polymorphism on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy youth].

OBJECTIVE: To investigate the effects of lipoprotein lipase gene (LPL) Ser447stop polymorphism on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy youth. METHODS: Fifty-six healthy subjects [(22.89 +/- 1.80) years) were given control diets of 31% fat and 54% carbohydrate for 7 days, followed by HC diets of 15% fat and 70% carbohydrate for 6 days, without total energy restriction. Serum lipid profiles at baseline, before and after HC diets, as well as LPL Ser447stop polymorphisms were analyzed. TG/ HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. RESULTS: No significant differences were found of the lipid ratios at baseline and before and after HC/LF diet between subjects of wild type (S447S) and mutation carriers (447XC) in the whole study population or males and females separately. When compared with those before HC/LF diet, significantly decreased LDL-C/HDL-C and TC/HDL-C were found regardless of LPL Ser447stop genotype (P < 0.05) and increased log (TG/HDL-C) in subjects with S447S (P < 0.05) in the whole study population. After gender was taken into account, LDL-C/HDL-C and TC/HDL-C were significantly decreased in males (P < 0.001) regardless of LPL Ser447stop polymorphism. TG/HDL-C and log (TG/HDL-C) were significantly increased (P < 0.05), and LDL-C/HDL-C and TC/HDL-C were significantly decreased (P < 0.05) in females with S447S. No significant differences were found in females with 447XC. CONCLUSION: The functional C to G mutation of LPL Ser447Stop could attenuate the elevated log (TG/HDL-C) induced by HC/LF diet. Interactions of LPL Ser447Stop polymorphism with HC/LF diet on the lipid ratios were gender-specific and effective only in females.

[Effects of Pvu II polymorphism in low density lipoprotein receptor gene on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy youth].

OBJECTIVE: To investigate the effects of low density lipoprotein receptor gene (LDLR) Pvu II polymorphism on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy youth. METHODS: After a regular diet for 7 days of wash-out, 56 health youth ((22.89 +/- 1.80) years old)] were given LF/HC diet for 6 days. The regular diet contained 54% carbohydrate, 15% protein, and 31% fat of the total energy. The LF/HC diet contained 70% carbohydrate, 15% proteine and 15% fat of the total energy. The serum lipids were measured on the 1st, the 8th and the 14th days. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. The polymorphism of LDLR was detected by PCR-RFLP method and its relationship with serum lipid ratios was analyzed. RESULTS: No significant difference was found of the lipid ratios at baseline in subjects with different genotypes in both genders. Before or after HC/LF diet, no significant difference was found of the lipid ratios between the subjects with different genotypes in the whole study population or in males and females separately. Compared with those of before HC/LF diet, all the subjects experienced significant decrease of TC/HDL-C and LDL-C/HDL-C (P < 0.05). When gender was taken into account, significant increases of TG/HDL-C and log(TG/HDL-C) were found only in females (P < 0.05). All the subjects experienced significant decrease of TC/HDL-C regardless of gender and genotype (P < 0.05). As for LDL-C/HDL-C, significant decrease was found only in males with P1P1 and female subjects (P < 0.05). CONCLUSION: Polymorphism of LDLR Pvu II may influence the response of LDL-C/HDL-C to HC/LF diet in males.

[Distribution Characteristics and Migration Rules of Pollutants in Sediments of Reservoirs with Eucalyptus Plantation, Southern China].

The safety of water quantity and quality caused by large-scale blackwater in reservoirs with Eucalyptus plantation is currently a point of great interest. Eucalyptus is largely planted in southern China, especially in Nanning, Guangxi, where more than 90% of the drinking water source reservoirs are surrounded by Eucalyptus, and different degrees of blackwater often occur in many reservoirs. Recent research has demonstrated that reservoir sediments play an important role in the migration and transformation of Fe2+, Mn2+, S2-, and dissolved organic carbon (DOC) in the overlying water. It is of great significance to explore the distribution characteristics and migration rules of pollutants in the sediment-water interface to reveal the mechanism of blackwater in reservoirs. Experiments were carried out three times in a typical blackwater reservoir (Tianbao Reservoir) in southern China from July to December 2018. The distribution characteristics and seasonal variations of iron, manganese, sulfide, and organic matter in sediments were analyzed, focusing mainly on the profile distribution and migration direction of Fe2+, Mn2+, S2- and DOC in pore water during blackwater periods. The results showed that:① The content of iron and manganese in sediments of reservoirs with Eucalyptus plantation is high, far exceeding the background value of soil content in China. The content of iron, manganese, and total organic carbon (TOC) in the surface sediments increases simultaneously, mainly caused by the input and settlement of the material (litter, decomposed liquids. and soil particles) in the Eucalyptus forest around the reservoir. ② The concentration of Fe2+(16.99 mg·L-1) and the content of DOC (36.80%) in pore water during the blackwater period are significantly higher than those in Taihu Lake during the black bloom (12.15 mg·L-1, 10.78%). The mean concentrations of Fe2+ and Mn2+ are more than 300 times higher than that of S2-, and the reduction conditions in the sediments are dominated by iron and manganese oxides. ③ The diffusion flux of Fe2+ is 27.4-33.5 mg·(m2·d)-1, which is 32.6, 4.9, and 30.8 times higher than those of Taihu Lake, Aha Reservoir, and Hongfeng Lake, respectively. This implies strong Fe2+ release ability from sediments to the overlying water. As a positive correction exists between Fe2+ and DOC, the complex reaction between Fe2+ and organic matter is one of the most important causes of blackwater in reservoirs with Eucalyptus plantation.

[Effects of cholesterol ester transfer protein taqIB polymorphism on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy youth].

OBJECTIVE: To investigate the effects of cholesterol ester transfer protein gene (CETP) TaqIB polymorphism on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy youth. METHODS: After on regular diet for 7 days, 56 health youth [(22.89+/-1.80) years] were given HC/LF diet for 6 days. The regular diet contained 54% carbohydrate, 15% protein, and 31% fat of the total energy. The LF/HC diet contained 70% carbohydrate, 15% protein, and 15% fat of the total energy. The serum lipids were measured on the 1st, the 8th and the 14th day. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. The polymorphism of CETP was analyzed by PCR-RFLP method. RESULTS: No significant difference was found of the lipid ratios at baseline in subjects with different genotypes in both genders. After the regular diet, TC/HDL-C was significantly lower in males carrying the B2 allele than B1B1 homozygotes (P<0.05). After HC/LF diet, no significant difference was found of the lipid ratios between the subjects with different genotypes in the whole study population or in males and females separately. Compared with those before HC/LF diet, subjects with B1B1 genotype experienced significant changes of the four lipid ratios after HC/LF diet (P<0.05), while the B2 carriers had only significant decrease of TC/HDL-C and LDL-C/HDL-C (P<0.05). No significant difference of the changes of the four lipid ratios before and after HC/LF diet was found between the subjects with different genotypes. When gender was taken into account, significant increases of TG/HDL-C and log (TG/HDL-C) were found in females with B1B1 genotype (P<0.05). All the subjects experienced significant decrease of TC/HDL-C and LDL-C/HDL-C regardless of gender and genotype (P<0.05). As for the changes of lipid ratios before and after HC/LF diet, difference of only TC/HDL-C was found between males with B1B1 and male carriers of B2 (P<0.05). CONCLUSION: Polymorphism of CETP TaqIB may influence the response of TC/HDL-C to HC/LF diet in males and the increases of TG/HDL-C and log (TG/HDL-C) induced by HC/LF diet in females.

No decrease of HDL cholesterol after 6 days of low fat and high carbohydrate diets in a young Chinese Han population.

More studies are needed on the hypertriacylglycerolemic effects of low fat and high carbohydrate (LF-HC) diet in young population, especially Chinese who generally have a diet containing lower fat and higher carbohydrate. To test them in a young Chinese Han population, 56 healthy subjects (22.89 +/- 1.80) years were given regular diet of 31% fat and 54% carbohydrate for 7 days, followed by LF-HC diet of 15% fat and 70% carbohydrate for 6 days, without total energy restriction. After the LF-HC diet, the male experienced an increase of high density lipoprotein (HDL) cholesterol and decreases of weight, body mass index (BMI), total cholesterol (TC), and LDL (low density lipoprotein) cholesterol (P < 0.05). The female experienced increased serum triacylglycerol and insulin, and decreased TC and LDL cholesterol (P < 0.05). When BMI was taken into account, all the subjects with low, medium, or high BMI experienced decreases of TC and LDL cholesterol although some changes were not significant. No significant decrease of HDL cholesterol was found, while significantly increased HDL cholesterol and apolipoprotein A-I (apo A-I) were found in the male subjects with low or high BMI (P < 0.05). Significant increase of triacylglycerol was observed only in the female subjects with low or medium BMI. In conclusion, subjects with different BMI and gender have different triacylglycerol and HDL cholesterol responses to LF-HC diets, and significant increase of HDL cholesterol and apolipoprotein A- I were observed in some young male subjects.

[Effects of high-carbohydrate/low-fat diet on serum lipid ratios in healthy young subjects].

OBJECTIVE: To investigate the effects of the short-term high-carbohydrate/low-fat (HC/LF) diet on the serum lipid ratios of healthy young subjects, which meant triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), the logarithm of TG/HDL-C [log (TG/HDL-C)], low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C), and total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C). METHODS: 56 healthy participants with the average age of (22.89 +/- 1.80) years took the normal diet for 7 days followed by HC/LF diet for 6 days. Venous blood samples in fasting were collected between 7 : 00 and 10 : 00 AM on the 1st, the 8th and 14th day, respectively. Serum concentrations of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were measured by regular methods. The ratios of TG/HDL-C, log (TG/HDL-C), LDL-C/HDL-C, and TC/ HDL-C were calculated. RESULTS: After HC/LF diet, both TG/HDL-C and log (TG/HDL-C) increased significantly for females (P < 0.05). For the males, these two ratios were decreased although not significant in statistics. When BMI or WHR was taken into account, the two ratios increased significantly after HC/LF diet, but only for the normal females (P < 0.05), not for the females with overall or abdominal adiposity. No significant changes of TG/HDL-C and log(TG/HDL-C) after HC/LF diet were observed between the males with different BMI or WHR. TC/HDL-C and LDL-C/HDL-C decreased significantly (P < 0.05) after HC/LF diet, but these changes were not found to associate with gender, BMI or WHR. CONCLUSION: The changes of TG/HDL-C and log (TG/HDL-C) induced by the short-term HC/LF diet are different in healthy young subjects with different gender, BMI or WHR, but there is no significant change happening to TC/HDL-C and LDL-C/HDL-C.

Long noncoding RNA ATB promotes the epithelial-mesenchymal transition by upregulating the miR-200c/Twist1 axe and predicts poor prognosis in breast cancer.

Recent studies indicate that the long noncoding RNA ATB (lncATB) can induce the epithelial-mesenchymal transition (EMT) in cancer cells, but the specific cellular targets of lncATB require further investigation. In the present study, the upregulation of lncATB in breast cancer cells was validated in a TGF-ß-induced EMT model. Gain- and loss-of-function studies demonstrated that lncATB enhanced cell migration, invasion and clonogenicity in vitro and in vivo. LncATB promoted the EMT by acting as a sponge for the miR-200 family and restoring Twist1 expression. Subsequently, the clinical significance of lncATB was investigated in a cohort of breast cancer patients (N = 131). Higher lncATB expression was correlated with increased nodal metastasis (P = 0.036) and advanced clinical stage (P = 0.011) as well as shorter disease-free survival (P = 0.043) and overall survival (P = 0.046). These findings define Twist1 as a major target of lncATB in the induction of the EMT and highlight lncATB as a biomarker in breast cancer patients.

[Effects of a high-carbohydrate, low-fat diet on the levels of serum phospholipids and triglycerides].

OBJECTIVE: To study the effects of a High-carbohydrate, Low-fat (HC/LF) diet on the levels of phospholipids and triglycerides in serum and analyze their association with anthropometric indexs and serum biochemical traits. METHODS: 56 healthy volunteers had a HC/LF diet for 6 days. The body weight, waist circumference, hip circumference, biceps circumference, and skinfold thickness were measured before and after the HC/LF diet. Venous blood was taken after fasting of 12 hours. The levers of high density lipoprotein-phospholipid (HDL-PL), high density lipoprotein-triglyceride (HDL-TG), high density lipoprotein-cholesterol (HDL-C) were enzymatically determined after precipitation of serum apoB containing lipoproteins with phosphotungistic acid and non-LDL-phospholipid (NLDL-PL), non-LDL-triglyceride (NLDL-TG), non-LDL-Cholesterol (NLDL-C) levels were enzymatically determined after precipitation of serum LDL with polyethylene sulfate. The levels of serum LDL-PL, LDL-TG, and LDL-C were calculated by minus of non-LDL from serum PL, TG, and TC levels, respectively. The level of TRL-TG was calculated by minus of HDL-TG, LDL-TG from total TG. The level of serum insulin was measured by electrochemical luminescence. RESULTS: The levels of fasting serum PL, HDL-PL and LDL-PL decreased significantly after HC/LF diet, whereas the levels of TG, HDL-TG and insulin increased. Correlation analyses indicated that after HC/LF diet the change of serum PL (APL) had a negative correlation with the change of BMI(deltaBMI),a positive correlation with the change of HDL-TG(deltaHDL-TG) and insulin (delta insulin). The change of serum LDL-PL (deltaLDL-PL) had a negative correlation with deltaBMI and waist circumference (deltaAWC), meanwhile the change of HDL-PL (deltaHDL-PL) had a negative correlation with deltaHDL-TG, a positive correlation with the change of HDL-C (deltaHDL-L). A positive correlation existed between deltaHDL-TG and wais/hip circumference ratio (deltaW/H). CONCLUSION: HC/LF diet can decrease serum PL, HDL-PL level but increase serum levels of TG and insulin. The change of serum PL level had a negative correlation with deltaBMI,a positive correlation with deltaHDL-TG and delta insulin.