Prenatal High-Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ-RXRg-ROS/Akt Signaling.

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.

Maternal High-Sucrose Diet Accelerates Vascular Stiffness in Aged Offspring via Suppressing Cav 1.2 and Contractile Phenotype of Vascular Smooth Muscle Cells.

SCOPE: The fetal programming in response to over-nutrition during pregnancy is involved in pathogenesis of cardiovascular diseases later in life. The authors' previous work reported that prenatal high-sucrose (HS) diet impaired functions of large-conductance Ca2+ -activated K+ channels (BK) in mesenteric arteries in the adolescent offspring rats. This study determines whether prenatal HS has a long-term impact on resistance vasculature in the aged offspring rats. METHODS AND RESULTS: Pregnant rats are fed with a high-sucrose diet until delivery. Aged offspring from prenatal HS exhibit elevated fasting insulin level, insulin resistance index, and diastolic pressure. Both pressure-induced myogenic responses and phenylephrine-stimulated contraction of mesenteric arteries in HS are weakened. Electrophysiological tests and western blot indicate that BK and L-type calcium channels (Cav 1.2) are impaired in HS group. On the other hand, expression of matrix metalloproteinase 2 of mesenteric arteries is reduced in HS group while expression of tissue inhibitors of metalloproteinase is increased, indicating that extra cellular matrix (ECM) is remodeled. Furthermore, expression of α-smooth muscle actin is decreased, and insulin/insulin receptor/phosphoinositide3-kinase (PI3K) signaling pathway is downregulated. CONCLUSION: The results suggest that prenatal HS induced stiffness of mesenteric arteries in aged offspring by inhibiting Cav 1.2 function and PI3K-associated contractile phenotype of VSMCs.

The clinical value and biological function of PTTG1 in colorectal cancer.

Pituitary tumor transforming gene-1 (PTTG1) has been suggested to serve as an oncogene in several types of human tumors, but little is known about the biological function of PTTG1 in colorectal cancer. PTTG1 mRNA and protein expressions in colorectal cancer tissues and cell lines were measured by qRT-PCR, western blot or immunohistochemistry. The association between PTTG1 protein expression and clinicopathological features was analyzed. The function of PTTG1 on colorectal cancer cell proliferation and metastasis were explored through MTT, colony formation, migration and invasion assays. In our results, PTTG1 mRNA and protein expressions were increased in colorectal cancer tissues and cell lines compared with normal colonic tissues and colon epithelial cell line. PTTG1 overexpression positively associated with clinical stage, T classification, N classification, M classification and differentiation. The univariate and multivariate analyses suggested PTTG1 overexpression was an independent poor prognostic factor for colorectal cancer patients. The in vitro experiments showed knocking down PTTG1 inhibited colorectal cancer growth and metastasis. In conclusion, PTTG1 is an independent prognostic factor and acts as an oncogene in colorectal cancer.

Effects of Bariatric Surgery on Renal Function in Obese Patients: A Systematic Review and Meta Analysis.

BACKGROUND: Obesity is an independent risk factor of development and progression of chronic kidney disease (CKD). Data on the benefits of bariatric surgery in obese patients with impaired kidney function have been conflicting. OBJECTIVE: To explore whether there is improvement in glomerular filtration rate (GFR), proteinuria or albuminuria after bariatric surgery. METHODS: We comprehensively searched the databases of MEDLINE, Embase, web of science and Cochrane for randomized, controlled trials and observational studies that examined bariatric surgery in obese subjects with impaired kidney function. Outcomes included the pre- and post-bariatric surgery GFR, proteinuria and albuminuria. In obese patients with hyperfiltration, we draw conclusions from studies using measured GFR (inulin or iothalamate clearance) unadjusted for BSA only. Study quality was evaluated using the Newcastle-Ottawa Scale. RESULTS: 32 observational studies met our inclusion criteria, and 30 studies were included in the meta-analysis. No matter in dichotomous data or in dichotomous data, there were statistically significant reduction in hyperfiltration, albuminuria and proteinuria after bariatric surgery. LIMITATIONS: The main limitation of this meta-analysis is the lack of randomized controlled trials (RCTs). Another limitation is the lack of long-term follow-up. CONCLUSIONS: Bariatric surgery could prevent further decline in renal function by reducing proteinuria, albuminuria and improving glomerular hyperfiltration in obese patients with impaired renal function. However, whether bariatric surgery reverses CKD or delays ESRD progression is still in question, large, randomized prospective studies with a longer follow-up are needed.

Transanal Pull-Through Procedure with Delayed versus Immediate Coloanal Anastomosis for Anus-Preserving Curative Resection of Lower Rectal Cancer: A Case-Control Study.

This case-control study compared the effectiveness and safety of transanal pull-through procedure (TPP) with delayed or immediate coloanal anastomosis (CAA) for anus-preserving curative resection of lower rectal cancer. Lower rectal cancer patients (n = 128) were hospitalized between January 2003 and December 2013 for elective anus-preserving curative resection through a TPP with delayed (n = 72) or immediate (n = 56) CAA. Main outcome measures including surgical safety, resection radicality, and defecation function were assessed. The two groups were comparable in age, sex, gross pathology, histology, and tumor-node-metastasis staging. Both the delayed and immediate CAA TPPs had similar resection radicality and safety profiles. The immediate CAA was associated with a significantly higher risk of anastomotic leakage and defecation impairment. None of patients in the delayed CAA group experienced anastomotic leakage. In conclusion, TPP with delayed CAA may be superior to immediate CAA in minimizing the risk of anastomotic leakage and relevant surgical morbidities, and does not require a temporary ileostomy and second-look restoration of ostomy.