Different effects of maternal homocysteine concentration, MTHFR and MTRR genetic polymorphisms on the occurrence of fetal aneuploidy.

RESEARCH QUESTION: Do maternal homocysteine (Hcy) concentrations, MTHFR and MTRR genes have effects on the occurrence of fetal aneuploidy? DESIGN: A total of 619 aneuploidy mothers and 192 control mothers were recruited in this study. Differences in distributions of maternal MTHFR 677C>T, MTHFR 1298A>C and MTRR 66A>G genetic polymorphisms and maternal Hcy concentrations between aneuploidy mothers and control mothers were analysed. RESULTS: The maternal MTHFR 677C>T polymorphism was found to be a risk factor for the occurrence of many fetal non-mosaic aneuploidies studied here, including trisomies 13, 15, 16, 18, 21, 22, TRA and TS. The maternal MTHFR 1298A>C polymorphism was found to be a risk factor specifically associated with the occurrence of fetal trisomy 15 and fetal TS. The maternal MTRR 66A>G polymorphism was found to be a risk factor only specifically associated with the occurrence of fetal trisomy 21. The Hcy concentrations of mothers of trisomies 22, 21, 18, 16, 15 and TS fetuses were significantly higher than the Hcy concentrations of control mothers. CONCLUSIONS: Overall, data suggested an association between these maternal polymorphisms and the susceptibility of fetal non-mosaic trisomy and Turner syndrome. However, these three maternal polymorphisms had different associations with the susceptibility of different fetal aneuploidies, and the elevated maternal Hcy concentration appeared to be a likely risk factor for fetal Turner syndrome and fetal trisomies.

Time-restricted feeding alleviates cardiac dysfunction induced by simulated microgravity via restoring cardiac FGF21 signaling.

Dietary restriction has been well-described to improve health metrics, but whether it could benefit pathophysiological adaptation to extreme environment, for example, microgravity, remains unknown. Here, we investigated the effects of a daily rhythm of fasting and feeding without reducing caloric intake on cardiac function and metabolism against simulated microgravity. Male rats under ad libitum feeding or time-restricted feeding (TRF; food access limited to 8 hours every day) were subjected to hindlimb unloading (HU) to simulate microgravity. HU for 6 weeks led to left ventricular dyssynchrony and declined cardiac function. HU also lowered pyruvate dehydrogenase (PDH) activity and impaired glucose utilization in the heart. All these were largely preserved by TRF. TRF showed no effects on HU-induced loss of cardiac mass, but significantly improved contractile function of cardiomyocytes. Interestingly, TRF raised liver-derived fibroblast growth factor 21 (FGF21) level and enhanced cardiac FGF21 signaling as manifested by upregulation of FGF receptor-1 (FGFR1) expression and its downstream markers in HU rats. In isolated cardiomyocytes, FGF21 treatment improved PDH activity and glucose utilization, consequently enhancing cell contractile function. Finally, both liver-specific knockdown (KD) of FGF21 and cardiac-specific FGFR1 KD abrogated the cardioprotective effects of TRF in HU rats. These data demonstrate that TRF improves cardiac glucose utilization and ameliorates cardiac dysfunction induced by simulated microgravity, at least partially, through restoring cardiac FGF21 signaling, suggesting TRF as a potential countermeasure for cardioprotection in long-term spaceflight.

Parental Genetic Variants, MTHFR 677C>T and MTRR 66A>G, Associated Differently with Fetal Congenital Heart Defect.

BACKGROUND: Congenital heart defect (CHD) is one of the most common birth defects in the world. The methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are two of the most important candidate genes for fetal CHD. However, the correlations between the two genes and fetal CHD were inconsistent in various reports. Therefore, this study is aimed to evaluate the parental effects of the two genes on fetal CHD via three genetic polymorphisms, MTHFR 677C>T (rs1801133), MTHFR 1298 A>C (rs1801131), and MTRR 66A>G (rs1801394). METHODS: Parents with pregnancy history of fetal CHD were divided into two subgroups: ventricular septal defect (VSD) (21) and non-VSD groups (78). VSD, non-VSD, and 114 control parents (controls) were analyzed in this study. Genotyping of these genetic polymorphisms was done by sequencing. RESULTS: The MTHFR 677C>T polymorphism of either mothers or fathers was independently associated with fetal non-VSD (P < 0.05) but not VSD, while the MTRR 66A>G polymorphism was independently associated with fetal VSD (P < 0.05) but not non-VSD. No significance was found for MTHFR 1298A>C polymorphism. CONCLUSION: In either maternal or paternal group, the MTHFR 677C>T polymorphism was independently related to fetal non-VSD, while the MTRR 66A>G polymorphism was independently related to fetal VSD.

[Exercise and redox signaling regulation].

ROS, identified as signaling molecules, are responsible for maintaining redox homeostasis in vivo. Appropriate exercise promotes the generation of physiological ROS, enhances the antioxidative potential, promotes exercise performance, and improves metabolism, as well as retards aging and related diseases; whereas overload exercise causes excess ROS, resulting in exercise-induced fatigue or even exercise-induced injury. Mitochondria are the main pool of ROS production and act as the key organelles in modulating intracellular redox homeostasis. Mitochondrial nutrients not only maintain physiological redox homeostasis, but also ameliorate oxidative stress and fatigue induced by overload exercise, eventually improving exercise performance and preventing/ameliorating exercise-induced injury.

[Effect of zinc on mRNA expression of ZIP4 in Caco2 cells].

OBJECTIVE: To study the effect of zinc on mRNA expression of ZIP4 in human intestinal Caco2 cells and its regularity. METHODS: Low zinc cell model was established by TPEN, a kind of chelating agent which chelates specially to zinc. ZIP4 cDNA fragment was obtained by RT-PCR. Expression of ZIP4 on 10 micromol/L TPEN exposure after 0, 2, 4, 6, 8 and 10 hours in Caco2 cells and its expression on various concentration of TPEN exposure (0,2.5,5,7.5 and 10 micromol/L) was measured by RT-PCR. RESULTS: A proper single fragment is obtained with the sequence conformable to the design. A proper single ZIP4 cDNA fragment was obtained. The mRNA expression of ZIP4 increased in accordance with the duration of low zinc. The peak mRNA level appeared at about 6h. And the ZIP4 mRNA increased in accordance with the concentration of TPEN in Caco2 cells. CONCLUSION: Zinc can regulate the mRNA expression of ZIP4 in Caco2 cells. And ZIP4 may play a role in the absorption of zinc in human intestine.