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Transforming growth factor‐β (TGF‐β) signaling pathway is involved in fibrosis in most, if not all forms of cardiac diseases. Here, we evaluate a positive feedback signaling the loop of TGF‐β1/promyelocytic leukemia (PML) SUMOylation/Pin1 promoting the cardiac fibrosis. To test this hypothesis, the mice underwent transverse aortic constriction (3 weeks) were developed and the morphological evidence showed obvious interstitial fibrosis with TGF‐β1, Pin1 upregulation, and increase in PML SUMOylation. In neonatal mouse cardiac fibroblasts (NMCFs), we found that exogenous TGF‐β1 induced the upregulation of TGF‐β1 itself in a time‐ and dose‐dependent manner, and also triggered the PML SUMOylation and the formation of PML nuclear bodies (PML‐NBs), and consequently recruited Pin1 into nuclear to colocalize with PML. Pharmacological inhibition of TGF‐β signal or Pin1 with LY364947 (3 μM) or Juglone (3 μM), the TGF‐β1‐induced PML SUMOylation was reduced significantly with downregulation of the messenger RNA and protein for TGF‐β1 and Pin1. To verify the cellular function of PML by means of gain‐ or loss‐of‐function, the positive feedback signaling loop was enhanced or declined, meanwhile, TGF‐β‐Smad signaling pathway was activated or weakened, respectively. In summary, we uncovered a novel reciprocal loop of TGF‐β1/PML SUMOylation/Pin1 leading to myocardial fibrosis. Exogenous transforming growth factor‐β (TGF‐β1) is added into neonatal mouse cardiac fibroblasts, triggering promyelocytic leukemia (PML) SUMOylation and PML nuclear bodies (NBs) formation. Meanwhile, Pin1 is recruited into the PML‐NBs and colocated in the nuclear body. Then, the messenger RNA level and protein level of TGF‐β1 are both increased, activating the TGF‐β/Smad‐2/3 signaling pathway, increasing collagen formation, and ultimately leading to cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect and its mechanism of salmon milt DNA (SMD) on age-related involutions in mouse thymus., Methods: Female BALB/C mice aged 10 months were divided randomly into three groups according to their weights. They were high dosage group (333.33 mg.kg(-1).b.w.d(-1)), low dosage group (166.67 mg.kg(-1).b.w.d(-1)) and control group (0 mg.kg(-1).b.w.d(-1)). After five weeks, their thymus indexes were measured and the thymocytes were counted and the thymus cortex thicknesses were also measured using Image-Pro Plus (version. 4.0) software in the thymus section. All the data were analyzed by SAS statistic software. Microarray technique was applied to screen the gene fragments, which were differentially expressed between the high dosage group and the control group, together with RT-PCR to further confirm some of them., Results: No significant differences of the variables including body weight, thymus weight and thymus indexes among the three groups were found. The thymocytes quantities of thymus cortex and medulla in the high dosage group were significantly higher than those of the control group (P < 0.01 and P < 0.05, respectively). The thymus cortex thicknesses of both SMD supplement groups were significantly higher than that of the control group (P < 0.01 and P < 0.05 respectively). 112 differently expressed gene fragments were isolated. Furthermore, we found the fragments with the logged number of U23789, X80232 and Aw209102 were highly expressed in the high dosage group when RT-PCR technique was used., Conclusions: SMD may reverse the age-related involutions in mouse thymus via up-regulation the expression of proliferation related genes and via up-regulation the expression of development and differentiation related genes simultaneously.

Objective: To study the effect of exogenous nucleic acid on physical functions, morphology of hepatic cells and brain neurons in aged rats., Methods: Thirty two aged Wistar rats (20 month-old) were divided randomly into four groups (one aged control group and three aged experimental groups) and eight young rats (3 month-old) was set as young control group. Control groups were fed on standard chow and experimental groups were fed on standard chow supplemented with 93.75 mg/kg (high-dosage group), 46.88 mg/kg (middle-dosage group) and 9.38 mg/kg (low-dosage group) of yeast RNA respectively. SOD, MDA, HDL, sex hormone and growth hormone were determined at the end of a 4-week observation. The microcosmic images of the hepatic cells and brain neurons using the image-pro plus (V.4.0) were also observed., Results: SOD, serum HDL and growth hormone levels in the high dosage group were significantly higher (P < 0.05) than that in the aged control group, and the levels were not different from that in the young control group. MDA level of all yeast RNA supplemented groups was significantly lower than that of aged control group (P < 0.05) and that was not different from the young control group. Serum testosterone of the high and middle dosage groups reached the level of young control group, and that was much higher than the aged control and low dosage group (P < 0.05). Estradiol levels among the aged rats were not different, and those were much lower than the young control group (P < 0.05). Much more number of brain neurons were observed in the high-dose group than other aged rats (P < 0.05). Brain neurons, hepatic cells and karyons in the high-dose group were bigger than that in other aged rats (P < 0.05)., Conclusion: Exogenous yeast RNA might play an important role in physical functions, the morphology of brain neurons and hepatic cells in natural aged rats. There might have a dose-effect relationship in the process.