A colony of cats affected with hypertrophic feline muscular dystrophy was used to study the occurrence of cardiomyopathy associated with dystrophin deficiency. Affected male and female cats, obligate carrier females, and unaffected healthy littermates were followed from 12 weeks of age into adulthood. Thoracic radiography, 2-D echocardiography, and 2-D-derived M-mode echocardiography were performed at 3-month intervals until 12 months of age and regularly thereafter. From 9 months of age, all affected cats had larger hearts than normal and carrier animals. Left ventricular wall thickness in systole and in diastole and interventricular septal thickness in systole were greater in affected cats 12 months and older when compared with normal or heterozygous animals (P < .05). The myocardium of affected cats was diffusely hypoechoic and thickened. Multiple hyperechoic foci were in the myocardium and papillary musculature. Shortening fraction was normal in all cats. Changes seen in carrier females included enlargement and hyperechogenicity of the papillary musculature after the age of 2 years. Gross and light microscopic examination revealed left ventricular wall thickening with multiple foci of mineralization in 2 of 5 hearts from dystrophin-deficient cats. Although approximately 10% of the normal dystrophin amount was present in the skeletal muscle, dystrophin could not be detected in the myocardium. Early onset concentric myocardial hypertrophy was present in all adult cats. Lesions were mainly localized in the myocardium of the left ventricular free wall and interventricular septum, papillary musculature, and the endocardium. Clinical signs of heart failure developed only infrequently in cats with hypertrophic feline muscular dystrophy.

A colony of cats affected with hypertrophic feline muscular dystrophy was used to study the occurrence of cardiomyopathy associated with dystrophin deficiency. Affected male and female cats, obligate carrier females, and unaffected healthy littermates were followed from 12 weeks of age into adulthood. Thoracic radiography, 2-D echocardiography, and 2-D-derived M-mode echocardiography were performed at 3-month intervals until 12 months of age and regularly thereafter. From 9 months of age, all affected cats had larger hearts than normal and carrier animals. Left ventricular wall thickness in systole and in diastole and interventricular septal thickness in systole were greater in affected cats 12 months and older when compared with normal or heterozygous animals (P < .05). The myocardium of affected cats was diffusely hypoechoic and thickened. Multiple hyperechoic foci were in the myocardium and papillary musculature. Shortening fraction was normal in all cats. Changes seen in carrier females included enlargement and hyperechogenicity of the papillary musculature after the age of 2 years. Gross and light microscopic examination revealed left ventricular wall thickening with multiple foci of mineralization in 2 of 5 hearts from dystrophin-deficient cats. Although approximately 10% of the normal dystrophin amount was present in the skeletal muscle, dystrophin could not be detected in the myocardium. Early onset concentric myocardial hypertrophy was present in all adult cats. Lesions were mainly localized in the myocardium of the left ventricular free wall and interventricular septum, papillary musculature, and the endocardium. Clinical signs of heart failure developed only infrequently in cats with hypertrophic feline muscular dystrophy.

No abstract

Deguelin, a natural component derived from leguminous plants, has been used as pesticide in some regions. Accumulating evidence show that deguelin has promising chemopreventive and therapeutic activities against cancer cells. This study shows that low concentrations of deguelin can lead to significant delay in zebrafish embryonic development through growth inhibition and induction of apoptosis. Furthermore, we identified fibroblast growth factor receptor 4 (FGFR4) as the putative target of deguelin. The candidate was initially identified by a microarray approach and then validated through in vitro experiments using hormone‐responsive (MCF‐7) and nonresponsive (MDA‐MB‐231) human breast cancer cell lines. The results show that deguelin suppressed cell proliferation and induced apoptosis in both cancer cell lines, but not in Hs 578Bst cells, by blocking PI3K/AKT and mitogen‐activated protein kinases (MAPK) signaling. The FGFR4 mRNA and protein level also diminished in a dose‐dependent manner. Interestingly, we found that forced FGFR4 overexpression attenuated deguelin‐induced proliferative suppression and apoptotic cell death in both zebrafish and MCF‐7 cell lines, p‐AKT and p‐ERK levels were restored upon FGFR4 overexpression. Taken together, our results strongly suggest that deguelin inhibition of PI3K/AKT and MAPK signaling in zebrafish and breast cancer cell lines is partially mediated through down‐regulation of FGFR4 activity.

Acute unilateral nephrectomy (AUN) results in natriuresis from the remaining kidney through reflex pathways involving the central nervous system and requiring an intact pituitary gland. The natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the N-terminal fragment (NTF) of proopiomelanocortin. We measured plasma immunoreactive NTF-like material (IR-NTF) before and after AUN in control rats and rats treated neonatally with monosodium glutamate (MSG), a procedure that produces neuroendocrine dysfunction by destroying cell bodies in the hypothalamic arcuate nucleus, median eminence, and other brain regions. In control rats, IR-NTF increased from 85.8 +/- 54.9 (SD) to 207 +/- 98.1 fmol/ml after AUN (P less than 0.02) as sodium excretion (UNaV) doubled. In MSG-treated rats, AUN produced no change in plasma IR-NTF concentration (58.8 +/- 21.3 vs. 68.3 +/- 18.5 fmol/ml (P = NS), nor did UNaV increase. Tissue content of IR-NTF was reduced in the arcuate nucleus and anterior lobe of pituitaries from MSG-treated rats compared with controls, but was no different in the neurointermediate lobe. These results indicate that the hypothalamic lesion produced by neonatal administration of MSG prevents both the increase in plasma IR-NTF concentration and the natriuresis after AUN, and therefore lend further support to the concept of a causal relationship between these two consequences of AUN.

No abstract

This study aims to evaluate the relationship between subclinical hypothyroidism (SCH) during the first trimester and gestational diabetes mellitus (GDM) that was happened later on in our cohort. A total of 6530 pregnant women who first visited before 13+6 gestational weeks and accepted routinely prenatal services in the third affiliated hospital of Sun Yat-Sen University from January 2015 to September 2018 were finally met the inclusion criteria and recruited. Thyroid functions were performed at the first visit and a 2h 75-g OGTTwas performed between 24-28 weeks. The glucose levels of OGTT were shown no differences between SCH and euthyroid women [0 hour: 4.17 mmol/L (3.99-4.38) vs. 4.16 mmol/L (3.97-4.39), P = 0.730; 1 hour: 7.61 mmol/L (6.64-8.66) vs. 7.68 mmol/L (664-8.75), P = 0.449; 2 hour: 6.66 mmol/L (5.85-7.68) vs. 6.75 mmol/L (5.93-7.74), P = 0.142]. The incidence of GDM was no change as the TSH level increased in either TPOAb negative or positive SCH women (all P &gt; 0.05). After using the multivariate logistic regression analysis adjusted for confounders (maternal age, educational levels and preBMI), elevated TSH and TPOAb status also had no effect on the incidence of GDM (Table 1). These results suggested maternal SCH in the first trimester was not related to GDM, regardless of the TPOAb status or the TSH levels. Disclosure P. Li: None. S. Lin: None. J. Fan: None. Funding Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314)

Objective: Islet amyloid polypeptide(IAPP) is a major component of islet amyloid deposition in type 2 diabetic patients. Our preliminary study showed that membrane protein Caveolin-1 (Cav1) silencing inhibited β-cell apoptosis and promote insulin secretion. The purpose of this study was to investigate the regulation of Cav1 on islet β-cell IAPP and its mechanism. Materials and Methods: Firstly, IAPP secretion of each group of primary islets was detected by ELISA, then Western blot and real-time quantitative PCR (qPCR) were used to detect the expression levels of IAPP, PAM(Peptidyl-glycine alpha-amidating monooxygenase), PC1(Prohormone Convertase-1), BACE2(Beta-secretase 2), IDE(Insulin-Degrading Enzyme), TXNIP(Thioredoxin interacting protein), and finally, it confirmed that Cav1 interacted with the protein of TXNIP by immunofluorescence confocal and co-immunoprecipitation (Co-IP). Results: The secretion of IAPP was decreased in primary pancreatic islets and Cav1 deficiency significantly down-regulated the expression of IAPP in NIT-1 cells, while over-expression of Cav1 in βTC-6 cells significantly up-regulated the expression of IAPP. This effect correlated with Cav1 silencing leading to down-regulation of PAM expression associated with IAPP synthesis and over-expression of Cav1 leading to up-regulation of PC1 associated with IAPP synthesis. On the other hand,Cav1 deficiency resulted in the up-regulation of the expression of BACE2 and IDE, the enzymes associated with IAPP decomposition. While over-expression of Cav1 leaded to down-regulation of BACE2 and IDE. Further studies indicated that Cav1 co-localized with TXNIP, and it interacted with and regulated the expression of TXNIP, which regulates IAPP gene transcription. Conclusion: Cav-1 can regulate the synthesis and decomposition of IAPP in islet β cell by interacting with TXNIP. This study suggests that Cav-1 may protect diabetic islet beta cells by reducing islet amyloid deposition. Disclosure K. Liu: None. W. Zeng: None. S. Lin: None. C. Lin: None. F. Xu: None. N. Cai: None. L. Zeng: None. Funding National Natural Science Funding of China (51873071); Natural Science Foundation of Guangdong Province (2018B030311012)