Salidroside ameliorates pathological cardiac hypertrophy via TLR4-TAK1-dependent signaling.

Salidroside, a prominent active ingredient in traditional Chinese medicines, is garnering increased attention because of its unique pharmacological effects against ischemic heart disease via MAPK signaling, which plays a critical role in regulating the evolution of ventricular hypertrophy. However, the function of Salidroside on myocardial hypertrophy has not yet been elucidated. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with Salidroside (100 mg kg-1  day-1 ) by oral gavage for 3 weeks starting 1 week after surgery. Four weeks after TAC surgery, the mice were subjected to echocardiography and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes were used to validate the protective effects of Salidroside in response to Angiotensin II (Ang II, 1 µM) stimulation. Here, we proved that Salidroside dramatically inhibited hypertrophic reactions generated by pressure overload and isoproterenol (ISO) injection. Salidroside prevented the activation of the TAK1-JNK/p38 axis. Salidroside pretreatment of TAK1-inhibited cardiomyocytes shows no additional attenuation of Ang II-induced cardiomyocytes hypertrophy and signaling pathway activation. The overexpression of constitutively active TAK1 removed the protective effects of Salidroside on myocardial hypertrophy. TAC-induced increase of TLR4 protein expression was reduced considerably in the Salidroside treated mice. Transient transfection of small interfering RNA targeting TLR4 (siTLR4) in cardiomyocytes did not further decrease the activation of the TAK1/JNK-p38 axis. In conclusion, Salidroside functioned as a TLR4 inhibitor and displayed anti-hypertrophic action via the TAK1/JNK-p38 pathway.

Bone morphogenetic protein 10 alleviates doxorubicin-induced cardiac injury via signal transducer and activator of transcription 3 signaling pathway.

Doxorubicin (DOX) has limited antitumor applications owing to its association with life-threatening cardiac injury. Oxidative damage and cardiac apoptosis are crucial in DOX-induced cardiac injury. Bone morphogenetic protein 10 (BMP10) is predominantly distributed in the heart and acts as a cardioprotective factor that preserves cardiac function. However, the role of BMP10 in DOX-induced cardiac injury has not yet been explored. The current study aimed to examine the function and mechanism of action of BMP10 in DOX-induced cardiac injury. An adeno-associated viral system was used for the overexpression or silencing of cardiac-specific BMP10, and subsequently, a single dose of DOX was intraperitoneally injected to induce cardiac injury. Results showed that DOX exposure decreased BMP10 expression in the heart. Cardiac-specific overexpression of BMP10 alleviated the oxidative stress and apoptosis and improved cardiac function. Conversely, cardiac-specific silencing of BMP10 aggravated the redox disorder and apoptosis and worsened the cardiac dysfunction caused by DOX. Exogenous BMP10 supplementation amelioratesd the DOX-induced cardiac contractile dysfunction. Mechanistically, we found that phosphorylation of signal transducer and activator of transcription 3 (STAT3) is reduced in DOX-induced cardiotoxicity, and, BMP10 activated impaired STAT3 via a non-canonical pathway. BMP10 lost its cardioprotective function in cardiomyocyte-specific STAT3 knockout (STAT3-cKO) mice. Based on our findings, we suggested that BMP10 is a potential therapeutic agent against DOX-induced cardiac injury and that the cardioprotective effects of BMP10 are dependent on the activation of STAT3.

Epidemiology of obscure gastrointestinal bleeding in China: A single-center series and comprehensive analysis of literature.

OBJECTIVE: To determine the etiologies of obscure gastrointestinal bleeding (OGIB) in a Chinese population using a retrospective case series and a systematic analysis of the literatures on OGIB in Chinese patients. METHODS: A large enteroscopy database in a tertiary endoscopic center was searched to identify patients with OGIB from 2010 to 2016. The patients' characteristics and diagnostic findings were collected and analyzed. A comprehensive search of the literature was carried out to harvest all relevant studies published from 2004 to 2016. RESULTS: In total, 708 patients were included in the case series. The most common causes of OGIB were inflammatory diseases (36.3%), non-small bowel lesions (10.2%) and neoplasms (10.0%). A systematic analysis of the literatures included 39 studies providing relevant data for 3145 patients with a pooled detection rate of 84.2%. Inflammatory lesions (27.4%), neoplasms (18.5%), vascular lesions (16.1%) and diverticula or intestinal duplication (11.9%) were the most common causes of OGIB. CONCLUSIONS: Inflammatory lesions, neoplasms, vascular lesions and diverticula or intestinal duplication are the most common in Chinese OGIB patients, while in pediatric patients diverticula or intestinal duplication, vascular lesions and Crohn's disease are prevalent. Furthermore, the etiologies of OGIB distribute differently across different areas in China.

Novel, de novo dysferlin gene mutations in a patient with Miyoshi myopathy.

Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy caused by mutations in the dysferlin gene (DYSF), a 150-kb gene on chromosome 2p13 that contains 55 coding exons. Many patients with MM harbour mutations in the DYSF gene, and most of these mutations are inherited from the patients' parents. Recently, we encountered novel, de novo mutations in the DYSF gene in a patient with MM. DYSF gene analysis was performed by targeted next-generation sequencing, and we found that the patient had compound heterozygous mutations, including a de novo mutation (c.613C > T) in exon 6 and a novel missense mutation (c.968T > C) in exon 11. The novel missense mutation, predicted to be a disease-causing mutation or affecting protein function by MutationTaster and Polyphen2, confirmed the diagnosis. These findings provide important insights into the pathogenesis and inheritance of MM.

The findings of CT and MRI in patients with metanephric adenoma.

BACKGROUND: Metanephric adenoma (MA) is a benign renal tumor that is difficult to distinguish from a malignant tumor via traditional radiography. The diagnosis of MA is often dependent on postsurgical histopathological examination. In the present report, the imaging features of MA on computer tomography (CT) and magnetic resonance imaging (MRI) were retrospectively evaluated. METHODS: Eight MA patients, 17-67 years of age, were pathologically confirmed and recruited between April 2009 and November 2014. Four of the eight patients were female. All patients underwent CT scanning, and one patient underwent MRI scanning. Three patients underwent CTA of the renal arteries. All patients underwent resection surgery (radical nephrectomy in five and nephron-sparing surgery in three patients). RESULTS: The average tumor size was 44.0 ± 23.6 mm. The lesions in 87.5 % cases were located both in the renal cortex and medulla and exhibited exophytic growth. Plain CT showed that MA tumors were solid, and the average CT value was 37.9 ± 6.7 HU. Dynamic contrast-enhanced CT revealed that enhanced degrees of MA tumors in the renal cortex, renal parenchymal, and pelvic phase were all lower than that of normal renal parenchyma. A slight enhancement in the renal cortex phase and an even higher enhancement in the renal parenchymal phase were observed in seven of the cases. Progressive enhancement in the pelvic phase was found in five cases and a slight decreased enhancement in the pelvic phase in two cases. MRI revealed that MA tumor was isointense on T1WI and isointense on T2WI with some slightly hyperintense areas in the center. CTA of the renal arteries revealed the nutrient artery in one patient and no nutrient artery in two. Immunohistochemical experiments demonstrated that most tumor cells were positive for vimentin, CK, and EMA. CONCLUSIONS: MA is a rare benign renal neoplasm. Detailed knowledge of the CT and MRI characteristics of MA plays an important role in MA diagnosis and treatment.