Contrast-enhanced ultrasound of polyp malignant transformation with multiple metastases in a patient with Peutz-Jeghers syndrome.

Multi-systemic metastasis in patients with Peutz-Jeghers syndrome (PJS) is very rare, and there are nearly no relevant imaging reports, especially in contrast-enhanced ultrasound (CEUS). We present here a 40-year-old male patient who underwent several partial small bowel resections and endoscopic polypectomy for intestinal polyps. After reviewing the patient's clinical diagnosis and treatment process, CEUS with sulfur hexafluoride microbubbles (SonoVue, Bracco, Milan, Italy) in the liver and gastrointestinal tract was performed. We imaged multiple abnormal masses with sonographic features consistent with malignancies. Combined with other imaging examinations and 18 gauge core-needle puncture biopsy of liver masses, multiple metastases outside the gastrointestinal tract were considered. This case report suggests CEUS may be an easy, effective, and supplementary method for evaluating PJS patients with suspected multi-systemic malignant lesions including the gastrointestinal tract.

TGF-ß1 induced activations of Smad2 and miRNAs inhibit SF-1- and LRH-1-dependent CYP19 expression in rat Leydig cells†.

P450 aromatase, encoded by the Cyp19 gene, catalyzes the synthesis of estrogen, which is crucial for mammalian germ cell differentiation. We have previously shown that transforming growth factor beta 1 (TGF-ß1) attenuated the accumulation of steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1) and eventually reduced the transcription of Cyp19 in rat Leydig cells (LCs). Here, we report that TGF-ß1 treatment-induced phosphorylation of Smad2 and decreased the expression levels of SF-1 and LRH-1 by elevating the expression levels of microRNA-21-3p and microRNA-339-5p in vivo and in vitro. Furthermore, both TGF-ß1 treatment and over-expression of Smad2 inhibited the SF-1 or LRH-1-regulated promoter activity of the Cyp19 gene, and p-Smad2 physically interacted with SF-1 and LRH-1. Our findings collectively suggest that TGF-ß1 may inhibit the expression of CYP19 in LCs mainly through two ways. On the one hand, TGF-ß1 acts through Smad2 to repress the accumulation of SF-1 and LRH-1 at post-transcriptional level by upregulating specific microRNAs. On the other hand, TGF-ß1 inhibits the transcriptional activity of Cyp19 through the interaction of p-Smad2 with SF-1/LRH-1.

microRNA-135a-5p regulates NOD-like receptor family pyrin domain containing 3 inflammasome-mediated hypertensive cardiac inflammation and fibrosis via thioredoxin-interacting protein.

Hypertension is a severe public health problem that induces cardiac injury with alterations of gene expressions. The current study sought to evaluate the mechanism of microRNA(miR)-135a-5p in NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediation of cardiac inflammation and hypertensive cardiac fibrosis. Firstly, hypertensive mouse models were established using angiotensin II (Ang II), followed by miR-135a-5p agomir treatment. Subsequently, mouse blood pressure and basic cardiac function indexes, histopathological changes, and cardiac fibrosis were all determined, in addition to detection of factors related to inflammation and fibrosis. Additionally, mice cardiac fibroblasts (CFs) were isolated and treated with Ang II. The binding relationship of miR-135a-5p and thioredoxin-interacting protein (TXNIP) was predicted and testified, while the interaction of TXNIP and NLRP3 was detected by means of a co-immunoprecipitation assay. It was found that miR-135a-5p was poorly-expressed in Ang II-treated mice and further exerted cardioprotective effects against hypertensive heart diseases. Moreover, over-expression of miR-135a-5p resulted in inhibition of inflammatory infiltration and almost eliminated cardiac fibrosis, as evidenced by decreased Collagen (COL)-I, COL-III, a-smooth muscle actin, NLRP3, tumor necrosis factor-α, and interleukin-6. Mechanically, miR-135a-5p inhibited TXNIP expression to block the binding of TXNIP and NLRP3. On the other hand, TXNIP up-regulation reversed the protective role of miR-135a-5p over-expression in CFs. Collectively, our findings indicated that miR-135a-5p over-expression inhibited TXNIP expression to block the binding of TXNIP and NLRP3, thereby alleviating hypertensive cardiac inflammation and fibrosis.

Colocalization of metastasis-associated proteins 1/2 and estrogen receptor alpha in rat epididymis.

It has been suggested that metastasis-associated proteins 1 and 2 (MTA1 and MTA2) are capable of suppressing estrogen receptor alpha (ERα) transactivation activity in breast cancer cells. ERα, which is present in the epididymis, is a crucial mediator of maintaining the luminal environment necessary for proper sperm maturation and function. The present study was undertaken to analyze the expression profile of both MTA1 and MTA2 in the epididymis of rats and to ascertain whether MTA1/2 colocalizes with ERα in the epididymis and primary cultured epididymal epithelial cells. Reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry analyses were utilized to demonstrate that MTA1 and MTA2 are expressed in the epididymis. Furthermore, these analyses revealed that MTA1 and MTA2 are predominantly localized in the nuclei of almost all epididymal epithelial cells. Immunofluorescence staining revealed that MTA1/2 colocalizes with ERα in epididymal epithelial cells. In conclusion, MTA1 and MTA2 are expressed in the epididymis of rats; these proteins colocalize with ERα in epididymal epithelial cells, suggesting that MTA1 and MTA2 may be involved in the regulation of ERα transactivation activity in the epididymis of rats to facilitate a stable environment in the lumen.

Protective effects of polydatin on experimental testicular torsion and detorsion injury in rats.

Oxidative stress plays a critical role in the process of testicular torsion and detorsion (T/D). The purpose of the present study was to investigate the protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly divided into three groups, a sham group, a group subjected to 2h torsion followed by 24h detorsion and a group subjected to T/D and injected i.p. with 20mgkg-1 PD 30min before detorsion. Unilateral orchiectomy was performed after 24h of reperfusion. Half the testes were prepared for histological examination by haematoxylin-eosin staining and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) technique. In the remaining tissues, levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were determined, as was the expression of several apoptosis-related proteins. Compared with the T/D group, PD pretreatment significantly ameliorated the morphological damage, lowered the Cosentino histological score and increased the mean number of germ cell layers and Johnsen's testicular biopsy score. In addition, PD treatment markedly decreased MDA levels and upregulated CAT, GPx and SOD activity. Furthermore, PD decreased T/D-induced germ cell-specific apoptosis, attenuated the activation of caspase-3, caspase-8, caspase-9 and poly(ADP-ribose) polymerase and increased the Bcl-2/Bax ratio. The findings indicate that PD has a protective effect against testicular T/D injuries, especially at the histological, antioxidative stress and antiapoptotic levels.

TGFB1 represses the expression of SF1 and LRH1 to inhibit E2 production in rat LCs.

Leydig cells (LCs) in the adult testis have been identified as the major sites of oestrogen production, which is crucial for mammalian germ cell differentiation. Our previous work showed that transforming growth factor beta 1 (TGFB1) inhibits estradiol (E2) secretion via down-regulating Cyp19 gene expression in mature rat LCs. However, the mechanism remains unclear. In the present study, the effects of TGFB1 on the expression levels of steroidogenic factor 1 (SF1), liver receptor homolog 1 (LRH1), cAMP response element-binding protein (CREB) and cAMP responsive element modulator (CREM) were evaluated both in primary cultured LCs and in rat testis. The involvement of TGFB1 signalling in the regulation of SF1 and LRH1 expression was then validated by applying the inhibitor of the TGFB type 1 receptor (TGFBR1) SB431542. Moreover, the expression of CYP19 in testicular LCs was investigated and the production of E2 in testicular interstitial fluid (TIF) was measured. The results showed that TGFB1 especially down-regulated the expression levels of SF1 and LRH1 both in primary cultured LCs and in rat testis. The down-regulations of TGFB1 in the production of E2 in TIF and the expression of CYP19 in testicular LCs were also observed in vivo These inhibitory effects could be reversed by TGFBR1 inhibitor SB431542. Our findings suggest that TGFB1 may act through the canonical signalling pathway involving ALK5 to restrain SF1 and LRH1 accumulation and eventually attenuate Cyp19 transcription and oestrogen production in LCs.

Polydatin Attenuates H2O2-Induced Oxidative Stress via PKC Pathway.

Oxidative stress plays an important role in the pathogenesis of endothelial dysfunction, which is found to precede the development of diverse cardiovascular diseases (CVDs). The aim of this study was to observe the protective effects of PD against H2O2-induced oxidative stress injury (OSI) in human umbilical vein endothelial cells (HUVECs) and the possible mechanism of PD in OSI treatment. HUVECs were subjected to H2O2 in the absence or presence of PD. It turned out that PD improved cell viability and adhesive and migratory abilities, inhibited the release of lactate dehydrogenase (LDH) and reactive oxygen species (ROS), and elevated the content of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). TUNEL, fluorometric assays, and Western blotting showed that OSI upregulated the apoptosis ratio, the activity of caspase-3 and the level of proapoptotic protein Bax and decreased the level of antiapoptotic protein Bcl-2. However, PD treatment partially reversed these damage effects and Protein Kinase C (PKC) activation by thymeleatoxin (THX) in turn eliminated the antiapoptotic effect of PD. Furthermore, PD attenuated the H2O2-induced phosphorylation of PKCs α and δ and increased the phosphorylation of PKC ε. Our results indicated that PD might exert protective effects against OSI through various interactions with PKC pathway.