Sequential biphasic changes in claudin1 and claudin4 expression are correlated to colorectal cancer progression and liver metastasis

Terminal progression of colorectal cancer (CRC) culminates in liver metastasis. To identify genes that are involved in the metastatic phenotype, cDNA microarrays were used to analyse mRNA expression profiles of colorectal carcinoma (CC)531 rat colon adenocarcinoma cells for changes related to their homing into the liver. Briefly, CC531 cells were intraportally implanted into the liver of Wag-Rij rats and re-isolated after 3, 6, 9, 14 and 21 days. Compared to control CC531 cells, claudin1 and claudin4 were among the ≥8-fold initially down-regulated genes. The co-culture of tumour cells with isolated rat hepatocytes and Kupffer cells did not induce down-regulation of either claudin1 or 4. When the environment effective on circulating tumour cells was simulated by cell culture conditions favouring their adhesion, only claudin4 showed augmented expression. Knockdown of claudin1 and claudin4 mediated by small interfering RNA caused significantly increased migration and decreased clonogenic growth of tumour cells (P < 0.05), but had no effect on their proliferation. These experimental results were paralleled by increased claudin1 and claudin4 expression in human CRC samples in Union for International Cancer Control (UICC) stages I-III, as evaluated by real-time PCR. Increased claudin4 levels were correlated with significantly reduced overall survival (log-rank test, P= 0.018). Further, significantly (P < 0.05) reduced expression of claudin1 and claudin4 was observed in stage IV and liver metastasis by immunohistochemistry. In conclusion, sequential biphasic changes in claudin1 and claudin4 expression occur during the homing of rat CC531 CRC cells to the liver. This modulation is reflected by significant changes in claudin expression in human primary and metastatic CRC.     

Identifying two moth species (Lepidoptera: Ditrysia) from Saudi Arabia using mitochondrial 16S rRNA sequences

The mitochondrial genetic markers are considered useful tools for discrimination between more closely related lepidopteran taxa. Therefore, the present study aimed to investigate the role of mitochondrial (mt) 16 s rRNA gene in the determination of the taxonomic position for two moth species within Ditrysia clade. Maximum likelihood analysis has indicated a well-supported dendrogram based on the Tamura-Nei model for the recovered lepidopterans. The mt 16 s rRNA query sequences from 24 species within seven families were analyzed. This analysis and bootstrap confidence revealed two major clades representing Glossata suborder within Lepidoptera, with a close relationship of Noctuoidea + (Pyraloidea (Hesperioidea + Papilionoidea)). The subfamily Heliothinae forming a sister group with Risobinae (Noctinae + Hadeninae). In addition, there is a clear observation about the close relation between Phycitinae + Galleriinae within Pyraloidea and Cyrestinae + Limenitidinae within Papilionoidea. The present study supported that the Helicoverpa and Meroptera species are the first accounts of these genera inhabiting Saudi Arabia.     

Molecular identification of forensically important beetles in Saudi Arabia based on mitochondrial 16 s rRNA gene

Forensic science uses scientific methods to help the scientists who study evidence to assist in the solving of crimes. Coleoptera is the most diverse and speciose group of insects that have an important role in many scientific fields especially forensic entomology. In addition, it is difficult to morphologically identify and discriminate between them. In the present study, the molecular analysis using mitochondrial DNA information was conducted to swiftly and accurately identify the recovered Coleoptera species. A molecular identification method involving a 221‐bp segment of the 16 s ribosomal RNA (16 s rRNA) gene from three beetle species, collected from a rabbit carcass, was evaluated. The analysis with maximum likelihood method recovered a generally well supported phylogeny, with most currently accepted taxa and species groups as monophyletic. These results will be instrumental for the implementation of the Saudian database of forensically relevant beetles.     

Novel double deletions in the MECP2 gene in Tunisian Rett patient

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively girls. Rett patients present an apparently normal psychomotor development during the first 6-18 months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. RTT is currently considered as monogenic X-linked dominant disorder due to mutations in the MECP2 gene, encoding the methyl-CpG binding protein 2. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient.The results showed the presence of a novel point mutation c.C1142T (p.P381L) and two deletions at the heterozygous state: a novel deletion c.1075delTTC (p.S359) and a known one c.1157del44 (p.L386Q fs X2) in the C-terminal region of MeCP2.     

Diazepam-Loaded Solid Lipid Nanoparticles: Design and Characterization

The aim of the present study was to investigate the feasibility of the inclusion of a water-insoluble drug (diazepam, DZ) into solid lipid nanoparticles (SLNs), which offer combined advantages of rapid onset and prolonged release of the drug. This work also describes a new approach to prepare suppositories containing DZ-loaded SLN dispersions, as potential drug carrier for the rectal route. Modified high-shear homogenization and ultrasound techniques were employed to prepare SLNs. The effect of incorporation of different concentrations of Compritol® ATO 888 or Imwitor® 900K and Poloxamer 188 or Tween 80 was investigated. Results showed that varying the type or concentration of lipid matrix or surfactant had a noticeable influence on the entrapment efficiencies, particle size, and release profiles of prepared SLNs. Differential scanning calorimetry and X-ray diffraction measurements showed that the majority of SLNs possessed less ordered arrangements of crystals than the corresponding bulk lipids, which was favorable for increasing the drug loading capacity. Transmission electron microscopy and laser diffractometry studies revealed that the prepared nanoparticles were round and homogeneous and 60% of the formulations were less than 500 nm. Additionally, SLN formulations showed significant (P?in vitro release of DZ from the suppositories prepared using DZ-loaded SLN dispersions (equivalent to 2 mg DZ) was significantly (P?相似文献   

Naringenin alleviate reproductive toxicity evoked by lead acetate via attenuation of sperm profile and biochemical alterations in male Wistar rat: Involvement of TGFβ/AKT/mTOR pathway

Exposure to Lead -causes testicular dysfunction through oxidative stress, inflammation, and apoptosis; however, naringenin (NGN) therapeutic impact against lead-evoked testicular dysfunction remains elusive. Herein, the point of the study was to examine the defensive impact of NGN on testicular dysfunction initiated by lead. Seventy-Two male Wistar rats were allotted into nine groups; control group, drug control groups, lead acetate group, as well as NGN treated groups (10, 25, and 50 mg/kg) respectively, given 5 days before lead acetate treatment. The result showed clearly the impact of lead on reduced sperm count, sperm motility as well as serum testosterone and LH levels. Additionally, it caused a significant rise in testicular inflammatory markers TNF-α, IL-1β, and TGFβ, effects that were accompanied by a reduction of AKT and mTOR levels. Lead acetate also caused degenerative changes in the testis, atrophy, and loss of spermatogenic series. Our findings revealed that NGN in a dose-dependent manner improved spermiotoxicity induced by lead acetate via restoration of the testicular function, preservation of spermatogenesis, halting inflammatory cytokines along with the enhancement of germ cell survival using upregulation of AKT/mTOR expressions. The present study discloses that NGN suppresses lead acetate toxicity that is involved in the antioxidant effect in a dose-dependent manner, besides its anti-inflammatory property.     

Effect of cerebrolysin on the cerebellum of diabetic rats: An imunohistochemical study

Background

Diabetes mellitus represents one of the disorders in the metabolism that affects all body systems including CNS. Cerebrolysin contains many neurotrophic factors, and many studies reported that it can be used treatment of many neurological disorders.