Manganese deficiency induces avian tibial dyschondroplasia by inhibiting chondrocyte proliferation and differentiation.

Manganese (Mn) is an essential trace element for bone growth, and its deficiency has been shown to increase the incidence of leg abnormalities in fast-growing broilers, such as tibial dyschondroplasia (TD). Proliferation and differentiation of growth plate chondrocyte are critical for tibia development, but their roles in Mn deficiency-induced TD remains to be elucidated. Thirty 1-day-old Arbor Acres chicks were randomly divided into two groups and fed with control diet (60 mg Mn/kg diet) and Mn-deficiency diet (22 mg Mn/kg diet) for 42 days, respectively. Mn deficiency-induced TD model was successfully established and samples from proximal tibia metaphysis and growth plate were collected for assays. Pathological observation showed that Mn deficiency induced morphological abnormality and irregular arrangement of chondrocytes in proliferative and hypertrophic zone of tibial growth plate. Also, Mn deficiency decreased mRNA and protein expression levels of type II collagen and type X collagen in tibial growth plate, indicating the impairment of proliferating and hypertrophic chondrocytes. Moreover, down-regulated gene expression levels of Sox9, Tgf-ß, Ihh, Runx2, Mef2c and Bmp-2 were shown in tibial growth plate of Mn-deficiency group, demonstrating that Mn deficiency inhibited the transcription levels of key regulators to disrupt chondrocyte proliferation and differentiation. Collectively, these findings confirmed that Mn deficiency affected the proliferation and differentiation of chondrocytes in tibial growth plate via inhibiting related regulatory factors, leading to TD in broilers.

Evaluation of 6-chloro-N-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-1,3-benzothiazol-2-amine Using Drug Design Concept for Their Targeted Activity Against Colon Cancer Cell Lines HCT-116, HCT15, and HT29.

BACKGROUND Colorectal adenocarcinoma is the second leading cause of cancer-related death in the world. The stage of the disease is related to the survival of the patient, and in early phases surgery is the main modality of treatment. The main aim of modern medicinal chemistry is to synthesize small molecules via drug designing, especially by targeting tumor cells. MATERIAL AND METHODS A new series of 19 compounds containing benzothiazole and thiazole were designed. Molecular docking studies were performed on the designed series of molecules. Compounds showing good binding affinity towards the EGFR receptor were selected for synthetic studies. Characterization of the synthesized compounds was done by FTIR, 1HNMR, Mass and C, H, N, analysis. RESULTS The anticancer evaluation of the synthesized compounds was done at NIC, USA at a single dose against colon cancer cell lines HCT 116, HCT15, and HC 29. The active compounds were further evaluated for the 5-dose testing. Compounds were designed by using docking analysis. To ascertain the interaction of EGFR tyrosine kinase binding, energy calculation was used. CONCLUSIONS The results of the present study indicate that the designed compounds show good activity against colon cancer cell lines, which may be further studied to design new potential molecules.

Prognosis and Clinicopathology of CXCR4 in Colorectal Cancer Patients: a Meta-analysis.

The chemokine receptor 4 (CXCR4) has been widely used in diagnosis and prognosis of colorectal cancer (CRC). However, there is no current consensus on the impact of CXCR4 on CRC patients. The purpose of this study was to evaluate the prognostic and clinicopathological importance of CXCR4 in CRC patients. Databases, such as PubMed, Cochrane library, CBM and EMBASE updated to 2014 were searched to include eligible articles. We analysed correlations between CXCR4 expression and clinicopathological features and overall survival (OS). A total of 1, 055 CRC patients from twelve studies were included in the study. The pooled odds ratios (ORs) which indicated CXCR4 expression was likely to be associated with TNM stage (OR=0.43, CI=0.34-0.55, P<0.00001), lymph node status (OR=2.23, CI=1.23-4.05, P=0.008) and vascular invasion (OR=2.21, CI=1.11-4.39, P=0.02). Poor overall survival of CRC cancer was found to be significantly related to CXCR4 overexpression (hazard ratio (HR) 1.36 CI=1.17-1.59, P<0.0001), whereas combined ORs revealed that CXCR4 expression had no correlation with gender or differentiation. Based on the published studies, CXCR4 overexpression in patients with CRC indicates poor survival outcome and clinicopathological factors.