The cellular mechanisms underlying the formation and organization of the human placenta remain poorly understood. Recent studies have demonstrated that E-cadherin, in association with the cytoplasmic protein known as beta-catenin, plays an integral role in the differentiation of the trophectoderm in the murine and bovine embryo. Although E-cadherin expression is regulated during the aggregation and fusion of human villous cytotrophoblasts, the expression of beta-catenin during the terminal differentiation of these primary cell cultures has not been determined. In this study, beta-catenin mRNA concentrations and protein expression were examined in primary cultures of human villous cytotrophoblasts using northern and western blot analysis. beta-catenin mRNA concentrations and protein expression were high in freshly isolated mononucleate cytotrophoblasts but decreased as these cells underwent aggregation and fusion to form syncytium. A similar pattern of expression was observed for the E-cadherin mRNA transcript and protein species present in these cell cultures. Immunoprecipitation studies demonstrated that the beta-catenin and E-cadherin protein species present in the mononucleate cytotrophoblasts were capable of forming intracellular complexes. In contrast, beta-catenin and E-cadherin mRNA and protein expression in JEG-3 choriocarcinoma cells remained constant over time in culture. beta-catenin and E-cadherin expression was subsequently immunolocalized to the aggregates of mononucleate cells present in both of these trophoblastic cell cultures and the villous cytotrophoblasts of the human first trimester and term placenta. Taken together, these observations indicate that the E-cadherin-beta-catenin complex plays a central role in the terminal differentiation of human trophoblasts in vitro and in vivo.

Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor-stromal interactions. Here we have validated the VMT platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment response in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional (2D) monolayer culture and 3dimensional (3D) spheroids.

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Multiple trauma can induce sepsis and organ failure, even threaten people's lives. To further study the mechanisms of multiple trauma, we analyzed microarray of GSE5760. GSE5760 was downloaded from the Gene Expression Omnibus including a total of 58 peripheral blood transcriptome from patients without (WT, n = 30) and carrying (MUT, n = 28) the tumor necrosis factor (TNF) rs1800629 A variant. The differentially expressed genes (DEGs) were screened using the limma package in R and the Benjamin and Hochberg method in a multi-test package. Then, functional enrichment analysis of DEGs was performed. Also, transcription factors significantly related to DEGs were searched using WebGestalt and interaction network of transcription factors and DEGs were constructed using STRING online software. Furthermore, pathway enrichment analysis for the DEGs in the interaction network was conducted using KO-Based Annotation System (KOBAS). We screened 39 DEGs including 27 upregulated and 12 downregulated genes. The enriched functions were associated with biological process (BP) (such as response to hypoxia, P value = 0.039803), cell components (CC) (such as mitochondrial part, P value = 0.043857), and molecular function (MF) (such as structural constituent of ribosome, P value = 0.008735). Besides, RPS7 and RPL17 were associated with ribosome and participated in ribosome pathway. PPP2R2B was related to mitochondrion. KCNMA1, ALAS2 and SOCS3 were associated with hypoxia. Moreover, transcription factors of LEF1, CHX10, ELK1, SP1, and MAZ were significantly related to DEGs. RPS7, RPL17, PPP2R2B, KCNMA1, ALAS2, and SOCS3 might relate to multiple trauma. And TNF-α mutation could cause sepsis in patients with multiple trauma by changing the expression of these genes.

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