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Hao-Xiang Tan,1–3 Zhen-Bin Cao,4 Ting-Ting He,5 Tao Huang,1,3Cai-Ling Xiang,1,3Yu Liu1,31Department of Gastrointestinal Surgery, Hunan Provincial People’s Hospital, Changsha 410002, People’s Republic of China; 2Department of Gastrointestinal Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, People’s Republic of China; 3Department of Gastrointestinal Surgery, First Affiliated Hospital of Hunan Normal University, Changsha 410002, People’s Republic of China; 4Department of Radiology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, People’s Republic of China; 5Department of Pathology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, People’s Republic of ChinaBackground and purpose: Colorectal cancer (CRC) frequently metastasizes to the liver, which involves the participation of multiple cytokines. Tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs) and tumor cells acts as an essential factor in cancer metastasis. Transforming growth factor β1 (TGFβ1) is a vital cytokine involved in migration and invasion of cancer cells. However, the underlying mechanisms remain unclear. In the present study, we aimed to investigate the role and molecular mechanisms of TGFβ1 in TME.Methods: The conditioned medium prepared from colorectal cancer HCT116 and HT29 cells was used to culture mesenchymal stem cells (MSCs). The differentiation of MSCs to CAFs was detected by flow cytometry. The role of TGFβ1 in colorectal cancer cells metastasis was examined by wound-healing assay and transwell assay. And the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway was measured by Western blot assay.Results: TGFβ1 induced the differentiation of MSCs to CAFs and improved HCT116 and HT29 cells migration and invasion. Meanwhile, TGFβ1 also upregulated the phosphorylation of STAT3 and enhanced the nuclear localization of p-STAT3, which activated JAK/STAT3 signaling pathway.Conclusion: TGFβ1 induced the differentiation of MSCs into CAFs and promoted the migration and invasion of HCT116 and HT29 cells, which depended on the activation of JAK/STAT3 signaling pathway.Keywords: TGFβ1, JAK/STAT3, MSCs-CAFs differentiation, migration and invasion

Background: Safety, quality and effectiveness of Chinese patent medicine (CPM) are highly relevant to the manufacturing process. However, the level of manufacturing practice (GMP) for CPM as implemented in China is less reported in literatures. Therefore, the aim of this paper was to reveal the implementation status of GMP for CPM in China, in terms of implementation principle, implementation content, industrial impacts, and implementation barriers from both macro and micro aspects.Methods: A comprehensive analysis was carried out with archival data and field work at CPM manufacturers.Results: Both implementation principle and content of GMP for CPM in China indicated a transformation from provision-oriented to human-oriented, leaving more flexible operation space to CPM manufacturers. However, poor manufacturing practices may still exist because the implementation of GMP in China is not strict enough to eliminate all the unqualified CPM manufacturers from market. Moreover, compared with international WHO GMP, there are barriers for implementing GMP for CPM, including main deficiencies in quality control management, cost of GMP renovation projects, lack of education and training, and lack of expertise.Conclusion: This paper found that the implementation of GMP for CPM still faced many barriers though GMP had generated some positive impacts on CPM manufacturing. Removal of implementation barriers could be considered, including strengthening personnel competence, improving the quality management system and enhancing the international communication with advanced GMP regulators.Keywords: good manufacturing practice, GMP, Chinese patent medicine, traditional Chinese medicine, quality risk management

In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (Et) according to their expression profiles. The results showed that the Et values of G protein-coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.