The Extract of Perilla frutescens Seed Residue Attenuated the Progression of Aberrant Crypt Foci in Rat Colon by Reducing Inflammatory Processes and Altered Gut Microbiota.

Perilla frutescens (PF) seed residue is a waste from perilla oil production that still contains nutrients and phytochemicals. This study aimed to investigate the chemoprotective action of PF seed residue crude ethanolic extract (PCE) on the inflammatory-induced promotion stage of rat colon carcinogenesis and cell culture models. PCE 0.1 and 1 g/kg body weight were administered by oral gavage to rats after receiving dimethylhydrazine (DMH) with one week of dextran sulfate sodium (DSS) supplementation. PCE at high dose exhibited a reduction in aberrant crypt foci (ACF) number (66.46%) and decreased pro-inflammatory cytokines compared to the DMH + DSS group (p < 0.01). Additionally, PCE could either modulate the inflammation induced in murine macrophage cells by bacterial toxins or suppress the proliferation of cancer cell lines, which was induced by the inflammatory process. These results demonstrate that the active components in PF seed residue showed a preventive effect on the aberrant colonic epithelial cell progression by modulating inflammatory microenvironments from the infiltrated macrophage or inflammatory response of aberrant cells. Moreover, consumption of PCE could alter rat microbiota, which might be related to health benefits. However, the mechanisms of PCE on the microbiota, which are related to inflammation and inflammatory-induced colon cancer progression, need to be further investigated.

LOC102553417 silencing facilitates the apoptosis of hepatic stellate cells via the miR­30e/MTDH axis.

Hepatic fibrosis is an inevitable pathological process in the progression of multiple chronic liver diseases and remains a major challenge in the treatment of liver diseases. The purpose of the present study was to demonstrate whether silencing of the long non­coding RNA LOC102553417 promoted hepatic stellate cell (HSC) apoptosis via the microRNA (miR)­30e/metadherin (MTDH) axis. A LOC102553417 silencing lentivirus was constructed and transduced into HSC­T6 cells. After confirming the silencing efficiency by reverse transcription­quantitative PCR, cell proliferation was assessed using the Cell Counting Kit­8 assay and apoptosis was assessed using flow cytometry. The interaction between LOC102553417 and miR­30e, and that between miR­30e and MTDH, was demonstrated using the dual­luciferase reporter assay and RNA binding protein immunoprecipitation. The apoptosis of HSC­T6 cells was detected after transfection of miR­30e mimics and inhibitors with or without silencing LOC102553417. Silencing of LOC102553417 curbed HSC­T6 cell proliferation and expedited their apoptosis. LOC102553417 was demonstrated to target miR­30e, whereas miR­30e targeted MTDH. In addition, LOC102553417 silencing significantly upregulated miR­30e expression levels, and significantly downregulated MTDH mRNA and protein expression levels, which resulted in a significantly reduced p­Akt/Akt ratio and significantly elevated p53 protein expression levels. Transfection with miR­30e mimic alone significantly enhanced HSC­T6 cell apoptosis and inhibits LOC102553417 and MTDH expressions, In addition, miR­30e mimic expedites the apoptosis of HSCs stimulated by LOC102553417 silencing; consistent results were obtained by reverse validation of miR­30e inhibitor. In conclusion, the present study demonstrated that LOC102553417 silencing stimulated the apoptosis of HSCs via the miR­30e/MTDH axis.

Ficus dubia latex extract prevent DMH-induced rat early colorectal carcinogenesis through the regulation of xenobiotic metabolism, inflammation, cell proliferation and apoptosis.

Ficus dubia latex is recognized as a remedy in Asian traditional medicine with various therapeutic effects. The present study aimed to determine the preventive action of Ficus dubia latex extract (FDLE) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis and its mechanisms. The experiment included an initiation model in which rats were orally administered with FDLE daily for 1 week before DMH injection until the end of the experiment, while only after DMH injection until the end in the post-initiation model. The results firstly indicated that FDLE treatment could reduce the level of methylazoxymethanol (MAM) in rat colonic lumen by inhibition of the activities of both phase I xenobiotic metabolizing enzymes in the liver and ß-glucuronidase in the colon, leading to reduced DNA methylation in colonic mucosal cells, related to the number of ACF in the initiation stage. Besides, FDLE modulated the inflammation which could suppress the growth and induce apoptosis of aberrant colonic mucosal cells, leading to retardation of ACF multiplicity. Therefore, FDLE showed the ability to suppress the DMH-induced rat ACF formation and inflammation promoted growth of ACF. In conclusion, FDLE had the potential to prevent carcinogens-induced rat colorectal carcinogenesis in the initiation stage.

Ficus dubia Latex Extract Induces Cell Cycle Arrest and Apoptosis by Regulating the NF-κB Pathway in Inflammatory Human Colorectal Cancer Cell Lines.

Colorectal cancer is one of the most diagnosed cancers that is associated with inflammation. Ficus dubia latex is recognized as a remedy with various therapeutic effects in traditional medicine, including anti-inflammatory and antioxidant activity. The present study aims to compare the anti-tumor activity of Ficus dubia latex extract (FDLE) against HCT-116 and HT-29 human colorectal cancer cell lines in normal and inflammatory condition and explore its mechanism of action. FDLE exhibited remarkable antiproliferative activity against HCT-116 and HT-29 colorectal cancer cell lines in both conditions using MTT and colony formation assays and more effective anti-proliferation was observed in inflammatory condition. Mechanistically, FDLE induced cell cycle arrest at G0/G1 phase by down-regulating NF-κB, cyclin D1, CDK4 and up-regulatingp21 in both cell in normal condition. In inflammatory condition, FDLE not only exhibited stronger induction of cell cycle arrest in both cells by down-regulating NF-κB, cyclin D1, CDK4 and down-regulating p21, but also selectively induced apoptosis in HCT-116 cells by down-regulating NF-κB and Bcl-xl and up-regulating Bid, Bak, cleaved caspase-7 and caspase-3 through stronger ability to regulate these proteins. Our results demonstrated that the phytochemical agent in the latex of Ficus dubia could potential be used for treatment and prevention of human colorectal cancer, especially in inflammation-induced hyperproliferation progression.

circ_PTN contributes to -cisplatin resistance in glioblastoma via PI3K/AKT signaling through the miR-542-3p/PIK3R3 pathway.

Glioblastoma has been identified as the most common and aggressive primary brain tumor in adults. Recently, it has been found that cisplatin (DDP) treatment is a common chemotherapeutic method for GBM patients. circ_PTN (ID number: hsa_circ_0003949) is a newly found circular (circRNA) which has been proved to be highly expressed in GBM cells, while its role in GBM remains unclear. Therefore, our study focused on investigating the role of circ_PTN in the DDP resistance of GBM cells. The expression of circ_PTN in DDP-sensitive and DDP-resistant GBM cells was detected in our assay. Functional experiments were utilized to unveil the effects of circ_PTN on the DDP resistance of GBM cells. Moreover, mechanism assays were conducted to confirm the mechanism of how circ_PTN affected the DDP resistance of GBM cells. According to the results, we found that circ_PTN promoted the DDP resistance of GBM cells through activation of the PI3K/AKT pathway. Moreover, circ_PTN silencing inhibited the DDP resistance of GBM tumors in vivo. To conclude, our study unveiled the influence of circ_PTN on the DDP resistance of GBM cells, which might provide a therapeutic target for GBM treatment via DDP.

NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun.

The prognosis of glioma is poor as its pathogenesis and mechanisms underlying cisplatin chemoresistance remain unclear. Nucleosome assembly protein 1 like 1 (NAP1L1) is regarded as a hallmark of malignant tumors. However, the role of NAP1L1 in glioma remains unknown. In this study, we aimed to investigate the molecular functions of NAP1L1 in glioma and its involvement in cisplatin chemoresistance, if any. NAP1L1 was found to be upregulated in samples from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry indicated that NAP1L1 and hepatoma-derived growth factor (HDGF) were enhanced in glioma as compared to the para-tumor tissues. High expressions of NAP1L1 and HDGF were positively correlated with the WHO grade, KPS, Ki-67 index, and recurrence. Moreover, NAP1L1 expression was also positively correlated with the HDGF expression in glioma tissues. Functional studies suggested that knocking down NAP1L1 could significantly inhibit glioma cell proliferation both in vitro and in vivo, as well as enhance the sensitivity of glioma cells to cisplatin (cDDP) in vitro. Mechanistically, NAP1L1 could interact with HDGF at the protein level and they co-localize in the cytoplasm. HDGF knockdown in NAP1L1-overexpressing glioma cells significantly inhibited cell proliferation. Furthermore, HDGF could interact with c-Jun, an oncogenic transcription factor, which eventually induced the expressions of cell cycle promoters, CCND1/CDK4/CDK6. This finding suggested that NAP1L1 could interact with HDGF, and the latter recruited c-Jun, a key oncogenic transcription factor, that further induced CCND1/CDK4/CDK6 expression, thereby promoting proliferation and chemoresistance in glioma cells. High expression of NAP1L1 in glioma tissues indicated shorter overall survival in glioma patients.

Serum Homocysteine Levels and Microalbuminuria in Patient with Systemic Lupus Erythematosus.

BACKGROUND: At present, the relationship between serum homocysteine and microalbuminuria (MAU) in systemic lupus erythematosus (SLE) patients is still unclear. Therefore, the aim of our study was to analyze the association between serum homocysteine and MAU in SLE patients. METHODS: The study analyzed 150 patients with SLE at Affiliated Hospital of Youjiang Medical University for Nationalities retrospectively, and we collected for clinical and laboratory data. RESULTS: We found a positive correlation between serum homocysteine and MAU in SLE patients (r = 0.430, p < 0.001). We found that serum homocysteine levels were increased in SLE patients with MAU positive compared to those who were MAU negative (p < 0.001). After adjusting for multiple confounding factors, we found that serum homocysteine maintained a positive correlation with MAU in patients with SLE in multivariate correlation analysis (p = 0.253, r = 0.002). The receiver operating characteristic (ROC) curve with an area under the curve of 0.730, and serum homocysteine had 72.2% sensitivity and 61.9% specificity with cutoff values 9.0 to identify the SLE patients with MAU positive. CONCLUSIONS: The current results found a correlation between serum homocysteine and MAU in SLE patients, suggesting that elevated serum homocysteine levels might be an adverse factor for SLE patients with kidney injury.

Upregulation of DEAD box helicase 5 and 17 are correlated with the progression and poor prognosis in gliomas.

Recent researches indicated Ddx5 and Ddx17 play crucial roles in tumorigenesis. However, the study of Ddx5 and Ddx17 in glioma remains a little. Our study investigated their expression in glioma and evaluated its association with clinical factors and prognostic significance. The expression of Ddx5 and Ddx17 were both upregulated in glioma tissues compared to normal brain tissues, and a significant positive correlation between Ddx5 and Ddx17 expression was identified by statistical analysis. Immunohistochemical staining verified the expression of Ddx5 and Ddx17 in peritumoral zone was lower than that in core zone but higher than normal brain tissues. Moreover, the increased expression of Ddx5 and Ddx17 was markedly correlated with WHO Grade and histological type, and high Ddx5 and Ddx17 were found to be significantly associated with the worse overall survival of glioma patients. In additional, higher expression of both Ddx5 and Ddx17 predicted shorter clinical survival time for high-grade glioma patients with radiotherapy or with chemotherapy. In conclusion, overexpressed Ddx5 and Ddx17 are involved in the clinical progression and poor prognosis of glioma patients, suggesting that their upregulation can be used as a reliable clinical predictor for tumor diagnosis and to predict survival in patients with glioma.

[Curcumin suppresses invasiveness and migration of human glioma cells in vitro by inhibiting HDGF/ß-catenin complex].

OBJECTIVE: To investigate the effect of curcumin on the invasion and migration of human glioma cells in vitro and explore the molecular mechanisms. METHODS: MTT assay was used for screening the optimal curcumin concentrations. The effects of curcumin on the invasion and metastasis of human glioma cell lines U251 and LN229 were tested using Transwell assay, Boyden assay and wound-healing assays. The expression of the related proteins and their interactions were determined using Western blotting and coimmunoprecipitation assay. RESULTS: Curcumin at the concentration of 20 µmol/L for 48 h was used as the optimal condition for subsequent cell treatment. In the two glioma cell lines, curcumin significantly suppressed the invasion and migration of the cells (P < 0.05) and lowered the expressions of hepatoma-derived growth factor (HDGF), Ncadherin, vimentin, Snail and Slug, but increased the expression of E-cadherin. Interference of HDGF in curcumin-treated glioma cells synergistically inhibited the epithelial-mesenchymal transition (EMT) signals, while overexpression of HDGF significantly reversed the inhibitory effect of curcumin on EMT; curcumin treatment could significantly reduce the binding of HDGF to ß-catenin. CONCLUSIONS: Curcumin suppresses EMT signal by reducing HDGF/ß-catenin complex and thereby lowers the migration and invasion abilities of human glioma cells in vitro.

Identification of the Transcriptional Networks and the Involvement in Angiotensin II-Induced Injury after CRISPR/Cas9-Mediated Knockdown of Cyr61 in HEK293T Cells.

BACKGROUND: The transcriptional networks of Cyr61 and its function in cell injury are poorly understood. The present study depicted the lncRNA and mRNA profiles and the involvement in angiotensin II-induced injury after Cyr61 knockdown mediated by CRISPR/Cas9 in HEK293T cells. METHODS: HEK293T cells were cultured, and Cyr61 knockdown was achieved by transfection of the CRISPR/Cas9 KO plasmid. lncRNA and mRNA microarrays were used to identify differentially expressed genes (DEGs). Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine biofunctions and signaling pathways. RT-PCR was used to validate the microarray results. Cells were divided into four groups: control, Cyr61 knockdown, angiotensin II (Ang II) without Cyr61 knockdown, and Ang II with Cyr61 knockdown. CCK8, western blotting, and flow cytometry analysis were carried out to dissect cellular function. RESULTS: A total of 23184 lncRNAs and 28264 mRNAs were normalized. 26 lncRNAs and 212 mRNAs were upregulated, and 74 lncRNAs and 233 mRNAs were downregulated after Cyr61 knockdown. Analysis of cellular components, molecular functions, biological processes, and regulatory pathways associated with the differentially expressed mRNAs revealed downstream mechanisms of the Cyr61 gene. The differentially expressed genes were affected for small cell lung cancer, axon guidance, Fc gamma R-mediated phagocytosis, MAPK signaling pathway, focal adhesion, insulin resistance, and metabolic pathways. In addition, Cyr61 expression was increased in accordance with induction of cell cycle arrest and apoptosis and inhibition of cell proliferation induced by Ang II. Knockdown of Cyr61 in HEK293T cells promoted cell cycle procession, decreased apoptosis, and promoted cell proliferation. CONCLUSIONS: The Cyr61 gene is involved in Ang II-induced injury in HEK293T cells. Functional mechanisms of the differentially expressed lncRNAs and mRNAs as well as identification of metabolic pathways will provide new therapeutic targets for Cyr61-realated diseases.

Overexpression of osteopontin promotes cell proliferation and migration in human nasopharyngeal carcinoma and is associated with poor prognosis.

Nasopharyngeal carcinoma (NPC), a malignant tumor at the top and side of the nasopharyngeal cavity, highly occurs in the southern region of China. Cancer cell metastasis is one of the leading causes of death in NPC patients. Osteopontin (OPN), is a phosphorylated extracellular matrix protein with a variety of functions, was found to be overexpressed in many cancers. However, the expression and role of OPN in patients with NPC in Guangxi, China are unclear. Here, we observed that NPC patients had upregulated OPN at mRNA protein and levels. Immunochemistry (IHC) analysis of OPN expression in 68 NPC clinical specimens indicated that high expression of OPN had positive correlation with NPC lymph node metastasis (P = 0.012), distant metastasis (P = 0.001) and TNM staging (P = 0.018). Moreover, compared with relatively low OPN, NPC patients with higher expression of OPN showed a poorer overall survival rate (P = 0.001, log rank test). Multivariate analysis showed that OPN expression in NPC was an independent prognostic marker. The proliferation, apoptosis and migration ability of CEN-2Z cancer cells in NPC were determined by MTT, flow cytometry and wound-healing assays, respectively. Upregulation of OPN in CEN-2Z cancer cells promoted cancer cell proliferation and migration, and suppressed apoptosis. In sum, our result suggests OPN could be used as a valuable oncoprotein and show that overexpression of OPN in NPC may serve as a potential prognostic marker.