Downregulation of RNF128 Inhibits the Proliferation, Migration, Invasion and EMT of Colorectal Cancer Cells.

Colorectal cancer has the third highest incidence and second highest mortality rate among all cancer types. Exploring the molecular mechanisms driving malignant proliferation and metastasis of colorectal cancer will benefit the treatment and management of cancer patients. Recent studies have reported diametrically opposed roles of Ring finger protein 128 (RNF128) in different types of cancer. However, the role of RNF128 in colorectal cancer is still completely unknown, which this study attempts to analyze. The differential expression of RNF128 mRNA and protein in 30 pairs of colorectal cancer and corresponding peritumoral tissues was detected using RT-qPCR, western blot and immunohistochemical staining. siRNA specifically targeting RNF128 was transfected into colorectal cancer cell lines (SW1116 and SW480) cultured in vitro. Proliferation, growth, migration, invasion and epithelial-mesenchymal transition (EMT) of colorectal cancer cells were examined by CCK-8, clone formation, wound-healing, transwell, western blot and immunofluorescence assays. Both RNF128 mRNA and protein levels were significantly increased in colorectal cancer tissues compared to pericarcinoma tissues. Knockdown of RNF128 significantly inhibited the proliferation, growth, migration, invasion and EMT of SW480 and SW1116 cells. Targeting RNF128 may benefit the treatment and management of colorectal cancer.

Pristimerin Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review.

Pristimerin, a natural triterpenoid isolated from the plants of southern snake vine and Maidenwood in the family Weseraceae, is anti-inflammatory, insecticidal, antibacterial, and antiviral substance and has been used for its cardioprotective and antitumor effects and in osteoporosis treatment. These qualities explain Pristimerin's therapeutic effects on different types of tumors and other diseases. More and more studies have shown that pristimerin acts in a wide range of biological activities and has shown great potential in various fields of modern and Chinese medicine. While Pristimerin's wide range of pharmacological effects have been widely studied by others, our comprehensive review suggests that its mechanism of action may be through affecting fundamental cellular events, including blocking the cell cycle, inducing apoptosis and autophagy, and inhibiting cell migration and invasion, or through activating or inhibiting certain key molecules in several cell signaling pathways, including nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/protein kinase B/mammalian-targeted macromycin (PI3K/Akt/mTOR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1/2 (ERK1/2), Jun amino-terminal kinase (JNK1/2/3), reactive oxygen species (ROS), wingless/integrin1 (Wnt)/ß-catenin, and other signaling pathways. This paper reviews the research progress of Pristimerin's pharmacological mechanism of action in recent years to provide a theoretical basis for the molecular targeting therapy and further development and utilization of Pristimerin. It also provides insights into improved treatments and therapies for clinical patients and the need to explore pristimerin as a potential facet of treatment.

Tripterygium wilfordii Hook. F. and Its Extracts for Psoriasis: Efficacy and Mechanism.

Psoriasis is an inflammatory autoimmune skin condition that is clinically marked by chronic erythema and scaling. The traditional Chinese herb Tripterygium wilfordii Hook. F. (TwHF) is commonly used in the treatment of immune-related skin illnesses, such as psoriasis. In clinical studies, PASI (Psoriasis Area and Severity Index) were dramatically decreased by TwHF and its extracts. Their benefits for psoriasis also include relief from psoriasis symptoms such as itching, dryness, overall lesion scores and quality of life. And the pathological mechanisms include anti-inflammation, immunomodulation and potentially signaling pathway modulations, which are achieved by modulating type-3 inflammatory cytokines including IL-22, IL-23, and IL-17 as well as immune cells like Th17 lymphocytes, γδT cells, and interfering with IFN-SOCS1, NF-κB and IL- 36α signaling pathways. TwHF and its extracts may cause various adverse drug reactions, such as gastrointestinal responses, aberrant hepatocytes, reproductive issues, and liver function impairment, but at adequate doses, they are regarded as an alternative therapy for the treatment of psoriasis. In this review, the effectiveness and mechanisms of TwHF and its extracts in psoriasis treatment are elucidated.

Targeting neddylation as a novel approach to lung cancer treatment (Review).

As a protein that resembles ubiquitin, neural precursor cell expressed developmentally downregulated 8 (NEDD8) takes part in neddylation, which modifies substrates in a manner similar to ubiquitination and alters the activity of target proteins. Neddylation may affect the activity of multiple signaling pathways, have a regulatory role in tumor formation, progression and metastasis, and influence the prognosis of cancer treatment. The present review summarizes the regulatory roles of NEDD8 in the MDM2­p53, NF­κB, PI3K/AKT/mTOR, hypoxia­inducible factor, Hippo and receptor tyrosine kinase signaling pathways, as well as in the development and progression of lung cancer.

Qingchang Mixture Prevents the Intestinal Ischemia-reperfusion Injury through TLR4/NF-kB Pathway.

OBJECT: This study aims to determine the protective effect and molecular responses of the traditional Chinese medicine Qingchang mixture on intestinal ischemia-reperfusion (IR) injury. METHODS: The rat intestinal IR model was prepared. The intestinal ischemic injury was evaluated by HE staining, biochemical assay and western blot. In addition, a human hypoxia-reoxygenation (HR) in vitro model was prepared using intestinal epithelial cells (IEC-6). The viability and apoptosis of IEC-6 cells were measured by CCK8 and apoptosis detection. TAK242 or PDTC was used as a small molecule inhibitor of TLR4 or NF-κB, respectively. RESULTS: Compared with the IR group, the pretreatment of the Qingchang mixture reduced the morphological damage, oxidative stress, inflammatory response, and barrier function damage of the small intestine tissue. IR significantly increased the expression of TLR4 and NF-κB, while the pretreatment of the Qingchang mixture inhibited the expression of TLR4 and NF-κB. Furthermore, the pretreatment of Qingchang mixture, TAK242, or PDTC effectively improved the viability and hindered apoptosis of the HR-induced IEC-6 cells. CONCLUSIONS: Traditional Chinese medicine Qingchang mixture prevents intestinal IR injury through TLR4/NF-kB pathway.

Sichong formula inhibits the proliferation and migration of human gastric cancer cells.

PURPOSE: Traditional Chinese medicine (TCM) has gained increasing attention for the treatment of multiple chronic diseases, such as cancer. Here we aim to identify the antitumor activity of Sichong formula, a novel TCM, in human gastric cancer cells and investigate the underlying mechanisms. METHODS: The AGS and MKN45 gastric cancer cells were treated with Sichong formula at different concentrations. The proliferation rates were tested by CCK-8 and colony formation assays. Cell migration and invasion were tested by scratch and transwell assays. Gelatin zymography was used to detect the matrix metalloproteinase 9 (MMP9) activity in cell suspendents. Cell apoptosis was analyzed by Annexin V/PI staining and flow cytometry. The expression of interest proteins was tested by Western blot. RESULTS: Cell proliferation analysis indicated that Sichong formula inhibited cell viability of AGS and MKN45 cells in a dose- and time-dependent manner. The IC50 values were 240 µg/mL and 200 µg/mL for AGS and MKN45 cells, respectively. Furthermore, we found that Sichong formula could inhibit the invasion and migration of gastric cancer cells, which might be mediated by the downregulation of MMP9 activity. Flow cytometry results indicated that Sichong formula induced apoptosis in gastric cancer cells through upregulation of Bax/Bcl2 ratio and activation of caspase cascade. The results from Western blot indicated that Sichong formula resulted in cell autophagy and inactivation of AKT signaling pathway. CONCLUSION: Our data suggest that Sichong formula inhibits the proliferation and migration and induces apoptosis in human gastric cancer cells. The inhibitory effect of Sichong formula was, at least partly, mediated by cell autophagy and AKT pathway.