Characteristics of ginsenoside Rd-induced effects on rat intestinal contractility with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a very common refractory disease. Its exact pathophysiological mechanism is still unclear. Despite the availability of plentiful drugs to control IBS, most patients do not respond well. Ginsenoside Rd is one of the major active components of Panax ginseng, which has been verified to produce various pharmacological actions. However, the role of ginsenoside Rd in modulating smooth muscle contractility is still undefined. The aim of this study is to investigate the effects of ginsenoside Rd on intestinal contractility and related mechanisms in IBS.

MIR4435-2HG regulates cancer cell behaviors in oral squamous cell carcinoma cell growth by upregulating TGF-ß1.

MIR4435-2HG has been characterized as an oncogenic lncRNA in several types of cancer, while its role in oral squamous cell carcinoma (OSCC, a major subtype of oral cancer) has not been characterized. We explored the functionality of MIR4435-2HG in OSCC and investigated its interactions with TGF-ß1. Blood samples were extracted from OSCC patients (n = 44) and healthy volunteers (n = 38), RT-qPCR, CCK-8, Transwell assays and western blot were performed in this study. The results showed that levels of MIR4435-2HG and TGF-ß1 in plasma were upregulated in OSCC. Across OSCC plasma samples, TGF-ß1 and MIR4435-2HG were significantly and positively correlated. Overexpression of MIR4435-2HG resulted in upregulated TGF-ß1 expression, while exogenous TGF-ß1 treatment had no effect on the expression of MIR4435-2HG. Overexpression of MIR4435-2HG and exogenous TGF-ß1 treatment led to promoted, while TGF-ß inhibitor led to inhibited migration, proliferation and invasion of cancer cells. Moreover, TGF-ß inhibitor led to reduced effects of overexpressing MIR4435-2HG. Therefore, MIR4435-2HG regulates the behaviors of OSCC cells by promoting the expression of TGF-ß1.

A polysaccharide from the alkaline extract of Glycyrrhiza inflata induces apoptosis of human oral cancer SCC-25 cells via mitochondrial pathway.

In the present study, we isolated and characterized a homogenous polysaccharide (GIAP1) from the alkaline extract of the roots of Glycyrrhiza inflata. The anti-tumor activity of GIAP1 toward human oral cancer SCC-25 cells and the underlying mechanisms were also examined in vitro. GIAP1 dose-dependently inhibited the proliferation of SCC-25 cells via inducing apoptosis. Moreover, GIAP1 downregulated Bax/Bcl-2 ratio, disrupted the mitochondrial membrane potential (MMP), and caused the release of cytochrome c to cytosol. Besides, GIAP1 triggered activation of capase-3 and caspase-9, as well as the degradation of poly (ADP-ribose) polymerase (PARP). In addition, the caspase-3 or caspase-9 inhibitor significantly inhibited GIAP1-induced apoptosis in SCC-25 cells. Collectively, we can conclude that the GIAP1 induces apoptosis in SCC-25 cells via a mitochondrial pathway.

A polysaccharide from Glycyrrhiza inflata Licorice inhibits proliferation of human oral cancer cells by inducing apoptosis via mitochondrial pathway.

In the present study, we isolated and characterized a water-soluble polysaccharide (GIP1) from the roots of Glycyrrhiza inflata. The goal of this study was to investigate the anti-tumor effect of GIP1 on the human oral cancer SCC-25 cell line and to explore the possible mechanism. Our experimental result showed that GIP1 (50, 100, and 200 µg/mL) specifically decreased cell viability of SCC-25 cells in a concentration-dependent manner via the induction of apoptosis. Furthermore, Western blot analysis showed that exposure of SCC-25 cells to GIP1 led to down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, thus causing a loss of mitochondrial membrane potential and the release of cytochrome c to the cytosol. Moreover, we observed activation of the initiator caspaes-9, and the effector caspases-3, but not caspase-8. Concomitantly, GIP1-induced apoptosis can be blocked by caspase-3- or caspase-9-specific inhibitor, but not caspase-8 inhibitor. As well, the cleaved poly (ADP-ribose) polymerase, as a caspae-3 substrate, occurred in SCC-25 cells following GIP1 treatment at three concentrations. Collectively, our results showed that the GIP1 induced apoptosis in SCC-25 cells involving a caspase-dependent mitochondrial signaling pathway.

Antimetastatic effects of licochalcone A on oral cancer via regulating metastasis-associated proteases.

Licochalcone A, a major phenolic constituent of the licorice species Glycyrrhiza inflata, has been proven to possess various biological benefits including anti-cancer activity. However, the detailed effects and molecular mechanisms of licochalcone A on the invasiveness and metastasis of oral cancer cells have not been fully understood. Thus, SCC-25 oral cancer cells were subjected to a treatment with licochalcone A at indicated concentrations (25, 50, and 100 µg/mL) for 36 h and then analyzed for the effect of licochalcone A on the cell migration and invasion. In vitro assays, including wound healing, cell adhesion, and cell invasion/migration assays, revealed that licochalcone A treatment significantly inhibited the cell migration/invasion capacities of SCC-25 cells. Also, results of zymography and Western blotting showed that activity and protein level of matrix metalloproteinase-2 (MMP-2) was suppressed, but TIMP-2 level was increased, indicating the important role of MMP-2 and TIPM-2 in anti-metastatic regulation of SCC-25 cells. Furthermore, licochalcone A was shown to suppress the nuclear factor-kappa B (NF-κB) signal, as evidenced by the decreased expression of phosphorylated p65 (p-65) protein in licochalcone A-treated SCC-25 cells. Notably, we also found that licochalcone A treatment increased the expression of the epithelial marker E-cadherin and decreased the expression of mesenchymal markers N-cadherin in SCC-25 cells. This is the first report describing the effects and possible mechanisms of licochalcone A on tumor invasion and metastasis of SCC-25 cells. Taken together, our findings support that licochalcone A can be developed to a potent anti-metastatic candidate for oral cancer therapy.

Functional and morphologic outcome after stapled transanal rectal resection for obstructed defecation syndrome.

BACKGROUND: Stapled transanal rectal resection is a novel surgery for obstructed defecation syndrome. Few data on the functional and morphologic outcome after the surgery have been reported. OBJECTIVE: This study aimed to evaluate the functional and morphologic outcome after stapled transanal rectal resection. DESIGN: This is a prospective study of consecutive patients undergoing transanal rectal resection. SETTING: The study was conducted at a tertiary referral hospital, Beijing, China, from May 2007 to May 2009. PARTICIPANTS: Eighty-six consecutive female patients with obstructed defecation syndrome were carefully selected. INTERVENTIONS: All patients underwent stapled transanal rectal resection. MAIN OUTCOME MEASURES: The main outcome measures were patients' symptoms, obstructed defecation syndrome score, Wexner incontinence score, anorectal manometry and defecography before and 1 year after surgery. RESULTS: The occurrence of all symptoms were significantly reduced after the procedure (P < .0001). Obstructed defecation syndrome score was decreased from 18.17 ± 4.68 preoperatively to 7.36 ± 3.52 postoperatively (P < .0001) with the Wexner incontinence score unchanged. Maximum tolerable rectal volume was significantly decreased (236.08 ± 50.00 vs 205.25 ± 29.60, P < .0001) after surgery with anal sphincter pressures unchanged. Postoperative defecography was performed in 64 patients. Rectocele disappeared in 40 of 62 patients. The depth of rectocele was reduced from 35.40 ± 4.58 mm preoperatively to 19.77 ± 9.19 mm postoperatively (P < .0001). Incomplete evacuation disappeared in 41 of 51 patients. Intussusception was completely corrected in 39 of 56 patients. The reduction of obstructed defection syndrome score was greater in patients with both rectocele and intussusception corrected than others (12.75 ± 2.24 vs 9.17 ± 3.47; P < .0001). LIMITATIONS: This study was limited owing to the lack of a control group and the medium-term results. CONCLUSIONS: Stapled transanal rectal resection is an effective procedure for obstructed defecation syndrome. The functional outcome is good with the preservation of sphincter function and continence postoperatively. The morphologic outcome confirmed its efficacy in correcting rectocele and intussusception, and correlated well with clinical improvement.