Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose-induced apoptosis via p21-p53-MDM2 signaling in INS-1 cells.

Pioglitazone/metformin adduct is a novel compound synthesized from pioglitazone and metformin combined at a molar mass ratio of 1:1. The aim of this study was to investigate the effects of pioglitazone/metformin adduct on high glucose-induced insulin secretion and apoptosis in INS-1 cells. Western blot and CCK8 analyses showed that the death rate of INS-1 cells increased in response to glucose treatment in a concentration-dependent manner. ELISA assays and Western blot analyses showed that insulin secretion peaked following treatment with glucose concentration at 33.33 mM. Treatment of INS-1 cells with 1 µM pioglitazone/metformin adduct in the presence of 33.33 mM glucose greatly improveded the levels of insulin and apoptosis rates compared to those of the control group. Analysis of mechanism underlying these effects revealed the involvement of the p21-p53-MDM2 signaling pathway. Our results indicate that pioglitazone/metformin adduct is superior to pioglitazone and/or metformin in regulating high glucose-induced insulin secretion and apoptosis in INS-1 cells.

Cardiac Tamponade as Initial Presentation of Angioimmunoblastic T-Cell Lymphoma.

A 21-year-old man presented initially with impending cardiac tamponade secondary to an angioimmunoblastic T-cell lymphoma (AITL). Following unsuccessful pericardiocentesis and subxiphoid pericardiostomy, the patient's deteriorating hemodynamics prompted an urgent sternotomy. Histopathological diagnosis confirmed AITL. While chemotherapy remains the most effective treatment of AITL, life-threatening complications of the tumor necessitates surgical intervention.

[A new species of Culicoides (Beltranmyia) from China (Diptera:Ceratopogonidae)].

OBJECTIVE: To investigate the species of blood-sucking midges of Shanghai. METHODS: The specimens were collected by light-trap from Pudong Airport (reed marshes), Shanghai, during the years of 2007-2009. The captured samples was briefly classified, and mounted slide specimens with phenol-balsam method. The microscopic examination including morphological and numerical characters for species identification. RESULTS: A new species of biting midges named Culicoides (Beltranmyia) shanghaiensis sp. nov. was obtained, its diagnostic characters were as follows: 1) wing without distinct pale or dark markings, only 0-7 macrotrichia find in basal cell; 2) the female eyes separate, with pubescence between facets, proboscis head ratio (P/H) 0.7, while the head proboscis ratio (H/P) 1.45, antennal ratio (AR) 1.18, sensila coeloconica present on segments 3-14 (frequency: 1.0, 0.7, 0.5, 0.5, 0.7, 0.5, 0.8, 0.7, 1.0, 1.0, 1.0, 1.0, respectively, n = 17) and absent on segments 4-10 indefinitely, with one developed spermatheca; 3) the male's parameres fused narrowly on base. The new species is allied to Culicoides homochrous Remm, but can be distinguished chiefly by: its wing with numerous macrotrichias distributing in basal cell; female eyes separate, bare, H/P 1.03-1.04; male's parameres separate. Besides, the Culicoides charadraeus Arnaud and Culicoides rarus Das Gupta also resembling with the new species, it can be differentiated from the two former species by the female eyes bare and contiguous (or narrowly separated), AR > 1.61, no macrotrichia in basal cell of the wings, and the different male genitalia features. CONCLUSION: A new species of biting midges collected from Shanghai is described, and some diagnostic characters are discussed for distinguishing the closely allied species.

Anticancer effects of oridonin on colon cancer are mediated via BMP7/p38 MAPK/p53 signaling.

Colon cancer is a prevalent malignancy affecting the gastrointestinal tract. Oridonin (ORI) is a promising chemotherapeutic drug used in the treatment of colon cancer. In this study, we examined the anticancer activity of ORI against colon cancer and elucidated the underlying molecular mechanisms. Cell counting kit-8, flow cytometric and western blot analyses were conducted to analyze the growth inhibitory effects of ORI on SW620 cells; we employed BMP7 and p53 recombinant adenovirus to detect the influence of ORI on the p38 MAPK signal pathway; PT-qPCR, cell immunofluorescence staining and western blot analysis were used to detect the expression of BMP7, p38 and p-p38, p53 and p-p53. A xenograft tumor model and histological evaluation were introduced to detect the effects of ORI and BMP7 in SW620 cells in vivo. ORI inhibited the proliferation of SW620 cells and induced apoptosis. ORI also increased the total and phosphorylated levels of p53. The overexpression of p53 was found to enhance the anti-proliferative effects of ORI on the SW620 cells, while the inhibition of p53 partially reversed these effects. ORI increased the expression of bone morphogenetic protein 7 (BMP7) in the SW620 cells. The overexpression of BMP7 also enhanced the antiproliferative effects of ORI on the SW620 cells and reduced the growth rate of tumors in mice. BMP7-induced immunosuppression markedly decreased the anti-proliferative effects of ORI. ORI was not found to exert any substantial effect on the phosphorylation levels of Smad1/5/8, although it increased the level of p-p38 significantly. The inhibition of p38 significantly attenuated the ORI-induced increase in the levels of p-p53. The overexpression of BMP7 enhanced the promoting effects of ORI on the p-p53 and p-p38 levels, while BMP7-induced immunosuppression reduced the effects of ORI on p-p38 and p-p53. On the whole, the findings of this study suggest that ORI may be a promising agent for use in the treatment of colon cancer, and the anticancer effects of ORI may be partially mediated through the BMP7/p38 MAPK/p53 signaling pathway.

BMP7 mediates the anticancer effect of honokiol by upregulating p53 in HCT116 cells.

Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner. HNK activates p53 in HCT116 and other colon cancer cells. Exogenous p53 potentiates the anticancer of HNK, while p53 inhibitor decreases this effect of HNK. Moreover, HNK upregulates the expression of bone morphogenetic protein 7 (BMP7) in colon cancer cells; Exogenous BMP7 enhances the anticancer activity of HNK and BMP7 specific antibody reduces this effect of HNK. For mechanism, we found that HNK cannot increase the level of Smad1/5/8; Exogenous BMP7 potentiates the HNK-induced activation of p53. On the contrary, BMP7 specific antibody inhibits the HNK-induced activation of p53 in colon cancer cells and partly decreases the total level of p53. Our findings suggested that HNK may be a promising anticancer drug for CRC; activation of p53 plays an important role in the anticancer activity of HNK, which may be initialized partly by the HNK-induced upregulation of BMP7.

TGF-ß1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells.

The diagnosis and treatment for colon cancer have been greatly developed, but the prognosis remains unsatisfactory. There is still a great clinical need to explore new efficacious drugs for colon cancer treatment. Tetrandrine (Tet) is a bis-benzylisoquinoline alkaloid. It has been shown that Tet may be a potential candidate for cancer treatment, but the explicit mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Tet in human colon cancer cells and dissected the possible mechanism. With cell viability assay and flow cytometry analysis, we confirmed that Tet can effectively inhibit the proliferation and induce apoptosis in HCT116 cells. Mechanically, we found that Tet greatly increases the mRNA and protein level of TGF-ß1 in HCT116 cells. Exogenous TGF-ß1 enhances the anti-proliferation and apoptosis inducing effect of Tet in HCT116 cells, which has been partly reversed by TGF-ß1 inhibitor. Tet decreases the phosphorylation of Akt1/2/3 in HCT116 cells. This effect can be enhanced by exogenous TGF-ß1, but partly reversed by TGF-ß1 inhibitor. Tet exhibits no effect on total level of PTEN, but decreases the phosphorylation of PTEN; exogenous TGF-ß1 enhances the effect of Tet on decreasing the phosphorylation of PTEN, which was partly reversed by TGF-ß1 inhibitor. Our findings suggested that Tet may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating TGF-ß1 to decrease the phosphorylation of PTEN.