[Recent research on the nuclear factor-kappa B signaling pathway in cardiac injury in children with Kawasaki disease]. / NF-κBä¿¡å·é€šè·¯åœ¨å„¿ç«¥å·å´Žç— å¿ƒè„æŸä¼¤ä¸­çš„ç ”ç©¶è¿›å±•.

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is a systemic acute vasculitis belonging to autoimmune disease. Up to now, the specific pathogenesis of this disease remains unclear, and it may involve various factors such as immune response, inflammatory response, and vascular endothelial injury caused by the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. In particular, children with KD and cardiac injury tend to have a poor prognosis, and researchers hope to explore the specific pathogenesis of cardiac injury in KD to provide new options for clinical diagnosis and treatment and reduce the incidence rate of this disorder. This article reviews the recent research on the role of the NF-κB signaling pathway in cardiac injury in children with KD, so as to provide a basis for future studies.

Identification of the New Psychoactive Substance Eutylone.

OBJECTIVES: To establish a method to identify unknown sample based on the combined use of Fourier transform infrared spectroscopy (FTIR), gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF-MS), ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS) and 1H-nuclear magnetic resonance spectroscopy (1H-NMR) technique. METHODS: The unknown sample was directly analyzed by FTIR. The unknown sample was dissolved in methanol solution containing internal standard SKF525A and the supernatant was detected by GC-QTOF-MS and UPLC-LTQ-Orbitrap MS. The unknown sample was dissolved in methanol-d4 solution for structural analysis of 1H-NMR. RESULTS: The characteristic absorption peaks of FTIR spectra obtained from unknown sample were 1 682 (C=O bond), 1 503, 1 488, 1 436, 1 363, 1 256, 1 092, 1 035, 935, 840 and 800 cm-1, the characteristic fragment ions (m/z) of GC-QTOF-MS were 86.096 4 (base peak), 58.065 1, 149.023 5, 121.028 6 and 65.038 6, the accurate mass [M+H]+ detected by UPLC-LTQ-Orbitrap MS was 236.127 7. The sample was identified as synthetic cathinone new psychoactive substance Eutylone by 1H-NMR. CONCLUSIONS: The method established in this study can be used for structural confirmation of Eutylone.

miR-186 inhibits proliferation, migration, and epithelial-mesenchymal transition in breast cancer cells by targeting Twist1.

OBJECTIVE: Breast cancer (BC) is the most prevalent malignancy in women worldwide. Our study aimed to investigate the expression and biological effect of miR-186 in BC. METHODS: Expression of miR-186 was determined by quantitative reverse transcription PCR. Kaplan-Meier curves were calculated for the survival data analysis. Functional assays were performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound healing assay. Protein expression was analyzed by Western blot. RESULTS: miR-186 was downregulated in BC tissues and cells. Downregulation of miR-186 was associated with tumor metastasis and a poor overall survival in patients with BC. Overexpression of miR-186 inhibited BC cells proliferation, migration, and epithelial-mesenchymal transition process; while suppression of miR-186 exhibited an opposite effects on BC cells. In addition, Twist1 was identified as a direct target of miR-186 in BC and restoration of Twist1 attenuated the biological effect of miR-186 on BC cells. CONCLUSION: Our findings suggest that miR-186 functions as a tumor suppressor by targeting Twist1 in BC. miR-186 may serve as a novel biomarker in BC diagnosis or a new therapeutic target in BC treatment.

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.

The E3 Ubiquitin Ligase CRL4 Regulates Proliferation and Progression Through Meiosis in Chinese Mitten Crab Eriocheir sinensis.

The Cullin-RING E3s are multisubunit ubiquitin ligases composed of a scaffold protein known as Cullin, a RING finger protein that regulates diverse cellular pathways; however, their contribution to male gonad development, especially the spermatogenesis of the Chinese mitten crab (Eriocheir sinensis), is not well understood. We identified five evolutionarily conserved Cullins from the transcriptome and genome ofE. sinensis that are potentially involved in regulating male gonad development. The aim of the current study was to determine the mechanisms of Cullin4's effects on spermatogenesis. We observed that Cullin4, p53, and proliferating cell nuclear antigen had a specific expression and localization in primary spermatocytes. We also investigated the accumulation of Cullin substrates by treatment with inhibitor of NEDD8-activating enzyme MLN4924 in vitro. Cell cycle inhibitors p27 and p21 accumulated significantly after 24 and 36 h, respectively. We speculated that p53-mediated spontaneous germ cell apoptosis acts as a quality control mechanism to eliminate defective germ cells and that the Cullin4 complex maintains p53, p21, and p27 homeostasis in primary spermatocytes to regulate spermatogenesis ofE. sinensis Given its widespread evolutionary conservation, Cullin4 may regulate germ line development similarly in other organisms.

Morphological alterations of all stages of spermatogenesis and acrosome reaction in Chinese mitten crab Eriocheir sinensis.

The Chinese mitten crab (Eriocheir sinensis) is a seasonally breeding species and its reproductive system comprises paired symmetrical structures: testes, vasa deferentia, seminal vesicles, accessory glands and ejaculatory ducts. Histological examination of the testis of mature males reveals regression of the gonads and inhibition of the process of spermatogenesis during December to April of the following year, the regeneration of the gonads during June to July and the occurrence of the highest level of spermatogenesis during August to October. Microscopic assessments and hematoxylin and eosin (H&E) staining were used to describe all spermatogenic stages (spermatogonia, primary and secondary spermatocytes, spermatids and spermatozoids). To observe the morphological changes during spermiogenesis, we successfully initiated primary cell culture using testis tissue of E. sinensis, which will lay a solid foundation for further work on the immortalization of crab cells. During the interaction between the sperm and oocyte, the fertilizing spermatozoon must undergo a series of terminal morphological changes, called the acrosome reaction (AR). This study also provides a detailed description of the structural alterations of the acrosome reaction of E. sinensis. The acrosome complex and cup-shaped nucleus are located at the anterior and posterior of the spermatozoon, respectively. Male germ cell development involves a tightly controlled sequence of differentiation switches. The purpose of this study is to increase our knowledge of the morphological alterations during spermatogenesis and the acrosome reaction, whose changes are a fundamental requirement for fertilization of E. sinensis.

[Distribution of Inflammatory Cells and Expression of PSGL-1 in Infant Brainstem Tissue Related Fatal Brainstem Encephalitis].

OBJECTIVE: To explore the distribution of inflammatory cells and positive expression of P-se- lectin glycoprotein ligand-1 (PSGL-1) in infant brainstem tissue from hand-foot-mouth disease related fatal brainstem encephalitis. METHODS: Twenty brainstem samples from infants suffered from brainstem en- cephalitis were collected as the experimental group. Ten brainstem samples from infants died of non- brain diseases and injuries were collected as the control group. The distribution of inflammatory cells and the expression of PSGL-1 in the two groups were examined by immunohistochemical method. The characteristics of the positive cells were observed. RESULTS: In brainstem tissue of the experimental group, there were sleeve infiltrations of inflammatory cells around the vessels and in the glial nodule. Microglia was the most and following was neutrophils around the vessels and in the glial nodule. There was a significant statistical difference among microglias, neutrophils and lymphocytes (P < 0.05). There was no sleeve infiltration in the control group. PSGL-1 protein was expressed widely in inflammatory cells in the experimental group, especially in the inflammatory cells around the vessels and in the glial nodule. But PSGL-1 positive staining could be observed significantly less in the control group comparing with the experimental group (P < 0.05). CONCLUSION: Microglia is the main type of inflammatory cells involved in the progress of the fatal disease. Moreover, PSGL-1 could participate in the pathogenesis of hand-foot-mouth disease related fatal brainstem encephalitis.

Vitamin D receptor rs2228570 polymorphism and susceptibly to ovarian cancer: a meta-analysis.

The role of vitamin D receptor (VDR) rs2228570 polymorphism on the risk of ovarian cancer has been studied in many studies, but the relationship between VDR rs2228570 polymorphism and ovarian cancer is still unclear. We thus performed a meta-analysis of published studies to provide a comprehensive assessment of the association. Fourteen individual studies with a total of 10,964 subjects were finally included into the meta-analysis. We assessed the association by calculating the pooled odds ratio (OR) with 95 % confidence intervals (95 % CI). There was no heterogeneity among those included studies. Meta-analysis of 14 studies showed that the VDR rs2228570 polymorphism was associated with risk of ovarian cancer under three main comparison models (T versus C: OR = 1.09, 95 % CI 1.03 to 1.15, P = 0.004; TT versus CC: OR = 1.17, 95 % CI 1.04 to 1.32, P = 0.01; and TT/CT versus CC: OR = 1.12, 95 % CI 1.03 to 1.21, P = 0.007). Subgroup analysis in Caucasians further identified the obvious association. There was no evidence of publications bias. These data from the meta-analysis suggest that VDR rs2228570 polymorphism is associated with risk of ovarian cancer in Caucasians. More studies are warranted to assess the association between the VDR rs2228570 polymorphism and ovarian cancer in Asians and Africans.

[Anti-tumor effects of a novel cyclophosphamide derivate 9b in vivo and in vitro].

This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.

Effects of Dietary Supplementation of Stimbiotics to Sows on Lactation Performance, Immune Function, and Anti-Inflammatory and Antioxidant Capacities during Late Gestation and Lactation.

Stimbiotic supplementation may provide an innovative feed additive solution to accelerate the proliferation of beneficial fiber-degrading bacteria in the distal intestine and the utilization of dietary fiber. Optimal utilization of dietary fiber has multiple benefits for gut health and nutrient utilization. This study was conducted to evaluate the late gestation and lactation performance, the plasma, colostrum, and milk immunoglobulin (IgA, IgG, and IgM) concentrations, and the anti-inflammatory and antioxidant biomarkers in plasma of sows fed with or without a stimbiotic during the late gestation and lactation phase. A total of 40 sows were allocated to two treatment groups: control (CT) with no supplementation or 100 mg/kg stimbiotic (VP), with 20 sows per treatment. Sows were fed the treatment diets from d 85 of gestation to d 28 of lactation. In the results, the average daily weight gain of piglets during lactation was greater from sows fed in the VP group compared to that in the CT group (p < 0.05). The plasma concentrations of IgM at farrowing and IgG at weaning of the sows fed the diet with the stimbiotic supplementation were much higher than those in the CT sows (p < 0.05), respectively. In addition, the dietary stimbiotic increased the concentrations of IgM in the colostrum and of IgA and IgM in the milk at d 14 of lactation (p < 0.05). Plasma concentrations of malondialdehyde (MDA) on d 0 and d 28 of lactation tended to be lower in sows fed the VP diets compared with those of the sows fed the CT diets. Thus, our study indicated that stimbiotic supplementation could improve the daily weight gain of piglets and the immune function of sows in lactation.

Attachment of Acidithiobacillus ferrooxidans onto different solid substrates and fitting through Langmuir and Freundlich equations.

Attachments of Acidithiobacillus ferrooxidans ATCC 23270 onto elemental sulfur, quartz and complex chalcopyrite were investigated by analysis of its extracellular polymeric substances as well as applying Langmuir and Freundlich equations. The two equations fitted the adsorption equilibrium data with significant correlation coefficient over 0.9. This indicated that bacterial attachment is complicated and involves Langmuir and Freundlich characterizations. Sulfur-grown cells showed the highest affinity for the three solid substrates. The investigated complex chalcopyrite possessed a higher maximum adsorption capacity for A. ferrooxidans than elemental sulfur or quartz. The Freundlich fitting parameters suggested that quartz had a weaker adsorption capacity and smaller adsorption areas than elemental sulfur or the complex chalcopyrite. It is not the content of total carbohydrates or proteins in EPS but their ratios that determine the affinity differences between cells and substrates.

Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice.

Alterations in energy metabolism are associated with depression. However, the role of glycolysis in the pathogenesis of depression and the underlying molecular mechanisms remain unexplored. Through an unbiased proteomic screen coupled with biochemical verifications, we show that the levels of glycolysis and lactate dehydrogenase A (LDHA), a glycolytic enzyme that catalyzes L-lactate production, are reduced in the dorsomedial prefrontal cortex (dmPFC) of stress-susceptible mice in chronic social defeat stress (CSDS) model. Conditional knockout of LDHA from the brain promotes depressive-like behaviors in both male and female mice, accompanied with reduced L-lactate levels and decreased neuronal excitability in the dmPFC. Moreover, these phenotypes could be duplicated by knockdown of LDHA in the dmPFC or specifically in astrocytes. In contrast, overexpression of LDHA reverses these phenotypic changes in CSDS-susceptible mice. Mechanistic studies demonstrate that L-lactate promotes neuronal excitability through monocarboxylic acid transporter 2 (MCT2) and by inhibiting large-conductance Ca2+-activated potassium (BK) channel. Together, these results reveal a role of LDHA in maintaining neuronal excitability to prevent depressive-like behaviors.

p66Shc-mediated oxidative stress is involved in gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a heightened level of oxidative stress, which is characterized by the overproduction of reactive oxygen species (ROS) from mitochondria. Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1 (Drp1) and p66Shc in GDM. AIM: The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM. METHODS: A total of 30 pregnant women, 15 with GDM and 15 without GDM, were enrolled. Peripheral blood mononuclear cells and placental tissue were collected. The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type (wt)-p66Shc and p66Shc siRNA. P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction. The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting. ROS was assayed by dihydroethidium staining. RESULTS: The p66Shc mRNA level was increased in the serum (P < 0.01) and placentas (P < 0.01) of women with GDM, and the expression of Drp1 mRNA and protein were also increased in placentas (P < 0.05). In JEG3 cells treated with 30 mmol/L glucose, the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h (both P < 0.05), 48 h (both P < 0.01) and 72 h (both P < 0.001). ROS expression was also increased. High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc (P < 0.01), and low levels were detected in JEG3 cells transfected with p66Shc siRNA (P < 0.05). CONCLUSION: The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM. Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.

Tetrandrine inhibits proliferation of colon cancer cells by BMP9/ PTEN/ PI3K/AKT signaling.

Despite advances in screening and treatment, colon cancer remains one of the leading causes of cancer-related death. Finding novel and useful drug treatment targets is also an urgent need for clinical applications. Tetrandrine (Tet) is extracted from the Chinese medicinal herbal medicine, which is a well-known calcium blocker with a variety of pharmacological activities, including anti-cancer. In this study, we recruited cell viability assay, flow cytometry analysis, cloning formation to confirm that Tet can inhibit the proliferation of SW620 cells, and induce apoptosis. Mechanically, we confirmed that Tet up-regulates the mRNA and protein level of BMP9 in SW620 cells. Over-expression BMP9 enhances the anti-cancer effects of Tet in SW620 cells, but these effects can be partly reversed by silencing BMP9. Also, Tet reduces phosphorylation of Aktl/2/3 in SW620 cells, which could be elevated by overexpressed BMP9 and impaired by silencing BMP9. Furthermore, we demonstrated that Tet reduces phosphorylated PTEN, which can be promoted by overexpressed BMP9, analogously also be attenuated through silencing BMP9. Finally, we introduced a xenograft tumor model to investigate the anti-proliferative effect of Tet, further to explore the effects of BMP9 and PTEN in SW620 cells. Our findings suggested that the anti-cancer activity of Tet in SW620 cells may be mediated partly by up-regulating BMP9, followed by inactivation PI3K/Akt through up-regulating PTEN at least.

Anti­proliferative effect of honokiol on SW620 cells through upregulating BMP7 expression via the TGF­ß1/p53 signaling pathway.

Honokiol (HNK), a natural pharmaceutically active component extracted from magnolia bark, has been used for clinical treatments and has anti­inflammatory, antiviral and antioxidative effects. In recent years, anticancer research has become a major hotspot. However, the underlying molecular mechanisms of how HNK inhibits colorectal cancer have remained elusive. The present study focused on elucidating the effects of HNK on the expression of bone morphogenetic protein (BMP)7 and its downstream interaction with transforming growth factor (TGF)­ß1 and p53 in colon cancer. In in vitro assays, cell viability, cell cycle distribution and apoptosis were examined using Cell Counting Kit­8, flow cytometry and reverse transcription­quantitative PCR, respectively. In addition, the expression of BMP7, TGF­ß1 and relevant signaling proteins was determined by western blot analysis. In vivo, the anticancer effect of HNK was assessed in xenografts in nude mice. Furthermore, immunohistochemistry was performed to evaluate the association between BMP7 and TGF­ß1 expression in colon cancer. The results indicated that HNK inhibited the proliferation of colon cancer cell lines, with SW620 cells being more sensitive than other colon cancer cell lines. Furthermore, HNK markedly promoted the expression of BMP7 at the mRNA and protein level. Exogenous BMP7 potentiated the effect of HNK on SW620 cells, while knocking down BMP7 inhibited it. As a downstream mechanism, HNK increased the expression of TGF­ß1 and p53, which was enhanced by exogenous BMP7 in SW620 cells. In addition, immunohistochemical analysis indicated a positive association between BMP7 and TGF­ß1 expression. Hence, the present results suggested that HNK is a promising agent for the treatment of colon cancer and enhanced the expression TGF­ß1 and p53 through stimulating BMP7 activity via the non­canonical TGF­ß signaling pathway.

[Effect of different levels of elevated CO2 concentration on leaf chlorophyll fluorescence cha-racteristics of Japonica rice]. / 不同CO2æµ“åº¦å‡é«˜æ°´å¹³å¯¹ç²³ç¨»å¶ç‰‡è§å ‰ç‰¹æ€§çš„å½±å“.

To examine the effects of elevated CO2 concentrations on chlorophyll fluorescence of rice leaf, a field experiment was conducted with automatic control system of CO2 concentration in open top-chambers (OTCs). There were three treatments, including atmospheric CO2 concentration (CK), CK+80 µmol·mol-1 CO2 (T1), and CK+200 µmol·mol-1 CO2 (T2). The fast chlorophyll fluorescence induction dynamic curves of flag leaves were measured using the plant efficiency analyzer at the main growth stages of rice. The results showed that T1 treatment significantly increased quantum yield for electron transfer (φEo), maximum photochemical efficiency (Fv/Fm), and performance index (PIABS), but decreased quantum yield for energy dissipation (φDo) at the flowe-ring, milk grain, ripening, and full ripeness stages. The values of φEo, Fv/Fm, and PIABS were increased by 7.3%-23.3%, 3.1%-7.1%, and 46.2%-93.0%, respectively. The φDo values were decreased by 10.3%-20.5%. T2 treatment significantly decreased φEo, Fv/Fm, PIABS by 68.7%, 41.4%, and 93.4%, respectively, but increased φDo by 78.4% at the jointing stage. T2 treatment significantly increased φEo, Fv/Fm, PIABS by 11.6%-19.8%, 4.8%-6.8%, and 53.0%-72.6%, respectively, and decreased φDo by 7.7%-19.4% at the flowering, milk grain, and ripening stages. Our results suggested that elevated CO2 concentration (80, 200 µmol·mol-1) would promote photosynthetic electron transport of PS2 in flag leaves of rice.

Flood risk assessment in metro systems of mega-cities using a GIS-based modeling approach.

Metro system is a vital component of mass transportation infrastructure, providing crucial social and economic service in urban area. Flood events may cause functional disruptions to metro systems; therefore, a better understanding of their vulnerability would enhance their resilience. A comparative study of flood risk in metro systems is presented using the analytic hierarchy process (AHP) and the interval AHP (I-AHP) methods. The flood risk in the Guangzhou metro system is evaluated according to recorded data. Evaluated results are validated using the flood event occurred in Guangzhou on May 10, 2016 (hereinafter called "May 10th event"), which inundated several metro stations. The flood risk is assessed within a range of 500 m around the metro line. The results show that >50% of metro lines are highly exposed to flood risk, indicating that the Guangzhou metro system is vulnerable to flood events. Comparisons between results from AHP and I-AHP show that the latter yields a wider range of high flooding risk than the former.

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.