Tanshinone IIA modulates cancer cell morphology and movement via Rho GTPases-mediated actin cytoskeleton remodeling.

Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin cytoskeleton regulation. 97H and Huh7 exhibited numerous tentacle-like protrusions that interacted with neighboring cells. Following treatment with Tan IIA, 97H and Huh7 showed a complete absence of cytoplasmic protrusion and adherens junctions, thereby effectively impeding their migration capability. The fluorescence staining of F-actin and microtubules indicated that these tentacle-like protrusions and cell-cell networks were actin-based structures that led to morphological changes after Tan IIA treatment by retracting and reorganizing beneath the membrane. Tan IIA can reverse the actin depolymerization and cell morphology alterations induced by latrunculin A. Tan IIA down-regulated actin and Rho GTPases expression significantly, as opposed to inducing Rho signaling activation. Preventing the activity of proteasomes and lysosomes had no discernible impact on the modifications in cellular structure and protein expression induced by Tan IIA. However, as demonstrated by the puromycin labeling technique, the newly synthesized proteins were significantly inhibited by Tan IIA. In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.

GSK2606414 Sensitizes ABCG2-Overexpressing Multidrug-Resistant Colorectal Cancer Cells to Chemotherapeutic Drugs.

Colorectal cancer is a common malignant tumor. A major factor in the high mortality rate of colorectal cancer is the emergence of multidrug resistance (MDR). Overexpression of the ABCG2 gene in cancer cells directly leads to MDR. Finding new inhibitors of ABCG2 may be an effective way to overcome drug resistance. We found that the compound GSK2606414 enhanced the sensitivity of the ABCG2 substrate to the chemotherapeutic drugs mitoxantrone and doxorubicin in ABCG2-overexpressing multidrug-resistant colorectal cancer cells by increasing their intracellular accumulation without affecting the protein expression of ABCG2. Molecular docking experiments predicted that GSK2606414 could stably bind in the drug-binding pocket of ABCG2. In conclusion, GSK2606414 can sensitize ABCG2-overexpressed multidrug-resistant colorectal cancer cells to chemotherapy drugs and can be used as a potential inhibitor of ABCG2.

A new method for estimating ore grade based on sample length weighting.

Estimation of ore grade is very important for the value evaluation of ore deposits, and it directly affects the development of mineral resources. To improve the accuracy of the inverse distance weighting (IDW) method in ore grade estimation and reduce the smoothing effect of the IDW method in grade estimation, the weight calculation method involved in the IDW method was improved. The length parameter of the ore sample was used to calculate the weight of the IDW method. The length of the ore samples was used as a new factor of the weighting calculation. A new method of IDW integrated with sample length weighting (IDWW) was proposed. The grade estimation of Li, Al, and Fe in porcelain clay ore was used as a case study. A comparative protocol for grade estimation via the IDWW method was designed and implemented. The number of samples involved in the estimation, sample combination, sample grade distribution, and other factors affecting the grade estimation were considered in the experimental scheme. The grade estimation results of the IDWW and the IDW methods were used for comparative analysis of grades of the original and combined samples. The estimated results of the IDWW method were also compared with those of the IDW method. The deviation analysis of the estimated grade mainly included the minimum, maximum, mean, and coefficient of variation of the ore grade. The estimation effect of IDWW method was verified. The minimum deviations of the estimated grade of Li, Al, and Fe were between 9.129% and 59.554%. The maximum deviations were between 4.210 and 22.375%. The mean deviations were between - 1.068 and 7.187%. The deviations in the coefficient of variation were between 3.076 and 36.186%. The deviations in the maximum, minimum, mean, and coefficients of variation of the IDWW were consistent with those of the IDW, demonstrating the accuracy and stability of the IDWW method. The more the samples involved in the estimation, the greater the estimation deviations of IDW and IDWW methods. The estimated deviations of Li, Al, and Fe were affected by the shape of the grade distribution, when the same estimation parameters were used. The grade distribution pattern of the samples significantly influenced the grade estimation results. The IDWW method offers significant theoretical advantages and addresses the adverse effects of uneven sample lengths on the estimates. The IDWW method can effectively reduce the smoothing effect and improves the utilization efficiency of the original samples.

Inhibiting the Activity of ABCG2 by KU55933 in Colorectal Cancer.

BACKGROUND: Therapeutic resistance is a frequent problem of cancer treatment and a leading cause of mortality in patients with metastatic colorectal cancer (CRC). Recent insight into the mechanisms that confer multidrug resistance has elucidated that the ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) assists cancer cells in escaping therapeutic stress caused by toxic chemotherapy. Therefore, it is necessary to develop ABCG2 inhibitors. OBJECTIVES: In the present study, we investigated the inhibitory effect of KU55933 on ABCG2 in CRC. METHODS: The cytotoxicity assay and drug accumulation assay were used to examine the inhibitory effect of KU55933 on ABCG2. The protein expressions were detected by Western blot assay. The docking assay was performed to predict the binding site and intermolecular interactions between KU55933 and ABCG2. RESULTS: KU55933 was more potent than the known ABCG2 inhibitor fumitremorgin C to enhance the sensitivity of mitoxantrone and doxorubicin and the intracellular accumulation of mitoxantrone, doxorubicin and rhodamine 123 inside CRC cells with ABCG2 overexpression. Moreover, KU55933 did not affect the protein level of ABCG2. Furthermore, the docking data showed that KU55933 was tightly located in the drug-binding pocket of ABCG2. CONCLUSION: In summary, our data presented that KU55933 could effectively inhibit the drug pump activity of ABCG2 in colorectal cancer, which is further supported by the predicted model that showed the hydrophobic interactions of KU55933 within the drug-binding pocket of ABCG2. KU55933 can potently inhibit the activity of ABCG2 in CRC.

The Meridian Tropism and Classification of Red Yeast Rice Investigated by Monitoring Dermal Electrical Potential.

Red yeast rice is a traditional Chinese medicine and food that has been purported to color food, ferment, and lower cholesterol. In order to study the antioxidative capacity of red yeast rice and the effects on electrical potential difference (EPD) of 12 acupuncture meridians, the pH value, oxidation reduction potential (ORP), ABTS, FRAP, T-SOD, and particle size distribution of red yeast rice were analyzed. 20 volunteers were recruited and randomly divided into two groups, the red yeast rice group (10 g red yeast rice and 40 g water) and control CK group (50 g water). The left 12 acupuncture meridians' EPD was real-time monitored. Samples were taken at the 10th minutes. The whole procedure continued for 70 minutes. It is shown that the pH value of the red yeast rice was 4.22, the ORP was 359.63 mV, the ABTS was 0.48 mmol Trolox, the FRAP was 0.08 mmol FeSO4, the T-SOD was 4.71 U, and the average particle size was 108 nm (7.1%) and 398.1 nm (92.9%). The results of 12 acupuncture meridians' EPD showed that the red yeast rice can significantly affect the EPD of stomach, heart, small intestine, and liver meridians.

AZ32 Reverses ABCG2-Mediated Multidrug Resistance in Colorectal Cancer.

Colorectal cancer is a common malignancy with the third highest incidence and second highest mortality rate among all cancers in the world. Chemotherapy resistance in colorectal cancer is an essential factor leading to the high mortality rate. The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) confers multidrug resistance (MDR) to a range of chemotherapeutic agents by decreasing their intracellular content. The development of novel ABCG2 inhibitors has emerged as a tractable strategy to circumvent drug resistance. In this study, an ABCG2-knockout colorectal cancer cell line was established to assist inhibitor screening. Additionally, we found that ataxia-telangiectasia mutated (ATM) kinase inhibitor AZ32 could sensitize ABCG2-overexpressing colorectal cancer cells to ABCG2 substrate chemotherapeutic drugs mitoxantrone and doxorubicin by retaining them inside cells. Western blot assay showed that AZ32 did not alter the expression of ABCG2. Moreover, molecule docking analysis predicted that AZ32 stably located in the transmembrane domain of ABCG2. In conclusion, our result demonstrated that AZ32 could potently reverse ABCG2-mediated MDR in colorectal cancer.

An E2F1/DDX11/EZH2 Positive Feedback Loop Promotes Cell Proliferation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for one of the leading causes of cancer-related death, and is attributed to the dysregulation of genes involved in genome stability. DDX11, a DNA helicase, has been implicated in rare genetic disease and human cancers. Yet, its clinical value, biological function, and the underlying mechanism in HCC progression are not fully understood. Here, we show that DDX11 is upregulated in HCC and exhibits oncogenic activity via EZH2/p21 signaling. High expression of DDX11 is significantly correlated with poor outcomes of HCC patients in two independent cohorts. DDX11 overexpression increases HCC cell viabilities and colony formation, whereas DDX11 knockdown arrests cells at G1 phase without alteration of p53 expression. Ectopic expression of DDX11 reduces, while depletion of DDX11 induces the expression of p21. Treatment of p21 siRNA markedly attenuates the cell growth suppression caused by DDX11 silence. Further studies reveal that DDX11 interacts with EZH2 in HCC cells to protect it from ubiquitination-mediated protein degradation, consequently resulting in the downregulation of p21. In addition, E2F1 is identified as one of the upstream regulators of DDX11, and forms a positive feedback loop with EZH2 to upregulate DDX11 and facilitate cell proliferation. Collectively, our data suggest DDX11 as a promising prognostic factor and an oncogene in HCC via a E2F1/DDX11/EZH2 positive feedback loop.

[Bufadienolides from venom of Bufo bufo gargarizans].

Twelve compounds were isolated from the venom of Bufo bufo gargarizans. On the basis of their physical and chemical properties and spectral data, their structures were identified as resibufagenin (1), bufotalin (2), desacetylcinobufagin (3), 19-oxodesacetylcinobufotalin (4), cinobufotalin (5), 1beta-hydroxylbufalin (6), 12alpha-hydroxybufalin (7), bufotalinin (8), Hellebrigenin (9), telocinobufagin (10), hellebrigenol (11) and cinobufagin-3-hemisuberate methyl ester (12), respectively. Compounds 7 and 12 are new natural products.

4-(4-Nitro-benzene-sulfonamido)pyridinium trichloro-acetate.

In the crystal structure of the title compound, C(11)H(10)N(3)O(4)S·C(2)Cl(3)O(2), the dihedral angle between the two six-membered rings is 69.2 (1)°. The mol-ecules are connected via inter-molecular N-H⋯O hydrogen bonding.

4-Hydr-oxy-2,2,6,6-tetra-methyl-piperidinium chloride-hydroxonium chloride (3/1).

The crystal structure of the title compound, C(9)H(20)NO(+)·Cl(-)·0.33(H(3)O(+)·Cl(-)), is composed of 4-hydr-oxy-2,2,6,6-tetra-methyl-piperidinium cations, hydroxonium cations and chloride anions, which are connected via O-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonding. The 4-hydr-oxy-2,2,6,6-tetra-methyl-piperidinium cation and one of the two crystallographically independent chloride anions are located on a mirror plane. The hydroxonium cation is located on a threefold axis and the second crystallographically independent chloride anion is located on a sixfold rotoinversion axis. Due to symmetry, the hydroxonium cation is disordered over two positions.

4-Hydr-oxy-2,2,6,6-tetra-methyl-piperidinium trichloro-acetate.

In the crystal structure of the title compound, C(9)H(20)NO(+)·Cl(3)CCOO(-), the cations and anions are connected via O-H⋯O, N-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonding. The six-membered ring adopts a chair conformation with the hydroxyl group in an equatorial position.

4-Hydr-oxy-2,2,6,6-tetra-methyl-piperidinium perchlorate.

In the title salt, C(9)H(20)NO(+)·ClO(4) (-), inter-molecular hydrogen bonds are observed, which determine the crystal packing.

[Effect of surface modification on surface energy of lactose and performance of dry powder inhalations].

AIM: To investigate the effects of surface modification of lactose carrier on performance of dry powder inhalations (DPIs). METHODS: Modified lactose surface was prepared using a "particle smoothing" process to obtain smooth carrier surface and low surface energy with the presence of magnesium stearate, colloidal silica dioxide and talc. Inverse gas chromatography (IGC) was used to assess the surface energy of treated lactose, and the in vitro deposition of carrier-based IFNa-2b DPIs was evaluated with twin stage impinger. RESULTS: The flowing property of lactose was greatly improved and the surface energy decreased by the "particle smoothing" process. Decreasing surface energy resulted in greater aspiration fraction of IFNa-2b. CONCLUSION: IGC is a potentially useful tool for rapid formulation design and screening.