Potent anticancer activity of (Z)-3-hexenyl-ß-D-glucopyranoside in pancreatic cancer cells.

This current study reports, for the first time, on the potent cytotoxicity of (Z)-3-hexenyl-ß-D-glucopyranoside, as well as its cellular and molecular apoptotic mechanisms against Panc1 cancer cells. The cytotoxicity of three compounds, namely (Z)-3-hexenyl-ß-D-glucopyranoside (1), gallic acid (2), and pyrogallol (3), which were isolated from C. rotang leaf, was investigated against certain cancer and normal cells using the MTT assay. The cellular apoptotic activity and Panc1 cell cycle impact of compound (1) were examined through flow cytometry analysis and Annexin V-FITC cellular apoptotic assays. Additionally, RT-PCR was employed to evaluate the effect of compound (1) on the Panc1 apoptotic genes Casp3 and Bax, as well as the antiapoptotic gene Bcl-2. (Z)-3-hexenyl-ß-D-glucopyranoside demonstrated the highest cytotoxic activity against Panc1 cancer cells, with an IC50 value of 7.6 µM. In comparison, gallic acid exhibited an IC50 value of 21.8 µM, and pyrogallol showed an IC50 value of 198.2 µM. However, (Z)-3-hexenyl-ß-D-glucopyranoside displayed minimal or no significant cytotoxic activity against HepG2 and MCF7 cancer cells as well as WI-38 normal cells, with IC50 values of 45.8 µM, 108.7 µM, and 194. µM, respectively. (Z)-3-hexenyl-ß-D-glucopyranoside (10 µM) was demonstrated to induce cellular apoptosis and cell growth arrest at the S phase of the cell cycle in Panc1 cells. These findings were supported by RT-PCR analysis, which revealed the upregulation of apoptotic genes (Casp3 and Bax) and the downregulation of the antiapoptotic gene Bcl-2. This study emphasizes the significant cellular potency of (Z)-3-hexenyl-ß-D-glucopyranoside in specifically inducing cytotoxicity in Panc1 cells.

Potent hepatoprotective activity of common rattan (Calamus rotang L.) leaf extract and its molecular mechanism.

BACKGROUND: Calamus rotang L. (CR) is an Indian shrub. The leaves and other organs of the plant are traditionally used in India for treatment of various diseases. The in vitro antioxidant property of the leaves extract was previously established. Thus, the current study aimed to evaluate the antioxidant and hepatoprotective effects of CR ethyl acetate extract at a dose of 350 mg/kg on CCl4 induced hepatotoxic rats through different mechanisms. METHODS: Histopathological examination of the treated rats' group in comparison with positive and negative controls were performed. Quantitative measuring of the proinflammatory cytokines (TNF α), inflammatory regulators (Arginase, PPAR α) and the antiapoptotic protein Bcl-2 in comparison with positive and negative control groups was achieved using immunohistochemical examination. HPLC profiling of the polyphenol contents and molecular docking of the identified compounds against BH3 proapoptotic protein were correspondingly studied to evaluate the potential antiapoptotic property. RESULTS: The CR extract greatly protects the liver tissue through the suppression of TNF α, arginase and PPAR α induced by CCl4 as well as its enhancement of the antiapoptotic Bcl-2 protein. Fourteen polyphenols of different classes were identified in CR extract and tested via molecular docking for their potential antiapoptotic activities against BH3 protein. Naringin, rutin, 7-hydroxy flavone, and ellagic acid compounds exhibit the highest affinity and potential inhibition of pro-apoptotic protein BH3 via molecular docking study. CONCLUSIONS: The ethyl acetate fraction of the leaves of C. rotang is rich in polyphenols that exhibited potent hepatoprotective effect on CCl4 induced hepatotoxic rats through its antioxidant, anti-inflammatory, anti-steatosis and antiapoptotic properties.

Volumetric parameters of the primary tumor and whole-body tumor burden derived from baseline 18F-FDG PET/CT can predict overall survival in non-small cell lung cancer patients: initial results from a single institution.

BACKGROUND: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters derived from 18F-FDG PET/CT, suggested to have a prognostic value in cancer patients. Our study aimed to test whether these volumetric parameters of the primary tumor and whole-body tumor burden (WBTB) can predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Thirty biopsy-proven NSCLC patients who had not begun anti-tumor therapy were included in this prospective study. A baseline 18F-FDG PET/CT study was acquired. Scans were interpreted visually and semi-quantitatively by drawing a 3D volume of interest (VOI) over the primary tumor and all positive lesions to calculate metabolic, volumetric parameters, and WBTB. The PET parameters were used to stratify patients into high- and low-risk categories. The overall survival was estimated from the date of scanning until the date of death or last follow-up. RESULTS: At a median follow-up of 22.73 months, the mean OS was shorter among patients with higher tu MTV and tu TLG and high WBTB. High WB TLG was independently associated with the risk of death (p < 0.025). Other parameters, e.g., SUVmax, SUVpeak, and SUVmean, were not predictive of outcomes in these patients. CONCLUSION: In patients with NSCLC, tu MTV, tu TLG, and WBTB determined on initial staging 18F-FDG PET/CT seems to be a strong, independent imaging biomarker to predict OS, superior to the clinical assessment of the primary tumor. The WB TLG was found to be the best predictor of OS.

New antimicrobial and cytotoxic benzofuran glucoside from Senecio glaucus L.

The ethyl acetate fraction of the dried aerial parts of Senecio glaucus L. exhibited significant antimicrobial activity against some of selected bacteria and fungi. Also, it showed potent cytotoxicity against PANC-1 cancer cell lines under glucose deficient medium. The ethyl acetate fraction was subjected to different chromatographic techniques for isolation of the bioactive compounds. A new benzofuran glucoside; 2,3-dihydro-3ß-hydroxyeuparin 3-O-glucopyranoside (1) was isolated. Additionally, two known flavonoid compounds isorhamentin 3-O-ß-D-glucoside (2), and isorhamentin 3-O-ß-D-rutinoside (3) were first identified in S. glaucus. Compound 1 exhibited potent antimicrobial activities against two Gram-positive bacteria, one Gram-negative bacteria, and two fungi. Also, it displayed potent cytotoxic activity against PANC-1 cancer cell lines under glucose deficient medium (IC50 7.5 µM). However, the isolated flavonoid glycosides (2 & 3) showed moderate antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, four fungi, and did not show any cytotoxic activity against PANC-1.

Shear bond strength of zirconia-based ceramics veneered with 2 different techniques.

STATEMENT OF PROBLEM: Delamination of veneering ceramic is reported as one of the most frequent problems associated with veneered zirconia restorations. PURPOSE: The purpose of this in vitro study was to compare the shear bond strength of sintered lithium disilicate to that of pressed fluorapatite glass-ceramic on a zirconia substrate. MATERIAL AND METHODS: Thirty zirconia blocks (20×15×2.5-mm thick) were cut, sintered, and divided into 2 groups. A pressed group, a zirconia liner, was applied and sintered, and the lost-wax technique was used to fabricate fluorapatite glass-ceramic blocks (3×3×3 mm), which were pressed onto the sintered zirconia blocks. A sintered group, lithium disilicate blocks, were cut (3×3×3 mm) and sintered to the sintered zirconia blocks by using a low-fusing glass-ceramic. The thickness of the low-fusing glass-ceramic was standardized to approximately 80 µm prior to sintering. The shear bond strength levels of the specimens were tested using a universal testing machine at a crosshead speed of 1 mm/min until failure. Representative separated specimen surfaces were examined for fracture characteristics, using scanning electron microscopy at ×50 magnification. Debonding data were compared using a 2-tailed, unpaired Student t test (α=.05). RESULTS: The sintered group demonstrated mean shear bond strength values (41.2 ±6.3 MPa), which were significantly higher (P<.001) than those of the pressed group (21.3 ±4.3 MPa). CONCLUSIONS: Sintering of computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate ceramic achieved higher shear bond strength values than pressing fluorapatite glass-ceramic to zirconia substructure material.

Characterisation of the metabolites of an antibacterial endophyte Botryodiplodia theobromae Pat. of Dracaena draco L. by LC-MS/MS.

Botryodiplodia theobromae Pat. belongs to the endophytic fungi that live within the tissues of medicinal plants and produce bioactive natural products. The endophyte was isolated from the leaves of Dracaena draco L. The LC-MS-based metabolite fingerprinting of the ethyl acetate extract of B. theobromae with antibacterial activity led to the identification of 13 metabolites pertaining to various classes: dipeptides (maculosin and L,L-cyclo(leucylprolyl), alkaloid (norharman), coumarin and isocoumarins (bergapten, meranzin and monocerin), sesquiterpene (dihydrocumambrin A), aldehyde (formyl indanone), fatty alcohol (halaminol A) and fatty acid amide (palmitoleamide, palmitamide, capsi-amide and oleamide). This study reports for the first time, the LC-MS and LC-MS/MS identification of 13 known bioactive metabolites from the antibacterial ethyl acetate extract of B.theobromae isolated from the leaves of D. draco L.

A new enniatin antibiotic from the endophyte Fusarium tricinctum Corda.

Enniatins (ENs), a group of antibiotics commonly produced by various strains of Fusarium, are six-membered cyclic depsipeptides formed by the union of three molecules of D-α-hydroxyisovaleric acid and three N-methyl-L-amino acids. The endophyte Fusarium tricinctum Corda was isolated from the fruits of Hordeum sativum Jess. and cultivated on a rice medium. The fungal metabolites were extracted with methanol and were identified, employing liquid chromatography-mass spectrometry as ENs A, A1, B, B1, B2 and Q. EN Q is a new analog of EN A and the occurrence of EN B2 is reported for the first time from this endophyte, in addition to four well-known ENs (A, A1, B and B1). The methanol extract of F. tricinctum showed mild antibacterial and antileishmanial activities. Additionally the tested extract displayed inhibition of the activity of thioredoxin reductase enzyme of Plasmodium falciparum.

LC-MS metabolite fingerprinting and MtSK-based screening of an endophyte Bartalinia pondoensis Marinc of Citrus aurantum L.

An endophyte Bartalinia pondoensis Marinc of Citrus aurantum L. var. dulcis was isolated and studied for its secondary metabolites and for their Mycobacterium tuberculosis shikimate kinase (MtSK) inhibitory activities. Using LC-MS metabolite fingerprinting of the constituents of the methanol extract, 19 compounds pertaining to various classes were identified: amino acids, proto-alkaloids, fatty acid amides and oxazole, aniline derivatives and aromatic compounds. We report here for the first time the presence of the [N-(ethyloxy, hydroxymethyl)phenylethylamine] as a new proto-alkaloid and 18 other known compounds are reported for the first time in the genus of Bartalinia. MtSK inhibitory activities of methanol extract and fractions obtained by solid phase extraction (SPE) at a concentration of 50 µg/mL may be attributed to the presence of aniline and oxazole derivatives present in all fractions in varying concentrations.

Evaluation of morphological/immunohistochemical versus nuclear medicine imaging modalities in detecting metastatic bone and/or marrow deposits in neuroblastoma patients.

BACKGROUND & PURPOSE: In planning diagnostic or follow-up investigational strategies, neuroblastoma (NB) metastatic deposits in bone and/or bone marrow (BM) should be detected as early as possible. Therefore, all investigational detection tools should be conducted simultaneously for precise staging. However, because of the financial conditions in our developing countries and in view of the cost/benefit relationship, the question is, can one detection tool only become satisfactory and replacing others? The purpose of our study is to compare simultaneous results of bone and metaiodobenzylguanidine (MIBG) scans versus BM biopsies with immunohistochemical (IHC) staining; in detecting bone and/or BM metastatic deposits in NB patients. MATERIAL AND METHODS: This study included 138 NB patients; 46 were de novo and 92 were under follow-up. They were subjected to bilateral BM biopsies, IHC staining (using NSE McAb) and Tc-99m methylene diphosphonate (Tc-99m MDP) bone scan (BS). Only 57/138 patients were, in addition, subjected to I-131 MIBG scan. RESULTS: Matched results between IHC-stained BM sections and bone scans (BSs) 107/138 (77.5%) were higher than the un-matched ones 31/138 (22.5%). There was a moderate agreement between the two methods in all studied cases (Kappa=0.538) and it was higher among de novo (Kappa=0.603) than follow-up group (Kappa=0.511). Among the 31 un-matched results, the most frequent (17/31) were due to the presence of minute amount of infiltrating NB cells that could be detected by IHC-stained BM sections and not by BSs. The less frequent (12/31) were due to the presence of metastatic deposits outside pelvic bones that could be detected by BSs and not by IHC-stained BM sections mainly in the follow-up cases (11/12) rather than de novo cases (1/12). The matched results between IHC-stained BM sections and MIBG scans 54/57 (94.7%) were higher than the un-matched ones 3/57 (5.3%). The agreement between the two methods was higher among de novo (Kappa=1.000) than follow-up group (Kappa=0.847). The agreement between IHC-stained BM sections and MIBG scans was substantial (Kappa=0.890) while that between IHC-stained BM sections and BSs was moderate (Kappa=0.538). CONCLUSIONS: We suggest a step-wise strategy to be applied, at least in developing countries, in approaching de novo and follow-up NB cases for detecting bone and/or BM metastatic deposits. This strategy might be beneficial if it is considered during application of NB guide-lines for diagnosis and follow-up.