PMID: 

Sci Rep. 2019 Jul 2 ;9(1):9527. Epub 2019 Jul 2. PMID: 31267009

Abstract Title: 

Liposomal formulation of Galbanic acid improved therapeutic efficacy of pegylated liposomal Doxorubicin in mouse colon carcinoma.

Abstract: 

Galbanic acid (Gba), a sesquiterpene coumarin, with strong antiangiogenic activity could serve as an excellent anti-cancer agent. However, Gba is a poor water-solube which hampered its clinical application. In this study, a pegylated liposomal Gba (PLGba) with HSPC/Cholesterol/mPEG-DSPE (56.2, 38.3, 5.3% molar ratio) was developed by the thin film hydration plus extrusion and calcium acetate gradient remote loading method, to address the issue of poor Gba solubility. Moreover, an integrin-targeting ligand (RGD peptide, cyclo[Arg-Gly-Asp-D-Tyr-Cys]) was post-inserted into liposomes in order to increase Gba cell delivery. Using fluorescently-labeled model liposomes, it was found that the targeting could improve the integrin-mediated cellular uptake of the liposomes in vitro in human umbilical vein endothelial cells (HUVECs), and in vivo as evidenced by chicken chorioallantoic membrane angiogenesis (CAM) model. It also could enrich the liposome accumulation in C26 tumor. Interestingly, co-treatment with PLGba and pegylated liposomal doxorubicin (PLD, also known as Doxil) had a synergistic and antagonistic antiproliferative effect on the C26 tumor cell line and the normal HUVEC, respectively. In C26 tumor bearing BALB/c mice, the PLGba and PLD combinatorial therapy improved the antitumor efficacy of the treatment as compared to those of single agents. This results have clear implications for cancer therapy.

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PMID: 

J Biochem Mol Toxicol. 2019 Nov ;33(11):e22402. Epub 2019 Oct 1. PMID: 31576639

Abstract Title: 

Galbanic acid: Induced antiproliferation in estrogen receptor-negative breast cancer cells and enhanced cellular redox state in the human dermal fibroblasts.

Abstract: 

INTRODUCTION: Galbanic acid (GA) is a natural bioactive compound abundantly distributed in Ferula species (Apiaceae), with a wide range of biological functions.METHODS: The present study investigated the anticancer properties of GA in human breast carcinoma MCF-7 and MDA-MB-231 cell lines using MTT (3,4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay. Further, the antioxidant activity of GA was determined in vitro. The plausible mechanisms of action of GA were further investigated using flow cytometry and gene expression analysis.RESULTS: Our study indicated that treatment with GA resulted in inhibition of proliferation and induction of apoptosis in MDA-MB-231 cells. The obtained results indicated that GA has strong cytotoxicity on MDA-MB-231 cells (IC = 48.75 µg/mL) compare to MCF-7 (IC = 56.65 µg/mL) and decrease cancer cell viability in the dose- and time-dependent manner. Meanwhile, microscopic examination and flow cytometry analysis confirmed the apoptosis cell death upon treatment with GA. The gene expression analysis revealed that GA could induce apoptosis-mediated proliferation inhibition in MDA-MB-231 cells through upregulation of bax and caspase-3 and downregulation of bcl2 genes. Besides, the GA exhibited free radical-scavenging activity and enhanced the cellular redox state in human dermal fibroblasts. The elevation of cellular redox status was confirmed byupregulating superoxide dismutase, catalase, and glutathione peroxidase genes.CONCLUSION: The results obtained in this study indicated that GA could be considered as a promising anticancer agent in breast cancer therapy and a bioactive antioxidant compound to be used in pharmaceutical and cosmetic industries.

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PMID: 

Life Sci. 2019 Dec 15 ;239:117044. Epub 2019 Nov 9. PMID: 31715187

Abstract Title: 

Curcumin potentiates the galbanic acid-induced anti-tumor effect in non-small cell lung cancer cells through inhibiting Akt/mTOR signaling pathway.

Abstract: 

BACKGROUND: Galbanic acid (GBA), which is known as a sesquiterpene coumarin, has been reported to have various anti-tumor activities in different cells. Our study intended to investigate whether curcumin potentiates GBA-induced anti-tumor effect in non-small cell lung cancer cells.MATERIALS AND METHODS: The combined effect of GBA and curcumin on cell viability was examined by MTT analysis. Cellular apoptosis was evaluated by flow cytometry analysis. Autophagy was defined by autophagosome observed by confocal microscopy after infected with GFP-LC3 adenovirus. In addition, the expression of marker proteins involved in cell apoptosis, autophagy, and Akt/mTOR signaling pathway were estimated by qRT-PCR and Western Blotting assay.RESULTS: 15 μM curcumin combined with 40 μM GBA could obtain better synergistic repressive efficacy on cell viability and notably induced cell apoptosis in A549 cells. Besides, curcumin in alliance with GBA could significantly inhibit cell migration and invasion. GFP-LC3 infection experiments elaborated that curcumin could potentiate GBA induced cell autophagy and restrain the phosphorylation of Akt/mTOR/P70s6k signaling pathway. What's more, the reaction of migration, apoptosis, and autophagy induced by curcumin and GBA treatment could be reversed by mTOR inhibitor rapamycin and AKT activator insulin.

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PMID: 

J Sci Food Agric. 2019 Mar 30 ;99(5):2521-2529. Epub 2018 Dec 14. PMID: 30393852

Abstract Title: 

Screening of Musa balbisiana Colla. seeds for antidiabetic properties and isolation of apiforol, a potential lead, with antidiabetic activity.

Abstract: 

BACKGROUND: 'Phytonutrients' have been reported to exert an incredible impact on the healthcare system and offer medical benefits including the prevention or treatment of lifestyle-associated diseases. We chose one of the most common and important plant families, Musaceae, for our present study and explored its antidiabetic potential.RESULTS: Seeds of the edible fruits of Musa balbisiana Colla. were investigated for their antidiabetic potential. After estimating the proximate composition, the seeds were extracted with various solvents and evaluated for antidiabetic potential in terms of the inhibition of digestive enzymes, antiglycation activity and in vitro glucose uptake. The acetone extract demonstrated the highest inhibition ofα-amylase and α-glucosidase enzymes with ICvalues of 36.67 ± 0.367 and 100.61 ± 0.707 µg mL, respectively. The extract also exhibited significant glycation inhibition with an ICvalue of 86.48 ± 0.751 µg mL. Furthermore, a major phytochemical, apiforol, was isolated from the acetone extract for the first time, which demonstrated promisingα-glucosidase inhibition (IC = 48.25 ± 0.255 µmol L), antiglycation property (IC = 114.23 ± 0.567 µmol L) and enhanced glucose uptake in L6 myoblasts. In molecular docking studies, apiforol efficiently bonded to the active sites ofα-glucosidase enzyme 3A4A.CONCLUSIONS: As dietary intervention is one of the effective strategies for addressing diabetes, special attention is always given to natural food bio-actives or agro-products for better human health. The results of our study suggest that Musa balbisiana has significant potential as an ingredient in health food formulations by reducing postprandial hyperglycaemia.© 2018 Society of Chemical Industry.

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PMID: 

Nutr Cancer. 2019 ;71(2):285-300. Epub 2018 Dec 29. PMID: 30596280

Abstract Title: 

Angio-Suppressive Effect of Partially Purified Lectin-like Protein from Musa acuminata pseudostem by Inhibition of VEGF-Mediated Neovascularization and Induces Apoptosis Both In Vitro and In Vivo.

Abstract: 

Lifestyle and nutritional changes have contributed much to the somatic genetic changes which have concurrently led to an increase cancer in humans. Hence the plant-based and nutritional involvements block oncogenic transformation are in good demand. We evaluate Phloem exudates of the dietary plant, Musa acuminate pseudostem, the initial domesticated plant species with the effective lectin activity for its functional role against the tumor development and its mechanism of action. Our experimental data exhibit that Musa acuminata Lectin Protein (MALP) shows a promising cytotoxic effect against the various human cancer cell lines. Supporting this, we evaluate the in vivo anti-tumor and anti-angiogenic activity of MALP in Ehrlich Ascites Carcinoma mice model (EAC). MALP treatment resulted in tumor growth inhibition and increased the lifespan of the EAC-bearing mice without showing any side effects on normal mice, as revealed by histological parameters. Further, a significant decrease in the ascites vascular endothelial growth factor (VEGF) secretion and microvessel density supports the anti-angiogenic property of the MALP. Apoptosis-inducing activity of MALP was revealed by DNA fragmentation assay, Caspase-3 inhibitor assay and cellular morphology were studied by fluorescence staining methods. Our study delivers the real evidence that MALP with a promising an anticancer potential expressively degenerates the tumor development by affecting angiogenesis and apoptosis.

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PMID: 

J Food Biochem. 2020 Jan 3:e13137. Epub 2020 Jan 3. PMID: 31899556

Abstract Title: 

Isolation of flavonoids from Musa acuminata Colla (Simili radjah, ABB) and the in vitro inhibitory effects of its leaf and fruit fractions on free radicals, acetylcholinesterase, 15-lipoxygenase, and carbohydrate hydrolyzing enzymes.

Abstract: 

Musa species are used traditionally for the management of many diseases. The study evaluated and compared anticholinesterase, anti-inflammatory, antioxidant, and antidiabetic activities of Musa acuminata (Simili radjah, ABB) fruits and leaves fractions and characterized the bioactive compounds using HPTLC-HRMS and NMR. Leaf fractions gave the higher biological activities than the fruit. Ethyl acetate fraction of the leaf had the highest total phenolic content (911.9 ± 1.7 mg GAE/g) and highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (IC9.0 ± 0.4 µg/ml). It also gave the most effective inhibition of acetylcholinesterase (IC404.4 ± 8.0 µg/ml) and α-glucosidase (IC4.9 ± 1.6 µg/ml), but a moderate α-amylase inhibition (IC444.3 ± 4.0 µg/ml). The anti-inflammatory activity of n-butanol (IC34.1 ± 2.6 µg/ml) and ethyl acetate fractions (IC, 43.1 ± 11.3 µg/ml) of the leaf were higher than the positive control, quercetin (IC, 54.8 ± 17.1 µg/ml). Kaempferol-3-O-rutinoside and quercetin-3-O-rutinoside (rutin) were identified as the bioactive compounds with antioxidant and antidiabetic activities from the ethyl acetate fraction of M. acuminata leaf. PRACTICAL APPLICATIONS: All parts of Musa acuminata are known to be usefulethnomedicinally even as food. The leaves are mostly used to serve food and used for wrapping purposes. However, this study concluded that M. acuminata leaf is rich in bioactive flavonoids such as kaempferol-3-O-rutinoside and rutin, with relatively high antioxidative, antidiabetic, and anti-inflammatory activities. Therefore, aside the fact that the leaves can serve as potential drug leads for pharmaceutical industries, it can also be embraced in the food sector to produce supplements and/or nutraceuticals in the management of Alzheimer's, diabetes and other inflammatory diseases.

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PMID: 

Pediatrics. 2014 Oct ;134(4):e1049-56. Epub 2014 Sep 15. PMID: 25225141

Abstract Title: 

Parent and adolescent knowledge of HPV and subsequent vaccination.

Abstract: 

OBJECTIVE: Human papillomavirus (HPV) vaccination has been shown to have important health benefits, but vaccination rates are low. Parental and adolescent knowledge could possibly promote vaccination, but the relationship between knowledge and subsequent vaccination is unclear. This study examines how strongly HPV vaccination among high-risk adolescents is related to their or their parents' previous knowledge.METHODS: A longitudinal cohort study enrolled participants from low-income, predominantly African American neighborhoods. Baseline questionnaires measuring knowledge of HPV and HPV vaccination, as well other variables, were completed by 211 adolescents and 149 parents of another adolescent sample. Adolescent vaccination was tracked prospectively for 12 months after baseline by using clinic reporting data. Analyses tested if parent or adolescent knowledge was associated with or predictive of adolescent HPV vaccination.RESULTS: On average, parents and adolescents answered slightly less than 50% of knowledge items correctly at baseline, with 5% of parents and 10% of adolescents not answering any knowledge items correctly. Within 12 months, 20 of 149 (13.4%) of the parents' daughters received an HPV vaccination and 32 of 211 (15.2%) of the other adolescent sample did so. Neither parental nor adolescent knowledge was associated with or predictive of adolescent vaccination. For example, when testing the relationship between adolescent vaccination and parental knowledge scores, all R(2) values were

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PMID: 

Vaccine. 2014 Oct 7 ;32(44):5845-53. Epub 2014 Aug 12. PMID: 25131743

Abstract Title: 

Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: a transmission-dynamic modelling study.

Abstract: 

BACKGROUND: Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls&boys HPV vaccination programmes in Canada.METHODS: We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost.FINDINGS: Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between $7900-24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated.INTERPRETATION: Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls&boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls.

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PMID: 

J Infect Dis. 2015 Jan 15 ;211(2):206-15. Epub 2014 Jul 23. PMID: 25057044

Abstract Title: 

Too late to vaccinate? The incremental benefits and cost-effectiveness of a delayed catch-up program using the 4-valent human papillomavirus vaccine in Norway.

Abstract: 

BACKGROUND: Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway.METHODS: We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity.RESULTS: The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage.CONCLUSIONS: HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain.

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PMID: 

J Infect Dis. 2015 Jan 15 ;211(2):172-4. Epub 2014 Jul 23. PMID: 25057043

Abstract Title: 

The cost-effectiveness of human papillomavirus vaccine catch-up programs for women.

Abstract: 

[n/a]

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