PMID: 

PLoS One. 2019 ;14(5):e0216604. Epub 2019 May 16. PMID: 31095579

Abstract Title: 

Short chain fatty acids enriched fermentation metabolites of soluble dietary fibre from Musa paradisiaca drives HT29 colon cancer cells to apoptosis.

Abstract: 

In this study, the prebiotic potential of soluble dietary fibre extracted from plantain inflorescence (PIF) was investigated. PIF demonstrated prebiotic potential by enhancing the growth of the probiotics under study and thereby hindered colon cancer development. The soluble dietary fibre from Musa paradisiaca inflorescence (PIF) was fermented using Lactobacillus casei and Bifidobacterium bifidum. The fermentation supernatants (LS and BS) were enriched with short chain fatty acids (SCFA) and were able to initiate apoptotic signalling in HT29 colon cancer cells leading to cell death. Both BS and LS exhibited cytotoxic effect; induced DNA damage and enhanced generation of reactive oxygen species in HT29 cells leading to apoptosis. The induction of apoptosis was facilitated by the reduction of membrane potential of mitochondria and ATP synthesis; enhanced delivery of cytochrome c and interference with the expression of pro/antiapoptotic proteins. BS, which exhibited better activity, was further analysed for the identification of differentially regulated proteins by performing two dimensional electrophoresis and MALDI-TOF mass spectrometry. Results emphasized on the fact that, the exposure to BSalteredthe HT29 proteins expression, particularly the upregulation of apoptosis- inducing factor-AIFM1 leading to apoptosis of HT29 cells.

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PMID: 

Toxicol In Vitro. 2019 Sep ;59:179-186. Epub 2019 Apr 21. PMID: 31018149

Abstract Title: 

Chemical composition and cytotoxic screening of Musa cavendish green peels extract: Antiproliferative activity by activation of different cellular death types.

Abstract: 

Musa cavendish, commonly known as banana, is a fruit with nutritional and therapeutic properties. We investigated the chemical composition and in vitro cytotoxic effect of M. cavendish green peel extract (MHE) on cancer cells for the first time. The compounds characterization was performed by HPLC-UV/Vis and FIA-ESI-IT-MS. We investigated in vitro cytotoxic effect of Musa cavendish green peels extract (MHE) in HepG2, A-375, MCF-7 and Caco-2 cancer cells. We evaluated the effect of MHE on proliferation of different cell lines through apoptosis, necrosis, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) content determination. We identified 12 compounds from different classes in the extract, including derivatives of phenolic acids, aglycone flavonoids, glycoside flavonoids and catecholamines. Our results indicate that MHE exerts, after 48 h treatment, an accentuated antiproliferative effect from the dose of 100 μg/mL in all cell lines tested. In HepG2 cells, these effects were related to the induction of cell death, both necrotic and apoptotic, and remarkable changes in cell morphology. Depolarization of MMP and high ROS content were also observed in the cells in a dose-dependent manner. Our results show that MHE may be used as a source of new drugs with anticancer activity.

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PMID: 

Assay Drug Dev Technol. 2019 Feb/Mar;17(2):68-76. PMID: 30869526

Abstract Title: 

Possible Antidiabetic and Antioxidative Activity of Hydro-Methanolic Extract of Musa balbisiana (Colla) Flower in Streptozotocin-Induced Diabetic Male Albino Wistar Strain Rat: A Genomic Approach.

Abstract: 

The aim of the investigation was to search out the possible corrective effect of hydro-methanolic extract:: 3:2 of Musa balbisiana flower on streptozotocin (STZ)-induced diabetic male rat. In this concern, glycemic profile, oxidative stress profile, lipid profile, and toxicity profile were studied where a genomic approach has been taken to explain the mechanism of action of the said extract for such recovery. Such enzyme kinetics domain and genomic domain of concerned profile were not covered till now to explore the mechanism of diabetes management by this plant part. As hexokinase is one of the important enzymes of glycolysis and glycogenesis, and GLUT-4 an important transporter of glucose in skeletal muscle, liver and adipose tissue these genes have been selected here. For focusing the status of apoptosis in hepatic tissue, an important organ for carbohydrate metabolism, Bax and Bcl-2 gene expression were included, which are the novelty of this study. The hydro-methanolic extract was administered orally at the dose of 10 mg/100 g body weight for 28 days to diabetic rats. Abovementioned extract exhibited a significant recovery in parameters like fasting blood glucose; serum insulin; glycated hemoglobin; antioxidative enzymes in hepatic and renal tissue; and carbohydrate metabolic enzymes in hepatic and skeleto-muscular tissue along with proappoptotic gene Bax and antiappoptotic gene Bcl-2, glycemic genes like Hex-I, and GLUT-4 in hepatic tissue of STZ-induced diabetic rat. This investigation demonstrated the potentiality of hydro-methanolic extract (3:2) of M. balbisiana flower for correction of diabetes and diabetes-induced oxidative stress.

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PMID: 

J Med Food. 2019 Jul 10. Epub 2019 Jul 10. PMID: 31268391

Abstract Title: 

Bactericidal Effect of the Leaf Extract fromspp. (AAB Group, Silk Subgroup), cv."Manzano"Against Multidrug-Resistant.

Abstract: 

Air-dried leaves of aspp. AAB, cv."Manzano"plant, known asin the Maya culture, were sequentially extracted with hexane, ethyl acetate, and methanol; the resulting extracts were investigated for their antimycobacterial activity against susceptible and drug-resistant strains of(MTB) using the Microplate Alamar Blue Assay. Both the n-hexane extract (HE) and ethyl acetate extract (EE) showed potent activity against both strains of MTB, with the EE exhibiting the strongest activity and a Minimum Inhibitory Concentration of 12.5 and 6.25 μg/mL against susceptible and drug-resistant strains, respectively. Both extracts also demonstrated a mycobactericidal effect and a very good selectivity index when tested for cytotoxic activity on Vero monkey kidney cells, using the Sulforhodamine B assay. Our results demonstrate the efficiencyand selectivity ofspp. AAB, cv."Manzano"against MTB strains and support its traditional use as remedy against tuberculosis in Maya traditional medicine.

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PMID: 

Front Physiol. 2019 ;10:899. Epub 2019 Jul 18. PMID: 31379604

Abstract Title: 

A Moderate Daily Dose of Resveratrol Mitigates Muscle Deconditioning in a Martian Gravity Analog.

Abstract: 

While there is a relatively good understanding of the effects of microgravity on human physiology based on five decades of experience, the physiological consequences of partial gravity remain far less well understood. Until recently, no model had been able to replicate partial gravity such as that experienced on Mars (0.38 g), which would be critical to help sustain long-term missions and ensure a safe return to Earth. Recent development of two partial weight bearing (PWB) models, one in mice and one in rats, now allows for quadrupedal partial unloading that mimics Martian gravity. Resveratrol (RSV), a polyphenol most commonly found in grapes and blueberries, has been extensively investigated for its health benefits, including its anti-inflammatory, anti-oxidative, and anti-diabetic effects. In the context of mechanical unloading, RSV has also been shown to preserve bone and muscle mass. However, there is a lack of research regarding its effect on the musculoskeletal system in partial gravity. We hypothesized that a moderate daily dose of RSV (150 mg/kg/day) would help mitigate muscle deconditioning in a Mars gravity analog. Indeed, our results demonstrate that RSV treatment during partial unloading significantly preserves muscle function (e.g., the average change in grip force after 14 days of PWB40 was of -6.18, and +10.92% when RSV was administered) and mitigates muscle atrophy (e.g., RSV supplementation led to an increase of 21.6% in soleus weight for the unloaded animals). This work suggests the potential of a nutraceutical approach to reduce musculoskeletal deconditioning on a long-term mission to Mars.

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PMID: 

J Food Biochem. 2019 Apr ;43(4):e12783. Epub 2019 Jan 24. PMID: 31353578

Abstract Title: 

Cooking has the potential to decrease the antitumor effect of fresh Betong watercress.

Abstract: 

Betong watercress (Nasturtium officinale R.Br.) contains phenethyl isothiocyanate (PEITC), derived from myrosinase-mediated hydrolysis of glucosinolates. Effects of fresh and cooked Betong watercress (FBW&CBW) on N-demethylation and C-8-hydroxylation of caffeine (CF) in rats were investigated. Wistar rats received a single dose of CF before and after pretreatments with a single or five-day administration of PEITC, FBW, and CBW dry powders. Plasma CF metabolic ratios (CMRs) were compared between before and after pretreatments. Single pretreatment with PEITC, FBW, but not CBW, significantly decreased CMRs. Five-day pretreatment with PEITC, FBW, and CBW significantly decreased CMRs. The decreases in CMRs after multiple doses of PEITC, FBW, and CBW were significantly higher than after a single dose. The decrease in CMRs caused by CBW was significantly lower than those by FBW, both single- and multiple doses. Cooking decreases the activity of FBW in inhibition of CYP1A2 mediating CF metabolism. PRACTICAL APPLICATIONS: PEITC and fresh watercress possess chemoprotective effects due to the inhibitory activity of PEITC on cytochrome P450s mediated bioactivation of carcinogens. Several clinical trials of the therapeutic uses of PEITC for cancer and other diseases are still in the pipeline. Betong watercress is a common ingredient in hot soup and stir-fried Thai recipes. Cooking heat inactivates plant myrosinase involving the production of PEITC. Consumption of watercress in cooked form may contribute less chemoprotective benefit. More appropriate preparation to deliver PEITC is needed to be evaluated.

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PMID: 

Toxicol In Vitro. 2009 Sep ;23(6):1092-9. Epub 2009 Jun 2. PMID: 19497362

Abstract Title: 

Increase in intracellular Zn2+ concentration by thimerosal in rat thymocytes: intracellular Zn2+ release induced by oxidative stress.

Abstract: 

Thimerosal (TMR), an ethylmercury-containing preservative in pharmaceutical products, was recently reported to increase intracellular Zn(2+) concentration. Therefore, some health concerns about the toxicity of TMR remain because of physiological and pathological roles of Zn(2+). To reveal the property of TMR-induced increase in intracellular Zn(2+) concentration, the effect of TMR on FluoZin-3 fluorescence, an indicator of intracellular Zn(2+), of rat thymocytes was examined. TMR at concentrations ranging from 0.3 microM to 10 microM increased the intensity of FluoZin-3 fluorescence in a concentration-dependent manner under external Ca(2+)- and Zn(2+)-free condition. The threshold concentration was 0.3-1 microM. The increase in the intensity was significant when TMR concentration was 1 microM or more. N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a chelator for intracellular Zn(2+), completely attenuated the TMR-induced augmentation of FluoZin-3 fluorescence. Hydrogen peroxide (H(2)O(2)) and N-ethylmaleimide, reducing cellular thiol content, significantly increased FluoZin-3 fluorescence intensity and decreased 5-chloromethylfluorescein (5-CMF) fluorescence intensity, an indicator for cellular thiol. The correlation coefficient between TMR-induced augmentation of FluoZin-3 fluorescence and attenuation of 5-CMF fluorescence was -0.882. TMR also attenuated the 5-CMF fluorescence in the presence of TPEN. Simultaneous application of H(2)O(2) and TMR synergistically augmented the FluoZin-3 fluorescence. It is suggested that TMR increases intracellular Zn(2+) concentration via decreasing cellular thiol content.

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PMID: 

Hum Exp Toxicol. 2013 May ;32(5):464-75. Epub 2012 Sep 27. PMID: 23023030

Abstract Title: 

Comparison of VAERS fetal-loss reports during three consecutive influenza seasons: was there a synergistic fetal toxicity associated with the two-vaccine 2009/2010 season?

Abstract: 

The aim of this study was to compare the number of inactivated-influenza vaccine-related spontaneous abortion and stillbirth (SB) reports in the Vaccine Adverse Event Reporting System (VAERS) database during three consecutive flu seasons beginning 2008/2009 and assess the relative fetal death reports associated with the two-vaccine 2009/2010 season. The VAERS database was searched for reports of fetal demise following administration of the influenza vaccine/vaccines to pregnant women. Utilization of an independent surveillance survey and VAERS, two-source capture-recapture analysis estimated the reporting completeness in the 2009/2010 flu season. Capture-recapture demonstrated that the VAERS database captured about 13.2% of the total 1321 (95% confidence interval (CI): 815-2795) estimated reports, yielding an ascertainment-corrected rate of 590 fetal-loss reports per million pregnant women vaccinated (or 1 per 1695). The unadjusted fetal-loss report rates for the three consecutive influenza seasons beginning 2008/2009 were 6.8 (95% CI: 0.1-13.1), 77.8 (95% CI: 66.3-89.4), and 12.6 (95% CI: 7.2-18.0) cases per million pregnant women vaccinated, respectively. The observed reporting bias was too low to explain the magnitude increase in fetal-demise reporting rates in the VAERS database relative to the reported annual trends. Thus, a synergistic fetal toxicity likely resulted from the administration of both the pandemic (A-H1N1) and seasonal influenza vaccines during the 2009/2010 season.

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PMID: 

Clin Gastroenterol Hepatol. 2019 Feb 5. Epub 2019 Feb 5. PMID: 30731196

Abstract Title: 

Acetaminophen is Undetectable in Plasma From More Than Half of Patients Believed to Have Acute Liver Failure Due to Overdose.

Abstract: 

BACKGROUND & AIMS: Evaluation of patients with acute liver injury (ALI) or acute liver failure (ALF) often includes measurement of plasma levels of acetaminophen, to determine exposure and/or toxicity. However, once liver injury has developed, acetaminophen might be undetectable in plasma. We investigated the association between level of acetaminophen measured and outcomes of patients designated as having ALF or ALI due to acetaminophen toxicity.METHODS: We performed a retrospective analysis of data from 434 subjects in the Acute Liver Failure Study Group who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) or ALI (severe liver injury with coagulopathy but no encephalopathy) due to acetaminophen toxicity from January 1, 2010 through December 31, 2014. We collected data on patient demographics, biochemical features, reported acetaminophen use, N-acetylcysteine therapy, liver transplant, and outcomes. Descriptive statistics were used to assess patient demographics, clinical characteristics, and outcomes whereas differences in continuous variables between patients with vs without acetaminophen detection on admission were analyzed using the Wilcoxon rank-sum test. The primary aim was to determine the proportion of patients with detectable plasma levels of acetaminophen.RESULTS: Acetaminophen was undetectable in serum samples from 227 patients (52%). There were no significant differences between groups of patients with detectable vs undetectable levels in demographic features, alcohol use, median levels of alanine aspartate, or use of N-acetylcysteine (given to 94.7% of patients with detectable acetaminophen vs 95.9% of those with undetectable acetaminophen; P=.63). We observed a significant difference in median dose taken between patients with detectable (29,500 mg; interquartile range, 15,000 mg-50,007 mg) vs no detectable parent compound (14,950 mg; interquartile range, 3960 mg-25,000) (P=.003). A lower proportion of patients with detectable plasma levels of acetaminophen (72.3%) survived without a liver transplant than of patients with undetectable levels (86.3%) in univariate analysis (P=.0006), although this was not significant in multivariable analysis (P=.12). Although most patients had unintentional overdoses, a higher proportion of patients with suicidal overdoses (43%) had detectable levels of acetaminophen than patients with accidental overdoses (29.3%; P=.01).CONCLUSION: More than half of patients who present at the hospital with acetaminophen-induced ALI or ALF have undetectable levels of acetaminophen. Clinicians should not exclude acetaminophen toxicity because of undetectable levels or withhold N-acetylcysteine for patients with ALI or ALF when acetaminophen toxicity is suspected.

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PMID: 

Environ Sci Pollut Res Int. 2019 Aug ;26(24):25301-25311. Epub 2019 Jun 29. PMID: 31256398

Abstract Title: 

Marine macro-algae attenuates nephrotoxicity and hepatotoxicity induced by cisplatin and acetaminophen in rats.

Abstract: 

Cisplatin is considered one of the best anticancer medications often used for the treatment of various cancers even with its adverse effects. Acetaminophen (paracetamol) is a widely used analgesic-antipyretic drug that causes hepatotoxicity at higher than the effective doses. The present study assesses the nephroprotective and hepatoprotective effects of two seaweeds against cisplatin and acetaminophen toxicity in rats. Damage to the liver and kidney was induced by administering a single intraperitoneal dose of acetaminophen (600 mg/kg) or cisplatin (7 mg/kg) to groups of rats. The damage to the liver and kidney was assessed by the elevated liver (ALT, AST, ALP, LDH, electrolytes) and kidney (urea, creatinine) biomarkers. The ethanol extract of brown seaweed reversed the elevated levels of kidney and liver biomarkers along with triglycerides, cholesterol, and glucose. Among the two seaweeds, Sargassum ilicifolium showed better nephroprotective and hepatoprotective effects than the standard drug N-Acetyl-cysteine, Halymenia porphyroides showed only limited protection. Findings of this study provide evidence of nephroprotective and hepatoprotective effects of S. ilicifolium. Seaweed could be a beneficial dietary supplement to attenuate nephrotoxicity and hepatotoxicity.

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