PMID: 

Cancer Prev Res (Phila). 2019 Jul ;12(7):421-432. Epub 2019 Jun 8. PMID: 31177203

Abstract Title: 

Lycopene Inhibits Smoke-Induced Chronic Obstructive Pulmonary Disease and Lung Carcinogenesis by Modulating Reverse Cholesterol Transport in Ferrets.

Abstract: 

Chronic obstructive pulmonary disease (COPD) and lung cancer share the same etiologic factor, cigarette smoking. Higher consumption of dietary lycopene has been associated with lower risks of COPD and lung cancer in smokers. We investigated whether lycopene feeding protects against COPD and lung cancer in ferrets, a nonrodent model that closely mimics cigarette smoke (CS)-induced chronic bronchitis, emphysema, and lung tumorigenesis in human. We also explored whether the protective effect of lycopene is associated with restoring reverse cholesterol transport (RCT), a key driver in persistent inflammation with CS exposure. Ferrets (4 groups,= 12-16/group) were exposed to a combination of tobacco carcinogen (NNK) and CS with or without consuming lycopene at low and high doses (equivalent to∼30 and ∼90 mg lycopene/day in human, respectively) for 22 weeks. Results showed that dietary lycopene at a high dose significantly inhibited NNK/CS-induced chronic bronchitis, emphysema, and preneoplastic lesions, including squamous metaplasia and atypical adenomatous hyperplasia, as compared with the NNK/CS alone (

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PMID: 

Curr Med Chem. 2014 Mar ;21(7):932-40. PMID: 24083601

Abstract Title: 

Melting profiles may affect detection of residual HPV L1 gene DNA fragments in Gardasil®.

Abstract: 

Gardasil® is a quadrivalent human papillomavirus (HPV) protein-based vaccine containing genotype-specific L1 capsid proteins of HPV-16, HPV-18, HPV-6 and HPV-11 in the form of virus-like-particles (VLPs) as the active ingredient. The VLPs are produced by a DNA recombinant technology. It is uncertain if theresidual HPV L1 gene DNA fragments in the vaccine products are considered contaminants or excipients of the Gardasil® vaccine. Because naked viral DNA fragments, if present in the vaccine, may bind to the insoluble amorphous aluminum hydroxyphosphate sulfate (AAHS) adjuvant which may help deliverthe foreign DNA into macrophages, causing unintended pathophysiologic effects, experiments were undertaken to develop tests for HPV L1 gene DNA fragments in the final products of Gardasil® by polymerase chain reaction (PCR) and direct DNA sequencing. The results showed that while the HPV-11 and HPV-18 L1 gene DNA fragments in Gardasil® were readily amplified by the common GP6/MY11 degenerate consensus primers, the HPV-16 L1 gene DNA may need specially designed non-degenerate PCR primers for amplification at different regions of the L1 gene and different stringency conditions for detection. These variable melting profiles of HPV DNA in the insoluble fraction of the Gardasil® vaccine suggest that the HPV DNA fragments are firmly bound to the aluminum AAHS adjuvant. All methods developed for detecting residual HPV DNA in the vaccine Gardasil® for quality assurance must take into consideration the variable melting profiles of the DNA to avoid false negative results.

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PMID: 

PLoS One. 2016 ;11(4):e0153867. Epub 2016 Apr 15. PMID: 27082865

Abstract Title: 

Short-Fragment DNA Residue from Vaccine Purification Processes Promotes Immune Response to the New Inactivated EV71 Vaccine by Upregulating TLR9 mRNA.

Abstract: 

To reduce potential oncogenic long genomic DNA in vaccines, nuclease treatment has been applied in the purification processes. However, this action increased the residue of short-fragment DNA and its effect on vaccine potency was still elusive. In this study, we found residual sf-DNA in an inactivated EV71 vaccine could enhance humoral immune response in mice. Ag stimulation in vitro and vaccine injection in vivo revealed that TLR9 transcription level was elevated, indicating that sf-DNA could activate TLR9. These new findings will help us to understand the molecular mechanism induced by vero-cell culture-derived vaccines.

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PMID: 

Hum Exp Toxicol. 2019 Nov ;38(11):1302-1313. Epub 2019 Jul 18. PMID: 31319718

Abstract Title: 

Testicular toxicity of gentamicin in adult rats: Ameliorative effect of lycopene.

Abstract: 

The current study was aimed to investigate the ameliorative effect of lycopene against gentamicin-induced testicular toxicity in adult rat testes. Pretreatment with lycopene (4 mg/kg/day) significantly prevented the decrease in the absolute testes weight and relative testes weight and the reduction in sperm count, motility, viability, and daily sperm production in gentamicin (100 mg/kg/day)-treated rats. Gentamicin significantly decreased the level of serum testosterone and testicular lactate dehydrogenase-X and G6PDH activities but a marked increase was observed upon pretreatment with lycopene. Testicular caspase-3 and -9 activities were significantly increased but lycopene showed significant protection from gentamicin-induced apoptosis. Oxidative stress was induced by gentamicin treatment as evidenced by increased hydrogen peroxide level and lipid peroxidation and decreased the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and glutathione content. These alterations were effectively prevented by lycopene pretreatment. Histopathological examination showed loss of spermatogenesis and morphological abnormalities of the testis after treatment with gentamycin. These abnormalities were effectively normalized by pretreatment with lycopene. In conclusion, gentamicin decreases rat testes weight and inhibits spermatogenesis. It induces oxidative stress and apoptosis by possible mitochondrial dysfunction. These data provide insight into the mode of action of gentamicin-induced testicular toxicity and the beneficial role provided by lycopene to restore the suppressed spermatogenesis.

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PMID: 

PLoS One. 2014 ;9(4):e94149. Epub 2014 Apr 10. PMID: 24722772

Abstract Title: 

Low-dose formaldehyde delays DNA damage recognition and DNA excision repair in human cells.

Abstract: 

OBJECTIVE: Formaldehyde is still widely employed as a universal crosslinking agent, preservative and disinfectant, despite its proven carcinogenicity in occupationally exposed workers. Therefore, it is of paramount importance to understand the possible impact of low-dose formaldehyde exposures in the general population. Due to the concomitant occurrence of multiple indoor and outdoor toxicants, we tested how formaldehyde, at micromolar concentrations, interferes with general DNA damage recognition and excision processes that remove some of the most frequently inflicted DNA lesions.METHODOLOGY/PRINCIPAL FINDINGS: The overall mobility of the DNA damage sensors UV-DDB (ultraviolet-damaged DNA-binding) and XPC (xeroderma pigmentosum group C) was analyzed by assessing real-time protein dynamics in the nucleus of cultured human cells exposed to non-cytotoxic (

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PMID: 

Toxicol Lett. 2011 Sep 10 ;205(3):235-40. Epub 2011 Jul 1. PMID: 21745553

Abstract Title: 

Effects of long-term low-dose formaldehyde exposure on global genomic hypomethylation in 16HBE cells.

Abstract: 

Formaldehyde (FA), a volatile organic compound, is a ubiquitous air pollutant that is classified as 'Carcinogenic to humans (Group 1)' by IARC (2006). As a well-recognized human carcinogen, its carcinogenic mechanisms are still poorly understood. Previous studies have emphasized on genetic changes. However, little is known about the epigenetic mechanisms of FA exposure. In this study, We not only characterized the epigenomic response to long-term low-dose FA exposure in 16HBE cells, but also examined the expression of DNA methyltransferases (DNMTs) and the methyl-CpG-binding protein DNA-binding domain protein 2 (MBD2). Each week the 16HBE cells were treated with 10μM FA for 24 h (h). After 24 weeks of exposure to FA, the level of genomic DNA methylation gradually decreased in a time-related manner. Moreover, our results showed that FA exposure down-regulated the expression of DNMT3a and DNMT3b at both mRNA and protein level, and up-regulated the levels of DNMT1 and MBD2 at both mRNA and protein level. Our study indicated that long-term FA exposure could disrupt genomic DNA methylation, which may be one of the possible underlying carcinogenic mechanisms of FA.

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PMID: 

Drug Chem Toxicol. 2019 Aug 30:1-11. Epub 2019 Aug 30. PMID: 31469002

Abstract Title: 

Fluted pumpkin seeds protect against busulfan-induced oxidative stress and testicular injuries in adult mice.

Abstract: 

Fluted pumpkin is traditionally claimed to improve fertility health of male adult subjects. This study evaluated the adjuvant protective potential of fluted pumpkin seeds (FPS) extract on the deleterious effects of busulfan on the testes. Tubular germ cell depletion was induced in the testis of mice byadministration of busulfan (15 mg/kg body wt. two injections, seven days apart) and the effect of ethanolic extract of FPS (200 mg/kg body wt.) was investigated after 40 days of oral administration. Busulfan caused extensive damage to the seminiferous epithelium, decreased Johnsen's score index for spermatogenesis and number of Leydig cells ( 

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PMID: 

J Investig Allergol Clin Immunol. 2016;26(6):394-396. PMID: 27996954

Abstract Title: 

Anaphylaxis Due to the Excipient Polysorbate 80.

Abstract: 

[n/a]

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PMID: 

J Physiol Pharmacol. 2019 Aug ;70(4). Epub 2019 Nov 15. PMID: 31741457

Abstract Title: 

Lycopene induces apoptosis by inhibiting nuclear translocation ofβ-catenin in gastric cancer cells.

Abstract: 

Reactive oxygen species (ROS) promote the development and progression of cancer by their effects on several signaling pathways. Lycopene, a major carotenoid natural product, is known to display antioxidant activity and to induce apoptosis of cancer cells. The aim of the present study was to investigate the mechanism by which lycopene induces apoptosis of the human gastric cancer AGS cells. In the present study, we showed that lycopene reduces the viability of AGS cells by inducing DNA fragmentation and increasing the Bax/Bcl-2 ratio. To determine the mechanistic basis for these effects, studies were conducted to assess the effects of this carotenoid on activation and nuclear translocation ofβ-catenin, and the expression of β-catenin target genes in AGS cells. The results showed that lycopene reduces the levels of ROS. It also inhibits activation of β-catenin signaling by changing the Wnt/β-catenin multi-protein complex such as a reduction in phosphorylation of glycogen synthase kinase 3β [GSK3β] and an increase in adenomatous polyposis coli [APC] and β-transducin repeats-containing proteins [β-TrCP]). It suppresses nuclear translocation of β-catenin and the expression of the β-catenin target survival genes c-myc and cyclin D1. Lycopene induces apoptosis by reducing ROSlevels and suppressing β-catenin-c-myc/cyclin D1 axis. Thus, lycopene induces apoptosis of gastric cancer cells by disrupting nuclear translocation of β-catenin and expression of key cell survival genes.

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PMID: 

Free Radic Biol Med. 2019 Nov 29. Epub 2019 Nov 29. PMID: 31790829

Abstract Title: 

Lycopene prevents the progression of lipotoxicity-induced nonalcoholic steatohepatitis by decreasing oxidative stress in mice.

Abstract: 

Excessive fatty acid uptake-induced oxidative stress causes liver injury and the consecutive recruitment of inflammatory immune cells, thereby promoting the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Lycopene, the most effective singlet oxygen scavenger of the antioxidant carotenoids, has anti-inflammatory activity. Here, we investigated the preventive and therapeutic effects of lycopene in a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet. Lycopene alleviated excessive hepatic lipid accumulation and enhanced lipolysis, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis, and subsequently reduced the recruitment of CD4and CD8T cells in the liver. Importantly, lycopene reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. In parallel, lycopene decreased LPS-/IFN-γ-/TNFα-induced M1 marker mRNA levels in peritoneal macrophages, as well as TGF-β1-induced expression of fibrogenic genes in a stellate cell line, in a dose-dependent manner. These results were associated with decreased oxidative stress in cells, which might be mediated by the expression of NADPHoxidase subunits. In summary, lycopene prevented and reversed lipotoxicity-induced inflammation and fibrosis in NASH mice by reducing oxidative stress. Therefore, it might be a novel and promising treatment for NASH.

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