Sayer Ji, author of REGENERATE: Unlocking Your Body’s Radical Resilience with the New Biology, explains what lead him to write the book, and what it’s all about! 

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PMID: 

J Food Biochem. 2020 Jan 14:e13147. Epub 2020 Jan 14. PMID: 31943241

Abstract Title: 

Grape seed proanthocyanidins prevent HO-induced mitochondrial dysfunction and apoptosis via SIRT 1 activation in embryonic kidney cells.

Abstract: 

Grape proanthocyanidins are compounds widely ingested in the diet. This study evaluated their effects on mitochondrial function, apoptosis, and sirtuin 1 and 3 expressions in HEK-293 cells exposed to HO. High-resolution mass spectrometry and high-performance liquid chromatography characterized the proanthocyanidins extract and the presence of procyanidins B and C was detected. The extract prevented HO-induced oxidative damage to proteins and lipids and depletion in superoxide dismutase activity. Moreover, it was able to regulate the expression of NADH: Ubiquinone oxidoreductase core subunit S7 and prevent mitochondrial electron transport chain dysfunction, ATP depletion, and apoptosis induced by HO. Finally, the extract was able to regulate sirtuin 1 and 3 expressions, thus maintaining cell viability. These data show that the grape seed proanthocyanidins can target mitochondrial proteins, which may represent an important approach for the management of numerous chronic illnesses associated with mitochondrial dysfunction. PRACTICAL APPLICATIONS: Proanthocyanidins are phenolic compounds abundant in regular diet, commonly found in grapes and derivatives, pomegranates, apples, and red fruits, all foods known for their beneficial effects on health. The current study highlights the role of proanthocyanidins as mitochondrial modulators that may explain the biological activity attributed to these compounds. This study brings evidence that proanthocyanidins might be considered as a value-added agent for the development of new nutraceutical and or pharmaceutical approaches.

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PMID: 

Folia Morphol (Warsz). 2020 Jan 13. Epub 2020 Jan 13. PMID: 31930466

Abstract Title: 

The potential gonadoprotective effects of grape seed extract against the histopathological alterations elicited in an animal model of cadmium-induced testicular toxicity.

Abstract: 

BACKGROUND: Grape seed extract (GSE) is a powerful antioxidant containing high levels of bioflavonoids, vitamin C and vitamin E. The aim of the work is to study the possible protective and ameliorative effects of grape seed extract in an animal model of cadmium (Cd)-induced testicular toxicity in rats.MATERIALS AND METHODS: A thirty-day oral gavage study in adult male albino rats was performed using 32 animals, randomly divided into 4 equal groups; negative control, cadmium (5 mg/k/day), grape seed extract (100 mg/k/day), and cadmium + GSE. Testicular weights were measured. Hematoxylin&eosin (H&E) staining and proliferating nuclear cell antigen (PCNA) immunohistochemistry, as a marker for proliferation were done. Morphometric parameters were assessed and subjected to statistical analysis.RESULTS: The H&E results showed atrophy and distortion of the seminiferous tubules (STs) with sloughing of the spermatogenic epithelium in cadmium group. The interstitial spaces were widened and showed edema and mononuclear cell infiltrations. No remarkable changes were observed in the grape-seed-only group when compared to the control group. In both combined group, maintaining of the STs and their lining cells was evident. The immunohistochemical results showed marked positive PCNA immunoreactivity in both control and GSE groups, while negative immunoreaction was noticed in Cd group. Limited positive PCNA immunoreactivity was ameliorated in Cd+ GSE group.CONCLUSIONS: GSE protected against cadmium-induced testicular toxicity in rats, reducing induced histopathological changes, and maintaining testicular histoarchitecture.

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PMID: 

Pharm Biol. 2020 Dec ;58(1):107-115. PMID: 31942829

Abstract Title: 

Protective effects of ascorbic acid and calcitriol combination on airway remodelling in ovalbumin-induced chronic asthma.

Abstract: 

Airway remodelling is one of the most refractory problems in asthma. According to the critical roles of oxidative stress and inflammation in airway remodelling, it is supposed that ascorbic acid and calcitriol have beneficial effects. However, a combination of antioxidants may be more effective for asthma therapy.This study investigated the protective effects of ascorbic acid in combination with calcitriol on airway remodelling in ovalbumin (OVA)-induced chronic asthma.BALB/c mice were assigned into seven groups: (1) Control; (2) Asthma; (3) Ineffective C (orally 39 mg/kg ascorbic acid); (4) Ineffective D (intraperitoneally 1.5 μg/kg calcitriol); (5) Effective C (orally 130 mg/kg ascorbic acid); (6) Effective D (intraperitoneally 5 μg/kg calcitriol); (7) Combination (orally 39 mg/kg ascorbic acid + intraperitoneally 1.5 μg/kg calcitriol). All animals were sensitized and challenged with OVA except in the control group (normal saline). In all treatment groups, mice were administrated vitamins 30 min before each challenge (three times per week for 8 consecutive weeks).In comparison with the asthma group, co-administration of ineffective doses of ascorbic acid and calcitriol led to the decreased levels of IL-13 (50.5 ± 1.85 vs. 42.13 ± 0.37 pg/mL, = 0.02) and IgE (58.74 ± 0.43 vs. 45.78 ± 2.05 ng/mL, = 0.003) as well as the reduction of goblet hyperplasia and subepithelial fibrosis (5 vs. 1 score, = 0.001 and 5 vs. 2 score, = 0.001, respectively).Combination of ascorbic acid with calcitriol in ineffective doses improves airway remodelling due to additive effects possibly through reduction of oxidative stress and inflammation. This study provides a scientific basis for further research and clinical applications of ascorbic acid and calcitriol and can be generalized to the broader pharmacological studies.

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PMID: 

Biomolecules. 2020 Jan 3 ;10(1). Epub 2020 Jan 3. PMID: 31947879

Abstract Title: 

Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells.

Abstract: 

Cancer remains one of the most feared and dreaded diseases in this era of modern medicine, claiming the lives of many, and affecting the quality of life of several others around the globe despite major advances in the diagnosis, treatment, palliative care and the immense resources invested into cancer research. While research in cancer has largely focused on the neoplasm/tumor and the cancerous cells that make up the tumor, more recently, the existence, proliferation, differentiation, migration and invasion of cancer stem cells (CSCs) and the role that CSCs play in tumor initiation, progression, metastasis, drug resistance and relapse/recurrence of the disease has gained widespread interest in cancer research. Although the conventional therapeutic approaches such as surgery, chemotherapy and radiation therapy are effective cancer treatments, very often these treatment modalities fail to target the CSCs, which then later become the source of disease recurrence. A majority of the anti-cancer agents target rapidly dividing cancer cells and normal cells and hence, have side effects that are not expected. Targeting CSCs remains a challenge due to their deviant nature with a low proliferation rate and increased drug resistance mechanism. Ascorbic acid/Vitamin C (Vit.C), a potent antioxidant, is a cofactor for several biosynthetic and gene regulatory enzymes and a vital contributor to immune defense of the body, and was found to be deficient in patients with advanced stages of cancer. Vit.C has gained importance in the treatment of cancer due to its ability to modulate the redox status of the cell and influence epigenetic modifications and significant roles in HIF1α signaling. Studies have reported that intravenous administration of Vit.C at pharmacological doses selectively kills tumor cells and targets CSCs when administered along with chemotherapeutic drugs. In the current article, we provide an in-depth review of how Vit.C plays an important role in targeting CSCs and its possible use as an adjuvant, neoadjuvant or co-treatment in the treatment of cancers.

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PMID: 

Antioxidants (Basel). 2020 Jan 10 ;9(1). Epub 2020 Jan 10. PMID: 31936782

Abstract Title: 

The Influence of In Vitro Gastrointestinal Digestion on the Anticancer Activity of Manuka Honey.

Abstract: 

Manuka honey (MH) is a natural food with many beneficial properties to human health, thanks to its high variety of bioactive compounds; however, little is known about its bioaccessibility. The aim of this study was to evaluate and compare the polyphenol compounds, the antioxidant capacity and the anticancer activity of MH subjected to an in vitro gastrointestinal digestion in human HCT-116 colon cancer cells. Raw MH and digested MH (DMH) were assessed for total polyphenols and flavonoids by spectrophotometric and HPLC-ESI-MS/MS analysis, and total antioxidant capacity (TAC) using different methods. Cell viability, intracellular ROS production, apoptosis, cell cycle and colony formation capacity were tested after treatment with MH or DMH. Results showed that total polyphenols, total flavonoids and TAC were significantly (

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PMID: 

Hum Reprod. 2014 Nov ;29(11):2512-21. Epub 2014 Sep 3. PMID: 25187598

Abstract Title: 

Transgenerational impaired male fertility with an Igf2 epigenetic defect in the rat are induced by the endocrine disruptor p,p'-DDE.

Abstract: 

STUDY QUESTION: What are the epigenetic mechanisms underlying the transgenerational effect of p,p'-DDE on male fertility?SUMMARY ANSWER: Impaired male fertility with an Igf2 epigenetic defect is transgenerationally inherited upon exposure of p,p'-DDE.WHAT IS KNOWN ALREADY: p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) is one of the primary metabolite products of the ancestral organochlorine pesticide dichlorodiphenoxytrichloroethane. As it is a known anti-androgen endocrine disruptor, it could cause harmful effects on the male reproductive system.STUDY DESIGN, SIZE, DURATION: Pregnant rats (F0) were administered with p,p'-DDE or corn oil at the critical time of testis development, i.e. from gestation days 8 to 15. Male and female rats of the F1 generation were mated with each other to produce F2 progeny. To reveal whether the transgenerational phenotype is produced by the maternal or paternal line, F3 progeny were generated by intercrossing control (C) and treated (DDE) males and females of the F2 generation according to the following groups: (i) C♂-C♀, (ii) DDE♂-DDE♀, (iii) DDE♂-C♀ and (iv) C♂-DDE♀.PARTICIPANTS/MATERIALS, SETTING, METHODS: Mature sperm and testes were collected from male offspring of the F1-F3 generations for the examination of male fertility parameters, i.e. sperm count and motility, testis histology and apoptosis. Expression of the imprinted genes, H19 and Igf2, was detected by real-time PCR. Igf2 DMR2 methylation was analyzed by bisulfite genomic sequencing.MAIN RESULTS AND THE ROLE OF CHANCE: Upon exposure of p,p'-DDE, the male F1 generation showed impaired male fertility and altered imprinted gene expression caused by Igf2 DMR2 hypomethylation. These defects were transferred to the F3 generation through the male germline.LIMITATIONS, REASONS FOR CAUTION: This study has examined the effect of p,p'-DDE only on the sperm number and motility and the possible mechanism of Igf2 DMR2 methylation in vivo and thus has some limitations. Further investigation is necessary to focus on the epigenetic effects of p,p'-DDE at the genome level and to include a more detailed semen quality analysis including sperm morphology assessment.WIDER IMPLICATIONS OF THE FINDINGS: Impaired male fertility with epigenetic alterations is transgenerationally inherited after environmental exposure of p,p'-DDE, posing significant implications in the etiology of male infertility.STUDY FUNDING/COMPETING INTERESTS: The present research was supported by National Natural Science Fund for Young Scholar (81102161), the Natural Science Fund of Zhejiang Province (LY14H260004) and funding from the Health Department of Zhejiang Province (201475777). No competing interests are declared.

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PMID: 

PLoS One. 2017 ;12(5):e0176155. Epub 2017 May 2. PMID: 28464002

Abstract Title: 

Mercury-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in zebrafish.

Abstract: 

Methylmercury (MeHg) is a ubiquitous environmental neurotoxicant, with human exposures predominantly resulting from fish consumption. Developmental exposure of zebrafish to MeHg is known to alter their neurobehavior. The current study investigated the direct exposure and transgenerational effects of MeHg, at tissue doses similar to those detected in exposed human populations, on sperm epimutations (i.e., differential DNA methylation regions [DMRs]) and neurobehavior (i.e., visual startle and spontaneous locomotion) in zebrafish, an established human health model. F0 generation embryos were exposed to MeHg (0, 1, 3, 10, 30, and 100 nM) for 24 hours ex vivo. F0 generation control and MeHg-exposed lineages were reared to adults and bred to yield the F1 generation, which was subsequently bred to the F2 generation. Direct exposure (F0 generation) and transgenerational actions (F2 generation) were then evaluated. Hyperactivity and visual deficit were observed in the unexposed descendants (F2 generation) of the MeHg-exposed lineage compared to control. An increase in F2 generation sperm epimutations was observed relative to the F0 generation. Investigation of the DMRs in the F2 generation MeHg-exposed lineage sperm revealed associated genes in the neuroactive ligand-receptor interaction and actin-cytoskeleton pathways being effected, which correlate to the observed neurobehavioral phenotypes. Developmental MeHg-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in F2 generation adult zebrafish. Therefore, mercury can promote the epigenetic transgenerational inheritance of disease in zebrafish, which significantly impacts its environmental health considerations in all species including humans.

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Researchers discover that ginger, supports the regeneration of cellular mitochondria and may reduce the effects of mitochondrial dysfunction

PMID: 

BMC Med. 2013 Oct 23 ;11:228. Epub 2013 Oct 23. PMID: 24228800

Abstract Title: 

Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity.

Abstract: 

BACKGROUND: Ancestral environmental exposures to a variety of environmental factors and toxicants have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The present work examined the potential transgenerational actions of the insecticide dichlorodiphenyltrichloroethane (DDT) on obesity and associated disease.METHODS: Outbred gestating female rats were transiently exposed to a vehicle control or DDT and the F1 generation offspring bred to generate the F2 generation and F2 generation bred to generate the F3 generation. The F1 and F3 generation control and DDT lineage rats were aged and various pathologies investigated. The F3 generation male sperm were collected to investigate methylation between the control and DDT lineage male sperm.RESULTS: The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats were not found to develop obesity. The F1 generation DDT lineage animals did develop kidney disease, prostate disease, ovary disease and tumor development as adults. Interestingly, the F3 generation (great grand-offspring) had over 50% of males and females develop obesity. Several transgenerational diseases previously shown to be associated with metabolic syndrome and obesity were observed in the testis, ovary and kidney. The transgenerational transmission of disease was through both female (egg) and male (sperm) germlines. F3 generation sperm epimutations, differential DNA methylation regions (DMR), induced by DDT were identified. A number of the genes associated with the DMR have previously been shown to be associated with obesity.CONCLUSIONS: Observations indicate ancestral exposure to DDT can promote obesity and associated disease transgenerationally. The etiology of disease such as obesity may be in part due to environmentally induced epigenetic transgenerational inheritance.

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