PMID: 

Int J Mol Sci. 2018 Jun 13 ;19(6). Epub 2018 Jun 13. PMID: 29899271

Abstract Title: 

The Effects of Combinatorial Genistein and Sulforaphane in Breast Tumor Inhibition: Role in Epigenetic Regulation.

Abstract: 

Dietary compounds that possess the properties of altering epigenetic processes are gaining popularity as targets for cancer prevention studies. These compounds when administered at optimal concentrations and especially in combination can have enhanced effects in cancer prevention or therapy. It is important to study the interaction of two or more compounds in order to assess their role in enhancing prevention. Genistein (GEN), found in soy, has been extensively studied for its role as an epigenetic modifier especially as a DNA methyltransferase (DNMT) inhibitor and sulforaphane (SFN), found in cruciferous vegetables, is known as a histone deacetylase (HDAC) inhibitor. However, very little is known about the effects of these two compounds in conjunction in breast cancer prevention or therapy. In our current study, we determined that, at certain doses, the compounds have synergistic effects in decreasing cellular viability of breast cancer cell lines. Our results indicate that the combination of GEN and SFN is much more effective than their single doses in increasing the rate of apoptosis and lowering the colony forming potential of these cells. We determined that these compounds inhibit cell cycle progression to G2 phase in MDA-MB-231 and G1 phase in MCF-7 breast cancer cell lines. Additionally, we determined that the combination is effective as an HDAC and histone methyltransferase (HMT) inhibitor. Furthermore, we demonstrated that this combination downregulates the levels of HDAC2 and HDAC3 both at the mRNA and protein levels. We also found that these compounds have the potential to downregulate KLF4 levels, which plays an important role in stem cell formation. The combination of GEN and SFN is also effective in downregulating hTERT levels, which is known to be activated when KLF4 binds to its promoter region. Our hypothesis is further strengthened bystudies, where the combination is administered to transgenic mice in the form of genistein and SFN-enriched broccoli sprouts. We have demonstrated that the combination is more effective in preventing or treating mammary cancer via extending tumor latency and reducing tumor volumes/sizes than either of these dietary components administered alone. These results are consistent with ourstudy suggesting potential preventive and therapeutic effects of this novel dietary combinatorial approach against breast cancer.

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PMID: 

Mol Nutr Food Res. 2018 09 ;62(18):e1800079. Epub 2018 Aug 29. PMID: 30079608

Abstract Title: 

Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention.

Abstract: 

Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although not yet completely understood, many mechanisms of anticancer activity at the steps of cancer initiation, promotion, and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro-growth, pro-survival, pro-inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their antitumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden.

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PMID: 

J BUON. 2019 Nov-Dec;24(6):2442-2447. PMID: 31983118

Abstract Title: 

Xanthohumol chalcone acts as a powerful inhibitor of carcinogenesis in drug-resistant human colon carcinoma and these effects are mediated via G2/M phase cell cycle arrest, activation of apoptotic pathways

Abstract: 

PURPOSE: Xanthohumol is a prenylated flavonoid of plant origin and has been reported to exhibit a spectrum of pharmacological properties including anticancer effects. However, the anticancer properties of Xanthohumol have not been thoroughly evaluated against drug-resistant colon cancer cells. This study was undertaken to evaluate the anticancer effects of Xanthohumol against the human colon cancer cell line HT-29 and normal CDD-18Co cell line.METHODS: HT-29 cell viability was evaluated by cell counting kit-8 (CCK8) assay. Apoptotic effects were examined by fluorescence microscopy using DAPI staining and flow cytometry using annexin V/propidium iodide (PI) staining. Effects on cell cycle were studied by flow cytometry while western blot analysis was done to study effects on protein expressions.RESULTS: The results showed that Xanthohumol causes a dramatic decrease in the HT-29 cell viability with an IC50 of 10µM. However, an IC50>100µM for Xanthohumol against the normal CDD-18Co cells suggested cancer cell specific activity. DAPI staining revealed nuclear fragmentation, suggesting xanthohumol induces apoptosis in HT-29 cells. Xanthohumol also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Cell cycle analysis showed that this molecule caused arrest of the HT-29 cells at the G2/M phase of the cell cycle. The induction of G2/M cell cycle was also accompanied with depletion of the expression of cyclin B1. The effects of Xanthohumol were also investigated on the Ras/MEK/ERK signalling pathway which revealed that Xanthohumol also blocks the MEK/ERK signalling pathway in colon cancer cells in a concentration-dependent manner.CONCLUSIONS: Xanthohumol may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.

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PMID: 

Spectrochim Acta A Mol Biomol Spectrosc. 2020 Jan 25 ;231:118112. Epub 2020 Jan 25. PMID: 32014658

Abstract Title: 

Prostate and breast cancer cells death induced by xanthohumol investigated with Fourier transform infrared spectroscopy.

Abstract: 

Fourier Transform Infrared spectroscopy was applied to detect in vitro cell death induced in prostate (PC-3) and breast (T47D) cancer cell lines treated with xanthohumol (XN). After incubation of the cancer cells with XN, specific spectral shifts in the infrared spectra arising from selected cellular components were identified that reflected biochemical changes characteristic for apoptosis and necrosis. Detailed analysis of specific absorbance intensity ratios revealed the compositional changes in the secondary structure of proteins and membrane lipids. In this study, for the first time we examined the changes in these molecular components and linked them to deduce the involvement of molecular mechanisms in the XN-induced death of the selected cancer cells. We showed that XN concentration-dependent changes were attributed to phospholipid ester carbonyl groups, especially in the case of T47D cells, suggesting that XN acts as an inhibitor of cell proliferation. Additionally, we observed distinct changes in the region assigned to the absorption of DNA, which were correlated with a specific marker of cell death and dependent on the XN dose and the type of cancer cells. The microscopic observation and flow cytometry analysis revealed that the decrease in cancer cell viability was mainly related to the induction of necrotic cell death. Moreover, the T47D cells were slightly more sensitive to XN than the PC-3 cells. Considering the results obtained, it can be assumed that apoptosis and necrosis induced by XN may contribute to the anti-proliferative and cytotoxic properties of this flavonoid against cancer cell lines PC-3 and T47D.

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PMID: 

Toxicol In Vitro. 2020 Feb 15:104799. Epub 2020 Feb 15. PMID: 32070777

Abstract Title: 

Combination of xanthohumol and phenethyl isothiocyanate inhibits NF-κB and activates Nrf2 in pancreatic cancer cells.

Abstract: 

Phytochemicals such as phenethyl isothiocyanate (PEITC), indole-3-carbinol (I3C), xanthohumol (XAN), and resveratrol (RES) have been shown to target signaling pathways that are involved in the proliferation and survival of different pancreatic cancer (PC) cell lines. While the activity of these compounds alone was extensively studied, their combinations were never assessed. Thus, the aim of this study was to evaluate and compare the effect of PEITC, I3C, XAN, and RES and their combinations on the expression and activation of NF-κB and Nrf2 in human PC cell line PANC-1. The combination of XAN and PEITC was more efficient than the single compounds in reducing the binding of NF-κB p65 subunits by 47-60% and expression of p65 gene by 28-48%. The combination of XAN and PEITC also enhanced the activation and expression of Nrf2and subsequently the expression of GSTP, NQO1, and SOD genes which are controlled by this transcription factor. Modulation of the activity of NF-κB and Nrf2 by the combination of XAN and PEITC was found to lead to reduced proliferation of PANC-1 cells. These results suggest that the combination ofXAN and PEITC might be considered as a novel strategy for the prophylaxis and/or treatment of PC.

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PMID: 

Mol Nutr Food Res. 2018 12 ;62(24):e1800427. Epub 2018 Nov 22. PMID: 30302904

Abstract Title: 

Sulforaphane Normalizes Intestinal Flora and Enhances Gut Barrier in Mice with BBN-Induced Bladder Cancer.

Abstract: 

SCOPE: Gut microbiota imbalance, inflammation, and gut barrier deficiency play an important role in carcinogenesis. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, has been proven to be highly effective in inhibiting cancer. The objective of this study is to investigate the potential roles of the gut microbiota in the inhibition of BBN-induced bladder cancer by SFN.METHODS AND RESULTS: N-butyl-N-(4-hydroxybutyl)-nitrosamine is used to induce bladder cancer in male C57BL/6 mice, with or without SFN for 23 weeks. SFN ameliorates the histological changes characteristic of bladder cancer, resulting in fewer submucosal capillaries. SFN normalizes gut microbiota dysbiosis in mice with BBN-induced bladder cancer with a significant increase in Bacteroides fragilis and Clostridium cluster I. SFN also increases butyric acid levels in the mouse colon, and repairs the injury to the mucosal epithelium of the colon and cecum through the upregulation of the expression of tight junction proteins and GLP2. SFN greatly decreases the release of cytokines (IL-6) and secretory immunoglobulin A in the mice with bladder cancer.CONCLUSION: These results suggest that SFN protects against chemical-induced bladder cancer through normalizing the composition of gut microbiota and repairing the physiological destruction of the gut barrier, as well as decreasing inflammation and the immune response.

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PMID: 

Neuroscience. 2020 Feb 4. Epub 2020 Feb 4. PMID: 32032666

Abstract Title: 

Meditation Increases the Entropy of Brain Oscillatory Activity.

Abstract: 

We address the hypothesis that the entropy of neural dynamics indexes the intensity and quality of conscious content. Previous work established that serotonergic psychedelics can have a dysregulating effect on brain activity, leading to subjective effects that present a considerable overlap with the phenomenology of certain meditative states. Here we propose that the prolonged practice of meditation results in endogenous increased entropy of brain oscillatory activity. We estimated the entropy of band-specific oscillations during the meditative state of traditions classified as 'focused attention' (Himalayan Yoga), 'open monitoring' (Vipassana), and 'open awareness' (Isha Shoonya Yoga). Among all traditions, Vipassana resulted in the highest entropy increases, predominantly in the alpha and low/high gamma bands. In agreement with previous studies, all meditation traditions increased the global coherence in the gamma band, but also stabilized gamma-range dynamics by lowering the metastability. Finally, machine learning classifiers could successfully generalize between certain pairs of meditation traditions based on the scalp distribution of gamma band entropies. Our results extend previous findings on the spectral changes observed during meditation, showing how long-term practice can lead to the capacity for achieving brain states of high entropy. This constitutes an example of an endogenous, self-induced high entropy state.

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PMID: 

Complement Ther Clin Pract. 2020 Feb ;38:101079. Epub 2019 Dec 14. PMID: 32056815

Abstract Title: 

Effects of yoga on anxiety and depression for high risk mothers on hospital bedrest.

Abstract: 

BACKGROUND: and purpose: In recent years, yoga practitioners have joined forces with medical programs to approach patients' well-being holistically. This study is a randomized controlled trial to assess the effects of a specialized adapted yoga program on anxiety and depression for high-risk expectant mothers on bedrest in a hospital setting.MATERIALS AND METHODS: Seventy-nine pregnant subjects on physician ordered hospitalized bedrest were randomized into two groups: receiving biweekly yoga sessions (intervention group) or receiving no yoga (control group). Data collection tool was the Hospital Anxiety and Depression Scale (HADS) to assess outcomes after delivery.RESULTS: Yoga, even as little as three sessions, showed significant impact in reducing anxiety and depression high-risk pregnant women on hospitalized bedrest. Perceived anxiety and depression overall scores were lower in the intervention group than in the control group (p 

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PMID: 

Neuroepidemiology. 2020 Feb 19:1-17. Epub 2020 Feb 19. PMID: 32074622

Abstract Title: 

Effectiveness of Yoga as the Public Health Intervention Module in the Management of Diabetes and Diabetes Associated Dementia in South East Asia: A Narrative Review.

Abstract: 

BACKGROUND: Diabetes mellitus (DM) is widely spread in South Asian (ASEAN) and Indian sub-continent. The increasing healthcare costs of DM can be prevented in the developing world by improved public healthcare interventions. Modifiable risk factors of DM like sedentary lifestyle, obesity, and stressful conditions are associated with its progression; however, the epidemiological data collected by Public Institutions are limited.SUMMARY: A review of published literature describing geographic distribution of DM and associated dementia in South Asian region, particularly India, was conducted with the purpose of assessing the feasibility and challenges associated with the Yoga-based risk reduction. PubMed and Google Scholar databases were searched for DM and dementia-related articles by using a combination of keywords: Diabetes, Diabetes related Dementia Southeast Asia, Pre-diabetes, Yoga, lifestyle modification, Dementia and Exercise. The epidemiological data generated from these diseases have not prompted to any major public health policies. Yoga can be a cost-effective intervention for the prevention of Type 2 DM (T2DM) and its associated cognitive decline when detected early. If nationwide intervention of Yoga is brought about by the state, its integration in health care will become more meaningful and acceptable. Key Message: Studies suggest that Yoga and change in lifestyle can modify the health risks associated with T2DM and associated dementia if it is mainstreamed with the public health initiative of Ayushman Bharat scheme.

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PMID: 

Arch Gynecol Obstet. 2020 Jan ;301(1):53-60. Epub 2020 Feb 14. PMID: 32060683

Abstract Title: 

Polycystic ovary syndrome management: a review of the possible amazing role of berberine.

Abstract: 

PURPOSE: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment.METHODS: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management.RESULTS: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates.CONCLUSIONS: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.

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