Biofilm, polyphenols, microRNA, MMPs, metastasis, and cancer

MicroRNA can be regulated by pomegranate polyphenols and fucoidan of brown seaweed which provides anti-cancer benefits.

Biofilm needs an introduction as "glycocalyx" or my phrase "our jelly lining". Picture our body as a donut 🍩 that has strawberry jam along the inner ring. Or a Jello filling in the center. For our cells to work right the fluid needs to be Jello-like. Puffy edema is too watery. If you pour acidic lemon juice onto a cold Jell-O mold then it will break down the structure wherever the higher acid liquid touched and spread from there.

Biofilm is a complex topic – a Goldilocks topic. We need biofilm in just the right amount. This post got long and I made it into a document, pdf in my sync file.

• The Glycocalyx – Our Jelly Lining. One of my very first posts has additional video of living tissue showing our extracellular matrix in action and other reference links at the end which I added later. Fiber rich foods to make our jelly lining was the initial focus of the post. *And it was my very first photo shoot for a blog graphic. (substack)

Strawberry jam on the sides of a glass jar.

I’m not sure if the jelly coated jar makes my visual point – our intestines are lined with a gooy gelatin-like layer.

Biofilm is just the same thing basically as our extracellular matrix except it is a thicker area of the Jello-like layer that surrounds cells and organs. We need this thicker goo layer along our intestinal cells to protect them. White blood cells will travel in that area looking for stuff to clean up and it helps them not be swept away with the flow of food/chyme in the intestine.

Eating a diet rich in fiber helps us have a good goo layer because it is made of fibrous starches holding onto water molecules by electrical attraction. Polyphenols and other plant chemicals also stabilize the gelatin structure of a cell.

The electricity of an acidic solution or if EMF can disrupt the goo layer like pouring lemonade on a chilled Jello mold would melt it.

<visual image, the Wicked Witch of the West being melted by Dorothy's bucket of water>.

Bacteria or cancer cells make a goo layer. Healthy cells make a goo layer. What we eat makes a difference in the goo and its ability to help white blood cells and out health or to harm it by being absent, too thin, allowing stuff in that shouldn't. And white blood cells can't travel in that, but they also would have trouble with thick sticky congestion. Some cancer cell types make thicker goo layer, or glycocalyx, and disrupting that can allow white blood cells to recognize the cells as something to remove. (Piplani, et al., 2024)

---- Biofilm is nose mucus or what we cough up from our lungs - except that would be unhealthy biofilm.

<Visual and smell image - bronchitis mucus turns greenish yellow and smells foul and that is when antibiotics are needed.>

Bitter tasting phytonutrients

Grapefruit or any other citrus peel is extremely effective at thinning over-thick mucus, and the bitter tasting phytonutrients also cause the airways to open more and cilia to move the thinned mucus up and out.

microRNA

Pomegranate and other functional foods have many phytonutrients that can help up or down regulate protein production in whichever direction is needed to reduce oxidative stress and restore balance. They do it via microRNA and that would correct epigenetic dysfunction causing production of too much if the wrong/inflammatory proteins. "Biofilm" is an important topic due to methylation cycle function in cell cytoplasm impacting whether there will be proper epigenetic control of cell nuclear DNA. No cytoplasm and mitochondrial methylation cycles and then no methylation in the nucleus and no epigenetic brakes in regarding cell growth. Like a developing baby - full forward growth but with no proper controls to guide it into baby shape.

Eating better helps make healthy cell fluid and glycocalyx/biofilm/jelly lining that will be protective and functional instead of watery or sticky and thick. "Cancer biofilm" is likely sticky and thick because cancer tends to occur in more acidic bodies and having a more acidic body is like pouring lemonade on your Jello it will mess it up. Or like adding too much vinegar to pickled eggs - the protein will condense into a tough rubbery texture instead of being like a tender hard boiled egg. Being overly acidic is also a sign that methylation cycles aren't working properly. There's lots more to correcting the dysfunction in methylation cycles but I need to go do other stuff. Healthy cell cytoplasm and jelly goo is a critical need and probably 'cancer cell biofilm' is thick sticky not healthy fluid balance in the body. Specific biofilm disrupted are not what I would focus on as much as how to get the entire body less acidic and more flowing properly.

Polyphenols from pomegranate and other superfoods are amazing because they can stabilize proteins or receptors in a beneficial shape, help stabilize the structured water - organized Jello-like aspect of our cell fluid, and turn off inflammatory protein production. So even if cells have genes saying "make this inflammatory stuff" and are producing messenger mRNA which would encode the inflammatory stuff, a plant polyphenol wants to reduce oxidative stress for the plant and it can cause microRNA to be made that will break down mRNA encoding inflammatory things.

Microbiome tangent

Pomegranate has several or more phytonutrients that help in varied ways. Whole fruit extract generally shows most benefit over isolated chemicals from it. However our healthy microbiome is part of that - of isolates, the post-biotic urolithin -A is very potent and can enter the brain. BUT only people with butyrate producing gut species will have it being made from ellagic acid from the pomegranate/ Sumac / goji berries / green tea. Those species are preferentially killed by spike. They need a lot of zinc, 30% of our intake goes to our gut microbiome. They also need resistant starch which includes the pectin/inner pith or tapioca, arrowroot or cold pasta or potatoes salad, or polenta. Corn is bad for our gut in other ways, skip the corn starch and polenta. Amaranth is polenta like after cooking and chilling.

microRNA and polyphenols:

Why do we care about microRNA? It affects gene transcription by breaking down mRNA - and polyphenols can help with the regulatory function by affecting the expression of microRNAs (miRNA).

“However, recent findings revealed that polyphenols could interact with cellular signaling cascades regulating the activity of transcription factors and consequently affecting the expression of genes. Together with this classical regulatory pathway, polyphenols have been shown to affect the expression of microRNAs (miRNA). miRNAs are small, noncoding RNAs implicated in the regulation of gene expression that control both physiological and pathological processes such as development and cancer. Furthermore, expression of miRNAs can be affected by different external stimuli including nutrients such as vitamins, lipids, and phytochemicals. In this paper, we review studies assessing modulation of miRNAs expression by dietary polyphenols that could constitute a new pathway by which these compounds may exert their health effects. Over 100miRNAs, involved in the control of different cellular processes such as inflammation or apoptosis, were identified as modulated by polyphenols.” (Milenkovic, Jude, Morand, 2013)

Solutions exist in nature.

Polyphenols including catechins can help epigenetics via modulatory effects on microRNA or non-coding RNA (ncRNA). (Shirazi-Tehrani, et al., 2022) Extensive detail about five microRNA promoted by nine different phytonutrients and the genes and pathways that they promote is available in a study by Milenkovic, et al., 2012 with apo-e -/- mice compared to wild type mice. The phytonutrient effects mitigated changes seen in the knockout mice compared to the wild type mice in addition to promoting anti-inflammatory and cell signaling effects.

The cancer industry will not listen though. Speaking to people directly is needed because good methods exist....in Mexico. Doctors have been run out of the US when they successfully treat cancer. The medical industry treats cancer as an enemy to kill and pay no attention to the fact that the body is also being killed. Then the cancer reoccurs - because the underlying issues were never addressed - AND because the cancer ‘treatments’ tend to make the underlying issues even worse (*disrupted methylation cycles, unhealthy cytoplasm and mitochondrial dysfunction).

Some people make positive changes in the effort to heal and sticking with those changes may keep them in remission, while others may still have the underlying factors going on and cancer reoccurs because something is causing methylation cycle dysfunction. That can include genetic metabolic differences, so a "healthy" diet and lifestyle might never be adequate because a high dose targeted/specific nutrient is needed or the methylation cycles slow down to acid producing rates and fatigue levels of speed.

The approach of disrupting the biofilm around a tumor to let a cancer killing agent get in better is focusing on the kill-the-enemy approach. Terrain rebuilding approach would look at making the cytoplasm healthier and promote immune function. And provide polyphenol type things that literally stop inflammatory protein production and literally stabilize our cytoplasm’s jello-like structure. Healthier cytoplasm supports aerobic methylation cycles which produce less acidic waste than anaerobic methods.

“One of the aberrations observed in cancer cells is increased glycosylation of the cell surface macromolecules [31] that collectively constitute the glycocalyx. Studies have shown that the cancer cell glycocalyx is lengthier and more heterogenous compared to normal cells [32] which leads to greater cell proliferation and invasion as a consequence of hyper-active PI3K-Akt signalling [33,34]. The glycocalyx also plays a pivotal role in modulating cell-ECM adhesions by channelling integrins at distinct sites of the cell membrane that have minimal glycosylation [33], and cell shape by altering the surface morphology [35]; both of which impact the metastatic potential. Interestingly, in breast cancer cell lines which exhibit considerable phenotypic heterogeneity, cancer stem cells (CSCs) expressing higher levels of CD44 glycoprotein were found to form the leading front during spheroid invasion [36]; similarly, overexpression of the carbohydrate binding protein - galectin-9 increased collective migration through the ECM via FAK mediated signalling [37].” […]

“Strikingly, enzymatic deglycosylation-mediated glycocalyx disruption not only reduced translocation efficiency but led to dramatic increase in the extent of nuclear damage. Collectively, these results illustrate the direct impact of the surface glycocalyx in conferring a pro-survival advantage to cancer cells by physically shielding migration-associated stresses.” (Piplani, et al., 2024)

The thicker glycocalyx protects cancer cells during migration so they are more able to metastasize without damage to the nucleus than cancer cells that had the glycocalyx broken down by deglycosylation (removal of surface sugars). (Piplani, et al., 2024)

Phytonutrients in pomegranate peel work synergistically – isolates don’t perform the same singly as a combination can perform together. (Teniente, et al., 2023) Some may affect the cancer cell glycocalyx and others affect a change that leads to apoptosis of the cancer cell.

“Similar results were obtained by Pandey et al. in SiHa cells treated with RU (40–200 µM) for 24 h, in which cell death was induced in a dose-dependent manner. This apoptotic effect was associated with the upregulation of bax and caspases 3 and 9 and the downregulation of bcl-2 expression. Moreover, the authors demonstrated that RU downregulated the expression of the jab1 oncogene, which plays a role in cancer progression by inactivating p53 and p27 tumor suppressors, leading to cell cycle arrest [99].” (Teniente, et al., 2023)

Others may affect a cancer cell’s overuse of MMP enzymes which help a metastasizing cell to ‘eat’ its way through the jello-like extracellular matrix. (Aytanski and Poretsky, 2018) Pomegranate peel extract has been observed to inhibit at least one type of MMP. (Aslam, Lansky, Varani, 2005)

“Migratory cancer cells show elevated expression MMPs, which are Calcium-dependent Zinc-containing endopeptidases capable of degrading extracellular matrix (ECM) proteins (Verma & Hansch 2007). There is a strong correlation between the MMP expression and cancer invasion and metastasis (Kanadaswami et al. 2005). MMPs participate in all stages of carcinogenesis and are particularly important for tumor invasion (McCawley & Matrisian 2000). Generally, overexpression of MMPs is linked to higher metastasis capacity in many tumors (Kanayama 2001; Saito et al. 2007; Castellano et al. 2008; Lee et al. 2008). Expression of MMPs is induced by growth factors (like epithelial growth factors [EGFs]) and receptor tyrosine kinase (RTKs) (such as EGF receptor [EGFR]) involving PI3K (phosphatidylinositol-3-kinase) and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling cascades (Sen & Chatterjee 2011).” (Aytanski and Poretsky, 2018)

Aside: Eating seaweed provides fucose, a monosaccharide that helps make necessary surface glycoproteins. Monosaccharides form a more complex language than amino acids within protein can. White blood cells recognize the branching surface sugar markers as ‘self’ or ‘foreign’. Cancer cells may form such a thick goo layer that white blood cells can’t identify what is on the cell’s surface. The modern diet is deficient in the range of monosaccharides that we need in addition to glucose to provide the complex ‘language’ that is possible with the shrubby or tree like surface glycoproteins.

We don’t need fructose, the main fruit sugar, but mannose found in cherries is one of the beneficial special monosaccharides. Glucose and fructose are the two monosaccharides that form the disaccharide, sucrose, Table sugar. Galactose and glucose are monosaccharides in lactose, the milk sugar disaccharide which some people have difficulty digesting due to lacking the enzyme lactase.

L-Fucose and D-Galactose, Fischer projection of the chemical form. Galactose has one more atom of oxygen than fucose. Both are 6 carbon monosaccharides like glucose. (Schneider, et al., 2017)

Fucose was found on 7.2% of 3299 surface glycoproteins that were examined in a study. Negatively charged sialic acid is the only more common sugar in surface proteins. We can make fucose from mannose but we would still need to eat the mannose. Ninety percent of our fucose may be formed internally from mannose. Mutations in the enzyme needed to convert mannose to fucose,  GDP-mannose-4,6-dehydratase (GMDS), has been observed in colon cancer cells. Too much or too little fucosylation may be seen in cancer cell types. (Miyoshi, et al., 2012)

“Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation.” (Miyoshi, et al., 2012)

There are thirteen known enzymes, fucosyltransferases, that can add fucose to a glycoprotein and three of them are critical for life. Genetically disabling those three causes death to knockout mice. Fucosylation can be involved in cancer and immunity. Differences in fucose are part of the difference between blood type O and types, A, B, and AB. H-antigen is secreted by people with A, B, or AB blood types and it may be protective by promoting more beneficial Lactobacillus and Bifidobacterium species in the gut, while non-secretors (about 20% of the population) may have more negative Prevotella species. The non-secretor gut microbiome profile is associated with Crohn’s disease, an inflammatory bowel condition. (Schneider, et al., 2017)

“Cancer metastasis

As a byproduct of their role in promoting selectin-mediated rolling and adhesion, Sialyl Lewis antigens play an important role in promoting cancer migration and metastasis (Kannagi 1997). These antigens are upregulated in a variety of cancer types including lung (Zenita et al. 1988), breast (Jeschke et al. 2005) and colorectal (Kudo et al. 1998; Zipin et al. 2004) cancers and serve as prognostic factors for increased risk of metastasis (Itai et al. 1991). Studies have shown that elimination of terminal fucose from these antigens with an α-l-fucosidase can impair their ability to roll within endothelial tissue and decrease cancer cell invasion (Yuan et al. 2008). Additionally, one study demonstrated that preventing terminal fucosylation by knocking down FUT1 and FUT4 inhibits tumor growth (Zhang et al. 2008). Similarly, endogenous fucosidases have been shown to play a role in preventing cancer cell proliferation. Decreased expression of α-l-fucosidase 1 (FUCA1) has been identified in a number of different cancer types including colorectal (Otero-Estévez et al. 2013; Ezawa et al. 2016), gastric (Liu et al. 2009) and breast (Cheng et al. 2015) cancers.

Altered fucosylation has also been implicated in affecting TNF-related apoptosis inducing ligand activity in colon cancer, a ligand important for promoting destruction of transformed cells. Although the precise role for fucose in the regulation of this signaling pathway remains unclear (Haltiwanger 2009), defects in the de novo synthesis of GDP-fucose cause increased tumor growth and metastasis of colon cancer in mice (Moriwaki et al. 2009).” (Schneider, et al., 2017)

How do polyphenols help against cancer metastasis? By inhibiting NFkB is the short answer. Pomegranate peel extract has also been seen to inhibit VEGF which is involved in excess blood vessel growth in a tumor.

“NF-κB is a main player in the metastatic process because it is crucial regulator of cell proliferation and survival. NF-κB levels may predict the potential of the tumor cells to metastasize (Jin et al. 2014). In resting cells NF-κB exists in inactive form, located in the cytoplasm, bound to a family of inhibitory proteins referred as IκB (inhibitors of κB). Members of IκB family include IκB-α, IκB-β, IκB-γ, IκB-ε, IκB-ζ, p105, p100, and bcl3, as IκB-α (also known as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha [NFKBIA]) is the most abundant among them. The control of NF-κB activity is carried out by IκB kinase (IKK) kinases which include mitogen-activated protein kinase kinase (MAPKK) family comprising of NF-κB-inducing kinase (NIK) and MAPK/ERK kinase kinase (MEKK) 1, 2, and 3. When activated, NF-κB translocates to the nucleus where it serves as transcription factor regulating genes controlling cell cycle, apoptosis, transformation, and other processes. Constitutively active NF-κB is characteristic for many cancers. It protects the activation of apoptotic signal by inhibiting p53 activity thus promoting the survival and neoplastic transformation of the cancer cells. The NF-κB signaling induces the expression of a number of target genes involved in angio- and lymphangiogenesis among them the vascular endothelial growth factor (VEGF). NF-κB directly induces the expression of urokinase-type plasminogen activator (uPA) (Sliva et al. 2002), MMP-9, and chemokine receptor CXCR4 (Helbig et al. 2003), which in turn results in promotion of ECM degradation and metastasis. The regulation of tumor metastasis by NF-κB is exerted by reciprocal regulation of prometastatic (heparanase, etc.) and antimetastatic (MMP-1, MMP-2, plasminogen activator inhibitor [PAI]-2, etc.) factors. Thus NF-κB is considered as an attractive candidate for metastasis treatment.”  (Avtanski and Poretsky, 2018

Fucoidan, found in brown seaweed helps against cancer by affecting two microRNAs. (Wu, et al., 2016) Species of seaweed with fucoidan include: Fucus vesiculosus (wracks), Cladosiphon okamuranus, Laminaria japonica (kombu, sugar kelp) and Undaria pinnatifida (wakame). (Wikipedia)

“In this study, we observed that brown seaweed fucoidan inhibited human breast cancer progression by upregulating microRNA (miR)-29c and downregulating miR-17-5p, thereby suppressing their target genes, a disintegrin and metalloproteinase 12 (ADAM12) and phosphatase and tensin homolog (PTEN), respectively.” (Wu, et al., 2016)

If breast cancer cell dysfunction can be controlled by microRNA affected by eating wakame and kombu, or pomegranate peel, or turmeric, then why are toxic chemotherapy and radiation still being used? If microRNA can prevent metalloproteinase overactivity, then a cancer cell would be unable to migrate as well, because it could no longer ‘eat’ its way through our Jello-like extracellular fluid.

Sialic Acid

Other background info: Sialic acid in surface proteins adds a negative charge which helps keep the sides of the intestinal wall open by constantly repelling each other. Red blood cells in health are covered with negatively charged sialic acid rich glycoproteins. Chimeric spike can disrupt sialic acid and red blood cell rouleaux/coin-stacking is seen in the blood.

We cannot eat sialic acid to get more, we have to make it or maybe swap – put extra sialic acid from one place onto another place. Eating foods with nucleotides can save some steps in the assembly process. That might include sardines and a variety of other animal products and for vegans, two teaspoons of Nutritional Yeast Flakes per day can help provide some nucleotides.

We have to make nucleotides or eat them in order to be able to make RNA and DNA. It takes 14 enzymatic steps to make one nucleotide. A strand of mRNA may have 100s of nucleotides. Eating some in our diet can save us energy and time. A fragile, malnourished, or elderly person may not be making a lot of chemicals as well as they used to, even if the genes to do so are not dysfunctional alleles - even if the person had been able to make the chemicals fine for the majority of their lives. Now they aren’t able to very well so eating more nutritious foods becomes more essential for basic function and overall health.

~~~

I’m not sure if I made my point - polyphenols and other phytonutrients can help the body stop making bad proteins even if a cell’s epigenetic control is lost. They can up or downregulate microRNA expression which can then stop mRNA from being made into a protein by a cell, or promote other types of mRNA. Plant nutrients figure out what is needed to restore balance and reduce inflammation based on the inflammatory environment that is present. Is it a drought or a flood? Is it cloudy and cold or super hot noonday sun? The plant chemicals respond to environmental cues without a cancer doctor being anywhere near.

Breaking up a biofilm layer on a pathogenic cell or thinning overly concentrated ‘mucus,’ extracellular fluid, is also part of what plant polyphenols are used to doing when necessary. Life is more like the ocean, and it is up to a cell or plant or animal to keep its fluid and mineral balance in the desirable ocean like ratio instead of becoming too watery or too thick and gooey. Breaking up the thick biofilm around cancer cells or a pathogenic microbe takes away its protective layer that can help a cancer cell to metastasize and protect the cancer or pathogenic microbe from being detected and removed by white blood cells.

While the underlying dysfunction in the cytoplasm that prevents methylation cycles from occurring aerobically needs to be corrected to prevent more cancer from occurring, eating the plant nutrients that can regulate microRNA can help mitigate for the bad epigenetics of cancer cells that are growing without epigenetic “off” switches. Why don’t all plants get nonstop growth? Because they have only certain functions turned on at any one time.

The cancer industry may not like being second fiddle to a not patentable seaweed or fruit peel, but that’s the facts Jack. (Bill Murray, Stripes)

Addition - my reply to a question about what seaweed to eat and how much.

Kombu is high in salicylate and is generally added to soup broth or a batch of beans, a one inch piece. It reduces gassiness of beans and makes the broth creamier.

Wakame is the lettuce like seaweed used to make a cold vegetable salad in Thai or Vietnamese cuisine.

This post, Meals for Trace Minerals and Iodine, has a menu handout by a different dietitian to which I added a section on types of seaweeds. Eating a serving (one tablespoon dried roughly) daily or 5 times a week would be a good dietary goal or any versus none. (substack) How much specific to breast cancer? that is harder to know but I would suggest just be sensible and try some, see how you feel. Bucket loads would be too much.

Hijiki is a seaweed that has been found to have some contaminants occasionally and Arame is similar and doesn't have that concern.

I have used this Emerald Cove brand of Arame and Wakame. vitacost.com/emerald-cove-pacific-arame Eden Foods is a reputable brand too. Japanese brands may be fine too, but I can’t read the Japanese label.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

References

(Aslam, Lansky, Varani, 2005) Aslam MN, Lansky EP, Varani J. Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells. J Ethnopharmacol. 2006 Feb 20;103(3):311-8. doi: 10.1016/j.jep.2005.07.027. Epub 2005 Oct 10. PMID: 16221534. https://pubmed.ncbi.nlm.nih.gov/16221534/

(Avtanski and Poretsky, 2018) Avtanski D, Poretsky L. Phyto-polyphenols as potential inhibitors of breast cancer metastasis. Mol Med. 2018 Jun 5;24(1):29. doi: 10.1186/s10020-018-0032-7. PMID: 30134816; PMCID: PMC6016885. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016885/

Milenkovic, D., Jude, B., Morand, C., (2013). ‘miRNA as molecular target ofpolyphenols underlying their biological effects’. Free Radic Biol Med.Sep;64:40-51. doi: 10.1016/j.freeradbiomed.2013.05.046. Epub 2013 Jun 7. PMID:23751562. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0891584913002748?via%3Dihub  (Accessed 24 Nov 2022)

Milenkovic, D., Deval, C., Gouranton, E., Landrier,J.F., Scalbert, A., Morand, C., Mazur, A., (2012). ‘Modulation of miRNA expression by dietary polyphenols in apoE deficient mice: a new mechanism of the action of polyphenols’. PLoS One. 7(1):e29837. doi:10.1371/journal.pone.0029837. Epub 2012 Jan 10. PMID: 22253797; PMCID:PMC3254631. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029837 (Accessed: 27 Nov 2022)

(Miyoshi, et al., 2012) Miyoshi E, Moriwaki K, Terao N, Tan C-C, Terao M, Nakagawa T, Matsumoto H, Shinzaki S, Kamada Y. Fucosylation Is a Promising Target for Cancer Diagnosis and Therapy. Biomolecules. 2012; 2(1):34-45. https://doi.org/10.3390/biom2010034 https://www.mdpi.com/2218-273X/2/1/34

(Piplani, et al., 2024) Niyati Piplani, Tanusri Roy, Neha Saxena, Shamik Sen, Bulky glycocalyx shields cancer cells from invasion-associated stresses, Translational Oncology, Volume 39, 2024, 101822, ISSN 1936-5233, https://doi.org/10.1016/j.tranon.2023.101822. https://www.sciencedirect.com/science/article/pii/S1936523323002085

(Schneider, et al., 2017) Schneider M, Al-Shareffi E, Haltiwanger RS. Biological functions of fucose in mammals. Glycobiology. 2017 Jul 1;27(7):601-618. doi: 10.1093/glycob/cwx034. PMID: 28430973; PMCID: PMC5458543. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458543/

Shirazi-Tehrani, E., Chamasemani, A., Firouzabadi, N., Mousaei, M., (2022). ‘‘ncRNAs and polyphenols: new therapeutic strategies for hypertension, RNA Biology, 19:1, 575-587, DOI: 10.1080/15476286.2022.2066335Available at: https://www.tandfonline.com/doi/full/10.1080/15476286.2022.2066335  (Accessed 24 Nov 2022)

(Teniente, et al., 2023) Teniente SL, Flores-Gallegos AC, Esparza-González SC, Campos-Múzquiz LG, Nery-Flores SD, Rodríguez-Herrera R. Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer. Antioxidants. 2023; 12(1):127. https://doi.org/10.3390/antiox12010127 https://www.mdpi.com/2076-3921/12/1/127

(Wu, et al., 2016) Wu SY, Wu AT, Yuan KS, Liu SH. Brown Seaweed Fucoidan Inhibits Cancer Progression by Dual Regulation of mir-29c/ADAM12 and miR-17-5p/PTEN Axes in Human Breast Cancer Cells. J Cancer. 2016 Dec 9;7(15):2408-2419. doi: 10.7150/jca.15703. PMID: 27994679; PMCID: PMC5166552. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166552/