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In this line of research, novel therapies aim to target apoptosis via mitochondria, using molecules that mimic BH3 proteins and disrupt the interactions of pro-apoptotic and anti-apoptotic proteins.

Therefore, the mechanisms by which mushroom extracts or isolated compounds induce mitochondrial-related apoptosis pathways are diverse and may be related with specific bioactive compounds. Modulation of pathways crucial for cell survival and alterations in lipid homeostasis seem to be related with the pro-apoptotic effects observed in HCC cell lines and in in-vivo xenograft models.

To sum up, mitochondria play a central role in the pathophysiology and progression of NAFLD as well as in the development of HCC, which can be a late-stage consequence of NASH. Hepatic mitochondria undergo bioenergetic remodelling to face the metabolic burden imposed by the increased FFAs load secondary to systemic IR. In turn, a decompensation of these processes may result in ROS formation and mitochondrial dysfunction, contributing to the development of NASH. Lastly, hepatic mitochondria also seem to be involved in anti-apoptotic oncogenic processes driving HCC. Targeting mitochondrial dysfunction is thus a promising approach for the treatment of the NAFLD continuum. The following section describes some of the in-vitro and in-vivo studies on the beneficial effects of mushroom-enriched diets or mushroom-derived compounds/extracts (Box 2) in preventing/reverting such liver damage.

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This review specifically focuses a current understanding on the dietary sources of polyphenols and their protective effects including mechanisms of action against various major human diseases.

ROS when increased or excessively produced can cause oxidative changes/damages to all cellular macromolecules

Several antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) aid in the removal of free radicals

Peroxynitrite can also destroy lipoproteins and causes lipid peroxidation of cell membranes

ROS can also affect protein synthesis and protein functions. Protein oxidation can result in amino acid modifications

Flavonoids are further classified into different subgroups based on their structures such as flavan-3-ols (examples: catechin, epicatechin, epigallocatechin), isoflavones (examples: genistein, genistin, daidzenin, daidzin, biochanin A, formononetin), flavones (examples: luteolin, apigenin, chrysin), flavonones (examples: hesperetin, naringenin), flavonols (examples: quercetin, kaempferol, galangin, fisetin, myricetin), flavononol (example: taxifolin), flavylium salts (examples: cyanidin, cyanin, pelargonidin), and flavanones (examples: hesperetin, naringenin, eriodictyol, isosakuranetin)

urther, OS exerts deleterious effects on DNA leading to the formation of DNA lesions, which can result in genomic instability and consequently lead to cell death.

Polyphenols are found naturally in fruits and vegetables such as cereals, pulses, dried legumes, spinach, tomatoes, beans, nuts, peppermint, cinnamon, pears, cherries, oranges, apples, red wine, tea, cocoa, coffee and so on (Arts and Hollman, 2005; Scalbert et al., 2005). Polyphenols are classified into different groups depending on the number of aromatic (phenolic) rings they contain and the structural elements that connect these rings. They are broadly grouped into phenolic acids, flavonoids, stilbenes and lignans

Dietary supplements containing elevated amounts of flavonoids from strawberries, lettuce, or blueberries aid in the reversal of age-related discrepancies in the brain and behavioral control in aged rats

Tea catechins

OS can be the primary or secondary reason for various CVDs. Preclinical evidence support that OS is linked to a variety of CVDs, including atherosclerosis, ischemia, stroke, cardiomyopathy, cardiac hypertrophy, and hypertension, as well as congestive heart failure

Dietary flavonoids may reduce endothelial disorders linked with various risk factors for atherosclerosis before plaque creation

The polyphenols of Hibiscus sabdariffa weaken diabetic nephropathy in terms of serum lipid profile and kidney oxidative markers

. Studies suggest that a diet that includes regular consumption of fruits and vegetables (rich in polyphenols such as catechins, resveratrol, ellagic acid, naringenin, quercetin etc.) significantly lowers the risk of developing many cancers.

Black tea polyphenols like EGCG, theaflavins and thearubigins have potent anticancer properties

Increased OS may lead to the vulnerability of the infection and also triggers the malfunctioning of cellular metabolism

which might represent a novel non-toxic alternative to conventional cancer therapy available today.

These results clearly indicate that dandelion root extract can inhibit the ability of colorectal cancer cells to migrate and invade, and therefore metastasize to secondary locations.

morphological differences in tissue slices between the control untreated and the DRE treated group

aken together, these results established that systemic oral intake of the DRE was safe and its anti-cancer efficacy should be further investigated.

, but the DRE treatment efficiently suppressed the growth of both p53 WT and p53 mutant tumors in-vivo (Figure 4B – 4C)

with no difference between the control and DRE treated samples of NCM460

We observed a decrease in the viability of cells treated with α-amyrin, with 10 μM as the most effective concentration.

The results showed a progressive destabilization of the mitochondrial membrane following the DRE treatment, which was observed as early as 30 minutes post treatment (Figure ​6C). Pro-caspase-8 (green) was localized in the mitochondria (red) in control untreated cells; however, following the DRE treatment, activated caspase-8 was released from the mitochondria into cytoplasmic space, as indicated by the dispersed green fluorescence (Figure ​6C

suggesting that in HT-29 colorectal cancer cells the DRE-induced cell death was caspase-8 independent.

Others suggest that following activation, caspases re-localize to the mitochondria, where they interact with other pro-apoptotic proteins during the progression of apoptosis [15]. A third option, put forward by Qin and colleagues, suggests that inactive caspases are kept in the mitochondria, but following apoptotic stimuli and activation, they are released from the mitochondria into the cytoplasmic peri-nuclear space [

However, these results indicate that DRE and its anti-cancer components must be absorbed and circulated, in order to reach the site of the tumor (in order to inhibit tumor growth).

, we confirmed the vulnerability of cancer cell mitochondria by showing that the DRE treatment led to a decrease in the mitochondrial membrane potential and increase in ROS levels in the isolated mitochondria.

caspase-8 specific inhibitor, IETD-fmk, did not change the DRE response in these cells. This was in contrast to our previous study in leukemia and pancreatic cancer cells

he pro-apoptotic genes including Caspase-1, Interferon gamma and the TNF ligands and receptors, were up-regulated in HT-29 cells, prior to the apoptosis induction, while the same genes were down-regulated in NCM460 cells.

Previous findings show that taraxasterol has anti-inflammatory and chemopreventive activit

suggesting its importance in the anti-cancer activity of dandelion root extract, especially on the expression levels of COX-2. Additionally, we show that 10 μM lupeol is not very effective on its own

With DRE having proven its efficacy in successfully killing this aggressive, chemoresistant form of skin cancer, DRE toxicity on normal cells had to be evaluated

DRE was found to reduce cell viability in a dose-dependent fashion, over time, in A375 melanoma cells as was measured by WST-1 assay. Based on metabolic activity of A375s, it was confirmed that treatment at 2.5 mg/mL DRE resulted in ~50% reduction in cell viability against control within 24 hours (Figure 1(a))

Higher doses were then used and a response was observed at a concentration of 10 mg/mL (

Typical apoptotic morphology was observed in G361 cells treated with DRE starting at 5 mg/mL concentrations for 72 hours

) is more than a worthy chemopreventative, it is fast-acting, nontoxic, and therefore specific in its targeting of human melanoma cancer cells, making it a valuable chemotherapeutic. We have investigated the induction of apoptosis in human malignant melanoma cells and observed its long-term effects in human melanoma cancer.

We are yet to determine the effect of each of the individual components (such as the family of triterpene alcohols and phenolic acids—found in the roots—and cinnamic acids, flavinoids and coumarins—that are found in the leaves

Given that DRE has traditionally been used naturopathically for a variety of ailments, we assume that it would be relatively nontoxic to healthy cells. Our results show that the Normal Human Fibroblasts (NHFs) (which were treated at a low population doubling where NHFs have the best proliferation rate) and Peripheral Blood Mononuclear Cells remained unaffected and healthy after a 96-hour and 48- hour exposure to DRE, respectively (Figures 2(a)–2(d)).

Lupeol,

taraxasterol

More importantly, an increase in ROS production indicates prooxidant behaviour of DRE on cancer cell mitochondria, which is contrary to the antioxidant convictions of traditional medicine and previous studies on Taraxacum extracts citing reductions in NO, ROS, RNS, and COX-2 [10, 11] in mouse macrophages.

There are two main points that must be stated here: firstly, that noncancerous cells are unaffected by DRE treatment, and secondly, melanoma cells retain the signals to commit suicide long after DRE has been removed from the system

By 48 hours, human melanoma A375 cells uncharacteristically showed susceptibility to apoptosis induction by DRE

We believe that this nontoxic extract can undergo precipitous translation from bench top to bedside, with dandelion products that are already commercially available in the form of tea and supplements.

plasticity, the ongoing process by which the complex networks and connections between neurons are wired and rewired during development and to support learning, memory, cognition, and motor function.

high levels of norepinephrine, the microglia became inactive and were unable to respond to local injuries and pulled back from their role in rewiring brain networks.

by PCR. F

Based on the results of the VlvSTS gene transcription analysis, seven transgenic tobacco lines were selected for further experiments.

Expression of the VlvSTS gene in tobacco plants led to a significant increase in the pollen grain size, but with a tendency to a decrease in the total number of pollen grains per anther

In all tests with E. carotovora bacteria, transgenic plants expressing the VlvSTS gene demonstrated a significantly higher resistance versus control plants

The leaf involvement was significantly smaller in transgenic plants expressing the VlvSTS gene.

Overexpression of the VlvSTS gene reduced the corolla pigmentation in transgenic plants.

binary vector

showed a significant fertility reduction,

For the first time it was shown that plants expressing the VlvSTS gene had enhanced resistance to the bacterial pathogen E. carotovora subsp. carotovora B15.

We were the first to show that transgenic tobacco plants carrying the VlvSTS gene had a significantly larger pollen grain size and a smaller number of pollen grains per anther. At the same time, the number of fertile pollen grains decreased, especially in the plant line with the highest expression of the VlvSTS gene.

For example, in apple plants with the grape stilbene synthase gene Vst1 under its own promoter, the expression of the gene had no effect on pollen development

The study showed that the expression of a VlvSTS stilbene syntase gene in tobacco transgenic plants increases their resistance to bacterial pathogen E. carotovora. There was a significant reduction of disease symptoms after infection of leaves by grey mould fungus B. cinerea, but not to Fusarium fungi. We were the first to show that transgenic tobacco plants carrying the VlvSTS gene had a significantly larger pollen grain size and a smaller number of pollen grains per anther. The number of fertile pollen grains decreased, especially in the plant line with the highest expression of the VlvSTS gene. These changes resulted in a decreased weight of seed bolls in the transgenic tobacco lines.