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Hannah Herrera

Space travel alters gene expression in white blood cells, weakening our immune system -... - 1 views

  • Space travel alters gene expression in white blood cells, weakening our immune system
    • Hannah Herrera
       
      very interesting article, there is a conclusion with insights to this underlining issue in the "read original paper" link in red. I overall think its a ear pricking issue that has yet to be solve or given the clear conclusion as to why it happens in the first place.
  • pre-flight strength: the length of this period is likely to depend on age, sex, genetic differences, and childhood exposure to pathogens.
  • These observations suggest that our immune system might be weakened by space travel.
    • Hannah Herrera
       
      could it have a possible connection with the strong gravitational pull while actually going up to space? (like the continuing feeling of a steep rollercoaster drop).
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  • change in gene expression of leukocytes under microgravity is triggered by ‘fluid shift’, where blood plasma is redistributed from the lower to the upper part of the body, including the lymphatic system. This causes a reduction in plasma volume by between 10% and 15% within the first few days in space. Fluid shift is known to be accompanied by large-scale physiological adaptations, apparently including altered gene expression.
katherine-medina

IJMS | Free Full-Text | Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched D... - 0 views

  • In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression.
  • non-alcoholic steatohepatitis (NASH)
    • katherine-medina
       
      I like the abbreviation
  • NASH is currently the third most common indication for liver transplantation in the United States and accounts for 10% of all HCC cases in Europe
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  • The increase in nutrient availability causes systemic metabolic alterations that lead to an increase in hepatic mitochondrial respiration as well as changes in the mitochondrial lipid membrane composition.
  • They are also rich in phenolic acids, such as hydroxybenzoic and hydroxycinnamic acid, flavonoids, tocopherols, ascorbic acid and carotenoids that are known for their antioxidant activity
    • katherine-medina
       
      They are high in polyphenols, just like I had thought, I do wonder if they have tried to single out a certain flavonoid or stilbene in order to determine whether or not it was the mechanism that caused the positive reaction.
  • Of note, indeed NAFLD patients present a “metabolic inflexibility”, that is, a reduced capacity to switch back from
    • katherine-medina
       
      I did not know that
  • The increased levels of β-oxidation seem to result in an increase in citrate within the mitochondrial matrix that can be transported to the cytosol via the citrate-malate shuttle and converted to acetyl-CoA and oxaloacetate by the enzyme ATP-citrate lyase [90,106]. Indeed, NAFLD patients present increased citrate levels in plasma
  • An alternative explanation for the deficient mitochondrial respiration might be the alterations in the mitochondria lipid composition, which are already present in steatosis.
  • As defined by mitohormesis, ROS production is physiological at low levels, acting as a crucial effector in proliferation, expression of antioxidant enzymes and insulin signalling. However, high levels of ROS formation causes oxidative stress and cell damage by reacting with its different components [90,114,115]. Oxidative stress occurs when the antioxidant capacity of the cell is not sufficient to neutralize the overproduction of ROS. ROS generation causes the peroxidation of phospholipids and cardiolipin at the mitochondrial membrane
  • All these mechanisms seem to be involved in the progression from NAFL to NASH. Indeed, NASH patients present increased ROS production, DNA damage, as measured by 8-Oxo-2’-deoxyguanosine (8OHdG) levels, and hepatic lipid peroxidation coupled with decreased expression of ETC Com
    • katherine-medina
       
      So essentially NASH patients have a higher level of ROS which damages their DNA. increase of ROS = DNA damage
  • In parallel, the negative regulation on the inhibitor of apoptosis proteins (IAPs) mediated by the translocation of a series of IAP antagonists such as Smac, HTRA2/Omi and apoptosis-related protein in the TGF-ß signalling pathway (ARTS) to the cytosol, results in the release and activation of caspases
  • Aiming at weight loss, calorie-restricted diets and regular physical activity can improve hepatic mitochondria dysfunction by decreasing FFA liver input and alleviating oxidative stress.
  • New therapies need to be developed to target NAFLD and NASH,
    • katherine-medina
       
      Are there any new therapies to treat NASH and NAFLD
  • showed lipid metabolism-modulating properties in the liver
  • This may lead to a decrease in lipogenesis and a concomitant increase in β-oxidation that could explain the reduction in IHTG content [203]. Similarly, the supplementation with a 1% aqueous extract of A. cinnamomea for 8 weeks reduced the expression of leptin and increased the expression of adiponectin, which was accompanied by an increase of AMPK and PGC-1α and a reduced expression of ACC, FAS and SREBP
  • IHTG content that was similar to the positive control group, treated with rosiglitazone, a PPAR-agonist antidiabetic drug
    • katherine-medina
       
      Interesting, I wonder if there is more that can be done with this extract with these types of effects.
  • herefore, these studies suggest a pivotal capacity of mushroom extracts to counteract the detrimental oxidative damage of mitochondria in NAFLD.
  • which seems to exacerbate NASH. H2O2 over-production may open the mPTP, while its transmembrane diffusion to the cytoplasm may even result in highly detrimental OH• formation. [93,131,132]. In contrast, the capacity of mushroom extracts from species such as Pleurotus ostreatus (Jacq.) P. Kumm. (oyster mushroom) or G. lucidum to elevate the entire antioxidant defence system of hepatocytes, seems a more promising therapeutic effect against the oxidative stress in NASH.
  • . Such evidence further supports the potential of G. lucidum extracts in reversing mitochondrial dysfunction in NAFLD.
  • 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.
  • Both aqueous and ethanol extracts, or isolated compounds (GL22 from Ganoderma leucocontextum T.H Li, W.Q. Deng, Dong M. Wang & H.P. Hu) increased the pro-apoptotic Bax to anti-apoptotic Bcl-2/Bcl-xL ratio
  • The antitumorigenic effects of mushroom extracts and isolated compounds have also been demonstrated in in-vivo xenograft models, resulting in tumour size reduction and increased animal survival rates (Table 2). Furthermore, in the HCC Huh7 xenograft mice model, fatty acid binding 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.
    • katherine-medina
       
      Cool
  • 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.
  • This distinct property of mushroom-based therapy or -containing diet is especially relevant in the multifactorial context of NAFLD and especially NASH, where systemic synergistic metabolic alterations need to be addressed.
  •  
    An article detailing a bit of the effects that mushrooms can have on the liver's mitochondrial cells.
katherine-medina

Effects of experimental increase in insulin-like growth factor 1 on feather growth rate... - 0 views

  • In mammals, IGF-1 also induces the proliferation of hair follicles and inhibits apoptosis, and therefore helps to keep them longer in the active (so-called anagen) phase and delay their transition to the regressive (catagen) phase
  • while a recently published study indicated a positive relationship between plumage quality, feather vane length and IGF-1 in a passerine species
  • Detailed quantification of the moulting stage was achieved by scoring the moult of the primary wing feathers and tail feathers on a scale of 0–5, using the standard protocol for recording the progress of feather growth as suggested by the British Trust for Ornithology and further described in
    • katherine-medina
       
      I had no idea one could predict when a bird will molt.
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  • As a result, 2 weeks after treatment, IGF-1-treated birds were in a more advanced stage of moult than controls
    • katherine-medina
       
      Interesting
  • In the longer term, IGF-1 treatment altered the intensity of moult: 2 weeks after treatment, control birds were moulting fewer feathers than at the start of the experiment, while IGF-1-treated birds showed the opposite pattern and increased the number of feathers being moulted simultaneously, albeit with substantial individual variation
  • We manipulated IGF-1 levels using an injection of poly-(lactic-co-glycolid acid) (PLGA) microspheres prepared by S.V.-K. and B.A.G. as described previousl
  • For example, stressors may cause a decrease in circulating IGF-1 levels (Tóth et al., 2018), and it may not be beneficial if that would affect the growth rate or the size of the developing flight feathers.
  • The fact that the growth of the tail feathers was also unaffected by the manipulation is more surprising as they are sexually selected ornaments in this species
    • katherine-medina
       
      Wow, I wonder why it had no effect on the growth of the tail feathers.
  • espite the robust lack of effect on feather growth speed, IGF-1 treatment maintained or even increased the number of feathers moulted simultaneously within 2 weeks, while the number of simultaneously growing feathers dropped in controls within the same period
    • katherine-medina
       
      Cool
  • In contrast to hair, the number of feather follicles that produce wing and tail feathers is small and shows no variation within species
    • katherine-medina
       
      I had no idea.
  • Some species, however, moult several wing and tail feathers simultaneously, which also applies to the bearded reedling
    • katherine-medina
       
      Why do some species of birds molt more feathers at the same time than others.
  • . Protein synthesis in tissues, for example, is partly promoted by and regulated through IGF-1 and this might also be of importance during the growth of feathers, in particular considering the increased demand for proteins during moulting
  • The interaction of corticosterone and IGF-1 has been suggested to predict fitness in growing songbirds (Lodjak et al., 2016). Corticosterone levels are known to have a seriously detrimental effect on growing feathers
    • katherine-medina
       
      How does corticosterone and IGF-1 interact?
  •  
    A study about the effect of insulin on the growth of feathers.
katherine-medina

Dandelion root extract affects colorectal cancer proliferation and survival through the... - 0 views

  • of an aqueous dandelion root extract
  • caspase-8 activation was not essential for the induction of cell death in colon cancer cells as an inhibition of caspase-8 activation did not alter the cytotoxicity of DRE
  • We have been able to identify four pharmacologically active components, α-amyrin, β-amyrin, lupeol and taraxasterol, in two out of the six bioactive fractions, but the anti-cancer activities of the individual compounds were not as strong as that of the unfractionated DRE indicating, clearly, the benefits of using the whole extract.
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  • 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.
    • katherine-medina
       
      Wow. I like to see that in 3 different studies DRE was proven to selectively pick the cancer cells, and ignore the normal cells.
  • 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.
    • katherine-medina
       
      I love the fact that they yet again state that I should look more into this topic.
  • , but the DRE treatment efficiently suppressed the growth of both p53 WT and p53 mutant tumors in-vivo (Figure 4B – 4C)
    • katherine-medina
       
      great, they suppressed the growth of the tumors.
  • with no difference between the control and DRE treated samples of NCM460
    • katherine-medina
       
      I would not have thought that the mitochondria would be left alone by the drug.
  • We observed a decrease in the viability of cells treated with α-amyrin, with 10 μM as the most effective concentration.
    • katherine-medina
       
      Hmm. the beginnings of narrowing down what it is about the plant that is able to fight cancer.
  • 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
    • katherine-medina
       
      Pro-capase-8 helps to fight against the cancer
  • suggesting that in HT-29 colorectal cancer cells the DRE-induced cell death was caspase-8 independent.
    • katherine-medina
       
      So essentially caspase 8 had nothing to do with it
  • 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).
    • katherine-medina
       
      So it needs to be drank, or swallowed in a pill form to work.
  • , 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
    • katherine-medina
       
      For each different cancer a new slightly different result is produced
  • 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
  •  
    Yet another article about how DRE can fight against cancer.
katherine-medina

Full article: Effect of Dandelion root extract on growth performance, immune function a... - 0 views

  • From days 12 to 14 and days 26 to 28, approximately 100 g of faeces was collected from each pen for 3 days and the faecal samples were stored at −20°C. The 3-d faecal collection was pooled by pen and then dried at 65°C for 72 h.
  • From days 12 to 14 and days 26 to 28, approximately 100 g of faeces was collected from each pen for 3 days and the faecal samples were stored at −20°C. The 3-d faecal collection was pooled by pen and then dried at 65°C for 72 h.
    • katherine-medina
       
      Kinda gross, but interesting to know how and when the collected the "feces."
  • There were no differences in the ATTD of GE, CP, NDF and ADF among the three treatments.
    • katherine-medina
       
      Interesting that there was no difference between the three groups in that category.
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  • uring days 15–28, pigs in the CHE group had lower (P < .05) diarrhoea frequency compared with those in the NC treatment, and dietary CHE supplementation decreased the diarrhoea frequency by 63.62% and 57.82% compared with the NC and PC groups, respectively
    • katherine-medina
       
      So the Chinese herbal extract did a better job at reducing the diarrhoea frequency by 63.62 and 57.82% in comparison to the NC and PC groups.
  • Moreover, the concentration of IL-6 in serum in pigs fed the CHE diet was greater (P < .05) than those fed the NC diet.
  • There were no differences in the concentrations of IgA, IgG, IgM, GSH-PX, MDA, TNF-α, IL-4 and IL-1β among the three treatments.
  • Furthermore, pigs in the CHE group had greater (P < .05) formic acid, propionate and butyrate concentrations in faeces compared with pigs in the PC group, and had greater (P < .05) formic acid, butyrate and valerate concentrations in faeces compared with pigs in the NC group
    • katherine-medina
       
      Cool to note that the CHE group had a lower lactic acid concentration in comparison to the PC group.
  • Pigs in the CHE group showed increased relative abundance of Sytrophococcus on genus level, and decreased (P < .05) relative abundance of Clostridiaceae_1
  • In addition, relative abundances of genus Selenomonas, Alloprevotella, Prevotella_2, Rjkenellaceae, and Kitasatospora all increased in faecal samples when pigs fed the PC diet.
  • CHE supplementation decreased the diarrhoea frequency of pigs compared with diets with or without antibiotics supplemented. Some previous studies also reported the positive effects of dietary Chinese herbs supplementation on diarrhoea frequency of weaned pigs
  • he increased concentrations of immune markers in serum and faecal SCFAs in weaned pigs consumed CHE in our study may explain the positive effects of CHE supplementation on diarrhoea frequency and nutrient digestibility
  • but decreased the incidence of diarrhoea and increased digestibility of some nutrients.
  • In addition, CHE supplementation improved faecal SCFAs concentrations and immune function of weaned pigs, and shaped faecal microbial community in weaned pigs. As a result, the traditional Chinese herb medicine, CHE, could act as a potential alternative to the antibiotics such as aureomycin used in weaned pig diets.
    • katherine-medina
       
      I do quite enjoy this closing statement, so in summary CHE works to decrease diarrhoea in weened pigs.
  •  
    An article showing that pigs who ate CHE had a significant decrease in diahrroea.
  •  
    Super interesting. Just remember that experimentation on mammals where diet is altered, etc... is a super tightrope walk. It is almost impossible to get those approved. You would have to really dig into the ISEF rules on that. However, you can always think about ways to transfer ideas and concepts down to a "lower" animal model for many studies.
katherine-medina

Increased 3-O-sulfated heparan sulfate in Alzheimer's disease brain is associated with ... - 1 views

  • Genetic factors contribute substantially to the pathological process of AD as demonstrated by the fact that the genetic heritability in AD is in the range of between 60 and 80% (10).
  • however, whether the variants alter the level of 3-OST-1 enzyme activity to change the structure of HS remains unknown
    • katherine-medina
       
      Good to note what exactly the article remains unsure about
  • The synthesis of additional 13C-labeled calibrants to cover these three reported 3-O-sulfated tetrasaccharides will be the subject for future study.
    • katherine-medina
       
      LOOK INTO THIS PART CAYSE THEY ARE SAYING THAT THEY ARE NOT FULLY SURE
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  • the elevation of total HS and the percentage of the 3-O-sulfated domain in HS.
  • HS and tau revealed that the sugar mainly interacts with the proline-rich region 2, a repeat domain 2 in tau protein
  • Further analysis of the distribution of 3-O-sulfated HS from different areas of AD brains will be of interest and the subject for a subsequent study.
  • Experimental design
    • katherine-medina
       
      READ THIS IF THIS TOPIC COMES BACK UP AGAIN
  •  
    A interesting study about a sulfate that suggests that Alzheimer's is genetic
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