User blogs
Researchers have demonstrated that nanoparticles coated with quercetin
molecules can selectively target and eliminate harmful senescent cells.
As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.wisepoqder Quercetin powder
Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.
By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging.
Senescent cells only make up a small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging and cancer; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.
The trouble with quercetin
Quercetin is a naturally occurring plant polyphenol, a category that often has poor water solubility, chemical instability, or poor bioavailability. These confounding factors could be muddling its effectiveness and making it unreliable as a senolytic therapy. This likely explains why different senolytic studies using quercetin have yielded conflicting results: there are simply too many processes that can influence these natural molecules for them to be reliable.
We have seen in past mouse studies and recent Mayo Clinic human trials that quercetin, when used in combination with the cancer drug dasatinib, can be the basis for an effective therapy for eliminating senescent cells. Unfortunately, on its own, quercetin does not have a significant senolytic effect, which is possibly due to its limitations as a polyphenol.
However, there are ways to overcome these issues with quercetin and other similar polyphenols, and that is by using special delivery systems that make the molecules more effective and controllable. Polymer nanoparticles, lipid-based carriers, inclusion complexes, micelles, and conjugate-based delivery systems are all examples of approaches that can deliver molecules more effectively.
Nanoparticles make quercetin more effective
The researchers of this study opted to use a nanoparticle-based delivery system to carry quercetin molecules to senescent cells in order to destroy them [1]. They created magnetite nanoparticles and coated their surface with quercetin molecules, then examined the senolytic action of this approach.
They found that the nanoparticles were effective at attenuating inflammatory signals, such as interleukin 8 and interferon beta, which are secreted by senescent cells. They also found that cells forced into early senescence via stress were destroyed by the nanoparticles and that the secretion of inflammatory signals was reduced.Doing this also led to an elevated activity of AMP-activated protein kinase (AMPK). This is a critical nutrient and energy sensing enzyme that is present in all mammalian cells and maintains energy homeostasis. When activated, it facilitates energy-generating processes, such as glucose uptake and fatty acid oxidation, and decreases energy-consuming processes, such as protein and lipid synthesis. AMPK is one of the four pathways that control our metabolism, and its deregulation is a proposed reason why we age and develop metabolic conditions such as type 2 diabetes.
Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.
As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.wisepoqder Quercetin powder
Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.
By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging.
Senescent cells only make up a small number of total cells in the body, but they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging and cancer; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.
The trouble with quercetin
Quercetin is a naturally occurring plant polyphenol, a category that often has poor water solubility, chemical instability, or poor bioavailability. These confounding factors could be muddling its effectiveness and making it unreliable as a senolytic therapy. This likely explains why different senolytic studies using quercetin have yielded conflicting results: there are simply too many processes that can influence these natural molecules for them to be reliable.
We have seen in past mouse studies and recent Mayo Clinic human trials that quercetin, when used in combination with the cancer drug dasatinib, can be the basis for an effective therapy for eliminating senescent cells. Unfortunately, on its own, quercetin does not have a significant senolytic effect, which is possibly due to its limitations as a polyphenol.
However, there are ways to overcome these issues with quercetin and other similar polyphenols, and that is by using special delivery systems that make the molecules more effective and controllable. Polymer nanoparticles, lipid-based carriers, inclusion complexes, micelles, and conjugate-based delivery systems are all examples of approaches that can deliver molecules more effectively.
Nanoparticles make quercetin more effective
The researchers of this study opted to use a nanoparticle-based delivery system to carry quercetin molecules to senescent cells in order to destroy them [1]. They created magnetite nanoparticles and coated their surface with quercetin molecules, then examined the senolytic action of this approach.
They found that the nanoparticles were effective at attenuating inflammatory signals, such as interleukin 8 and interferon beta, which are secreted by senescent cells. They also found that cells forced into early senescence via stress were destroyed by the nanoparticles and that the secretion of inflammatory signals was reduced.Doing this also led to an elevated activity of AMP-activated protein kinase (AMPK). This is a critical nutrient and energy sensing enzyme that is present in all mammalian cells and maintains energy homeostasis. When activated, it facilitates energy-generating processes, such as glucose uptake and fatty acid oxidation, and decreases energy-consuming processes, such as protein and lipid synthesis. AMPK is one of the four pathways that control our metabolism, and its deregulation is a proposed reason why we age and develop metabolic conditions such as type 2 diabetes.
Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.
NAD+ availability decreases with age and in certain disease conditions.
Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been
shown to enhance NAD+ biosynthesis and ameliorate various pathologies in
mouse disease models. In this study, we conducted a 12-month-long NMN
administration to regular chow-fed wild-type C57BL/6N mice during their
normal aging. Orally administered NMN was quickly utilized to synthesize
NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated
physiological decline in mice. Without any obvious toxicity or
deleterious effects, NMN suppressed age-associated body weight gain,
enhanced energy metabolism, promoted physical activity, improved insulin
sensitivity and plasma lipid profile, and ameliorated eye function and
other pathophysiologies. Consistent with these phenotypes, NMN prevented
age-associated gene expression changes in key metabolic organs and
enhanced mitochondrial oxidative metabolism and mitonuclear protein
imbalance in skeletal muscle. These effects of NMN highlight the
preventive and therapeutic potential of NAD+ intermediates as effective
anti-aging interventions in humans.wisepoqder beta-Nicotinamide mononucleotide powder
Historically unprecedented worldwide trends in population aging are predicted to become an incessant burden on governmental healthcare finances (OECD, 2013). To make the process of aging healthy and prevent expensive age-associated health problems, efforts to develop effective, affordable, anti-aging interventions have recently been intensified, leading to some promising compounds, such as metformin, rapamycin, and SIRT1 activators (Barzilai et al., 2016, Hubbard and Sinclair, 2014, Lamming et al., 2013). Whereas these compounds were originally developed as pharmaceutical drugs, some endogenous compounds might also have the potential to achieve healthy and productive lives even at a very old age (Imai, 2010, Imai and Guarente, 2014).
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), key NAD+ intermediates in mammals, could be such candidates (Imai, 2010). NMN is synthesized from nicotinamide (Nic), an amide form of vitamin B3, and 5′-phosphoribosyl-pyrophosphate (PRPP) by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this particular NAD+ biosynthetic pathway (Cantó et al., 2015, Imai and Guarente, 2014). NR is phosphorylated to NMN by nicotinamide riboside kinases (NRKs) (Belenky et al., 2007). Once NMN is synthesized, it is converted to NAD+ by three NMN adenylyltransferases, NMNAT1-3. The short-term administration of either NMN or NR has been reported to have remarkable therapeutic effects on metabolic complications and other disease conditions. For example, we have shown that NMN ameliorates impairments in glucose-stimulated insulin secretion in aged wild-type mice and some genetic mouse models (Ramsey et al., 2008, Revollo et al., 2007). NMN treatment also significantly improves both insulin action and secretion in diet- and age-induced type 2 diabetic or obese mouse models (Caton et al., 2011, Yoshino et al., 2011). Furthermore, NMN protects the heart from ischemia/reperfusion injury by preventing NAD+ decrease induced by ischemia (Yamamoto et al., 2014), maintains the neural stem/progenitor cell population, and restores skeletal muscle mitochondrial function and arterial function in aged mice (de Picciotto et al., 2016, Gomes et al., 2013, Stein and Imai, 2014), ameliorates mitochondrial function, neural death, and cognitive function in Alzheimer’s disease rodent models (Long et al., 2015, Wang et al., 2016). NR is also able to ameliorate mitochondrial dysfunction in obese mouse models (Cantó et al., 2012, Gariani et al., 2015, Lee et al., 2015) and various mitochondrial disease models (Cerutti et al., 2014, Khan et al., 2014), attenuate cognitive deterioration in Alzheimer’s disease model mice (Gong et al., 2013), prevent DNA damage and hepatocellular carcinoma formation (Tummala et al., 2014), improve noise-induced hearing loss (Brown et al., 2014), and maintain muscle stem cell function (Zhang et al., 2016). Collectively, these findings strongly suggest that enhancing NAD+ biosynthesis by administering NMN or NR is an efficient therapeutic intervention against many disease conditions (Imai and Guarente, 2014).
Interestingly, it has been demonstrated that enhancing NAD+ biosynthesis extends lifespan in yeast, worms, and flies (Anderson et al., 2002, Balan et al., 2008, Mouchiroud et al., 2013). In rodents and humans, a number of studies have reported that NAD+ content declines with age in multiple organs, such as pancreas, adipose tissue, skeletal muscle, liver, skin, and brain (Gomes et al., 2013, Massudi et al., 2012, Mouchiroud et al., 2013, Stein and Imai, 2014, Yoshino et al., 2011, Zhu et al., 2015). Thus, enhancing NAD+ biosynthesis with NMN or NR is expected to provide significant preventive effects on various pathophysiological changes in the natural process of aging. To address this critical question, long-term administration studies need to be performed under normal conditions in wild-type mice.
To examine whether long-term administration of NMN shows preventive effects on age-associated pathophysiological changes, we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water. We assessed a variety of functional traits, as well as long-term safety and toxicity, and found that NMN is remarkably capable of ameliorating age-associated physiological decline in mice. Our findings from this long-term administration study provide a proof of concept to develop NMN as an effective anti-aging compound that prevents age-associated physiological decline, hoping to translate the results to humans.
Historically unprecedented worldwide trends in population aging are predicted to become an incessant burden on governmental healthcare finances (OECD, 2013). To make the process of aging healthy and prevent expensive age-associated health problems, efforts to develop effective, affordable, anti-aging interventions have recently been intensified, leading to some promising compounds, such as metformin, rapamycin, and SIRT1 activators (Barzilai et al., 2016, Hubbard and Sinclair, 2014, Lamming et al., 2013). Whereas these compounds were originally developed as pharmaceutical drugs, some endogenous compounds might also have the potential to achieve healthy and productive lives even at a very old age (Imai, 2010, Imai and Guarente, 2014).
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), key NAD+ intermediates in mammals, could be such candidates (Imai, 2010). NMN is synthesized from nicotinamide (Nic), an amide form of vitamin B3, and 5′-phosphoribosyl-pyrophosphate (PRPP) by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this particular NAD+ biosynthetic pathway (Cantó et al., 2015, Imai and Guarente, 2014). NR is phosphorylated to NMN by nicotinamide riboside kinases (NRKs) (Belenky et al., 2007). Once NMN is synthesized, it is converted to NAD+ by three NMN adenylyltransferases, NMNAT1-3. The short-term administration of either NMN or NR has been reported to have remarkable therapeutic effects on metabolic complications and other disease conditions. For example, we have shown that NMN ameliorates impairments in glucose-stimulated insulin secretion in aged wild-type mice and some genetic mouse models (Ramsey et al., 2008, Revollo et al., 2007). NMN treatment also significantly improves both insulin action and secretion in diet- and age-induced type 2 diabetic or obese mouse models (Caton et al., 2011, Yoshino et al., 2011). Furthermore, NMN protects the heart from ischemia/reperfusion injury by preventing NAD+ decrease induced by ischemia (Yamamoto et al., 2014), maintains the neural stem/progenitor cell population, and restores skeletal muscle mitochondrial function and arterial function in aged mice (de Picciotto et al., 2016, Gomes et al., 2013, Stein and Imai, 2014), ameliorates mitochondrial function, neural death, and cognitive function in Alzheimer’s disease rodent models (Long et al., 2015, Wang et al., 2016). NR is also able to ameliorate mitochondrial dysfunction in obese mouse models (Cantó et al., 2012, Gariani et al., 2015, Lee et al., 2015) and various mitochondrial disease models (Cerutti et al., 2014, Khan et al., 2014), attenuate cognitive deterioration in Alzheimer’s disease model mice (Gong et al., 2013), prevent DNA damage and hepatocellular carcinoma formation (Tummala et al., 2014), improve noise-induced hearing loss (Brown et al., 2014), and maintain muscle stem cell function (Zhang et al., 2016). Collectively, these findings strongly suggest that enhancing NAD+ biosynthesis by administering NMN or NR is an efficient therapeutic intervention against many disease conditions (Imai and Guarente, 2014).
Interestingly, it has been demonstrated that enhancing NAD+ biosynthesis extends lifespan in yeast, worms, and flies (Anderson et al., 2002, Balan et al., 2008, Mouchiroud et al., 2013). In rodents and humans, a number of studies have reported that NAD+ content declines with age in multiple organs, such as pancreas, adipose tissue, skeletal muscle, liver, skin, and brain (Gomes et al., 2013, Massudi et al., 2012, Mouchiroud et al., 2013, Stein and Imai, 2014, Yoshino et al., 2011, Zhu et al., 2015). Thus, enhancing NAD+ biosynthesis with NMN or NR is expected to provide significant preventive effects on various pathophysiological changes in the natural process of aging. To address this critical question, long-term administration studies need to be performed under normal conditions in wild-type mice.
To examine whether long-term administration of NMN shows preventive effects on age-associated pathophysiological changes, we treated regular chow-fed wild-type mice for 12 months with two different doses of NMN in their drinking water. We assessed a variety of functional traits, as well as long-term safety and toxicity, and found that NMN is remarkably capable of ameliorating age-associated physiological decline in mice. Our findings from this long-term administration study provide a proof of concept to develop NMN as an effective anti-aging compound that prevents age-associated physiological decline, hoping to translate the results to humans.
Pyrroloquinoline Quinone (PQQ) is a unique micro-nutrient; a
vitamin-like compound found naturally in plant foods and green tea. PQQ
has been shown to provide a wide range of benefits to brain and body
function based upon clinical evaluations. PQQ has been researched and
studied closely for over 30 years.wisepoqder Pyrroloquinoline quinone
PQQ is a powerful anti-oxidant capable of catalyzing repeated oxidation and reduction reactions to a much greater degree compared to other anti-oxidants. PQQ promotes the generation of new mitochondria within aging cells, called mitochondrial biogenesis, and improves mitochondrial function; a “fountain of youth” effect”. This support of mitochondrial growth improves energy production.
PQQ has tremendous potential to help with neurological conditions that revolve around low mitochondrial function and can support the body’s efforts to combat against the loss of memory and cognitive skills, as the body ages.
TAKING PQQ
If you want to add a PQQ supplement to your diet, it’s important to remember that a little goes a long way. Since it doesn’t take much PQQ to have an effect, most dosages are kept small. As a result, most people don’t have to worry about any PQQ side effects.
PQQ is a very effective nootropic that everyone should include in their stack of choice. It may provide you with more energy, improved sleep, and an enhanced memory in addition to some possible other benefits. There’s a lot to be gained from taking PQQ.
PQQ is a powerful anti-oxidant capable of catalyzing repeated oxidation and reduction reactions to a much greater degree compared to other anti-oxidants. PQQ promotes the generation of new mitochondria within aging cells, called mitochondrial biogenesis, and improves mitochondrial function; a “fountain of youth” effect”. This support of mitochondrial growth improves energy production.
PQQ has tremendous potential to help with neurological conditions that revolve around low mitochondrial function and can support the body’s efforts to combat against the loss of memory and cognitive skills, as the body ages.
TAKING PQQ
If you want to add a PQQ supplement to your diet, it’s important to remember that a little goes a long way. Since it doesn’t take much PQQ to have an effect, most dosages are kept small. As a result, most people don’t have to worry about any PQQ side effects.
PQQ is a very effective nootropic that everyone should include in their stack of choice. It may provide you with more energy, improved sleep, and an enhanced memory in addition to some possible other benefits. There’s a lot to be gained from taking PQQ.
Pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in
various foods and mammalian tissues, has received an increasing amount
of attention because of a number of health benefits that can be
attributed to its ability to enhance mitochondrial biogenesis. However,
its underlying molecular mechanism remains incompletely understood. We
have now established that the exposure of mouse NIH/3T3 fibroblasts to a
physiologically relevant concentration of PQQ significantly stimulates
mitochondrial biogenesis.
The exposure of NIH/3T3 cells to 10–100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). wisepoqder Pyrroloquinoline quinone powder
Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD+ levels, but not the total NAD+ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.
The exposure of NIH/3T3 cells to 10–100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). wisepoqder Pyrroloquinoline quinone powder
Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD+ levels, but not the total NAD+ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.
Kylie’s been busy extending her make-up empire and fans have seen her
pushing her latest venture, Kylie Skin, across social media. We’ve had
promo videos, fresh-faced selfies and that 10-second face wash tutorial
that even Kim Kardashion poked fun of – but, anything Kylie can do, Will
can do better. The Aladdin star took to Instagram with his own ‘beauty
tips’ and ‘beauty secrets’, giving the Keeping Up With The Kardashians
star a run for her money and we loved every second.atasi jerawat
Will plays Genie in the live action re-make of the Disney movie and decided to film a little something to reveal the key to his ‘Genie magic’. Eyeliner – in case you were wondering. And a good face mask. Posting his spoof tutorial to Instagram, Will is sat in his dressing room and says: ‘The big part I hate about not being able to play Genie is eyeliner. I really like wearing eyeliner. ‘You see how pretty my eyes are?’ Next, he moves on to that Genie glow and applies a mask with a face exfoliator. We told you, he’s dedicated.
I don’t want Kylie Jenner stealing my stuff,’ he joked while layering on the ‘brown stuff’. If the Kylie dig wasn’t enough to have you in stitches, then Will’s demonstration will. ‘The brown stuff has nature in it,’ he says while going to town with the exfoliator. ‘It goes in a circular motion and you go in a circular motion and you’ve always got to keep the battery low, so it barely works.’ Totally deadpan, he then goes: ‘Oh, and you’ve got to be careful because it makes your skin black… and that’s why my skin looks so good.’
Him throwing shade at Kylie comes after he and his wife Jada Pinkett Smith were on hand to support her former BFF Jordyn Woods when the whole Tristan Thompson scandal broke. Jordyn has been tight with Will and Jada ever since she was little and Jada gave her the platform to set the record straight on what really happened with Tristan on her talk show Red Table Talk.
Jordyn and Tristan were caught cheating at a house party in LA, but the model insisted they never slept together – Tristan had kissed her goodbye when she left the party. It was enough for Khloe Kardashian to dump her baby daddy Tristan, ending their three year relationship. Kylie has reportedly cut ties with Jordyn – washing her hands off their long-term friendship just like she did her face.
Will plays Genie in the live action re-make of the Disney movie and decided to film a little something to reveal the key to his ‘Genie magic’. Eyeliner – in case you were wondering. And a good face mask. Posting his spoof tutorial to Instagram, Will is sat in his dressing room and says: ‘The big part I hate about not being able to play Genie is eyeliner. I really like wearing eyeliner. ‘You see how pretty my eyes are?’ Next, he moves on to that Genie glow and applies a mask with a face exfoliator. We told you, he’s dedicated.
I don’t want Kylie Jenner stealing my stuff,’ he joked while layering on the ‘brown stuff’. If the Kylie dig wasn’t enough to have you in stitches, then Will’s demonstration will. ‘The brown stuff has nature in it,’ he says while going to town with the exfoliator. ‘It goes in a circular motion and you go in a circular motion and you’ve always got to keep the battery low, so it barely works.’ Totally deadpan, he then goes: ‘Oh, and you’ve got to be careful because it makes your skin black… and that’s why my skin looks so good.’
Him throwing shade at Kylie comes after he and his wife Jada Pinkett Smith were on hand to support her former BFF Jordyn Woods when the whole Tristan Thompson scandal broke. Jordyn has been tight with Will and Jada ever since she was little and Jada gave her the platform to set the record straight on what really happened with Tristan on her talk show Red Table Talk.
Jordyn and Tristan were caught cheating at a house party in LA, but the model insisted they never slept together – Tristan had kissed her goodbye when she left the party. It was enough for Khloe Kardashian to dump her baby daddy Tristan, ending their three year relationship. Kylie has reportedly cut ties with Jordyn – washing her hands off their long-term friendship just like she did her face.
Millie Bobby Brown has responded to accusations that she oddly “didn't
apply anything” to her face in new video highlighting products from her
clean beauty line, Florence by Mills.
In recent days, the "Stranger Things" star shared her “nighttime skin routine” with the cosmetics on social media, but many viewers agreed that it didn’t look like she was doing anything to her face at all.angkat komedo
In the nearly two-minute clip, which has since been deleted from Instagram but remains on YouTube, Brown demonstrates a face mist, a scrub, a facewash, a moisturizer, and lip oil, claiming to have washed off her face between at least two of the steps.But, as some pointed out, the 15-year-old actress appears to retain her eye makeup throughout, leading some to believe she was just pretending to use the products and rubbing her dry hands all over her face.
“The mist is the only thing she actually used!” on YouTube commenter complained. “This girl basically just spent two minutes rubbing her face with her bare hands.”
“Wow, a magic invisible product that we couldn't even see being applied,” another smirked. “Millie is such a great actress.”I am so confused… if she was actually applying something then all her makeup would be smudging and coming off,” one added.
On Sept. 12, Brown took the makeup matter into her own hands and responded to the accusations on Instagram with a new post.“I'm still learning the best way to share my routines as I get to know this space better – I'm not an expert,” the “Godzilla” star admitted. “I thought doing a quick video replicating my personal process that night was okay, but that's not what was conveyed. I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too!”
In recent days, the "Stranger Things" star shared her “nighttime skin routine” with the cosmetics on social media, but many viewers agreed that it didn’t look like she was doing anything to her face at all.angkat komedo
In the nearly two-minute clip, which has since been deleted from Instagram but remains on YouTube, Brown demonstrates a face mist, a scrub, a facewash, a moisturizer, and lip oil, claiming to have washed off her face between at least two of the steps.But, as some pointed out, the 15-year-old actress appears to retain her eye makeup throughout, leading some to believe she was just pretending to use the products and rubbing her dry hands all over her face.
“The mist is the only thing she actually used!” on YouTube commenter complained. “This girl basically just spent two minutes rubbing her face with her bare hands.”
“Wow, a magic invisible product that we couldn't even see being applied,” another smirked. “Millie is such a great actress.”I am so confused… if she was actually applying something then all her makeup would be smudging and coming off,” one added.
On Sept. 12, Brown took the makeup matter into her own hands and responded to the accusations on Instagram with a new post.“I'm still learning the best way to share my routines as I get to know this space better – I'm not an expert,” the “Godzilla” star admitted. “I thought doing a quick video replicating my personal process that night was okay, but that's not what was conveyed. I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too!”
The Stranger Things star took to Instagram on Thursday to address the
criticism she received over a nighttime skincare routine tutorial.
"I'm still learning the best way to share my routines as I get to know this space better—I'm not an expert," she wrote in a note posted to the social network. "I thought doing a quick video replicating my personal process for that night was okay, but that's not what was conveyed. I understand, I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too. Ily guys x #LovedAndLight."Tutorial makeup
The 15-year-old actress posted the tutorial on YouTube last weekend. In the one-minute and 50-second clip, the celebrity talked about the products from her Florence by Mills line and walked viewers through a routine, which included using a face mist, a scrub, a face wash, a moisturizer and a lip oil.However, viewers had some serious questions about the video—mainly over if she actually used the products. For instance, some wondered why her hair was still dry and why her makeup was still intact after allegedly washing her face.
"You know how when you actually wash your face with water your hair gets a little bit wet or damp around the face? She kept saying she was washing the soap off, but her hair was perfectly dry at all times," one YouTube commenter wrote. "I would have expected to see a little remnant of the rinsing process at least since she rinsed at least twice over. And the [mist] kinda didn't get on her face. This was weird. The eye makeup was still on."
Others questioned the sporadic cuts throughout the video, which usually took place right after she said she was going to "wash off." Some even accused the celebrity of using empty bottles.
"I'm still learning the best way to share my routines as I get to know this space better—I'm not an expert," she wrote in a note posted to the social network. "I thought doing a quick video replicating my personal process for that night was okay, but that's not what was conveyed. I understand, I appreciate all of your feedback on this journey, please keep sharing your thoughts and I will too. Ily guys x #LovedAndLight."Tutorial makeup
The 15-year-old actress posted the tutorial on YouTube last weekend. In the one-minute and 50-second clip, the celebrity talked about the products from her Florence by Mills line and walked viewers through a routine, which included using a face mist, a scrub, a face wash, a moisturizer and a lip oil.However, viewers had some serious questions about the video—mainly over if she actually used the products. For instance, some wondered why her hair was still dry and why her makeup was still intact after allegedly washing her face.
"You know how when you actually wash your face with water your hair gets a little bit wet or damp around the face? She kept saying she was washing the soap off, but her hair was perfectly dry at all times," one YouTube commenter wrote. "I would have expected to see a little remnant of the rinsing process at least since she rinsed at least twice over. And the [mist] kinda didn't get on her face. This was weird. The eye makeup was still on."
Others questioned the sporadic cuts throughout the video, which usually took place right after she said she was going to "wash off." Some even accused the celebrity of using empty bottles.
The quality of your online casino experience will depend on the site you
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your jurisdiction, then try to assess them based on the criteria listed
below.gambling affiliate program
When you visit an online casino, your first step should be to check for a license issued by an internationally recognized regulatory body. Legitimate casinos don’t hide licensing information from their customers—in most cases, you should be able to find it at the bottom of the casino website’s main page.
The industry is highly competitive, so international casinos tend to be based in jurisdictions with low gambling taxes, such as Curacao, Malta, Gibraltar, the United Kingdom, the Isle of Man, and Costa Rica. If the local regulations prohibit you from joining casinos with a global reach, stick to platforms that operate under a license issued by your local gambling authorities.
Once you’ve made sure that the paperwork checks out, you should also verify the casino’s reputation. We recommend following a simple rule of thumb to avoid getting bogged down in conflicting customer reviews—if the casino hasn’t been involved in any scandal around withdrawal requests or the terms and conditions of promotions, you should be good to go.Every online casino offers its own lineup of slots, table games, and specialty games, but you’d be hard-pressed to find a title that’s exclusive to any particular site. This is because casino operators generally don’t design their games in-house. Instead, they rely on games from dedicated software development companies such as Playtech, Microgaming, NetEnt, Konami, or BetSoft.
If game variety is an important consideration for you, you should focus on casinos that are partnered with a diverse selection of software providers. On the other hand, if you’re more of a profit-seeking player, you’ll want to prioritize casinos that offer games with the most advantageous characteristics. For example, if you’re hoping to turn a profit while playing slots, you should be looking for high-volatility games with a low house edge.
When you visit an online casino, your first step should be to check for a license issued by an internationally recognized regulatory body. Legitimate casinos don’t hide licensing information from their customers—in most cases, you should be able to find it at the bottom of the casino website’s main page.
The industry is highly competitive, so international casinos tend to be based in jurisdictions with low gambling taxes, such as Curacao, Malta, Gibraltar, the United Kingdom, the Isle of Man, and Costa Rica. If the local regulations prohibit you from joining casinos with a global reach, stick to platforms that operate under a license issued by your local gambling authorities.
Once you’ve made sure that the paperwork checks out, you should also verify the casino’s reputation. We recommend following a simple rule of thumb to avoid getting bogged down in conflicting customer reviews—if the casino hasn’t been involved in any scandal around withdrawal requests or the terms and conditions of promotions, you should be good to go.Every online casino offers its own lineup of slots, table games, and specialty games, but you’d be hard-pressed to find a title that’s exclusive to any particular site. This is because casino operators generally don’t design their games in-house. Instead, they rely on games from dedicated software development companies such as Playtech, Microgaming, NetEnt, Konami, or BetSoft.
If game variety is an important consideration for you, you should focus on casinos that are partnered with a diverse selection of software providers. On the other hand, if you’re more of a profit-seeking player, you’ll want to prioritize casinos that offer games with the most advantageous characteristics. For example, if you’re hoping to turn a profit while playing slots, you should be looking for high-volatility games with a low house edge.
When most people consider Missouri, they probably think of Branson, a
tourist mecca filled with arts, crafts, and a variety of musical acts.
While the area nestled in the Ozark Mountains certainly does its part to
draw in out-of-state revenue, the casinos scattered about Missouri are
just as proficient at generating cash for the government’s coffers.
Missouri is more liberal on gambling than they are in most other areas, and were one of the first states in the country to authorize commercial casinos. These casinos came in the form of riverboats, which basically just means that they were built on barges, which technically puts them in the water; the ‘boats’ don’t go anywhere.affiliate program
Other forms of gambling in the state include charitable gaming, which also allows for certain games of skill. The organizations conducting the gambling pay license fees while the taxes are assessed on the sale of the gambling products, in other words, the suppliers of the products pay the taxes.
Horse racing is legal within the state, as is pari-mutuel wagering; however, the state currently has no horse racing tracks and there are not any simulcast wagering sections at the casinos. We can expect that to change if Missouri ever passes a sports betting bill, which they have still failed to do (as of the time of this writing). The Kansas City Star is not particularly pleased.
That’s absolutely right! The writer also (simultaneously) makes an excellent case for legalizing and regulating online casinos, as well. The state should also legalize and regulate video lottery parlors in the manner of states such as Illinois, West Virginia and Montana. When will this happen? According to the Star, Kansas Rep. John Barker had this to say:
Having lived in the state, I can say that there are only two speeds at which anything happens in the State of Missouri: Extremely slow and stop. “Giving it some priority,” will, at best, move sports betting into the extremely slow category. I don’t know why the state doesn’t feel like it couldn’t get its hands on those sweet, sweet tax revenues soon enough, but apparently, it’s not a huge concern for them. In the meantime, as mentioned by the Star, residents will just make the bets elsewhere.
That’s great news because, if Missouri (as a state) were to ever enter a race, the result would be DNF. (Did not finish) If the people of Missouri were anything like the politicians, no housefire would ever be escaped because they’d be too busy diddling around. Granted, Barker is a representative from the state of Kansas, but you’d have to live on the western side of Missouri or eastern side of Kansas to even know where one stops and the other starts, and even then, you often end up in the opposite state without even knowing it.
We doubt if online gambling is going to be on the table anytime soon, especially given the state’s preference for doing things approximately 457 years after all of the other states do. Surprisingly, Missouri was one of the first states to authorize and regulate daily fantasy sports (DFS) because they considered it a game of skill.
We guess they’re just liberal when it comes to the casino gambling and pretty conservative when it comes to everything else. In addition to the offshore online sports betting, some of the states bordering Missouri were extremely quick to license and regulate sports betting, perhaps most notably Illinois, bordering the eastern side of the state.
Missouri is more liberal on gambling than they are in most other areas, and were one of the first states in the country to authorize commercial casinos. These casinos came in the form of riverboats, which basically just means that they were built on barges, which technically puts them in the water; the ‘boats’ don’t go anywhere.affiliate program
Other forms of gambling in the state include charitable gaming, which also allows for certain games of skill. The organizations conducting the gambling pay license fees while the taxes are assessed on the sale of the gambling products, in other words, the suppliers of the products pay the taxes.
Horse racing is legal within the state, as is pari-mutuel wagering; however, the state currently has no horse racing tracks and there are not any simulcast wagering sections at the casinos. We can expect that to change if Missouri ever passes a sports betting bill, which they have still failed to do (as of the time of this writing). The Kansas City Star is not particularly pleased.
That’s absolutely right! The writer also (simultaneously) makes an excellent case for legalizing and regulating online casinos, as well. The state should also legalize and regulate video lottery parlors in the manner of states such as Illinois, West Virginia and Montana. When will this happen? According to the Star, Kansas Rep. John Barker had this to say:
Having lived in the state, I can say that there are only two speeds at which anything happens in the State of Missouri: Extremely slow and stop. “Giving it some priority,” will, at best, move sports betting into the extremely slow category. I don’t know why the state doesn’t feel like it couldn’t get its hands on those sweet, sweet tax revenues soon enough, but apparently, it’s not a huge concern for them. In the meantime, as mentioned by the Star, residents will just make the bets elsewhere.
That’s great news because, if Missouri (as a state) were to ever enter a race, the result would be DNF. (Did not finish) If the people of Missouri were anything like the politicians, no housefire would ever be escaped because they’d be too busy diddling around. Granted, Barker is a representative from the state of Kansas, but you’d have to live on the western side of Missouri or eastern side of Kansas to even know where one stops and the other starts, and even then, you often end up in the opposite state without even knowing it.
We doubt if online gambling is going to be on the table anytime soon, especially given the state’s preference for doing things approximately 457 years after all of the other states do. Surprisingly, Missouri was one of the first states to authorize and regulate daily fantasy sports (DFS) because they considered it a game of skill.
We guess they’re just liberal when it comes to the casino gambling and pretty conservative when it comes to everything else. In addition to the offshore online sports betting, some of the states bordering Missouri were extremely quick to license and regulate sports betting, perhaps most notably Illinois, bordering the eastern side of the state.
Solicitations for proposals for a casino project in Danville’s Southgate
Industrial Park area were scheduled to go out this morning to
prospective operators throughout the country.
Developer Dave Cocagne said casino developers will be asked for information regarding 17 different criteria, including their experience, annual revenues, numbers of jobs their project would create and other amenities it would include — data needed to help a local steering committee decide with whom the city should partner.most popular casinos
While Danville will be competing with existing and new casinos — possibly one an hour away in Terre Haute, Ind. — Cocagne said Danville can capitalize on its rich history and unique assets by incorporating them into the project’s design, branding and marketing, and other attractions.
“We don’t want this to be an island,” Cocagne said, meaning it shouldn’t be just a casino.“We want this to be an asset to the community,” said Cocagne, who envisions a project with restaurants, retail and other entertainment and attractions.
The city and Vermilion Advantage have partnered with Cocagne — president and CEO of Vermilion Development, which got its start in Danville in 1992 — who will help guide the city through the process of finding the right casino developer and submitting a license application to the Illinois Gaming Board by the deadline at October’s end.
At Tuesday’s city council meeting, he outlined the application process, the hefty financial investment the developer needs to make, the type of site they’re looking for and the “enormous” role the city plays, including signing off on a site and developer and passing a resolution or ordinance in support of a casino in the community.“All of this has to be done before the application is submitted,” Cocagne said, adding that any project needs the city’s buy-in.
He commended Mayor Rickey Williams Jr. for acting quickly to put together a steering committee, which will use an evaluation matrix to review proposals, make a short list of and interview finalists and ultimately recommend a casino developer to the council for approval.
Besides Williams, the panel includes Vicki Haugen and Tinisha Shade-Spain of Vermilion Advantage; interim Police Chief Chris Yates; attorney and former Corporation Counsel Dave Wesner; Gardner Peck of Danville Metal Stamping; Jerry Connolly of Venture Mechanical; and Alderman Mike Puhr.Williams and Haugen, president and CEO of Vermilion Advantage, recommend two adjoining parcels — one 40 acres, the other 32 — in Southgate as the potential site, and the steering committee endorsed the idea.
Haugen said she researched sites with at least 20 to 25 acres along Interstate 74 — a location seen as vital for visibility and accessibility — and based on other site requirements. While she looked at a number of options near all of the Danville interstate exits, she ruled most of them out because they were outside of the city or didn’t have the required acreage, room to expand, infrastructure or landowners willing to sell.
Developer Dave Cocagne said casino developers will be asked for information regarding 17 different criteria, including their experience, annual revenues, numbers of jobs their project would create and other amenities it would include — data needed to help a local steering committee decide with whom the city should partner.most popular casinos
While Danville will be competing with existing and new casinos — possibly one an hour away in Terre Haute, Ind. — Cocagne said Danville can capitalize on its rich history and unique assets by incorporating them into the project’s design, branding and marketing, and other attractions.
“We don’t want this to be an island,” Cocagne said, meaning it shouldn’t be just a casino.“We want this to be an asset to the community,” said Cocagne, who envisions a project with restaurants, retail and other entertainment and attractions.
The city and Vermilion Advantage have partnered with Cocagne — president and CEO of Vermilion Development, which got its start in Danville in 1992 — who will help guide the city through the process of finding the right casino developer and submitting a license application to the Illinois Gaming Board by the deadline at October’s end.
At Tuesday’s city council meeting, he outlined the application process, the hefty financial investment the developer needs to make, the type of site they’re looking for and the “enormous” role the city plays, including signing off on a site and developer and passing a resolution or ordinance in support of a casino in the community.“All of this has to be done before the application is submitted,” Cocagne said, adding that any project needs the city’s buy-in.
He commended Mayor Rickey Williams Jr. for acting quickly to put together a steering committee, which will use an evaluation matrix to review proposals, make a short list of and interview finalists and ultimately recommend a casino developer to the council for approval.
Besides Williams, the panel includes Vicki Haugen and Tinisha Shade-Spain of Vermilion Advantage; interim Police Chief Chris Yates; attorney and former Corporation Counsel Dave Wesner; Gardner Peck of Danville Metal Stamping; Jerry Connolly of Venture Mechanical; and Alderman Mike Puhr.Williams and Haugen, president and CEO of Vermilion Advantage, recommend two adjoining parcels — one 40 acres, the other 32 — in Southgate as the potential site, and the steering committee endorsed the idea.
Haugen said she researched sites with at least 20 to 25 acres along Interstate 74 — a location seen as vital for visibility and accessibility — and based on other site requirements. While she looked at a number of options near all of the Danville interstate exits, she ruled most of them out because they were outside of the city or didn’t have the required acreage, room to expand, infrastructure or landowners willing to sell.