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Osteogenic potential of mesenchymal stromal cells contributes to primary myelofibrosis

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm which is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize PMF, which is also associated with bone marrow (BM) stromal alterations marked by fibrosis, neoangiogenesis and osteomyelosclerosis. In particular, contributions to PMF from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that BM MSC from PMF patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. PMF-MSC overexpressed heparin-binding cytokines, including pro-inflammatory TGF-β1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGF-β1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in PMF-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibiting the endogenous TGF-β1 receptor TGFβR1 impaired osteogenic differentiation in these MSC. Taken together, our results define the source of a critical osteogenic function in PMF that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in PMF patients may heighten therapeutic efficacy.

Does caffeine fight cancer?

Epidemiological studies have shown that caffeinated drinks may help prevent skin cancer by inhibiting a DNA repair pathway, thus killing potentially precancerous cells. In English, it means that drinking drinks containing caffeine will reduce one’s chances of developing some types of cancer, including UV-associated skin cancer. That just proves that caffeine fight cancer. The results, published in the Proceedings of the National Academy of Sciences, lend support to the idea that caffeine could be added to sunblock to increase its protective effects. At the cellular level, they’re showing that caffeine is working in this way of inducing an apoptotic mechanism. This statement was then made by cancer epidemiologist Joanne Kotsopoulos of the University of Toronto.

In the 2007, a study stated that woman who drank caffeinated coffee on a daily basis had a 10 percent lower risk of nonmelanoma skin cancer. Six or more cups of coffee a day translated to a 30 percent reduction in risk. Mouse studies have also confirmed the link, with both ingested and topically-applied caffeine lowering skin cancer rates in the animals. But exactly how the stimulant protected against cancer remained mysterious. One possibility is the drug’s inhibition of ataxia telangiectasia and Rad3-related (ATR), a large protein kinase that senses incomplete DNA replication often a result of DNA damage and signals the cell to not divide. By inhibiting ATR activity, caffeine could make cells more likely to die in response to UV damage, preventing damaged cells from ever becoming cancerous.

Studies have shown that the caffeine molecule acts as a sunscreen. It therefore blocks the penetration of UV rays. And that is why today we see many sunblocks with a good amount of caffeine in them.

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Can sugar consumption cause breast cancer?

A recent study stated that drinking three sugar sweetened drinks a week would increase the risk of having breast cancer. The study had 776 pre-menopausal women and 779 post-menopausal women. Each women’s breast density was assessed by examining their mammograms. The women were told to make a note of sweet they consumed such as chocolates, cakes, ice cream or any sweet drinks. Also they were asked to make a note of how much of spoonful of sugar they add to the drinks.

It was then found out that post-menopausal women who consumed more of sugar, an increase in the density of breast. While the pre-menopausal women observed an increase in breast density when they consumed sugar food. These women, in a week were just consuming three sugar sweetened drinks. The study then further stated that sugar tends to increase the migration of breast cells together. This explains the fact that the premenopausal women who consumed sugar-sweetened drinks were 3 percent more likely to have dense breasts than those who didn’t consume the drinks. And having dense breasts increases your risk of breast cancer by making it difficult to see tumors on mammograms.

However, there is more to be studied on this matter. But until then there is still a link between the sugar consumption and breast density. About 40% of women in the US have dense breast and they are totally unaware of it. Doctors say that women with a dense breast are five time more likely to have a breast cancer and 10 times more likely to miss the tumor in the mammogram test.

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