New Year's Eve menue

This New Year's eve will be accompanied by hors d'oeuvres, or as I prefer to call them, appetizers.

Here is my game plan for now:

1. some good chips and toasted homemade bread

2. roasted red pepper dip with feta cheese, I will try this recipe

3. cashew dip, such as this, but with less water and some apple cider vinegar

4. potato salad: boiled potatoes with grated carrots, onion, apple and spiced up with apple cider vinegar, black pepper, mustard, mayo, and salt

5. cabbage salad with grated carrots and an apple, spiced up with apple cider vinegar and olive oil

6. lots of olives

7. cheeses

8. hot Italian turkey sausage

9. toasted walnuts


The drink will be cold mint tea with sliced limes. The dessert - baked apples with some vanilla ice cream and probably a few grapes.

Wnt Signaling And The Immune Response To Breast Cancer

Wnt signaling seems to be associated with the immune response to breast cancer.  Abstract:

BACKGROUND:

Inhibition of lymphocytes infiltration and activity may impair antitumor immune response and limit treatment responsiveness. Wnt/β-catenin pathway has been suggested to contribute to immune evasion in tumor by suppressing the function of immune cells and excluding T cell infiltration. However, the effects of Wnt/β-catenin on TILs recruitment remain controversial.

OBJECTIVE:

We aimed to investigate whether intratumoral Wnt/β-catenin signaling could affect the lymphocyte infiltration in breast cancer.

METHODS:

The distribution of stromal TILs, CD8+ and FOXP3+ TIL subsets, and the expression of β-catenin were separately assessed on consecutive sections of 96 breast cancer specimens.

RESULTS:

Both stromal infiltrated TILs and β-catenin expression were upregulated in hormone receptor negative HER2-enriched and TNBC subtypes. Furthermore, high levels of stromal TILs as well as CD8+ or FOXP3+ TIL subsets were associated with β-catenin overexpression by breast cancer, respectively.

CONCLUSIONS:

For the first time, we demonstrated that rather than excluding lymphocytes infiltration as reported in mela-noma, high levels of TILs were associated with β-catenin overexpression in BC. Wnt/β-catenin signaling may play a critical role in BC immunity, particularly in HER2-enriched and triple negative BC, and may serve as a potential target for regulating immune infiltrates in breast cancer.

Dessert for any festive table

I decided to try a new dessert for New Year's Eve. Unlike my vegan Christmas Eve, I can use any products to prepare the festive spread for the last evening of the year.

In the past, my mom used to make the most divine dessert from gelled plain yogurt. There were three layers, one was vanilla with preserved white cherries, another was with lemon zest, and the third one was with cocoa powder. Mom would layer the three flavors in tall crystal glasses.  The presentation was spectacular, the taste was even better.

So, I decided to replicate at least the main idea.  Instead of gelatin and sugar, I decided to prepare a healthier version of the dessert. Hopefully, it would taste half as good as my mom's. Below is my Yogurt Banana Dessert.

Yogurt Banana Dessert

Ingredients (for six portions)
4 ripe bananas
1 Tbsp vanilla essence
1 (32 oz) container plain yogurt (low fat)
4 Tbsp chia seeds
2 Tbsp sugar (optional)
zest of one lemon
1 Tbsp of lemon juice
8 oz of frozen blueberries (or any other fruit, frozen or fresh)
2 Tbsp cocoa powder (unsweetened)
nuts to decorate

Directions
Blend the bananas, yogurt and vanilla, add the chia seeds. Leave in the refrigerator overnight. On the next day, divide into three batches and prepare the three layers. One batch of the yogurt mix is prepared with the frozen blueberries. The second with the zest and juice of a lemon. The third with cocoa powder. Decorate with anything you love. I had a few walnuts at hand.

Before I layered my dessert this morning, I read this post about what a great husband could do for the love of his life.  I sent the post to my daughter. Hopefully, she will read it too.

Are you happy

If you ever feel down, please read this blog. This is real. 

The posts are the distilled and final lessons of life. 

If you ever pity yourself read about a real fighter, Ellie.

I loved all Ellie's posts; this and this one are some of the many good ones. I visited almost all recommended in the blog websites. I even watched "A good year". It is a nice movie.

I shed lots of tears:

"... My advice is to feel everything. Feel the joy of hugging your children, feel the coldness of swimming in the ocean, feel the warmth of a bath, feel the sand underneath your feet, feel the pages of a book… Feel feel feel. Say what you mean and do what you love."
 

The biggest lesson learned from this blog? 

Live in the present. Feel the present.

I have read about this before. However, after reading Ellie's blog, I understood the advice better.

Read this blog

By the way, I would like to share something I just learned: how to find free accommodations if you love to travel. See this website for a host, but you will need to work for the roof above you....

Christmas Eve menu

Happy Christmas Eve!

Overnight, Santa sent his preliminary gift of fine white dusting. The light snow icing delineated every single branch on the trees and made the the scene truly Christmas-y.

In many countries, Christmas Eve comes with the tradition of a vegan dinner. In my home, we do odd number of vegan dishes.

This year, we narrowed the menu to the following:

1. Tofu (the way Jenny Mustard prepares it)

2. Brown rice with garlic, onion, turmeric and black pepper

3. Sauteed veggies with garlic, soy sauce, hot pepper flakes, honey and apple cider vinegar (we have broccoli, red bell pepper, baby carrots and celery)

4. Cashew cream cheese (a new recipe that we will try for the first time)

5. Baked apples (I cut these in half, core them, sprinkle lightly with cinnamon, bake with foil on top at 400F until soft)

6. Bulgur dessert (see recipe below)

7. Home-made bread (I am using this recipe)

8. Roasted walnuts (I already prepared these spiced up with salt and cayenne pepper)

9. Frozen fruit with chia seeds (here is the recipe from Pick up Limes)

Bulgur dessert

Ingredients:
1 cup bulgur + 1 cup boiling water
1 cup of finely crushed walnuts
the zest of one lemon
2 Tbsp of freshly squeezed lemon juice
2 Tbsp of crystal sugar

Directions:
Mix the bulgur with the boiling water, cover and let it stay at room temperature for one hour. Add the rest of the ingredients, mix, store in a glass jar in the refrigerator. 
Enjoy it on its own or added to the baked apples.

Happy holidays!

Metformin And mTOR Signaling

Metformin seems to block mTOR signaling; abstract:

Recent findings have shed new light on the mechanisms of action through which biguanides exert their anti-aging and cytostatic effects in Caenorhabditis elegans and human cell lines. The drop in energy charge resulting from the metformin mediated inhibition of mitochondrial activity affects the function of the nuclear pore complex, blocks mTOR signaling and enhances the expression of ACAD10. Whether the inhibition of this pathway is truly responsible for the anti-diabetic and cancer effects of the drug in mammals remains to be established.

The importance of mTOR is explained here.  This pathway has been linked to a number of disorders, and so these are important findings.  But lifestyle changes also play an important role in preventing, or treating, diseases like diabetes and cancer that drugs are used for.  Always ask your physician when the drug is prescribed: is there anything else I should be doing?  Should I also change my diet? Exercise?  

Resistance to Cancer Immune Therapy: TNF Signaling

Resistance to cancer immune therapy seems to involve downregulation of tumor necrosis factor (TNF) signaling, which possibly in the future can be a focal point of new therapies to make immune-based treatment more effective.  Abstract:

Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo. Deletion of a number of genes in the TNF pathway also emerged as the key mechanism of immune evasion from primary NK cells. Our screens also identified that the metabolic protein 2-aminoethanethiol dioxygenase (Ado) modulates sensitivity to TNF-mediated killing by cytotoxic lymphocytes and is required for optimal control of tumors in vivo. Remarkably, we found that tumors delete the same genes when exposed to perforin-deficient CD8+ T cells, demonstrating that the dominant immune evasion strategy used by tumor cells is acquired resistance to T cell-derived cytokine-mediated antitumor effects. We demonstrate that TNF-mediated bystander killing is a potent T cell effector mechanism capable of killing antigen-negative tumor cells. In addition to highlighting the importance of TNF in CD8+ T cell- and NK cell-mediated killing of tumor cells, our study also provides a comprehensive picture of the roles of the TNF, IFN, and antigen presentation pathways in immune-mediated tumor surveillance.

Anti-Epileptic Drugs And Bone Loss

Drugs against epilepsy can cause bone loss, particularly in post-menopausal women.  A study in rats demonstrated that this is due to changes in Wnt signaling and this effect was especially pronounced in ovariectomised rats, showing that estrogen loss from menopause can enhance the problem. Abstract:

Secondary osteoporosis is the major concern associated with long term intake of antiepileptic drugs (AEDs). Women are the vulnerable targets owing to post-menopausal bone loss. In the present work, we evaluated the effect of 10 weeks of treatment with AED therapy (carbamazepine, CBZ, 75 mg/kg; sodium valproate, SVP, 300 mg/kg; levetiracetam, LTM, 150 mg/kg) on bone mineral density and microarchitecture at femoral epiphysis, lumbar vertebrae and proximal tibia of normal and ovariectomised Wistar rats. In addition, we measured serum levels of vitamin D, receptor activator of nuclear factor kappa β-ligand (RANKL), procollagen type 1 amino-terminal propeptide (P1NP) and wnt inhibitors (sclerostin and DKK-1) following AED therapy. Micro-computed tomography analysis of bones revealed significant reduction in BMD at femur epiphysis and lumbar vertebrae with all the three AEDs evaluated. At proximal tibia, only CBZ showed a significant decline. The reduction in BMD was more pronounced in ovariectomised rats. AEDs also resulted in alteration of micro-CT parameters. These changes were accompanied by an increased serum RANKL with all AEDs while vitamin D levels were reduced only with CBZ treatment and P1NP levels were reduced with SVP and CBZ. Serum sclerostin levels were elevated following all AEDs in normal and ovariectomised rats except with CBZ in normal rats. However, increase in DKK-1 levels was observed with only LTM. Ovariectomy itself resulted in increased RANKL, sclerostin and DKK-1 and reduced vitamin D and P1NP levels. Significant differences were discernible between normal and ovariectomised rats treated with AEDs in all the parameters. However, while sclerostin increased further upon AEDs treatment, P1NP decreased with SVP and CBZ and serum DKK-1 levels showed a declining trend with all the three AEDs studied. We confirm adverse effects on bone following AEDs in female rats. Further, our results demonstrate for the first time that these effects are more pronounced in ovariectomised rats as compared to normal rats and that this could be related to estrogen deficiency which in turn enhances bone resorption via increased RANKL and reduces bone formation via increased sclerostin and reduced P1NP. Finally, our study demonstrated for the first time that AED treatment displayed changes in the serum levels of wnt inhibitors and hence modulation of wnt inhibitors might be partly involved in their adverse effects on bone.

Immune Response To Vaccination

How does the human immune system react to vaccination to confer immunity?  Using Yellow Fever vaccine, it has been shown that certain T cells divide within the first two weeks after exposure to the antigen and thereafter slowly divide, with an epigenetic profile allowing for rapid response upon re-exposure to the antigen.  Abstract:

The differentiation of human memory CD8 T cells is not well understood. Here we address this issue using the live yellow fever virus (YFV) vaccine, which induces long-term immunity in humans. We used in vivo deuterium labelling to mark CD8 T cells that proliferated in response to the virus and then assessed cellular turnover and longevity by quantifying deuterium dilution kinetics in YFV-specific CD8 T cells using mass spectrometry. This longitudinal analysis showed that the memory pool originates from CD8 T cells that divided extensively during the first two weeks after infection and is maintained by quiescent cells that divide less than once every year (doubling time of over 450 days). Although these long-lived YFV-specific memory CD8 T cells did not express effector molecules, their epigenetic landscape resembled that of effector CD8 T cells. This open chromatin profile at effector genes was maintained in memory CD8 T cells isolated even a decade after vaccination, indicating that these cells retain an epigenetic fingerprint of their effector history and remain poised to respond rapidly upon re-exposure to the pathogen.

Watch a garden grow and indulge on an orange muffin

I love gardens, flowers, veggies, trees, greens. Everything green is attractive to me. This is why I filled a dozen jars, vases and buckets with greenery from the backyard garden.

Winters in northeast U.S. deprive me of my favorite time in the garden. So, at this time of the year (it is December now), I desperately seek blogs and YouTube videos about gardens. 

This morning I found the YouTube channel Suburban Homestead. The creator of the channel offers quiet, calming videos on gardening and related topics. The guy throws in a few recipes as well. And here is a good episode to start with:

Calm and in control: this is how I feel in my garden. It is a sort of “active” mediation. Instead of sitting and focusing on my breathing, I work in the garden and free my mind of all the noise and nonsense of the day. Watching the videos of the Suburban Homesteader has more or less the same effect on my brain (sadly, not my physical activity levels).

This weekend, I, the anti-sugar fanatic, baked oatmeal-orange muffins. The recipe might have come from a fiction book or Pinterest (I do not remember how I obtained it), but I substituted the sugar, milk and oil with bananas, water and applesauce, respectively, so in a way it is a new experimental recipe.

Orange muffins (for 24 cupcakes):

Ingredients:
1 and 1/2 cups oats
2 and 2/3 cups of flour (I use 1:1 whole wheat and white flour)
2 ripe bananas, mashed
4 tsp baking powder 
3 large eggs
1 cup of water
2 cups unsweetened applesauce
12 Tbsp orange marmalade
the zest from one orange (grate the peel of one orange)

Directions 
Preheat the oven at 400F. Line the muffin pans with cupcake papers. Mix the flour, oats, and baking powder. Separately, mix the eggs, water, applesauce, orange zest and mashed bananas. Add to the dry ingredients and mix only until combined. Distribute 1 Tbsp of batter to each muffin cup, spread on the bottom. Drop ½ Tbsp marmalade in the center of each muffin cup. Fill the muffins with the rest of the batter. Bake for 25 minutes.

The verdict: the muffins tasted fine; however, next time, I will make my own marmalade filling from 2-3 oranges and their peel. The store-bought marmalade was too sweet and a bit runny, so it leaked to the paper liners. Peeling the paper cups from the muffins was a feat. I may have to non-stick spray even the cupcake papers next time!

Genetic Variation And Immune Checkpoint Therapy

Patient response to immune checkpoint therapy is influenced by patient genotype.  It may be necessary to determine individual genetic variation before applying this therapy; alternatively, is it possible to adjust therapy to make it more effective even for patients with less optimal (for therapy) immune genotypes.  Abstract:

CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I, was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed unique elements that may impair CD8+ T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.

Lentils, potatoes and sausage

There is nothing better than a steaming, fragrant bowl of soup on a chilly winter day. The one hour of soup cooking warms up the house and sharpens the senses for the upcoming treat.  

The added benefit is that the soup is high in fiber and it will support your effort for normal body weight.

Be prepared to cook for a crowd with this recipe! The low price of the ingredients puts this soup recipe on my short list of dishes for the winter.

Best lentil soup ever 

Ingredients
1 lb green lentils
1 large sweet onion, chopped into cubes
celery, sliced thinly (optional and to the taste)
1 cup carrots, chopped into chunks (or a handful of baby carrots)
garlic, chopped (I usually peel one entire head)
2 large potatoes, cubed (any type)
sausage (any type you like, in any quantity)
spices: salt, winter savory, paprika, hot pepper flakes, mint (anything beyond salt is optional, to your taste)
1 Tbsp olive oil (optional)
to serve: your favorite vinegar or lemon juice
 

Directions
Start with baking the sausage and cutting it into cubes.
While the sausage is baking, take the largest soup pot you have and in it, combine all vegetables except the lentils with 2-3 cups of water and a spoonful of olive oil (optional). Bring to boil and cook until the potatoes are soft (add water, as needed). 

Once the potatoes are soft, stop the heat and mash everything in the pot with a hand masher. After some of the potatoes are mashed (to create the thicker texture of the soup), add the lentils and water to almost the final volume of the soup. I usually add hot water pre-warmed in the microwave or on an additional stove burner.

Once the soup is boiling again, add the cubed sausage and cook until the lentils are ready. Add salt and spices according to your taste. Some suggestions on seasonings are listed above; however, you could change the soup taste by using cardamom, turmeric, bay leaf, etc. I usually stick to winter savory, mint, and hot flakes.

The aroma during the cooking is irresistible. You might notice the rest of the family being attracted to the kitchen by the tantalizing smell. Be patient! Once you add a few drops of lemon or apple cider vinegar to your  bowl, enjoy the most fragrant and nourishing soup ever! 

Bon appetit!

As I indicated, I cook the soup amount for a battalion (well, maybe for 18 - 20 servings).  Therefore, I usually portion the soup into glass jars and freeze. If you do so, be careful not to fill the jars to the brim (otherwise, they may break)!