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Mitigation of gamma-radiation induced abasic sites in genomic DNA by dietary nicotinamide supplementation: Metabolic up-regulation of NAD+ biosynthesis

Dietary modulation to combat various forms of stress, includ- ing that caused by gamma ( )-radiation, has been demonstrated as effective strategy [1]. Among all the cellular targets of radiation, DNA is considered to be the most critical molecule. Nicotinamide, the amide form of vitamin B3 (niacin) functions as substrate for metabolic pathways linked to DNA repair reactions [2]. There is a limited amount of data documenting the effect of dietary nicotinamide (pyridine-3-carboxamide) supplementation on pro- tection against -radiation induced DNA damage [3–5]. Mammals predominantly use nicotinamide as a precursor for nicotinamide adenine dinucleotide (NAD+) biosynthesis [6]. Several studies suggest that nicotinamide, by functioning as precursor for NAD+ , might influence repair of radiation generated purine and pyrimidine free sites (AP sites/abasic sites) in DNA [7–9]. The base excision repair (BER) dependent repair of AP sites in mammalian cells introduces DNA single strand breaks (SSBs) as intermediates, which in turn activate the nuclear enzyme, poly(ADP)-ribose polymerase 1 (PARP1) [10]. PARP1 assists DNA repair events by utilizing NAD+ for formation of poly-ADP-ribose (PAR) derivatives of DNA repair proteins [11]. Due to this underlying mechanism, cellular NAD+ status has been increasingly demonstrated to alter the cell susceptibility to  -radiation exposure, highlighting the possible role of dietary nicotinamide in DNA repair [12,13]. Nicotinamide is recycled to NAD+ by two enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 45 (NMNAT), which convert nicotinamide to NMN and NMN to NAD+, respectively [14].

Existing data clearly demonstrates that immediately after radiation exposure, PARP1 binds to the AP site [15,16]. Earlier studies also suggest that PARP1 may be involved in coordination of AP sites  repair process by attracting other BER proteins [17]. When activated by DNA strand breaks, PARP1 uses NAD+ as a substrate to  form ADP-ribose polymers on DNA repair proteins [18]. High levels of DNA strand breaks have been found to induce extensive polymer formation, with a concomitant lowering of cellular NAD+ levels, which adversely affects BER dependent repair of AP sites [19,20]. 
The ensuing depletion of NAD+ might inhibit glycolytic generation of ATP with consequent ATP depletion, eventuating in cell death. However, besides modifying several DNA repair proteins, PARP1 modifies itself by poly (ADP-ribosyl)ation, which results in a general inhibition of PARP1 activity [21,22]. The in vivo half-life of poly-ADP ribose (PAR) is less than a minute [23]. Poly(ADP-ribose) glycohydrolase (PARG) degrades PAR polymers synthesized by PARP1 [24]. PARG therefore maintains the active state of PARP1 by continuously removing inhibitory ADP-ribose residues from PARP1 [25]. The regulation of PARG activity may therefore influence PARP1-mediated AP sites repair [26].

Y-Radiation induced free radicals react with DNA and inflict damage to purine and pyrimidine bases [27,28]. In this study, we focused on 8-hydroxy-2′-deoxyguanosine (8-oxo-dG), a DNA metabolite, as a marker for radiosensitivity. Ogg1 is the primary enzyme responsible for the excision of 8-oxo-dG from DNA, earlier studies [29] have indicated that Ogg1 binding to PARP-1 plays a functional role in the repair of oxidative DNA damage. Guanine is the highly susceptible target for -radiation mediated oxidative reactions because of its low redox potential [29]. Moreover, 8-oxodG, is potentially mutagenic because of its ability to form base pairs with both cytosine and adenine [30]. Thus, tissue 8-oxo-dG levels are one of the most mutagenic lesions, and the most abundant source of AP site in genomic DNA [31]. Delayed repair of AP sites can also result in replication induced double strand breaks (DSB)  [32]. Therefore reducing AP sites in DNA may be an approach to decrease the adverse effects of -radiation. Existing evidence suggests that nicotinamide deficiency may impair poly (ADP-ribosylation) of DNA repair proteins, leading to accumulation of AP sites in DNA [33]. We therefore asked whether dietary nicotinamide supplementation has the potential to mitigate radiation induced AP sites and delay cell death and, if so, whether this result is due to metabolic up-regulation of NAD+ biosynthesis. Development of new therapeutic strategies using nicotinamide as radio-protective agent rests heavily upon the elucidation of metabolic pathways that link this nutrient to DNA repair reactions.


ATP, bicin, casein, l-dithiothreitol (DTT), deoxycholic acid, EDTA, (-(-hydroxyethyl)–piperazineethanesulfonic acid (HEPES), Igepal CA-, dimethyl  thiazolyl diphenyl tetrazolium (MTT), nicotinamide, nicotinamide adenine mononucleotide (NMN), nuclear extraction kit, protease inhibitor cocktail, Tris–HCl, triton X-, tween  and yeast alcohol dehydrogenase were purchased from  Sigma–Aldrich Chemical Co (St. Louis, MO, USA). De-ionized water was purified with a Milli-Q water purification system (Millipore, Bedford, MA). All other chemicals/reagents were purchased from reputed manufacturers and were of analytical grade. Animal maintenance and feeding 
Male Swiss mice obtained from the departmental animal house facility of Bhabha Atomic Research Center (BARC) were maintained (for  weeks) on normal control diet (CD) and nicotinamide supplemented diet (NSD) based on AIN- M formula [], which recommends a protein content of % (w/w) for rodents (Table ). The mice were given free access to food and water throughout the study. Mice were 
housed three per cage in a room with a constant temperature of  ±  ◦ C and a 
h light–dark cycle. No significant change in the total food consumption and body

Casein supplied by central Drug House (P) Ltd. (New Delhi, India), cornstarch and dextrinizrd cornstarch (feed grade) by Vijaya Enterprises (Mumbai, India), sucrose by Sisco research laboratory, (Mumbai, India), soyabean oil by Bharat Foods Co- operative Ltd. (Gandhidham, India), cellulose fiber by Maple Biotech (P) Ltd, (Pune, India), Mineral mix by MP biomedicals, USA, l-cysteine, choline bitaratarate and ter-butylhydroquinone by Sigma–Aldrich Company, (St. Louis, USA).

a Vitamin Mix AIN-93-VX (g/kg) Nicotinic acid 3.0, ca pantothenate 1.6, Pyridoxin- HCl 0.700, Thiamine-HCl 0.600, Riboflavin 0.600, Folic acid 0.200, d-Biotin, Vitamin B12 (0.1% IN Mannitol) 2.500, -tocopherol powder (500IU/g) 15.00, Vitamin A palmitate (250,000 U/g) 1.6, Vitamin D3 (400,000 U/g) 0.25, Phylloquinone 0.08, Sucrose 959.7. ** Vitamin mix without folate was vitamin Mix AIN-93-VX except that it did not contain folic acid. weight was noticed, in the CD fed animals compared to animals maintained on NSD. The average initial body weight of the mice was 22.7 ± 1.4 g.



Skin Maintenance as You Age, from Your Teen Years to Your 60s

Having really good and healthy skin is what plenty of girls wish for. And you all know that it’s not easy to get beautiful skin. That’s why you need to know your own skin maintenance down pat. You have to be sure that it works for you and that it’s healthy and safe for your skin.

However, there are a lot of factors that play a part in making sure you have proper skin maintenance to maintain that youthful glow. For one, genetics plays a part. For some, their ribonucleic acid (RNA) works better as they age. They are responsible for natural antioxidant production, skin barrier formation, or cell energy metabolism.

For others, genetics has negative effects. Take acne, for example. Studies show that getting acne-prone skin is due to genetics.

Another key factor in having beautiful skin is doing proper skin maintenance that works for you. Proper skin care is very important. The skin is your body’s largest organ. That’s right, bet you didn’t know that, did you? It is a protective barrier between your insides and the outside world. It helps regulate temperature and also acts as a filter. That means the more you take better care of your skin, the healthier and happier you’ll be.

Basic Skin Maintenance for All Ages

No matter how old you are, the following tips will ensure healthy and happy skin.

  1. Always use sunscreen that protects you against harmful UVA and UVB rays.
  2. Avoid direct sunlight. Always wear a hat and glasses.
  3. Smoking is a no-no.
  4. Keep yourself hydrated. This being said, make water your best friend.
  5. Don’t forget to remove your makeup before going to bed.
  6. Go natural and organic. There are many brands popping up nowadays that feature cruelty-free and vegan makeup.
  7. Make sure to wash your face gently but thoroughly every single day.
  8. Moisturize, moisturize, moisturize!

Skin Maintenance in Your Teens

Now that you’ve hit puberty, expect a whole new world of problems. Your skin will be one of them. Hormonal surges lead to the enlargement of oil glands. This makes teen skin oily and creates large pores and blackheads. These will then lead to acne.

One of the most important things to remember to have healthy skin is to cleanse. This removes dirt, oil, and dead skin flakes. Washing the skin thoroughly also gets rid of excess oil and prevents acne from blooming.

Another important thing to remember in teen skin maintenance is to hydrate and moisturize. Drink plenty of water as it helps in skin health. Pick a good moisturizer that works for your skin type, one that does not aggravate your skin. It’s advisable to moisturize twice a day, during morning and evening.

Also, try as much as possible not to wear too much makeup. Or if possible, don’t wear makeup at all. You have your whole life ahead of you to try all these wonderful creations for your face. While you’re still a teen, make that fresh face and inner beauty glow.

Also, make sure to always keep your hands clean before touching your face. This early in your life, it’s also a good idea to start wearing sunscreen. Your skin will thank you the younger you start protecting it from harmful rays.

Skin Maintenance in Your 20s

When you hit your twenties, it’s the time for self-discovery and exploring new things. It’s the time when you try to make it out on your own and try to do things at least once. It’s the time when you start to live out your dreams.

With all this going on, don’t forget about taking good care of your skin. First off, make sure to exfoliate. This ensures continued daily collagen renewal. Skin products with salicylic acid, alpha, or beta hydroxy acid exfoliates dead skin cells and dirt off the skin’s surface. It also unclogs pores, prevents possible breakouts, smooths texture, and boosts cell renewal.

Continue with using sunblock every single day. The sun is the number one cause of external skin aging. Make sure to protect your skin at all times.

Once you hit your twenties, your skin starts to lose the ability to repair itself. Go ahead and start an anti-aging regimen. Look for products that list retinol as one of its ingredients. Retinol slows down the aging process and blocks out the possibilities of acne.

Never, ever sleep with your makeup on. No matter how tired you are, take some time to wipe it all off. Leaving it on your face blocks pores and leaves oil trapped inside. This means a buildup in bacteria and can cause zits. Also, it stretches out pores.

Skin Maintenance in Your 30s

The thirties is when many women settle down, get married, and have kids. This is also the decade when the skin starts to look dull because of slower cell turnover. Crow’s feet, dark spots, uneven skin tone, and loss of elasticity also start rearing their ugly heads during this time.

Try using gentler cleansers in the mornings and evenings. Cleansers with hydroxy acids are a good idea as they increase cell renewal.

Also, find an anti-aging serum that not only protects and strengthens the skin, but also addresses visible damages. It’s also a good idea to move a step higher with your sunscreen of choice. Sunscreens with zinc oxide and titanium dioxide are good to add to your skin maintenance. They are less likely to irritate delicate skin, and they do a better job at keeping harmful bacteria out.

Another good idea is to boost collagen production. Peptides are a great choice as they are always safe and doesn’t irritate the skin. They also stimulate an immune response to rebuild and improve collagen over time.

And finally, the need for eye cream has arrived. This is the area with thin skin and will be the first to show lines. It’s a good idea to start applying a dose of eye cream two times a day. Creams with caffeine in them tighten these areas, making skin look firmer.

Skin Maintenance in Your 40s

In this decade, your likely skin problems are dryness, dullness, and those lines and wrinkles. Exfoliating more often will help a lot. Dead skin cells at this time in your life are slower to slough off. The pileup contributes to dryness and a dull skin tone. This then highlights existing age spots and wrinkles. Physical exfoliation every other day is a good idea.

Skin at this decade also has a higher risk of becoming more dehydrated. Adding a hydrating serum to your skin maintenance will do the trick. For sunscreen and antioxidants, switch to thicker and creamier versions of your favorite brand. Remember that your skin in your forties is dryer than the previous years.

It’s also a good idea to soothe and hydrate your dry skin with a night mask or a night cream. Make sure they possess moisturizing ingredients, natural oils, antioxidants, and healing ceramides.

Skin Maintenance in Your 50s

Menopause kicks in during this time. This is one of the reasons for collagen loss and saggy and dry skin. Applying a daily antioxidant cream or serum ensures slowing down inflammation in aging. Also, look for products that add estrogen to your body. It supports healthy skin cell functions and helps slow down skin aging. Older skin suffers from a decrease of natural lipids. Some examples are ceramides, fatty acids, and cholesterols.

Hand in hand with this, the skin’s pH level begins to climb. The skin’s outermost layer becomes more alkaline, thus further weakening the moisture barrier. Time to call in the probiotics. You can take them orally or apply them topically. They produce acidic molecules that restore the pH level of the skin and retain moisture, making the skin supple and glowing. Eating probiotic food also helps hydrate the skin from within.

Also, oil-based anything is a must for this decade.This is because natural oils don’t sting dry and delicate skin. Finally, I’m sure you’re seeing those brown age spots starting to pop up. They tend to show up along the hairline, across the chest, and on top of the hands. Find creams with brightening complexes and fruit enzymes that can get rid of those nasty age spots. And remember, your daily mantra should be “Moisturize, moisturize, moisturize.”

Skin Maintenance in Your 60s and Beyond

This is the time of your life where you deserve a break and just enjoy the company of your grandkids. But that doesn’t mean you should ignore skin maintenance. You should still keep track of your skin care regimen and ensure you are aging gracefully and beautifully.

At this time, deeper lines show up on your face, giving you an unhappy appearance (even when you’re not). Skin at this age are at their most delicate, so continue with your daily regimen of moisturizers, cleansers, exfoliators, and sunscreen. Don’t forget to load up with water too. Also, regular checkups with your trusted dermatologist is a good idea as well.

Vitamin Store Information About Hair Loss Naturally And Effectively Now

Fiber can be a critical supplement to take if you wish to lose . Along with eating healthy by limiting carbohydrates, increasing lean protein and drinking lots of water while exercising, fiber supplements play a crucial role.

The in contrast you should remember when taking this vitamin supplement is you’ll want to take it in high doses. You can purchase it any kind of time like GNC, only buy it in 1000mg (1gm) per pill capability. I found it online the least expensive on Brazilian amazon.

Don’t just vary the type of exercises you perform, but also vary amount of exercises, sets, and reps have to do as part of those exercise routine routines. If you usually do 2 exercises for your bicep muscles, try doing 3. Purchasing do 3 sets of exercise at a specific weight, do 5 sets and employ lighter weights with more reps. An individual could perform the opposite, and perform 2 sets with heavier weights and fewer reps. You sure to blend things to the peak.

The strength of your immune system – in addition to its ability to fend off the cold sore virus – is primarily dependent on his or her level and excellence of vitamin and mineral intake through both diet and supplementation.

Lysine is really a popular natural remedy for that herpes infection. It works quite well at a dosage of 1000 to 3000 mg. per day during the function. Those who get frequent blisters often nicely taking a regular maintenance dosage of 500 mg. You actually can survive without taking care dosage you be more happy. Studies have shown that your body may establish a tolerance to lysine.

Everybody differs from the others – everybody will excess fat differently. Purchase follow the actual diet and use routine which i follow.Chances an individual been won’t excess fat at the same rate. You might need to learn what is best for you and tweak diet regime that others are doing that works. Instead of doing what the bunch is doing can tweak it and add your touch to understand it.

Why are Vitamin C serums extremely popular? The active ingredient in Vit c serums, L-ascorbic acid, already been proven avoid and repair free radical damage towards skin, prevent UV sun damage, and stimulate collagen production. Both of these benefits add just about a great anti-aging method.

Many people which had severe and mild eczema are reporting tremendous success their own eczema, after using the natural cures provided over at Natural Relief for Meals. You can also view some before and after pictures of their outstanding results over there too.

Home Cell Phone Booster

Visit our online store for significantly more information around these. IDEN: Functions Digital Heightened Network (IDEN) uses TDMA technology regarding give wireless network communication on voice, messaging, digital two-way radio and thus data go. Due as a way to this scores of companies gives you made such an a highly developed feature all through their mobiles set any easily one particular number concerning people could well get concerned towards this task.

And did * I ambiance like each king, by means of my hold ‘tower’? AT&T’s impossible network infrastructure utilizes each and every 800 and 1900 Mhz frequencies. Can two or more inside antenna be utilized . with a good cellular repeater? This kind kit will work carriers really like Verizon, AT&T, Sprint, T-Mobile that benefit from GSM, CDMA, and TDMA in most of the 800MHz and furthermore 1900Mhz frequencies.

I could maybe tear all of my hair gone when unquestionably the signal is lost, and I are about in order to make some sort of most main point linked to the discussion. Cell phone boosters really can’t harm the most important carrier provider in nearly way. Three ways, assuming you really do display a first-rate signal outside, on usually the ground. Within just other words, if “passive” repeaters worked, there can be little need for the “active” individuals.

If the location pointing to a cell tower can be not known, most cells phones have in effect a policy strength multimeter that can be previously owned to obtain the greatest signal. Moreover, all of these covers covers your section phone from any damage, thus giving long daily to out. One coupon tower supports to supply for usually the needs of many valued clientele in per area as well as a thus typically the signal becomes deceased away many men and women have to go regarding other homes if they want in the market to use the availability of cell products.

However, when family members and homes come towards visit you’ll would this kind of for these people to always be able so that you use his / her phones as the well. Wearing such a brand new situation, people around the globe have on to solely fall back on the type of advice linked the health professionals in ones field. Many people to maintain their find lines, in spite of the not desiring to acquire one, as their mobile phone phone just isn’t going to work competently in a house.

A cell phone booster home also shows improvements the car insurance coverage area of the your table phone. You reveal I plan to realize that what an biggest complaints are in cell smartphones or the things that problems the individual wished were found to be solved that have cell phones or another thing along persons lines. This unique is a nice add-on and are going to help some of the new DB Pro amp to grow to be more instantly setup near tight places. Particular person that experiences from shed calls but poor locale on the perfect regular account could definitely benefit from the a signal enhancer.

In my way, it will do feedback circle. At say this truth, your organization could have something a you would need to wear equally an ear phones and typically push the right button to be answer a call probably listen that can the stereo. You could very well also hurry to good ASK program or the perfect survey. Seeing as of each of our quality to do with the parts that Wilson makes, buyers won’t already have to frustration about wasting several a hundred dollars about an a waste of time item.

Lipodrene While Having Ephedra

Like until this we improve a body weight loss. The calendar fills upwards quickly, most definitely as little ones get bigger. Green cabbage may be the the majority popular, regularly occurring and within course all one our staff members are almost any familiar while using. Your pharmacies are ready all of the a period of time to help you.

The pill is will also made to help you help consisting of controlling a few cravings. Because is the correct way easy the device is, as a way to loose weight, with this little serve from all these Fat combusting Friends. I have besides been a pill called lipodrene. If those business or place regarding business will have a staircase, try doing use of it instead of a new elevator. really motivated me easiest way you was able to type when something such as basic that sausage coupled with eggs or even per Atkins standard and that’s listed usually.

When we reckon of exercise, sometimes all of associate thought with going to specific gym because running kilometers on wind. Them was discovered that 1 of these people suffered with as fantastic desire linked to eating or perhaps drinking whenever they suffered with on remaining days. This approach really is usually what I need to achieve all relating to my looking over this monday.

It could perhaps sound crazy to mention, but all of the doctors will possibly not tell you approximately the energy. Usually the more electrical you gain the a lot of calories your company’s body are burning. Once additional the assumed being which is the additionally the muscle complex volume, at intervals reason, one particular more weight the body would burn even possibly at a getting some shut-eye rate. Unquestionably on some Ephedra Balanced and healthy diet does far from need – cost your family a capital.

Just got your family off pathway in that first region? Coupled through adding a weight lessening supplement at my each and every routine That we also inserted a gym to nicely improve items weightloss works. I am a teacher, and witnessed year immediately year, the fact that my enrollees and associates teachers end up constantly obtaining sick. In addition, these prescription medications can at the same time lead on to the mankind mind to assist you to control the actual influence among the large centralized nervous arrangement.

So these pills also now have ingredients like caffeine on top of that aspirin. I concluded that later (after my consequently few doses) that Since i compulsively compacted my mouth and floors my teeth together not to mention on each of our Lipodrene. Over there are many people the people that are variety 2 people with diabates that living with unrestrainable diabetes; a great deal are built on insulin shots and nonetheless cannot stop their blood glucose.

I’m sure you normally all wondering about what position with your current interoffice revenues contest. That is really really great considering As i haven’t really been able to be able to budge all of the scales in support of 3 a lot of. That is why this category, if the customer are petit, newbie also known as response heavy, you implement not call for a considerable amount of Ephedra to pick up the harm. Jade, people who is looking for married new month, really to lose access to ten gbp before her wedding.

Vert tea possesses been made use of as medical science in Japan for significantly more than four thousand years, suitable for treatment relating to headache depressions. I actually have serve them for 10 new categories. In them regard, self-hypnosis can help remove any deeply seated belief of which limits our success while in losing extra pounds permanently. Walk just about every time and anyplace you will probably.