#chemopreventive effects

[chinesegreenteagoldentriangle]

Mechanism of EGCG binding to p53 revealed: Polyphenolic compounds in green tea may enhance anti-tumor activity by stabilizing p53.

A new study has found that epigallocatechin gallate (EGCG), a polyphenolic compound found in green tea, can induce apoptosis in cancer cells, but its potential molecular mechanisms are not well understood. Recently, a team led by Chunyu Wang at Rensselaer Polytechnic Institute (with China Agricultural University as the first author's affiliation and Jing Zhao as the first author of the paper) published a study in Nature Communications titled "EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction". The study used SPR and NMR to report the direct interaction between EGCG and the tumor suppressor p53 (KD = 1.6 ± 1.4 μM), with the disordered N-terminal domain (NTD) identified as the main binding site (KD = 4 ± 2 μM). Large-scale atomic simulations (>100 μs), SAXS, and AUC showed that the EGCG-NTD interaction is dynamic, with EGCG leading to a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupted the interaction between p53 and its regulatory E3 ligase MDM2 and inhibited MDM2-mediated ubiquitination of p53 in vitro, potentially stabilizing p53's anti-tumor activity. Overall, this study provides insights into the anti-cancer mechanism of EGCG and identifies the p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.

In recent years, diet-based cancer prevention and treatment have received considerable attention. Green tea is a popular beverage worldwide and has been reported to have inhibitory effects on various types of cancers, such as breast cancer, lung cancer, prostate cancer, and colon cancer. Most of the chemopreventive effects of green tea on cancer are attributed to polyphenolic compounds, with epigallocatechin-3-gallate (EGCG) being the most important. EGCG accounts for 50-80% of the catechins in green tea. A cup of brewed green tea (240 mL) contains 200-300 mg of EGCG. A serum concentration of 0.1-1 μM EGCG can be achieved by drinking a cup of green tea or taking an EGCG tablet. The anticancer effects of EGCG have been confirmed in epidemiological, cell culture and animal studies, as well as clinical trials.

A 10-year prospective study by Nakachi and Imai reported that people who drink more than 10 cups of green tea per day have a lower risk of cancer compared to those who drink less than 3 cups per day. Recently, Shin et al. found in a randomized clinical trial in Korea that green tea extract can reduce the recurrence rate of colorectal adenomas by 44.2%. In vitro, EGCG has been shown to promote growth arrest and induce apoptosis in a variety of human cancer cell lines, including prostate cancer cells, epidermoid carcinoma cells, bladder cancer cells, and colon cancer cells.

In mice, oral administration of green tea or intravenous injection of purified EGCG can inhibit angiogenesis and suppress the growth of solid tumors. At the molecular level, EGCG has been shown to interact with cancer-associated proteins, such as glucose-regulated protein 78 (GRP78) and Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), with an affinity of approximately μM.

In EGCG-induced apoptosis and growth arrest, p53 plays an important role. p53, often referred to as the "guardian of the genome," is a critical tumor suppressor that is mutated in over 50% of human cancers. p53 promotes cell cycle arrest or apoptosis as a response to cellular stress stimuli such as oxidative stress, oncogene activation, and DNA damage. As a transcription factor, p53 is tightly regulated and has a short half-life. p53 protein is typically maintained at low levels in healthy mammalian cells through continuous ubiquitination and subsequent degradation.

Under cellular stress, ubiquitination of p53 is inhibited, and p53 is stabilized. Then p53 accumulates in the cell nucleus and activates the expression of target genes, thereby triggering cell cycle arrest, apoptosis, and DNA repair processes. In addition to serving as a transcription factor, p53 can also be translocated to the cytoplasm or mitochondria. p53 directly interacts with anti-apoptotic proteins such as Bax and Bcl2 to induce apoptosis and also participates in the anti-aging effects of EGCG.

Full-length p53 consists of an N-terminal domain (NTD), a DNA-binding domain (DBD), a tetramerization domain (TET), and a C-terminal regulatory domain (REG). The NTD is further divided into two transcription activation domains (TAD1 and TAD2) and a proline-rich domain (PRD). The NTD is an intrinsically disordered protein (IDP) that interacts with many proteins and serves as a hub for cellular signal transduction. The NTD is not only necessary for transactivation but also interacts with MDM2 to mediate the ubiquitination and degradation of p53.

Independent of ubiquitination, MDM2 also inhibits transcription by preventing the general transcription factors from binding to the NTD. The apoptotic effect of EGCG on human cancer cells is related to its interference with MDM2-mediated ubiquitination of p53. It has been reported that EGCG can also stabilize p53 and increase the phosphorylation of critical serine residues. In a recent study, EGCG was identified as an inhibitor of the p53-MDM2 interaction from a library of 2,295 plant chemicals. However, the molecular mechanism by which EGCG disrupts the MDM2-p53 interaction is not yet clear.

In this work, direct binding between EGCG and p53 mediated by the NTD of p53 was demonstrated. The study suggests that the EGCG-p53 interaction disrupts the MDM2-p53 interaction and inhibits the ubiquitination of p53, potentially stabilizing p53's anti-tumor activity and providing a structural mechanism for the anti-cancer effects of EGCG.

[brookebeebe-blog]

July 19th - Gold Mine, Jiufen Mountain Village, and Lantern Lighting

Today, I got some really good sleep, which was very exciting. I woke up refreshed and ready to go. I was also really excited for the itinerary today. We went to a gold museum first and I got to touch a huge block of gold that weighed around 485 lbs. Then, we went to the Jiufen Mountain Village. This area had a lot of shops and there were tea houses further down. It had a beautiful view. I finally finished buying souvenirs for everyone in my family here, but what I learned is that Zoe and I should not be allowed to shop together. We kept convincing each other to buy things and I ended up spending around $2500, which was not what I had intended. I also bought some food from around the area, which was really good. Later, we were supposed to go to a mining museum, but it was closed. This turned out to be a good thing though, because we got to light lanterns and it’s something I have always wanted to do. First, they let us paint our wishes on the lantern and then we took it out to the train tracks to send it up. The bus rides were long today, but honestly I didn’t mind because we got some time to rest before each activity.

Academic Reflection

Since we went to a bunch of tea shops today, I will focus on the reading about tea’s health benefits. According to the reading, tea contains something called polyphenols, which may reduce the risk of cancer, cardiovascular disease, arthritis, and diabetes. Tea has also been linked to a reduced link of Parkinson’s. Green tea especially, is becoming world renowned for its healing properties, although that is not the only kind that is beneficial. It can be chemopreventive and some research even suggests it can increase metabolism. Although results look positive, the testing on animals is in much higher doses and experimental conditions are optimized for the best effect. The research would have to be conducted on humans in more realistic scenarios and quantities in order to provide accurate results, but it appears tea is good for all kinds of health reasons. Not only is tea super good for your health, it is also a big part of the culture in Taiwan and I was really glad I got to see a tea house in person, especially one overlooking the mountains.

[didanawisgi]

Papers Reviewed:

2020 (Sarami et al) - Study on the Effect of Ethanol Ginger Extract on Cell Viability And p53 Level in Breast and Pancreatic Cancer

2021 Jun (Zadorozhna et al) - Mechanisms of Chemopreventive and Therapeutic Proprieties of Ginger Extracts in Cancer

2022 May (Ozkur et al) - Ginger for Healthy Ageing: A Systematic Review on Current Evidence of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties

2022 May (Abdel-Rasol et al) - The Antitumor Activity of Ginger against Colorectal Cancer Induced by Dimethylhydrazine in Rats

2022 Sep (Kim et al) - Efficacy and Safety of Ginger on the Side Effects of Chemotherapy in Breast Cancer Patients: Systematic Review and Meta-Analysis

2023 Nov (Chen et al) - Research progress of ginger in the treatment of gastrointestinal tumors

2024 Apr (Xiang et al) - Pharmacodynamic components and mechanisms of ginger (Zingiber officinale) in the prevention and treatment of colorectal cancer

[discoverybody]

What Effect does Beetroot Have on Cancer?

When it comes to human health, beetroot, which is a versatile tuber in addition to being rich in nutrients, has a number of benefits. Although it is low in calories, it is high in a variety of nutrients, such as protein, fiber, calcium, iron, and medicinal compounds like flavonoids and polyphenols. The possibility that beetroot could play a part in the treatment and prevention of cancer is one of the most fascinating elements of this vegetable.

There is evidence that the high folate and B vitamin content of beetroot may reduce the likelihood of developing some cancers, according to research. Additionally, the dietary pigment betalain, which is responsible for the red color of beetroot, has been found to display cancer-protective benefits. These effects include the inhibition of the synthesis of carcinogens as well as the promotion of immune cell and enzyme development.

The power of beetroot to prevent and manage the development of cancer metastases has been acknowledged in traditional Persian medicine as well as in other therapeutic systems. Studies conducted in clinical settings have demonstrated that beetroot juice is beneficial for people suffering from breast, prostate, and colon cancer. Betelains, flavonoids, polyphenols, and saponins are some of the micronutrients and bioactive chemicals that beetroot contains. These substances are responsible for the association between beetroot and the prevention of cancer. In addition to exhibiting anti-inflammatory and antioxidant activities, these substances have been discovered to possess chemopreventive capabilities.

Other health benefits are associated with beetroot, in addition to the possibility that it has a role in the prevention of cancer. In addition to enhancing detoxification, the antioxidants in it shield the liver from oxidative stress and inflammation. Beetroot, which contains a high amount of nitrate, has been shown to improve the power of the cardiac muscle and can improve exercise performance by increasing the amount of oxygen that supplies the muscles. Through the stimulation of nitric oxide synthesis and the widening of blood arteries, it also contributes to the regulation of blood pressure. Additionally, beetroot contains nutrients such as magnesium, which are responsible for maintaining healthy bones.

[drforambhuta]

Utilization of Precision Oncology in Breast Cancer Management

The implementation of precision oncology has transformed the approach to treating breast cancer across its various subtypes, presenting novel pathways for tailored therapeutic interventions and individualized treatment methodologies. Key facets of applying precision oncology in breast cancer management encompass:

1. Tailored Treatments: Precision oncology facilitates the recognition of actionable molecular targets like HER2 amplification or mutations in genes such as BRCA1/2. Therapeutic interventions, such as HER2-targeted medications (e.g., trastuzumab) or PARP inhibitors (e.g., olaparib), selectively impede aberrant signaling pathways or exploit vulnerabilities in cancer cells, thereby enhancing treatment efficacy and minimizing adverse effects compared to conventional chemotherapy.

2. Immunotherapy: Immune checkpoint inhibitors, which harness the body's immune response to combat cancer cells, have emerged as a promising therapeutic avenue in breast cancer. Precision oncology aids in identifying individuals likely to benefit from immunotherapy based on specific biomarkers like PD-L1 expression or tumor mutational burden (TMB).

3. Understanding Resistance Mechanisms: Resistance to conventional therapies poses a significant obstacle in breast cancer management. Precision oncology elucidates the mechanisms behind treatment resistance by pinpointing secondary mutations or alternative signaling pathways activated in resistant tumors. This comprehension informs the development of combination therapies or innovative treatment modalities to surmount resistance and enhance patient outcomes.

4. Tailoring Clinical Trials: Precision oncology facilitates the design of clinical trials targeting precise molecular subtypes or genetic alterations in breast cancer. Basket trials, which enroll participants based on shared molecular characteristics rather than tumor types, enable the evaluation of targeted therapies across diverse cancer types, expediting drug discovery and development.

5. Liquid Biopsies: In addition to conventional tissue biopsies, precision oncology harnesses liquid biopsies like circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) to monitor disease progression, detect minimal residual disease, and identify treatment resistance. Liquid biopsies offer a minimally invasive and real-time approach to assessing tumor dynamics and informing treatment decisions.

6. Risk Assessment and Prevention: Precision oncology extends beyond treatment to encompass risk assessment and preventive strategies. By analyzing germline and somatic mutations linked to breast cancer predisposition, precision oncology identifies individuals at heightened risk of developing the disease. This enables personalized screening protocols, risk-reducing interventions, and targeted preventive measures like chemoprevention or prophylactic surgery to mitigate the risk of breast cancer onset.

7. Psychosocial Support and Survivorship: Precision oncology underscores the significance of comprehensive care, encompassing psychosocial support and survivorship programs. A cancer diagnosis can exert profound psychological and emotional effects on patients and their loved ones. Precision oncology integrates psychosocial interventions such as counseling, support groups, and survivorship care plans to address the emotional, social, and practical needs of patients throughout their cancer journey.

Doctors suggest undergoing regular health checkups for the diagnosis of conditions like cancer at their early stage. There are many good hospitals in India that offer a full body health checkup package for the early detection and management of breast cancer.

[oaresearchpaper]

Garlic Oil: Protecting Against Doxorubicin's Effects

Abstract

Doxorubicin, also known as Adriamycin, is a highly effective antineoplastic agent, but it is well known for its oxidative damage to various body organs, such as hepatotoxicity. The present study aimed to investigate the possible protective role of the natural antioxidant garlic oil on Doxorubicin-induced liver toxicity. Studies were performed on four groups of mice. Control group, garlic oil group, doxorubicin group for seven doses, and doxorubicin plus garlic oil group. Histological examination of liver sections revealed that doxorubicin caused pathological changes in liver cells as well as the reduction in the liver nuclear area and nuclear volume. Administration of garlic oil plus doxorubicin showed a reduction in liver damage induced by DOX.

Introduction

The liver is one of the largest and most important organs in the body and has diverse functions in metabolism, detoxification and synthesis of many biomolecules and it is the first organ affected by DOX treatment (Prasanna et al., 2020). Doxorubicin (DOX is one of the most effective anthracycline antibiotics and anti-tumour agents used to treat a variety of human malignancies, including hepatocellular carcinoma (Osama and Suzan, 2008). Doxorubicin has a greater effect on cells that are multiplying rapidly, but it can kill both healthy and cancerous cells (Saalu et al., 2009.). Doxorubicin has many side effects, including hepatotoxic, cardiotoxic, nephrotoxic, and immunosuppression (Chaudhary et al., 2016). Liver damage is a relatively common adverse effect in patients with other cancers who are treated with doxorubicin (Cainelli and Vallone, 2009). Oxidative stress is generally considered a major cause of DOX hepatotoxicity. Dox produces hydroxy radical, which destroys DNA primarily in cancerous cells. Doxorubicin can cause an imbalance of oxygen free radicals and antioxidants which causes damage to liver tissue (Mohan et al., 2014). Natural products, including plants, have been used by humans in traditional medicines to treat and alleviate different diseases and are valued for their ability to protect against all types of diseases (Wambi et al., 2009). Several natural and synthetic antioxidants have been suggested to protect against DOX-derived cardiotoxicity (Asensio-Lopez et al., 2012; El-Bakly et al., 2012). Plant phenolic compounds such as flavonoids and isoflavones have an important role in the treatment of many diseases and some of them induce a potent antioxidant and hepatoprotective effect (Seif, 2016). Garlic (Alium sativum) is a bulbous plant whose bulb has a strong taste and characteristic odor. Garlic has been well known for its medicinal use since ancient times and has been reported to have antioxidant properties in vitro (Reitz et al., 1995). Garlic is used as hypolipidemic and cardiotonic. Some garlic preparations also appear to possess hepatoprotective, immune-enhancing, anticancer, chemopreventive and antioxidant activities (Harunobu et al., 2001). In mammals, garlic has effects of hypolipidaemia, hypoglycemia, hypotriglyceridaemia and hypocholesterolaemia (Ali et al., 2000).

The aim of the present study is to investigate the potential beneficial role of garlic administration against histomorphometrical alterations induced in the liver by doxorubicin in male mice

source : The protective role of garlic oil against doxorubicin-induced hepatotoxicity in male mice

[periwinklemeanderings]

"Important issues concerning folate chemoprevention

Although folate appears to be an ideal candidate for chemoprevention given its proven safety and cost (73), the safe and effective dose range of folate supplementation and optimal timing of folate chemoprevention have not been clearly established in humans. Animal and some clinical studies have suggested that folate supplementation may increase cancer risk and accelerate tumor progression if too much is given or if it is provided after neoplastic foci are present in the target organ. Therefore, it appears that modest levels of folate supplementation should be implemented before the development of precursor lesions in the target organ or in individuals free of any evidence of neoplastic foci. -

[aayushi1806]

12 Health Benefits Of Beer

Beer is an alcoholic beverage brewed from cereal grains which are responsible for its nutritional values. People usually prefer to drink it with certain meals and it is the third most popular drink preceded by tea and water.

Beer has a greater protein and��vitamin B content than wine, while its antioxidant content is equivalent to that of wine. Hops, a major component for brewing this beverage, are rich sources of flavonoids, which are potent antioxidants.

It is a very good source of certain minerals that play essential roles in various metabolic processes. If taken in moderate quantities, it can definitely boost your health in a number of ways.

BEER BENEFIT 1: Prevents Cancer

Could beer prevent cancer? Scientists at the University of Idaho think so.

At the National Meeting of the American Chemical Society in January, researchers presented findings that suggested a key ingredient in beer could be used in the fight against cancer and inflammatory diseases.

A flavonoid compound called xanthohumol is found in the hops commonly used in brewing beer. It has been seen to play a major role in the chemoprevention of cancer, including prostate cancer. According to Bio-medicine, it is also a good source of polyphenols, due to the grains used for fermentation. It has been proven effective in fighting cancer, just like red wine.

Acids called humulones and lupulones, which are also found in hops, possess the ability to halt bacterial growth and disease, and scientists hope to find a way to extract these compounds or synthesise them in a lab in order to develop active agents for cancer-treating pharmaceuticals.

BEER BENEFIT 2: Beer lowers the risk of kidney stones

Last year, a study suggested that the risk of developing kidney stones decreases with increasing beer consumption.

Researchers of the National Public Health Institute at Helsinki used their detailed study of 27,000 middle-aged men to conclude that “each bottle of beer consumed per day was estimated to reduce risk by 40 per cent”.

The study authors noted that both the water and alcohol found in beer are shown to increase urine flow and dilute urine, thereby reducing the risk of stones forming. Alcohol may also increase the excretion of calcium, the prime constituent of kidney stones.

BEER BENEFIT 3: Beer protects you from heart attacks

Another research held found that dark ales and stouts can reduce the incidence of heart attacks.

Atherosclerosis – when artery walls become furred-up with cholesterol and other fatty substances – is known to cause heart problems, but a different study revealed that beer can cut the risk of this disease by as much as half.

However, the most important thing here was that moderation is the key.

Beer contains vitamin B6, which protects against heart diseases by preventing the build-up of a compound called homocysteine. It has a thinning effect on the blood and prevents the formation of clots, which cause blockages in the coronary arteries. Moderate consumption also reduces the risk of inflammation, the root cause of atherosclerosis, which is cholesterol and plaque building up on the blood vessels and artery walls.

BEER BENEFIT 4: Beer reduces the risk of strokes

Studies by both Harvard Medical School and the American Stroke Association have shown that people who drink moderate amounts of beer can cut their risk of strokes by up to a 50pc, compared to non-drinkers.

Ischaemic strokes are the most common type of stroke. They occur when a blood clot blocks the flow of blood and oxygen to the brain. However, when you drink beer, your arteries become flexible and blood flow improves significantly.

As a result, no blood clots form, and your risk of having a stroke drops exponentially.

BEER BENEFIT 5: Beer strengthens your bones

Beer is known to contain high levels of silicon, an element that promotes bone growth.

But you have to get the balance right. A very shocking research concluded that whilst one or two glasses of beer a day could significantly reduce your risk of fracturing bones, more than that would actually raise the risk of breakages.

So be careful when you visit the pub: if you drink too much, your bones will be weakened and those drunken nigh time tumbles could result in nasty fractures. Drink the right amount, however, and you’ll walk home with your bones and dignity in-tact.

BEER BENEFIT 6: Beer decreases the chance of diabetes

In 2011, Harvard researchers found that middle-aged men who drink one or two glasses of beer each day appear to reduce their risk of developing type 2 diabetes by up to 25pc.

A professor at the Harvard School of Public Health, studied 38,000 middle-aged men, and concluded that the alcohol content in beer increases insulin sensitivity, which helps prevent diabetes. Additionally, beer is a good source of soluble fibre – a dietary material that helps to control blood sugar and plays an important role in the diet of people suffering from diabetes.

So, whether you’ve got diabetes or not, a glass of beer is just what the doctor ordered.

Dutch researchers analysed 38,000 male health professionals and found that when men who weren’t big boozers began drinking moderately over 4 years, they were significantly less likely to be diagnosed with type 2 diabetes.

Increased alcohol consumption over time didn’t lower the risk in men who already had a couple drinks a day, so moderation is the key word here

BEER BENEFIT 7: Beer reduces the risk of Alzheimer’s

Studies dating back to 1977 have suggested that beer drinkers can be up to 23pc less likely to develop cognitive impairment, Alzheimer’s disease or other forms of dementia.

However, despite the statistics speaking for themselves – one study surveyed over 365,000 people – it is unknown why moderate drinking can have a beneficial effect. One theory suggests that the well-known cardiovascular benefits of moderate alcohol consumption, such as raising good cholesterol, also can improve blood flow in the brain and thus brain metabolism.

The silicon content of beer could also be responsible. Silicon is thought to protect the brain from the harmful effects of aluminum in the body – one of the possible causes of Alzheimer’s.

BEER BENEFIT 8: Beer can cure insomnia

Beer is a natural nightcap. Ales, stouts and lagers have been found to stimulate the production of dopamine, a compound that may be prescribed to insomnia sufferers by a doctor, in the brain.

According to research, simply tasting beer increases the amount of dopamine in the brain – and thus make drinkers feel calmer and more relaxed. However, the academics clarified that these effects are achieved after only a taste, and so a paltry 15 millilitre serving is all you need – the equivalent of one tablespoon of beer.

BEER BENEFIT 9: Beer can stop cataracts

Too much and your vision will get blurry, but consume just the right amount of beer and your eyes will benefit.

Researchers at the University of Western Ontario found that the antioxidants found in beer, particularly ales and stouts, protected against mitochondrial damage.

Cataracts are formed when the mitochondria – parts of a cell responsible for converting glucose into the energy – of the eye’s outer lens are damaged. Antioxidants protect the mitochondria against this damage, and therefore the study authors recommend one drink a day to keep the eye doctor away.

BEER BENEFIT 11: Beer helps you lose weight

It may seem a strange one, considering we’ve named the ‘beer belly’ after the weighty effects of alcohol, but researchers seem to think that beer can help you shed some pounds.

Scientists published a study earlier this year showing that a compound called xanthohumol, commonly found in hops, can lower an individual’s chances of developing metabolic syndrome – a condition that indicates obesity, elevated blood pressure, increased blood sugar, and bad high-density lipoprotein (HDL) cholesterol levels.

Sadly, the researchers concluded that humans would have to drink over 3,500 pints of beer a day to feel the benefits of the ‘miracle’ compound – by which point they’d need a miracle just to be alive.

BEER BENEFIT 12: Think Like A Genius

Knocking back a beer or two won’t make you smarter, but it could boost your creativity, according to a study in the journal Consciousness and Cognition.

When 40 men watched a movie while completing verbal puzzles, beer-buzzed guys with a blood alcohol content of .075 solved the problems a few seconds faster than their sober counterparts.

Official guidance says that it is safest to drink less than 14 units a week. If you do regularly exceed this, it’s best to spread your drinking over three or more days.

[yourcancerguru]

Medicinal Mushrooms and Their Role in Cancer Care

Medicinal mushrooms have gained significant attention in recent years due to their potential benefits for individuals with cancer. While it's important to note that medicinal mushrooms should not replace conventional cancer treatments, they may provide certain advantages and support. Here are some potential benefits associated with medicinal mushrooms:

Immune system support: Certain medicinal mushrooms, such as reishi (Ganoderma lucidum), maitake (Grifola frondosa), and turkey tail (Trametes versicolor), contain compounds that can enhance immune function. These mushrooms can stimulate the activity of immune cells, such as natural killer cells and macrophages, which plays a crucial role in identifying and eliminating cancer cells.

Anti-inflammatory properties: Chronic inflammation is often associated with cancer progression. Some mushrooms, like shiitake (Lentinula edodes) and cordyceps (Cordyceps sinensis), possess anti-inflammatory properties. By reducing inflammation, these mushrooms may help create a less favorable environment for cancer cells to thrive.

Antioxidant effects: Many medicinal mushrooms are rich in antioxidants, such as polyphenols and beta-glucans. Antioxidants can neutralize free radicals in the body, which can damage cells and DNA and contribute to the development of cancer. By reducing oxidative stress, mushrooms can help protect healthy cells from damage.

Chemopreventive potential: Some medicinal mushrooms exhibit chemopreventive properties, meaning they may help prevent the development of cancer or inhibit its progression. For example, mushrooms like agaricus blazei and maitake have been studied for their potential to inhibit tumor growth and prevent metastasis in various types of cancer.

Supportive effects during treatment: Medicinal mushrooms can offer supportive benefits for individuals undergoing cancer treatments, such as chemotherapy and radiation therapy. They may help alleviate side effects like nausea, fatigue, and weakened immune function, thus improving one’s overall well-being.

It's important to emphasize that while medicinal mushrooms have shown promise in clinical trials, further research is needed to fully understand their efficacy, optimal dosages, and potential interactions with other medications. If you're considering using medicinal mushrooms as part of your treatment plan, it's essential to consult with a healthcare professional experienced in integrative oncology to ensure safe and appropriate use. Medicinal mushrooms are containdicated in certain cancers and there are several factors to consider:

Safety and Quality: Ensure that the medicinal mushrooms you plan to use are from a reputable source and have undergone quality testing. This can help ensure the product is free from contaminants and is properly labeled. It's also important to note that some wild mushrooms can be toxic, so caution should be exercised if harvesting mushrooms yourself.

Individualized Approach: Each person's cancer and treatment plan are unique. What works for one individual may not be appropriate for another. It's important to consult with an integrative oncology healthcare professional who can consider your specific situation, medical history, and treatment plan when recommending or discussing the use of medicinal mushrooms.

Scientific Evidence: While there is growing scientific interest in medicinal mushrooms, the research is still evolving. It's important to have realistic expectations and recognize that medicinal mushrooms should not replace conventional cancer treatments.

Potential Side Effects: While medicinal mushrooms are generally considered safe for most people, they can still cause side effects in some individuals. These may include gastrointestinal symptoms like nausea, diarrhea, or upset stomach. Allergic reactions are also possible, especially if you have a known allergy to mushrooms. Monitor your body's response to any supplements and discuss any concerns or side effects with your healthcare team.

Dosage and Formulation: Determining the appropriate dosage and formulation of medicinal mushrooms can be challenging, as research is still ongoing. Different mushrooms and products may have varying concentrations of active compounds. It's important to follow the recommended dosage instructions provided by the manufacturer or as advised by a knowledgeable healthcare professional.

Always remember that medicinal mushrooms should be seen as an integrative approach and not a substitute for conventional cancer treatments. It's crucial to have open and honest communication with your healthcare team, inform them of all the supplements you are considering, and seek their guidance to ensure your safety in your overall treatment plan.

[prnlive]

Gary Null’s Show Notes 01 09 23 P

If you listen to Gary’s show, you know that he begins with the latest findings in natural approaches to health and nutrition. Starting this week, we will make some of those findings available each weekday to subscribers to the Gary Null Newsletter.

Study confirms the antitumor effects of pomegranates

Have you heard of magnolia bark? Studies have shown it to play a beneficial role in healthy sleep

Have you heard of magnolia bark? Studies have shown it to play a beneficial role in healthy sleep

Time spent in nature appears to slow Parkinson’s, Alzheimer’s

The joy of giving lasts longer than the joy of getting

Aging slowly turns the immune system into fat, study reveals

Curcumin Eases Post-Workout Muscle Soreness

Monday Bonus Recipe

Study confirms the antitumor effects of pomegranates

Tiradentes University (Brazil), December 22, 2022

One of the natural products that have shown potential use as alternative treatments to cancer is the pomegranate (Punica granatum) fruit. Countless studies have looked into the anticancer potential of pomegranate. However, it wasn’t until recently that researchers from Brazil were able to observe pomegranate’s anticancer properties in an in vivo study. Their findings, which were published in the Journal of Medicinal Plants Research, included the potential systemic effects of pomegranate, which were not evaluated in previous in vitro studies.

Pomegranate fruit has long been used as a traditional remedy for health problems such as sore throats, coughs, urinary tract infections, digestive disorders, skin disorders, and arthritis. With the current advancements in science, researchers were able to identify the bioactive compounds in the fruit that are potentially involved in these applications. They found that pomegranates are rich in tannins like punicalagin, punicalin, gallic acid, ellagic acid, and ellagic acid derivatives. Existing publications also attribute the healing, antimicrobial, chemopreventive, and antitumor effects of pomegranates to these compounds.

In this study, the researchers improved upon previous studies assessing the anticancer properties of pomegranates by conducting an in vivo study involving male Swiss mice that were transplanted with sarcoma tumor cells. The mice were treated with either aqueous pomegranate extracts or 5-fluorouracil, which is a conventional cancer treatment. After eight days, the researchers observed that both treatments significantly increased the number of apoptotic cancer cells. This indicates that pomegranates work against cancer by inducing programmed cell death, which will then signal immune cells to eliminate them without triggering an inflammatory response.

To determine if the treatments used in the study have unwanted toxic effects, the researchers conducted hematological, biochemical, histopathological, and morphological analyses of the tumor and organs. They found that mice treated with 5-fluorouracil suffered from a loss in body weight, spleen atrophy, and a reduced number of white blood cells, which indicate toxic effects. On the contrary, pomegranate-treated mice did not exhibit any signs of toxicity, proving that it is safe for use.

Have you heard of magnolia bark? Studies have shown it to play a beneficial role in healthy sleep

Johns Hopkins University, December 20, 2022

Magnolia (Magnolia officinalis) is a flowering tree whose bark and flowers are commonly used in traditional Chinese, Japanese, and Korean medicine. However, most people today are not that familiar with the herb, which is very unfortunate since it is associated with a wide variety of health benefits. One of the most common uses of the magnolia bark is to promote sleep and relaxation.

The bark of the magnolia tree is rich in bioactive compounds, such as magnolol and honokiol, that have been shown to have anti-inflammatory, antibacterial, and anti-allergy properties. It also has many properties that contribute to its overall effectiveness as a soporific.

Scientists have observed that magnolia bark can boost the production of gamma-aminobutyric acid (GABA), a brain chemical that induces a calming effect on the brain. By increasing the amount of this neurotransmitter, you can effectively prevent insomnia, a sleep disorder associated with low GABA levels.

Adrenaline and cortisol are some of the other substances in the body that are affected by magnolia bark intake. However, unlike GABA, these two are reduced in the presence of the herb. This is beneficial for those who need more sleep since adrenaline and cortisol are associated with a state of alertness and vigilance.

Furthermore, magnolia bark contains at least one compound that increases the amount of time a person spends in rapid eye movement (REM) and non-REM sleep, which are also known as active and quiet sleep, respectively. It is important to undergo these two phases since they have distinct contributions to sleep. According to a study published in the journal The Neuroscientist, the NREM phase is when the recovery of cells occurs. Meanwhile, the same article said that REM sleep allows for the selection of cells that are already in top shape since they don’t have to be fixed in the subsequent NREM phase. Unfortunately, the specific substances responsible for these activities, which also includes reducing the time needed to fall asleep, have not been identified.

Time spent in nature appears to slow Parkinson’s, Alzheimer’s

Harvard School of Public Health, December 27, 2022

Living in an area with easy access to parks and rivers appears to slow the progression of devastating neurological diseases, such as Alzheimer’s and Parkinson’s.

That’s the conclusion of a new study based on more than a decade and a half tracking disease risk among nearly 62 million Americans 65 years old and up.

“Prior research showed that natural environments—such as forests, parks and rivers—can help to reduce stress and restore attention,�� noted lead author Jochem Klompmaker, a postdoctoral research fellow at Harvard T. H. Chan School of Public Health in Boston. “In addition, natural environments provide settings for physical activity and social interactions, and may reduce exposure to air pollution, extreme heat and traffic noise.”

To build on such observations, his and his colleagues looked at hospital admissions for Alzheimer’s and related dementia, as well as Parkinson’s disease.

By focusing on hospital admission, Klompmaker stressed that his team was not assessing the initial risk for developing either disease. Instead, researchers wanted to know if increased exposure to nature lowered the odds that either disease would progress quickly.

And on that front, Klompmaker said, researchers observed significant protective links: The greener an older individual’s surrounding environment, the lower their risk of hospitalization for either neurological illness.

To explore the potential protective benefit of nature, researchers focused on seniors on Medicare living in the U.S. mainland.

About 55% were women, and about 84% were white people. All were 65 to 74 years of age when they entered the study pool.

Over the study’s 16 years, nearly 7.7 million were hospitalized for Alzheimer’s or other forms of dementia, and nearly 1.2 million were hospitalized for Parkinson’s.

Throughout, researchers stacked each patient’s ZIP code up against several types of geological survey data that collectively tallied a region’s overall “greenness.” That data included the amount of vegetation present, as well as the percentage of land devoted to parks and waterways.

Results were positive with respect to the movement disorder Parkinson’s: By all measures studied, living in a greener environment meant a lower risk for hospitalization.

For every increase of 16% in park coverage the risk for hospitalization due to Parkinson’s fell by 3%, for example. And living in a ZIP code in which 1% or more of the studied space was water, the risk of Parkinson’s hospitalization fell 3% relative to those in ZIP codes with fewer water bodies.

“Research shows that green spaces trigger people’s positive emotions, such as happiness, and reduce negative emotions such as anger, all related to lower stress levels,” Navarrete-Hernandez said. “Laboratory experiments also show that exposure to nature after stressful events helps reduce the body’s stress responses,” including levels of the stress hormone cortisol.

The joy of giving lasts longer than the joy of getting

University of Chicago Business School & Northwestern University, December 20, 2022

The happiness we feel after a particular event or activity diminishes each time we experience that event, a phenomenon known as hedonic adaptation. But giving to others may be the exception to this rule, according to research in Psychological Science, a journal of the Association for Psychological Science.

In two studies, psychology researchers Ed O’Brien (University of Chicago Booth School of Business) and Samantha Kassirer (Northwestern University Kellogg School of Management) found that participants’ happiness did not decline, or declined much slower, if they repeatedly bestowed gifts on others versus repeatedly receiving those same gifts themselves.

“If you want to sustain happiness over time, past research tells us that we need to take a break from what we’re currently consuming and experience something new. Our research reveals that the kind of thing may matter more than assumed: Repeated giving, even in identical ways to identical others, may continue to feel relatively fresh and relatively pleasurable the more that we do it,” O’Brien explains.

In one experiment, university student participants received $5 every day for 5 days; they were required to spend the money on the exact same thing each time. The researchers randomly assigned participants to spend the money either on themselves or on someone else, such as by leaving money in a tip jar at the same café or making an online donation to the same charity every day. The participants reflected on their spending experience and overall happiness at the end of each day.

The data, from a total of 96 participants, showed a clear pattern: Participants started off with similar levels of self-reported happiness and those who spent money on themselves reported a steady decline in happiness over the 5-day period. But happiness did not seem to fade for those who gave their money to someone else. The joy from giving for the fifth time in a row was just as strong as it was at the start.

O’Brien and Kassirer then conducted a second experiment online, which allowed them to keep the tasks consistent across participants. In this experiment, 502 participants played 10 rounds of a word puzzle game. They won $0.05 per round, which they either kept or donated to a charity of their choice. After each round, participants disclosed the degree to which winning made them feel happy, elated, and joyful.

Again, the self-reported happiness of those who gave their winnings away declined far more slowly than did the happiness reported by those who kept their winnings.

“We considered many such possibilities, and measured over a dozen of them,” says O’Brien. “None of them could explain our results; there were very few incidental differences between ‘get’ and ‘give’ conditions, and the key difference in happiness remained unchanged when controlling for these other variables in the analyses.”

Adaptation to happiness-inducing experiences can be functional to the extent that it motivates us to pursue and acquire new resources. Why doesn’t this also happen with the happiness we feel when we give?

The researchers note that when people focus on an outcome, such as getting paid, they can easily compare outcomes, which diminishes their sensitivity to each experience. When people focus on an action, such as donating to a charity, they may focus less on comparison and instead experience each act of giving as a unique happiness-inducing event.

We may also be slower to adapt to happiness generated by giving because giving to others helps us maintain our prosocial reputation, reinforcing our sense of social connection and belonging.

Aging slowly turns the immune system into fat, study reveals

Uppsala University (Sweden), December 27, 2022

Even our immune systems tend to pack on a few extra pounds as we grow older. Now, researchers from Uppsala University in Sweden are detailing why human lymph nodes tend to gradually accumulate fat and lose their function with age, as well as how this influences the effectiveness of our immune system.

Lymph nodes are small bean-shaped structures which scientists consider the “headquarters” of the human immune system. Whenever someone develops an infection, for example, the lymph nodes are the sites where immune cells congregate, activate, and proliferate to put together an effective immune defense. However, as a person grows older, studies show the normal tissues in lymph nodes (the stroma) tend to gradually disappear, replaced by adipose tissue (fat). This is called lymph node lipomatosis, and, while it is very common and increases with age, there has been little research into understanding lipomatosis.

Study authors analyzed more than 200 lymph nodes, demonstrating that lipomatosis begins in the central part of the lymph node — the medulla. They also collected evidence linking lipomatosis to the transformation of the supporting cells of lymph nodes (fibroblasts) into adipocytes (fat cells). Notably, specific types of fibroblasts located in the medulla were especially prone to becoming adipocytes.

Even during the early stages of lipomatosis, researchers noted negative changes that hindered the lymph nodes’ abilities to provide effective immunity. More specifically, the specialized blood and lymphatic vessels that normally provide channels for immune cells to enter and exit the lymph node were destroyed in parts of the node where fat had formed.

Consequently, researchers theorize lipomatosis of lymph nodes, even at early stages, may be an important factor in the documented poorer response to vaccinations observed in elderly people. Eventually, fat consumes the entire lymph node, rendering it totally unable to function.

“Our study is a first step towards understanding why lipomatosis occur, and towards the longer term goal of finding ways to prevent its progression and the destruction of the lymph node,” says Tove Bekkhus, first author of the study, in a media release.

Curcumin Eases Post-Workout Muscle Soreness

Japan Institute of Sports Science, December 18, 2022

It’s no secret how effective turmeric is for easing temporary joint pain and inflammation. But if you’re still on the fence about putting down the ibuprofen and reaching for a nutritional supplement to treat muscle aches and pains, a study on curcumin may prove to be just the incentive you need to stop the harmful NSAIDs forever

A cross-functional team of Japanese researchers who had already proven the efficacy of curcumin in relieving muscle soreness brought on by strenuous exercise, endeavored to identify the most effective timing of curcumin ingestion for optimum pain relief.

Published in the Journal of Nutritional Science and Vitaminology, the clinical study was single-blind, meaning only the investigators knew which treatment type participants received. It was conducted as a parallel study, indicating that only two types of interventions were used, and randomized to ensure more accurate results with a lower risk of bias.

Researchers assembled 24 healthy young men and had them perform a series of 30 isokinetic, eccentric contractions of the elbow flexors (an eccentric contraction is the motion of an active muscle while it is lengthening under load). An isokinetic dynamometer was used to measure the resistance of the muscles to the applied force.

A 180-milligram (mg) daily dose of oral curcumin was provided to the men in the pre-workout group for seven days before exercising. The same dose of curcumin was provided to men in the post-workout group for four days after exercise. Men in the control group received an oral placebo for four days after exercise.

Supplements of curcumin or placebo were given in twice-daily 90-mg doses, the first capsule after breakfast and the second capsule after dinner.

Muscle damage markers were measured and recorded before, immediately after and one to four days post-exercise. Researchers observed the maximal voluntary contraction (MVC) torque of the elbow flexors, elbow joint range of motion (ROM), muscle soreness and serum creatine kinase (CK) activity. Changes in these variables were compared over time.

Results of the study indicated that curcumin ingestion post-workout had a more beneficial effect on range of motion and muscle soreness than did pre-workout ingestion of curcumin and placebo. Torque of the elbow flexors and serum creatine kinase markers showed no significant differences among the groups.

These findings led researchers to conclude that curcumin ingestion after exercise had a more beneficial effect in attenuating muscle soreness than ingesting curcumin before exercise.

Monday Bonus Recipe

About Gary Null

An internationally renowned expert in the field of health and nutrition, Gary Null, Ph.D is the author of over 70 best-selling books on healthy living and the director of over 100 critically acclaimed full-feature documentary films on natural health, self-empowerment and the environment. He is the host of ‘The Progressive Commentary Hour” and “The Gary Null Show”, the country’s longest running nationally syndicated health radio talk show which can be heard daily on here on the Progressive Radio Network.

Throughout his career, Gary Null has made hundreds of radio and television broadcasts throughout the country as an environmentalist, consumer advocate, investigative reporter and nutrition educator. More than 28 different Gary Null television specials have appeared on PBS stations throughout the nation, inspiring and motivating millions of viewers. He originated and completed more than one hundred major investigations on health issues resulting in the use of material by 20/20 and 60 Minutes. Dr. Null started this network to provide his followers with a media outlet for health and advocacy. For more of Dr. Null’s Work visit the Gary Null’s Work Section or Blog.GaryNull.com In addition to the Progressive Radio Network, Dr. Null has a full line of all-natural home and healthcare products that can be purchased at his Online Store.

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[andre4785]

How to use rapamycin cream and capsules to live a better longer life.

Researchers really do caution that nobody ought to take rapamycin cream as a lifestyle choice longer since it is a silencer of the invulnerable framework. With regards to the invulnerable framework, we must be very cautious since it is the body's defensive framework. The way to disease is in the cells, the essential inquiry is: how would you kill the growths without clearing out the whole or a lot of cells in the organ? Cell treatment is hence in this strategy better than customary chemotherapy which kills a lot of cells. With Resveratrol, researchers and doctors work in the field of disease treatment can deliver against growth movement in the impacted cell region. In an examination distributed in Malignant growth LETTERS in Feb 2001, Charis Eng, MD, Ph.D., Seat of the Genomic Medication Establishment of Cleveland Facility's Lerner Exploration Organization, drove her group to concentrate on the impact of joining resveratrol, a chemopreventive medication tracked down in numerous normal mixtures, with buy rapamycin on bosom disease cells. where to buy rapamycin has been in clinical preliminaries as a medication for disease therapy, it has had a few impacts as a suppresant to cancer development, however sadly, sooner or later the malignant growth cells fostered a protection from the medication. Thus, the researchers in this study consolidated Resveratrol with Rapamycin in the therapy of bosom malignant growth. The outcomes were extremely fascinating. This is the very thing that Dr Eng needed to say regarding the outcomes: "Our discoveries show that resveratrol appears to alleviate rapamycin cream-prompted drug opposition in bosom diseases, to some extent in the laboratory. In the event that these perceptions turn out as expected in the center setting, partaking in a glass of red wine or eating a bowl of bubbled peanuts - - which has a higher resveratrol content than red wine - - before rapamycin therapy for disease may be a reasonable methodology CR enacts AMPK to repress TOR and the remainder of the control components in this pathway, as far as possible back to AMPK. Set forth plainly, a vertical bolt close to AMPK brings about a descending bolt close to all the other things. Got that scratch pad? Introduce bolts, presently. Alternately, restraint of AMPK abbreviates life, and every one of the bolts point the other way. Very straightforward, right? Indeed, yes and negative, in light of the fact that the unseen details are the main problem, and every part can be actuated exclusively or in mix. So keep that scratch pad good to go. For example, there are drugs, like metformin and rapamycin buy, nutriceuticals, for example, resveratrol, and chemicals like development chemical and thyroxine, which can act separately or in blend on various pieces of the pathway to one or the other copy or go against CR. In addition to other things, this pathway controls the structure (neogenesis) and productivity (regenesis) of the mitochondrion, the significant oxygen utilizing fuel consuming unit in every single creature cell. The mitochondrion sits between PGC-1alpha and ROS. Disease cells experience the ill effects of mutational confusions that modify non-oxygen fuel consuming in a cycle we call constrained hyper-glycolysis. New drugs are being found which upset these disturbances, and yield useful results. Thus, as may be obvious, from one perspective it is very basic, however then again it can get somewhat furry. We want examinations and we want them prior instead of later. However, rodents live at least five years, and rodents are not individuals, (as gone against, oft-times, to the reverse way around). Over the counter metformin is north of 10 years away, if at any point, and buy rapamycin is too hazardous to become road legitimate in any time, aspect or reality. Metformin, when utilized with development chemical to robotically force the framework to toggle to and fro among neogenesis and regenesis could eventually end up being the best enemy of maturing in addition to restoration accomplishment ever. This could genuinely make cells act more as they do in the adolescent stage. The timing, dose and testing expected in such a situation would be basic. This is playing with some genuinely enormous magic, here, and it would be unlawful without a medicine under a doctor's consideration. Just individuals, in their initial center years, say past thirty, could partake in such a program, securely." CR actuates AMPK to hinder TOR and the remainder of the control components in this pathway, as far as possible back to AMPK. Set forth plainly, a vertical bolt close to AMPK brings about a descending bolt close to all the other things. Got that notebook? Introduce bolts, presently. On the other hand, hindrance of AMPK abbreviates life, and every one of the bolts point the other way. Very basic, right? All things considered, yes and negative, on the grounds that the overlooked details are the main problem, and every part can be enacted exclusively or in mix. So keep that notebook primed and ready. For example, there are drugs, like metformin and rapamycin buy, nutriceuticals, for example, resveratrol, and chemicals like development chemical and thyroxine, which can act separately or in blend on various pieces of the pathway to one or the other copy or go against CR. In addition to other things, this pathway controls the structure (neogenesis) and proficiency (regenesis) of the mitochondrion, the significant oxygen utilizing fuel consuming unit in every creature cell. The mitochondrion sits between PGC-1alpha and ROS. Malignant growth cells experience the ill effects of mutational confusions that change non-oxygen fuel consuming in a cycle we call constrained hyper-glycolysis. New drugs are being found which disturb these confusions, and yield valuable results. Thus, as may be obvious, from one perspective it is very basic, however then again it can get somewhat shaggy.

[periwinklemeanderings]

D-Limonene:

"Because of its gastric acid-neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer." -

[wwwsarms4musclecom]

Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa.

Lunasin is a novel, cancer-preventive peptide whose efficacy against chemical carcinogens and oncogenes has been demonstrated in mammalian cells and in a skin cancer mouse model. Isolated and characterized in soy, lunasin peptide is also documented in barley.

Lunasin, a cancer fighting peptide Lunasin, a natural killer cell activating peptide, is a novel peptide found in the soybean 2S albumin seed protein. Lunasin also found in barley, wheat, and rye. The peptide has both anticancer and anti-inflammatory activities. Lunasin was originally isolated from the soybean cotyledon, the seed leaf, and because of its properties this peptide was termed lunasin from the Tagalog word “lunas” for cure. Lunasin contains 43 amino acid residues having a unique sequence that includes the cell adhesion motif RGD and a carboxylic acid tail composed of nine aspartic acid residues. Its sequence is SKWQHQQDSC RKQKQGVNLT PCEKHIMEKI QGRGDDDDDDD DD. Peptides containing the RGD motif have been reported to prevent metastasis of tumor cells by competitive adhesion to extracellular matrices. Various studies showed that lunasin suppresses both chemical and oncogene driven transformation of mammalian cells. The peptide acts as a chemopreventive agent by suppressing cell transformation and subsequent carcinogenesis. The treatment of different mammalian cells with synthetic lunasin showed preferential adherence of this peptide to chromatin, leading to disruption of the kinetochore and inhibition of mitosis. This activity appears to be due to the binding of its negatively charged poly-D carboxyl end to the highly basic histones found within the nucleosomes of condensed chromosomes. It is thought that lunasin binds to regions that are more positively charged, such as the core histones in chromatin regions found in telomeres and centromeres. This binding is facilitated by the poly-aspartyl end of the peptide. The amino acid region 23 to 31 targets lunasin to chromatin.

[irispublisherscancerresearch]

A Simple Screening Test for Cancer-Iris Publishers

Authored by AbulKalam M Shamsuddin*

Abstract

Comparative and correlative studies of the pathology and pathogenesis of colon cancer in animal models and human disease have resulted in conceptualization of ‘field effect” theory, and identification of a simple carbohydrate marker that is expressed early during carcinogenesis. This assimilated body of knowledge has resulted in development of a simple screening test for cancers of the lung, breast, colorectum, uterus, pancreas, and prostate. The marker galactose-N acetyl-galactosamine (Gal-GalNAc) is expressed in the cell surface and secreted glycoproteins of otherwise normal appearing tissues remote from cancer or precancerous lesions and is detected by enzymatic oxidation (10 minutes) followed by color reaction (1 minute). The high sensitivity, specificity, and cost-effectiveness of this point-of-care test makes it a great tool in our strategies for early detection, hence control of cancer. It would also reduce the number of unnecessary and expensive procedures, thereby decreasing the total national health-care cost to the societies and governments, globally.

Keywords: Screening test; Lung cancer; Breast cancer; Prostate cancer; Colon cancer; FOBT

Abbreviations: AOM: azoxymethane; FOBT: fecal occult blood test; Gal-GalNAc: galactose-N acetyl- galactosamine; GOS: galactose oxidase Schiff; MNNG: N-methyl-N’-nitro-N-nitroso-guanidine; NCI: National Cancer Institute; T-Ag or TF-Ag: Thomsen-Friedenreich antigen

Introduction

Regrettably, in 2020 approximately 10 million people were killed by cancer; now-a-days there is hardly a family that is not affected by cancer. Additionally, the healthcare cost, and loss of productivity owing to morbidity and poor quality of life, has been immensely draining to families, societies, and governments alike, everywhere. This scourge has been around for a very long time with no end in sight. As in SARS-Cov-2 now, in 1971 President Richard Nixon had declared ‘War on Cancer’ to combat this menace. Alas, 50 years later, conquering cancer remains an elusive goal despite progress in treatment, albeit modest. Again, akin to SARS-Cov-2, prevention is our best alternative. Cancer prevention includes (a) detection at the very early stage of the disease (secondary prevention) to reduce cancer mortality and increase the survival rate of patients; and (b) etiology prevention or primary prevention to reverse precancerous lesions or in situ carcinomas (a cancer that is still confined) to normal or stop them from progressing to invasive malignancies in populations at high risk – ‘nipping in the bud’. Thus, early detection is fundamental to prevention, and the key is to find the marker which is differentially expressed in highrisk tissues (cancer and precancer) but not in normal. Biomarker(s) meeting this criterion is/are logical choice for establishing accurate methods to detect cancers at infancy; it may also help in monitoring the efficacy of chemoprevention program by serving as intermediate endpoint marker [1].

Fundamental to the success of prevention programs of any disease is the detection of the problems. It includes identification of people with existing disease and those who are at risk of developing the disease. Identification of people with cancer is relatively simple for most cancers because of signs and symptoms from the disease; the individual, now a patient seeks medical attention. Extensive work-up including a battery of diagnostic tests are performed and appropriate therapy is administered; regrettably, it is usually too late for many, if not for most as it does not prevent the disease. Hence the adage: an ounce of prevention is better than a pound of cure. For an effective prevention program, we must actively seek individuals with cancer or high risk thereof from an apparently healthy noncompliant population. This is done by separating i.e., screening individuals into groups with high and low probability of cancer with the help of rapid, simple, accurate, and inexpensive tests (screening tests). Implicit in the definition of screening is a promise that there is a benefit for those who participate; they will be followed with further diagnostic tests and future management of the problem. But a screening test is never intended to give the full diagnosis, hence the distinction from diagnostic tests [2]. An individual who is screening test positive will need to undergo diagnostic procedures to confirm the presence of the disease. Ideal screening tests should have a high sensitivity (proportion of diseased subjects who are test- positive) and specificity (proportion of non-diseased subjects who are testnegative), be simple and non- invasive or minimally invasive, easy to administer – therefore enjoying a high acceptability amongst populations and of course cost-effective. It would not be successful if it is shunned for discomfort, cultural, religious, or other reasons or just too expensive [2]. Currently, except for colon cancer, there are no true good screening tests for other cancers at early stages. Imaging technologies such as mammogram, chest X-ray, low dose CT etc. cannot detect early cancers, for a tumor must attain a minimum size before it can be ‘visible’ by these. And that is too late!

The Galactose Oxidase-Schiff Test

The Galactose Oxidase-Schiff Test is one such screening test that fits all the criteria of an ideal screening test as it is rapid, simple, non-invasive, easy to administer, and inexpensive. Its high accuracy has been consistently and reproducibly demonstrated independently by numerous investigators in three continents. That is not surprising because of extensive scientific research on carcinogenesis and operation of i) field-effect of carcinogens and ii) a marker differentially and specifically expressed during carcinogenesis, shared by both cancer and precancer, but not by normal or regenerating tissue.

Field-effect

I studied early detection of cancer using colon cancer as a model since 1975 at the University of Maryland School of Medicine as my PhD dissertation. The advantages of colon as a model include a) relatively easy access to samples, b) well known precancerous changes (polyps) and conditions e.g., ulcerative colitis, Crohn’s disease etc.; c) well developed animal models with d) well characterized steps of carcinogenesis viz. initiation → promotion → progression; etc. Both in vivo and in vitro carcinogenesis experiments with rats and mice were performed to see how colon cancer forms in them, and to identify the earliest recognizable changes by microscopy and histochemistry [3,4]. Colon tissue from rats and human were cultured in the Petri dishes and exposed to the carcinogens N-methyl-N’-nitro-N-nitroso- guanidine (MNNG) for rat colon [3], and fecapentaene-12 a suspected human carcinogen, for human colon explants [5]. The findings were correlated with in vivo animal models, and ultimately to the human disease [6]: what does the human colon near and far from the cancer look like (Figure 1)?

It has been observed that the earliest recognizable change in the carcinogen-exposed tissue is an alteration in the composition of secreted mucus that persists through precancerous and cancerous tissues. The microscopic and histochemical changes in the human colon away from cancer are identical to those seen in the colons of rats (mouse colon is distinctly different from human or rat colon [7]) treated with the carcinogen azoxymethane in vivo, or MNNG for rat explants and fecapentaene-12 for human explants in vitro in Petri dishes. These changes are therefore the earliest evidence (or markers) of cancer formation – even before a cancer has formed. Using high iron diamine alcian blue technique, the mucus in the colon away from the cancer that looked normal by naked eye appears as blue (Figure 2, lower frame) as opposed to black in truly normal human colon without cancer, in the upper frame (Figure 2). Also note that the colonic glands or crypts in a cancer bearing colon appear distorted – changes identical to the rat carcinogenesis models. It was reasoned that because of the generalized effect of the carcinogen throughout the entire field of the large intestine, it is most likely that the tissue away from an obvious cancer would be abnormal – Field-Effect. The carcinogens in our environment such as the air we breathe, the food we eat etc. expose the entire lung or large bowel. Therefore, it is logical that their effect would be observed throughout the exposed field. While the vast majority of the cells will undergo DNA repair, and other host defense mechanisms such as NK cell will prevent them to progress to cancer, a few cells will be promoted and even fewer progressed to precancer and cancer who may share the same early changes as the rest of the exposed tissue in the field. (Figures 2,3).

Field-Effect phenomenon indicates that the entire field bears the brunt of the carcinogenic assault and expresses variable changes throughout. In the schematic drawing of the large intestine (Figure 3), it is depicted that irrespective of where a cancer or a precancerous polyp may be, areas of the otherwise normal appearing mucosa will show expression of the marker perhaps in a patchy manner (it is not practical to sample the entire large intestine to see if every millimeter has the change; hence this assumption of “patchy”). Rectum being a part of the large intestinal “field” and a convenient sampling site is therefore likely to show the same changes. Since digital rectal examination is a part of routine physical examination (though not practiced diligently by many primary care physicians now-a-days), it is simple and noninvasive. It also allows the physician to examine the prostate in males, and uterus, cervix, and adnexa in females. Samples from lungs such as coughed up sputum, nipple aspirate from breast, endocervical mucus, or prostatic secretion are likewise simple and noninvasive.

The marker: gal-galnac

The observed mucin histochemical change has further been identified as due to a biochemical alteration in the cell surface and secreted glycoprotein – presence of the carbohydrate moiety D- galactose-ß-(1-3)-N-acetyl-D-galactosamine (Gal-GalNAc, also called Thomsen-Friedenreich antigen or T- Ag, or TF antigen, though it may be different). In normal cells, a terminal sialic acid blocks the T-Ag from being recognized by the lectin peanut agglutinin (PNA), or the enzyme galactose oxidase; in cancer and precancer owing to loss of the sialic acid it is now recognizable. D-galactose oxidase specifically oxidizes C-6 hydroxyl groups of D-galactopyranose and N-acetyl galactosamine residues of Gal-GalNAc, generating two vicinal aldehyde groups that react with basic fuchsin to give magenta/purple coloration. Thus, Gal- GalNAc can be visualized by a simple enzymatic reaction with galactose oxidase followed by Schiff’s reagent, resulting in the development of a simple test for early detection, initially of colorectal cancer [8] by using rectal mucus sample.

What is an Ideal Cancer Marker According to the National Cancer Institute (NCI)?

Kelloff et al of the Division of Cancer Control and Prevention (DCCP) at the National Cancer Institute [1] outlined six criteria for intermediate endpoint biomarkers of use in chemoprevention, and here is how Gal-GalNAc and STEDi live up to those expectations:

Is the intermediate biomarker differentially expressed in normal and high-risk tissue? YES!

Figure 4 shows the expression of Gal-GalNAc (magenta) in a colon cancer but, not by the normal human colon (Figure 5). The normal tissues were obtained from healthy normal people without any cancer. Note the absence of magenta color in the mucus of normal colonic goblet cells. Also note that the colonic glands or crypts in truly normal humans appear uniform test tube shaped as compared to the those in cancer-bearing colon or in rats treated with the carcinogen azoxymethane (see Figure 4-6).

At what stage of carcinogenesis does the marker appear?

The earlier a reliable marker appears in the carcinogenic process, the greater is the chance for successful intervention. Answer: Gal-GalNAc is expressed very early during carcinogenesis. Not only the marker is expressed early during the carcinogenesis in rats in vivo (Figure 6 left panel) but also by human precancerous polyp (right panel appearing as purplish). The colors are slightly different owing to different batch of staining and tissue preparation. The mucus alteration is also observed in rat and human explants exposed to carcinogens in vitro [4,5]. Note the distorted appearance of the colonic glands as opposed to uniform test tube shaped ones in normal (Figures 5,6).

Does the marker and its assay provide acceptable sensitivity, specificity, and accuracy?

Answer: Both the marker [9,10] and the assay [11-14, Table I] enjoy 70-100% sensitivity and specificity. That it is not expressed by regenerating cells following wounding is an added evidence that Gal-GalNAc is carcinogenesis specific [10]. Please see the results on colon cancer in the following Table: results on other organ sites are provided after this: (Table 1)

Table 1: Performance Summary of GOS Test for Colorectal Cancer.

The proof of field-Effect: Schematic diagram of the human large intestine depicting the location of the cancers detected by the rectal mucus test. That the “field-effect” phenomenon is operational is proved by the detection of cancers in the various segments of the colon remote from the rectum where the mucus was sampled from. Note that 4 of 5 cancers (80%) of the ascending (or the right) colon, 5 of 7 (71.4%) of the descending (or the left) colon and 29 of 33 (87.9%) of the sigmoid colon were detected in the two studies by Sakamoto et al [11,12] (Figure 7). The widely used current fecal occult blood test (FOBT) for colon cancer screening has been notoriously inaccurate; “Occult blood testing is, at best an imperfect approach to the screening of colorectal cancer” concluded Dr. Ahlquist [15]. And that is not surprising since blood is not a marker of cancer or precancer. A newer test combining FOBT and DNA in stool appears to have better sensitivity and specificity albeit at a very high price.

Gal-GalNAc is a common tumor marker: The usefulness of the tumor marker Gal-GalNAc in differentiating the benign from the malignant and pre-malignant lesions of the prostate was tested [16] yielding similarly high sensitivity and specificity (vide infra). Having determined that the principle is practicable in colon and prostate, studies were conducted on other cancers. The expression of Gal-GalNAc determined in a total of 133 tissue samples from 81 cases of the carcinomas of the breast, ovary, pancreas, stomach, and endometrium and 52 cases of respective normal controls [17]. None of the 52 cases of normal tissues (except 15 cases of stomach) showed expression of Gal-GalNAc. In contrast, 100% of adenocarcinomas from the breast (19 of 19), ovary (15 of 15), and pancreas (6 of 6), and 94.1% of stomach (16 of 17) cancers, and 91.7% (11 of 12) of uterine adenocarcinomas expressed Gal- GalNAc. The normal epithelia and their secretions in the vicinity of the carcinoma (within the “field”) in the breast, bronchus, endometrium, and pancreatic duct also expressed Gal-GalNAc in contrast to normal tissues obtained from non-cancerous individuals, which were totally non-reactive. Thus, the tumor marker Gal- GalNAc recognized by galactose oxidase-Schiff sequence was highly expressed not only by a variety of adenocarcinomas but also by the apparently normal-appearing epithelia and their secretions in the vicinity of carcinomas confirming the operation of a field effect phenomenon by carcinogenic agent(s) in these organs as well, setting the stage for identification of the marker in these secretions for mass screening for these cancers too [17].

Studies on lung cancer: Twelve of 12 pulmonary adenocarcinomas expressed Gal-GalNAc. The bronchial tissue away from the cancer were available in 4 cases, all of whom also expressed the marker both in the epithelial lining cells as well as in the secreted mucus [17]. Coughed-up sputum therefore can be used to screen people for cancers of the lungs. Indeed, three clinical studies on lung cancer were performed on coughed up sputum [18-20]. Lai et al [18] reported the results of their study on sputum specimens from 116 healthy persons; and 216 cases of benign and malignant lung diseases were tested for the marker Gal-GalNAc. The result showed that 165 of the 182 patients (90.7% sensitivity) with lung cancer, confirmed by cytology and histology, had positive results, whereas 22 of 116 (19.0%) healthy controls were positive (81.0% specificity, Table 2). In 28 cases of patients whose sputum cytology showed various degrees of dysplasia-a precancerous condition that progresses to cancer, 21 were found Gal-GalNAc positive, of which 15 patients were identified to have lung cancer on further work-up! Thus, the concept of “false positive” as generally used does not apply to Gal-GalNAc and the GOS Test since they take the precancerous lesions and early cancers into consideration. In addition, three cases of early lung cancer in this study were also positive, supporting the fact that Gal-GalNAc is expressed at an earlier stage in the malignant process of the lung as well. The studies by Cox & Miller [19] and Miller et al [20] had smaller sample size and showed sensitivities of 64.7 – 88% and specificities of 77.8 – 93.6%. The test revealed 20 of 23 lung cancers among 76 patients. The other 53 patients were either healthy or had benign lung disease such as bronchitis. Even more germane to the issue of prevention is the fact that 13 of 15 cancers detected were early stage (Stage I and II). Of note is that a tumor must attain a minimum size before it can be detected by imaging techniques. And that is late! (Figures 8,9) (Table 2).

Table 2: Lung Cancer study.

Breast cancer study: Gal-GalNAc is also expressed by the normal-looking breast tissue away from an obvious cancer by way of the field-effect phenomenon [17]. The marker was positive in 19 of 19 histological specimens of breast cancer giving it a 100% sensitivity. More importantly, and germane to our screening, the ducts away from the cancers and close to the nipple also express the marker both in the cells as well as in the secretions in the ducts. Thus, the nipple aspirate from a breast harboring a cancer should express the marker. Kumar et al [21] demonstrated that Gal-GalNAc (or TF antigen) is differentially expressed in nipple aspirate, albeit using a different technique – monoclonal anti- TF antibody. Nineteen of 25 cancer patients and none of the 25 healthy controls were positive yielding a 100% specificity and 76% sensitivity. The relatively low sensitivity of the test in nipple aspirate as opposed to tissue expression may be due to the use of different techniques for identifying the marker – galactose oxidase Schiff’s v monoclonal anti-TF antibody. Chagpar et al [22] also reported the utility of using nipple aspirate and Gal-GalNAc in screening for breast cancer. They investigated 23 women with biopsy confirmed, unilateral stage I or II breast cancer. They took samples (nipple aspirate by way of a suction cup attached to a syringe) from both breasts prior to surgery. Most, but not all the women were able to provide large enough fluid samples that could then be evaluated. Based on the resulting color of the test strips one could differentiate between a healthy and cancerous breast (Figures 10,11).

Prostate cancer study: The current screening test-PSA is inaccurate primarily because it is non-specific; its level goes up in benign conditions as well. The marker Gal-GalNAc is differentially and specifically expressed in prostate has also been observed in histological sections taken from 65 cases of adenocarcinoma [16]. While none of the 35 benign prostates and 11 foci of adenosis expressed Gal-GalNAc (100% specificity), 62 (95.4% sensitivity) of 65 adenocarcinomas expressed the marker. That the expression of the marker is not non-specific (meeting the NCI’s criteria #3) has been demonstrated by the absence in 25 samples of benign prostatic hyperplasia (BPH) and 11 of adenosis, neither of which are precancerous, nor were the normal prostates (10 samples) giving the marker a specificity of 100%. Notably, foci of prostatic intraepithelial neoplasia when present in some of the cancer specimens were also positive (Figure 12), demonstrating the useful of this marker in identifying early cancers [16]. As for colon, lungs, and breast, testing prostatic massage secretion or seminal fluid with GOS test should yield similar results (Figure 12).

Uterine cancer: Currently there are no screening tests for uterine cancers except for maybe the Pap smear wherein a uterine cancer could be detected by chance; but it is usually advanced when the cancer cells shed from endometrium are detected in Pap smear. Expression of Gal-GalNAc with high sensitivity (91.7%) was observed in 12 cases of uterine endometrial adenocarcinoma [17]. In all three cases where endocervical tissues was available, the endocervical mucus was positive for Gal- GalNAc. The photomicrograph (Figure 13) shows histological section of endocervix of a patient with endometrial adenocarcinoma; magenta coloration of the mucus in the endocervical glands and in endocervix is evident. Again, this supports the Field-Effect of carcinogenesis. More importantly, this makes it a simple, convenient, and non-invasive method of screening for endometrial adenocarcinoma while a gynecologist routinely collects samples for Pap smear (Figure13).

Pancreatic cancer: Pancreatic cancer is one of the deadliest of all cancers, primarily because of its silent inception; and owing to its location, signs and symptoms do not show till very late. All 6 of 6 cases of adenocarcinoma of pancreas were positive for Gal- GalNAc, and the normal ducts away from the cancers also showed positive reaction [17]. Thus, GOS test could be performed on fluid samples including pancreatic juice obtained during ERCP (endoscopic retrograde cholangiopancreatography) thereby providing additional value to the screening of the cancer. Figure 14 shows an adenocarcinoma of the pancreas with magenta color in the cancerous ducts and glands. (Figure14).

How easily can the marker be measured?

Answer: GOS test for detection of the marker is non-invasive done on mucus sample obtained during routine digital rectal examination, coughed-up sputum, nipple aspirate, prostatic massage secretion, endocervical mucus etc., and the entire assay period is ~15 min. This is the only point-of-care test for breast, lung, colon, prostate, and uterus; the results are available before the individual is ready to leave the doctor’s office. The test sample is placed on a special paper and reacted with galactose oxidase for 10 minutes, rinsed with distilled water, reacted with Schiff’s basic fuchsin for 1 minute, washed with tap water and dried. A pinkmagenta- purple color is positive, no color is negative (Figure 15). Positive indicates the presence of the marker Gal-GalNAc which is correlated with the presence of precancer, precancer or a high-risk thereof (Figure15).

Note: Though desirable, quantitative evaluation of the color reaction is neither practical nor meaningful as studies have shown no correlation between the intensity of color and the underlying disease.

Can the marker be modulated by chemo preventive agents?

Answer: YES! Sakamoto et al. [23] and Yang & Shamsuddin [24] have demonstrated that; indeed Gal-GalNAc expression can be suppressed by the chemo preventive agent IP6 [25,26]. Figure 16 shows that HT-29 human colon cancer cells express the marker Gal- GalNAc (magenta color in mucus of cells in left panel). Following IP6 treatment, HT-29 cells terminally differentiate and produce mucin, yet not Gal-GalNAc, akin to normal goblet cells (right panel showing a differentiated HT-29 cell that has a mucus vacuole yet not expressing the marker [23,24]. Clinical studies are needed to validate this, but that would take a very long time. In this regard of particular importance is the study on colon cancer by Vucenik et al [13] where 32 of 53 (60%) samples collected from patients after tumor resection showed persistence of the biochemical change; 5 out of these 32 (16%) post-operative cases with positive GOS Test had tumor recurrence within a year. Thus, persistently positive test may serve as a predictor of tumor recurrence (Figure16).

Does modulation of the intermediate biomarker correlate with a decrease in cancer rate?

This would require a long time-years if not decades, and additional resources.

In conclusion, GOS test is a point-of-care screening test that is very simple, rapid, non-invasive, and inexpensive yet accurate for identifying asymptomatic people who may be at high risk of cancer or precancer of the lung, breast, colon, pancreas, prostate, and uterus. It is based on robust scientific background; researched and validated over three decades in >20 independent clinical studies in North America, Europe, and Asia. It exploits a disaccharide marker expressed early during carcinogenesis that persists in precancer and cancer and, satisfies all the practical rigid criteria set forth by NCI for an ideal marker. Given the fact that cancers of the lungs, breast, colon, prostate, and uterus comprise the most cancers, it is in the interest of public health that they are identified at a very early stage, or even before they are formed. The sooner it is used, the more lives could be saved from these cancers.

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Uses of Sesame Seeds

 Sesamum indicum L. or sesame is a crop. It is grown mainly for the oil in its seeds, which is why it is considered an oilseed. This seed is native to the areas in Asia, Africa, and South America.

In Pakistan, they are grown in almost 65 districts, and it is commonly known as irrigated, and rain fed crop. The sesame seed contain 50% to 60% oil and 22 % protein. In 2019, sesame seeds of over 400 million tons worth Rs 9000 million were exported. The land of Gujrat, Gujranwala, Attock, Bhakkar, and Faisalabad in Punjab is used for the cultivation of best quality sesame seed from Pakistan.  Like many other exporters from Pakistan, Bhandari food is the leading example as a sesame seeds exporter as they are vigilant with their production quality and meeting international demands.

Uses of Sesame Seeds

Sesame seeds are famous for their rich nutrients values that contain protein, vitamins, minerals, and antioxidants. They are also commonly used in a variety of foods to add nutty flavor and crunchy texture. They are also used in abundance in medicine, lubricants, soaps, and cosmetics. Following are some of the wide uses of sesame seeds:

1-     Used to Lower Cholesterol

Sesame seeds contain large components of lignans and phytosterols, which are plant based compounds used for lowering the cholesterol. Moreover, phytosterols are also famous for boosting the immune system simultaneously decreasing the risk of certain types of cancers. It contains the highest percentage of phytosterols out of all the nuts and seeds used in or diets, which is 400 mg in every 100 g of sesame seeds.

2-     Used to Fight Infections

Sesame seeds exporters know its widespread use and they thrive to meet the market demands. The sesamin and sesamolin properties in these seeds are famous for their antibacterial properties. These compounds help to protect your body by slowing down the damage to body cells.

Sesame seeds are famous for fighting the staph infections and strep throat. It can also help with fungal issues of the skin, like athlete’s foot.

3-     Used for Oral Care

Sesame seeds are commonly used to fight the bacteria that caused plaque on your teeth. It is a ancient ritual through which the people use the technique of oil pulling to keep their teeth free from bacteria. Sesame seed oil is the most common oil used to practice this ancient ritual. It involves swishing a tablespoon of sesame oil in your mouth right after waking up.

4-     Used in Diabetes Treatment

Sesame seeds are used in the treatment of diabetes, particularly type 2. It is not used as a medicine itself, rather it is used to enhance the effects of the prescribed medicine. Type 2 diabetes is a life long disease in which your body can not generate insulin. Eating sesame seeds can help people reach they sugar levels and fill in the deficiency. Moreover, the antioxidants in these seeds also help to reduce enhanced sugar levels.

5-     Used in Cancer Treatment and Prevention

The sesamol in sesame seeds have antioxidant, anti-mutagenic, anti-hepatotoxic, anti-inflammatory, anti-aging, and chemopreventive properties. This makes it one of the best supplements for treating and preventing cancer cells. Each of these components play a very vital role in the prevention of cancer in living beings. It is considered to target cells at various stages of the cell cycle. Therefore, adding these seeds in your daily diet is necessary.

6-     Used in Nutrition

Sesame seeds are known to have variety of healthy nutrients and as a rich protein source, they are great for vegetarians and people who have vegan diets. These seeds are also rich in copper that help to make red blood cells and boost the immune system functions. One cup of sesame seeds can give your 163% of your daily copper value.

Moreover, these seeds are excellent sources of magnesium and calcium. It helps to keep your bones strong. Magnesium helps in lowering bad cholesterol in your body that ultimately provides you better health. Calcium is also known to play a vital role in nerve signal transmission, muscle movement, hormone control, and blood vessel functions.

There are abundant of nutrients in these seeds, including:

Ø  Phosphorous

Ø  Iron

Ø  Zinc

Ø  Magnesium

Ø  Vitamin B1

Ø  Selenium

Ø  Molybdenum

These are the widespread uses of sesame seeds which has increased their demands in the market, locally and internationally. Sesame seeds exporters are aware of their uses and rising demands and they work with great efforts to meet them.