Heroes [Solved] Filipino inventions & influence around the world.

First prototype and is powered by a Honda B16A engine

A close to production prototype with Mitsubishi 4G63T turbocharged engine

 

Lunasin’s biological and cancer-preventive activity was discovered by a Filipino doctor during his post-doctoral research --- Dr. Alfredo Galvez in Dr. Benito de Lumen’s (another Filipino doctor) laboratory in the University of California – Berkeley in 1997. This is an excerpt from Dr. de Lumen’s statement on the discovery of Lunasin, “Many years ago, my laboratory initiated a project on enhancing the nutritional of soy protein and other legumes through bioengineering. This requires increasing the level of methionine, the essential amino acid, which is most limiting in soy and other legumes, including mung bean. The strategy is quite straightforward: clone a gene coding for methionine-rich protein (MRP) and over-express the gene in soy or any target legume. We were faced with two choices for the source of the MRP gene – obtain it from other plants or from soy itself. I made the fateful decision to clone the MRP gene from soy itself, which eventually led to the discovery of lunasin as a cancer preventive agent.”

 

“The choice to clone the MRP gene from soy is based on the hypothesis that there must be non-abundant MRPs in soy because most of the proteins in soy seed are notoriously low in methionine and therefore, there must be other MRPs that contribute to the overall methionine content of soy protein but they are non-abundant. The process of cloning the MRP gene turned out to be not easy, taking about four years, two graduate students and a postdoctoral scientist. One of the graduate students is a Filipina (now Dr. Jamie Revilleza from UPLB), and the postdoctoral scientist is another Filipino from UPLB (Dr. Alfredo Galvez). Dr. Revilleza contributed to the purification of the MRP from soy that eventually led to the cloning of the gene, and Dr. Galvez took over the project and discovered the anti-mitotic effect of the lunasin gene when transfected into mammalian cells and the cancer preventive effect of the lunasin peptide. While it was not by design that the major contributors to lunasin discovery were both Filipinos, it is a source of pride to point this out.”

Cancer research

 

Lunasin has a unique epigenetic mechanism that interferes at the very early stages of the carcinogenic process; Lunasin is non tissue-specific and would be effective against different types of cancer. In addition, Lunasin has no known toxic effects, which is consistent with its presence in soybean that has been consumed in Asia for centuries.

 

Dr. Galvez was the first to identify the peptide’s ability to prevent the transformation of normal cells into cancerous tumors in cell culture. Animal studies validated the findings when lunasin significantly reduced the tumor incidence in mice skin exposed to chemical carcinogens. In the original 2001 study that discovered and named lunasin, the authors wrote that their results "suggest a mechanism whereby lunasin selectively induces apoptosis, mostly in cells undergoing transformation, by preventing histone acetylation"—the protein could cause cell death in developing cancer cells, while not affecting regular cells, in mice. This led to the speculation that lunasin might explain the numerous epidemiological associations between consumption of soy products and the low cancer incidence observed in Asian populations. In 2003 a study conducted by Bio-Rad Laboratories showed that the protein also did not affect immortalized and established cancer cells.

 

In 2008 a study performed by Dr. de Lumen found that lunasin was found to help prevent chemical carcinogens and oncogenes from causing cancer in a skin cancer mouse model. The peptide becomes bioavailable in mice through ingestion within a few minutes and reaches the nucleus of cells within eighteen hours. The effectiveness was shown only against non-established cancer cell lines in this study. In 2009 another study was performed at the Andong National University, that found further evidence of the inhibition of histone acetyl transferase. In addition, lunasin has also been shown to bind deacetylated histones, which can also help to prevent cancer. Wayne R. Bidlack and Raymond L. Rodriguez wrote that the inability for lunasin to kill established cancer cells was due to a genetic change in cells when they are first becoming cancerous, which disappears when a cell becomes fully cancerous. They also write that the food has the potential to reduce cancer risk, though not affect existing cancer cells in a patient, and could provide help in explaining an inverse correlation between soy consumption and the risk of some cancers.

 

Extensive researches on Lunasin's cancer-preventive ability shows that Lunasin internalizes inside the cell and ends up mostly in the nucleus; inhibiting core histone acetylation and activating tumor suppressor genes such as PTEN.

 

Lunasin selectively inhibits transcription, a dynamic process that occurs at various locations and at different times in the cell and is initiated by unfolding of the chromosomes; a process facilitated by histone acetylation.

 

It is proposed that during the initiation of the carcinogenic process that involves transcription, the dynamic process of histone acetylation-deacetylation is disrupted. This evidence demonstrates that the molecular mechanism for Lunasin is profound, compared to other cancer preventative agents in that it selectively kills cells that are transforming into cancer cells, without affecting normal cells. 

 

Since Lunasin has a unique epigenetic mechanism that interferes at the very early stages of the carcinogenic process, this suggests that Lunasin is non tissue-specific and would be effective against different types of cancer. In addition, Lunasin has no known toxic effects, which is consistent with its presence in soybean that has been consumed in Asia for centuries.

 

The novel mechanism of action by Lunasin makes it an important research tool in understanding epigenetic control of gene expression during cancer development. Together with powerful tools in genomics and proteomics, Lunasin can be used to identify potential drug targets and diagnostic biomarkers.

Cardiovascular and cholesterol management research

 

Lunasin's ability to support cardiovascular health was acknowledged by the American Heart Association at their Annual Scientific Session in November, 2012, and Dr. Alfredo Galvez's presentation abstract was selected for publication in the AHA Journal, Circulation. 

 

Lunasin works in two ways to lower serum LDL cholesterol levels. First, it selectively disrupts a necessary step in the production of a key enzyme, HMG-CoA reductase. Lunasin reduces the acetylation of the Histone H3 tail by PCAF (lunasin blocks PCAF's specific binding position at K14), thus reducing the level of expression of the HMG-CoA reductase gene. With levels of the HMG-CoA reductase enzyme lowered and available for the liver to carry out cholesterol synthesis, the liver in turn produces less cholesterol.

 

Secondly, Lunasin upregulates the expression of the LDL-receptor gene. With an increase in the number of receptors available to clear LDL cholesterol from the bloodstream, LDL levels also decrease. Studies show that in the presence of Lunasin, the levels of SP1 (the coactivator of SREBP for LDL-receptor production) are two times higher than without Lunasin present. With SP1 more readily available to bind with SREBP, the LDL receptors are produced more efficiently, so more LDL cholesterol is pulled from the bloodstream, thereby reducing the circulating serum LDL levels.

 

Since 70-80% of the circulating cholesterol in your body is produced within your liver, it is important to target this process in addition to consuming less saturated fat and cholesterol in your diet. Lunasin works at an earlier stage in your body’s internal cholesterol production process than prescription statins. Lunasin reduces the amount of HMG-CoA reductase enzyme produced by the HMG-CoA reductase gene. Statin drugs work by blocking the HMG-CoA reductase enzyme after it has been produced when it is on its way to carry out the body’s internal cholesterol production cycle. Statin drugs can oftentimes be too efficient and block too much of the HMG-CoA enzyme. This leads to serious side effects because a minimum level of cholesterol is required in the body for certain necessary cellular functions such as maintaining cell membrane integrity and hormone production.

 

 

Other studies have shown that lunasin has the ability to inhibit the aberrant inflammation that can occur in chronic diseases, including cancer. This property was also discovered by a team including Benito O. de Lumen, along with Elvira Gonzalez de Mejia, Vermont P. Dia, as well as others, as a part of research attempts to create purified lunasin through a more inexpensive means.

Benefits of Lunasin

• Bio-active peptide with an epigenetic mode of action
• Natural component of soy and other seeds – favorable public perception
• GRAS (Generally Recognized as Safe) by the FDA
• Ideal chemo-preventative agent to fight skin cancer
• Extends cell longevity (anti-aging) *Unpublished
• Anti-oxidant effect: especially protects DNA from oxidation as well lipids
• Anti-inflammatory effect
• Effective dose is minimal
• Non-invasive treatment

Lunasin’s patents

A bottle of LunaRich XTM

 

• Chickenjoy - fried chicken
• Champ - a half-pound burger with tomato, lettuce, cheese, pickles, etc. (similar to McDonalds' Big Mac)
• Jolly Spaghetti - spaghetti with the typical Filipino-style sauce (sweet and a bit spicy), hotdog slices and spiced ham
• French Fries
• Yumburger - regular hamburger with special dressing
• Yumburger with Cheese
• TLC Burger - hamburger with tomato, lettuce and cheese
• Mushroom and Cheese Burger - hamburger with sauteed mushrooms and a cheese sauce
• Aloha Burger - hamburger with bacon and pineapple ring
• Burger Steak - served with mushroom sauce
• Jolly Hotdog - hotdog sandwich topped with manhattan sauce (similar to 7-11's hotdog sandwich) and grated cheese

• 8-7000 Jollibee Express Delivery Service
• Jollibee Kids Party
• Jollibee Drive Thru
• 24-hour Service
• 8 success secrets from Jollibee, which aims to be in world’s top 3

1. Customer focus — “The market is so dynamic and fast-changing, so we do a lot of research. When Jollibee was small and we had little research funds, we directly asked customers their needs and wants.” 
2. Vision — Tanmantiong said, “When we started in 1978, people asked why we didn’t get a US franchise. We already wanted to create our own brand because we didn’t want to be limited to the Philippine market. Since the start, our vision was, first, to become No. 1 in the Philippines; second, to eventually expand overseas. Now our vision is we want to be one of the top three largest and among the most profitable restaurant companies in the world. Again, this is a big dream.” 
3. Spirit of family and fun — “Among the Jollibee core values are unity and team work. We have less than 10 family members working at Jollibee group. We now have over 40,000 employees, roughly 4,000 of whom are managers. If you include the other brands, we have maybe more than 60,000 employees.” 
4. Good quality — Tanmantiong said that the consistently “superior taste” of Jollibee foods is one success secret of their business. The family’s eldest sister Virgie Tan Chua was the one who started Jollibee spaghetti. When I asked if they had paid her for this recipe, Ato Tanmantiong laughed, saying, “Don’t give her the idea!”
5. Location — Jollibee makes sure that its stores and affiliates are conveniently located.
6. Good partners — Jollibee group has grown phenomenally due to good business partners through its franchising system. Today, 50 percent of Jollibee stores are owned by franchisees. Each franchise now costs about P25 million.
7. Culture — “We make sure the whole organization shares our vision and values, meaning they’re all part of that,” Tanmantiong said. “Our corporate values are excellence, spirit of family and fun, humility to learn and listen, integrity, frugality, respect for the individual, and teamwork. Anybody who is not a fit to all that, we remove from the organization. Our people are more engaged and committed.”
8. Marketing — The overall marketing programs and efforts have contributed to the success of Jollibee, from the brand name, logo, the popular mascot, TV commercials and print ads, to their very own TV show. Their top celebrity endorsers include Aga Muhlach, Sarah Geronimo, Gerald Anderson, Enchong Dee, Kim Chiu, international brand ambassador Jessica Sanchez and the very first endorser of the early 1980s, singer Gary Valenciano.