Cellular proteome, coregulators, endocrine system and the human brain: the Regulatory biology of humanism
The Regulatory Biology of Humanism
There is little doubt that humans are the masters of their known universe. A lively debate could center on why this is so. Although humans have many specialized physical features, such as the marvelous human hand and fingers, other species also have distinguishing features that outclass similar physical features of humans – features such as more acute hearing, smell, or sight. There is little debate, however, that our crowning evolutionary achievement is the human brain. There appears to be no species or other mammal capable of competing with our ability to reason, plan, calculate, and emote. How did this impressive jump in evolution occur? Although not a question that can be answered by hard data, it remains a lively topic for discussion. In my opinion, the two most advanced biologic ‘systems’ that we humans have are (1) the central and peripheral endocrine system and (2) the cellular proteome. It is these two points I would like to further develop in this Perspective.
Our endocrine system and our cellular proteome form an intimate connection with the human brain to construct a powerful troika responsible for our unique capacities as a species. This partnership likely co-evolved to cope with the diversity of our environment and with the intense metabolic demands required to nurture, operate and preserve the human brain. Hormones comprise the endocrine system. The word itself emanates from the Latin word ‘hormo’ which means to ‘set in motion’. Hormones do that in great fashion, as they move all cells and organs of our body into action. Our cells and tissues would be relatively inert without them. These chemical regulators control our genesis, development, maturation, and then function in adulthood to support the growth and metabolic functions of all organs, including the brain and its peripheral links. Hormones are not unique to humans, however. They exist even in plants, worms and flies. Mammals, however, have a more highly developed endocrine system that contains many specialized hormones. It is uncertain as to how many hormones actually exist in mammals. We often list ~50 of the more common hormones, but the actual numbers likely are in the hundreds, and perhaps will reach closer to a thousand when finally all are identified. At an earlier period in the field of Endocrinology, we defined hormones as ‘chemical signals released from an organ into the blood stream to act on distant target tissues. Clearly, this definition has been outdated for some years, and a compete list of hormones probably should include a variety of paracrine and autocrine chemical signals, including growth factors, immune cell secretions, cytokines, chemokines, and perhaps even neurotransmitters. There is no greater diversity of environmental signals and physical and emotional stresses for a mammal to bear than those to which a human being has been subjected over the course of evolution.
When people discuss modern medicine, precision plays one of the most important roles and human lives are directly dependent on it. Hereby, any researches pertaining to medicine are necessary to comply with the highest standards. The issue nowadays is that any conclusions of researches can be published online and used as a reference without being thoroughly verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this problem and tried to come up with an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been founded back in 2010. The major principle of this journal is based on Altmetric scores that are used as a quality indicator. That helps both readers and authors to quality-check publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a full publications list with corresponding scores above 100 as well as reports discussed above. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the required help to anybody, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was published back in 2018 by Oncotarget and completed by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The publication has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Hence, the paper about melanoma, was utilized for citations in different news articles 69 times. Besides that, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This publication has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive useful scientific facts. Oncotarget is proud to have the chance to share with online readers this highly appreciated and top-quality information, that is trustworthy and reliable.
Mikhail (Misha) V. Blagosklonny graduated with an MD and PhD from First Pavlov State Medical University of St. Petersburg, Russia. Dr. Mikhail V. Blagosklonny has then immigrated to the United States, where he received the prestigious Fogarty Fellowship from the National Institutes of Health. During his fellowship in Leonard Neckers’ lab at the National Cancer Institute (NCI), he was a co-author of 18 publications on various biomedical themes, including targeting HSP90, p53, Bcl2, Erb2, and Raf-1. He also was the last author for a clinical phase I/II trial article.
After authoring seven papers during a brief yet productive senior research fellowship in the El-Deiry Cancer Research Lab at the University of Pennsylvania, Dr. Blagosklonny returned to NCI to work with Tito Fojo. Together, they published 26 papers. Moreover, Dr. Blagosklonny published many of experimental research papers and theoretical papers as sole author. The abovementioned sole-author articles discussed two crucial topics. The first of these discussed selectively killing cancer cells with deregulated cell cycle or drug resistance via verifying their resistance. The outcomes and underlying notion were so revolutionary that they were incorrectly cited by other scientists as “reversal of resistance,” even though the publication was titled, “Exploiting of drug resistance instead of its reversal.” One big supporter of this concept was the world-famous scientist Arthur Pardee, with whom Dr. Blagosklonny co-authored a joint publication in 2001.
The second theme throughout Dr. Blagosklonny’s sole-author articles is a research method to develop knowledge by bringing several facts together from seemingly irrelevant areas. This results in new notions with testable forecasts, which in turn can be “tested” via analyzing the literature further. Likewise, the concept was co-authored by Arthur Pardee in a 2002 article in Nature. The first success of the new research methodology was the description of the feedback regulation of p53, as confirmed by the discovery of mdm2/p53 loop; and the explanation why mutant p53 is always overexpressed, published in 1997. The most important result revealed by Dr. Blagosklonny’s research methodology is the hyperfunction (or quasi-programmed) theory of aging and the revelation of rapamycin as an exclusively well-tolerated anti-aging drug, published in 2006. As mentioned in Scientific American, Michael Hall, who discovered mTOR in 1991, gives Dr. Blagosklonny credit for “connecting dots that others can’t even see.”
In 2002, Dr. Blagosklonny became associate professor of medicine at New York Medical College. He agreed to accept responsibilities as a senior scientist at Ordway Research Institute in Albany, New York, in 2005, before receiving another position at Roswell Park Cancer Institute as professor of oncology in 2009.
Since coming to Roswell Park Comprehensive Cancer Center in 2009, Dr. Blagosklonny has studied the prevention of cancer (an age-related disease) via stopping organism aging - in other words, “preventing cancer via staying young.” His laboratory closely worked together with Andrei Gudkov’s and conducted research on the suppression of cellular senescence, namely suppression of cellular conversion from healthy quiescence to permanent senescence. This led to the discovery of additional anti-aging medicines beyond rapamycin. The cell culture studies were complemented by studies in mice, including several models like normal and aging mice, p53-deficient mice, and mice on a high-fat diet.
Dr. Blagosklonny has also published extensively on the stoppage of cellular senescence via rapamycin and other mTOR inhibitors, life extension and cancer stoppage in mice, and combinations of anti-aging medicines to be taken by humans. A rapamycin-based combination of seven clinically available medications has been named the “Koschei Formula” and is now used for the treatment of aging in patients at the Alan Green Clinic in Little Neck, New York.
https://triberr.com/mishablagosklonny
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