Medicine Prize Research Articles

[The development of innovative therapeutic drugs targeting hypoxia responses].

The 2019 Nobel Prize in Physiology or Medicine was awarded to Dr. William G. Kaelin Jr, Dr. Peter J. Ratcliffe, and Dr. Gregg L. Semenza for their elucidation of new physiological mechanisms "How cells sense and adapt to oxygen availability". Moreover, two different drugs, HIF-PH inhibitors and HIF-2 inhibitors were also developed based on the discovery. Interestingly, those three doctors have different backgrounds as a medical oncologist, a nephrologist, and a pediatrician, respectively. They have started the research based on their own unique perspectives and eventually merged as "the elucidation of the response mechanism of living organisms to hypoxic environments". In this review, we will explain how the translational research that has begun to solve unmet clinical needs successfully contributed to the development of innovative therapeutic drugs.

[Clinical application and future perspectives of HIF-PH inhibitors].

Anemia in chronic kidney disease (CKD) occurs due to insufficient production of erythropoietin to compensate for the decrease in hemoglobin. Anemia in CKD has traditionally been treated with periodic injections of erythropoiesis-stimulating agents (ESAs), which are recombinant human erythropoietin preparations. Although ESA improved anemia in CKD and dramatically improved the quality of life of patients, there are some patients who are hyporesponsive to ESA, and the use of large doses of ESA in these patients may have a negative impact on patient prognosis. Currently, HIF prolyl hydroxylase (HIF-PH) inhibitors have been approved in Japan as a new treatment for anemia in CKD. HIF-PH inhibitors activate HIF and promote the production of endogenous erythropoietin. The 2019 Nobel Prize in Physiology or Medicine was awarded for groundbreaking research that uncovered the HIF pathway. Because HIF-PH inhibitors improve both erythropoietin production and iron metabolism, they are expected to be effective in treating ESA hyporesponsiveness and solve the inconvenience of injectable preparations. On the other hand, its effects are systemic and multifaceted, and long-term effects must be closely monitored.

Roger Sperry, the maverick brain scientist who was haunted by psyche.

This paper describes the scientific figure of Roger Sperry as a maverick researcher, an original thinker who arrived at definitive notions about the working of the brain mostly by distancing himself from the prevalent views of his peers. After solving the riddle of the functions of the corpus callosum, he won a Nobel prize in physiology or medicine for identifying the different cognitive abilities of the disconnected right and left hemispheres of the human brain. He could have won another Nobel prize for his work on the prenatal formation of behavioral neuronal networks and their growth and development after birth. In the last part of his life, he fought a courageous but inconclusive battle for demonstrating that mental and spiritual factors can direct brain activity and behavior without violating the laws of orthodox neurophysiology. Some nodal points in his scientific career and some sources of inspirations for his thinking are identified and discussed within the historical background of the neurosciences of the twentieth century.

Artemisia spp. Essential Oils: From Their Ethnobotanical Use to Unraveling the Microbiota Modulation Potential.

The 2015 Nobel Prize in Medicine, awarded for the discovery of artemisinin in Artemisia annua, reignited interest in aromatic plants, including Artemisia absinthium L. This article delves into the historical, ethnopharmacological and medicinal significance of A. absinthium, examining its bitter taste noted since ancient Greek times and its association with medicinal properties throughout history. Despite being banned in the 20th century due to perceived health risks; recent research has led to the reconsideration of A. absinthium's potential applications. This study focuses on the prebiotic efficacy of essential oils (EOs) from two Artemisia species: A. absinthium and A. annua. A broth microdilution test, growth curve test and in vivo models were used to study the impact of low doses (from 0.5% v/v to 0.00048 v/v) of Artemisia spp-EO on the three probiotic strains (Lactobacillus, Lactobacillus casei and Saccharomyces boulardii). These essential oils, when used in minimal concentrations (lower than 0.06% v/v), are safe and exhibit prebiotic effects on major probiotic strains, supporting the traditional culinary use of Artemisia spp. This research opens avenues for potential applications in the food industry, emphasizing the need for further exploration into the prebiotic properties of Artemisia spp-EOs and their influence on the microbiota.

H. pylori infection: A 40-year journey through shifting the paradigm to transforming the management.

Background Helicobacter pylori (H.pylori) was discovered 40 years ago and has set a milestone in human medicine. The discovery led to rejection of the dogma of the acidic stomach as a sterile organ and requested to rewrite the chapters on gastric pathophysiology and gastroduodenal diseases . Summary Over a period of 40 years following the discovery ,more than 50.000 articles can be retrieved in Pubmed as of today and illustrate the amount and the intensity of research around the role of this bacterium. H.pylori emerged as cause of chronic gastritis and principal cause of peptic ulcer disease (PUD). Eradication of H.pylori became standard of care in management in PUD. The importance of this was highlighted in 2005 with the Nobel prize in Medicine awarded to Barry Marshall and Robin Warren. H.pylori became eventually recognized for its oncogenic potential in the stomach and as the main risk factor for gastric cancer development. Key messages H.pylori gastritis is defined as infectious disease and requires therapy in all infected individuals. Strategies of gastric cancer prevention and development of therapies to overcome the increasing antibiotic resistance are main targets in clinical research of today.

India lost one more chance to get the Nobel Prize in Medicine or Physiology: When waiting will be over?

India lost one more chance to get the Nobel Prize in Medicine or Physiology: When waiting will be over?

The Nobel Prize in Physiology or Medicine 2023 was awarded for discoveries concerning base modifications that enabled the development of effective mRNA vaccines against COVID-19

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TR(i)P Goes On: Auxiliary TRP Channel Subunits?

Transient receptor potential (TRP) cation channels are a diverse family of channels whose members play prominent roles as cellular sensors and effectors. The important role of TRP channels (and mechanosensitive piezo channels) in the complex interaction of our senses with the environment was underlined by the award of the Nobel Prize in Physiology or Medicine to 2 pioneers in this field, David Julius and Ardem Patapoutian. There are many competent and comprehensive reviews on many aspects of the TRP channels, and there is no intention to expand on them. Rather, after an introduction to the nomenclature, the molecular architecture of native TRP channel/protein complexes in vivo will be summarized using TRP channels of the canonical transient receptor potential subfamily as an example. This molecular architecture provides the basis for the signatures of native canonical transient receptor potential currents and their control by endogenous modulators and potential drugs.

Celebrating vaccines: The 2023 Nobel prize in medicine or physiology

Celebrating vaccines: The 2023 Nobel prize in medicine or physiology

Nobel Prize in physiology or medicine 2023: Development of mRNA therapeutics that paved the path of formulation of COVID-19 vaccine

Since the concept of the vaccine was developed by Edward Jenner in 1796, vaccinology has traveled a long way with gradual improvement toward developing better methods of formulation of vaccines. In this premises in the 1990s, Karikó and Weissman joined their hands and minds aiming at understanding how different RNA species interact with the immune system. During their long journey in this direction, they performed extensive studies involving well-conceived molecular biology-based experiments that resulted in a breakthrough discovery relating to RNA therapeutics in general and messenger RNA (mRNA) therapeutics in particular. In this endeavor, they developed mRNA technology that actually paved the path leading to the development of mRNA vaccine that has many advantages. In December 2019, when the deadly virus SARS-CoV-2 emerged, which, in no time, caused a pandemic as well as an epidemic, thereby throwing a fierce challenge to the total healthcare systems worldwide, it was possible to take care of that challenge through the formulation and manufacturing on a large scale the mRNA vaccine against SARS-CoV-2 using the above technology. Thus, mRNA technology has created a strong platform that has spelled out a great promise toward controlling any pathogen infection and saving human life through the development of mRNA vaccine at a quick pace. In this short review, an attempt will be made to highlight the contributions of Karikó and Weissman and how they led the formulation of a vaccine against COVID-19, which fetched them the Nobel Prize in Medicine or Physiology, 2023.

The Nobel family

Nobel laureates cluster together. 696 of the 727 winners of the Nobel Prize in physics, chemistry, medicine, and economics belong to one single academic family tree. 668 trace their ancestry to Emmanuel Stupanus, 228 to Lord Rayleigh (physics, 1904). Craig Mello (medicine, 2006) counts 51 Nobelists among his ancestors. Chemistry laureates have the most Nobel ancestors and descendants, economics laureates the fewest. Chemistry is the central discipline. Its Nobelists have trained and are trained by Nobelists in other fields. Nobelists in physics (medicine) have trained (by) others. Economics stands apart. Openness to other disciplines is the same in recent and earlier times. The familial concentration of Nobelists is lower now than it used to be.

Disparities in funding for Nobel Prize awards in medicine and physiology across nationalities, races, and gender.

Since 1901, the Nobel Prize in Physiology and Medicine has been awarded to numerous individuals for their outstanding contributions. This article presents a comprehensive analysis of the Nobel Prize recipients, focusing on gender, race, and nationality. We observe that an alarming disparity emerges when we examine the underrepresentation of Black scientists among Nobel laureates. Furthermore, trends in nationalities show how Americans make up the majority of Nobel Prize winners, while there is a noticeable lack of gender and racial minority winners of the Nobel Prize in Physiology and Medicine. Together, this highlights the importance of diversity and inclusion in scientific achievement. We offer suggestions and techniques, including funding opportunities and expanding nominators, to improve the gender, racial, and geographical diversity of Nobel Prizes.

ВИНАХІД КОМП‘ЮТЕРНОЇ ТОМОГРАФІЇ І ЙОГО ЗНАЧЕННЯ В ІСТОРІЇ ПУЛЬМОНОЛОГІЇ

Imaging diagnostic methods in pulmonology originate from the discovery of X-rays. Radiography is the first-line tool for chest imaging, but in many cases its capabilities are limited. The aim was to study the history of the invention of computed tomography. Since the radiogram is a two-dimensional summation image of a three-dimensional anatomical structure, there was a need to visualize separate layers of the pathological process. Since 1913, many technical solutions of tomography have been tested. Linear tomography for some time served for the diagnosis of lung pathology, helped to determine the localization more accurately, examine a prevalence, nature and structure of the pathological process, to detect small pathological formations and cavities. But the quality of tomography was not satisfactory. The two outstanding inventors of computed tomography who were awarded the 1979 Nobel Prize in Medicine were not the physicians. Allan McLeod Cormack (Professor and Head of the Institute of Physics at Tufts University, Medford, Massachusetts, USA) was the first to outline the principles of cross-sectional tissue reconstruction in an organ based on X-ray projections in 1963. Godfrey Newbold Hounsfield (Head of Medical Research at Electric and Musical Industries, Middlesex, England) not only reproduced the mathematical algorithms of the technique, but also designed the tomograph and directly participated in its clinical implementation in 1971. Among the developers of the idea of three-dimensional X-ray tomography in 19571958 were the scientists of Kyiv Polytechnic Institute Semyon Tetelbaum and Boris Korenblyum. Key words: radiology, computed tomography, history of pulmonology.

Roles of TRP and PIEZO receptors in autoimmune diseases.

Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.

Sleeping Beauty 2000: an evaluation index of leading and original literature based on the Nobel Prize in Physiology or Medicine

Sleeping Beauty 2000: an evaluation index of leading and original literature based on the Nobel Prize in Physiology or Medicine

"All for One and One for All": The Secreted Heat Shock Protein gp96-Ig Based Vaccines.

It has been 50 years since Peter Charles Doherty and Rolf M Zinkernagel proposed the principle of "simultaneous dual recognition", according to which adaptive immune cells recognized "self" and "non-self" simultaneously to establish immunological efficacy. These two scientists shared the 1996 Nobel Prize in Physiology or Medicine for this discovery. Their basic immunological principle became the foundation for the development of numerous vaccine approaches against infectious diseases and tumors, including promising strategies grounded on the use of recombinant gp96-Ig developed by our lab over the last two decades. In this review, we will highlight three major principles of the gp96-Ig vaccine strategy: (1) presentation of pathogenic antigens to T cells (specificity); (2) activation of innate immune responses (adjuvanticity); (3) priming of T cells to home to the epithelial compartments (mucosal immunity). In summary, we provide a paradigm for a vaccine approach that can be rapidly engineered and customized for any future pathogens that require induction of effective tissue-resident memory responses in epithelial tissues.

Charles Brenton Huggins: A historical review of the Nobel laureate's pioneering discoveries.

Androgen deprivation therapy for prostate cancer was pioneered by Charles Huggins, laureate of the Nobel Prize in Medicine in 1966. The authors tried to understand the scientific context and how previous findings paved Huggins way to his discoveries. With the help of summary or review articles on androgen deprivation therapy, the authors identified key publications and used his Nobel Prize speech as a basis to understand his discoveries. Furthermore, they used a recording of the laboratory-talk interview he gave about his findings to guide them to relevant publications. The authors found that the basis for Huggins' discoveries was the isolation of testosterone in 1935, not long before Huggins' 1941 hallmark publication. Huggins' work follows major experiments in the 19th century in orchiectomy done as a treatment for prostate hypertrophy. Researching the etiology of idiopathic hydrocele, Huggins analyzed the composition of prostate fluid. Further research led to the discovery of the influence of castration, testosterone, and estrogen on acid phosphatase. Recently developed methods facilitated the measurement of the phosphatases. He, therefore, had a biomarker for metastatic prostate cancer to measure treatment response. Very early on, he reported clinical improvements after castration in metastatic patients. Although the effect of orchiectomy on prostate hypertrophy was already known, Huggins was the first to show that testosterone stimulated and estrogen decreased the activity of prostate cancer. Huggins also established phosphatases as a tumor marker to measure disease response.

CREATIVITY AND ORIGINALITY ARE KEY ELEMENTS IN MEDICAL RESEARCH: RECENT ILLUSTRATION BY THE 2023 NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE TO KATALIN KARIKO AND DREW WEISSMAN

For at least a century, an often-debated topic is what is of primary importance to make breakthrough in biomedical research: originality/creativity or sophisticated methods/equipment. We present here a short historical overview arguing about the importance of creativity, originality, and persistence. Namely, the best living example of this is the 2023 Nobel Prize in Physiology or Medicine awarded to Drs. Katalin Kariko and Drew Weissman for the invention and development of mRNA-based vaccine against COVID-19. Katalin Kariko had a life-long obsession to use mRNA for cancer therapy, but when the structure of SARS-CoV-2 was announced, she shifted her interest to develop an mRNA-based vaccine against the new virus. But since the mRNA molecule is notoriously unstable and easily degraded if injected intracellularly, she teamed up with Dr. Weissman who was working on techniques to deliver mRNA molecules intracellularly. This creative teamwork with original ideas of vaccine development illustrates what other creative scientists, like Alexander Flemming, Hans Selye, Leon Popielski and James Black discovered in their fields. The sad part of the story is that only two of these scientists got the Nobel Prize.

Neurosciences and Nobel Prizes in Medicine and Physiology, A Brief Historical Sketch

In order to stimulate and promote the development of humanity, Alfred Bernhard Nobel, in his will, established with his fortune a fund with which the best exponents in Literature, Physiology or Medicine, Physics, Chemistry and Peace would be rewarded. Over the years, awardees have come from various fields related to physiology and medicine. This review was motivated by the large number of Nobel Prize winners in Medicine and Physiology in the neuroscientific field. Despite there being numerous publications about this award, there are few that specifically deal with neuroscience, so it was decided to briefly describe it. the Nobel Prizes that were awarded to this branch of medicine, highlighting those that were considered most important by the authors and mentioning the others.

The pivotal role of uridine modifications in the development of mRNA technology

In 2023, Katalin Karikó and Drew Weissman were awarded the Nobel Prize in Physiology or Medicine for their nucleoside base modifications research that later enabled mRNA vaccine development against COVID-19. This paper briefly reviews these achievements in the context of the development of mRNA technology and its enormous potential for medicine in the prevention of various infectious diseases and cancer treatment, including personalised therapies. Without a doubt, Karikó and Weissman's discoveries were vital in getting around one of the biggest problems with using mRNA molecules in real life: they had to be recognised by endosomal Toll-like receptors and the innate immune response that came after, causing exogenous mRNA molecules to have less translational activity and break down.. Although the Nobel Prize for Karikó and Weissman is fully justified, it must be stressed that mRNA technology would never unfold its potential for public health without a collective scientific effort encompassing over 40 years of research.