BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration

It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.

/pdf/evidence-for-cardiomyocyte-renewal-in-humans-a5djz8s7ml.pdf

Evidence for cardiomyocyte renewal in humans

Attempts to repair myocardial infarcts by transplanting cardiomyocytes or skeletal myoblasts have failed to reconstitute healthy myocardium and coronary vessels integrated structurally and functionally with the remaining viable portion of the ventricular wall. The recently discovered growth and transdifferentiation potential of primitive bone marrow cells (BMC) prompted us, in an earlier study, to inject in the border zone of acute infarcts Lin− c-kitPOS BMC from syngeneic animals. These BMC differentiated into myocytes and vascular structures, ameliorating the function of the infarcted heart. Two critical determinants seem to be required for the transdifferentiation of primitive BMC: tissue damage and a high level of pluripotent cells. On this basis, we hypothesized here that BMC, mobilized by stem cell factor and granulocyte-colony stimulating factor, would home to the infarcted region, replicate, differentiate, and ultimately promote myocardial repair. We report that, in the presence of an acute myocardial infarct, cytokine-mediated translocation of BMC resulted in a significant degree of tissue regeneration 27 days later. Cytokine-induced cardiac repair decreased mortality by 68%, infarct size by 40%, cavitary dilation by 26%, and diastolic stress by 70%. Ejection fraction progressively increased and hemodynamics significantly improved as a consequence of the formation of 15 × 106 new myocytes with arterioles and capillaries connected with the circulation of the unaffected ventricle. In conclusion, mobilization of primitive BMC by cytokines might offer a noninvasive therapeutic strategy for the regeneration of the myocardium lost as a result of ischemic heart disease and, perhaps, other forms of cardiac pathology.

https://www.pnas.org/content/pnas/98/18/10344.full.pdf

Mobilized bone marrow cells repair the infarcted heart, improving function and survival

Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.

Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy

// Shaomin Yan 1 and Guang Wu 1 1 Bioscience and Technology Research Center, Guangxi Academy of Sciences, Nanning, Guangxi, 530007, China Correspondence to: Guang Wu, email: hongguanglishibahao@yahoo.com Keywords: aldehyde dehydrogenase 2; ALDH2 * 2; East Asian; stem cell; ovarian cancer Received: July 03, 2017      Accepted: December 16, 2017      Published: December 22, 2017 ABSTRACT It is curious that East Asian women have a low incidence and mortality of ovarian cancer in various epidemiological studies. Although different explanations were given, they appear unsubstantial. We notice that East Asian population usually are inactive aldehyde dehydrogenase 2 mutation (ALDH2 * 2) carriers, and ALDH plays an important role in the resistance of ovarian cancer to chemotherapeutics, especially in ovarian cancer stem cells. Therefore, we hypothesize whether ALDH2 mutation is the major reason for low incidence and mortality of ovarian cancer in East Asian women, and use the evidence from literature, transcriptomic data with average 5-year overall survival to confirm our hypothesis.

/pdf/could-aldh2-2-be-the-reason-for-low-incidence-and-mortality-3vozny9i4b.pdf

Could ALDH2*2 be the reason for low incidence and mortality of ovarian cancer for East Asia women?

To study the quantitative relationship between the mutant N-acetylgalactosamine-6-sulfatase and the occurrence of mucopolysaccharidosis IVA, the human N-acetylgalactosamine-6-sulfatase with 117 mutations was quantified using the amino-acid distribution probability, then the mutations and clinical outcomes were coupled using the cross-impact analysis. The results show that a patient has 0.94 chance of being mucopolysaccharidosis IVA when a new mutation occurs in N-acetylgalactosamine-6-sulfatase.

Descriptively quantitative relationship between mutated N-acetylgalactosamine-6-sulfatase and mucopolysaccharidosis IVA.

Of many factors affecting protein crystallization, randomness in proteins has been given less attention although highly structured proteins would be at low entropy state. The factors, which impact on protein crystallization, are almost exclusively related to non-random amino acid properties such as physiochemical properties of amino acids. In this study, we used logistic regression and neural network to model the success rate of crystallization of 420 proteins from Staphylococcus aureus with each of non-random and random amino acid properties in order to determine whether randomness in a protein plays a role in the crystallization process. The results show that randomness is indeed involved in the crystallization process, and this rationale would enrich our knowledge on crystallization process and enhance our ability to crystallize more important proteins.

Randomness in crystallization of proteins from Staphylococcus aureus.

Summary

This is a continuation of our studies previously published in this journal to use data analysis to explore why the reassortment of genetic segments from different host species and from different subtypes of influenza A viruses occurred frequently, which was considered the main reason for the generation of new strains. Of eleven proteins from influenza A virus, we have studied seven proteins in our previous studies. To get a full picture, 2352 polymerase basic proteins 1 from influenza A viruses were analysed. The results showed that the variations between host species/subtypes are smaller than those within host species/subtype. In combination with the results obtained from hemagglutinin, neuraminidase, nucleoprotein, matrix proteins 1 and 2, polymerase acidic protein and polymerase basic proteins 1 and 2, the results suggested that the predisposition to reassortment of genetic segments of influenza A virus from different host species and subtypes was mainly because of the small variations between the virus isolates.

Small variations between species/subtypes attributed to reassortment evidenced from polymerase basic protein 1 with other seven proteins from influenza A virus.

Global warming affects not only the environment where we live, but also all living species to different degree, including influenza A virus. We recently conducted several studies on the possible impact of global warming on the protein families of influenza A virus. More studies are needed in order to have a full picture of the impact of global warming on living organisms, especially its effect on viruses. In this study, we correlate trends in global warming with evolution of the nucleoprotein from influenza A virus and then analyse the trends with respect to northern/southern hemispheres, virus subtypes and sampling species. The results suggest that global warming may have an impact on the evolution of the nucleoprotein from influenza A virus.

Shaomin Yan

Papers

Could ALDH2*2 be the reason for low incidence and mortality of ovarian cancer for East Asia women?

Descriptively quantitative relationship between mutated N-acetylgalactosamine-6-sulfatase and mucopolysaccharidosis IVA.

Randomness in crystallization of proteins from Staphylococcus aureus.

Small variations between species/subtypes attributed to reassortment evidenced from polymerase basic protein 1 with other seven proteins from influenza A virus.

Trends in global warming and evolution of nucleoproteins from influenza A viruses since 1918.