Presentation time including discussion: 40 min (keynote/invited talk); 20 min (oral presentation)

Online link: https://snu-ac-kr.zoom.us/j/4129135434

❖ ISPS 2021 PRESIDENT

• - Pan-Dong Ryu

❖ ISPS 2021 SENIOR ADVISORS

• - Kwang-Sup Soh

❖ ISPS 2021 ORGANIZING COMMITTEE

• - Pan-Dong Ryu

• - Chang-Su Na

• - Sung Chul Kim

• - Hee-Young Kim

• - Sang-Suk Lee

• - Sang Wook Oh

• - Su Ho Park

• - Min-Su Kim

• - Ku-Yeon Baik

• - Min-Seob Shin

• - Sujung Yeo

• - You-Sik Hong

• - Hoon Gi Kim

• - Jiyoon Lee

❖ ISPS 2021 SCIENTIFIC COMMITTEE

• - Pan-Dong Ryu

• - Sung Chul Kim

• - Hee-Young Kim

• - Sang-Suk Lee

• - Sang Wook Oh

• - Ku-Yeon Baik

(Status : May 27, 2021)

Online link: https://snu-ac-kr.zoom.us/j/4129135434

Thursday May 27^th

(Status : May 28, 2021)

Online link: https://snu-ac-kr.zoom.us/j/4129135434

Friday May 28^th

(Status : May 29, 2021)

Online link: https://snu-ac-kr.zoom.us/j/4129135434

Saturday May 29^th

Presentation time: 40 min including discussion

❖ Keynote talks

1. Achievements of PVS Research from the Perspective of Science & Technology Studies

Prof. Hoon Gi Kim, Hongik University, Republic of Korea

2. Primo Vascular Node in Rat Bone Marrow

Prof. Vitaly Vodyanoy, Aburn University, USA

3. Adrenergic Modulation of Primo Vascular System

Prof. Pan-Dong Ryu, Seoul National University, Republic of Korea

❖ Invited talks

1. Lymphatic Window from and into the Brain: New Concept of Lymphatic/Primo-vascular Pathways of Drug Brain Delivery

Prof. Oxana Semyachkina-Glushkovskaya, Saratov State University, Russia

2. Cellular Architecture of the Primo Vascular System

Prof. Fatma El-Zahraa A. Mustafa, Assiut University, Egypt

3. An update on my journey investigating the primo vascular system: From a research stay in South Korea to own research in rats and on human placentas

Dr. Felix Scholkmann, University Hospital Zurich, University of Zurich, Switzerland

4. PVS: before the past, bizarre present and peek after the future!

Prof. Miroslav Stefanov, Trakia University, Bulgaria

5. Primo-vascular System: from Science Research to Therapeutic Application

Dr Paul Roberts, Somatic Educator SOSA Osteopathy & Somatic Therapy Center, Hong Kong

Achievements of PVS research from the perspective of STS

Hoongi Kim

College of Liberal Arts, Hongik University, Republic of Korea

Corresponding author e-mail address: wolfkim8@gmail.com

Abstract: The purpose of this paper is to compare the biological research carried out in North Korea with the modern outcomes in the same field, from the perspective of Science and Technology Studies. In the 1960s, the group led by Bonghan Kim asserted the existence of a fundamental circulatory system in the human body which was structurally and functionally distinct from the blood, lymphatic, and nervous systems. Their findings were published in five papers as well as in the newspaper Rodong Sinmun. The size of the group, the range of equipment, and their findings expanded gradually, and the final paper on blood cells would be only published one of over sixty papers reported at that time. In the five papers, some unclear or inconsistent content was found. Meanwhile, over the past two decades in the 2000s, PVS researchers have published over one hundred papers which aimed to prove the existence of this new circulatory system by developing new dyeing and microscopic observation methods. Some trends have emerged in approximately sixty papers, which can be summarized as follows: The research on the identification of the anatomical and histological characteristics has gradually expanded to encompass the system's own functioning. Also, new visual results (e.g. before and after dyeing, and its comparison with blood clotting) and the exploration of possible medical applications (e.g. cancer metastasis channels or stem cells location) have been proposed. However, it is difficult to identify papers which comprehensively represent the structural and functional elements claimed by Bonghan Kim's group. In addition, relevant papers have been published to a greater extent in alternative or oriental medicine journals than in Western biology or medical journals. Therefore, it seems necessary to demonstrate the existence of the system with a higher degree of reproducibility, and to report the outcomes in more influential journals.

PVS: BEFORE THE PAST, BIZZARE PRESENT AND PEEK AFTER THE FUTURE!

Miroslav Stefanov

Trakia university, Agricultural faculty, Dept. of Morphology, Physiology and Nutrition, Bulgaria

Corresponding author e-mail address: miroslav.stefanov@trakia-uni.bg

INTRODUCTION. Is PVS a paradox? Is PVS a phenomenon? Is PVS a myth? This is the essence of the questions that are often asked by critics. More embarrassingly, critics provide no evidence of their doubts. Analyzing the specific characteristics of PVS it has a fundamental chance to provide answers to discover the deepest secret: what is life. Finding the connection between PVS as a carrier of information existing inside and outside organisms and the body’s reactions at the micro and macro levels, through physiological and pathological changes, will be the starting point in understanding the meaning of life as such.

BEFORE THE PAST OF PVS KNOWLEDGE. The initial phase of medicine in all cultures is reduced to the transfer of specific energy by special pathways throughout the body! This is the case in China, India, Japan, Korea, Tibet, etc. Whether the pathways will be called sen, meridians, channels, vessels or Nadis, the essence of the matter is the transfer of vital life force, prana or chi which accomplishes healing purposes of body and soul. The specific energy on which life is based is characterized as an energy flow of bio-electrical, resonant or vibrational nature. Undoubtedly, the five articles by B. H. Kim published in the early 1960s are considered to be the past of PVS.

STRANGE PRESENT. PVS studies after 2002 are accepted as a present. Most of the articles on the topic are in journals with editors-in-chief originating and/or accepting the achievements of Eastern medicine. Is the science of PVS local since its research is in journals that publish mainly articles on Eastern medicine? Why few of the articles concerning PVS are in Western medicine journals? One of the reasons the range of understanding of Meridian system has grown slowly in the West is possibly because of the belief that it has no anatomical basis. But, very strangely, when many scientific teams from different laboratories using strictly scientific methods and protocols, prove the presence of anatomical basis of the Meridian System, the leading scientific journals, refuse to publish them. Strangely why!?

PVS: AFTER THE FUTURE OR SOME CONCLUSIONS AND PROPOSALS. Western medicine is basically biochemical while Eastern medicine is physical. What would be the new paradigm in medicine!? In my opinion, Information Medicine is the new challenge facing humanity. While the chemical formula is the passport of the substance in the field of chemistry, the information copy of the substance is its passport in the field of physics. All substances, objects, biological objects generate a weak electromagnetic radiation typical for each of them which is a passport of the information. PVS has all the data to be the main carrier of information. Information Biology can serve as a basis for medicine and biomedical sciences and it should explain the processes that exist for the change of DNA and organisms in general, in accordance with and in response to external causes and internal changes.

Cellular architecture of the primo vascular system

Fatma El-Zahraa A. Mustafa

Department of Anatomy and Histology, Faculty of Vet. Medicine, Assiut University, 71515, Egypt

Corresponding author e-mail address: f.histology@aun.edu.eg

Abstract: The primo vascular system (PVS) is one of the most interesting points for Scientists in the last few years. PVS has a role in stem cell migration, immune function, erythropoiesis, tissue regeneration, and cancer metastasis. Kim 1960, a North Korean scientist, described it as a new independent system distributed in the body of different animals. Several cells were discovered as an important constituent of the primo vascular system. Some cells are considered hallmarks for the identification of the PVS as the endothelial cells. The endothelial cells lined the sinuses of the primo vessels and were characterized by the arrangement of its rod-shaped nuclei in parallel broken line fashion along the primo vessel. Also, Immune cells as mast cells, eosinophils, neutrophils, and lymphocytes are considered as one of the hallmarks for the identification of the primo vascular system. One of the most interesting cells in the PVS is the p-microcells. Primo node is considered as a stem cell niche due to p-microcells content which expressed stem cell biomarkers as CD133, and Oct 4. Mature erythrocytes and hematopoietic stem cells were observed in the PVS. Hematopoietic stem cells were the source of the cellular component of the blood. Also, adrenalin and noradrenaline-producing cells, mesothelial cells, and smooth muscle-like were described on the PVS.

Primo vascular node in rat bone marrow

Vitaly Vodyanoy^a,b*, Oleg Pustovyy^a, and Ludmila Globa^a

^a Department Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn, AL 36849, USA

^b School of Kinesiology, Auburn University, Auburn, AL 36849, USA

*Corresponding author e-mail address: vodyavi@auburn.edu

Abstract: We identified in rat bone marrow highly vascularized node-like compartments that meet the requirements for primo vascular node. These nodes are round or oval structures of about one millimeter in diameter that are surrounded by a fine capsule, have incoming and out coming vessels, are filled with the extracellular matrix and mesenchymal, hematopoietic, endothelial stem cells, and contain cells of the megakaryocyte family, found in other primo nodes. The nodes were extracted from the split in halves femur rat bone. The lifting of the stained vessel exposed the nodes. The vessel that was lifted in the nearby space of an epiphysis contains a distal node with efferent vessel branching in several thin sub-vessels. The nodes were characterized by high-resolution fluorescent microscopy, immunohistochemistry, Western blots, and RNA analysis. The longitudinal and transversal vessels create a single vascular system within the node. The central vessel of about 50 μm in diameter contains the lumen with thick walls girded by surrounding rib-like structures. The blood vessel and lymphatic endothelial cell markers reveled that node vessels do not belong to blood or lymph vasculatures. RNA analysis showed that node has a very different gene transcript expression and representative gene distribution in comparison to the lymph node, bone marrow, and blood vessel. This implies that the node is different from the other three samples by a genetic nature. We characterize the node cells using markers for mesenchymal, endothelial, and progenitor stem cells. In addition to the stem cells, the node contains many p-microcells cells scattered in the node cross-sections and inside vessels. Small p-microcells are accompanied by cells of about 25 μm in diameter. The small p-microcells are clearly labeled and visible inside the large cells. The most likely candidate for the large size cells is megakaryocytes or hemocytoblast – the multipotent hematopoietic stem cell. Based on our results we propose a node vessel structure composed of four layers. Layer 1, the outmost layer of the node vessel, chiefly comprises of fibroblastic cells oriented on the main axis of the vessel The thickness of Layer 1 is 3–5 μm. Layer 2 mainly comprises of vascular smooth muscle cells of 4.6 μm in diameter and 22–25 μm in length. The cells are arranged circumferentially around the vessel just underneath the outmost Layer 1, constituting a continuous helix. Layer 3 comprises of longitudinally oriented thinly dispersed smooth muscle cells and bundles of collagen fibrils. The average diameter of these muscle cells is 3.5 μm, whereas their length is up to 15 μm. The Layer 4 represents a continuous endothelium. On average, the endothelial cells are 5.7 μm wide and 18.6 μm long and oriented parallel to the long axis of the vessel. The endothelial cell in Layer 4 passes together with a thin bundle of fiber. Overall, our results suggest that a node inside the bone marrow belongs to intraorganic primo vascular system.

This work was supported by a grant from the Lake Erie College of Osteopathic Medicine, Erie, PA, USA.

Lymphatic window from and into the brain: new concept of lymphatic/primo-vascular pathways of drug brain delivery

O. Semyachkina-Glushkovskaya^{1,2 *}, I. Fedosov2, A. Shirokov^2,3, N. Navolokin^2,4, G. Maslyakova^2,4, A. Bucharskaya^2,4, A. Mamedova², M. Klimova², I. Blokhina², A. Terskov², V. Ageev², A. Dubrovsky², V. Vinnik². A. Zven², A. Evsyukova², T. Antonova², V. Ponomarenko², D. Postnov², T. Penzel^2,5, and J. Kurths^1,2,6

¹Humboldt University, Newtonstrasse 15, 12489 Berlin, Germany

²Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia

³Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Prospekt Entuziastov 13, Saratov 410049, Russia

⁴Saratov State Medical University, B. Kazachaya str., 112, Saratov, 410012, Russia

⁵Interdisciplinary Center of Sleep Medicine, Charité–Universitä tsmedizin Berlin, Berlin, Germany

⁶Potsdam Institute for Climate Impact Research, Telegrafenberg A31, 14473 Potsdam, Germany

*Corresponding author e-mail address: glushkovskaya@mail.ru

Abstract: The classical characteristics of the central nervous system (CNS) is a luck of the lymphatic vessels (LVs). The LVs have been discovered in the dura mater of humans and rodents^1-3. However, these studies did not confute the dogma that lymphatics in CNS do not exist. In fact, dura mater is not a component of the brain but covers, along with the other meningeal layers, both the brain and the spinal cord.

In our pioneering studies, we discovered the cerebral LVs (cLVs) in affected human brain using confocal colocolization analysis of Lyve1/Prox1, electron microscopy and immunohistochemistry⁴. This discovery is a revolutionary step a reassessment of basic assumptions of our understanding of lymphatic pathways of toxins clearance from the brain as well as lymphatic door into the brain^5-7.

In our experimental research, we clearly demonstrate that cLVs are a door from and into the brain, which maintains balance between the exit and the entrance of molecules and cells from and into CNS contributing Yin and Yang in the cerebral homeostasis. We show that the some acupuncture points are the crucial part of lymphatic/primo-vascular pathways of drug brain delivery. These findings open a new era for therapy of brain diseases via the lymphatic doors from and into the brain.

Funding: This work was supported by the Project of RF Government, Grant No. 075-15-2019-1885, Russian Science Foundation No. 20-15-0090, 19-15-00201 Russian Foundation for Basic Research, Grant No. 19-515-55016 and Grant No. 20-015-00308.

References:

[1] A. Louveau, et al., Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337–341 (2015). doi: 10.1038/nature14432

[2] A. Aspelund, et al., A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212, 991–999 (2015). doi: 10.1084/jem.20142290

[3] J. H. Ahn, et al., Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature 572, 62–66 (2019). doi: 10.1038/s41586-019-1419-5

[4] O. Semyachkina-Glushkovskaya, et al., Pilot identification of the initial lymphatic capillaries in the affected human brain. Science (2021) (submitted. ).

[5] O. Semyachkina-Glushkovskaya, et al., Biophotonic strategies of measurement and stimulation of the cranial and the extracranial lymphatic drainage function. IEEE Journal of Selected Topics in Quantum Electronics, 27(4), 1-13 (2021). doi: 10.1109/JSTQE.2020.3045834

[6] O. Semyachkina-Glushkovskaya, et al. Phenomenon of music-induced opening of the blood-brain barrier in healthy mice. Proc. R. Soc. 287, 20202337 (2020). doi: 10.1098/rspb.2020.2337

[7] O. Semyachkina-Glushkovskaya, et al. Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer’s Disease and the Blood-Brain Barrier. Int. J. Mol. Sci. 2020, 21(17), 6293; doi.org/10.3390/ijms21176293

Adrenergic modulation of primo vascular system

Yiming Shen, Yu Jeong Kim, and Pan-Dong Ryu*

Departments of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea

*Corresponding author e-mail address: pdryu@snu.ac.kr

Abstract: Previously we observed that the size of the organ surface PVS samples and the number of the tissue with red color are larger in the PVS tissue from the rats with heart failure (HF)¹, or hemolytic anemia². Based on these and other previous observation³, we hypothesized that the reduced tissue perfusion in both disease models induces sympathetic hyperactivation which in turn brings the morphological changes in the PVS tissues. Here, we first examined whether exercise training also inhibit the HF-induced-morphological changes in the PVS since exercise training is known to reduce the elevated sympathetic tone in HF⁴. HF model rats were prepared by ligating the left descending coronary artery. In HF rats, we observed an increase in the size of the primo nodes (p<0.01), the number of the PVS tissue samples per rat (p<0.05), the proportion of PVS tissue samples with red chromophore (p<0.001), and the number of RBCs (p<0.001) in the primo nodes. Exercise training ameliorated these HF-induced changes in the PVS. Blocking sympathetic activity with 6-hydroxydopamine, a chemical sympathectomy agent dramatically reduced the number of samples per rat in normal rats. In the rats with hemolytic anemia induced by phenylhydrazine, the treatment of 6-hydroxydopamine also normalized the enlarged primo node size (p<0.05) and the elevated proportion of the tissues with red chromophore (p<0.001). The increase in the size and number of the samples per rat was induced by administration of noradrenaline via subcutaneous osmotic pump. In contrast, the incidence of the tissue with red chromophore was not altered by noradrenaline. The noradrenaline-induced enlargement of the PVS tissue were blocked in the rat treated with propranolol (β-adrenoceptor antagonist), but not with pentolamine (α-adrenoceptor antagonist). Taken together, the results indicate that sympathetic stimulation may induce the enlargement of PVS tissue via β-adrenoceptor in the rats with heart failure or hemolytic anemia. This study is the first to show experimental evidence for sympathetic modulation of the PVS tissue. Much further study is needed to understand detailed receptor mechanisms underlying the morphological and extramedullary erythropoiesis in the normal and disease states.

Acknowledgment: This study was supported by the National Research Foundation of Korea funded by the Ministry of Education (2018R1D1A1B07043448).

References:

[1] Lim CJ, Shen Y, Lee SY, Ryu PD. Potential Erythropoiesis in the Primo-Vascular System in Heart Failure. Adv Exp Med Biol. 2017;977:409-415.

[2] Shen Y, Lim CJ, Lee SY, Ryu PD. Acute Anemia Induces Erythropoiesis in Rat Organ Surface Primo-Vascular Tissue. Adv Exp Med Biol. 2020;1232:385-392.

[3] Shen Y, Park JB, Lee SY, Han SK, Ryu PD. Exercise training normalizes elevated firing rate of hypothalamic presympathetic neurons in heart failure rats. Am J Physiol Regul Integr Comp Physiol. 2019;316(2):R110-R120.

[4] Ogay V et al. Catecholamine-producing novel endocrine organ: Bonghan System. Med Acupunt 2008;20(2):97-102.

PRIMO-VASCULAR SYSTEM: FROM SCIENTIFIC RESEARCH TO THERAPEUTIC APPLICATION

Paul Roberts, B.Sc.O

Osteopathic Therapist, Somatic Educator SOSA Osteopathy & Somatic Therapy Center, Hong Kong

Corresponding author e-mail address: paulroberts01@gmail.com

Abstract: Scientific research has illuminated the primo-vascular system, prompting new considerations in our current understanding of the body. With so much research coming to the forefront, this now tangible system is properly approachable by those in the touch-based field of manual therapy. As the primo-vascular system enters the manual therapist’s field of awareness, a resonance is formed, and thus interaction becomes available. This presentation will discuss how the PVS may be approached from the perspective of manual therapy. How does one locate and palpate the PVS? How is it differentiated via touch from other biological systems? How then is it assessed? And how can we influence this system and its components via touch to affect therapeutic change?

In terms of clinical reasoning and application, what does the structure, the location, and the interrelations of the PVS with other anatomical systems suggest to us about potential therapeutic interaction? As the therapist approaches working with the components of this novel system, local, regional, and global treatment possibilities may all be considered. However, when beginning to explore the primo-vascular system, challenges inevitably arise when attempting to compare the existing meridian model and the theories surrounding it. Can a manual therapeutic approach for the PVS be developed and integrated clinically with existing manual practices?

An update on my journey investigating the primo vascular system: From a research stay in South Korea to own research in rats and on human placentas

Felix Scholkmann

Biomedical Optics Research Laboratory, Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

Corresponding author e-mail address: Felix.Scholkmann@usz.ch

Abstract: In my talk, I will summarise my work investigating the primo vascular system (PVS). My research in this area started in 2018 with a one-month visit to the laboratory of Prof. Pan-Dong Ryu in South Korea where I learned to identify, extract and analyse the PVS in rats. Once back in Switzerland, I continued my own research, extracting PVS samples from rabbits and identifying and analysing the PVS in human placentas. My talk will conclude with an outlook of my research plans relating to the PVS for the next couple of years.

Acupuncture reduces cocaine psychomotor responses by activating the rostromedial tegmental nucleus

Suchan Chang¹, Yu Fan^1,6, Soo Min Lee¹, Yeonhee Ryu², Bong Hyo Lee¹, Sang Chan Kim³, Kyle B. Bills^4,5, Scott C. Steffensen⁵, Chae Ha Yang¹, and Hee Young Kim^1,*

¹Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea

²Korean Medicine Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea

³Medical Research Center, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Korea

⁴Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA

⁵Department of Psychology and Neuroscience, Brigham Young University, Provo, UT 84602, USA

⁶Department of Human Anatomy and Histoembryolgy, Nanjing University of Chinese Medicine, Nanjing 210023, China

*Corresponding author e-mail address: hykim@dhu.ac.kr

Abstract: The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has emerged as an integral player in both rewarding and nociceptive responses. While previous studies have demonstrated that acupuncture modulates DA transmission in the mesolimbic reward system originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) and can reduce drug self-administration, the central links between peripheral acupuncture signals and brain reward systems are not well-characterized. Thus, we hypothesized that acupuncture would elicit inhibitory signals from RMTg neurons to brain reward systems. Acupuncture reduced acute cocaine-induced locomotor activity and DA release in a point-specific manner, which was blocked by optogenetic silencing or chemical lesion of the RMTg. The acupuncture effect was mimicked by chemical activation of the RMTg. Acupuncture activated RMTg GABA neurons. In addition, the inhibitory effects of acupuncture on acute cocaine-induced locomotor activity were prevented by electrolytic lesions of the lateral habenula (LHb) or fasciculus retroflexus (FR), areas known to project to the RMTg. These findings suggest that acupuncture recruits the RMTg to reduce the psychomotor responses enhanced by acute cocaine.

Acknowledgements: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2018R1A5A2025272, 2019R1A2C1002555 and 2020R1C1C1006534) and the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (No. 9991006790, KMDF_PR_20200901_0117)

New Education Course opening with “Acupuncture, Acupressure and Exercise” at Auburn University

Min Su Kim^a,* and Vitaly Vodyanov^b

^aCollege of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea

^bDepartment of Anatomy, Physiology, and Pharmacology, Auburn University, USA

*Corresponding author e-mail address: minsukim@snu.ac.kr

Abstract: Acupuncture as an important part of traditional oriental medicine is increasingly practiced in the United States by physicians and veterinarians and is comparable in effectiveness to conventional treatments for many medical conditions. The anatomy and location of acupuncture meridian have not been identified so far. According to contemporary interpretation, traditional meridians are the superficial representation of a channel network, the nodes of which underlie the acupoints on the body's surface. The material (Qi) that flows through the channels is essential for health. As these discoveries and knowledge need to be shared with students and researchers, Auburn University will open a new educational course “Acupuncture, Acupressure, and Exercise”. This course shows anatomical structures underpinning the acupuncture meridian system. Physical activity including movement and exercise together with probiotics supports this system and promotes overall health and well-being.

Increased Slc6a4 expression associated with decreased dopaminergic neurons in MPTP induced parkinsonism mouse model

Sujung Yeo^a,b

^aCollege of Korean Medicine, Sangji University, Wonju, Republic of Korea

^bOmit Research Institute of Korean Medicine, Sangji Univeristy. Wonju, Republic of Korea

Corresponding author e-mail address: pinkteeth@naver.com

Abstract: Parkinson's disease is a neurodegenerative disease caused by a decrease in dopaminergic neurons in the subtantia nigra. Abnormal expression of Solute Carrier Family 6 Member 4 (Slc6a4) has been reported in patients with Parkinson's disease. In this study, we used MPTP to examine changes in the expression of Slc6a4 in the brain of mice with Parkinson's disease and investigate its effect on dopaminergic neuronal cell death. As a result of examining the expression of Slc6a4 in the subtantia nigra of MPTP-treated mice for 4 weeks, it was observed that the gene expression was increased compared to the normal group. To investigate the relationship between Slc6a4 and dopaminergic neurons, we performed the experience using siRNA of Slc6a4.in the dopaminergic neuronal cell line SH-SY5Y. Gene expression using siRNA of Slc6a4 showed that the expression of tyrosine hydroxylase (TH) was increased when Slc6a4 was decreased. It was confirmed that it has an effect on dopaminergic neurons, and as a result of examining factors related to apoptosis in particular, it was confirmed that the value of bax/bcl2 decreased and affected. These results suggest that decreased Slc6a4 expression induces an increase in TH expression, providing a mechanism of action for dopaminergic neurons regulated by Slc6a4 expression. In conclusion, Slc6a4 is thought to be involved in the regulation of dopaminergic neurons, suggesting that increased Slc6a4 expression damaged by MPTP may affect the reduction of dopaminergic neurons.

Genes Expression of Agtr-1 and Agtr-2 in Primo Vessels inside Lymph Vessels of the Rabbit

Sang-Heon Choi, Boram Lee, Yukyoung Choi, Hyunsook Lee, and Sang-Suk Lee*

Department of Oriental Biomedical Engineering, Sangji Univeristy. Wonju, Korea

*Corresponding author e-mail address: sslee@sangji.ac.kr

Abstract: The genes expression of Agtr-1 and Agtr-2 for the isolated primo vessels (PVs) and composite lymphatic vessels (LVs) containing PVs (LVs+PVs) was investigated by RNA-sequencing (Seq) and quantitative polymerase chain reaction (qRT-PCR) analysis. RNA-Seq on the passed 10 samples on RNA-QC for two experimental groups with PVs and PVs+LVs proceeded to the library construction stage automatically and analyzed differentially expressed genes (DEGs). From the real-time qRT-PCR analysis data, we found the marker genes of Agtr-1 and Agtr-2 genes were some enriched in an isolated PVs compared to LVs, respectively. Based on mRNA transcriptional data, Agtr-1 and Agtr-2 were large increased in PVs and LVs+PVs under lipopolysaccharide (LPS) treatment and by acupuncture electric stimulation (AES), respectively. Agtr-1 and Agtr-2 are involved in contracting blood vessels to induce hypertension, to inhibit the absorption of water, and to discharge them out of the body. These genes have recently been shown to be associated with the LV; however, no data in PV existed. Both genes showed a slightly higher expression in primo without significance, showing no specificity for PV. So far, investigated genes were displayed in LV as well as PV. This finding indicates that high levels of the gene expression of Agtr-1 and Agtr-2 in LV and PV by acupoint stimulation with statistical significance may be involved in the function of PVs and that pathophysiological and physiological condition could progress into inflamed lymphatic endothelial cells expanding the PV within the LV.

In addition to, we investigated the morphological change of primo vessel according to the injection into lymphatic node of anti-CD3 monoclone antibody for the conjugation of T-cell.

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Effects

SU-IL IN

DGIST/Department of Energy Science & Engineering, DGIST, South Korea

Corresponding author e-mail address: insuil@dgist.ac.kr

Abstract: Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. We investigate molecular changes in colorectal cancer (CRC) rats by acupuncture treatment using the nanoporous needles. Treatment at acupoint HT7 is found most effective at reducing average tumor size, β-catenin expression levels, and the number of aberrant crypt foci in the colon endothelium. Surface modification of acupuncture needles further enhances the therapeutic effects of acupuncture treatment in CRC rats.

References:

Su-il In*, Young S. Gwak, Hye Rim Kim, Abdul Razzaq, Kyeong-Seok Lee, Hee Young Kim, SuChan Chang, Bong Hyo Lee, Craig A. Grimes, and Chae Ha Yang*, "Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties", Scientific Reports 6, 34061 (2016)

Bo Ram Lee, Hye-Rim Kim, Eun-Sook Choi, Jung-Hoon Cho, Nam-Jun Kim, Jung-Hee Kim, Kyeong-Min Lee, Abdul Razzaq, Hansaem Choi, Yunju Hwang, Craig A. Grimes, Bong-Hyo Lee*, Eunjoo Kim*, and Su-il In*, "Enhanced Therapeutic Treatment of Colorectal Cancer Using Surface-Modified Nanoporous Acupuncture Needles", Scientific Reports 7 12900 (2017)

Characterization of Monoclonal Antibody to Primo Vascular System of Rat and Ultrastructure of Primo Vascular System by X-ray tomography

Linlin Zhang^a,b and Sang Wook Oh^c,*

^aDepartment of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China

^bAdvanced Materials Institute of TCM External Therapy, Shandong University of Traditional Chinese Medicine, Jinan, China

^cDepartment of Biology Education, Institute of Fusion Science, Jeonbuk National University, Jeonju, South Korea

*Corresponding author e-mail address: sangwoh@jeonbuk.ac.kr

Abstract: MAbs against PVS of rats were generated by a classical traditional method, and their specificities were characterized in ELISA, Western blotting (WB), and immunofluorescence microscopy (IF). α-rPVS-m1-1~1-4 and α-rPVS-m4-1~4-28 had strong binding affinities to PVS in both ELISA and WB but did not show specificities at all in IF. On the contrary, α-rPVS-m3-2 and α-rPVS-m3-4 almost did not respond in WB but had strong binding affinities in ELISA and specificities in IF. Two mAbs stained predominantly at the extracellular matrix and cell membrane of PVS of rat in IF. Thus, α-rPVS-m3-2 and α-rPVS-m3-4 can be used as a tool in discriminating PVS from the blood vessel (BV) and lymphatic vessel (LV) and other similar tissues of rat in IF.

The ultrastructural properties of PVS in rat were examined with the synchrotron X-ray computed tomography (CT). It was utilized for high resolution images, which was constructed at the 7C X-ray Nano Imaging (XNI) beamline of Pohang Light Source-II (PLS-II) in Pohang.

The CT images demonstrated that a single primo vessel (PV) on the organ surface consisted of multiple sub-ducts and the outer surface of PV had randomly localized holes, as expected from data of SEM and other cases. The sub-ducts structure was also detected in the primo node (PN) of organ surface. The CT was visualized that the sub-ducts had very rough outer surfaces and the two or three sub-ducts were connected together as they ran along, and one sub-duct was branched to two subducts. And it also showed that the prepared LV had only one PV inside it. The synchrotron X-ray CT was useful for understanding the morphological structures of the intact PVS tissues.

Effects of acupuncture and herbal medication on changes in metabolites of colitis

Myeong Hun Kim, Yu Mi Lee, and Chang Su Na*

Department of Acupoint and Meridian, Korean Medical College, Dongshin University, Naju 520-714, Republic of Korea

*Corresponding author e-mail address: csna@dsu.ac.kr

Abstract: This study verified the efficacy of a combination treatment with acupuncture for inflammatory bowel diseases through investigating changes in immune-mediated factors and metabolites. Jakyakgamcho-tang and acupuncture treatment (CV12.ST25.CV4) were administered for inflammatory bowel diseases induced through dextrane sulfate.

In the case of TNF-α and IL-23, evoked in active macrophages, Jakyakgamcho-tang (JGT), acupuncture (Acu), and JGT+Acu groups all showed significant reductions compared with controls. And the case of IFN-γ emission in Th1 cytokine active factor manifestations, the JGT and JGT+Acu groups, showed a significant decrease compared with the control group. Also the case of IL-5 and IL-13, in the Th2 cytokine active factor manifestations, significant reductions in the JGT, Acu, and JGT+Acu groups, among which the largest reduction rates were for the JGT+Acu group.

The JGT+Acu group showed a more normal level compared with the 5-ASA group, JGT group, and Acu group for changes in colorectal tissue H&E and weight and DAI score. In addition, a total of 20 metabolites were found to contribute to the differences between the counties. Results from three JGT groups, 10 Acu groups, and seven Acu groups suggested that acupuncture may have a direct effect on metabolic control.

These results indicate that the simultaneous treatment of Jakeyakgamcho-tang administration and acupuncture procedures provides better control of the inflammatory expression of inflammatory bowel diseases than acupuncture or a single treatment, and it was confirmed that this effect is correlated with the immune-mediated inflammatory pathways of Th1 and Th2.

With regard to metabolic changes, more metabolites were expressed in the Acu group and JGT+Acu group, which suggests that acupuncture can have a direct effect on metabolic control; therefore, it is believed that microbial control in the intestines can be achieved by acupuncture stimulation as well as by taking medicine.

A Method for the Observation of the Primo Vascular System in the Thoracic Duct of a Rat

Sungha Kim^1,*, Sharon Jiyoon Jung^2,3, Sang Yeon Cho², Yoon Kyu Song³, Kwang-Sup Soh², and Sungchul Kim⁴

¹Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Korea

²Nano Primo Research Center, Advanced Institute of Convergence Technology, Seoul National University, Suwon, Korea

³Graduate School of Convergence Science Technology, Seoul National University, Suwon, Korea

⁴Department of Acupuncture & Moxibustion, Wonkwang University, Gwangju Medical Hospital, Gwangju, Korea

*Corresponding author e-mail address: bozzol@kiom.re.kr

Abstract: Even though the primo vascular system (PVS) has been observed in large caliber lymph vessels by several independent teams, the presence of the PVS in the thoracic duct has been reported by only one team, probably because reproducing the experiment is technically difficult. This brief report presents a new, relatively straightforward method, which is a simple modification of the previous method of dye injection into the lumbar node, to observe the PVS in a thoracic duct of a rat by injecting Alcian blue into the renal node. When this new method was applied to a rat, the branching of the primo vessel in the thoracic duct was clearly displayed. Thus, this new method is expected to extend the network of the PVS from abdominal lymph ducts to thoracic ones.

Study of Gene Expression and Acupuncture Needle Movement of Skin Primo Nodes During Acupuncture in Rats

Tingting Wang and Sungchul Kim*

Professional Graduate School, Wonkwang University, Republic of Korea

*Corresponding author e-mail address: kscndl@hanmail.net

Abstract: Primo Vascular System (PVS) was proposed by Dr. Bong-Han Kim, who believes that PVS is related to acupuncture and meridian in both anatomy and physiology. Recently, Professor Sungchul Kim’s team discovered skin primo nodes, and antibody studies are under way to prove skin primo nodes are the external manifestation of PVS on the skin. The purpose of this first study is to explore the difference between acupunctured skin primo nodes and non-acupunctured skin primo nodes through RNA-Sequencing. The purpose of the second study is observing the movement of acupuncture needles to determine if there is an electrophysiological relationship with skin primo nodes.

The RNA-seq was performed on the skin primo nodes after 30 minutes of acupuncture and skin primo nodes without acupuncture. As a result, there are 29 significantly differently expressed genes with 4 up-regulation and 25 down-regulation. After Gene Ontology enrichment analysis, the functional enrichment of differentially expressed genes is mainly manifested in calcium ion transport, cell difference, cellular processes and muscle processes. In pathway, it is mainly reflected in Axon guidance pathway and Neurotrophin signaling pathway.

The movement of needle tip on skin primo nodes and non-skin primo nodes was also analyzed by using video tracking technique. The results showed that the displacement deviations of the needle tips were statistically significant difference (p<0.05) in the skin primo nodes and non-skin primo nodes. The skin primo nodes showed a regular range of movement rather than the non-skin primo nodes.

In conclusion, since calcium ionization and muscle regeneration genes of skin primo nodes appear after acupuncture, acupuncture is believed to have a great effect on neurotransmission and tissue regeneration when acting on skin primo nodes. It can be inferred that skin primo nodes are acupoints, but the evidence is still insufficient, requiring various functional studies in the future.

Implementation of Smart Electronic Acupuncture Systems and Herbal Recommendation Systems

You Sik Hong^a,*, So Jung Kim^b, and Sang-Suk Lee^c

^aDepartment of Information Communication Software Engineering, Sangji University, Korea

^bDepartment of Master of Business Administration, Chichester University, England

^cDepartment of Oriental Bio Medical Engineering, Sangji University, Korea

*Corresponding author e-mail address: h5674korea@gmail.com

Abstract: Western medicine has contributed a lot to treating many diseases early and extending their life expectancy to 80 years, but it is still an unfortunate reality that various cancer diseases, Parkinson's, dementia, diabetes, and heart disease still have no exact cause and treatment. In the human body, there is a channel that circulates energy with blood vessels, called meridian.

A total of 12 meridians connect the inside and outside of the body, so if a patient develops a disease, a reaction point appears on the surface of the body and stimulates this reaction point to treat the problem. In other words, oriental medicine research systems say that when treated with saliva or moxibustion, we deliver strong energy impulses to the site of the transurethra located in the patient's body. Therefore, it is known that there are approximately 365 meridians in the body as an important reaction site of the skin or muscle, and the channel through which the blood donation circulates is called meridians.

In oriental medicine, a person has 12 meridians and 365 meridians, and if the meridians are well controlled, they can treat patients with chronic diseases. In humans, when a tissue is damaged, the tissue site is more electrical resistance than the surrounding tissue. This is because the level of electrical resistance in the wound is high, and the current is not flowing well. Therefore, the wound has the characteristic of having less current flow and less absolute current flow in the cell. In this paper, to treat chronic diseases, we conducted a computer simulation to restore the patient's health condition by stimulating electronic acupuncture to meridians and meridians. Furthermore, we propose an algorithm to recommend a patient's custom herb based on the ideological constitution.

Hope for Rare Incurable Diseases: A Scientific Approach to Treatment of Amyotrophic Lateral Sclerosis (ALS) Using Primo Vascular Systems

Sungchul Kim

Director of ALS center Center of Amyotrophic lateral Sclerosis, Wonkwang University Hospital 543-8, Juweol1-Dong, Nam-Gu, Gwangju, South Korea

*Corresponding author e-mail address: kscndl@hanmail.net

Abstract: Among the rare incurable diseases, Lou Gehrig's disease, one of the most aggressive and destructive degenerative brain diseases in the world, will be presented focusing on scientific and grounded treatments for Korean traditional medicine(herbal medicine-Mecasin, KCHO-1, Gamijackyakgamchotang, Saam Acupuncture) and immune and regeneraion Pharmacopuncture using the Primo Vascular System.

In Traditional Korean Medicine (TKM), Saam Acupuncture is used to improve internal organ function and immune-regeneration pharmacopuncture using PVS is a new treatment method (Kim's PVS Method) that can utilize the effects of acupuncture and pharmacological effects at the same time by injecting various herbal extracts on specific acupoints.