The Blue Vanguard Vol.22

Yonsei Student Pharmacist

BLUE VANGUARD

THE

JANUARY JANUARY01 012023 2022 VOL.22 Vol.22

MAIN ARTICLES MAIN ARTICLES Feature Interviews

Antimicrobial Copper - From Ancient Plates to Wearable hNanomes Antimicrobial CopperFrom Ancient Plates to Wearable Nanomesh

Pharmaceuticals Pharmaceuticals

Metabolic Anticancer Drug - Starving Cancer Metabolic anticancer drug – starving cancer cells Cells Immunosuppressant Free forfor Organ Transplant Patients Immunosuppressant FreeFutures Futures Organ Transplant Patients

Issues Issues

Parkinson's DiseaseMedications MedicationsWhat is Parkinson's Disease?

Parkinson’s Disease - What is Parkinson’s Disease?

Liquid biopsy future of cancer treatment Liquid Biopsy– -the The Future of Cancer Treatment

Column Column

Next Generation generation new drug development platform Next New Drug Development Platform Digital Biomarkers, Tools in Healthcare and Drug Digital Biomarkers,Promising Promising Tools in Healthcare andDevelopment Drug Development

Campus Life Campus Life

AKARAKA and Daedongjae BackBack to ourto School Life in Three Years AKARAKA and Daedongjae our School Life in Three Years

Editor's note Jimin Seo

Hello readers!

It is my utmost pleasure to introduce the 22th edition of the Blue Vanguard, in which we cover various topics ranging from space medicine to emerging novel drugs to long-awaited campus festivals held, at last, in person. We always hope that the Blue Vanguard will be able to provide valuable knowledge and insight into the ever-morphing industry of pharmaceuticals and healthcare.

One of the more prevalent and obvious of such trends is the melding of technology with medicine and patient care. As we transition into the era of digital healthcare, this is Blue Vanguard’ s at tempt to e xplore the various technological applications - including but not limited to nanomedicine, smart devices, drug development platforms - as well as related issues, concerns, and implications through a series of thoroughlyresearched, meticulously-written articles.

Special thanks to professor Jong Hyeok Sung and the International Copper Association for their support - which we hope to reciprocate by aiding their cause to spread awareness on antimicrobial copper and shed light on its potential.

Two of the core responsibilities of a pharmacist, as outlined by the WHO, are being a communicator and a life-long learner. I have no doubt that our Blue Vanguardians have already proved themselves more than competent to excel in such aspects, given their desire to explore the latest pharmaceutical research and willingness to share their acquired knowledge with subscribers.

It has been a delight working with everyone.

With that said, I hope you enjoy our 22nd issue. B

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contents 1) Feature

•Antimicrobial Copper - From Ancient Plates to Wearable Nanomesh

2) Pharmaceuticals

•Natural Steroid : Glycyrrhizin Acid •Nanomedicine •Anorexiant •Metabolic Anticancer Drug – Starving Cancer Cells •Immunosuppressant Free Futures for Organ Transplant Patients

3) Issues •Parkinson’s Disease Medications - What is Parkinson’s Disease?

•Monkeypox •Space Medicine •Liquid Biopsy – The Future of Cancer Treatment

4) Column

• Next Generation New Drug Development Platform •Smart Watch: Wearing Healthcare on Your Wrist •Bioinformatics •Digital Biomarkers, Promising Tools in Healthcare and Drug Development

5) Campus Life • AKARAKA and Daedongjae Back to our School Life in Three Years 2022 VOL.22

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FEATURE

Antimicrobial Copper

From Ancient Plates to Wearable Nanomesh Jimin Seo

jmdemi@hanmail.net

E

ven before humanity had a grasp of microbial knowledge, copper was an element that was used as early as ancient Egyptian times as plates and sterilizers for its antimicrobial properties Recently its effectiveness in combating antimicrobial resistance - a big threat to modern medicine - have been highlighted and studied for various applications Antimicrobial resistance AMR arises when bacteria develop resistance to antibiotics via adaptation and evolution, rendering them useless when it comes to preventing infections As this is applied from mild conditions to critical situations such as organ transplant proceudres and chemotherapy, AMR clearly has serious consequences And it’s only getting harder and harder for the antibiotics pipeline to catch up with the speed at which resistant bacteria are emerging ne prominent reservoir of bacteria are touch surfaces Hospitals are particularly prone to sporadic cases and outbreaks of healthcare-associated infections HA s , which often originate from contaminated surfaces with bacterial pathogens and are assosciated with significant morbidity and mortality The problem is that high touch surfaces don’t only facilitate transmission of bacteria from person to person - it also is the perfect environment for genetic material to be transferred between bacterial species in a process called horizontal gene transfer This signifies that once one strain of bacteria develops resistance, it can be passed to many others to create new resistant strains f course, deep cleaning of environments like airports and hospitals can effectively reduce microbial populations, hence infection But practically there’s a limit to how much cleaning can be done, which calls for the employment of an effective, durable antimicrobial material - copper

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Antimicrobial Copper Copper surfaces readily kill bacteria, yeast, and viruses, via a process coined “contact killing”. Its potential use in health care settings have given copper renewed attention. Copper’s killing of microorganisms is observed to take place at a rate of 7~8 logs per hour, and the microorganisms rarely recover after periods of prolonged incubation. The antimicrobial activity of copper and its alloys is well established, and copper is registered in the U.S. Environmental Protection Agency evaluated for use on touch surfaces such as door handles, infections. microbial death is controversial, its relative contribution method is the physical interaction of copper nanoparticles (CuNP) with the cell, virus or plasma membrane, leaving copper ions and ultimately leading to its destruction.

This mechanism is favored by smaller NPs (1~10nm), as

been suggested that the release of copper ions, Cu+ and Cu2+, can damage the cell membrane and induce an The conclusion is that copper’s microbial killing is a combination of aforementioned mechanisms, the relative importance of each dependent on the microorganism.

FEATURE

Application 1 - Copper Films

Application 2 - Copper Nanomesh

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PHARMACEUTICALS

NATURAL STEROID

: GLYCYRRHIZIC ACID Seoyoung Kim

katherina623@naver.com

What is Glycyrrhizic Acid?

Glycyrrhizinor20-carboxy-1-oxo-30-norolean-12-en-32-yl--O-2 2-d-glucopyranurosyl-K-d-glucopyranosidu ronic acid is a triterpenoid glycoside (saponin) with glycyrrhetinic acid. The major constituents are glycyrrhetinic acid,flavonoids,hydroxylcoumarins,andb-sitosterol.

Use of Glycyrrhizic Acid

As a therapeutic agent, the glycyrrhizic acid as been used in a vast variety of formulations as it is reported to be anti-inflammatory, anti-ulcer, anti-allergic, antioxidant, anti-tumor, anti-diabetic and h it can stimulate endogenous production of interferons. Due to these properties, it has been used in the treatment of premenstrual syndrome, treatment of viral infections, anti-lipidemic and antihyperglycemic. It is also known to be used as a remedy for peptic ulcers, and other stomach diseases.

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Mechanism of Action Glycyrrhizic acid exists as alpha and beta forms. The alpha form is predominant in the liver and duodenum.

Thus, it is thought that the alpha form is responsible for the anti-inflammatory liver euect of this drug. Its anti-inflammatoryeuectisgeneratedviathesuppression of TNF alpha and caspase 3. It also inhibits the translocation of NF-kB into the nuclei and conjugates free radicals. Some studies have shown a glycyrrhizicdriven inhibition of CD4+ T cell proliferation via JNK, ERK, and PI3K/AKT. Glycyrrhizic acid also has antiviral activity, which includes the inhibition of viral replication and immune regulation. The antiviral activity of glycyrrhizic acid has a broad spectrum that covers several diuerent viral types such as vaccinia virus, herpes simplex virus, Newcastle disease virus, and vesicular stomatitis virus.

The euect of glycyrrhizic acid on metabolism is Adverse Effect thought to be related with its inhibitory activity towards Themostwidelyreportedsideeuectofglycyrrhiz 1-beta-hydroxysteroid dehydrogenase type 1 which is the reduction of blood potassium levels. This can in turn decreases the activity of hexose-6-phosphate auect body fluid balance and the function of nerve dehydrogenase. On the other hand, some studies have Chronic consumption of black licorice seems to shown the potential of inducing lipoprotein lipase in increase blood pressure, cause irregular heart rhythm, non-hepatic tissues to improve dyslipidemic conditions. and may have adverse interactions with prescription The glycyrrhizic acid also targets many other proteins in drugs. In extreme cases, death can occur as a result of human. It is an antagonist of tumor necrosis factor and excess consumption caspase-and 3, atranslocationinhibitorofnuclear factor of glycyrrhizin acid.

Glycyrrhizicacidgeneratesaninhibitorof1-bet NF-kappa-B. hydroxysteroid dehydrogenase in the kidney which will When orally administered, glycyrrhizic acid is increase the cortisol levels in the kidney. Moreover, the almost completely hydrolyzed by intestinal bacteria intravenous use of the ammoniated form was shown for the formation of glycyrrhetinic acid, which is an to produce convulsions and hemolysis. Preclinical active metabolite and can enter systemic circulation, and overdose studies have shown that glycyrrhizic acid two molecules of glucuronic acid. This metabolite is may produce excess mineralocorticoids in the body. transported and taken to the liver for its metabolization However, glycyrrhizic acid has been proven not to have to form glucuronide and sulfate conjugates. mutagenic, genotoxic, teratogenic, or carcinogenic euects.

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NANOMEDICINE Dah Eun Kim

kcherry429@yonsei.ac.kr

WhatisNanomedicine?

The greek word “nanos” means a dwarf, so the term nanotechnology translates to “technology to do with small things”.

In science, nano also means a billionth. Hence, nanotechnology is science, engineering and technology conducted at the nanoscale.

What if you could swallow a drug that could perform surgery on a DNA or cell-by-cell basis? What if you put a drug in a nano-scale spherical shape and take it easily, and the ingested drug is systematically delivered to the target site in the body? These drugs are nothing new. In 194, a drug called Docso was approved, which is a lipids OMAformulat of a drug called doxorubicin. A lipids OMA formulation is a form of fat particle which can play a role in catching and delivering drugs. As a new version of this, nanomolecule were developed by researchers at MIT and collaborators in the fieldoftherapy.Whenadministered,nanomoleculescangoaroundthebodyandcirculateunderthe system,findingdiseasedtissuesandgettingintotheircells.Andoncetheyarein,theyrelease inside. It is like a search-and-destroy system, which has the advantage of minimizing the side eu targeting diseases aimed at elimination.

TargetingMechanismsofNanomedicine

Nanomedicinereachesthetargetsiteintwomainways.Thefirstispassivetargeting.Aphenomen targetsubstancesarenotlabeledselectively,butarelabeledasdiuerencesinthebiologi the target tissue is usually referred to as “manual targeting”. In general, vascular tissues are formed somewhat loosely near cancer tissues that grow rapidly, and drug support may be greater than general blood vessels. At this time, nanomedicine, which circulates in the body and accumulates near cancer tissues, or penetrates through lymphatic vessels that are not properly connected due to fast growth rate, may not escape again and accumulate near cancer tissues. The phenomenon in which such a material of some size stays near cancer tissue for a long time is called the “Enhanced Permeability and Retention (EPR) euect”, and nanoparticles of less than 20 nanometers are known to be the most accumulation euect is not only explained by size, but the degree of passive targeting can be cont as the interaction between nanomedicine and tissues or molecules in vivo, half-life of blood circulation, extravation, permeation to lesion tissue, et cetera.

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Amethod of introducing a ligand which binds specifically to the target membrane of a disease c surface of nanomedicine is called “active targeting”. One of the advantages of nanomedicine over existing drugs is that it can maintain the properties of drugs while controlling surface chemistry. Breast cancer treatments Herceptin, folate, epidermal growth factor, transferrin, and galactose are used as target-oriented substance However,whennanomedicineisexposedtotheinvivoenvironment,itcanbenon-specificallyatta theparticleforminga‘corona’.Thisisaphenomenoninwhichsomeoftheproteinsinplasmaarenons on the surface of nanomedicine, which induces the phagocytosis of nanomedicine into phagocytes. Best examples of these adsorbed proteins include opsonin and immunoglobulin. This action can significantly a size, colloidal stability, surface charge, intracellular granularity, circulation period in vivo, and toxicity of nanomedicine.

Eventually, even if a marker is bio-bonded to nanomedicine for active labeling, its evcacy in vivo the corona euect.At the same time, it has also been reported that hypersensitivity reaction patientsduetothiscoronaeuect.Therefore,nanomedicine’stargetinghasbeenprogressedst in general and is inching its way towards active targeting.

Nanomedicine’sResearchDirectionandChallengesintheFuture

In order to actually apply nanomedicine to clinical treatment and diagnostic medical use, it is essential to develop an evcient and reproducible method of synthesizing nanomedicine. Most synthesis methods for f are problematic in that the polydispersity of nanomedicine (which refers to nonuniformity among nanoparticles, mostly size, shape, and surface properties) is very large. The synthesis technology of nanoparticles usin substrates is in the spotlight as it is suitable for the synthesis of nanoparticles with narrow size distribution and high reproducibility.

In addition, it is essential to implement a mass production method for nanomedicine, which is about to be commercialized duetoitsprovenevcacyinpatients.Simpleliposomeorpolymer-basednanomedicineisrelativel produce. However, nanomedicine that must be synthesized through bioconjugation of labeling factors or synthesize itself throughmulti-stagereactionsisstilldivculttomass-producesincetheyield B ofeachstepis

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ANOREXIANT Jiwon Son

sonjw119@naver.com

A

reyoufindingyourselfbecomingfatterandchubbierrecently?Ifso,whatwouldyoudotoloseweight and regain your past self? There are indeed people who would attempt to achieve healthy weight loss by implementing healthy eating patterns and exercising regularly. But some of them would go for medications. There are diCerent types of weight-loss medication such as carbohydrate blockers, lipolysis inhibitors,awwwwndmetabolismboosters,butthemostpopulartreatmentsareundoubtedlyanorexiants.More and more people in Korea are looking for anorexiants, appetite suppressants, and prescriptions are increasin yearbyyear.Whatisitexactlyandhowdoesitwork?Isitsafe?Let’sfindout.

Hunger and Appetite

Whydowegethungryinthefirstplace?Everythingstartsfromthebrain.Thebraincontrolsou behavior, thoughts, and even hunger. Since the brain is hardwired to maintain energy homeostasis, it sends signals to our gastrointestinal tract to stimulate the appetite when our body gets low on energy. There are 2 ways for our complex body system to measure the amount of energy in our body.

Thefirstwayisbysimplyrecognizingtheexistenceoffoodinthedigestivesystem.Whenourstoma so-called “hunger hormones” such as ghrelin are secreted in the stomach and stimulate food intake. When the stomach isfull,GLP-1andcholecystokinin,whichareappetite-suppressinghormones,arereleasedintoth The second way is by identifying the amount of energy reserves in our body. Leptin, which acts on the appetiteregulating center of the brain and suppresses appetite, is secreted from the fat cells, and the amount of leptin secreted is proportional to that of the adipose tissue. To sum up, Ghrelin, GLP-l, cholecystokinin, and leptin are all hormones that act on the appetite control center in the hypothalamus that either stimulate or suppress hunger.

Types of Anorexiant

What are anorexiants, exactly? Anorexiants are drugs that suppress appetite by stimulating hypothalamic and limbic regions, which are known to control satiety. Taking anorexiants results in lower food consumption and ultimately weight loss.

Typesofanorexiantscanbeclassifiedintotwogroups.Oneisthepsychotrpicanorexiant,andth psychotropic anorexiant. Typical examples of each drug group are listed below.

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The term “psychotropic” is added to anorexiants like phentermine and phendimetrazine because they act on the central nervous system(CNS) and can do serious harm to our human body when misused or abused.

Psychotropic anorexiant exhibits pharmacological action by increasing the secretion of neurotransmitters such as epinephrine, norepinephrine, or dopamine in the appetite control center in the hypothalamus.

Phentermine, phendimetrazine, diethylpropion, and mazindol act on our brain by regulating the adrenaline receptors; eachdrugincreasestheactivityofthe2-adrenergicreceptor,K-adrenergicreceptor,andK1-adrenerg On the other hand, mazindol suppresses appetite by increasing the concentration of catecholamine neurotransmitters in the synapses by blocking catecholamine reabsorption.

Non-psychotropic anorexiant is considered a safer medication choice. The combination of bupropion and naltrexone inhibits dopamine and noradrenaline reabsorption and activates the appetite-suppressing center, pro-opiomelanocortin (POMC), in the hypothalamus. Naltrexone, an opioid antagonist, is usually added to block the self-suppression of POMCassociatedwithopioidreceptors,ultimatelystrengtheningtheappetite-suppressinge Liraglutide is an anorexiant that was previously approved and used as a treatment for diabetes, which is more known byitsproductnameSaxenda.Itistheworld’sfirstglucagon-likepeptide-1(GLP-analog 1) obesitytreatme itsmechanismofactionhasnotbeenidentifiedyet,GLP-is 1 assumedtoactontheGLP-receptor 1 intheh decreasinggastrointestinalmotilityandincreasingsatiety. SinceitslaunchinKoreain2018,it obesity treatment market for the past three years.

Safe Use Guideline for Psychotropic Anorexiants The Ministry of Food and Drug Safety designates and manages psychotropic drugs that may develop dependence or resistance, and has drawn up a safe use guideline for psychotropic anorexigenic drugs. The following covers the key points of the guideline.

1.

2.

<Safe Use Guideline> CNS-stimulating anorexigenic drugs should be used for obesity treatment purposes.

The possibility of abuse and dependence should always be kept in mind when using and prescribing CNS-stimulating anorexigenic drugs.

3.

“Phentermine, phendimetrazine, diethylpropion, and mazindol” must be prescribed for a short period, within four weeks

4.

5.

CNS-stimulating anorexigenic drugs should not be used in combination with other CNS-stimulating anorexigenic drugs.

of the permitted dose, and should be used within a maximum of three months.

Children and adolescents should not be using CNS-stimulating anorexigenic drugs should.

Prescription Status of Anorexiants and Related Policies

Prescription of psychotropic anorexiants should be controlled with extra care because they can cause some serious issues when abused. To prevent drug abuse and dependence, the Ministry of Food and Drug Safety has implementedthe‘voluntaryreportingsystem’andthe‘pre-notificationsystem’.

The pre-alarm system, first implemented in 20, analyzes data reported as an integrated drug system and informs doctors suspected of prescribing and administering drugs outside of safety standards. The voluntary reporting system is a system that requires doctors to report drugs in advance when they inevitably violate the safety standards.

Although the causal relationship has not been demonstrated, the total number of users has decreased slightly frommillion 1.3 tomillion 1.27 sincetheimplementationofthepre-alarmsystem.Furthermore,whilet of patients prescribed over three months and the number of patients prescribed by two or more medical institutions have not shown noticeable change, the ratio of the number of patients prescribed and the number of patients by combination period decreased to one-tenth.

The number of abuse cases has indeed decreased thanks to the implementation of the systems above; however, appetite suppressants are still indiscriminately prescribed, and this remains a task to be solved in the future. B 2022 VOL.22

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METABOLIC ANTICANCER DRUG

– Starving Cancer Cells Nam Kyu Oh

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An Effort to Conquer Cancer

dhskarb1997@gmail.com

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The Energy Metabolism of Cancer Cells

Cancer cells multiply rapidly and require more oxygen A variety of anticancer drugs have been developed and so far to conquer cancer. Although chemotherapyenergy (1st sources in the process. In order to overcome the environment that lacks oxygen and glucose, cancer generation), targeted therapy (2nd generation), and cells immunotherapy (3rd generation) for cancers have beenhave several metabolisms diuerent from n cells. In the presence of oxygen, normal cells produce developed, it remains a human task to completely conquer ATP through oxidative phosphorylation carried out in cancer due to their adverse drug euects (chemotherapy) , mitochondria. In contrast, cancer cells use glycolysis resistance (targeted therapy), and narrow coverage producing lactic acid as their main energy metabolism (immunotherapy). Recently, metabolic anticancer drugs, rather than energy-evcient oxidative phosphory the 4th generation anticancer drugs, are expected to solve even in an environment where oxygen is present. This these problems. The Metabolic anticancer drug induces characteristic of the cancer cell metabolism is called the energy deficiency in cancer cells by blocking metabolic Warburgeuect.Althoughthedetailedmechanismsoft pathways that nourish them. In other words, it is a drug metabolic anticancer drugs currently being developed that starves cancer cells to death. are all diuerent, they generally target a specific p of this ‘aerobic glycolysis’ in mitochondria.

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Various Mechanisms of Metabolic Anticancer Drugs

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R&D for metabolic anticancer drugs is also actively underway by some bio companies in Korea. Among them, here are some mechanisms of metabolic anticancer drugs being developed by several well-known companies.

1) Starvanip (NYH817100) Haim Bio, a domestic bio company, is developing a metabolic anticancer drug called Starvanip. Starvanip is a drug administered in combination with NYH817G (Aldehyde dehydrogenase inhibitor) and NYH100P (mitochondria complex 1 inhibitor). In some cancer cells, aldehyde dehydrogenase (ALDH) is overexpressed in mitochondria, which enables the new drug to inhibit the production of NADH produced by ALDH. Because NADH plays an important role in ATP production through the formation of hydrogen concentration gradient in the mitochondrial electron transport system, inhibition of ALDH specifically inhibits ATP production in cancer cells.

2) KAT-101 (3-Bromopyruvate) NewG Lab Pharma, another domestic bio company, is developing a metabolic anticancer drug called KAT-101 (3-Bromopyruvate). Cancer cells produce ATP through anaerobic metabolism even in an environment where oxygen is present, so lactic acid accumulates in the cells. Since it causes changes in pH of the cells, the monocarboxylate transporters (MCTs), the lactic acid channels, are opened to release lactic acid out of the cells. KAT is an analog of lactic acid, allowing it to enter the cell through this channel. In cells, KAT binds to mutated HK2 (overexpressed in cancer cells), lactate dehydrogenase (LDH), and ATPase, inhibiting ATP production of cancer cells.

3) Glutamine metabolism in mitochondria Cancer cells use glutamine as their main energy source. Glutamine works in mitochondria, but it had been unknown how glutamine is transported into the mitochondria of cancer cells. In 2020, a Yonsei University research team, led by professor Han Jeongmin, found a transporter that delivers glutamine to the mitochondria. This transporter is a gene variant produced by a gene SLC1A5, and it has been revealed that the gene expression is increased by a specific transcription factor (HIF-2 α) in a low-oxygen environment. Thanks to this study, the mitochondrial glutamine metabolism that appears specifically in cancer cells has been more clearly revealed. Furthermore, it is expected to be used as an important target of anticancer drug for glutamine-dependent cancer cells.

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Future of Anticancer Drugs

These new anticancer drugs being developed by Korean bio companies are currently undergoing clinical trials.

Starvanip(byHaimBio)hassuccessfullycompletedphase1clinicaltrialsatSeverancehospita applyforINDofphaseclinical 2 trials.KAT-(by 10 NewGLabPharma)hasbeenapprovedforINDofphaseand 1 2a clinical trials by both MFDS and FDA, starting clinical trials in earnest. As R&D of metabolic anticancer drugs are actively underway, it can be expected that first-in-class anticancer drugs will be develop it is too early to expect. The mechanism of metabolic anticancer drugs is very persuasive and attractive in theory, buttheactualhumanmetabolismismuchmorecomplexthanthelaboratorysettings. So,itisd the success of metabolic anticancer drugs until they are proven to be euective through the Nevertheless,wehopethatthesenewattemptstohelpmanypatientssuueringfromcancerwil closer to the dream of Conquest of cancer by mankind. B

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IMUUNOSUPPRESSANT FREE FUTURES FOR ORGAN TRANSPLANT PATIENTS Daeun Choi daeundownchoi@naver.com

Although organ transplantation can be challenging, it is frequently the best or the only treatment for end stage organ failure. Organ transplant surgery in Korea began on March 25, 169, in Seoul St. Mary’s hospital. At that time, Korea’s medical technology was very poor, since removing one’s organ and transplanting it to another patient was a historic challenge. In 1972, immunos were developed and produced in Switzerland.

These immunosuppressants drastically reduced organ transplant rejections in patients. With immunosuppressants and the development of medical technology, the number of organ transplant casess in Korea tripled from 1,370 per year in 201 to 16 4, in 2018. Amongst them, the number of liver transplants quadrupled from 364 in 20 to 1,482 in 2017.

Survivalratesafterorgantransplantshavealsoimprovedsignificantly.Inthecaseofli 5-yearsurvivalrateoflivercancerpatientshasincreasedfromin 30-4% theearly190stothesedays.

70-8% The10-yearsurvivalrateofkidneytransplantshasalsorisenfrom25%inthe1970sto92%sincethe201s.

However, after organ transplantation, patients must consume immunosuppressants for the rest of their lives.

Our immune system plays an important role in defending our body from external foreign substances. After organ transplantation, the transplanted organ is recognized as an external foreign substance and our immune system rejects it by attacking it. Thus, patients take immunosuppressants to prevent organ rejections and to ensure that the transplanted organ functions well.

Tooptimizepost-transplantationcare,acombinationoftwoorthreediuerentimmunosup ondiuerentmechanismsisbeingusedsimultaneously.Thiscanblockvariousimmuneprocess bestoppedbytheusageofonlyonedrug,reducesideeuects,andincreaseeuectivenessofthedr the dose of each drug. A combination of one of the calcineurin inhibitor drugs (cyclosporine, tacrolimus), mycophenolic acid, and steroids is widely used. However, the side euects of the immunosuppre quite severe. Side euects include vomiting, gastrointestinal disorders, and hair loss. Th the world are eager to develop new organ transplant technologies that do not require immunosuppressants.

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PHARMACEUTICALS

imm suppunoressa nt t n a l p s n a r t n orga atients p

In a new study, scientists created a long-term chimerism treatment protocol in kidne patients had pre-surgical treatment with chemotherapy and radiation to knock down their own immune systems. A day after the transplant surgery, they received infusions of a complex cellular cocktail derived from the donor’s bone marrow. The mixture included not only blood-forming stem cells, but also the rare “graft-facilitating” cells. These cells, first isolated nearly 20 years ago, are thought to he cells get established in recipient’s bone marrow. The researchers also removed donor immune cells that are likely to attack the transplant recipient’s own body. One month after the transpla hadavarietyofimmunecellsderivedfromthekidneydonorintheirbloodstream.Withinayea patients had achieved a long-lasting chimerism, with the donated immune cells eventually crowding out the recipient’s own immune cells. By then, these patients had stopped taking immunosuppressant drugs, and their transplanted organs continued to thrive. None of the patients showed signs of graft-versus-host disease.

In 2019, Professor Park Jae-beom and Professor Lee Kyo-won of Samsung Medical Center’s Organ Transplant Center also announced the results of kidney transplantation based on the previous chimerism protocol in 8 adult patients with chronic renal failure with mi tissue complexes from December 1 20 to December 2018. According to the research team, 5 out of 8 patients successfully stopped taking immunosuppressants, and 4 of them ha maintaining healthy transplanted kidneys without taking immunosuppressants for up to 55 months.

The results from these new protocols may have a major impact on the future of organ transplantation.

With the refinement of this treatment, recipients may eventually stop taking harsh imm medications, even after they had received mismatched organs. These preliminary findings m reduce the need for anti-rejection drugs and lead to more options for patients awaiting organ transplants. B

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ISSUES

PARKINSON’S DISEASE MEDICATIONS

What is Parkinson’s Disease?

HyunJin Lee

jennyhyunjinlee@gmail.com

What is Parkinson’s Disease?

Parkinson’s Disease(PD) is a long-term degenerative brain disorder that causes unintended or uncontrollable movements, such

asstiuness,shaking,anddivcultywithbalanceandcoordination.Itoccurswhencentralnervecellsare

nigra that secretes dopamine, and it worsens as you get older. Additionally, PD has a pathological charac accumulates abnormally in the nervous system, resulting in excessive protein aggregates. Moreover, Alzheimer’s and Parkinson’s

Disease can be thought of as the same disease since they both cause dementia, but each has diuerent c Alzheimer’s destroys nerve cells in the brain area, which are important for maintaining intellectual ability, while Parkinson’s Disease destroys the substantia nigra that are involved in the body’s sophisticated movement, reducing stride, or being speechless.

ThemainsymptomsofParkinson’sDiseasearetremorsatrest,bradykinesia/hypokinesia,rigidity,andpo addition, some symptoms are not related to motor function, such as urination disorders, constipation, and hypotension. There are also sensory abnormalities that cause pain in the waist, limbs, and neck muscles; and ‘mental dysfunction’ that slows down the speed of thinking and frequently accompanies depression and anxiety. Lastly, there are also symptoms related to the administration

oftherapeuticdrugsincludingabnormalmotility,motorfluctuation,cognitiveandbehavioraldisorder

Parkinson’s Disease Risk Factors and Causes There are only a few factors that have the epidemiological evidence and the biological plausibility to be considered risky

(pesticides,dairyproducts,2-adrenoreceptorantagonists)orprotective(smoking,caueineintake,physical

intake,non-steroidalanti-inflammatorydrugsand2-adrenoreceptorantagonists)factorsforPD.Possiblemo PD might depend on the uncertain biological and neuropathological reliability of clinical subtypes. However, advancing age, genetics, and environmental causes could be risk factors. It may be possible to target some of these factors for preventive interventions aimed at reducing the risk of developing and the rate of progression of PD.

There is no one definitive cause of PD, and is unknown yet, with both inherited and environmental facto role. Also, there is no clear understanding of the reason why the nerve cell of substantia nigra degeneration occurs, and there is no way to treat the underlying cause. The term “idiopathic” is used when the cause of this apparent outbreak is unknown, and most PD corresponds to idiopathic PD.

PathologicalsigninpatientswithPDistheagglutinationofK-synucleininLewybodiesfoundinbrainles atypical protein, which aggregates to form lysosomes, and builds up mainly in black cells in the brain stem. The agglomeration of

abnormalK-synucleinisassociatedwithPD,anditisnotyetclearwhatprocesstheaccumulationofagglomer

ofPD.However,manystudieshaveshownthatmutationandoverexpressionofK-synucleinareassociatedwith

aggregation across the brain is associated with various degenerative neurological diseases. K-synu

lysosomes when it becomes unnecessary, and mutations in K-synuclein proteins not only block the lysosom but also prevent the breakdown of other proteins that need to be removed. As a result, neurons die, leading to neurodegenerative diseases. The association between PD and genetic variation lies in the SNCA gene expressing K-synuclein,

overlap increases the amount of K-synuclein protein expressed in the body, resulting in PD. Additionally, a

publishedthatK-synucleinsecretedfromtheintestinalnervoussystemformsacohesivenucleusandist

PD. These studies lead to the conclusion of removing K-synuclein or disabling agglomerate activity as ways disorders, including PD.

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What are Treatments for Parkinson’s Disease?

Types of PD treatments currently in place are largely medication and surgical treatment. Medication includes standard therapy

with levodopa, a precursor of dopamine. This levodopa formulation has the disadvantage of disappearin symptoms during long-term treatment, so dopamine antagonists have been attracting attention as an early treatment of PD since the 2000s. In addition, there are anti-choline drugs and NDMA antagonists that balance dopamine by lowering the concentration of acetylcholine, such as MaoB inhibitors that suppress dopamine concentrations to maintain dopamine concentrations and Comt inhibitors that increase levodopa’s action. Surgical treatments include local surgery, deep brain stimulation, and gene therapy.

These treatments are currently focused on “symptom relief”, and there are no treatments that change the progress of the disease, or fundamental treatments yet. Therefore, research on the development of various treatments is being actively conducted to solve this problem, and it is essential to know some trends in the development of treatments for PD.

Trends and Future Development of Parkinson’s Disease

First,treatmentforPDbasedontheK-synucleinmechanismisbeingdeveloped.ThefunctionofK-synucleinisn

playsanimportantroleintheintercellularsignalingprocess.PDshowsanincreaseinflexibleK-synucleinan in substantia nigra in normal aging. Also, genetic defects, chromosomal mutations, and pathological conditions cause pathological

or disease conditions by increasing K-synuclein. Thus, a decrease in K-synuclein at the cellular level is

the development of a treatment for PD. In fact, the treatment of PD through the K-synuclein mechanism is be

directions:decreasing 1) theoverallnumberofK-synuclein,inhibiting 2) thevariationoragglomerationofK-syn

the formation of Lewy body, 3) eliminating intracellular K-synuclein, 4) eliminating extracellular K-synuclein

intercellularmetastasis.Bythere 20, areclinical 21 trialsofK-synucleinrelatedtoPDtreatment.However,t

isthedevelopmentofabiomarkerthatcanobjectivelymeasurethelevelofK-synucleinsincenobiomarke

analyzeK-synucleininthebeforeandafterevaluationofthetreatment.Iftheseobjectivemarkersared the future of PD treatment development.

Inadditiontothis,thereisaclinicaltrendof‘stemcelltreatment’forPD.Currently,thereareatota

toPDusingstemcells,andasofMarch25,0mostclinicalstudiesareinphase1and2,andphase3isbeingconductedin one case. Most researchers use mesenchymal stem cells that are relatively free from safety issues, but there is no commercialized

stemcelltreatmentforPD. Iftechnologicaladvancesinimprovinginvitro/invivodiuerentiationevcien cells, checking cell function accurately, improving cell survival after transplantation, and ensuring the safety of transplanted cells, it is undeniable that stem cell-based technology is emerging as a new treatment for PD soon.

Furthermore, there is a recent study that shows that diabetes drugs currently in use can be reborn as a treatment for PD. Studies

haveshownthatDPP-4inhibitorsnotonlypreventnervecelllossinPDbutalsoindirectlyconfirmthatth

euects.AlthoughresearchisunderwayaroundtheworldondrugsthatsuppresstheprogressionofPD,DPP-inhi 4 to play an important role in inhibiting the progression of PD. Lastly, ‘nanobody’, which is the smallest unit of antibodies that has the binding ability and is very stable, is called the hope of

treatingPD. K-synucleinismainlydepositedincells,sonanobodiesthataresmallerandeasiertopenetr

than relatively large antibodies. Moreover, the researchers removed the disulfide bonds of the nanob

them to facilitate penetration of brain cells, maintain stability within cells, and enable binding to

typeofnanobody,hastheadvantagethatitbindsonlytoK-synucleinthatcausesPDsymptoms.Asaresult,PFFN

K-synucleincomplexinmousebraintissueandinhibitedcomplexformation.Therefore,theresearchersbelie

drugs will be potential treatments for K-synuclein-related diseases. As such, research is constantly b fundamental treatment for PD. B

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MONKEYPOX Jungeun Kim

A

zoekim2000@naver.com

few monkeypox virus (MPV) cases were reported in Europe earlier this year, and now it has been classified as an internationalpublichealthemergencybytheWorldHealthOrganization( WHO)Having . experiencedCOVID-for 19 thepasttwoandahalfyears,wearenaturallyanxiousabout erethewh monkeypoxoutbreakwillleadto.

WhatisMonkeypox?

Monkeypox, an enveloped double-strand DNA virus, is a viral zoonosis with symptoms similar to those of smallpox patients.ItisamemberoftheOrthopoxvirusgenusinthefamilyPoxviridae,andwasfirstdiscover outbreaks of a pox-like disease occurred in monkey colonies used for research. Regardless of its name, the source of the disease still remains unknown.

WhataretheSymptoms?

Major symptoms include fever, headaches, muscle aches, swollen lymph nodes, exhaustion, chills, and a painful rash.

A rash may appear on the genitals, face, chest, hands, feet, or any other part of the body. These symptoms usually last from 2 to 4 weeks. The interval from infection to the onset of symptoms is usually from 6 to 13 days. The in can be divided into 2 periods: the invasion period where symptoms appear, and the skin eruption period where rashes becomesevere. Severecasescanoccurinchildrenandpeoplewithunderlyingimmunedeficiencies monkeypox include secondary infections, bronchopneumonia, sepsis, encephalitis, and infection of the cornea resulting in loss of vision. Monkeypox might not seem that horrible compared to smallpox, which at its worst killed roughly one out of every three auected people. However, without medical treatment or vaccination, one in t monkeypox are at risk of fatal complications. In several observational studies, vaccination for smallpox was shown to be 85%euectiveinpreventingmonkeypox.

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HowDoesMonkeypoxSpread?

Since monkeypox is a zoonotic virus, transmission occurs through an animal-to-human route and a human-to-human route. Human-to-human transmission can also occur from close contact with one’s respiratory secretions, their skin lesions, or recently contaminated objects. The first human case of monkeypox was in 1970. Before 20, monke had been reported in several central and western African countries. Before the recent outbreak, monkeypox cases were all linked to international travel to African countries. However, recent cases have shown people who had not been to thosecountries.Therehasbeenafiercedebateoverthespreadofmonkeypoxthroughsex.Because involved young men who self-identify themselves as having sex with men, experts are currently arguing over whether or not to classify monkeypox as a sexually transmitted infection.

CanWeTreatIt?

Monkeypox virus infection does not yet have an approved treatment. However, there are three antivirals used to treat smallpox and conditions related to monkeypox. These three antivirals are TPOXX(Tecovirimat), Tembexa(Brincidofovir), and Vistide(Cidofovir). Also, intravenous vaccination immune globulin is licensed for the treatment of complications from smallpox vaccination and monkeypox. TPOXX is an investigational drug, that has not yet been approved by the FDAtotreatmonkeypox.Researchonthesedrugsiscurrentlyongoingtoverifytheirsafetyandeue

WillItbetheNewPandemic?

On July 23rd, 20, the WHO ovcially announced the outbreak of monkeypox to be a global health emergency o internationalconcern.Morethancases 160 acrosscountries 74 hadbeenreportedasoftheannounc is still coming to a consensus on whether the highest level of caution is required for monkeypox. Many experts have agreedthatincomparisontoCOVID-monkeypox 19, isnotexpectedtocausedrasticchangesindailylifel The virus could remain endemic in a few countries since monkeypox is not a new virus and it spreads mainly through closecontact.OnebigdiuerencebetweenmonkeypoxandCOVID-19isthatmonkeypoxspreadsmuchlesseu Unlike COVID, monkeypox cannot aerosolize into the air and remain in the air for hours and days. Also, to be infected with monkeypox, a high dose is required. On the other hand, some experts claim that it may be the next pandemic, but diuerentthanCOVID.Casesinseveralcountries,especiallytheUS,arerapidlyincreasing.Sincemo auecting a specific risk group that involves intimate contact, it has a possibility of becomin ‘nicer’ pandemic than COVID. B

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SPACE MEDICINE Seung Yeon Noh

rsy9901@yonsei.ac.kr

S

pace medicine is a field of aerospace which studies new surroundings that humans will go through in space to maintain human performance in extreme conditions. It makes investigations on medical problems by minimizinghumanbodychangeinweightlessnessorbydevelopinginnovativemedicaltechnologies.Inother words,thestudyonspacemedicineisconductedintwoaspects.Oneisastudyonmedicalproblemsthatcanoccur in human body when exposed to space, and the other is a study on the application technology in medical devices andpharmaceuticalssuchasproteindrugsandcelltherapydrugsusingspaceenvironment.Theaerospaceindust whichweareveryawareofisabranchthatdevelopsprojectiletechnologiessuchasenginesorsatellites,butspa developed countries are already paying attention to space medicine beyond these traditional space industri be honest, you might think this field of space medicine may sound irrelevant to most people except astronauts.

However,expertsbelievethatwhateverstudiedinspacemedicinewillbeofgreathelptohumanityontheground.

Physical Changes in Space

Physical changes resulting from space exposure are mostly due to microgravity and space radiation, causing diseases in musculoskeletal system, vascular circulation system, brain nervous system, sensory nervous system, and endocrine system. When entering microgravity, blood and other fluids are no longer pulled down, the redistribution of fluid toward the head, causing the altered responses of baroreceptor systems. In terms of musculoskeletal system, microgravity induces the uncoupling of bone transformation between resorption and formation resulting in bone demineralization and muscle atrophy. Some studies suggested that the cause of bone loss may be due to the impairment of vitamin D production rather than the imbalance of hormones.

Also, muscles lose both strength and mass as they are anti-gravity muscles, whose main function is to maintain our body upright in the gravitational environment.

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Utilization of Space Medicine

As the support of the government is essential for the development of space medicine, in early 2022, the Techshot along with NASA succeeded in building Ministry of Health and Welfare and the Korea Centers heartmusclesusing3DprinterontheInternationalSpace for Disease Control and Prevention proposed a project Station. Though technology for making tissues with 3D to build a space medicine research platform by investing printers is being actively studied on the ground, cells 45.6 billion won over five years from 203 to 207. are spread flat on earth due to strong gravity, making it However, it is pointed out that there is no content related divcult for the tissue to grow from top to bottom and to space medicine in the Health and Medical Technology from side to side. As the space station rotates around Promotion Act and Space Development Promotion Act, the Earth at a high speed, the tissue is well layered in a which could become a half-way race focusing only on weightless state which makes three-dimensional culture the machinery sector. Therefore, national investment is through3Dprinterpossible.Assuch,cellscangrowmuch needed in the mid-to-long-term roadmap to raise the level faster in outer space, away from the constraints of gravity, of domestic R&D and infrastructure for international revolutionizing medicine that replaces or regenerates joint research. human cells, tissues, and organs. Additionally, several multinational pharmaceutical companies have also Prospects embarked on space medicine research. Merck managed Space medicine, a sort of special environmental to manufacture the immuno-oncology ‘Keytruda’ on the medicine, can expand the scope of research to the space International Space Station. Due to weightlessness, the environmentandyieldnewresults.Thisfieldofmedi lumps do not sink to the floor making the drug more can prevent or treat diseases provoked by changes in the homogeneous which increases the purity and medicinal musculoskeletal system, vascular circulation system, euectsofthedrug. brain nervous system, sensory nervous system, and Aside from these, many countries are now preparing endocrine system owing to the exposure to the space to enter space station experiments. China is planning environment in manned space activities. In addition, research using its own space station, Tiangong, and India through compound library screening, it is possible to and Russia are also preparing for the space station. Israel is bring about a group of drug candidates that can have developing a technology to use Cube satellites to conduct therapeutic euects, which control the express space medicine experiments in a weightless environment genes related to exposure to noxious stimuli in the space without having to go to the space station. This is a method environment. This makes it possible to evaluate the of installing medical experiment equipment in a cube development potential of a new drug through in vivo satellite and performing experiments by remote control preclinicalverificationofcandidates,contribut after launching it. research on drug application technology. B

Current State of Korea Inha University's Aerospace Research Institute is the first private medical institution to establish a research foundation for space medicine in 2018. Research is largely conducted in three parts: the equilibrium system, the cardiovascular system, and the immune metabolism system. In the equilibrium part, they study alterations in the nervous system that recognizes the surrounding space, and in the cardiovascular part, they conduct research on the way to respond to cardiovascular changes that can be caused by space radiation and zero gravity. Lastly in the immune metabolism part, they study how immunological competence changes in high gravity in order to deal with a weightless environment.

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LIQUID BIOPSY

The Future of Cancer Treatment Kyubin Kim

kkb5252@naver.com

What is a Liquid Biopsy?

The term ‘liquid biopsies’ refers to specific biomarkers found in body fluids that provide umanity has suCered from cancer for a long information on the patient’s malignancy. The two main time. Many patients with advanced-stage derivatives of liquid biopsy include circulating tumor canceroftenresultinpoorsurvivaloutcomes.

To improve the prognosis of cancer, researchers DNA(ctDNA) and circulating tumor cells(CTCs).

Extracellular exosomes and vesicles can also be used have been taking great eCorts to detect cancer sooner in a minimally invasive way and liquid as biomarkers. As cells die within the body, DNA biopsy has emerged as the key. In recent years, fragments are released into the blood. If a patient has the analysis of cancers using specific biomarkers cancer, the blood contains not only normal DNA but such as circulating DNA from cancer - has gained remarkable attention. These biomarkers derivedalso DNA from tumor cells, which are ctDNA. ctDNA from tumors have more potential to provideis known to be originated from apoptosis and necrosis of cancer cells. CTCs are cells detached from either information for malignancy than a tissue biopsy, which is a traditional method to diagnose cancer the primary tumor or the sites of metastasis. These thathasthetissuetakenfromthebody. cells represent the existence of malignancy and are more easily obtainable than the original cancer tissue.

Liquid biopsy is a test that uses ctDNA and CTCs in thefieldofcancerdiagnosisandprognosis,whichha great therapeutic potential.

H

Technological Method for Liquid Biopsy

The current state of liquid biopsy technology is simple. Blood tests are done and analyzed. Specific proteins such as prostate-specific antigen(PSA) an carcinoembryonic antigen(CEA) from blood suggest malignancy. However, these tests have high falsepositive rates since it prioritizes sensitivity to detect the proteins, which leads researchers to come up with additional methods such as next-generation sequencing to overcome the shortcomings. Nextgeneration sequencing(NGS) is a technology used to determine DNA/RNA sequences and analyze any genetic variations that are associated with diseases.

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Unlike the traditional Sanger sequencing methods Liquid biopsy is used not only for diagnosing which analyze a single DNA strand one at a time, a tumor but also used to find the most suitable NGS enabled the sequencing of thousands of genes in euective treatment for an individual. Aliquid bi multiple samples at once. NGS enables the detection can be used to easily determine whether the tumor of ctDNA and CTCs – even in low abundance – with responds to a particular therapy, and it may also help ahighdegreeofbothsensitivityandspecificity. to monitor NGS response and relapse. The decrease of covers a wide range of mutations and can easily ctDNAs to undetectable levels indicates that the current identify tumor-derived alterations. treatment is successful and increased biomarkers in the bloodstream imply crucial things regarding therapy such as the tumor has developed mutations.

Therapeutic Significance of Liquid Biopsy

Conclusion

A Liquid biopsy is a powerful tool when it comes There are still remaining challenges, including to every aspect of immunotherapy. It is used not only finding methods to detect mutations that are i for cancer screening and early diagnosis, but also used frequency and diagnosing cancer at an early stage when to make treatment decisions and monitor treatment there are extremely low levels of ctDNAs or CTCs. responses. Furthermore, liquid biopsy technology can Detecting single mutations in early-stage patients is help to prevent relapse. tremendously demanding. Lack of standardization is The 5-year relative survival for pancreatic cancer another problem, allowing only a few preclinical and is 10%. This is due to late diagnosis since more than clinical trials so far. Nevertheless, it is clear that liquid half of pancreatic cancer patients are diagnosed in biopsy technologies have great clinical potential. It the state of distant metastasis, after cancer spreads to may be the key to early diagnosis and individualized other organs such as the liver or lungs. To change the patient treatment, which are crucial to reducing the outcome of the survival rate of such cancer, we need morbidity rate of cancer. More research, investment, to diagnose earlier, when the tumor is regional or and trials will be needed, and hopefully we may soon localized. The reason why early diagnosis is divcult find liquid biopsy used worldwide, becoming the key is that the malignant tissue is inaccessible at the early to cancer treatment. B stages. But by looking at ctDNA or CTCs, there is no need to access the original tissue; all we need is the DNA or cell derived from the tissue, which makes diagnosis much easier.

The Liquid biopsy also increases the accessibility of testing. Traditional methods such as solid tumor biopsy, which is a method of detecting tumors by invasively getting a sample of the tumor tissue can be divculttocarryoutandmayhaveseveresideeuects.

Liquid biopsy is very much less invasive than solid tumor biopsy and it may reduce the burden on patients.

Additionally, liquid biopsy is a very much euective tool when it comes to cancers with tumors that are divculttoaccess,suchastumorsinthebrainorlungs.

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NEXT GENERATION nEW DRUG dEVELOPMENT PLATFORM JinYoo Park

truthfree@yonsei.ac.kr

ow is life structured, and how does it works?Cell Simulation Status Organisms are made up of cells, which are the It seems that the era of realizing cells in the virtual basic structural and functional units. Among them, space of a computer and simulating the reaction when humans are made up of 30 to 40 trillion cells. Cells work administering drugs is not far away. Scientists at the through the interaction of numerous molecules. Protein, University one of the substances that play a crucial role in cells, is of Illinois at Urbana-Champaign have created a D 3 simulation in virtual computer space based estimatedtobeto 50, million 3 percell.Whenseveral physicochemical interactions. The research results on proteins aggregate and interact, properties that do not appear when only one protein is present appear. This this were published in Cell in January 2022. To create characteristic is called emergence. Emergence in the living simulation, the researchers wanted to implement things produces surprising results. One of the results mycoplasma, the world’s simplest cell. Mycoplasma lives is the vast signaling system inside the cell. If we look at with fewer than 500 genes. Compared to humans with emergence from a reductionist point of view, the result more than 20,000 genes, it is a very simple organism. Zaida of emergence is ultimately revealed by the elements Luthey-Schulten, the paper’s corresponding author and coconstituting the system and the interaction between the components. Inotherwords,ifweknowthefeaturesthatdirector of the university’s Center for the Physics of Living make up a cell and can calculate the interactions,Cells, we can said she got enough data from the simulations. She predict the behavior of the cell. This possibility is a very also emphasized that the reason the simulatio interesting topic for the pharmaceutical world. This is reality well was not that the motion itself was programmed because if the appropriate elements and interaction logic but because the logic with which the molecules interact are discovered for a cell, what will happen when a drug is waswellmatchedtoreality.Thepaper’sfirstautho putintothecellcanbepredicted.Thequestionofwhether this is feasible has been resolved by the rapid growthThornburg, of said that many calculations were made possible computerscience. through parallel calculations, suggesting the possibility of

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<3D simulation in virtual computer space>

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making the calculations faster.

What impact will the development of cell simulations have? Cell simulations will give scientists new insights and ideas to explore uncharted territory for living things. And the data obtained by verifying this will repeat the virtuous cycle that becomes the basis for developing the simulation again. In addition, technological advances will increase observation technology, advances in hardware will enable faster computational speed, and advances in software will enable more evcient computation. This suggests more sophisticated simulations will be developed. These developments are still taking place today. In February 2022, Professor Jaeseung Jeong of KAIST published a paper titled “Development of high-accuracy robotic arm control brain-machineinterfacebasedonartificialintell genetic algorithms.”

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Next-Generation Drug Development Platform and Pharmacist

Where will the pharmacists be when the next-generation drug development platform emerges? You can jump into platform development with computational thinking skills.

In this case, it is possible to find ways to explore ne drug possibilities in the platform development process.

In the process of processing a large amount data, the data necessary for drug development is collected and developed <Development of high-accuracy robotic arm control brain-machine> so that users can use it easily. Another method is to extract the essential data from a lot of data after the platform is The key is to move the arm only by imagination by developed to derive the possibility of a new drug. In order analyzing the signals from the cerebral cortex that are to select and use data necessary for new drug development generated when the arm is about to move. What gained among more than 500,000 protein data, it is required to have awas fundamental understanding of drugs. Therefore, the newinsightsthroughartificialintelligence theinverse pharmacist is essential to this role. Of course, pharmacists analysis of artificial intelligence’s computational model to specify the areas of the cerebral cortex involved in will need to be prepared to handle large amounts of data.

imagining directions. Although it is an application on a As long as minimal cell simulation has already been larger scale than cell simulation, this case shows new developed, it is expected that future development will possibilities for artificial intelligence.proceed In this way, the cell faster than expected. Alpha Fold, an artific simulation will be more sophisticated. And it is thought intelligence for protein structure prediction, predicted that we will move on to the simulation of human cells. protein 360, structuresayearagobuthasnowpredicted Unlike prokaryotic cells, human cells have organelles, and 10 million structures. If enough logic is prepared like thewaygenesworkisverydiuerent.However,ifthis, thebasic the development of artificial intelligence wi logic is well structured, moving to this stage may not be in an instant. At the same time, if more detailed data for the such a big obstacle. development of artificial intelligence models are a If human cell simulation becomes possible, it is possible the development of life science technology and engineering technology are added, it will not be too far for topredictwhateuectitwillhaveoncellsobservation byadministering drugs designed in the previous step in the virtual world. a simulation of a human cell to be created.

It has already been calculated based on the interaction This simulation is not simply limited to the fiel between substances in the movement of cell components. research. Even a pharmacist at a large hospital will use Thatis,itisnotdivculttorunasimulation whenagene-based single cell simulation to determine drug a patient’s substance is added. Through this, it will be possible to suitability. From this point of view, cell simulation will confirmwhetherthedrugactuallybindstothe expected site when considering personalized be in a critical position within the cell or whether there is an unexpectedly bound medicine for the next generation of medical professionals. site.

In addition, if you are in the field of research or new As human cell simulations are developed, new drug drug development, it is expected that the pharmacist will development research will accelerate, and the next- be in a position where you need to touch and deal with generation drug development platform will appear. The cell simulation more closely than this. In the role of next-generation drug development platform refers to a pharmacists that will gradually expand, we think that we system that can obtain virtual results by searching for a need to recognize the existence of cell simulation and target for a drug to act through simulation and actually prepare to adapt and utilize the massive data obtained from administering the medication. simulation one step at a time. B 2022 VOL.22

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SMART WATCH

: Wearing Healthcare on Your Wrist YouYoung Cho youyoung0129@naver.com

Today, watches are no longer used only for checking time. The new emerging main functions are digital health care and sports functions. For instance, the Apple Watch Series 2 has a built-in GPS, which allows the wearer to measure exercise records, and has a heart rate sensor and a waterproof function that can be used up in water to 50m deep. Also, ApplehascollaboratedwithNiketolaunchanAppleWatchforpeoplewhoworkout.Althoughther in depth and variety of functions compared to sports-specific smartwatches such as GARMIN, it cr exercise environment without having to wear a heavy mobile device on the armband. As such, after smartwatches demonstrated their ability to improve quality of life, companies began to produce smartwatches as a main celling item.

TheglobalsmartwatchmarketsizewasUSDbillion 18.62 inThe 20. marketisprojectedtogrowfromUSD2.0 billioninto 201 USDbillion 58.21 bywith 208, aCAGR(compoundannualgrowthrate)ofThe 14.9 globalmarket exhibitedastellargrowthofin 21.3% as 20 comparedtotheaverageyear-on-yeargrowthduringThe 2017-9. growing consumers’ inclination towards technological devices owing to incredible attributes to help simplify their life hasasignificantcontributiontowardsspikingtheproductusage. Nowadays,keybrands,includi Amazfit,andImmo,areoueringinnovativewristwatches.

The devices come with multiple positive aspects, including navigation, fitness tracking, notific checking, and others, which thus help users with various needs ranging from athletes, tech enthusiasts to regular users. But among them, the most unique function of smartwatches is the digital healthcare technology.

What is Digital Health Care?

The broad scope of digital health includes categories such as mobile health and telemedicine. Health information technology, wearable devices and personalized medicine are also included. Digital health technologies implement computing platforms, connectivity, software, and sensors. They include technologies intended for use as a medical product, in a medical product, as companion diagnostics, or as an adjunct to other medical products (devices, drugs, and biologics). Digital health tools have the vast potential in improving our ability to accurately diagnose and treat disease. Also, they are useful in enhancing the delivery of health care.

Most smartwatches have built-in HR measurement functions. Then let’s find out what this m us, the principle of measurement, and the accuracy. Next, we will look at what happens to other health indicators.

Furthermore, we will look into the future of digital healthcare.

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What Does Your HR Tell You?

Aman from the UK whose heart stopped 138 times in Another exemplary case is of a 27-year-old woman hours 48 wassavedbyhisApplewatchDavidLast,age who 54, quickly discovered her hyperthyroidism through her received the watch as a birthday gift from his wife Sarah. heart rate. Heather Hendershoy, a Kansas resident, was The watch immediately showed that his resting heart rate a 26-year-old woman who was confident in her health. was as low as 30bpm. The resting heart rates for an This adult wass because she worked out steadily at a young age male are usually between 60-1bpm. David initially and had no history of ailment. One night, while resting thought the watch was faulty and didn’t take much notice of on the sofa, she was warned by her Apple Watch that the readings - despite Sarah urging him to get checked out. her heart rate was over 120 times per minute. Thinkin Eventually he went to see his doctor who referred him to a strangely of the reading, she visited the hospital the next cardiologist at Norfolk and Norwich University Hospital, morning and was diagnosed with hyperthyroidism after where he was booked in for an MRI scan. When the results several tests, so she was able to receive quick treatment of the scan came out, doctors told him that he was at risk Heart rate anomalies can show the onset of diseases of sudden cardiac death. He said that the hospital sounded as such. Although the watch cannot diagnose just by “really panicky” on the phone. Once he got there, they had reading heart rate abnormalities, it can urge you to visit abedreadyimmediately.Infact,hishearthadstopped the hospital 138 where a medical expert can give you one. times in 10 second intervals over a 48-hour period.

The Heart abnormalities of the body that HR can inform are block is a condition where the heart beats slower or with an mostly abnormalities in the heart and blood vessels, and abnormal rhythm. There are three variations of how severe hyperthyroidism. aheartblockis-withtheleastseverecategorizedasa1stdegree heart block, which may not cause symptoms, while 3rd-degreeheartblockcanbeamedicalemergency.

How Smart Watch Measures Your Heart Rate : Photoplethysmography

The optical heart sensor can also use infrared light.

The optical heart sensor in Apple Watch uses what is This mode is what Apple Watch uses when it measures known as photoplethysmography. Most smartwatches your heart rate in the background, and also for heart measure HR in the same way. This technology, while rate notifications. Apple Watch uses green LED light divcult to pronounce, is based on a very simple fact: to measure heart rate during workouts and Breathe blood is red because it reflects red light and absorbsyour green sessions, and to calculate Heart Rate Variability (HRV). light. Apple Watch uses green LED lights paired with B light‑sensitive photodiodes to detect the amount of blood flowing through your wrist at any given moment. When your heart beats, the blood flow in your wrist — and the green light absorption — is greater. Between beats, it’s less. By flashing its LED lights hundreds of times per second, Apple Watch can calculate the number of times the heartbeatseachminute—yourheartrate.Theopticalheart sensor supports a range of 30–210 beats per minute. In addition, the optical heart sensor is designed to compensate for low signal levels by increasing both LED brightness and sampling rate.

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BIOINFORMATICS Jihui Jeong

jihuijeong21@yonsei.ac.kr

T

hroughouthistory,scientistshavestrivedtounderstandthemiracleoflife.Theyhavestudiedeveryliving thing,exploringdeeperanddeeper.Biologistsandclinicianshavealwaysstruggledtocollectvariousd and clues to find the correct answers to fundamental questions. New technology eventually enabled themtocapturemorebiologicaldataatunprecedentedspeed,thankstotheeCortsofaninternationalproject called‘theHumanGenomeProject(HGP)’.Indeed,somuchdatahasbecomeavailablethatitcannolongerbe processedbythehumanmindalone.Thisiswherebioinformaticscomesintoaction.

What is Bioinformatics?

Bioinformatics is a hybrid science that links biological data to techniques for information storage, distribution,andanalysistosupportmultipleareasofscientificresearch. Data-intensi problems can be resolved by using a computational approach. According to the National Human Genome ResearchInstitute,bioinformatics,asrelatedtogeneticsandgenomics,isascientificsubd using computer technology to collect, store, analyze and disseminate biological data and information, such as DNA and amino acid sequences or annotations about those sequences. Simply put, it is the application of computertechnologytotheunderstandingandeuectiveutilizationofbiologicaldata.Tha we can uncover the biological information hidden inside mass sequences.

The Data of Bioinformatics

Data banks are used to store and organize data. The journal Nucleic Acids Research regularly publishes special issues on biological databases and has a list of such databases. A few popular databases are GenBank from NCBI (National Center for Biotechnology Information), EMBL from EBI (European Bioinformatics Institute European Bioinformatics Institute), SwissProt from the Swiss Institute of Bioinformatics, and PIR from the Protein Information Resource. GenBank (Genetic Sequence Databank) is one of the fastest-growing repositories of known genetic sequences which provides nucleotide sequences. The EMBL nucleotide sequence databaseisacomprehensivedatabaseofDNAandRNAsequencescollectedfromscientificliter applications. Lastly, SwissProt and PIR is a protein sequence database of minimized redundancy and enhanced integration with other databases.

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Applications of Bioinformatics

Not only is bioinformatics vital for basic biology research, but it also has a major impact on biotechnology.

Applicationsofbioinformaticshavebeenfoundinmanyfields,particularlyinthefieldofmedicine can be used to identify correlations between gene sequences and diseases, discover protein structure and their functionsfromaminoacidsequences,designnoveldrugs,andprovidebetter-targetedthera personalized medicine. Currently, it is applied in genomics, proteomics, metabolomics, transcriptomics, and molecular phylogenomics. Let’s take a closer look at proteomics, the study of the overall composition of intracellular protein, protein structure, and protein interaction. For example, the function of a protein can often be estimated based on the similarity of its amino acid sequence with those of proteins whose functions are already known.AlongwiththeNeedleman-Wunschalgorithm,thefirstalgorithmtobeproposedtomeasu homology, another computer algorithm variation known as BLAST (basic local alignment search tool) is used to rapidly search through a database of known protein sequences to find those with significa sequence of a query protein. Also, experimental data can be expanded based on predictions. The spontaneous folding of proteins can be predicted from an amino acid sequence by biennial CASP (Critical Assessment of Structure Prediction) programs. Furthermore, bioinformatics can be used to predict docking systems which is a key step in drug development. The bioinformatic analysis includes similarity searching, clustering, QSAR modeling, virtual screening, etc. Such analyses will play an increasingly important role in almost all aspects of drug discovery and development. Computer programs can simulate and predict optimal spatial relationships by calculating weak interactions, such as the burial of hydrophobic surfaces, hydrogen bonds, and van der Waals forces.Forexample,aninhibitorofanoctamin1(ANOa 1), calcium-activatedchloridechannel,wasdisc using three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmaco was used to identify the essential chemical features required in the inhibition ofANO1. In t medicine will become more personalized with the development of pharmacogenomics. Doctors will be able to analyzeapatient’sgeneticprofileandprescribethebesttreatmentaccordingly.

Conclusion

Bioinformatics has become an essential interdisciplinary field that incorporates biology to process large sets of biological data. To simply talk about the future of bioinformatics, in the short term, bioinformatic analyses will prompt a big step forward in the development of targeted therapy by identifying more disease genes and designing new drug targets. In the long term, integrative bioinformatic analysis of genomic,pathological,andclinicaldatainclinicaltrialswillrevealpotentialadverse through simple tests. Ultimately, pharmacogenomics will likely bring a new age of personalized medicine - that is, individualized therapy and targeted medicine free from side euects, taking each patie profileintoaccount.

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Digital Biomarkers, Promising Tools in Healthcare and Drug Development Jungyoon Ryu jungyoon_r@yonsei.ac.kr

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DIgital biomarkers

Traditional Biomarkers and Digital Biomarkers

Traditional biomarkers, or biological markers, are indexes that can be used to objectively confirm presence and track the progress of a disease or assess reactions to a particular regimen. Biomarkers thus must be accurate and reliable while being characteristic to a certain condition so that they act as a specific in of it. Hence, its usefulness encompasses various fie including biomedical research, diagnostics, therapeutics, andprognostics.Traditionalbiomarkerscanbecla into four types based on their characteristics: molecular (e.g. blood glucose level), radiographic (e.g. bone mineral density), histologic (e.g. grading and staging of Digital Biomarkers, Promising Tools cancers), and physiologic (e.g. blood pressure, heart rate) in Healthcare and Drug Development biomarkers. Such traditional biomarkers can usually The advent of digital means to access reports on be obtained usually by way of invasive and expensive individuals’ health status or measurements of bodily methods that requires the aid of a skilled practitioner and functions revolutionized the way people approach the visitation of the subject to a clinical facility. healthcare. Especially prevalent in the context of our Digital biomarkers, on the other hand, are relatively daily lives nowadays are wearable Internet-of-Things recent and innovative tools that make up for the limitations (IoT)devicessuchassmartwatchesandfitnessof bands with traditional biomarkers. Digital biomarkers share all the multiple health and wellness features: heart rate monitors, requirementsthattraditionalbiomarkerssat physical activity trackers, sleep monitors, etc. Such in that they are collected based on digital technology. digital tools are bestowing a wider range of freedom upon Since data is assembled digitally through rather simple the public to track quantifiable data regarding their own maneuvers, they can be tracked regardless of the subject’s physicalfitness. Foronething,ithasbecomealocation. common The methods for obtaining information are practice at the gym for people to evaluate their workout usually non-invasive and low-cost, which makes it even routine based on the heart rate data collected via their more patient-friendly. wearable devices of choice. However, the digitization There are various measures that can be adopted for of data acquisition in health-related fields opens up biomarkers, including wearable the collection of digital possibilities for much more than just personal healthcare devices, mobile apps, other devices and platforms, or PCguides. Together with the advance in data analysis and based software. Wearable devices include fitness b communications technology, the availability of such or smart watches that collect data based on consistent digital health data, otherwise termed ‘digital biomarkers’, physical contact on the wrist or chest. Apple, Samsung, lays the foundation for telemedicine, personalized and Garmin, and Fitbit have respective series of smartwatches preventive healthcare, and time-saving transformations in and fitness bands that allow monitoring of phys drug development procedures. activities and an array of physiological biomarkers.

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An Israeli startup ‘Beyond Verbal’ouers a program t AliveCor’s Kardiamobile is a portable device for analyzes vocal intonations to monitor depression. Also, taking an ECG regardless of time and location, compatible motor skills, eye movements, sleep patterns can be with a mobile app that reads the results using an AI-based digitally measured by sensors so that the resulting data algorithm. Mobile apps are often used as a channel for can be processed to discern whether they are indicative of managing and analyzing measurements made by sensors Alzheimer’s disease. on separate devices or also used as a system for keeping track of and reporting simple measurements of fitness.

Most digital therapeutics nowadays are converting Digital Biomarkers in Drug Development cognitive behavioral therapy to online methods per The COVID-19 pandemic has brought about mobile apps as such. Even more recently, there are changes in drug development procedures in that they attempts to integrate the use of implantable or ingestible generated novel barriers in conducting clinical trials. biosensors with apps on smartphones, thereby ouering Due to restraints in social activities, clinical trials were digital biomarkers to carry data collected from beneath forced to experience early termination or postponement. the surface of the skin or inside the internal organs. Since Considering the colossal budget put into clinical trials, it data can be acquired via various routes, a data integration stands to sense that pharmaceutical companies turned to system is necessary for organizing and controlling all the methods that enable procedures to be carried out remotely. diuerenttypesofinformation.

The use of digital biomarkers makes remote patient monitoring and decentralized clinical trials a feasible choice since researchers can obtain clinical data of patients from a distance through digital methods, thereby Applications of abatingtheneedforin-personcontact.Thissignific Digital Biomarkers in Medical Care acceleratesphases2and3ofclinicaltrials.Butnot Digital biomarkers are gaining attention in related is the application of digital biomarkers in clinical studies fields owing to their potential applications andbut is qualitatively advantageou time-evcient anticipated improvements in medicine. Physiological it makes available longitudinal, real-world data which and behavioral cues of diseases can be detected from provides more comprehensive insights into the outcomes digital biomarkers collected in the course of one’s daily of therapeutic interventions. life. Such physiological and behavioral markers can The application of digital biomarkers is useful over add on to the pool of information practitioners can use the entire process of drug development even other than to assess patients’ health over a distance, laying grounds clinical trials. Digitally acquired data can be processed for more precise diagnostic experiences in telemedicine.

by AI-based data integration systems which elicit Moreover, digital biomarkers can be used to promote useful information that can be used as guides for patient personalized or preventive medicine since more intimate recruitment or drug discovery. information of the patient can be accessed. Closer patient Despite the enticing aspects of employing digital monitoring and real-life data acquisition takes us a step biomarkers in healthcare and drug development, there is closer to precision medicine, which tends to the more yet a lot of progress to be made for complete application personalized needs of a patient in a very specific of Utilizing digital biomarkers entails of the state technology. a disease. Data collected daily can be analyzed by AI or challenges concerning privacy, adherence problems, a machine learning to be matched to symptoms linked to an shortage of infrastructure, and divculties in va impending disease. Hence, preventive measures can be The technical aspect of the solution necessitates the taken so that the disease does not take on a serious path. involvement of more complex analyses and bigger data storage. Once these obstacles are overcome and reliability Currently, there are attempts to apply digital as well as feasibility are confirmed, digital bioma biomarkers in diagnostics, therapeutics, prognostics, will become powerful tools to enhance quality of life in and preventive care of mental illnesses or neurological terms of health in the digital era. B disorders such as depression and Alzheimer’s disease.

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AKARAKA & Daedongjae Back to our School Life in Three Years Ha Neul Roh

skyroh0416@yonsei.ac.kr

D

ue to the COVID-19 pandemic, students have not been able to enjoy the usual things that they have been enjoying for granted. This was the same for all universities. For the past three years, since most university festivals have not been held. Many students had a sense of loss because university festivals can be said be a crucial source of the vitality of college life. There were even some students who came to Yonsei University dreaming to participate in the festival ‘AKARAKA’. As the social distancing eased early this year, universities have gradually begun to return to normal. Likewise, Yonsei University was able to reopen the festival after three yea FromSeptember21stto23rd,the 20, GeneralStudentCouncilEmergencyExigencyCommitteehostedthe137th school anniversary Muak Daedongjae. Yonsei University’s cheering squad held the festival ‘AKARAKA’. As it is the firstfestivalinthreeyears,manystudentshavebeenlookingforwardtoit,andtheDaedongjaePlanningGroupals preparedalottorevivetheexpectationandtosuccessfully thefestival. host

ThefestivalbeganonSeptember21st,attheInternationalCampusinSongdo.TheYonseiIntern Student Representative Council(YIC) held various sports competitions such as the ‘YIC Olympics’, which includes group jump rope, jegichagi, and the three-legged race. In addition, the Daedongjae Planning Group held a stamp event to increase student participation. Also, there were various food trucks and meal zones, where students could eat freely. In front of the Underwood Memorial Library many club performances were held. ‘One Beer’, a band club of the College of Pharmacy, performed as well. “The weather was so nice, and I was very happy to once again feel the lively energy of the International Campus after a long time! All the One Beer members worked hard to prepare for the Daedongjae, and we had a lot of fun as well! Many students from our major came to see the performance, and it was so fun to perform on an open stage outdoor!” said Jiwon Yang, a 4th grade Pharmacy and the president of One Beer. ‘Blue Knights’, the color guard of Yonsei University, came to cheer along with students in the International Campus after all club performances were done. The Songdo Muak Daedongjae was a festival that revitalized the international campus where about 20,000 freshmen along with the students of the College of Pharmacy live in.

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Muak Daedongjae at Sinchon Campus was held for two days from September 2nd to 23rd. There were various department and club unit booths along Baekyang-ro. Students from the College of Dentistry opened a free oral examination booth. It was a meaningful opportunity for people to volunteer their talents related to what they are majoring in. The food booth which many people anticipated the most was open in the baseball stadium.

Atotal of 53 organizations held booths at the baseball stadium during the two days. Many students could enjoy food from various food trucks. At the Grand Stadium, many performing clubs performed dances, songs, and band performances. Since it wasthefirstface-to-faceDaedongjaeFestivalinalongtime,the Daedongjae Planning Group also held a special event. In front of the alumni plaza, the large Bellygom bear was set as a photo zone. The KBS entertainment show “Hong-Kim dongjeon” visited Yonsei University as well. “It was very nice to have a festival at school after a long time, and the campus felt livelier!

I bought dinner with my friends at the baseball stadium food truck, looked around the booths, and made a lot of memories.

It felt like I was enjoying my campus life!” said Jungyun Ryu, a 3rd grade Pharmacy student. As such, students were able to enjoy the festival and have a meaningful time, making good memories with their friends.

‘AKARAKA’ has become one of the largest university events since it first started in meaningful as it was the university’s first cheering event hosted byYonsei Universit It is a festival that is held at the outdoor amphitheater called the Nocheon Theater. ‘AKARAKA’ was not held in 20 and 201, and it was the first face-to-face event since COVID19. On September 24th, the YonseiUniversityamphitheaterwasfilledwithbluewaves,andstudentswerethrill thecheeringsquad.Thefirstpartofthefestivalstartedwithclubperformancesandc guestperformances,andfinishedwithcheeringwiththecheeringsquad.YonseiUniversi ‘Jazz Feel’, ‘HARIE’, and ‘Sonagi’ performed. After that there was a cheering session led by the cheering squad where the students could learn the school fight songs. The second part of the fe performances which is what most of the students look forward to. Many famous artists visited to celebrate thefestivalwiththestudents. NewJeans,10cm,LESSERAFIM,WINNER,andZicoperformed,which shows ou the prestige of Yonsei University’s festival. Finally, the last part of the fe fireworks.Allthestudentsenjoyedcheeringalongwith Bthecheeringsquad.

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Members Editor in chief Jimin Seo

VICE Editor in chief Jungeun Kim

COPY MANAGER Ji Won Son

Journalist

You Young Cho

Dah Eun Kim

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Seung Yeon Noh

Namkyu Oh

Kyubin Kim

Seo Yeong Kim

Daeun Choi

Ha Neul Roh

Jinyoo Park

Jungyoon Ryu

Hyunjin Lee

Jihui Jeong

Designer

Design MANAGER Ji Won Kim

Ji In Shin

Seo Kyung Kim

Tae Ho Kim

Hwan Lee

Yeong Seo Park

Jinyoo Park

jihyun kim

Ji Won Yang

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Yonsei Student Pharmacist Magazine