East Asians can be more susceptible to heavy alcohol consumption than others, due to genetic variations. In addition, alcohol drinking has been suspected as a cause of type 2 diabetes (T2D). To clarify the integrated toxic mechanisms of alcohol on T2D in East Asians, we performed epigenome-wide association studies using methylation profiling arrays among four groups of South Korean men (N = 80): drinking (DK), diabetic (DM), both drinking and diabetic (DK + DM), and non-drinking and non-diabetic controls (Con). We screened hypermethylated or hypomethylated sites in both DK and DM, compared to Con, and found 15 more and 10 fewer methylated sites in DK + DM than in DK or DM among the screened sites. Furthermore, we confirmed the involvement of SLC8A1, IGFBP7, ZBED3, etc., in alcohol-related diseases and T2D and observed that these epigenetic sites were related to the negative regulation of chemokines, response to hexose, transport, glucose, regulation of cell communication, response to insulin, sodium ion transmembrane transport, and sodium ion transport. MUL1, GPLD1, ZBED3, and SLC8A1 showed multiple associations with these pathways. Finally, we found that some of the 25 epigenetic sites, including CCRL2 for inflammation, ACTG1 for cell shape, and NDUFB9 for oxidoreduction, were hubs of the STRING network. In conclusion, our findings suggest that alcohol-induced T2D development involves two interconnected pathophysiological mechanisms, mitochondrial dysfunction and errors in cell communication and ion transport that contribute to pancreatic β-cell failure.

Background: The intake of red or processed meat remains controversial as a crucial factor for CRC. Thus, we performed in-depth biological monitoring. Methods: We performed a case- control study and analyzed various exposure and response biomarkers including 1-OHP, MeIQx, and PhIP, and malondialdehyde (MDA), and heterocyclic amine (HCA)-DNA adducts in Korean cases and controls (N = 218). Results: They consumed 53.4 ± 74.0 g/day of red meat and 1.1 ± 3.7 g/day of processed meat. The CRC presence was associated with sex, BMI, tobacco smoking, alcohol drinking, cooking method of meat, and vegetable consumption, rather than red or processed meat intake. The levels of MDA were positively associated with those of 1-OHP, MeIQx, or PhIP. The sum of 1-OHP, MeIQx, and PhIP was associated with the levels of HCA-DNA adducts and cooking method of meat. In addition, the above biomarkers for CRC were associated with each other. However, most of these biomarkers were not higher in CRC patients than those in controls. Conclusion: The present in-depth biological monitoring provides that red or processed meat may induce oxidative stress; however, present intake of the meat and the intake-related oxidative stress may not affect CRC prevalence among the Korean population, who consume less meat than Westerners.

Gestational diabetes mellitus (GDM) requires lifestyle changes that may alter exposure to endocrine-disrupting chemicals (EDCs). This study aimed to assess maternal and fetal exposure to EDCs—including bisphenol-A (BPA), monoethyl phthalate (MEP), and perfluorooctanoic acid (PFOA)—during the COVID-19 pandemic and to evaluate their association with fetal birthweight. Maternal urine (second and third trimester) and paired cord blood samples were analyzed from 58 GDM and 118 non-GDM pregnancies using UPLC-MS/MS. Significant correlations were found between maternal urine and cord blood levels of BPA and MEP. Cord blood BPA levels were significantly lower in GDM mothers (0.35 vs. 0.72 μg/L, p < 0.05), suggesting reduced exposure due to dietary interventions. However, maternal urinary BPA levels in GDM pregnancies were positively associated with fetal birthweight (β = 2.69, p < 0.05), indicating increased susceptibility to obesogenic effects. PFOA was present in all cord blood but only 41% of maternal urine samples. These findings underscore the dual impact of GDM-related lifestyle changes: reduced EDC transfer to the fetus, yet persistent metabolic vulnerability.

Aims: To investigate the effects of magnesium (Mg) from deep ocean sources, we conducted a randomized clinical trial involving adults with hypertension, diabetes, or hyperlipidemia. Methods: Subjects consumed either Mg-enriched water (MEW) or a placebo (80 or 6 mg of Mg per 2 L/day, respectively) for 4 weeks. We examined the detoxifying effects of MEW on environmental toxicants, including polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and its impact on gut microbiome composition (N = 30; 49.26 +/- 9.55 yrs). Results: Most subjects consumed less Mg than the RDA, enabling their participation in the trial. Despite limitations in serum Mg measurement to assess Mg intake, MEW intake led to improvements in body mass index (BMI), insulin levels, triglycerides, glucose-BMI, and fatigue. Regardless of Mg content, water consumption reduced urinary levels of 1-hydroxypyrene, a major PAH metabolite, and malondialdehyde, an oxidative stress biomarker. Moreover, the MEW group exhibited greater diversity in gut microbiome composition than the placebo group. Notably, MEW kept the abundance of Clostridium, Dorea, or Desulfovibrio, indicating a balanced Mg intake. Conclusion: MEW (80 mg of Mg/day) appears safe for RDA and effective for preventing CVD or T2DM, as evidenced by gut microbiome and biomarker outcomes.

Korean pears and Chlorella have shown potential in detoxifying various xenobiotics. Thus, we investigated their combined effects on the detoxification of endocrine-disrupting chemicals (EDCs), and EDC-related fat and muscle health using a non-inferiority clinical trial and in vivo and in vitro tests. The human doses of pear extracts, chlorella, and positive control (L-carnitine tartrate) were safe levels, based on previous clinical trials and the approvement by Korean government. The combination increased hand grip strength. Total cholesterol, lowdensity lipoprotein, apoA-I, and apoB levels were alleviated by the combination, which also modulated ACC, FASN, and HSL to affect fatty acid synthesis and lipidosis or R-oxidation in high-fat-diet- and bisphenol-A-treated mice and in 3 T3-L1 adipocytes. Consistently, in vitro experiments showed that the combination treatment suppressed adipocyte differentiation, downregulated PPAR gamma expression, promoted lipid breakdown, and enhanced myoblast differentiation. In conclusion, the combination can be useful to prevent from EDCs on fat and muscle health.

INTRODUCTION:Tobacco smoke is a mixture of endocrine disrupting chemicals (EDCs), which may accelerate biological ageing. METHODS:Within this cross-sectional study we recruited adult and adolescent subjects (2013-2014) and performed biological monitoring to clarify health end points of tobacco smoking between adolescents and adults (n=620) with exposure biomarkers, i.e. CO, urinary cotinine, t,t-muconic acid (TTMA), malondialdehyde (MDA), and obtained information of behavioral factors and tobacco addiction status in South Korea. We also analyzed the 96 SNPs for metabolism, addiction, and expression differences and compared mtDNA abnormalities in buccal and blood cells. RESULTS:There was an association between tobacco smoking and oxidative stress with urinary cotinine and MDA levels. Youth smokers showed lower frequency in some of mtDNA alteration, SNPs for consistent bases between buccal and blood cells, than youth non-smokers or adult smokers. Among the SNPs, the polymorphisms on SULT1A1, DRD2, and ADH1B were related to multiple of the above exposure biomarkers. Interestingly, urinary MDA or TTMA in youth were similar to those in adults (MDA, 2.7 ± 1.5 vs 2.4 ± 1.3 μM; TTMA, 74.1 ± 129.9 vs 98.8 ± 126.1 μg/L), although urinary cotinine levels were approximately four-fold lower in youth than adults (0.1 ± 0.4 vs 0.6 ± 0.9 mg/L; p<0.0001). Urinary MDA, an oxidative stress biomarker, were negatively associated with the growth rate among the adolescents. CONCLUSIONS:The present biological monitoring study assessed the impact of combustible cigarette smoking with various exposure, susceptibility and response biomarkers to clarify how tobacco smoking differently affects adolescents and adults in South Korea.

Tobacco smoke is an environmental mixture including polycyclic aromatic hydrocarbons and may interfere in endocrine system as an EDC in aging. Thus, we performed a molecular epidemiological approach with in-depth biological monitoring of combustible cigarette smoking among adolescents and adults in South Korea (N=620) with exposure biomarkers, i.e., exhaled CO, urinary cotinine, t,t-muconic acid (TTMA), malondialdehyde (MDA), and obtained information of their lifestyle and tobacco addiction status. We also diagnosed the genetic polymorphisms on the 96 SNPs for tobacco-metabolism, -addiction, and expression differences and compared mtDNA abnormalities in buccal and blood cells. As results, there were positive associations among the above tobacco exposure biomarkers. Man or youth smokers showed high frequency in some of mtDNA alteration, such as ‘SNPs for inconsistent bases between buccal and blood cells’. Among the SNPs, the polymorphisms on SULT1A1, DRD2, and ADH1B were related to multi-exposure biomarkers. Interestingly, youth showed similar levels of urinary TTMA and MDA to adults, although their pack-year was approx. 1/6 volume of that of adults. We also observed the negative association between urinary MDA levels and the growth rate in the adolescents (p<0.05). In conclusion, the present biological monitoring provides high susceptible population, i.e., adolescents rather than adults, and reliable genetic factors affecting tobacco exposure. The inferred environment-gene-gene interaction suggests tobacco smoking accelerats aging in adolescents as an EDC.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary’s Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (β = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 μg/g creatinine vs. 1.71 μg/g creatinine [p < 0.05]; cord blood BPA, 1.96 μg/L vs. −0.86 μg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Pears are ancient functional foods for modern times. Particularly, Korean pears (Pyrus pyrifolia cv.) have been used as folk medicine for respiratory diseases and have strong potential for the treatment of hazardous aerosol-related diseases. Thus, the effects of pear ethanol extracts on air pollution-related respiratory hypersensitivity were studied by toxicokinetics, pro-inflammatory cytokines, and microbiomics in preclinical and randomized double-blind clinical studies. The mild-asthma subjects, who lived in the same city, Seoul, Korea, were separated into the placebo and the treatment (pear extracts, as brix 55; arbutin 5.01 mg and chlorogenic acid 0.18 mg/3 mL per day) groups for 4 weeks (n = 20). As results, there were positive associations between urinary 2-naphthol (NT) or 1-hydroxypyrene (OHP), exposure biomarkers for polyaromatic hydrocarbons in PM2.5, and pro-inflammatory cytokines, interleukin (IL)-4 or IgE, respectively, in the human subjects. The pear extracts somewhat reduced 2-NT and 1-OHP levels. The proportions of fiber-degrading bacteria that stimulate growth of beneficial microflora for immune defense, that is, Bifidobacterium and Eubacterium, were significantly higher in the pear consuming group than in the placebo group. Moreover, pro-inflammatory cytokines, including IgE, IL-4, IL-5, and IL-13, were significantly suppressed by the pear extracts in the preclinical tests of the ovalbumin-induced asthma mice. Thus, we suggest that air pollution-related respiratory hypersensitivity can be alleviated by Korean pear extracts by modulation of microbiome and immunocytokines.

Shiitake (Lentinula edodes) and reishi mushrooms (Ganoderma sichuanense) have been noticed for desirable chemoprevention, such as improving immunity, overcoming anticancer drug resistance, etc. Particularly, beta-glucans have been mostly mentioned as the active component of the mushrooms. However, the right preparation and effective usage of the mushrooms for cancers are unclear, yet. Thus, we screened various extractions of the two mushrooms and combinations of the extracts, using a high throughput screening of 3D cell culture system on 384-pillar plates with various cancer cells and Cell Titer-Glo 3D cell viability assay kit (Promega). We also quantified the beta-glucans in all extractions with the Megazyme Mushroom and Yeast Beta-Glucan kit (K-YBGL) by excluding the alpha-glucans content from the total-glucans. As results, most of the extracts showed cytotoxicity on the lung cancer cells, A549 cells, rather than on the other cells, such as HepG2 (N=9 for each treatment). The extracts of reishi mushroom in 60% of methanol (dose range, 0.21-2.3 mg/ml) showed the strongest cytotoxicity on the lung cells, IC50=0.90 +/- 0.01 mg/ml, among the extracts of different methanol contents (10-60%) or different temperatures (50-90 °C) of hot water. However, the 60 % of methanol reishi extracts included relatively low levels of beta-glucans, compared to other extracts (18.57 +/- 0.31 vs. 22.42 +/- 5.56 % w/w). In addition, the levels of beta-glucans in all of reishi mushroom extracts were lower than those in all of the shiitake extracts (17.70 +/- 1.89 % vs. 27.05 +/- 4.21 % w/w: p<0.01). Moreover, there was no association between the levels of beta-glucans and IC50 in A549 cells. Interestingly, the combination (1:1) of the above 60% of methanol extracts of reishi mushroom and the 30% methanol extracts of shiitake (dose range, 0.30-3.26 mg/ml) showed synergic effects, i.e., 2-7 fold stronger effects (average of IC50=0.40 mg/ml) than every single treatment (average of IC50=0.90-2.63 mg/ml). Taken together, the reishi mushroom may have other strong chemopreventive materials rather than beta-glucans, while the shiitake may have a potentiation effect, when combined with the reishi mushroom. In conclusion, our 3D cell culture system showed high throughput performance to find the right preparation and effective usage of the two mushrooms and provided useful information for the next clinical studies for lung cancer. Citation Format: Mihi Yang, Hee-Kyung Jang, Huiwon Kang. How do shiitake and reishi mushrooms work on lung cancer?: A high throughput screening of 3D cell culture. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4553.

Abstract Shiitake (Lentinula edodes) and reishi mushrooms (Ganoderma sichuanense) have been noticed for desirable chemoprevention, such as improving immunity, overcoming anticancer drug resistance, etc. Particularly, beta-glucans have been mostly mentioned as the active component of the mushrooms. However, the right preparation and effective usage of the mushrooms for cancers are unclear, yet. Thus, we screened various extractions of the two mushrooms and combinations of the extracts, using a high throughput screening of 3D cell culture system on 384-pillar plates with various cancer cells and Cell Titer-Glo 3D cell viability assay kit (Promega). We also quantified the beta-glucans in all extractions with the Megazyme Mushroom and Yeast Beta-Glucan kit (K-YBGL) by excluding the alpha-glucans content from the total-glucans. As results, most of the extracts showed cytotoxicity on the lung cancer cells, A549 cells, rather than on the other cells, such as HepG2 (N=9 for each treatment). The extracts of reishi mushroom in 60% of methanol (dose range, 0.21-2.3 mg/ml) showed the strongest cytotoxicity on the lung cells, IC50=0.90 +/- 0.01 mg/ml, among the extracts of different methanol contents (10-60%) or different temperatures (50-90 °C) of hot water. However, the 60 % of methanol reishi extracts included relatively low levels of beta-glucans, compared to other extracts (18.57 +/- 0.31 vs. 22.42 +/- 5.56 % w/w). In addition, the levels of beta-glucans in all of reishi mushroom extracts were lower than those in all of the shiitake extracts (17.70 +/- 1.89 % vs. 27.05 +/- 4.21 % w/w: p<0.01). Moreover, there was no association between the levels of beta-glucans and IC50 in A549 cells. Interestingly, the combination (1:1) of the above 60% of methanol extracts of reishi mushroom and the 30% methanol extracts of shiitake (dose range, 0.30-3.26 mg/ml) showed synergic effects, i.e., 2-7 fold stronger effects (average of IC50=0.40 mg/ml) than every single treatment (average of IC50=0.90-2.63 mg/ml). Taken together, the reishi mushroom may have other strong chemopreventive materials rather than beta-glucans, while the shiitake may have a potentiation effect, when combined with the reishi mushroom. In conclusion, our 3D cell culture system showed high throughput performance to find the right preparation and effective usage of the two mushrooms and provided useful information for the next clinical studies for lung cancer. Citation Format: Mihi Yang, Hee-Kyung Jang, Huiwon Kang. How do shiitake and reishi mushrooms work on lung cancer?: A high throughput screening of 3D cell culture. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4553.

Shiitake (Lentinula edodes) and reishi mushrooms (Ganoderma sichuanense) have been noticed for desirable chemoprevention, such as improving immunity, overcoming anticancer drug resistance, etc. Particularly, beta-glucans have been mostly mentioned as the active component of the mushrooms. However, the right preparation and effective usage of the mushrooms for cancers are unclear, yet. Thus, we screened various extractions of the two mushrooms and combinations of the extracts, using a high throughput screening of 3D cell culture system on 384-pillar plates with various cancer cells and Cell Titer-Glo 3D cell viability assay kit (Promega). We also quantified the beta-glucans in all extractions with the Megazyme Mushroom and Yeast Beta-Glucan kit (K-YBGL) by excluding the alpha-glucans content from the total-glucans. As results, most of the extracts showed cytotoxicity on the lung cancer cells, A549 cells, rather than on the other cells, such as HepG2 (N=9 for each treatment). The extracts of reishi mushroom in 60% of methanol (dose range, 0.21-2.3 mg/ml) showed the strongest cytotoxicity on the lung cells, IC50=0.90 +/- 0.01 mg/ml, among the extracts of different methanol contents (10-60%) or different temperatures (50-90 °C) of hot water. However, the 60 % of methanol reishi extracts included relatively low levels of beta-glucans, compared to other extracts (18.57 +/- 0.31 vs. 22.42 +/- 5.56 % w/w). In addition, the levels of beta-glucans in all of reishi mushroom extracts were lower than those in all of the shiitake extracts (17.70 +/- 1.89 % vs. 27.05 +/- 4.21 % w/w: p<0.01). Moreover, there was no association between the levels of beta-glucans and IC50 in A549 cells. Interestingly, the combination (1:1) of the above 60% of methanol extracts of reishi mushroom and the 30% methanol extracts of shiitake (dose range, 0.30-3.26 mg/ml) showed synergic effects, i.e., 2-7 fold stronger effects (average of IC50=0.40 mg/ml) than every single treatment (average of IC50=0.90-2.63 mg/ml). Taken together, the reishi mushroom may have other strong chemopreventive materials rather than beta-glucans, while the shiitake may have a potentiation effect, when combined with the reishi mushroom. In conclusion, our 3D cell culture system showed high throughput performance to find the right preparation and effective usage of the two mushrooms and provided useful information for the next clinical studies for lung cancer. Citation Format: Mihi Yang, Hee-Kyung Jang, Huiwon Kang. How do shiitake and reishi mushrooms work on lung cancer?: A high throughput screening of 3D cell culture. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4553.

High-throughput, pillar-strip-based assays have been proposed as a drug-safety screening tool for developmental toxicity. In the assay described here, muscle cell culture and differentiation were allowed to occur at the end of a pillar strip (eight pillars) compatible with commercially available 96-well plates. Previous approaches to characterize cellular differentiation with immunostaining required a burdensome number of washing steps; these multiple washes also resulted in a high proportion of cellular loss resulting in poor yield. To overcome these limitations, the approach described here utilizes cell growth by easily moving the pillars for washing and immunostaining without significant loss of cells. Thus, the present pillar-strip approach is deemed suitable for monitoring high-throughput myogenic differentiation. Using this experimental high-throughput approach, eight drugs (including two well-known myogenic inhibitory drugs) were tested at six doses in triplicate, which allows for the generation of dose–response curves of nuclei and myotubes in a 96-well platform. As a result of comparing these F-actin (an actin-cytoskeleton protein), nucleus, and myotube data, two proposed differentiation indices—curve-area-based differentiation index (CA-DI) and maximum-point-based differentiation index (MP-DI) were generated. Both indices successfully allowed for screening of high-myogenic inhibitory drugs, and the maximum-point-based differentiation index (MP-DI) experimentally demonstrated sensitivity for quantifying drugs that inhibited myogenic differentiation.

The incidence of colorectal cancer (CRC) has increased in Korea, a newly-industrialized Asian country, with the dramatic increase of meat intake. To assess the risks of red or processed meat consumption on CRC, we performed a case-control study with biological monitoring of urinary1-OHP, PhIP, and MeIQx for the meat exposure; dG-C8 MeIQx and dG-C8 PhIP for HCA-induced DNA adducts; and homocysteine and C-reactive protein (CRP) in blood as well as malondialdehyde (MDA) and 31fatty acids in urine for inflammation and lipid alteration. We further analyzed global DNA methylation and expression of 15 CRC-related genes. As a result, the consumption of red or processed meat was not higher in the cases than in the controls. However, urinary MeIQx and PhIP were associated with the intake of red meat and urinary 1-OHP. MDA and multiple fatty acids were related to the exposure biomarkers. Most of the 31 fatty acids and multiple saturated fatty acids were higher in the cases than in the controls. Finally, the cases showed upregulation of PTGS2, which is related to pro-inflammatory fatty acids. This study describes indirect mechanisms of CRC via lipid alteration with a series of processes including exposure to red meat, alteration of fatty acids, and relevant gene expression.

Background Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia. Methods We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears. Results We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro, in vivo, and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, -hyperlipidemic, -inflammatory, -mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM2.5 among high susceptible people with multiple underlying diseases. Conclusion For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.

A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In this study, we have tested potential BPA detoxification with Korean pear (Pyrus pyrifolia) extract, stimulators of ADH and ALDH, as well as arbutin, a reference compound in the pears, on the micropillar/microwell chip platform with human liver cells. Surprisingly, the toxicity of BPA was reduced in the presence of Korean pear extract, indicated by significantly increased IC50 values. The IC50 value of BPA with Korean pear extract tested against HepG2 cells was shifted from 151 to 451 μM, whereas those tested against Hep3B cells was shifted from 110 to 204 μM. Among the tested various concentrations, 1.25, 2.5, and 5 mg/mL of the extract significantly reduced BPA toxicity (Ps < 0.05). However, there was no such detoxification effects with arbutin. This result was supported by changes in protein levels of ADH in the liver cells.

Interest in global engagement among schools and colleges of pharmacy in the United States and Asian countries is growing. To develop fruitful relationships and engage in mutually enriching experiences, the cultural aspects of these countries need to be understood and respected. The aim of this paper is to facilitate culturally sensitive interactions between practitioners, faculty members, and students in the United States and those in Asian countries when they engage in health care practice and/or education. This paper introduces general information about China (including Macau and Hong Kong), Japan, South Korea, and Taiwan. Unique characteristics of the health care system and pharmacy education are described for each country. Stereotypes and misconceptions are discussed. Recommendations are included for initiating interactions and developing learning programs and scholarly collaborations while promoting culturally sensitive engagement. These recommendations are provided for US scholars, health care professionals, and students traveling to these countries as well as for those hosting visitors from these countries in the United States.