CD44 Receptor-Mediated/Reactive Oxygen Species-Sensitive Delivery of Nanophotosensitizers against Cervical Cancer Cells.

Stimulus-sensitive, nanomedicine-based photosensitizer delivery has an opportunity to target tumor tissues since oxidative stress and the expression of molecular proteins, such as CD44 receptors, are elevated in the tumor microenvironment. The aim of this study is to investigate the CD44 receptor- and reactive oxygen species (ROS)-sensitive delivery of nanophotosensitizers of chlorin e6 (Ce6)-conjugated hyaluronic acid (HA) against HeLa human cervical cancer cells. For the synthesis of nanophotosensitizers, thioketal diamine was conjugated with the carboxyl group in HA and then the amine end group of HA-thioketal amine conjugates was conjugated again with Ce6 (Abbreviated as HAthCe6). The HAthCe6 nanophotosensitizers were of small diameter, with sizes less than 200. Their morphology was round-shaped in the observations using a transmission electron microscope (TEM). The HAthCe6 nanophotosensitizers responded to oxidative stress-induced changes in size distribution when H2O2 was added to the nanophotosensitizer aqueous solution, i.e., their monomodal distribution pattern at 0 mM H2O2 was changed to dual- and/or multi-modal distribution patterns at higher concentrations of H2O2. Furthermore, the oxidative stress induced by the H2O2 addition contributed to the disintegration of HAthCe6 nanophotosensitizers in morphology, and this phenomenon accelerated the release rate of Ce6 from nanophotosensitizers. In a cell culture study using HeLa cells, nanophotosensitizers increased Ce6 uptake ratio, ROS generation and PDT efficacy compared to free Ce6. Since HA specifically bonds with the CD44 receptor of cancer cells, the pretreatment of free HA against HeLa cells decreased the Ce6 uptake ratio, ROS generation and PDT efficacy of HAthCe6 nanophotosensitizers. These results indicated that intracellular delivery of HAthCe6 nanophotosensitizers can be controlled by the CD44 receptor-mediated pathway. Furthermore, these phenomena induced CD44 receptor-controllable ROS generation and PDT efficacy by HAthCe6 nanophotosensitizers. During in vivo tumor imaging using HeLa cells, nanophotosensitizer administration showed that the fluorescence intensity of tumor tissues was relatively higher than that of other organs. When free HA was pretreated, the fluorescence intensity of tumor tissue was relatively lower than those of other organs, indicating that HAthCe6 nanophotosensitizers have CD44 receptor sensitivity and that they can be delivered by receptor-specific manner. We suggest that HAthCe6 nanophotosensitizers are promising candidates for PDT in cervical cancer.

[Relationship between performance on the Digital Trail Making Peg test and cognitive function in older adults].

AIM: To determine the relationship between performance on the Digital Trail Making Peg test (DTMP) and cognitive function in older adults. METHODS: A total of 203 community-dwelling older adults (mean age: 76.4±5.1 years old) participated in this study. The five-cog test was used to assess the cognitive function. The DTMP measured completion time, number of errors and intra-individual variability for performance variability (coefficient of variation, CV; inter-elemental variability, IEV). Spearman's rank correlation coefficient (ρ) was calculated to examine the association between each variable. In addition, a multiple regression analysis was performed with the cognitive function score as the dependent variable and the DTMP completion time, number of errors, CV, and IEV as the independent variables, with adjusting for the sex, age, years of education, body mass index, medical history, depression, and physical function. RESULTS: The rank correlation coefficients with cognitive function scores were as follows: completion time, ρ = -0.479 (P < 0.01), number of errors, ρ = -0.068 (P = 0.332), CV, ρ = 0.085 (P = 0.225), IEV, ρ = -0.316 (P < 0.01). The results of the multiple regression analysis showed that completion time (ß = -0.566), CV (ß = 0.164), IEV (ß = 2.736) were significantly associated with cognitive function scores. CONCLUSIONS: The shorter the DTMP completion time, the better the overall cognitive function. However, the intra-individual variability of CV and IEV did not show consistent results, with smaller values indicating less intra-individual variability.

HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG-I.

RIG-I is a key cytosolic sensor that detects RNA viruses through its C-terminal region and activates the production of antiviral interferons (IFNs) and proinflammatory cytokines. While posttranslational modification has been demonstrated to regulate RIG-I signaling activity, its significance for the sensing of viral RNAs remains unclear. Here, we first show that the RIG-I C-terminal region undergoes deacetylation to regulate its viral RNA-sensing activity and that the HDAC6-mediated deacetylation of RIG-I is critical for viral RNA detection. HDAC6 transiently bound to RIG-I and removed the lysine 909 acetylation in the presence of viral RNAs, promoting RIG-I sensing of viral RNAs. Depletion of HDAC6 expression led to impaired antiviral responses against RNA viruses, but not against DNA viruses. Consequently, HDAC6 knockout mice were highly susceptible to RNA virus infections compared to wild-type mice. These findings underscore the critical role of HDAC6 in the modulation of the RIG-I-mediated antiviral sensing pathway.

Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants.

PURPOSE: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants. METHODS: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants. RESULTS: The number of rare likely deleterious variants in functionally intolerant genes ("other hits") correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with their carrier family members. Probands with 16p12.1 deletion and a strong family history presented more severe clinical features (p=0.04) and higher burden of other hits compared with those with mild/no family history (p=0.001). The number of other hits also correlated with severity of cognitive impairment in probands carrying pathogenic CNVs (n=53) or de novo pathogenic variants in disease genes (n=290), and negatively correlated with head size among 80 probands with 16p11.2 deletion. These co-occurring hits involved known disease-associated genes such as SETD5, AUTS2, and NRXN1, and were enriched for cellular and developmental processes. CONCLUSION: Accurate genetic diagnosis of complex disorders will require complete evaluation of the genetic background even after a candidate disease-associated variant is identified.

Effects of N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain and self-reported knee function in middle-aged and older Japanese adults: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: There was no evidence of satisfying the standard to decide the efficacies of glucosamine and chondroitin in middle-aged and older Japanese adults with knee pain and/or stiffness. AIM: To investigate the effects of 24 week oral N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain, self-reported knee function, physical activity, and physical performance. METHODS: We randomly assigned 11 men and 39 women (aged 52-87 years) to receive 100 mg of N-acetyl glucosamine and 180 mg of chondroitin sulfate daily (Glu/Cho group) or a placebo (control, C group) for 24 weeks. The primary outcomes were a 100 mm visual analog pain scale (VAS) and the Japanese Knee Osteoarthritis Measure (JKOM) score. The secondary outcomes were physical activity and physical performance. RESULTS: We observed a significant group × time interaction on the JKOM score. According to the post hoc test, it significantly decreased (i.e., improved knee function) from the 4- to 12-week follow-up in the Glu/Cho group and the Glu/Cho group score was significantly lower than the C group at the 12-week follow-up. We found a significant interaction on household physical activity. There was no significant interaction on VAS or physical performance tests. DISCUSSION: The results of the present study were consistent with previous studies mainly conducted in European and American countries. CONCLUSION: These results suggest that consumption of N-acetyl glucosamine and chondroitin sulfate for 12 weeks or longer has a positive effect on self-reported knee function and household physical activity in middle-aged and older Japanese adults with knee pain and/or stiffness.

Inhibitory effects of an aqueous extract from Cortex Phellodendri on the growth and replication of broad-spectrum of viruses in vitro and in vivo.

BACKGROUND: Cortex Phellodendri (C. Phellodendri), the dried trunk bark of Phellodendron amurense Ruprecht, has been known as a traditional herbal medicine, showing several bioactivities. However, antiviral activity of C. Phellodendri aqueous extract (CP) not reported in detail, particularly aiming the prophylactic effectiveness. METHODS: In vitro CP antiviral activity evaluated against Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Newcastle Disease Virus (NDV), Herpes Simplex Virus (HSV), Coxsackie Virus (H3-GFP) and Enterovirus-71 (EV-71) infection on immune (RAW264.7) and epithelial (HEK293T/HeLa) cells. Such antiviral effects were explained by the induction of antiviral state which was determined by phosphorylation of signal molecules, secretion of IFNs and cytokines, and cellular antiviral mRNA expression. Furthermore, Compounds present in the aqueous fractions confirmed by HPLC analysis and evaluated their anti-viral activities. Additionally, in vivo protective effect of CP against divergent influenza A subtypes was determined in a BALB/c mouse infection model. RESULTS: An effective dose of CP significantly reduced the virus replication both in immune and epithelial cells. Mechanically, CP induced mRNA expression of anti-viral genes and cytokine secretion in both RAW264.7 and HEK293T cells. Furthermore, the main compound identified was berberine, and shows promising antiviral properties similar to CP. Finally, BALB/c mice treated with CP displayed higher protection levels against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). CONCLUSION: CP including berberine play an immunomodulatory role with broad spectrum antiviral activity, due to induction of antiviral state via type I IFN stimulation mechanism. Consequently, C. Phellodendri could be a potential source for promising natural antivirals or to design other antiviral agents for animal and humans.

Click approach to the discovery of 1,2,3-triazolylsalicylamides as potent Aurora kinase inhibitors.

A series of 1,2,3-triazolylsalicylamide derivatives has been developed from the antiproliferative agent 7 and was evaluated for their Aurora kinase inhibitory activity. The novel 1,2,3-triazolylsalicylamide scaffold could be readily assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition, allowing rapid access to the structurally diverse analogues. The synthesized 1,2,3-triazolylsalicylamide derivatives revealed a significant Aurora kinase inhibitory activity. In particular, 8g inhibited Aurora A with IC50 values of 0.37µM. The critical role of phenolic -OH in the binding was confirmed by a molecular modeling study.

Effects of Desert Olive Tree Pearls Containing High Hydroxytyrosol Concentrations on the Cognitive Functions of Middle-Aged and Older Adults.

The Japanese population has the world's longest life expectancy but faces the challenge of extending the healthy life expectancy without developing chronic diseases. Therefore, the effectiveness of products derived from olives used in the Mediterranean diet as a potential dietary solution has attracted attention. This study examined the effects of desert olive tree pearls (DOTPs), which contain 162 times more polyphenol hydroxytyrosol than olive oil, on the cognitive function of middle-aged and older adults using the Cognitrax test. Participants (aged 51-82 years) were assigned to the DOTP intake (n = 36) or placebo group (n = 36) in a randomized, double-blind, placebo-controlled, parallel-group study. The participants received 3 g of DOTPs or placebo in olive oil twice daily for 12 weeks. Among cognitive domains, complex attention had a significant time × group interaction effect (p = 0.049) between the DOTP and placebo groups. The simple main effect for this item was significantly different (p < 0.001 and p = 0.572, respectively). Time effects were significant (p < 0.05) for the psychomotor speed, reaction time, cognitive flexibility, processing speed, and executive function domains. Therefore, DOTPs have the potential to alleviate cognitive problems faced by middle-aged and older adults in Japan.

Evaluation of Cognitive and Physical Function Among Older Adults by Their Physical Activity: A Cross-Sectional Kasama Study, Japan.

BACKGROUND: The amyloid-ß1-42 (Aß42) level is a biomarker that is widely used to evaluate individual cognitive dysfunction early in neurodegenerative diseases, as well as differentiate between normal cognitive function, mild cognitive impairment, Alzheimer's disease, and vascular cognitive impairment. OBJECTIVE: Our cross-sectional study evaluated the association between daily exercise and physical and cognitive function and Aß42 levels among a subsample of 325 older adults from the Kasama Study. METHODS: Participants (age: 74.5 [range 65-90] years) were classified into three exercise groups: the dual-task (DEG, n = 128), single-task (SEG, n = 122), and non-exercise (NEG, n = 75) groups. The main outcomes were the plasma Aß42 levels and the scores of the five cognitive (5-COG) tests and five cognition-related physical function (5-PHYS) tests. RESULTS: The Aß42 levels and 5-COG and 5-PHYS scores were higher in the SEG and DEG than in the NEG. The Aß42 levels were higher in the DEG than in the NEG (p = 0.008). CONCLUSIONS: Physical activities such as regular exercise may benefit older adults, improving their cognitive and physical function.

Influence of chemotherapy on nitric oxide synthase, indole-amine-2,3-dioxygenase and CD124 expression in granulocytes and monocytes of non-small cell lung cancer.

There is no specific marker to evaluate the immuno-suppressive status of cancer patients. Several markers, such as CD124, latency-associated peptide (LAP), arginase I, indole-amine-2,3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), are known to be associated with immune suppression. However, there is little research regarding the change in these parameters after chemotherapy. The present study enrolled 23 chemo-naïve non-small cell lung cancer (NSCLC) patients and 19 healthy donors. From the 23 NSCLC patients, 11 post-chemotherapy samples were collected. Surface and functional markers were analyzed by flow-cytometry. The mean fluorescence intensities (MFI) of iNOS were higher and the MFI of LAP were lower in NSCLC patient than in healthy donors (P < 0.05). In a comparison of pre-chemotherapy and post-chemotherapy groups with NSCLC, the MFI of iNOS on granulocytes and monocytes and IDO on monocytes were significantly lower in the post-chemotherapy group than in the pre-chemotherapy group (P < 0.05). In a serial analysis with 10 patients who had paired samples and who showed clinical benefits from chemotherapy, the MFI of iNOS for both cell types, and of IDO and CD124 for monocytes decreased significantly after chemotherapy, compared with those before chemotherapy (iNOS, 4.79 ± 1.75 vs 2.83 ± 0.77, P = 0.005, for granulocytes and 6.15 ± 2.94 vs 2.76 ± 1.05, P = 0.005 for monocytes; IDO, 6.81 ± 3.43 vs 4.64 ± 1.55, P = 0.012 for monocytes; CD124, 2.31 ± 0.39 vs 1.94 ± 0.43, P = 0.008 for monocytes). The changes in arginase I and LAP expression were not significant. The changes in iNOS, IDO and CD124 expression were significant after chemotherapy in NSCLC. Further evaluation of the possibility of immune status monitoring using these parameters is needed.

Associations of physical activity with neighborhood environments and transportation modes in older Japanese adults.

OBJECTIVE: We investigated associations of walking and other leisure-time physical activity (LTPA) with environmental characteristics and transportation modes in older Japanese adults. METHODS: This cross-sectional study in 2010-2011 used data from 421 community-dwelling older adults aged 65-85 years living in Kasama City, rural Japan. We used the Physical Activity Scale for the Elderly to assess walking and other LTPAs, and the International Physical Activity Questionnaire Environment Module for neighborhood environments. RESULTS: After adjusting for confounders, we found that good traffic safety and aesthetics were positively associated with high levels of walking (ORs=1.64-2.12); whereas, good access to public transportation was negatively associated with walking (OR=0.64, 95% CI=0.42-0.98). Good access to recreational facilities, presence of sidewalks, absence of hills, seeing people exercise, and aesthetically pleasing surroundings were positively associated with high levels of LTPA except walking (ORs=1.61-2.13). Individuals who rode bicycles more than once per week were more likely to engage in a LTPA except walking (1-3 days: OR=1.72, 95% CI=1.03-2.87; ≥4 days: OR=2.90, 95% CI=1.71-4.93). CONCLUSION: This study adds information on correlates of physical activity among older Japanese adults; the positive association between LTPA except walking and the frequency of bicycle travel is an especially new and intriguing finding.

Cognitive and physical benefits of a game-like dual-task exercise among the oldest nursing home residents in Japan.

Introduction: Dual-task (DT) exercise can act as a substitute, which can help improve both physical and cognitive functions. Thus, this study investigated the effects of a game-like cognitive DT exercise called "Synapsology" (SYNAP) among the oldest residents of a nursing home. Methods: Participants (aged 85-97 years) were assigned to the intervention group (n = 12) and the control group (n = 12). The intervention group underwent 60-minute sessions, twice a week for 24 weeks. Results: A comparison of the Mini-Mental State Examination scores and six physical function tests, before and after the intervention, shows that the SYNAP had a positive impact on the cognitive and physical functions among the intervention group. Discussion: These findings suggest that SYNAP may help maintain or improve cognitive and physical functions among older adults compared to no interventions. Therefore, SYNAP would act as a beneficial tool amidst a "superaging" society like Japan.

Characterization of Medication Errors in a Medical Intensive Care Unit of a University Teaching Hospital in South Korea.

OBJECTIVES: The objective of this study was to characterize the current status of medication errors (MEs) throughout the medication therapy process from prescribing to use and monitoring in a medical intensive care unit (MICU) in Korea. METHODS: Four trained research pharmacists collected data through retrospectively reviewing electronic medical records for adults hospitalized in the MICU in 2017. The occurrence of MEs was determined through interprofessional team discussion led by an academic faculty pharmacist and a medical intensivist based on the medication administration records (MARs). The type of MEs and the consequent ME-related outcome severity were categorized according to the Pharmaceutical Care Network Europe and the National Coordinating Council for Medication Error Reporting and Prevention, respectively. RESULTS: Overall, electronic medical records for 293 patients with 78,761 MARs were reviewed in this study. At least one type of ME occurred in 271 patients (92.5%) in association with 16,203 MARs (21%), primarily caused by inappropriate dose (35.5%), drug (27.8%), and treatment duration (25.1%). Clinically significant harmful events occurred in 24 patients (8%), including life-threatening (n = 5) and death (n = 2) cases. The 2 patients died of enoxaparin-induced fatal hemorrhage and neutropenia associated with ganciclovir and cefepime. Antibiotics were the most common culprit medications leading to clinically significant harmful events. CONCLUSIONS: In conclusion, MEs are prevalent in the MICU in Korea, most commonly prescribing errors. Although mostly benign, harmful events including deaths may occur due to MEs, mainly associated with antibiotics. Systematic strategies to minimize these potentially fatal MEs are urgently needed.

Syntheses of 1,2,3-triazolyl salicylamides with inhibitory activity on lipopolysaccharide-induced nitric oxide production.

A 28-membered 1,2,3-triazolyl salicylamide library was synthesized via a Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition and evaluated for their abilities to inhibit NO production in LPS-activated RAW264.7 macrophage cells. Among 28 analogues, 29 g showed a significant inhibitory activity (IC(50) = 12.8 µM). The inhibitory effects of 29 g on LPS-mediated NO production in macrophage cells appeared to be associated with the suppression of iNOS expression.

A rapid synthesis of lavendustin-mimetic small molecules by click fragment assembly.

Lavendustin-mimetic small molecules modifying the linker -CH(2)-NH- with an 1,2,3-triazole ring have been synthesized via a click chemistry. Two pharmacophoric fragments of lavendustin were varied to investigate chemical space and the auxophoric -CH(2)-NH- was altered to an 1,2,3-triazole for rapid click conjugation. The small molecules were evaluated against HCT116 colon cancer and CCRF-CEM leukemia cell lines. Among 28 analogues, 3-phenylpropyl ester 26b inhibited CCRF-CEM leukemia cell growth with GI(50) value of 0.9microM.

Evaluation of beneficial effect of a dual-task exercise based on Japanese transitional games in older adults: a pilot study.

Not only does Japan has the world's longest healthy life expectancy, but also the world's longest average life span. This study investigated the effect of a novel dual-task (DT) exercise called "Synapsology" (SYNAP), developed as a game-like activity to improve older adults' physical and cognitive functions. Participants (n=24) with a mean age of 70.6 years (65-77 years) were randomly assigned to the SYNAP exercise group (SG, n=15) and the control group (CG, n=9). The SG participated in the DT intervention consisting of 60-minute sessions, twice a week, for 8 weeks. Physical function in timed-up-and-go had significant pre- and post- trial differences (P=0.017) in SG. In addition, cognitive function results in the a 25-hole trail-making peg test (P=0.004) and an oxidative stress marker (P=0.039) had a statistically significant difference within the SG. However, there were no significant differences in the physical and cognitive functions between SG and CG. In the study, older adults who participated in cognitive-motor DT intervention improved significantly with regard to motor ability and cognitive function results. Thus, a game-like DT exercise may help maintain the healthy life of older adults compared to no intervention.

Small Heterodimer Partner Controls the Virus-Mediated Antiviral Immune Response by Targeting CREB-Binding Protein in the Nucleus.

Small heterodimer partner (SHP) is an orphan nuclear receptor that acts as a transcriptional co-repressor by interacting with nuclear receptors and transcription factors. Although SHP plays a negative regulatory function in various signaling pathways, its role in virus infection has not been studied. Here, we report that SHP is a potent negative regulator of the virus-mediated type I IFN signaling that maintains homeostasis within the antiviral innate immune system. Upon virus infection, SHP interacts specifically with CREB-binding protein (CBP) in the nucleus, thereby obstructing CBP/ß-catenin interaction competitively. Consequently, SHP-deficient cells enhance antiviral responses, including transcription of the type I IFN gene, upon virus infection. Furthermore, SHP-deficient mice show higher levels of IFN production and are more resistant to influenza A virus infection. Our results suggest that SHP is a nuclear regulator that blocks transcription of the type I IFN gene to inhibit excessive innate immune responses.

Evaluation of maslinic acid with whole-body vibration training in elderly women with knee osteoarthritis.

PURPOSE: Maslinic acid (MA) is a component derived from a natural olive-based extract known to have pharmacological functions that include suppressing inflammation. This study examined how MA, in conjunction with whole-body vibration training (WBVT), can improve knee and muscle function in elderly women with knee osteoarthritis (OA). METHODS: The study was a double-blinded, placebo-controlled, randomized intervention study that enrolled individuals with knee pain. Participants were 26 females aged 65-85 years with knee OA. They performed WBVT and ingested either 16.7 mg of MA or a placebo daily for 20 weeks. We compared the effect of WBVT with placebo (WBVT/P) and WBVT with MA (WBVT/MA) in participants with various degrees of knee OA (Kellgren and Lawrence (K-L) grade) using the Japanese Orthopaedic Association (JOA) score and isokinetic dynamometer measurements to evaluate knee and muscle function with two-way ANOVA. RESULTS: Based on the results of two-way ANOVA analysis of muscle function measurements, there was significant interaction (time × group) (P = 0.03) in the "isokinetic extension peak torque" domain for severe OA (K-L grade ≥ 3). The simple main effect of time in the WBVT/MA group (P = 0.04) contributed to this interaction. The JOA score for WBVT/MA supported the main effect of group as having a significant correlation in the "pain on walking" (P = 0.04) and "range of motion" (P < 0.01) domains. Participants with severe knee OA in the WBVT/MA group improved in these domains, whereas the WBVT/P group had few positive results. CONCLUSIONS: Participants with severe OA who ingested MA in conjunction with WBVT improved their knee and muscle function. This study suggests that ingesting the anti-inflammatory supplement MA while participating in WBVT, elderly women can reduce knee OA and improve their knee muscle strength.

Retraction Note: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components.

The above article by Weeratunga et al. has been retracted from Journal of Microbiology at the request of the corresponding author. The authors found that they were unable to reproduce Figure 1, Figure 3(A), Figure 4(A) and Figure 7(D) presented in this paper. All of the authors agreed to this retraction. The authors regret any inconvenience that this may cause and apologize sincerely to the readers, reviewers, and editors of Journal of Microbiology.

Strategic Priorities to Improve Effectiveness of Anti-smoking Interventions for the Korean Military: An Application of the Analytic Hierarchy Process.

Introduction: As South Korea remains technically at war with the North, higher smoking prevalence in the military might adversely affect the South Korea's military power and contribute to lifetime smoking in men with mandatory military service. This study was to identify priorities among the anti-smoking strategies to improve the existing smoking cessation programs for the Korean military. Methods: The analytic hierarchy process model with a goal, decision criteria, and sub-criteria as well as candidate strategies, was developed following a literature search and expert group discussion. A survey for pairwise comparison was conducted to determine the priority of the (sub-)criteria and strategies by 14 experts. The Super-Decisions software was used to determine the priorities and to analyze their consistency ratios and sensitivities. The study was approved by the ethics committee of the Korea Ministry of Health and Welfare. Results: Eight candidate strategies were developed to improve the effectiveness of military anti-smoking interventions as follows: (1) development of outcome enhancement plans for smoking cessation programs for the military, (2) development of differentiated smoking cessation programs for specific groups, (3) building of community network for continuity and accessibility of anti-smoking project, (4) building of industry-academia-government networks for anti-smoking project, (5) improvement of the perception of and strengthen the reward for smoking cessation, (6) development of a training system for army clinicians for the delivery of smoking cessation services, (7) creation of a certification system for smoking cessation programs, and (8) development of an evaluation system of project performance for smoking cessation. Through the analytic hierarchy process survey, the military specificity and its sub-criterion of practicality were selected as the top concerns of decision criteria for the anti-smoking strategies among the decision criteria of outcome improvement, military specificity, publicness, and economic efficiency. The most important strategy was to improve the perception of and strengthen the reward for smoking cessation. This strategy was most focused on the creation of an anti-smoking environment and improvement of the effectiveness of the projects. The creation of a training system for army clinicians for the delivery of smoking cessation services ranked second. Conclusion: In conclusion, motivating smoking cessation and utilizing well-trained army clinicians were found to be the most important anti-smoking strategies for the Korean military. This study might provide valuable insights for policy makers to reduce tobacco use in the Korean military.