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Background: Exercise and dietary nutrition are considered crucial in human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) treatment protocols and people living with HIV/AIDS (PLWHA) rehabilitation care. However, there is no well-studied research evaluating the effects of combined interventions on the fitness and immune systems of PLWHA. Therefore, this study aimed to analyze the effects of exercise and dietary intervention on physical fitness, quality of life and immune response in PLWHA., Methods: This was an experimental study, with a sample of 25 male PLWHA divided into two groups: the intervention group (IG: 12 participants) and the control group (CG: 13 participants). All participants have not had any exercise habits and nutritional supplements in the past six months. The participants in the IG completed 45 min of exercise (60-80% HRmax) 4 times per week for 4 weeks. The exercise was in the form of brisk walking or running. They were also given a nutritional dietary supplement 3 times a day for 4 weeks. The 13 individuals in the CG continued their normal daily life (physical activity and diet). The following parameters were evaluated before and after the intervention: body composition, physical fitness, immune response, quality of life (QoL), stress, dietary behavior, dietary habits, exercise motivation, and physical self-efficacy., Results: The significant changes were observed in burnout of stress variables and physical efficiency index (PEI) of physical fitness in the IG (p =.023). Moreover, in the saliva samples, sal-T levels significantly increased only after the intervention in the IG (p =.012). Additionally, regarding the analysis of the interaction (group × time), there was a significant improvement in the reaction speed (p =.001) and grip strength (left: p =.002, right: p =.030) and a significant difference in physical satisfaction in QoL (p =.001), stress burnout (p =.043), self-confidence in physical efficacy (p =.045), external display (p =.008), and fulfillment (p =.047) in exercise motivation. Moreover, the significant effect of the intervention on emotional eating in dietary behavior was shown in the comparison of the IG before and after intervention (p =.001) and in the comparison of the IG group with the CG after the experiment (p =.013). However, there was no significant effect of time or interaction between the condition and time on body composition., Conclusions: In conclusion, exercise training and diet therapy caused changes in physical fitness and Sal-T levels, which had positive effects on the health promotion of PLWHA., (© 2024. The Author(s).)

The purpose of this study is to analyze the effect of proprioceptive exercise training on soccer skills and physical fitness in young soccer players. Nineteen young soccer players participated in the study. Participants were divided into proprioceptive exercises training (PT) and control (Cont) groups. The physical fitness and soccer skill performance test assessed at pre- and posttraining. Balance ability and power significantly improved in both groups after 8 weeks of training ( P <0.05). Dribble in the PT group was similar between pre- and posttraining, with a statistically significant difference in the Cont group ( P <0.05). There were no significant differences within and between groups according to training in the left and right feet for juggling. The PT and Cont groups did not differ significantly regarding short passes posttraining. However, a significant improvement in long passes was observed in the PT group after training period ( P <0.05). Shooting was no different between and within the groups. In conclusion, these inconsistent findings are thought to be due to the applied exercise method, training duration, and the specificity of the physical growth period of the young players. Therefore, it is necessary to increase the frequency and time of proprioceptive exercise training and apply factors for cognitive ability improvement to training programs for young soccer players in future studies. These studies could suggest appropriate training methods necessary to improve the performance of young soccer players., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2024 Korean Society of Exercise Rehabilitation.)

The purpose of this study is to analyze the effects of the combined recovery method of cold water immersion (CWI) and protein supplement intake after eccentric exercise that causes muscle fatigue in elite soccer players. Eleven semiprofessional soccer players participated in this study. Participants were divided into CWI group, combined protein and CWI group (PCWI), and passive resting group (CON). The participants completed the eccentric exercise for one hour and performed one of three recovery methods. The muscle strength of the quadriceps and hamstring muscles significantly decreased at 48-hr postexercise compared to before exercise in all recovery groups ( P <0.05), with no significantly different between the recovery groups. The time required to sprint 40 m was significantly longer in all groups at 24 hr and 48 hr after exercise than before exercise ( P <0.05). The vertical jump height was significantly decreased at 48 hr after exercise compared to before exercise in the CON and CWI groups ( P <0.05). The muscle soreness values were higher at 6 hr, 24 hr, and 48 hr after exercise than before exercise in all groups ( P <0.001). The perceived recovery quality was reduced after exercise in the PCWI ( P <0.01) and CON groups ( P <0.001) compared to before exercise; it was unchanged in the CWI group. The recovery quality decreased at 6 hr, 24 hr, and 48 hr after exercise in all recovery groups ( P <0.01). In conclusion, the combined recovery method was less effective than CWI alone for the recovery of exercise performance., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2023 Korean Society of Exercise Rehabilitation.)

The aim of this study was to analyze the daily physical activity and the relationship between the physical activity levels and psychological variables of Koreans with HIV. Twenty-two people with HIV participated in this study. The participants completed questionnaires, and we assessed the daily physical activity for 2 weeks. The daily physical activity level of most of the participants was low-intensity; high-intensity activities were only performed for approximately 1 minute. The participants had unhealthy dietary habits, such as eating 2 meals a day, eating irregularly, and skipping breakfast. Psychological well-being and environmental satisfaction were higher in the high-intensity group than in the medium- and low-intensity groups (P < .05). The overall stress level among the groups was statistically significantly different (P < .05), and the stress level was lower in the high-intensity group than in the low- and medium-intensity groups. Restraint eating was higher in the low-intensity group than in the medium- and high-intensity groups (P < .05). However, among the groups, the external eating variable was highest in the high-intensity group (P < .05). Daily physical activity during positively affects the physical and mental well-being of people living with HIV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

It is necessary to understand movement characteristics of elite female soccer players during a match to develop effective training program. The purpose of this study is to analyze the physical demands of Korean female professional soccer players during a competitive season. Twenty-four female professional players (age: 27.8±3.9 years; height: 165.7± 5.1 cm) from a team, belonging to the women's professional soccer league in South Korea participated in the study. The players participated in 11 home matches and 10 away matches from April 26 to November 9 of the 2011 season. Body weight and body mass index decreased during the first half-season compared to the preseason ( P <0.05), and the decreased values were maintained until the second half-season. Total distance covered by the players was more than 9.5 km per match. No difference was found in the total distance, movement distance by exercise intensities, number of sprints and accelerations, and maximum speed between the first half- and second half-seasons. Midfielders covered the most distance during a match compared to other positions ( P <0.05). Wing forward covered the most distance of high-intensity exercise. Maximum speed during the match was higher among wing forward and forward than in other positions ( P <0.05). There were no significant differences between home and away matches in all variables ( P >0.05). In conclusion, in order to improve the performance of female soccer players and prevent injuries, a training program should be constructed that considers the characteristics of each player and playing position rather than uniform training in a team., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 Korean Society of Exercise Rehabilitation.)

Exercise training involving exercises of optimal intensity and duration improves psychological and medical variables in relative leisure-deprived people living with HIV/AIDS. This study aimed to analyze associated psychological variables and the effect of exercise intensity and duration on immune responses in relative leisure-deprived people infected with HIV. The participants completed different moderate-intensity exercises (30 min (60−80% HRmax) and 45 min (60−80% HRmax)) and high-intensity exercise for 10 min (>80% HRmax). Levels higher than “normal” were rated for relative leisure deprivation, indicating relative deprivation of leisure among participants. The overall level of quality of life was “normal”, indicating that quality of life was not considered high. The stress level was psychologically considered low. Time had a significant effect on cortisol levels (p < 0.05). Compared to pre-exercise, cortisol level was significantly decreased immediately after moderate exercise for 45 min and 3 h post-exercise after high-intensity exercise for 10 min (p < 0.05). However, time and the interaction of condition and time had no significant effect on IL-6 and sIgA levels (p > 0.05). Despite the small sample size of this pilot study, the results demonstrate that moderate-intensity exercise can be recommended to improve the health and quality of life of people infected with HIV.

The purpose of this study was to analyze the characteristics of injuries in female national soccer players. The injuries data were recorded by Korea Football Association medical staff using the Daily Medical Report provided by the Asian Football Confederation during a total 21 training camps and friendly and official matches from January 2014 to December 2018. A total of 483 players in the national team training camps and matches participated in the study, of which 377 players experienced more than one injury. Sports injuries accounted for 89% of the total 1,019 injuries; general diseases accounted for the remaining 11%. The number of injuries per 1,000 exposure hours was higher in matches than in training sessions. Most injuries that occurred during training and matches involved the lower extremities (79%). The most common injury diagnosed during training and matches was muscle rigidity (45%), followed by contusions/hematomas/bruises (22%) and sprain (15%). The largest proportions of injuries in terms of absence from soccer play were minimal injury (67%), followed by mild (29%), moderate (3.5%), and severe (1%). As conclusion, the characteristics of injuries during training sessions and matches were different. Rehabilitation and injury prevention programs need to developed for female soccer players to improve the players' performance., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 Korean Society of Exercise Rehabilitation.)

Exercise performance is reduced in hot environments due to physiological responses caused by increased body temperature. A proper residential environment is important for improving the performance and maintaining physical condition of soccer players in the summer. The purpose of this study was to determine the effect of indoor temperature of the resting space during the summer on the fitness and condition of soccer players. A total of 12 K-3 League semiprofessional players without serious injuries in the last 3 months voluntarily participated in the study. Participants performed speed (10 m, 20 m, and 30 m), soccer-specific coordination skill (dribbling), agility, repeated sprints, Yo-Yo intermittent level 2, vertical jump, and questionnaire (fatigue, sleep quality, muscle soreness, stress, and mood) after staying indoor temperature at 20°C, 26°C, and 30°C for one night, respectively. There was no difference among groups in physical fitness (speed, agility, jump, coordination, Yo-Yo intermittent level 2, and repeated sprints). The differences in fatigue and sleep quality were not statistically significant among groups, but they tended to be different. Muscle soreness was similar among all groups. Significant differences were observed between the 20°C and 30°C groups in stress and mood levels. The present study concluded that, while the physical fitness did not differ among groups, the 30°C residential environment was shown to have a negative psychological effect. Considering that many diseases associated with hot weather occur in low residential temperatures, a room temperature of 26°C is recommended for elite soccer players in hot summer weather., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Society of Exercise Rehabilitation.)

There may be an optimal period of time to maximize the improvement of physical fitness during adolescence. The aim of this study was to examine the magnitude of changes in physical fitness after 8 weeks of preseason training according to chronological ages after the age at peak high velocity. Thirty male young football players from an elite football team (U-16, n=10; U-17, n=10; U-18, n=10) participated in the study. The players completed an 8-week general preseason football training and participated in the pre- and posttests to measure physical fitness. The 8-week preseason training improved the power of all young players ( P <0.05). The 20-m sprint performance was improved by training in U-16 and U-18 ( P <0.05), but no changes were found in the U-17 group ( P >0.05). Significant differences were found in the arrowhead left in U-16 and U-18 ( P <0.05) after training; however, no difference was observed in U-17 ( P >0.05). Coordination was enhanced further in U-16 and U-17 ( P <0.05) compared with that in U-18 ( P >0.05). The performance of repeated sprints and Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1) were similar between pre- and posttraining in all age groups ( P >0.05). Collectively, the results emphasized the importance of systematic and scientific training methods to improve the fitness levels of young football players in the preseason training period. Moreover, training to improve coordination in young football players is effective at younger ages., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2020 Korean Society of Exercise Rehabilitation.)

As a new class of cancer therapeutic agents, oncolytic viruses (OVs) have gained much attention not only due to their ability to selectively replicate in and lyse tumor cells, but also for their potential to stimulate antitumor immune responses. As a result, there is an increasing need for in vitro modeling systems capable of recapitulating the 3D physiological tumor microenvironment. Here, we investigated the potential of our recently developed microphysiological system (MPS), featuring a vessel-like channel to reflect the in vivo tumor microenvironment and serving as culture spaces for 3D multicellular tumor spheroids (MCTSs). The MCTSs consist of cancer A549 cells, stromal MRC5 cells, endothelial HUVECs, as well as the extracellular matrix. 3D MCTSs residing in the MPS were infected with oncolytic VSV expressing GFP (oVSV-GFP). Post-infection, GFP signal intensity increased only in A549 cells of the MPS. On the other hand, HUVECs were susceptible to virus infection under 2D culture and IFN-β secretion was quite delayed in HUVECs. These results thus demonstrate that OV antitumoral characteristics can be readily monitored in the MPS and that its behavior therein somewhat differs compared to its activity in 2D system. In conclusion, we present the first application of the MPS, an in vitro model that was developed to better reflect in vivo conditions. Its various advantages suggest the 3D MCTS-integrated MPS can serve as a first line monitoring system to validate oncolytic virus efficacy., Competing Interests: The authors declare no competing interests.

Immune reactions are controlled by the delicate spatiotemporal orchestration of multiple cells communicating by cytokines. Studies of cytokines that began with the discovery of IFN focused on positive regulatory mechanisms that induce secretion in response to harmful stimuli. However, there is a growing awareness that negative regulatory mechanisms that stop secretion of cytokines at specific times and spaces are also important for a successful immune reaction. Type I IFN is the primary cytokine in innate immunity. Although its induction is a prerequisite for the consequent adaptive immune reaction, its oversecretion can cause destructive tissue damage. IFN regulatory factor 7 (IRF7) is a master transcription factor of type I IFN, and multiple observations indicate the key role of IRF7 and the importance of its negative regulation. In this study, we found that the inducible heat shock protein 70 (HSP70) regulated the early type I IFN response by using mice knockout for HSP70. HSP70 dampened IRF7 activation; the inhibitory effect of HSP70 over IKKε-mediated IRF7 activation originated from simple competitive binding. This suggests the possibility of blocking the feed-forward loop between IRF7 and type I IFN in stress environments with increased expression of HSP70., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Replicable oncolytic viruses (OVs) induce tumor cell lysis and release viral progeny. The released progeny virions and cell debris can spread within surrounding tumor cells or blood vessels. These released molecules may also induce bystander damage in additional tumor cells through spreading within surrounding tumor cells or blood vessels. However, this effect has not been clearly demonstrated due to the difficulty of direct observation. Here, the bystander infection of OVs by vessel delivery and selective infection in 3D multicellular tumoroids (MCTs) in an in vitro microphysiological system (MPS) with integrated medium flow is demonstrated. This study uses replicable vesicular stomatitis virus (VSV)-green fluorescence protein (GFP) to identify the location of infection in 3D MCTs. Using this MPS, the oncoselective infection by VSV-GFP and the spreading by delivery of OVs through flow via block-to-block linkage of the primary infected MPS with uninfected 3D MCTs in an integrated MPS is observed. This MPS enables real-time monitoring and various analysis for the bystander infection of OVs. It is expected that the 3D in vitro MPS can be suitable to investigate the oncoselective spreading and bystander infection of OVs., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The purpose of this study was to identify the frequency and characteristics of injuries that occurred during the training camps and matches of the national soccer teams (under-20 [U-20], under-23 [U-23], A men's national teams). The research data were based on injuries that occurred from January 2016 to December 2017. The athletic trainer, a member of the Korea Football Association, recorded injuries based on the recording sheet of the Asian Football Confederation Daily Medical Report. A total of 1,689 (984 in 2014; 705 in 2017) injuries were reported for the 2 years. Most injuries were sports injuries (95%, sprains, etc.), and other conditions such as respiratory, digestive, and ocular, comprised only 5% of cases. The most injured areas of the national team players were the lower limbs (85%, 1,366). The frequency of the head/trunk and upper extremity injuries were relatively low (8.4%, 135; 6.5%, 105). The frequency of injuries according to positions were as follows: midfielder (40.3%, 648), defender (36.6%, 688), forward (17.8%, 286), and goalkeeper (5.2%, 84). The most common types of injuries were contusions (37.3%, 599), followed by muscle rigidity (29.0%, 466) and sprains (16.8%, 270). The characteristics of injuries amongst national soccer teams, according to age, were similar, but the injury characteristics for each position were different. Therefore, when organizing training programs for prevention and rehabilitation of athlete injuries and improvement of performance, it is necessary to consider the performance characteristics of each position., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Society of Exercise Rehabilitation.)

Joo, CH and Jee, H. Activity profiles of top-class players and referees and accuracy in foul decision-making during Korean national league soccer games. J Strength Cond Res 33(9): 2530-2540, 2019-The aims of this study were to compare the activity profiles between the top-class referees and players and elucidate the factors related to foul decision-making. Three hundred thirty-five elite-level players and referees were analyzed for distance covered during 20 matches of nationally held 2016 Korean league competitions. Distance covered by the players and referees was analyzed for the activity zones (slow walking, walking, jogging, running, high-intensity running, and sprinting) and 15-minute match periods. Mean distance between foul play and referee locations, foul plays, and 15-minute match periods were compared with the foul decision errors. Foul play and decision error rates (%) were also analyzed per segmented pitch zone. Although the total distance covered during a match and distances covered by jogging, running, and sprinting were significantly different between the players and referees, differences were within 1%. Significant differences in the distance covered before and after halftime were observed. The greatest distance between the foul play and referee locations, number of foul plays, and number of foul decision errors were observed at the 75-minute match period. Finally, the greater number of foul plays was observed in the neutral and attacking zones, and the foul decision errors were observed in the right defensive and left attacking zones 1. In conclusion, although the activity profiles may be different, referees should maintain certain level of physical fitness to match that of the players. To reduce the number of foul decision errors, factors such as match time, foul occurring location, and distance between foul play and referee locations should be considered.

The airway is the major entry route of pathogens due to continuous gas exchange with the environment. In particular, the nasal epithelial layer is the common site of airborne mucotropic virus infections. The inflammatory response to such infections must be tightly controlled due to its non-specific nature. Unrestrained inflammation breaks down the physiological mucosal defense system and leads to secondary bacterial or fungal infections. Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease that compromises quality of life. In spite of its importance in the initiation of inflammation, the role of interferon signaling in nasal airway epithelial cells is largely unknown. We analyzed the expression of interferon signaling genes using clinical lavage specimens and nasal airway epithelial cells collected from CRS patients and controls. Basal expression of IFNAs, IKBKE, STAT1, and some CXC chemokines was elevated in samples from CRS patients. In subsequent in vitro studies, we found IKKε to be the key molecule and augmented CXCL10 secretion. Based on our findings and review of the literature, we hypothesized that high levels of IKKε might induce intractable inflammation via CXCL10. We tested the hypothesis in an animal model and found not only that IKKε induced severe eosinophilic inflammation with CXCL10 over-production, but also that inhibition of IKKε resolved the inflammation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to examine the effects of aerobic high-intensity training with reduced volume and training cessation on body composition and physical fitness after the end of season and the time required to recapture physical fitness with intensified retraining following two weeks of detraining in elite soccer players., Method: Twenty male semi-professional soccer players participated in this study. The soccer players were assigned to either a group that completed high-intensity aerobic training (HAT, n = 10) or to a detraining and retraining group (DHAT, n = 10) for a 5-week period immediately after the end of the season. The first 2 weeks of the period, members of the HAT group performed high-intensity aerobic exercise (80-90% of HRmax, 12 min × 3, three times per week), whereas members of the DHAT group abstained from any physical activity. During the subsequent 3 weeks, members of both the HAT and DHAT groups completed high-intensity aerobic exercise. Exercise performance testing and body composition analysis were performed before; after 2 weeks of detraining; and at 1, 2 and 3 weeks of retraining., Results: Intensified high-intensity training for 5 weeks maintained the performance in the Yo-Yo Intermittent Recovery level 2 test (Yo-Yo IR2) and repeated sprints at any time point (P > 0.05). However 2 weeks of detraining resulted in significant decreases in the performance on the Yo-Yo IR2 (P < 0.01) and repeated sprints test (P < 0.05). Performance on the Yo-Yo IR2 enhanced after 2 weeks of retraining and was maintained up to 3 weeks after retraining, with no significant differences between conditions (P > 0.05). In addition, repeated sprint performance markedly decreased after the detraining period (P < 0.05) and was continuously lower compared to the baseline at 2 weeks after retraining (P < 0.05). Furthermore, this value reached baseline level at the end of the experimental period (P > 0.05). There were no significant differences between conditions in body composition, performance of agility, or sprint ability throughout the 5-week experimental period (P > 0.05)., Conclusions: The present data suggest that short-term detraining after the competitive season can markedly decrease performances in the Yo-Yo IR2 test and repeated sprints. To return to a previous level of ability on the Yo-Yo IR2 and/or sprint test with retraining through high-intensity aerobic training after a period of detraining, a similar or longer period of retraining is required. However, the high-intensity training with reduced amount of training after competitive season can prevent reductions in physical fitness.

The aims of this study were to examine the differences in technical aspects and physical demands between small-size games (SSG; 8 vs. 8) and regular-size games (RSG; 11 vs. 11) in young Korean soccer players. Seventy-nine young soccer players from 6 teams (U-12) volunteered to participate in the study. The players completed 4 games (2 SSG, 62×51 m, and 2 RSG, 80×54 m) in 2 days. Each game was filmed to evaluate technical actions. Physical demand variables were measured using global positioning system technology. SSG showed significantly greater numbers of technical plays among 17 variables when compared to RSG ( P <0.05). The players covered significantly greater total distance during low-, moderate-, and high-speed running and sprinting in SSG than in RSG ( P <0.05). Higher numbers of high-intensity activities (repeated high-intensity efforts, explosive efforts, decelera-tions, accelerations, and sprinting) were observed in SSG compared to RSG ( P <0.05). Mean heart rate was also higher in SSG than in RSG ( P <0.05). Despite the greater physical demands during SSG, the exercise intensity was similar to that reported in previous studies. Therefore, the SSG format applied in the present study can be a suitable official game format for Korean young soccer players, resulting in significantly greater exposure to technical plays without excessive physical demands., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported.

The purpose of this study was to compare performance factors of youth soccer players according to position. A total of 101 high school soccer players were selected and were classified into goalkeeper (n=7), defense (n=37), midfield (n=39), and forward (n=18) positions. All subjects were subjected to the Wingate test for anaerobic capacity, shuttle run test for aerobic capacity, and pass, kick, dribble, and shooting tests for soccer skills. There was no significant difference in aerobic capacity according to position. However, anaerobic capacity was significantly higher in defenders than midfielders ( P <0.05), and soccer skills were significant lower in goalies than in other positions ( P <0.01). The results show significant differences in anaerobic capacity and soccer skills according to position in youth soccer players. Therefore, we suggest that middle and high school soccer players should improve aerobic, an-aerobic capacity, and soccer skills irrespective position to achieve high-level soccer performance.

Purpose: We tested the hypothesis that both post-exercise and passive cold water immersion (CWI) increases PGC-1α and VEGF mRNA expression in human skeletal muscle., Method: Study 1 Nine males completed an intermittent running protocol (8 × 3-min bouts at 90 % [Formula: see text], interspersed with 3-min active recovery (1.5-min at 25 % and 1.5-min at 50 % [Formula: see text]) before undergoing CWI (10 min at 8 °C) or seated rest (CONT) in a counterbalanced, randomised manner. Study 2 Ten males underwent an identical CWI protocol under passive conditions., Results: Study 1 PGC-1α mRNA increased in CONT (~3.4-fold; P < 0.001) and CWI (~5.9-fold; P < 0.001) at 3 h post-exercise with a greater increase observed in CWI (P < 0.001). VEGFtotal mRNA increased after CWI only (~2.4-fold) compared with CONT (~1.1-fold) at 3 h post-exercise (P < 0.01). Study 2 Following CWI, PGC-1α mRNA expression was significantly increased ~1.3-fold (P = 0.001) and 1.4-fold (P = 0.0004) at 3 and 6 h, respectively. Similarly, VEGF165 mRNA was significantly increased in CWI ~1.9-fold (P = 0.03) and 2.2-fold (P = 0.009) at 3 and 6 h post-immersion., Conclusions: Data confirm post-exercise CWI augments the acute exercise-induced expression of PGC-1α mRNA in human skeletal muscle compared to exercise per se. Additionally CWI per se mediates the activation of PGC-1α and VEGF mRNA expression in human skeletal muscle. Cold water may therefore enhance the adaptive response to acute exercise., Competing Interests: Conflicts of Interest: None declared. Funding No funding is declared.

Joo, CH, Hwang-Bo, K, and Jee, H. Technical and physical activities of small-sided games in young Korean soccer players. J Strength Cond Res 30(8): 2164-2173, 2016-The aim of this study was to examine the technical aspects and physical demands during small-sided games (SSGs) with different sized pitches in young Korean soccer players. Participants were randomly selected during a nationally held youth competition. Three different game formats were used: SSG8 (8 vs. 8 played on a small-sized field [68 × 47 m]), RSG8 (8 vs. 8 played on a regular-sized field [75 × 47 m]), and RSG11 (11 vs. 11 played on a regular-sized field). Eleven technical (ball touches, passes, and shots) and 6 physical demand variables (exercise frequency by intensity) were observed and analyzed. Same variables were also analyzed for the goalkeepers. As a result, SSG8 and RSG8 showed significantly greater numbers of technical plays in 5 and 4 variables in comparison to RSG11, respectively. In addition, although the exercise intensities increased slightly in both SSG formats, the amount was within the similar range as previous reports. In conclusion, the SSGs with reduced number of players may be referred in young players to effectively train them in technical aspects of the game by allowing greater ball exposure time without excessive physical demands. Various confounding factors such as pitch dimension should be carefully considered for training specific technical and physical variables in young Korean players.

The aim of the present study was to determine whether 1 week of training cessation can affect exercise performance in well-trained soccer players. Upon the completion of a competitive season, 11 male soccer players went through 1-week training cessation. Performances in the 5-m (1.05±0.04 sec vs 1.02±0.03 sec, P=0.03) and 10-m (1.79±0.06 sec vs 1.74±0.06 sec, P=0.03) sprints were significantly increased after 1 week of detraining with a trend for an increase in the 20-m sprint performance (3.07±0.06 sec vs 3.02±0.07 sec, P=0.06). However, the repeated sprint performance (total sprint time [45.7±2.6 sec vs 48.0±2.6 sec, P=0.01] and fatigue index [5.8%±2.8% vs 7.8%±3.2%; P=0.04]) were reduced. In addition, no significant differences were observed for the 30 m (4.23±0.06 sec vs 4.24±0.09 sec, P=0.63), agility (right: 8.08±0.17 sec vs 8.03±0.37 sec, P=0.54; left: 8.05±0.21 sec vs 8.04±0.30 sec, P=0.84), coordination (13.98±1.21 sec vs 14.06±1.34 sec, P=0.75), Yo-Yo intermittent recovery level 2 (1,040.0±291.8 m vs 1,134.5±232.7 m, P=0.08), and knee extensors and flexors peak torques at all applied angular velocities (P<0.05) after detraining. These results indicate that short-term detraining for well-trained soccer players has a significant effect on the speed endurance performance. It is therefore important for the players and their coaches to plan a suitable training program to maintain exercise performance especially speed endurance during off-season.

Human interferon alpha-2b (IFNα-2b) has therapeutic applications as an antiviral and antiproliferative drug and has been used for a wide range of indications. Efficient production of IFNα-2b in Escherichia coli has been difficult because the protein tends to form inclusion bodies. This obstacle has garnered interest in efficiently expressing IFNα-2b and overcoming its poor solubility. In this study, seven N-terminal fusion partners - hexahistidine (His6), thioredoxin, glutathione S-transferase (GST), maltose-binding protein (MBP), N-utilization substance protein A, protein disulfide bond isomerase (PDI), and b'a' domain of PDI - were tested for soluble overexpression of codon-optimized IFNα-2b in E. coli. Low temperature increased the expression level of all of the tagged proteins except for the GST fusion. All the tags, except for His6 and GST, improved solubility. We purified IFNα-2b from the MBP-tagged fusion using immobilized metal affinity chromatography and anion exchange chromatography, and obtained a final yield of 7.2 mg from an initial 500-ml culture. The endotoxin level was 0.46 EU/µg. Biological activity was demonstrated using a luciferase assay, which showed a dose-dependent response with a calculated EC50 of 10.3 ± 5.9 pM. Our results demonstrate that using an MBP-tagged fusion is an efficient way to produce pure IFNα-2b., (© 2016 S. Karger AG, Basel.)

The aim of the present study was to devise a non-damaging high-intensity intermittent running protocol. Ten healthy active men completed high-intensity interval running (8× 3-min bouts at 90% of maximal oxygen uptake interspersed with 3-min recovery) on a motorized treadmill under normal laboratory temperatures. Mean heart rate and rating of perceived exertion significantly increased during the intermittent protocol (the first bout, 15.3± 1.2; the final bout, 18.6± 0.9; P< 0.001). Blood lactate concentrations were significantly elevated following bout 1 compared with resting values (1.2± 0.3 mmol/L vs 5.4± 2.4 mmol/L; P = 0.03). However, no significant reduction in maximal voluntary contraction was observed immediately after completing the last exercise bout (623.9± 143.6 N) or during the subsequent 7-d period compared to pre-exercise values (P = 0.59). Creatine kinase (CK) concentrations were not significantly increased following exercise or during the subsequent 7-d period (P = 0.96). Myoglobin (Mb) content was significantly increased following exercise (P = 0.01), however, values returned towards pre-exercise concentrations after 24 h. These results indicate that the high-intensity intermittent running protocol induced changes in physiological and subjective indices that are consistent with the effects of acute fatigue as opposed to those changes normally associated with exercise-induced muscle damage. This exercise protocol can therefore be used to investigate the influence of high-intensity exercise from physiological responses to molecular adaptation.

Human rhinovirus (HRV)-A and -B is a common cause of upper respiratory tract infections. Recently, a third species, HRV-C, was categorized based on molecular typing studies. The results showed that the HRV-C genome had diverged from that of HRV-A and -B. Despite its late identification, increasing evidence suggests that HRV-C causes more severe pathogenic infections than HRV-A or -B; however, a large amount of epidemiological data is required to confirm this association in different clinical settings. Consequently, a simple and rapid method for identifying HRV-C is required to expedite such epidemiological studies. Here, two degenerate primer sets (HEV and HRVC) were designed based on bioinformatic analyses. The HEV set targeting the fifth IRES domain sequence within the 5'-UTR, which is highly conserved among enteroviruses, was designed to detect all enteroviruses, whereas the HRVC set, which targeted the VP2 coding region, was designed to detect HRV-C alone. Both primer sets were tested against a panel of standard enteroviruses and clinical lavage samples. HEV detected all enteroviruses tested whereas HRVC was specific for HRV-C. Although the primer design strategy was confirmed with a limited number of samples, extensive tests are required to be applied in clinical settings., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) can be aggravated by viral upper respiratory infections. We aimed to investigate whether any specific human rhinovirus (HRV) serotype is more common in the mucosa of CRS patients, and to find any defining clinical characteristics, according to the various HRV serotypes., Methods: A prospective case-control study was conducted to determine HRV serotypes in 111 CRS patients and 51 non-CRS controls. No participant had a history of upper respiratory infection over a 4-week period. Nasal lavage fluids and turbinate epithelial cells were collected prospectively. When HRV was detected with multiplex polymerase chain reaction (PCR), strains were further characterized by sequencing the VP4/VP2 region of the HRV genome., Results: HRV was detected in 40 CRS subjects (36%) and 11 non-CRS controls (21%). The overall detection rates of HRV in CRS patients were higher than in non-CRS controls (p < 0.05). Of the 8 serotypes detected in CRS patients, 5 belonged to HRV-A and 3 belonged to HRV-B; HRV-C was not detected. In non-CRS controls, only HRV-A was identified, with only 2 serotypes detected (HRV-A13 and HRV-A16). HRV-B and C were not detected., Conclusion: The high prevalence of HRV in CRS patients was confirmed in our study. However, we were unable to determine whether certain HRV serotypes are more predominant in CRS patients than non-CRS controls. HRV-A13 was the most common serotype in both CRS patients and non-CRS controls. We could not find any differences in the clinical characteristics according to the HRV serotypes in CRS patients., (© 2014 ARS-AAOA, LLC.)

The aim of the current study was to quantify oxygen uptake, heart rate and molecular responses of human skeletal muscle associated with mitochondrial biogenesis following an acute bout of simulated soccer training. Muscle biopsies (vastus lateralis) were obtained from nine active men immediately pre-completion, post-completion and 3 h post-completion of a laboratory-based soccer-specific training simulation on a motorised treadmill. The soccer-specific simulation was a similar intensity (55 ± 6% [Formula: see text]) and duration (60 min) as that observed in professional soccer training (e.g. standing 41%, walking 37%, jogging 11%, high-speed running 9% and sprinting 2%). Post-exercise, muscle glycogen decreased (Pre; 397 ± 86 mmol∙kg(-1) dw, Post; 344 ± 64 mmol∙kg(-1) dw; P = 0.03), plasma lactate increased (P < 0.001) up to ~4-5 mmol∙L(-1), non-esterified fatty acids and glycerol increased (P < 0.001) to values of 0.6 ± 0.2 mmol∙L(-1) and 145 ± 54 μmol∙L(-1), respectively. PGC-1α mRNA increased (P = 0.009) fivefold 3 h post-exercise. We provide novel data by demonstrating that soccer-specific training is associated with increases in PGC-1α mRNA. These data may have implications for practitioners in better understanding the metabolic and muscle responses to soccer-specific training protocols in the field.

Unlabelled: Beta interferon (IFN-β) is involved in a wide range of cellular functions, and its secretion must be tightly controlled to inhibit viral spreading while minimizing cellular damage. Intracellular viral replication triggers cellular signaling cascades leading to the activation of the transcription factors NF-κB and interferon regulatory factor 3 (IRF3) and IRF7 (IRF3/7), which synergistically bind to the IFN-β gene promoter to induce its expression. The mitochondrial antiviral signaling protein (MAVS) is a governing adaptor protein that mediates signaling communications between virus-sensing proteins and transcription factors. The activity of MAVS in the regulation of IFN-β secretion is affected by many cellular factors. However, the mechanism of MAVS-mediated IRF3/7 activation is not completely understood. Here, we identified a highly conserved DLAIS motif at amino acid positions 438 to 442 of MAVS that is indispensable for IRF3/7 activation. Specifically, the L439S and A440R mutations suppress IRF3/7 activation. Pulldown experiments using wild-type and mutant MAVS showed that mindbomb E3 ubiquitin protein ligase 2 (MIB2) binds to the DLAIS motif. Furthermore, the DLAIS motif was found to be critical for MIB2 binding, the ligation of K63-linked ubiquitin to TANK-binding kinase 1, and phosphorylation-mediated IRF3/7 activation. Our results suggest that MIB2 plays a putative role in MAVS-mediated interferon signaling., Importance: Mitochondrial antiviral signaling protein (MAVS) mediates signaling from virus-sensing proteins to transcription factors for the induction of beta interferon. However, the mechanism underlying activation of MAVS-mediated interferon regulatory factors 3 and 7 (IRF3/7) is not completely understood. We found a highly conserved DLAIS motif in MAVS that is indispensable for IRF3/7 activation through TANK-binding kinase 1 (TBK1) and identified it as the binding site for mindbomb E3 ubiquitin protein ligase 2 (MIB2). The mutations that targeted the DLAIS motif abolished MIB2 binding, attenuated the K63-linked ubiquitination of TBK1, and decreased the phosphorylation-mediated activation of IRF3/7., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

IFN regulatory factor 7 (IRF7) is a major regulator of type I (αβ) IFN secretion. A growing body of evidence shows that IRF7 is involved in a wide variety of pathologic conditions in addition to infections; however, the detailed mechanism of IRF7 transactivation remains elusive. Our current knowledge of IRF7 transactivation is based on studies of IRF3, another major regulator of IFN-β secretion. IRF3 and IRF7 are closely related homologs with high sequence similarity in their C-terminal regions, and both proteins are activated by phosphorylation of a specific serine cluster (SC). Nevertheless, the functional domains of the two proteins are arranged in an inverted manner. We generated a model structure of the IRF7 C-terminal region using homology modeling and used it to guide subsequent functional domain studies. The model structure led to the identification of a tripod-helix structure containing the SC. Based on the model and experimental data, we hypothesized that phosphorylation-mediated IRF7 transactivation is controlled by a tripod-helix structure. Inducible IκB kinase binds a tripod-helix structure. Serial phosphorylation of the SC by the kinase liberates C-terminal helix from an inhibitory hydrophobic pocket. A histone acetyltransferase P300 binds the liberated helix. The difference in the P300 binding sites explains why the domain arrangement of IRF7 is inverted relative to that of IRF3., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Hepatitis C virus (HCV) affects 2-3% of the global population. Approximately one-quarter of acute infections cause chronic hepatitis that leads to liver cirrhosis or hepatocellular carcinoma. The major obstacle of current research is the extremely narrow host tropism of HCV. A single HCV strain can replicate in the Huh7 human hepatoma cell line. Huh7 cells can be adapted under selective pressure in vitro to identify host factors that influence viral replication. Here, we extended this strategy to the in vivo condition and generated a series of cell lines by multiple rounds of adaptation in immunocompromised mice. Adaptation increased the cellular resistance to HCV infection. Microarray analyses revealed that the expression levels of several genes were associated with HCV resistance. Notably, up-regulation of the mRNA encoding cysteine-rich secretory protein 3 (CRISP3), a glycoprotein with unknown function that is secreted from multiple exocrine glands, was correlated with HCV resistance. The presence of CRISP3 in the culture medium limited HCV replication at the early phase of infection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: This study aimed to determine the influence of cold (8°C) and cool (22°C) water immersion on femoral artery and cutaneous blood flow after exercise., Methods: Twelve men completed a continuous cycle exercise protocol at 70% peak oxygen uptake until a core temperature of 38°C was attained. Subjects were then immersed semireclined into 8°C or 22°C water to the iliac crest for 10 min or rested. Rectal and thigh skin temperature, deep and superficial muscle temperature, thigh and calf skin blood flow (laser Doppler flowmetry), and superficial femoral artery blood flow (duplex ultrasound) were measured before and up to 30 min after immersion. Indices of vascular conductance were calculated (flux and blood flow/mean arterial pressure)., Results: Reductions in rectal temperature were similar (0.6°C-0.7°C) in all three trials (P = 0.38). The mean ± SD thigh skin temperature during recovery was 25.4°C ± 3.8°C in the 8°C trial, which was lower than the 28.2°C ± 1.4°C and 33.78°C ± 1.0°C in the 22°C and control trials, respectively (P < 0.001). Recovery muscle temperature was also lowest in the 8°C trial (P < 0.01). Femoral artery conductance was similar after immersion in both cooling conditions and was lower (∼55%) compared with the control condition 30 min after immersion (P < 0.01). Similarly, there was greater thigh (P < 0.01) and calf (P < 0.05) cutaneous vasoconstriction during and after immersion in both cooling conditions relative to the control condition., Conclusion: Colder water temperatures may be more effective in the treatment of exercise-induced muscle damage and injury rehabilitation by virtue of greater reductions in muscle temperature and not muscle blood flow.

Natural killer (NK) cells are multicompetent lymphocytes of the innate immune system that play a central role in host defense and immune regulation. Although increasing evidence suggests that innate immunity plays a key role in the pathogenesis of chronic rhinosinusitis (CRS), the role of NK cells in CRS has been poorly studied. This study aimed to characterize the peripheral blood NK cells from patients with CRS, and to compare the functions of these cells with those from non-CRS controls. The correlation between NK cell functional activity and prognosis was also assessed. Eighteen CRS patients and 19 healthy non-CRS controls were included. The patients with CRS were classified into two subgroups, namely a treatment-responsive group and recalcitrant group. NK cell degranulation was determined by measuring the cell surface expression of CD107a against 721.221 and K562 cells. Intracytoplasmic cytokine production was determined by flow cytometry. Compared to the controls, the NK cells of CRS group had an impaired ability to degranulate and to produce cytokines such as IFN-γ and TNF-α. The recalcitrant subgroup showed the most severe defects in NK cell effector functions. Moreover, the decreased NK cell functions in patients with CRS were associated with poor prognostic factors such as concomitant asthma and peripheral blood eosinophilia. NK cells, which were originally named for their ability to mediate spontaneous cytotoxicity towards diseased cells including infected cells, may play an important role in regulating the inflammatory process in CRS pathogenesis.

We report a case of hemodynamic instability after aortic valve replacement, due to the anomalous origin of the right coronary artery. During the cardiopulmonary bypass weaning process, hemodynamic instability occurred. The cause was not identified at first, and compression of the anomalous right coronary artery was thought to be the culprit, thereafter.

Purpose: The aim of this study was to test the hypothesis that postexercise cold-water immersion (CWI, via its associated reductions in skeletal muscle blood flow) attenuates muscle glycogen resynthesis during short-term recovery from exhaustive exercise., Methods: In a repeated-measures design, nine recreationally active men performed an exhaustive glycogen depleting cycling protocol (consisting of intermittent exercise the night before and steady-state exercise on the subsequent morning of the main trial) followed by 10 min of lower-limb CWI (8°C) or remained seated in normal ambient conditions (CONT). Subjects were fed carbohydrate (CHO) at an ingestion rate of 0.6 g·kg body mass at 30 min postexercise and at 1, 2, and 3 h postexercise., Results: Reductions in thigh skin temperature and muscle temperature during postexercise recovery were greater in CWI compared with CONT (P < 0.01). In addition, norepinephrine and blood glucose concentrations were increased and decreased, respectively, during recovery in CWI compared with CONT (P < 0.01). Postexercise muscle glycogen (CONT and CWI postexercise = 76 ± 43 and 77 ± 26 mmol·kg dry weight [dw], respectively; mean ± SD) progressively increased (P < 0.01) during recovery, although rates of resynthesis did not differ (P = 0.719) between conditions (CONT and CWI 4 h postexercise = 160 ± 34 and 157 ± 59 mmol·kg dw, respectively). Total glycogen synthesis during recovery was comparable (CONT and CWI = 83 ± 43 and 79 ± 58 mmol·kg dw, respectively)., Conclusions: Postexercise CWI does not attenuate muscle glycogen resynthesis rates during short-term recovery even when CHO availability is considered suboptimal. Athletes who regularly incorporate CWI as a recovery strategy to alleviate symptoms of exercise-induced muscle damage should therefore not be concerned with potential negative effects of the associated reductions in muscle blood flow on the restoration of muscle glycogen stores.

The current study aims to verify the existing equations for incipient motion for a rigid rectangular channel. Data from experimental work on incipient motion from a rectangular flume with two different widths, namely 0.3 and 0.6 m, were compared with the critical velocity value predicted by the equations of Novak & Nalluri and El-Zaemey. The equation by El-Zaemey performed better with an average discrepancy ratio value of 1.06 compared with the equation by Novak & Nalluri with an average discrepancy ratio value of 0.87. However, as the sediment deposit thickness increased, the equation by El-Zaemey became less accurate. A plot on the Shields Diagram using the experimental data had shown the significant effect of the sediment deposit thickness where, as the deposit becomes thicker, the dimensionless shear stress θ value also increased. A new equation had been proposed by incorporating the sediment deposit thickness. The new equation gave improved prediction with an average discrepancy ratio value of 1.02.

Acetaminophen is one of the most popular and widely used analgesics for the treatment of pain and fever but few studies have evaluated its effects on neuropathic pain. This study examined the effect of acetaminophen on thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain. Male Sprague-Dawley rats were prepared by tightly ligating the left L5 and L6 spinal nerves to produce a model of neuropathic pain. Sixty neuropathic rats were assigned randomly into six groups. Normal saline and acetaminophen (25, 50, 100, 200 and 300 mg/kg) were administered intraperitoneally to these individual groups. Thermal hyperalgesia, mechanical and cold allodynia were examined at preadministration and at 15, 30, 60, 90, 120, 180, 240 and 360 min after administering the drug. Mechanical allodynia was quantified by measuring the paw withdrawal threshold to stimuli with von Frey filaments. Cold allodynia was quantified by measuring the frequency of foot lift after applying 100% acetone. Thermal hyperalgesia was quantified by measuring the thermal withdrawal threshold. The rotarod performance was measured to detect any drug-induced adverse effects, such as drowsiness. The hepatic and renal adverse effect was also assessed by measuring the serum levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine. The paw withdrawal thresholds to mechanical stimuli and the thermal withdrawal threshold were increased significantly and withdrawal frequencies to cold stimuli were reduced by acetaminophen administration in a dose-dependent manner. Acetaminophen reduces thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain, and might be useful for managing neuropathic pain., (Copyright © 2012. Published by Elsevier B.V.)

We investigated whether Korean red ginseng (KRG) and highly active antiretroviral therapy (HAART) affect the frequency of gross deletion in 5'LTR/gag in 20 hemophiliacs. This study is a prospective study in 20 hemophiliacs who were infected with Korean subclade B of HIV-1 from two cash-paid plasma donors in 1990. Over a 13-year period, we obtained 436 amplicons of 5'LTR/gag genes by nested polymerase chain reaction using 147 peripheral blood mononuclear cells. Of the 436 amplicons, 92 (21.1%) showed gross deletion in 5'LTR/gag. Despite of a 2.3-fold higher monthly dose of KRG intake, the frequency of gross deletion in 5'LTR/gag (16.4%) was significantly decreased during HAART compared with 28.1% prior to HAART (p<0.01). Gross deletion in 5'LTR/gag was 10% more detected on KRG-therapy than prior to KRG-therapy (p<0.05). In addition, we also obtained 28 amplicons containing premature stop codon or isoleucine at initiation codon of 254 amplicons sequenced on KRG intake (7.5%) or HAART (13.6%) compared with 0% before KRG intake. These findings indicate that high frequency of gross deletion in 5'LTR/gag and genetic defects prior to HAART are significantly associated with KRG intake and the detection of gross deletion in 5'LTR/gag is decreased by HAART.

Many viruses, including hepatitis C virus (HCV), are major threats to public health, but few treatment options are available. Systemic administration of a combination of interferon-a and ribavirin is the only approved treatment for HCV. However, half of all patients are not cured by such treatment and a wide spectrum of systemic side-effects limits its effectiveness. I developed a gene therapy approach with three goals: 1) the restoration of local interferon secretion in cells infected with HCV, 2) no secretion of interferon in normal cells not infected with the virus, and 3) suppression of the emergence of resistant viral strains. A recombinant transcription factor was constructed, the intracellular localization of which is controlled by a viral protease to stimulate focal interferon secretion at sites of infection. A recombinant adenovirus associated virus expressing the transcription factor based on the described strategy inhibited HCV replication effectively in a HCV in vitro culture system.

The hepatitis C virus (HCV) is a continuing threat to public health. The systemic administration of interferon alpha with ribavirin is the only currently approved treatment. However, this treatment is associated with a wide spectrum of systemic side effects that limits its effectiveness; thus, there is an urgent need for new treatment modalities. In this study, we describe a novel anti-HCV strategy employing a recombinant transcription factor that we have engineered in such a way that NS3/4a viral protease controls its intracellular localization, thereby restoring interferon secretion specifically in cells infected with HCV. Proof-of-concept experiments validated the strategy, showing that the recombinant transcription factor was triggered to stimulate interferon promoter by NS3/4A and remained inactive in cells without NS3/4a. Using an adenovirus-associated viral vector delivery system, we found that the recombinant transcription factor inhibited HCV replication effectively in vitro in cultured cells.

A major concern of antiviral therapy using small interfering RNAs (siRNAs) targeting RNA viral genome is high sequence diversity and mutation rate due to genetic instability. To overcome this problem, it is indispensable to design siRNAs targeting highly conserved regions. We thus designed CAPSID (Convenient Application Program for siRNA Design), a novel bioinformatics program to identify siRNAs targeting highly conserved regions within RNA viral genomes. From a set of input RNAs of diverse sequences, CAPSID rapidly searches conserved patterns and suggests highly potent siRNA candidates in a hierarchical manner. To validate the usefulness of this novel program, we investigated the antiviral potency of universal siRNA for various Human enterovirus B (HEB) serotypes. Assessment of antiviral efficacy using Hela cells, clearly demonstrates that HEB-specific siRNAs exhibit protective effects against all HEBs examined. These findings strongly indicate that CAPSID can be applied to select universal antiviral siRNAs against highly divergent viral genomes.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were analyzed in freshwater fish (crucian carp) taken from 16 locations in nine rivers and a wetland in Korea, during 2000-2004. Dioxin-like polychlorinated biphenyls (DL-PCBs) were also analyzed in the same samples but over shorter period (2002-2004). Concentrations on a wet weight basis for 3 years (2002-2004) ranged from below the detection limit (DL) to 0.36 pg TEQ g(-1) wet wt. for PCDDs, below the DL to 2.0 for PCDFs, and from 0.02 to 1.9 for DL-PCBs, with a mean of 0.07, 0.33 and 0.83 pg TEQ g(-1) wet wt., respectively. The proportions of PCDDs, PCDFs and DL-PCBs in the total dioxin TEQ for 2002-2004 were 7%, 26% and 67%, respectively. While the temporal trend showed a significant decrease in PCDDs/DFs concentrations over the 5-year study period, DL-PCBs did not show significant change in concentration over the 3-year period. The results suggest that DL-PCBs concentrations should be determined when total dioxin TEQ is analyzed in freshwater fish.

Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway, which is mediated by IFN regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Despite its association with significant human health problems, activities of Epstein-Barr virus (EBV), a human tumor-inducing herpesvirus, to evade host IFN-mediated innate immunity have not been well characterized. To search for EBV genes that block IFN signal transduction, we carried out a screening of EBV open reading frames for their abilities to block IFN-alpha/beta-mediated luciferase expression upon Sendai virus infection. This screening demonstrates that EBV LF2 tegument protein specifically interacts with the central inhibitory association domain of IRF7, and this interaction leads to inhibition of the dimerization of IRF7, which suppresses IFN-alpha production and IFN-mediated immunity. This demonstrates a novel immune evasion mechanism of EBV LF2 in blocking cellular IRF7-mediated innate immunity.

Coxsackievirus A24 (CVA24) is responsible for acute hemorrhagic conjunctivitis, a highly contagious eye disease for which no prevention or treatment is currently available. We thus assessed the antiviral potential of a small interfering RNA (siRNA) targeting CVA24. HeLa cells with or without four different siRNAs complementary to 2C or 3D genome region, were challenged with various CVA24s. Among several siRNAs, a siRNA targeting the highly conserved genome region called the cis-acting replication element (CVA24-CRE), was the only siRNA that decreased virus replication and subsequent cytotoxicity by both CVA24 variant and clinical isolates. Furthermore, CVA24-CRE had effective antiviral activity against CVA24 in primary human conjunctival cells. In addition, CVA24-CRE was highly resistant to the emergence of genetically altered escape mutants. Collectively, the present study provides evidence that CVA24-CRE targeting a conserved viral genome region had universal, prolonged anti-CVA24 activity. This siRNA may thus hold a potential to act clinically as a novel anti-CVA24 agent.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent associated with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Hypoxia-inducible factor-1 (HIF-1) is the master regulator of both developmental and pathologic angiogenesis, composed of an oxygen-sensitive alpha-subunit and a constitutively expressed beta-subunit. HIF-1 activity in tumors depends on the availability of the HIF-1 alpha subunit, the levels of which are increased under hypoxic conditions. Recent studies have shown that HIF-1 plays an important role in KSHV reactivation from latency and pathogenesis. Here, we report a novel mechanism by which KSHV activates HIF-1 activity. Specific interaction between KSHV viral IFN regulatory factor 3 (vIRF3) and the HIF-1 alpha subunit led to the HIF-1 alpha stabilization and transcriptional activation, which induced vascular endothelial growth factor expression and ultimately facilitated endothelial tube formation. Remarkably, the central domain of vIRF3, containing double alpha-helix motifs, was sufficient not only for binding to HIF-1 alpha but also for blocking its degradation in normoxic conditions. This indicates that KSHV has developed a unique mechanism to enhance HIF-1 alpha protein stability and transcriptional activity by incorporating a viral homologue of cellular IRF gene into its genome, which may contribute to viral pathogenesis.

Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway that is mediated by IFN regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate the host IFN-mediated immune response. Kaposi's sarcoma-associated herpesvirus (KSHV), a human tumor-inducing herpesvirus, has developed a unique mechanism for antagonizing cellular IFN-mediated antiviral activity by incorporating viral homologs of the cellular IRFs, called vIRFs. Here, we report a novel immune evasion mechanism of KSHV vIRF3 to block cellular IRF7-mediated innate immunity in response to viral infection. KSHV vIRF3 specifically interacts with either the DNA binding domain or the central IRF association domain of IRF7, and this interaction leads to the inhibition of IRF7 DNA binding activity and, therefore, suppression of alpha interferon (IFN-alpha) production and IFN-mediated immunity. Remarkably, the central 40 amino acids of vIRF3, containing the double alpha helix motifs, are sufficient not only for binding to IRF7, but also for inhibiting IRF7 DNA binding activity. Consequently, the expression of the double alpha helix motif-containing peptide effectively suppresses IRF7-mediated IFN-alpha production. This demonstrates a remarkably efficient means of viral avoidance of host antiviral activity.

The promising potential of RNA interference-based antiviral therapies has been well established. However, the antiviral efficacy is largely limited by genomic diversity and genetic instability of various viruses, including human enterovirus B (HEB). In this work, the first evidence supporting the anti-HEB activity of the small interfering RNA (siRNA) targeting the highly conserved cis-acting replication element (CRE) within virus coding region 2C is presented. HeLa cells pre-treated with siRNA complementary to the conserved sequence of the loop region of CRE(2C) were effectively rescued from the cytopathic effects of HEBs. Downregulation of virus replication and attenuation of cytotoxicity were consistently observed in various reference strains and clinical isolates. Cells treated with this siRNA were resistant to the emergence of viable escape mutants and showed sustained antiviral ability. Collectively, the data suggest that the siRNA based on the disordered structure within the highly conserved cis-acting coding region has potential as a universal, persistent anti-HEB agent. The same strategy can be successfully applied to the development of siRNA with consistent antiviral effects in other virus groups possessing similar RNA elements.