Polyporus ulleungus mycelia cultured in MEB medium produce metabolites with anticancer property.

Cancer cells are characterized by apoptosis evasion and uncontrolled cell cycle progression. To combat these characteristics, efforts have been made to find novel natural-source anticancer compounds. The aim of this work is to find new anticancer compounds in Polyporus ulleungus (P. ulleungus) mycelial culture extracts. P. ulleungus mycelium was cultured on four individual media (DYB, MEB, MYB, and PDB) and four extracts were generated from the mycelium culture media. Extracts of P. ulleungus mycelium cultured in MEB medium (pu-MEB) significantly reduced cancer cell growth by triggering apoptosis and S phase arrest. Furthermore, the anticancer effects of pu-MEB were not confined to one type of cancer. Taken together, our results confirmed that P. ulleungus mycelia cultured in MEB medium produce metabolites that exhibit anticancer properties. Development of an optimal medium for P. ulleungus mycelium through optimization of medium components will enable P. ulleungus mycelium to produce metabolites with more anticancer efficacy.

Comparative Analysis of Anticancer and Antibacterial Activities among Seven Trametes Species.

Species in the genus Trametes (Basidiomycota, Polyporales) have been used in natural medicine for a long time. Many studies reported that mycelia or fruiting bodies of Trametes spp. exhibited effects of antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. However, comparative analysis in this genus is scarce due to limitation of morphological identification and the sample number. In this study, the 19 strains of seven Trametes species were chosen to generate a five-gene-based phylogeny with the 31 global references. In addition, 39 culture extracts were prepared for 13 strains to test for anticancer and antibacterial activities. Strong anticancer activities were found in several extracts from T. hirsuta and T. suaveolens. Anticancer activities of T. suaveolens, T. cf. junipericola and T. trogii were first described here. The antibacterial ability of T. versicolor and T. hirsuta extracts has been confirmed. The antibacterial activities of T. suaveolens have been reported at the first time in this study. These results suggest an efficient application of the genus Trametes as the drug resources especially for anticancer agents.

Chemical screening identifies the anticancer properties of Polyporous tuberaster.

Most conventional anticancer drugs cause resistance to chemotherapy, which has emerged as one of the major obstacles to cancer treatment. In order to address this issue, efforts have been made to select new anticancer compounds from natural sources. The aim of this study is to identify novel anticancer compounds from mycelial culture extracts belonging to Polyporus tuberaster (P. tuberaster). Here, we found that mycelial culture extracts of P. tuberaster cultured in PDB medium (pt-PDB) effectively inhibited cancer cell growth. pt-PDB reduced the growth of cancer cells through apoptosis induction and S-phase arrest. The anticancer efficacy of pt-PDB was not to limited to one type of cancer. Furthermore, unlike traditional anticancer medications, pt-PDB did not increase the proportion of side population (SP) cells, which plays a key role in the development of chemoresistance. Taken together, we discovered a novel anticancer drug candidate that has anticancer properties without increasing the proportion of SP cells. This new drug candidate can be used for the treatment of cancer, especially chemoresistant malignancies, and will provide a breakthrough in the treatment of chemoresistant cancer.

Chemical screening identifies the anticancer properties of Polyporous parvovarius.

One of the biggest obstacles in cancer treatment is the development of chemoresistance. To overcome this, attempts have been made to screen novel anticancer substances derived from natural products. The purpose of this study is to find new anticancer candidates in the mycelium culture extract of mushrooms belonging to Polyporus. Here, we used a high-throughput screening to find agents capable of inhibiting cancer cell proliferation. The culture extract of Polyporus Parvovarius mycelium in DY medium (pp-DY) was effective. pp-DY inhibited cancer cell proliferation by inducing apoptosis and S-phase arrest. The anticancer property of pp-DY was not only effective against one type of cancer, but also against another type of cancer. Compound fractionation was performed, and the active ingredient exhibiting anticancer effects in pp-DY was identified as 3,4-dihydroxybenzaldehyde (Protocatechualdehyde, PCA). PCA, like pp-DY, inhibited the proliferation of cancer cells by inducing apoptosis and S-phase arrest. Furthermore, unlike conventional anticancer drugs, PCA did not increase the proportion of the side population that plays the most important role in the development of chemoresistance. Taken together, our data revealed the novel mycelium culture extract that exhibited anticancer property, and identified active ingredients that did not activate a proportion of the side population. These novel findings may have clinical applications in the treatment of cancer, particularly chemo-resistant cancer.

Corrigendum to "Physical activity in the era of climate change and COVID-19 pandemic: Results from the South Korea's 2022 Report Card on physical activity for children and adolescents" [J Exercise Sci Fitness 21(1) (2023) 26-33].

[This corrects the article DOI: 10.1016/j.jesf.2022.10.014.].

Physical activity in the era of climate change and COVID-19 pandemic: Results from the South Korea's 2022 Report Card on physical activity for children and adolescents.

Background: With intensifying air pollutant levels and the COVID-19 pandemic, physical inactivity of South Korean children and adolescents may be threatened. Therefore, monitoring and surveillance of physical activity (PA) and relevant indicators are important for policy making pertaining to health promotion. Report Card is a third comprehensive evaluation of PA-related behaviors among and the sources of influence for South Korean children and adolescents. Purpose: To provide the outcome of the South Korea's 2022 Report Card on PA for children and adolescents. Methods: Based on a variety of sources including national surveys collected pre- and during-COVID-19 and information collected from government webpages, 11 indicators were graded by a committee of experts informed by the best available evidence. Data from during-COVID-19 were available for Overall PA, Sedentary Behavior, and Sleep and considered together in generating the overall grades. Results: Grades were assigned to behavioral indicators (Overall PA: D-; Active Transportation: B+; Sedentary Behavior: D; Sleep: F) and sources of Influence (Family and Peers: C-; School: A; Community and Environment: B-; Government: A). Organized Sport and PA, Active Play, and Physical Fitness could not be graded due to the lack of data. The results largely indicated that children and adolescents show unfavorable behavioral grades even with favorable grades observed for the sources of influence indicators. Trivial differences were observed pre- and during-pandemic for Overall PA (≥60 min of MVPA for ≥4 d/wk: 20.8% vs 19.9%) and Sleep (met age-specific recommendation: 14.1% vs 15.0%); however, a marked increase in Sedentary Behavior was observed (≤2 h/d screen time: 28.8% vs 20.1%). A stark weekday vs weekend difference was observed in sleep duration. In terms of PA related sources of influence, high accessibility to PA facilities (81.1%) and high satisfaction of neighborhood public transit (74.6%) and safety (80.7%) were well reflected in our Active Transportation grade (B+). Nonetheless, perception of green environments including outdoor air quality (44.0%), noise (39.6%) and green space (56.5%) showed lower scores, suggesting that new barriers to active lifestyles are emerging for South Korean children and adolescents. Gender differences were also observed for overall PA (≥60 min of MVPA for ≥4 d/wk: 29.1% for boys vs 11.3% for girls) and sleep (met age-specific recommendations: 17.3% for boys vs 11.4% for girls), but not for sedentary behavior (≤2 h/d screen time: 26.4% for boys and 24.9% for girls). Conclusions: Government and school policies/programs and the built environment are, in general, conducive to physically active lifestyles for South Korean children and adolescents; however, behavioural indicators received poor grades except for Active Transportation. A thorough evaluation of policies/programs at government, local, and school levels is needed to ensure that the efforts to have PA-enhancing infrastructure and systems are actually being translated into the behavior of children and adolescents in South Korea. Furthermore, improving PA surveillance, monitoring, and advocacy to ultimately establish healthy lifestyle patterns among children and adolescents is a top priority.

Behcet disease: an undifferentiating and complex vasculitis.

Behçet Disease is a relapsing and remitting variable vessel vasculitis characterized by recurrent mucocutaneous ulcers that can involve almost every organ system in the body. Indeed, the presence of recurrent oral or genital ulcers with other auto-inflammatory symptoms should raise suspicion for this elusive disease. It is unique among the vasculitides in that it can affect vessels of small, medium, and large size and tends to involve venous rather than arterial circulation, and its effects on the pulmonary venous circulation are particularly notable for their role in disease mortality. Classically seen in Mediterranean, Middle-Eastern, and eastern Asian countries, and relatively rare in the United States, prevalence has been increasing, prompting an increased need for internists to be aware of Behcet's clinical presentation and treatment. As early recognition and diagnosis of the disease is key to successful treatment and better prognosis, this review provides a brief summary of the current etiological theories, important clinical manifestations, and treatments including newer biologic alternatives.

Transcriptome expression profile of compound-K-enriched red ginseng extract (DDK-401) in Korean volunteers and its apoptotic properties.

Ginseng and ginsenosides have been reported to have various pharmacological effects, but their efficacies depend on intestinal absorption. Compound K (CK) is gaining prominence for its biological and pharmaceutical properties. In this study, CK-enriched fermented red ginseng extract (DDK-401) was prepared by enzymatic reactions. To examine its pharmacokinetics, a randomized, single-dose, two-sequence, crossover study was performed with eleven healthy Korean male and female volunteers. The volunteers were assigned to take a single oral dose of one of two extracts, DDK-401 or common red ginseng extract (DDK-204), during the initial period. After a 7-day washout, they received the other extract. The pharmacokinetics of DDK-401 showed that its maximum plasma concentration (Cmax) occurred at 184.8 ± 39.64 ng/mL, Tmax was at 2.4 h, and AUC0-12h was 920.3 ± 194.70 ng h/mL, which were all better than those of DDK-204. The maximum CK absorption in the female volunteers was higher than that in the male volunteers. The differentially expressed genes from the male and female groups were subjected to a KEGG pathway analysis, which showed results in the cell death pathway, such as apoptosis and necroptosis. In cytotoxicity tests, DDK-401 and DDK-204 were not particularly toxic to normal (HaCaT) cells, but at a concentration of 250 µg/mL, DDK-401 had a much higher toxicity to human lung cancer (A549) cells than DDK-204. DDK-401 also showed a stronger antioxidant capacity than DDK-204 in both the DPPH and potassium ferricyanide reducing power assays. DDK-401 reduced the reactive oxygen species production in HaCaT cells with induced oxidative stress and led to apoptosis in the A549 cells. In the mRNA sequence analysis, a signaling pathway with selected marker genes was assessed by RT-PCR. In the HaCaT cells, DDK-401 and DDK-204 did not regulate FOXO3, TLR4, MMP-9, or p38 expression; however, in the A549 cells, DDK-401 downregulated the expressions of MMP9 and TLR4 as well as upregulated the expressions of the p38 and caspase-8 genes compared to DDK-204. These results suggest that DDK-401 could act as a molecular switch for these two cellular processes in response to cell damage signaling and that it could be a potential candidate for further evaluations in health promotion studies.

Effects of Self-acupunctural Hand Massage Using Aromatic Oil on Alleviating the Stress, Fatigue, and Vital Signs of Korean Middle-Aged Women.

The study aimed to examine the effects of self-acupunctural hand massage using aromatic oil on the stress, fatigue, and vital signs of Korean middle-aged women. A quasi-experimental study using a pretest/posttest control group, nonsynchronized design was employed. The study participants consisted of 55 middle-aged women (27 in the experiment group and 28 in the control group), who visited a community center in Seoul, South Korea. Self-acupunctural hand massage using aromatic oil as an experimental intervention was performed once per day, 6 minutes per session for the left and right hands each, for 3 weeks. A questionnaire was designed to measure the general characteristics, stress, fatigue, and vital signs (blood pressure and pulse rate). There were significant differences in the degrees of stress, fatigue, and vital signs (blood pressure) between the 2 groups. Self-acupunctural hand massage using aromatic oil decreased the stress, fatigue, and vital signs (blood pressure) of Korean middle-aged women. Self-acupunctural hand massage using aromatic oil can be utilized as an effective nursing intervention for decreasing stress, fatigue, and vital signs (blood pressure) for middle-aged women in clinical practice.

The Effect of Athletes' Probiotic Intake May Depend on Protein and Dietary Fiber Intake.

Studies investigating exercise-induced gut microbiota have reported that people who exercise regularly have a healthy gut microbial environment compared with sedentary individuals. In contrast, recent studies have shown that high protein intake without dietary fiber not only offsets the positive effect of exercise on gut microbiota but also significantly lowers the relative abundance of beneficial bacteria. In this study, to resolve this conundrum and find the root cause, we decided to narrow down subjects according to diet. Almost all of the studies had subjects on an ad libitum diet, however, we wanted subjects on a simplified diet. Bodybuilders who consumed an extremely high-protein/low-carbohydrate diet were randomly assigned to a probiotics intake group (n = 8) and a placebo group (n = 7) to find the intervention effect. Probiotics, comprising Lactobacillus acidophilus, L. casei, L. helveticus, and Bifidobacterium bifidum, were consumed for 60 days. As a result, supplement intake did not lead to a positive effect on the gut microbial environment or concentration of short-chain fatty acids (SCFAs). It has been shown that probiotic intake is not as effective as ergogenic aids for athletes such as bodybuilders with extreme dietary regimens, especially protein and dietary fiber. To clarify the influence of nutrition-related factors that affect the gut microbial environment, we divided the bodybuilders (n = 28) into groups according to their protein and dietary fiber intake and compared their gut microbial environment with that of sedentary male subjects (n = 15). Based on sedentary Korean recommended dietary allowance (KRDA), the bodybuilders' intake of protein and dietary fiber was categorized into low, proper, and excessive groups, as follows: high-protein/restricted dietary fiber (n = 12), high-protein/adequate dietary fiber (n = 10), or adequate protein/restricted dietary fiber (n = 6). We found no significant differences in gut microbial diversity or beneficial bacteria between the high-protein/restricted dietary fiber and the healthy sedentary groups. However, when either protein or dietary fiber intake met the KRDA, gut microbial diversity and the relative abundance of beneficial bacteria showed significant differences to those of healthy sedentary subjects. These results suggest that the positive effect of exercise on gut microbiota is dependent on protein and dietary fiber intake. The results also suggest that the question of adequate nutrition should be addressed before supplementation with probiotics to derive complete benefits from the intervention.

The combination of sport and sport-specific diet is associated with characteristics of gut microbiota: an observational study.

BACKGROUND: Recently, gut microbiota have been studied extensively for health promotion, disease prevention, disease treatment, and exercise performance. It is recommended that athletes avoid dietary fiber and resistant starch to promote gastric emptying and reduce gastrointestinal distress during exercise, but this diet may reduce microbial diversity and compromise the health of the athlete's gut microbiota. OBJECTIVE: This study compared fecal microbiota characteristics using high-throughput sequencing among healthy sedentary men (as controls), bodybuilders, and distance runners, as well as the relationships between microbiota characteristics, body composition, and nutritional status. METHODS: Body composition was measured using DXA, and physical activity level was assessed using IPAQ. Dietary intake was analyzed with the computerized nutritional evaluation program. The DNA of fecal samples was extracted and it was sequenced for the analysis of gut microbial diversity through bioinformatics cloud platform. RESULTS: We showed that exercise type was associated with athlete diet patterns (bodybuilders: high protein, high fat, low carbohydrate, and low dietary fiber diet; distance runners: low carbohydrate and low dietary fiber diet). However, athlete type did not differ in regard to gut microbiota alpha and beta diversity. Athlete type was significantly associated with the relative abundance of gut microbiota at the genus and species level: Faecalibacterium, Sutterella, Clostridium, Haemophilus, and Eisenbergiella were the highest (p < 0.05) in bodybuilders, while Bifidobacterium and Parasutterella were the lowest (p < 0.05). At the species level, intestinal beneficial bacteria widely used as probiotics (Bifidobacterium adolescentis group, Bifidobacterium longum group, Lactobacillus sakei group) and those producing short chain fatty acids (Blautia wexlerae, Eubacterium hallii) were the lowest in bodybuilders and the highest in controls. In addition, aerobic or resistance exercise training with an unbalanced intake of macronutrients and low intake of dietary fiber led to similar diversity of gut microbiota. Specifically, daily protein intake was negatively correlated with operation taxonomic unit (r = - 0.53, p < 0.05), ACE (r = - 0.51, p < 0.05), and Shannon index (r = - 0.64, p < 0.01) in distance runners.. CONCLUSION: Results suggest that high-protein diets may have a negative impact on gut microbiota diversity for athletes, while athletes in resistance sports that carry out the high protein low carbohydrates diet demonstrate a decrease in short chain fatty acid-producing commensal bacteria.

Results from South Korea's 2018 Report Card on physical activity for children and youth.

BACKGROUND/OBJECTIVE: South Korea's 2018 Report Card on Physical Activity for Children and Youth is the second comprehensive evaluation of physical activity and the sources of influence based on the 10 core indicators provided by the Active Healthy Kids Global Alliance. It will serve as an advocacy tool to promote physical activity among children and youth. METHODS: Three national surveillance data (i.e., 2017 Korea Youth Risk Behavior Web-based Survey, 2016 Korea National Health and Nutrition Examination Survey, 2016 Physical Activity Promotion System) were used as main sources to evaluate the indicators. Descriptive statistics were performed to obtain prevalence estimates of physical activity-related indicators. In addition, expert opinions as well as the most recently available published or unpublished relevant sources were synthesized. RESULTS: South Korea's 2018 Report Card, compared to the 2016 Report Card, showed favourable changes in the Active Transportation (B+), Organized Sports Participation (C), Sedentary Behaviours (D), and School (D+) indicators, while unfavourable changes were shown in Overall Physical Activity (F) and Government (D). Physical Fitness was graded as D+. In parallel with the 2016 Report Card, Active Play, Family and Peers, and Community and Environment remain ungraded due to insufficient data. CONCLUSIONS: Successes as well as gaps and research needs were identified in the 2018 Report Card. Though some indicators have shown improvement, most children and youth continue to be insufficiently physically active with overall poor grades (Average of D+). To achieve substantial improvement in all grades in future Report Cards, more institutional and governmental support and investment is needed to promote physical activity. Furthermore, effort should be made to generate data pertaining to the indicators that were ungraded.

RSL Class II Transcription Factors Guide the Nuclear Localization of RHL1 to Regulate Root Hair Development.

Root hairs are important for absorption of nutrients and water from the rhizosphere. The Root Hair Defective-Six Like (RSL) Class II family of transcription factors is expressed preferentially in root hairs and has a conserved role in root hair development in land plants. We functionally characterized the seven members of the RSL Class II subfamily in the rice (Oryza sativa) genome. In root hairs, six of these genes were preferentially expressed and four were strongly expressed. Phenotypic analysis of each mutant revealed that Os07g39940 plays a major role in root hair formation, based on observations of a short root hair phenotype in those mutants. Overexpression (OX) for each of four family members in rice resulted in an increase in the density and length of root hairs. These four members contain a transcription activation domain and are targeted to the nucleus. They interact with rice Root Hairless1 (OsRHL1), a key regulator of root hair development. When heterologously expressed in epidermal cells of Nicotiana benthamiana leaves, OsRHL1 was predominantly localized to the cytoplasm. When coexpressed with each of the four RSL Class II members, however, OsRLH1 was translocated to the nucleus. Transcriptome analysis using Os07g39940-OX plants revealed that 86 genes, including Class III peroxidases, were highly up-regulated. Furthermore, reactive oxygen species levels in the root hairs were increased in Os07g39940-OX plants but were drastically reduced in the os07g39940 and rhl1 mutants. Our results demonstrate that RSL Class II members function as essential regulators of root hair development in rice.

Weight loss practice, nutritional status, bone health, and injury history: A profile of professional jockeys in Korea.

PURPOSE: The purpose of this study was to investigate the impact of weight loss practices on nutritional status, bone health, and injury history among Korean professional jockeys. METHODS: Forty-three male jockeys completed a questionnaire to assess their weight loss practices. Of these, 10 jockeys were selected for in-depth assessment of their nutritional status, bone health, and injury history. RESULTS: The questionnaires revealed that 81.4% of jockeys lost weight every week mainly by dieting and/or exercising. None of the jockeys consumed enough food during the weight loss period. Two jockeys were diagnosed with osteopenia and one was diagnosed with osteoporosis. Only history of fracture showed a significant correlation with low bone mineral density. All jockeys had more than one injury experience throughout their career. Fracture was the most common type of injury, occurring during practice and/or competition and caused mainly by difficulties in handling the horses. CONCLUSION: Professional jockeys in Korea use extreme weight loss methods. Their repeated periods of poor nutritional intake may result in seriously low bone mineral density, which may aggravate injuries sustained during horse races. Implementation of balanced dietary programs and delivery of health education on weight management are urgently required.

Results From South Korea's 2016 Report Card on Physical Activity for Children and Youth.

BACKGROUND: South Korea's 2016 Report Card on Physical Activity for Children and Youth is the first assessment of physical activity according to the indicators set by Active Healthy Kids Global Alliance. METHODS: National surveys were used as preferred sources of data. This was then supported by peer-reviewed papers and government reports identified by a systematic search of the literature written in English or Korean. A Research Working Group then graded indicators based on the collected evidence. RESULTS: Each indicator was graded as follows: Overall Physical Activity, D-; Organized Sport and Physical Activity Participation, C-; Active Transport, C+; Sedentary Behavior, F; School, D; Government and Investment, C; Active Play, Physical Literacy, Family and Peers, and Community and Built Environment were graded INC (incomplete) due to lack of available evidence. CONCLUSIONS: Though the final grades of key indicators for South Korean children and youth are not satisfactory, increasing interests and investments have been demonstrated at a national level. More evidence is required for comprehensive assessment on all indicators to better inform policy and practice. This should be accompanied by the use of consistent criteria to contribute to global efforts for active healthy kids.

A Systematic View of the MLO Family in Rice Suggests Their Novel Roles in Morphological Development, Diurnal Responses, the Light-Signaling Pathway, and Various Stress Responses.

The Mildew resistance Locus O (MLO) family is unique to plants, containing genes that were initially identified as a susceptibility factor to powdery mildew pathogens. However, little is known about the roles and functional diversity of this family in rice, a model crop plant. The rice genome has 12 potential MLO family members. To achieve systematic functional assignments, we performed a phylogenomic analysis by integrating meta-expression data obtained from public sources of microarray data and real-time expression data into a phylogenic tree. Subsequently, we identified 12 MLO genes with various tissue-preferred patterns, including leaf, root, pollen, and ubiquitous expression. This suggested their functional diversity for morphological agronomic traits. We also used these integrated transcriptome data within a phylogenetic context to estimate the functional redundancy or specificity among OsMLO family members. Here, OsMLO12 showed preferential expression in mature pollen; OsMLO4, in the root tips; OsMLO10, throughout the roots except at the tips; and OsMLO8, expression preferential to the leaves and trinucleate pollen. Of particular interest to us was the diurnal expression of OsMLO1, OsMLO3, and OsMLO8, which indicated that they are potentially significant in responses to environmental changes. In osdxr mutants that show defects in the light response, OsMLO1, OsMLO3, OsMLO8, and four calmodulin genes were down-regulated. This finding provides insight into the novel functions of MLO proteins associated with the light-responsive methylerythritol 4-phosphate pathway. In addition, abiotic stress meta-expression data and real-time expression analysis implied that four and five MLO genes in rice are associated with responses to heat and cold stress, respectively. Upregulation of OsMLO3 by Magnaporthe oryzae infection further suggested that this gene participates in the response to pathogens. Our analysis has produced fundamental information that will enhance future studies of the diverse developmental or physiological phenomena mediated by the MLO family in this model plant system.

Treatment of non-vital immature teeth with amoxicillin-containing triple antibiotic paste resulting in apexification.

A recent treatment option for non-vital immature teeth in young patients is revascularization with triple antibiotic paste (TAP). However, tooth discoloration was reported with the use of conventional minocycline-containing TAP. In this case report, amoxicillin-containing TAP was used for revascularization of non-vital immature teeth to prevent tooth discoloration. At the 1 yr follow up, the teeth were asymptomatic on clinical examination and showed slight discoloration of the crown due to mineral trioxide aggregate (MTA) filling rather than amoxicillin-containing TAP. Radiographic examination revealed complete resolution of the periapical radiolucency, and closed apex with obvious periodontal ligament space. However, the root growth was limited, and the treatment outcome was more like apexification rather than revascularization. These results may be due to unstable blood clot formation which could not resist the condensation force of MTA filling, whether or not a collagen matrix was in place. These cases showed that although revascularization was not successful, apexification could be expected, resulting in the resolution of the periapical radiolucency and the closure of the apex. Therefore, it is worthwhile attempting revascularization of non-vital immature teeth in young patients.

Six week swimming followed by acute uptakes of ginsenoside Rg1 may affect aerobic capacity of SD rats.

PURPOSE: The purpose of this study is to examine the effects of six-weeks of endurance swim training and short-term intake of Rg1 on the expression of related proteins as well as improvement of aerobic exercise capacity in 8-week-old male SD rats. METHODS: The groups were divided into placebo (NP, n=6), Rg1 (NRG, n=6), exercise+placebo (EP, n=7), and exercise+Rg1 (ERG, n=7). On completion of the 6-week swimming exercise, Rg1-intake groups were treated with acute uptakes (3 times within 24hrs) of Rg1. After the treatment, all groups were subjected to a swim to exhaustion test, and then the mass of muscle tissue, mRNA expression level and activity of citrate synthase (CS) were analyzed on plantaris. RESULTS: There were no differences in the effect of 6-week swimming exercise and short-term intake of Rg1 on body weight and muscle mass between groups. Although the CS mRNA expression was elevated in the exercise group and combined treatment group, there was no significant difference in CS activity. Acute uptakes of Rg1 did not affect swimming time to exhaustion, but it was increased by 235% and 314% by the 6-weeks of exercise and combined treatment of exercise and Rg1, respectively, which suggests that the combined treatment increased the effect on the capacity of aerobic exercise. CONCLUSION: Based on these results, it was confirmed that even a short-term treatment of Rg1 can give an additive effect for improvement of exercise function, and additional studies are needed for the mechanisms and modes of its working.

Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor.

To survive and replicate within the human host, malaria parasites must invade erythrocytes. Invasion can be mediated by the P. falciparum reticulocyte-binding homologue protein 4 (PfRh4) on the merozoite surface interacting with complement receptor type 1 (CR1, CD35) on the erythrocyte membrane. The PfRh4 attachment site lies within the three N-terminal complement control protein modules (CCPs 1-3) of CR1, which intriguingly also accommodate binding and regulatory sites for the key complement activation-specific proteolytic products, C3b and C4b. One of these regulatory activities is decay-accelerating activity. Although PfRh4 does not impact C3b/C4b binding, it does inhibit this convertase disassociating capability. Here, we have employed ELISA, co-immunoprecipitation, and surface plasmon resonance to demonstrate that CCP 1 contains all the critical residues for PfRh4 interaction. We fine mapped by homologous substitution mutagenesis the PfRh4-binding site on CCP 1 and visualized it with a solution structure of CCPs 1-3 derived by NMR and small angle x-ray scattering. We cross-validated these results by creating an artificial PfRh4-binding site through substitution of putative PfRh4-interacting residues from CCP 1 into their homologous positions within CCP 8; strikingly, this engineered binding site had an ∼30-fold higher affinity for PfRh4 than the native one in CCP 1. These experiments define a candidate site on CR1 by which P. falciparum merozoites gain access to human erythrocytes in a non-sialic acid-dependent pathway of merozoite invasion.