Porcine Brain Enzyme Hydrolysate Enhances Immune Function and Antioxidant Defense via Modulation of Gut Microbiota in a Cyclophosphamide-Induced Immunodeficiency Model.

This study examined how consuming porcine brain enzyme hydrolysate (PBEH) affects the immune function and composition of the gut microbiota in an immunodeficient animal model. Male Wistar rats aged 6 weeks were fed casein (control), 100 mg/kg body weight (BW), red ginseng extract (positive-control), and 6, 13, and 26 mg PBEH per kg BW (PBEH-L, PBEH-M, and PBEH-H, respectively) daily for 4 weeks. At 30 min after consuming assigned compounds, they were orally administered cyclophosphamide (CTX; 5 mg/kg BW), an immunosuppressive agent, to suppress the immune system by inhibiting the proliferation of lymphocytes. The normal-control rats were fed casein and water instead of CTX. Natural killer cell activity and splenocyte proliferation induced by 1 µg/mL lipopolysaccharide were lower in the control group than the normal-control group, and they significantly increased with PBEH consumption, particularly at high doses. The PBEH consumption increased dose-dependently in the Th1/Th2 ratio compared to the control. The lipid peroxide contents were lower in the PBEH group than in the control group. Moreover, PBEH m and PBEH-H consumption mitigated white pulp cell damage, reduced red pulp congestion, and increased spleen mast cells in the histological analysis. Intestinal microbiota composition demonstrated differences between the groups at the genus levels, with Akkermansia being more abundant in the control group than the normal-control group and the PBEH-H group showing a decrease. However, Bifidobacterium decreased in the control group but increased in the PBEH-H group. The ß-diversity revealed distinct microbial communities of PBEH and positive-control groups compared to the control group (p < 0.05). The metagenome predictions revealed that PBEH-H influenced amino acid metabolism, antioxidant defense, insulin sensitivity, and longevity pathways. In conclusion, PBEH-H intake boosted immune responses and reduced lipid peroxides by modulating gut microbiota composition. These findings suggest that PBEH-H has the potential as a dietary supplement for improving immune function and gut health in individuals with immunodeficiency.

Augmentation of NK-cell activity and immunity by combined natural polyphenols and saccharides in vitro and in vivo.

Curcuma longa and Sargassum coreanum are commonly used in traditional pharmaceutical medicine to improve immune function in chronic diseases. The present study was designed to systematically elucidate the in vitro and in vivo immuno-enhancing effects of a combination of C. longa and S. coreanum extracts (CS) that contain polyphenols and saccharides as functional molecules in a cyclophosphamide (Cy)-induced model of immunosuppression. In primary splenocytes, we observed the ameliorative effects of CS on a Cy-induced immunosuppression model with low cytotoxicity and an optimal mixture procedure. CS treatment enhanced T- and B-cell proliferation, increased splenic natural killer-cell activity, and restored cytokine release. Wistar rats were orally administered low (30 mg/kg), intermediate (100 mg/kg), or high (300 mg/kg) doses of CS for four weeks, followed by oral administration of Cy (5 mg/kg) for four weeks. Compared with the vehicle group, low-, intermediate-, and high-dose CS treatment accelerated dose-dependent recovery of the serum level of tumor necrosis factor-α, interferon-γ, interleukin-2, and interleukin-12. These results suggest that CS treatment accelerates the amelioration of immune deficiency in Cy-treated primary splenocytes and rats, which supports considering it for immunity maintenance. Our findings provide experimental evidence for further research and clinical application in immunosuppressed patients.

Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism.

Introduction: Hypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES). Methods: Participants were categorized into the Low-HDL (case; n = 16,980) and Normal-HDL (n = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (<40 mg/dL for men and < 50 mg/dL for women) and included those taking medication for dyslipidemia. The genes associated with hypo-HDL-C were determined through a genome-wide association study (GWAS) in a city hospital-based cohort, and the results were validated in the Ansan/Anung study. The genetic variants for the single nucleotide polymorphism (SNP)-SNP interaction were selected using a generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS) generated was evaluated for interaction with lifestyle parameters. Results: The participants with hypo-HDL-C showed a 1.45 and 1.36-fold higher association with myocardial infarction and stroke, respectively. The High-PRS with four SNPs, namely ZPR1_rs3741297, CETP_rs708272, BUD13_rs180327, and ALDH1A2_rs588136, and that with the 11q23.3 haplotype were positively associated with hypo-HDL-C by about 3 times, which was a 2.4-fold higher association than the PRS of 24 SNP with p < 5×10-8. The risk alleles of CETP_rs708272 and ALDH1A2_rs588136 were linked to increased expression in the heart and decreased in the brain, respectively. The selected SNPs were linked to the reverse cholesterol transport pathway, triglyceride-rich lipoprotein particle remodeling pathway, cholesterol storage, and macrophage-derived foam cell differentiation regulation. The PRS of the 4-SNP model interacted with energy intake and smoking status, while that of the haplotype interacted with a glycemic index of the diet, sulfur microbial diet, and smoking status. Discussion: Adults with a genetic risk for hypo-HDL-C need to modulate their diet and smoking status to reduce their risk.

The Effect of the Mixed Extract of Kalopanax pictus Nakai and Achyranthes japonica Nakai on the Improvement of Degenerative Osteoarthritis through Inflammation Inhibition in the Monosodium Iodoacetate-Induced Mouse Model.

Osteoarthritis is a chronic inflammatory disease, and, due to the lack of fundamental treatment, the main objective is to alleviate pain and prevent cartilage damage. Kalopanax pictus Nakai and Achyranthes japonica Nakai are herbal plants known for their excellent anti-inflammatory properties. The objective of this study is to confirm the potential of a mixture extract of Kalopanax pictus Nakai and Achyranthes japonica Nakai as a functional raw material for improving osteoarthritis through anti-inflammatory effects in macrophages and MIA-induced arthritis experimental animals. In macrophages inflamed by lipopolysaccharide (LPS), treatment of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture inhibits NF-κB and mitogen-activated protein kinase (MAPK) activities, thereby inhibiting inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), inflammatory factors PGE2, MMP-2, and MMP-9, and nitric oxide (NO) was reduced. In addition, in an animal model of arthritis induced by MIA (monosodium iodoacetate), administration of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture reduced blood levels of inflammatory cytokines TNF-α and IL-6, inflammatory factors prostaglandin E2(PGE2), matrix metalloproteinase-2(MMP-2), and NO. Through these anti-inflammatory effects, MIA-induced pain reduction (recovery of clinical index, increase in weight bearing, and increase in area and width of the foot), recovery of meniscus damage, loss of cartilage tissue or inflammatory cells in tissue infiltration reduction, and recovery of the proteglycan layer were confirmed. Therefore, it is considered that Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture has the potential as a functional raw material that promotes joint health.

Euonymus alatus (Thunb.) Siebold leaf extract enhanced immunostimulatory effects in a cyclophosphamide-induced immunosuppressed rat model.

Background: Euonymus alatus (Thunb.) Siebold (EA) is a medicinal plant used in some Asian countries to treat various diseases, including cancer, hyperglycemia, diabetes, urticaria, dysmenorrhea, and arthritis. Owing to the wide range of pharmacological applications of EA, various roles of EA are being studied. Objective: We evaluated the immune-enhancing effect of EA treatment in a cyclophosphamide (Cy)-induced immunosuppressed rat model. Design: We analyzed the immune enhancement effect of EA on macrophages by western blotting. In addition, cell viability and natural killer (NK) cell activity were analyzed in splenocytes following EA treatment. For in vivo studies, analysis of weekly body weight, spleen weight, immune cell count, cytokine levels, and spleen histological findings was performed following EA administration in Cy-induced immunocompromised rats. Results: EA significantly increased cell viability and phospho-nuclear factor-kappa B and phospho-extracellular signal-regulated kinase protein levels in the macrophages. EA significantly increased NK cell activity in splenocytes compared with the control group. In Cy-induced immunosuppressed rats, EA administration increased spleen tissue weight and the contents of leukocytes, lymphocytes, granulocytes, intermediate cells, and plasma cytokines (tumor necrosis factor-α and interferon-γ). In addition, improvement in the damaged spleen tissue was observed. Conclusions: These findings confirm that EA exerts an immune-enhancing effect, thereby suggesting its potential as an immunostimulatory agent or functional food.

Inverse Association of the Adequacy and Balance Scores in the Modified Healthy Eating Index with Type 2 Diabetes in Women.

Type 2 diabetes (T2DM) has markedly increased among Asians as their diets and lifestyles become more westernized. We, therefore, investigated the hypothesis that the Korean healthy eating index (KHEI) scores are associated with gender-specific T2DM risk in adults. The hypothesis was tested using the data from the Korea National Health and Nutrition Examination Survey-VI (2013-2017) with a complex sample survey design. Along with the KHEI scores, the modified KHEI (MKHEI) scores for the Korean- (KSD) and Western-style diets (WSD) were used as independent parameters, calculated using a validated semi-quantitative food-frequency questionnaire (SQFFQ). We estimated the association between the KHEI or MKHEI and the T2DM risk using logistic regression after adjusting for T2DM-related covariates. The adults with T2DM were more frequently older men who were less educated, married, on a lower income, and living in rural areas compared to those without T2DM. Not only the fasting serum glucose concentrations but also the waist circumferences and serum triglyceride concentrations were much higher in adults with T2DM than in those without T2DM in both genders. Serum HDL concentrations in the non-T2DM subjects exhibited a greater inverse relationship to serum glucose than in the T2DM group in both genders. Twenty-four-hour recall data revealed that women, but not men, had higher calcium, vitamin C, saturated and monounsaturated fatty acids, retinol, and vitamin B2 intakes than the T2DM group. Furthermore, overall, the KHEI score and the adequacy and balance scores among its components were significantly higher in the non-T2DM group than in the T2DM group, but only in women. The KHEI scores were inversely associated with T2DM only in women. The mixed grain intake score was higher in the non-T2DM than the T2DM group only in men. However, there were no differences between the groups in the MKHEI scores for KSD and WSD. In conclusion, high KHEI scores in the adequacy and balance components might prevent and/or delay T2DM risk, but only in women.

Consistency of dose rates after applying machine-specific reference correction factors for the gamma knife 16 mm collimator field.

BACKGROUND: The machine-specific reference (msr) correction factors ( k Q msr , Q 0 f msr , f ref $k_{{Q_{{\rm{msr}}}},\;{Q_0}}^{{f_{{\rm{msr}}}},{f_{{\rm{ref}}}}}$ ) were introduced in International Atomic Energy Agency (IAEA) Technical Report Series 483 (TRS-483) for reference dosimetry of small fields. Several correction factor sets exist for a Leksell Gamma Knife (GK) Perfexion or Icon. Nevertheless, experiments have not rigorously validated the correction factors from different studies. PURPOSE: This study aimed to assess the role and accuracy of k Q msr , Q 0 f msr , f ref $k_{{Q_{{\rm{msr}}}},\;{Q_0}}^{{f_{{\rm{msr}}}},{f_{{\rm{ref}}}}}$ values in determining the absorbed dose rates to water in the reference dosimetry of Gamma Knife. METHODS: The dose rates in the 16 mm collimator field of a GK were determined following the international code of practices with three ionization chambers: PTW T31010, PTW T31016 (PTW Freiberg GmbH, New York, NY), and Exradin A16 (Standard Imaging, Inc., Middleton, WI). A chamber was placed at the center of a solid water phantom (Elekta AB, Stockholm, Sweden) using a detector-specific insert. The reference point of the ionization chamber was confirmed using cone-beam CT images. Consistency checks were repeated five times at a GK site and performed once at seven GK sites. Correction factors from six simulations reported in previous studies were employed. Variations in the dose rates and relative dose rates before and after applying the k Q m s r , Q 0 f m s r , f r e f $k_{{Q_{msr}},\;{Q_0}}^{{f_{msr}},{f_{ref}}}$ were statistically compared. RESULTS: The standard deviation of the dose rates measured by the three chambers decreased significantly after any correction method was applied (p = 0.000). When the correction factors of all studies were averaged, the standard deviation was reduced significantly more than when any single correction method was applied (p ≤ 0.030), except for the IAEA TRS-483 correction factors (p = 0.148). Before any correction was applied, there were statistically significant differences among the relative dose rates measured by the three chambers (p = 0.000). None of the single correction methods could remove the differences among the ionization chambers (p ≤ 0.038). After TRS-483 correction, the dose rate of Exradin A16 differed from those of the other two chambers (p ≤ 0.025). After the averaged factors were applied, there were no statistically significant differences between any pairs of chambers according to Scheffe's post hoc analyses (p ≥ 0.051); however, PTW T31010 differed from PTW 31016 according to Tukey's HSD analyses (p = 0.040). CONCLUSION: The k Q msr , Q 0 f msr , f ref $k_{{Q_{{\rm{msr}}}},\;{Q_0}}^{{f_{{\rm{msr}}}},{f_{{\rm{ref}}}}}$ significantly reduced variations in the dose rates measured by the three ionization chambers. The mean correction factors of the six simulations produced the most consistent results, but this finding was not explicitly proven in the statistical analyses.

Inverse association of a traditional Korean diet composed of a multigrain rice-containing meal with fruits and nuts with metabolic syndrome risk: The KoGES.

Background: Hansik, a traditional Korean diet, may have a beneficial impact on metabolic syndrome (MetS) risk as dietary westernization increases its prevalence. We examined the hypothesis that adherence to the hansik diet may be inversely associated with the risk of MetS and its components and sought to understand the gender differences in 58,701 men and women aged over 40. Materials and methods: Hansik was defined using 14 components from which the Korean dietary pattern index (Kdiet-index) was generated by summing their scores. Low-hansik intake was defined as the Kdiet-index with <8. MetS was categorized based on the 2005 revised NCEP-ATP III criteria modified for Asians. Results: The Kdiet-index score was negatively associated with the dietary inflammation index and showed that the high intake of a meal with multigrain rice, fruits, and their products, and nuts, and low intake of fried foods were inversely associated with MetS by 0.707, 0.864, 0.769, and 0.918 times, respectively, after adjusting for covariates. More women and participants with more educated and lower income belonged to the high-hansik group, and participants with high self-rated health scores consumed more hansik. All participants on a high-hansik diet were associated with a 0.87 time lower risk of MetS. Specifically, the association between hansik intake and MetS risk was not significant among men following stratification by gender. Body composition, including the body mass index, waist circumference, and fat mass, was inversely associated with hansik intake, while the skeletal muscle mass index was positively associated with the hansik intake in each gender and all participants. In all the participants in the high-hansik group, no significant changes were seen in the serum glucose and HDL concentration. However, a high-hansik intake showed lower blood pressure and serum LDL and triglyceride concentrations only in men and a higher glomerular filtration rate in both genders. Conclusions: Hansik intake might improve MetS risk, with its primary beneficial effects on body composition, dyslipidemia, and blood pressure gender-dependently.

Potential Effect of Enzymatic Porcine Placental Hydrolysate (EPPH) to Improve Alcoholic Liver Disease (ALD) by Promoting Lipolysis in the Liver.

Alcoholic liver disease is associated with the production of highly reactive free radicals by ethanol and its metabolites. Free radicals not only induce liver oxidation and damage tissues, but also stimulate an inflammatory response in hepatocytes, leading to severe liver disease. In order to improve alcoholic liver disease, enzymatic porcine placenta hydrolysate was studied by exploring various materials. Enzymatic porcine placenta hydrolysate (EPPH) contains various amino acids, peptides, and proteins, and is used as a useful substance in the body. In this study, changes were confirmed in indicators related to the antioxidant efficacy of EPPH in vitro and in vivo. EPPH inhibits an EtOH-induced decrease in superoxide dismutase and catalase activity through inhibition of free radicals without endogenous cytotoxicity. EPPH has been observed to have a partial effect on common liver function factors such as liver weight, ALT, AST, ALP, and GGT. In addition, EPPH affected changes in fat regulators and inflammatory cytokines in blood biochemical assays. It was confirmed that EPPH was involved in fat metabolism in hepatocytes by regulating PPARα in an alcoholic liver disease animal model. Therefore, EPPH strongly modulates Bcl-2 and BAX involved in apoptosis, thereby exhibiting cytochrome P450 (CYP)-inhibitory effects in alcoholic liver disease cells. As a result, this study confirmed that EPPH is a substance that can help liver health by improving liver disease in an alcoholic liver disease animal model.

Association of Polygenic Variants with Type 2 Diabetes Risk and Their Interaction with Lifestyles in Asians.

Over the last several decades, there has been a considerable growth in type 2 diabetes (T2DM) in Asians. A pathophysiological mechanism in Asian T2DM is closely linked to low insulin secretion, ß-cell mass, and inability to compensate for insulin resistance. We hypothesized that genetic variants associated with lower ß-cell mass and function and their combination with unhealthy lifestyle factors significantly raise T2DM risk among Asians. This hypothesis was explored with participants aged over 40. Participants were categorized into T2DM (case; n = 5383) and control (n = 53,318) groups. The genetic variants associated with a higher risk of T2DM were selected from a genome-wide association study in a city hospital-based cohort, and they were confirmed with a replicate study in Ansan/Ansung plus rural cohorts. The interacted genetic variants were identified with generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS)-nutrient interactions were examined. The 8-SNP model was positively associated with T2DM risk by about 10 times, exhibiting a higher association than the 20-SNP model, including all T2DM-linked SNPs with p < 5 × 10−6. The SNPs in the models were primarily involved in pancreatic ß-cell growth and survival. The PRS of the 8-SNP model interacted with three lifestyle factors: energy intake based on the estimated energy requirement (EER), Western-style diet (WSD), and smoking status. Fasting serum glucose concentrations were much higher in the participants with High-PRS in rather low EER intake and high-WSD compared to the High-EER and Low-WSD, respectively. They were shown to be higher in the participants with High-PRS in smokers than in non-smokers. In conclusion, the genetic impact of T2DM risk was mainly involved with regulating pancreatic ß-cell mass and function, and the PRS interacted with lifestyles. These results highlight the interaction between genetic impacts and lifestyles in precision nutrition.

Assessment of a Therapeutic X-ray Radiation Dose Measurement System Based on a Flexible Copper Indium Gallium Selenide Solar Cell.

Several detectors have been developed to measure radiation doses during radiotherapy. However, most detectors are not flexible. Consequently, the airgaps between the patient surface and detector could reduce the measurement accuracy. Thus, this study proposes a dose measurement system based on a flexible copper indium gallium selenide (CIGS) solar cell. Our system comprises a customized CIGS solar cell (with a size 10 × 10 cm2 and thickness 0.33 mm), voltage amplifier, data acquisition module, and laptop with in-house software. In the study, the dosimetric characteristics, such as dose linearity, dose rate independence, energy independence, and field size output, of the dose measurement system in therapeutic X-ray radiation were quantified. For dose linearity, the slope of the linear fitted curve and the R-square value were 1.00 and 0.9999, respectively. The differences in the measured signals according to changes in the dose rates and photon energies were <2% and <3%, respectively. The field size output measured using our system exhibited a substantial increase as the field size increased, contrary to that measured using the ion chamber/film. Our findings demonstrate that our system has good dosimetric characteristics as a flexible in vivo dosimeter. Furthermore, the size and shape of the solar cell can be easily customized, which is an advantage over other flexible dosimeters based on an a-Si solar cell.

Immune-Enhancing Effects of Co-treatment With Kalopanax pictus Nakai Bark and Nelumbo nucifera Gaertner Leaf Extract in a Cyclophosphamide-Induced Immunosuppressed Rat Model.

Objective: Immune system disorders can result in various pathological conditions, such as infections and cancer. Identifying therapies that enhance the immune response might be crucial for immunocompromised individuals. Therefore, we assessed the immune-enhancing effect of co-treatment with Kalopanax pictus Nakai Bark and Nelumbo nucifera Gaertner leaf extract (KPNN) in a cyclophosphamide (Cy)-induced immunosuppressed rat model. Materials and Methods: For in vitro studies, macrophages and splenocytes were treated with various KPNN doses in the presence or absence of Cy. Macrophage viability, nitric oxide production, splenocyte viability, cytokine production and natural killer (NK) cell activity were analyzed. For in vivo studies, analysis of weekly body weight, dietary intake, tissue weight, immune-related blood cell count, cytokine levels, and spleen biopsy was performed in a Cy-induced immunocompromised animal model. Results: KPNN significantly increased phospho-NF-κB and phospho-ERK protein levels and cell viability in macrophages. KPNN significantly increased the NK cell activity in splenocytes compared to that in the control. Cy treatment decreased tumor necrosis factor (TNF)-α, interleukin (IL)-6, and interferon-γ production. In the Cy-induced immunosuppression rat model, KPNN-treated rats had significantly higher body weights and tissue weights than the Cy-treated rats. Additionally, KPNN treatment restored the immune-related factors, such as total leukocyte, lymphocyte, and intermediate cell contents, to their normal levels in the blood. The blood cytokines (TNF-α and IL-6) were increased, and spleen tissue damage was significantly alleviated. Conclusions: Collectively, KPNN exerts an immune-enhancing effect suggesting their potential as an immunostimulatory agent or functional food.

Beneficial Effects of a Low-Glycemic Diet on Serum Metabolites and Gut Microbiota in Obese Women With Prevotella and Bacteriodes Enterotypes: A Randomized Clinical Trial.

Generalized healthy eating patterns may not benefit everyone due to different genetics and enterotypes. We aimed to compare the effects of a low-glycemic diet representing the Korean traditional balanced diet (Low-GID) and westernized diet as a control diet (CD) on anthropometry, serum metabolites, and fecal bacteria in a randomized clinical trial according to enterotypes. We recruited 52 obese women aged 30-50 years, and they consumed Low-GID and CD meals for 1 month, with a 1-month washout period, in a crossover randomized clinical trial. The Low-GID was mainly composed of whole grains with fish, vegetables, seaweeds, and perilla oil, whereas CD contained refined rice, bread, noodles, meats, and processed foods. Serum lipid profiles, metabolomics, serum short-chain fatty acids, and fecal bacteria were analyzed. The important variables influenced by Low-GID and CD were determined by SHAP value in the XGBoost algorithm according to Bacteroides (ET-B) and Prevotella (ET-P). Low-GID and CD interventions did not change the enterotypes, but they modified serum metabolites and some fecal bacterial species differently according to enterotypes. The 10-fold cross-validation of the XGBoost classifier in the ET-P and ET-B clusters was 0.91 ± 0.04 and 0.8 ± 0.07, respectively. In the ET-P cluster, serum L-homocysteine, glutamate, leucine concentrations, and muscle mass were higher in the CD group than in the Low-GID group, whereas serum 3-hydroxybutyric acid concentration was significantly higher in the Low-GID group than in the CD group (p < 0.05). In fecal bacteria, Gemmiger formicilis, Collinsella aerofaciens, and Escherichia coli were higher in the CD group than in the Low-GID group. In the ET-B cohort, serum tryptophan and total cholesterol concentrations were higher in the CD group than in the Low-GID group, whereas serum glutathione and 3-hydroxybutyric acid concentrations were significantly higher in the Low-GID group than in the CD group (p < 0.05). However, Bifidobacterium longum was higher in CD than Low-GID in the ET-B cluster, but serum butyric acid levels were higher in the Low-GID than in the CD group. In conclusion, Low-GID can be recommended in obese women with both ET-P and ET-B enterotypes, although its efficacy was more effective in ET-P. Clinical Trial Registration: [https://cris.nih.go.kr/cris/search/detailSearch.do/17398], identifier [KCT0005340].

Long-Term Effect of Porcine Brain Enzyme Hydrolysate Intake on Scopolamine-Induced Memory Impairment in Rats.

No study has revealed the effect of porcine brain enzyme hydrolysate (PBEH) on memory impairment. We aimed to examine the hypothesis that PBEH intake modulates memory deficits and cognitive behavior in scopolamine (SC)-induced amnesia rats, and its mechanism, including gut microbiota changes, was determined. Sprague-Dawley male rats had intraperitoneal injections of SC (2 mg/kg body weight/day) at 30 min after daily feeding of casein (MD-control), PBEH (7 mg total nitrogen/mL) at 0.053 mL (Low-PBEH), 0.159 mL (Medium-PBEH), 0.478 mL (High-PBEH), or 10 mg donepezil (Positive-control) per kilogram body weight per day through a feeding needle for six weeks. The Normal-control rats had casein feeding without SC injection. PBEH dose-dependently protected against memory deficits determined by passive avoidance test, Y-maze, water-maze, and novel object recognition test in SC-induced rats compared to the MD-control. The High-PBEH group had a similar memory function to the Positive-control group. Systemic insulin resistance determined by HOMA-IR was lower in the PBEH groups than in the Normal-control but not the Positive-control. In parallel with systemic insulin resistance, decreased cholesterol and increased glycogen contents in the hippocampus in the Medium-PBEH and High-PBEH represented reduced brain insulin resistance. PBEH intake prevented the increment of serum TNF-α and IL-1ß concentrations in the SC-injected rats. Hippocampal lipid peroxide and TNF-α contents and mRNA TNF-α and IL-1ß expression were dose-dependently reduced in PBEH and Positive-control. PBEH decreased the hippocampal acetylcholinesterase activity compared to the MD-control, but not as much as the Positive-control. PBEH intake increased the α-diversity of the gut microbiota compared to the MD-control, and the gut microbiota community was separated from MD-control. In metagenome function analysis, PBEH increased the energy metabolism-related pathways of the gut microbiota, including citric acid cycle, oxidative phosphorylation, glycolysis, and amino acid metabolism, which were lower in the MD-control than the Normal-control. In conclusion, alleviated memory deficit by PBEH was associated potentially with not only reducing acetylcholinesterase activity but also improving brain insulin resistance and neuroinflammation potentially through modulating gut microbiota. PBEH intake (1.5-4.5 mL of 7 mg total nitrogen/mL for human equivalent) can be a potential therapeutic agent for improving memory impairment.

Feasibility of isodose-shaped scintillation detectors for the measurement of gamma knife output factors.

PURPOSE: Scintillation detectors were 3D printed based on a gamma knife (GK) dose distribution to calculate the volume averaging effect. The collimator output factors were measured using isodose-shaped scintillators (ISSs) and compared with those of a micro-diamond detector and previous reports. METHODS: An absorbed dose distribution in a spherical dosimetry phantom with a radius of 8 cm was obtained from GK treatment planning software (Leksell GammaPlan [LGP], Elekta AB, Stockholm, Sweden). Two types of ISSs were fabricated to fit the 97.2% (ISS-1) and 95.6% (ISS-2) isodose surfaces. The volume averaging correction factors were obtained by dividing the absorbed dose to water in the central voxel (CV) by that in the ISS. The correction effect due to the difference between the ISS and water was calculated by Monte Carlo simulations. Ten ISS detectors, five of each type, were used to measure the output factors of the 4- and 8-mm collimators of a GK Icon to assess system consistency. The output factors of seven GKs were measured using two ISS detectors, one of each type, and a PTW T60019 (PTW, Freiburg, Germany) micro-diamond detector. RESULTS: The detector output ratios (DORs) measured using the five ISSs of each type were consistent, with standard uncertainties less than 0.2%. In the 4-mm field, the volume averaging correction factor ratios were 1.018 and 1.026, and the output factors after all corrections were 0.827 (0.006) and 0.825 (0.006) for ISS-1 and ISS-2, respectively. In the 8-mm field, the volume averaging correction factor ratios were 1.000 for both ISS types, and the output factors were 0.898 (0.003) and 0.900 (0.003) for ISS-1 and ISS-2, respectively. The ISS detectors could measure the output factors of a GK with uncertainties comparable to that of the PTW 60019 detector. The output factors of all detectors decreased with the dose rate. CONCLUSION: The volume averaging effect of an ISS developed in-house could be calculated using known dose distributions. The collimator output factors of the GK Perfexion/Icon models measured using ISS detectors were consistent with those of a commercial synthetic micro-diamond detector and recent studies.

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial.

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30-40 years, who were randomly assigned to two groups-a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.

A multivariate approach to determine electron beam parameters for a Monte Carlo 6 MV Linac model: Statistical and machine learning methods.

PURPOSE: This study aimed to determine the optimal initial electron beam parameters of a Linac for radiotherapy with a multivariate approach using statistical and machine-learning tools. METHODS: For MC beam commissioning, a 6 MV Varian Clinac was simulated using the Geant4 toolkit. The authors investigated the relations between simulated dose distribution and initial electron beam parameters, namely, mean energy (E), energy spread (ES), and radial beam size (RS). The goodness of simulation was evaluated by the slope of differences between the simulated and the golden beam data. The best-fit combination of the electron beam parameters that minimized the slope of dose difference was searched through multivariate methods using conventional statistical methods and machine-learning tools of the scikit-learn library. RESULTS: Simulation results with 87 combinations of the electron beam parameters were analyzed. Regardless of being univariate or multivariate, traditional statistical models did not recommend a single parameter set simultaneously minimizing slope of dose differences for percent depth dose (PDD) and lateral dose profile (LDP). Two machine learning classification modules, RandomForestClassifier and BaggingClassifier, agreed in recommending (E = 6.3 MeV, ES = ±5.0%, RS = 1.0 mm) for predicting simultaneous acceptance of PDD and LDP. CONCLUSIONS: The machine learning with random-forest and bagging classifier modules recommended a consistent result. It was possible to draw an optimal electron beam parameter set using multivariate methods for MC simulation of a radiotherapy 6 MV Linac.

Interactions between Polygenic Risk Scores, Dietary Pattern, and Menarche Age with the Obesity Risk in a Large Hospital-Based Cohort.

Obese Asians are more susceptible to metabolic diseases than obese Caucasians of the same body mass index (BMI). We hypothesized that the genetic variants associated with obesity risk interact with the lifestyles of middle-aged and elderly adults, possibly allowing the development of personalized interventions based on genotype. We aimed to examine this hypothesis in a large city hospital-based cohort in Korea. The participants with cancers, thyroid diseases, chronic kidney disease, or brain-related diseases were excluded. The participants were divided into case and control according to their BMI: ≥25 kg/m2 (case; n = 17,545) and <25 kg/m2 (control; n = 36,283). The genetic variants that affected obesity risk were selected using a genome-wide association study, and the genetic variants that interacted with each other were identified by generalized multifactor dimensionality reduction analysis. The selected genetic variants were confirmed in the Ansan/Ansung cohort, and polygenetic risk scores (PRS)-nutrient interactions for obesity risk were determined. A high BMI was associated with a high-fat mass (odds ratio (OR) = 20.71) and a high skeletal muscle-mass index (OR = 3.38). A high BMI was positively related to metabolic syndrome and its components, including lipid profiles, whereas the initial menstruation age was inversely associated with a high BMI (OR = 0.78). The best model with 5-SNPs included SEC16B_rs543874, DNAJC27_rs713586, BDNF_rs6265, MC4R_rs6567160, and GIPR_rs1444988703. The high PRS with the 5-SNP model was positively associated with an obesity risk of 1.629 (1.475-1.798) after adjusting for the covariates. The 5-SNP model interacted with the initial menstruation age, fried foods, and plant-based diet for BMI risk. The participants with a high PRS also had a higher obesity risk when combined with early menarche, low plant-based diet, and a high fried-food intake than in participants with late menarche, high plant-based diet, and low fried-food intake. In conclusion, people with a high PRS and earlier menarche age are recommended to consume fewer fried foods and a more plant-based diet to decrease obesity risk. This result can be applied to personalized nutrition for preventing obesity.

Efficacy and Safety of Aronia, Red Ginseng, Shiitake Mushroom, and Nattokinase Mixture on Insulin Resistance in Prediabetic Adults: A Randomized, Double-Blinded, Placebo-Controlled Trial.

We determined whether oral consumption of Aronia, red ginseng, shiitake mushroom, and nattokinase mixture (3.4: 4.1: 2.4: 0.1 w/w; AGM) improved glucose metabolism and insulin resistance in prediabetic adults in a 12-week randomized, double-blinded clinical trial. Participants with fasting serum glucose concentrations of 100-140 mg/dL were recruited and randomly assigned to an AGM or placebo group. Participants of the AGM group (n = 40) were given an AGM granule containing 4 g of freeze-dried Aronia, red ginseng, shiitake mushroom, and nattokinase (3.4: 4.1: 2.4: 0.1 w/w) twice daily for 12 weeks, and the placebo group participants (n = 40) were provided with corn starch granules identical in appearance, weight, and flavor for 12 weeks. Serum glucose and insulin concentrations were measured during oral-glucose tolerance tests (OGTT) after administering 75 g of glucose in a fasted state. HOMA-IR, liver damage, and inflammation indices were determined, and safety parameters and adverse reactions were assessed. As determined by OGTT, serum glucose concentrations were not significantly different between the AGM and placebo groups after the intervention. However, changes in serum insulin concentrations in the fasted state and Homeostatic model assessment-insulin resistance (HOMA-IR) index after the intervention were significantly lower in the AGM group than in the placebo group (-3.07 ± 7.06 vs. 0.05 ± 6.12, p = 0.043 for serum insulin; -0.85 ± 2.14 vs. 0.07 ± 1.92, p = 0.049 for HOMA-IR). Serum adiponectin concentrations were reduced by intervention in the placebo group but not in the AGM group. Changes in liver damage indexes, including serum activities of the γ-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase, were lower in the AGM group and significantly reduced in the AGM group more than in the placebo group (p < 0.05). Changes in serum high sensitive-C-reactive protein concentrations in AGM and placebo groups were significantly different (-0.12 ± 0.81 vs. 0.51 ± 1.95, p = 0.06). In conclusion, AGM possibly improves insulin sensitivity and ß-cell function and reduces liver damage and inflammation in prediabetic adults.

Aqueous Blackcurrant Extract Improves Insulin Sensitivity and Secretion and Modulates the Gut Microbiome in Non-Obese Type 2 Diabetic Rats.

This study was undertaken to determine whether aqueous blackcurrant extracts (BC) improve glucose metabolism and gut microbiomes in non-obese type 2 diabetic animals fed a high-fat diet and to identify the mechanism involved. Partially pancreatectomized male Sprague-Dawley rats were provided a high-fat diet containing 0% (control), 0.2% (L-BC; low dosage), 0.6% (M-BC; medium dosage), and 1.8% (H-BC; high dosage) blackcurrant extracts; 0.2% metformin (positive-C); plus 1.8%, 1.6%, 1.2%, 0%, and 1.6% dextrin, specifically indigestible dextrin, daily for 8 weeks. Daily blackcurrant extract intakes were equivalent to 100, 300, and 900 mg/kg body weight (bw). After a 2 g glucose or maltose/kg bw challenge, serum glucose and insulin concentrations during peak and final states were obviously lower in the M-BC and H-BC groups than in the control group (p < 0.05). Intraperitoneal insulin tolerance testing showed that M-BC and H-BC improved insulin resistance. Hepatic triglyceride deposition, TNF-α expression, and malondialdehyde contents were lower in the M-BC and H-BC groups than in the control group. Improvements in insulin resistance in the M-BC and H-BC groups were associated with reduced inflammation and oxidative stress (p < 0.05). Hyperglycemic clamp testing showed that insulin secretion capacity increased in the acute phase (2 to 10 min) in the M-BC and H-BC groups and that insulin sensitivity in the hyperglycemic state was greater in these groups than in the control group (p < 0.05). Pancreatic ß-cell mass was greater in the M-BC, H-BC, and positive-C groups than in the control group. Furthermore, ß-cell proliferation appeared to be elevated and apoptosis was suppressed in these three groups (p < 0.05). Serum propionate and butyrate concentrations were higher in the M-BC and H-BC groups than in the control group. BC dose-dependently increased α-diversity of the gut microbiota and predicted the enhancement of oxidative phosphorylation-related microbiome genes and downregulation of carbohydrate digestion and absorption-related genes, as determined by PICRUSt2 analysis. In conclusion, BC enhanced insulin sensitivity and glucose-stimulated insulin secretion, which improved glucose homeostasis, and these improvements were associated with an incremental increase of the α-diversity of gut microbiota and suppressed inflammation and oxidative stress.