Dietary yeast cell wall enhanced intestinal health of broiler chickens by modulating intestinal integrity, immune responses, and microbiota.

This study was conducted to determine the effects of dietary yeast cell wall (YCW) on growth performance, intestinal health, and immune responses of broiler chickens. In a randomized completely block design (block: initial body weight), a total of 800 broilers (Ross 308; 45.18 ± 3.13 g of initial body weight) were assigned to 2 dietary treatments (40 birds/pen; 10 replicates/treatment) and fed for 5 wk: 1) a basal broiler diet based on corn-soybean meal (CON) and 2) CON + 0.05% dietary YCW. Growth performance was measured at intervals in 3 phase feed program. On the final day of the study, one bird per pen was randomly selected and euthanized for sample collection. Broilers fed YCW had decreased (P < 0.05) feed conversion ratio during the grower phase compared with those fed CON. The YCW increased (P < 0.05) villus height to crypt depth ratio in the duodenum, jejunum, and ileum compared with the CON. In addition, the YCW tended to higher (P < 0.10) number of goblet cells in the duodenum than in the CON. Broilers fed YCW had increased (P < 0.05) serum TGF- ß1, ileal gene expression of the claudin family, and relative abundance of Lactobacillus, Prevotella, and Enterococcus compared with the CON, but decreased serum TNF-α (P < 0.05), IL-1ß (P < 0.05), and IL-6 (P < 0.10), ileal gene expression of IL-6 (P < 0.05), and relative abundance of Clostridium (P < 0.05). The present study demonstrated that the addition of dietary YCW in broiler diets enhanced the intestinal health of broiler chickens and may be associated with modulated intestinal morphology and integrity by upregulating tight junction-related protein gene expression and modifying the ileal microbiota. In addition, dietary YCW modulated immune responses and inflammatory cytokine gene expression in the ileum.

Weight Control Registry Using Korean Medicine: A Protocol for a Prospective Registry Study.

Lifestyle and physical characteristics affect body weight, and understanding these factors improves the precision of weight loss treatment. Many obese patients in Korea are receiving Korean medicine (KM) treatment, including herbal medicine and acupuncture, for weight loss. However, the real-world data (RWD) are insufficient in terms of being longitudinal and diverse. Weight Control Registry using KM is a prospective registry study that enrolls patients receiving KM treatment for weight loss and collects RWD from multiple clinics. The patients who are eligible for this study are aged 19-65 years, receive KM weight loss treatment, understand the study objectives, and consent voluntarily. Clinical data of patient characteristics and KM treatment patterns will be regularly collected until 2026. The longitudinal accumulation of various RWD will establish a high-quality study database for KM weight loss treatment. With this study, we expect to contribute to understanding the current trend of weight loss treatment with KM and solve further questions regarding this treatment.

The Applicability of Virtual Reality-Based Training for Controlling Anger in Aggressive Individuals.

Because a failure of anger control leads to emotional and social problems, appropriate anger management may be important for social well-being. Virtual reality (VR) may potentially be effectively utilized in anger management, and this study aimed to verify the applicability of the VR-based anger control training program. The data obtained by having 60 young male participants divided into 2 groups, the high aggression group and the low aggression group, based on their Aggression Questionnaire scores to execute this program were analyzed. The program consisted of "Anger Exposure Training" for provoking anger and facilitating anger control and "Mindfulness Training" for providing the meditation experience for controlling anger. The anger scores and comfort scores obtained from these tasks, respectively, were analyzed for differences between the groups and between the experimental conditions. The anger regulation and comfort enhancement rates were analyzed for correlations with psychological variables. In Anger Exposure Training, the anger scores in angry expression were reduced in managed expression of anger in both groups. In Mindfulness Training, meditation increased comfort score as well in both groups, and the comfort enhancement rates were negatively correlated with the levels of self-differentiation and open communication with mother only in the high aggression group. These results indicate that the VR environments can provide an effective means of trainings for managing anger. Therefore, further research on the effectiveness of the VR-based anger control training program is worthy conducting in individuals who express excessive aggression.

Exogenous emulsifiers and multi-enzyme combination improves growth performance of the young broiler chickens fed low energy diets containing vegetable oil.

OBJECTIVE: The present study examined the effects of exogenous emulsifiers and multi-enzyme supplementation into a low energy density diet on growth performance, visceral organ parameters, blood metabolites, ileal morphology, and nutrient digestibility in broiler chickens from hatch to 21 days. METHODS: One hundred and sixty-eight one-day-old Ross 308 broiler chickens were allocated in a completely randomized design to 24 pens and each pen was assigned to one of four dietary treatments to give six replications with seven chickens in a cage. Dietary treatments were: i) positive control with standard energy level (PC); ii) negative control with 100 kcal/kg lower energy of the standard level (NC); iii) NC diet supplemented 0.05% calcium stearoyl-2 lactylate as an emulsifier (NC+E); and iv) NC diet supplemented with both 0.05% calcium stearoyl-2 lactylate and 0.05% multi-enzyme (NC+E+M). Corn and soybean meal-based control diets containing vegetable oil were formulated to meet the Ross 308 nutrition specification. Chickens were fed ad-libitum with the treatment diets and sampling was conducted on day 21. RESULTS: Our results revealed that emulsifier and multi-enzyme supplementation into NC diets improved (p<0.05) feed efficiency of the broiler chickens compared to the broiler chickens fed NC diets from hatch to 21 days. Supplementation of emulsifier and multi-enzyme into NC diet improved (p<0.05) nutrient digestibility of the broiler chickens. However, emulsifier and multi-enzymesupplementation into diet did not influence (p>0.05) visceral organ weight, blood metabolites, and intestinal morphology in broiler chickens fed NC diets. CONCLUSION: Supplementation of emulsifier and multi-enzyme in the NC diet would support improving growth performance in young broiler chickens with improved feed efficiency and increased nutrient digestibility thereby curtailing the negative impact of energy reduction in the diets.

Supplementation of live yeast culture modulates intestinal health, immune responses, and microbiota diversity in broiler chickens.

The present study investigated the effects of live yeast cultures (LYC) on growth performance, gut health indicators, and immune responses in broiler chickens. A total of 720 mixed-sex broilers (40 birds/pen; 9 replicates/treatment) were randomly allocated to two dietary treatments: (1) a basal diet based on corn-soybean meal (CON) and (2) CON with 1 g/kg LYC. At 35 d of age, one bird per replicate pen was chosen for biopsy. LYC group tended (P < 0.10) to increase average daily gain during the grower phase compared with CON group. Broilers fed LYC diet had increased (P = 0.046) duodenal villus height and area but reduced (P = 0.003) duodenal crypt depth compared with those fed CON diet. Birds fed LYC diet presented alleviated (P < 0.05) serum TNF-α, IL-1ß, and IL-6 levels compared with those fed CON diet. Further, birds fed LYC diet exhibited upregulated (P < 0.05) ileal tight junction-related proteins and pro-inflammatory cytokines in the ileal tissue compared with those fed CON diet. Inverse Simpson's diversity (P = 0.038) revealed that birds fed CON diet had a more diverse microbiota community in the ileal digesta, compared with those fed LYC diet, while no significant difference between the treatments on Chao1 and Shannon's indices was observed. Based on the weighted UniFrac distance, the PCoA showed that microbiota in the ileal digesta of the LYC group was different from that of the CON group. LYC group increased the abundance of the phyla Firmicutes and genera Lactobacillus, Prevotella, and Enterococcus compared with CON group. The present study demonstrated that supplemental LYC as a feed additive provide supportive effects on enhancing gut functionality by improving the upper intestinal morphology and gut integrity, and modulating the immune system and microbiota communities of birds.

Live yeast culture (LYC) is composed of Saccharomyces cerevisiae and its metabolites such as mannan-oligosaccharides, peptides, nucleotides, vitamins and unknown growth factors. The supplementation of LYC is expected to exert health benefits in animals; however, the responses of broiler chickens to supplemental LYC is not fully explored. Thus, the present study evaluated the effects of LYC supplementation on growth performance, immune responses and intestinal health in broiler chickens. Based on the results from the present study, supplementation of LYC to a corn-based diet did not affect growth performance. Nonetheless, supplemental LYC improved intestinal morphology, upregulated tight junction-related protein genes and altered ileal microbiota diversity, suggesting its health benefits in improving gut health. In addition, supplemental LYC modulated serum immune responses and ileal cytokine genes expression, presenting its immunomodulatory potential.

Effects of a multimodal approach to food art therapy on people with mild cognitive impairment and mild dementia.

BACKGROUND: Food art therapy (FAT) has multiple modalities in which cognition, emotion, and social changes are stimulated. The purpose of this study was to design a multimodal approach to a food art therapy (MM-FAT) program and identify its effects on cognitive ability, daily living functioning, depression, self-esteem, self-efficacy, self-expression, and social functioning in individuals with mild cognitive impairment (MCI) and mild dementia by employing a mixed methods research design. METHODS: The participants included 39 patients from a public dementia care centre in Seoul, Korea. The intervention group, which comprised 20 participants, received 12 MM-FAT sessions 3 times a week for 4 weeks, and the control group, which included 19 participants, received usual care. The MM-FAT program was evaluated based on its effectiveness on cognitive, daily living, emotional, and social functioning outcome measures at three time points using repeated measures analysis of variance. Semi-structured interviews (n = 9) were conducted to evaluate the overall experience of the MM-FAT program and its outcomes. RESULTS: The findings reveal that MM-FAT has a positive effect on the cognitive, emotional, and social functioning of individuals with MCI and mild dementia. However, there were no enhancements in individuals' daily living functioning, and the lasting effects of the intervention could not be assessed. Cognition and depression increased significantly at the end of the MM-FAT program. Self-expression and self-efficacy were significantly higher in the MM-FAT group than in the control group. The semi-structured interviews revealed improvements in participants' behaviour, communication, and interaction. CONCLUSION: This mixed methods study focused on individuals with MCI or mild dementia contributes to an understanding of the effectiveness of a FAT program employing a multimodal approach. Despite the COVID-19 pandemic, the study was able to enrich the effects of MM-FAT on cognitive, emotional, and social functioning through qualitative findings.

Brain functional connectivity during and after imagery of gaming and alternative leisure activities in patients with internet gaming disorder.

BACKGROUND: The effect of gaming cue exposure on brain activity in patients with internet gaming disorder (IGD) has been investigated a lot, but the effect on brain connectivity has not. This study aimed to investigate the effects of imageries of gaming and alternative leisure activities on functional connectivity during the during-task and post-task states in patients with IGD. METHODS: Twenty-nine patients and 20 healthy controls were scanned in the 6-min states before, during, and after the imagery tasks for gaming and alternative leisure behaviors using fMRI. Seed-based functional connectivity during and after the tasks were analyzed. The seeds were the nucleus accumbens (NAcc), ventral tegmental area (VTA), caudate, putamen, anterior cingulate cortex (ACC), and posterior cingulate cortex. RESULTS: The group-by-state interaction effects for the during-tasks were found in caudate-, putamen-, and ACC-based connectivity, whereas those for the post-tasks were shown only in NAcc-based connectivity. In particular, patients showed that caudate-right parahippocampal gyrus connectivity and putamen-right orbitofrontal cortex connectivity increased during gaming and decreased during alternative, whereas NAcc-right precuneus connectivity decreased at baseline, increased in post-gaming, and were not different in post-alternative. CONCLUSION: Differences in during-task connectivity of the habit/motor and salience networks and post-task resting-state connectivity of the reward and limbic networks between the two imagery tasks may differ between the groups. In the treatment of IGD, when these network connections are reactive to alternative leisure activity, just as to gaming activity, they seem to be freed from gaming addiction.

Moderate dietary boron supplementation improved growth performance, crude protein digestibility and diarrhea index in weaner pigs regardless of the sanitary condition.

OBJECTIVE: The study was conducted to investigate the impact of boron supplementation on nutrient digestibility, inflammatory responses, blood metabolites and diarrhea index, and their relevance to growth performance in weaned pigs housed in good and poor sanitary environments for 14 days after weaning. METHODS: A total of 108 male pigs (Duroc×[Yorkshire×Landrace]) weaned at 21 days of age were used in a randomized complete block design with 2×3 factorial arrangement. Pigs were assigned to three boron treatments (0, 5, and 10 mg/kg) under two environments (good and poor sanitary) to give six replicates per treatment (3 pigs per replicate). On 0, 7, and 14 days, one pig per replicate was euthanized to collect, ileum tissue samples, and rectal fecal samples. RESULTS: Boron supplementation quadratically influenced (p<0.001) feed intake and weight gain in pigs housed in good sanitary conditions from 1 to 14 days post-weaning where pigs offered 5 mg/kg boron optimized weight gain and feed intake. There is a quadratic interaction (p = 0.019) on feed intake for 1 to 14 days post-weaning where 5 mg/kg boron increased feed intake in good sanitary conditions. Pigs housed in the poor sanitary environment decreased (p<0.001) villus height and crypt depth in ileum at days 7 and 14. On day 7 and 14, crude protein digestibility was quadratically influenced (p<0.05) by boron supplementation. Boron supplementation linearly increased (p<0.05) plasma calcium and cholesterol levels whilst linearly (p = 0.005) reducing plasma triglyceride concentrations. Diarrhea index was quadratically influenced (p<0.05) by boron supplementations regardless of sanitary conditions where 5 mg/kg boron inclusion achieved the lowest diarrhea index. CONCLUSION: Pigs offered 5 mg/kg of boron increased weight gain which may be deduced by improved dry matter, crude protein, and energy digestibility regardless of the sanitary conditions.

Oral Intake of Enzymatically Decomposed AP Collagen Peptides Improves Skin Moisture and Ceramide and Natural Moisturizing Factor Contents in the Stratum Corneum.

The stratum corneum (SC) is the outermost layer of the epidermis and plays an important role in maintaining skin moisture and protecting the skin from the external environment. Ceramide and natural moisturizing factor (NMF) are the major SC components that maintain skin moisture. In this study, we investigated whether the oral intake of enzymatically decomposed AP collagen peptides (APCPs) can improve skin moisture and barrier function by assessing changes in the ceramide and NMF contents in the SC after APCP ingestion with the aim to develop a skin functional food. Fifty participants orally ingested APCP (1000 mg) or placebo for 12 weeks, and then, skin hydration and skin texture were evaluated. SC samples were collected to analyze skin scaling, ceramide, and NMF contents. Participants in the APCP group exhibited improved skin moisture content by 7.33% (p = 0.031) and roughness by -4.09% (p = 0.036) when compared with those in the placebo group. NMF content; the amounts of amino acids (AA), including glycine and proline; and AA derivatives were significantly increased in the APCP group (31.98 µg/mg protein) compared to those in the placebo group (-16.01 µg/mg protein) (p = 0.006). The amounts of total ceramides and ceramide subclasses were significantly higher in the APCP group than in the placebo group (p = 0.014). In conclusion, our results demonstrate that APCP intake improves skin moisture and increase the ceramide and NMF contents in the SC, thereby enhancing the skin barrier function.

Feasibility of a Virtual Reality Program in Managing Test Anxiety: A Pilot Study.

Test anxiety has been a growing problem in school-aged children, especially for students in East-Asian countries where the pressure for academic achievement is high. These students are more vulnerable to academic stress, which could further lead to anxiety disorders. For this reason, this study examined the feasibility of virtual reality (VR) test anxiety program in managing anxiety in students. A total of 22 typically developing children with varying levels of test anxiety and no history of psychiatric illnesses participated in the study (mean age = 11.6 and standard deviation [SD] = 1.84). A self-reported questionnaire measuring test anxiety, state-trait anxiety, and depression was administered. Heart rate (HR) variability and subjective anxiety were also measured to examine the changes during each of the anxiety-inducing (Exam 1 and Exam 2) and meditation (Med 1 and Med 2) sessions in the program. There was a significant difference in self-perceived anxiety during the program (p < 0.001), as well as a significant main effect of time on the standard deviation of R-R interval (p = 0.002). In addition, a significant relationship between changes in HR and perceived anxiety during Exam 1 (p = 0.003), Med 1 (p < 0.001), and Med 2 (p = 0.011) was found. In conclusion, this work demonstrates the feasibility of the virtual environment to induce different levels of anxiety and explores the potential use of VR program as a viable method to manage the negative emotion in students. This work shows the potential of technology-enhanced tools in addressing psychological problems in school-aged children. Further study is needed to validate the use of the program in clinical practice.

Broilers fed a low protein diet supplemented with synthetic amino acids maintained growth performance and retained intestinal integrity while reducing nitrogen excretion when raised under poor sanitary conditions.

The present study investigated the effects of supplementing a low protein (LP) diet supplemented with key essential amino acids (AA) to broilers on growth performance, intestinal tract function, blood metabolites, and nitrogen excretion when the animals were maintained under various sanitary conditions for 35 D after hatching. Three hundred eighty-four one-day-old male broilers (Ross 308) were randomly allotted to groups that received one of 6 dietary treatments in a 2 × 3 factorial arrangement (i.e., 2 environmental conditions and 3 dietary treatments) to give 8 replicates per treatment. Broilers were challenged with 2 environmental conditions (sanitary vs. poor sanitary). The dietary treatments were (1) high protein (HP) diet, (2) LP diet, and (3) LP diet with synthetic key essential AA (LPA): the LP diet was supplemented with synthetic AA up to the required levels for broilers. On day 14, birds consumed the LP diet impaired growth performance compared with those fed the HP diet, while the average daily weight gain-to-feed conversion ratio of birds fed the LPA diet improved to the level of birds fed the HP diet under poor sanitary conditions (P < 0.05). Broilers raised under poor sanitary conditions and fed the LP diet displayed higher (P < 0.05) zonula occludens (ZO-1) expression on day 14 than broilers fed either the HP or LPA diet. Under sanitary conditions, birds fed HP and LPA diets showed higher villus height and crypt depth compared with those of broilers fed the LP diet on day 35. Moreover, broilers raised in the poor sanitary environment had higher (P < 0.05) serum endotoxins than those raised in the sanitary environment. Broilers fed the LPA diet showed reduced (P < 0.05) nitrogen excretion on days 14 and 35 compared with those fed the LP and HP diets independent of the environment. In conclusion, the LPA diet did not impair growth performance under poor sanitary conditions for 14 D after hatch while resulting in lower nitrogen excretion in any environment conditions throughout the experiment.

Effect of calcium stearoyl-2 lactylate and lipase supplementation on growth performance, gut health, and nutrient digestibility of broiler chickens.

OBJECTIVE: To evaluate calcium stearoyl-2 lactylate (CSL) performance as an exogenous emulsifier together with lipase for broiler diets. METHODS: In total, 252 one-day-old Ross 308 broiler chickens were allocated in a completely randomized design to give 6 replications per treatment with 7 birds in each cage. There were six dietary treatments representing a 2×3 factorial arrangement consisted of two energy levels (standard energy [positive control, PC] and -100 kcal/kg of the requirement level [negative control, NC]) and three dietary treatments (without additives [CON], CON+CSL [CSL], and CON+CSL+lipase [CSL-Lipase]). Corn and soybean meal-based experimental diets containing vegetable oil were formulated. Growth performance, blood parameters, visceral organ weights, ileal morphology, nutrient digestibility, and cytokine gene expression were measured. RESULTS: Birds fed a diet including CSL increased (p<0.05) lipase level in blood compared to birds fed a diet including CSL-Lipase on day 21. Similarly, higher (p<0.05) liver weight was observed in birds fed a diet including either CSL or CSL-Lipase on day 21. Birds fed NC diet with CSL improved (p<0.05) nutrient digestibility compared to the NC diet on day 21. However, birds fed a diet supplemented with CSL or CSL-Lipase did not affect (p>0.05) the weight gain, feed efficiency, ileal morphology, and cytokine concentrations during the experiment period, regardless of dietary energy levels. CONCLUSION: Our results indicated that CSL has a role in improving nutrient digestibility in young birds when supplemented to a corn-soybean meal based broiler diet.

MRI T2 and T2* relaxometry to visualize neuromelanin in the dorsal substantia nigra pars compacta.

Visualizing gradual changes in neuromelanin distribution within the substantia nigra is an important metric used to monitor the progression of Parkinsonism. This study aimed to identify the origin of the mismatch region between magnetic resonance transverse relaxation times (T2 and T2*) in the substantia nigra and investigate its feasibility and implications for in vivo detection of neuromelanin as a clinical biomarker. The relationships between neuromelanin distribution assessed by histological staining and the area of T2 and T2* mismatch determined by high- and low-resolution magnetic resonance relaxometry at 7T were directly compared in two normal and one depigmented substantia nigra collected at postmortem. In vivo feasibility of assessing T2 and T2* mismatch, clinically, was investigated using 3T magnetic resonance imaging. In the normal postmortem substantia nigra tissue, the T2 and T2* mismatch region exhibiting a linear pattern was strongly colocalized with neuromelanin distribution along the dorsal substantia nigra pars compacta, but a negligible amount of dorsal mismatch was observed in the depigmented brain. The regions of T2 and T2* mismatch from MRI, neuromelanin pigments from histology, and elevated iron signals from mass spectrometry were spatially overlapped for a normal postmortem brain. In preliminary in vivo studies, a similar, linear T2 and T2* mismatch region was observed in the dorsal area of the substantia nigra in eight normal subjects; this mismatch was significantly obscured in eight Parkinson's disease patients. The length of the dorsal linear mismatch line based on the T2*-T2 mask was significantly shorter in the Parkinson's disease patients compared to normal controls; this result was corroborated by reduced striatal uptake of [18F] FP-CIT dopamine transporters assessed by positron emission tomography scans. In conclusion, the measurement of T2 and T2* mismatch could serve as a complementary imaging biomarker to visualize the dorsal region of the substantia nigra pars compacta, which contains large amounts of neuromelanin.

Targeted removal of leukemia cells from the circulating system by whole-body magnetic hyperthermia in mice.

Until now, magnetic hyperthermia was used to remove solid tumors by targeting magnetic nanoparticles (MNPs) to tumor sites. In this study, leukemia cells in the bloodstream were directly removed by whole-body hyperthermia, using leukemia cell-specific MNPs. An epithelial cellular adhesion molecule (EpCAM) antibody was immobilized on the surface of MNPs (EpCAM-MNPs) to introduce the specificity of MNPs to leukemia cells. The viability of THP1 cells (human monocytic leukemia cells) was decreased to 40.8% of that in control samples by hyperthermia using EpCAM-MNPs. In AKR mice, an animal model of lymphoblastic leukemia, the number of leukemia cells was measured following the intravenous injection of EpCAM-MNPs and subsequent whole-body hyperthermia treatment. The result showed that the leukemia cell number was also decreased to 43.8% of that without the treatment of hyperthermia, determined by Leishman staining of leukemia cells. To support the results, simulation analysis of heat transfer from MNPs to leukemia cells was performed using COMSOL Multiphysics simulation software. The surface temperature of leukemia cells adhered to EpCAM-MNPs was predicted to be increased to 82 °C, whereas the temperature of free cells without adhered MNPs was predicted to be 38 °C. Taken together, leukemia cells were selectively removed by magnetic hyperthermia from the bloodstream, because EpCAM-modified magnetic particles were specifically attached to leukemia cell surfaces. This approach has the potential to remove metastatic cancer cells, and pathogenic bacteria and viruses floating in the bloodstream.

In vivo removal of radioactive cesium compound using Prussian blue-deposited iron oxide nanoparticles.

Aim: To mitigate the side effects of medical treatment by Prussian blue (PB), a well-known adsorbent for radioactive cesium (Cs), PB-deposited magnetic nanoparticles (MNPs), were prepared and analyzed on the adsorbent capacity for Cs removal. Materials & methods: The PB-deposited MNPs were prepared by photo-deposition method and investigated for their Cs adsorption properties in vitro and in vivo. The distribution of the adsorbents was also evaluated in C57BL/6 mice. Results: PB-deposited MNPs provided an improved adsorbent capacity for Cs removal and reduced toxicity to blood cells compared with those of bulk PB. Conclusion: PB-deposited MNPs could be considered as an alternative of PB-based medicine to reduce the possible hazards caused by high dose of PB intake.

Piperine inhibits adipocyte differentiation via dynamic regulation of histone modifications.

Previously, we reported that piperine, one of the major pungent components in black pepper, attenuates adipogenesis by repressing PPARγ activity in 3T3-L1 preadipocytes. However, the epigenetic mechanisms underlying this activity remain unexplored. Here, gene set enrichment analysis using microarray data indicated that there was significant downregulation of adipogenesis-associated and PPARγ target genes and upregulation of genes bound with H3K27me3 in response to piperine. As shown by Gene Ontology analysis, the upregulated genes are related to lipid oxidation and polycomb repressive complex 2 (PRC2). Chromatin immunoprecipitation assays revealed that PPARγ (and its coactivators), H3K4me3, and H3K9ac were less enriched at the PPAR response element of three adipogenic genes, whereas increased accumulation of H3K9me2, H3K27me3, and Ezh2 was found, which likely led to the reduced gene expression. Further analysis using three lipolytic genes revealed the opposite enrichment pattern of H3K4me3 and H3K27me3 at the Ezh2 binding site. Treatment with GSK343, an Ezh2 inhibitor, elevated lipolytic gene expression by decreasing the enrichment of H3K27me3 during adipogenesis, which confirms that Ezh2 plays a repressive role in lipolysis. Overall, these results suggest that piperine regulates the expression of adipogenic and lipolytic genes by dynamic regulation of histone modifications, leading to the repression of adipocyte differentiation.

Establishment of a multicomponent dietary bioactive human equivalent dose to delete damaged Lgr5+ stem cells using a mouse colon tumor initiation model.

Multicomponent therapy has gained interest for its potential to synergize and subsequently lower the effective dose of each constituent required to reduce colon cancer risk. We have previously showed that rapidly cycling Lgr5 stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk. In the present study, we quantified the dose-dependent synergistic properties of dietary n-3 polyunsaturated fatty acids (PUFA) and curcumin (Cur) to promote targeted apoptotic deletion of damaged colonic Lgr5 stem cells. For this purpose, both heterogeneous bulk colonocytes and Lgr5 stem cells were isolated from Lgr5-EGFP-IRES-CreER knock-in mice injected with azoxymethane (AOM). Isolated cells were analyzed for DNA damage (γH2AX), apoptosis (cleaved caspase-3), and targeted apoptosis (both γH2AX and cleaved caspase-3) at 12 h post-AOM injection. Comparison of the percentage of targeted apoptosis in Lgr5 stem cells (GFP) across a broad bioactive dose-range revealed an ED50 of 16.0 mg/day n-3 PUFA + 15.9 mg/day Cur. This corresponded to a human equivalent dose of 3.0 g n-3 PUFA + 3.0 g Cur. In summary, our results provide evidence that a low dose (n-3 PUFA + Cur) combination diet reduces AOM-induced DNA damage in Lgr5 stem cells and enhances targeted apoptosis of DNA-damaged cells, implying that a lower human equivalent dose can be utilized in future human clinical trials.

Acer okamotoanum Nakai Leaf Extract Inhibits Adipogenesis Via Suppressing Expression of PPAR γ and C/EBP α in 3T3-L1 Cells.

The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the anti-adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes. Adipogenesis is one of the cell differentiation processes, which converts preadipocytes into mature adipocytes. Nowadays, inhibition of adipogenesis is considered as an effective strategy in the field of anti-obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during adipogenesis and down-regulated the expression of key adipogenic transcription factors such as peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/enhancer binding protein α (C/EBP α). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR γ. LEAO also activated ß-catenin signaling, which prevents the adipogenic program by suppressing the expression of PPAR γ. Therefore, we found that treatment with LEAO is effective for attenuating adipogenesis in 3T3-L1 cells. Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing obesity.

Omega-3 fatty acids, membrane remodeling and cancer prevention.

Proteins are often credited as the macromolecule responsible for performing critical cellular functions, however lipids have recently garnered more attention as our understanding of their role in cell function and human health becomes more apparent. Although cellular membranes are the lipid environment in which many proteins function, it is now apparent that protein and lipid assemblies can be organized to form distinct micro- or nanodomains that facilitate signaling events. Indeed, it is now appreciated that cellular function is partly regulated by the specific spatiotemporal lipid composition of the membrane, down to the nanosecond and nanometer scale. Furthermore, membrane composition is altered during human disease processes such as cancer and obesity. For example, an increased rate of lipid/cholesterol synthesis in cancerous tissues has long been recognized as an important aspect of the rewired metabolism of transformed cells. However, the contribution of lipids/cholesterol to cellular function in disease models is not yet fully understood. Furthermore, an important consideration in regard to human health is that diet is a major modulator of cell membrane composition. This can occur directly through incorporation of membrane substrates, such as fatty acids, e.g., n-3 polyunsaturated fatty acids (n-3 PUFA) and cholesterol. In this review, we describe scenarios in which changes in membrane composition impact human health. Particular focus is placed on the importance of intrinsic lipid/cholesterol biosynthesis and metabolism and extrinsic dietary modification in cancer and its effect on plasma membrane properties.

The moderating effect of religiosity on caregiving burden and depressive symptoms in caregivers of patients with dementia.

OBJECTIVES: This study explored whether religiosity/spirituality has a protective role against negative caregiving outcomes, in a large multicenter nationwide sample of caregivers of patients with dementia in South Korea. Additionally, this study was the first to examine whether religiosity/spirituality could affect caregiving outcomes according to the various religious affiliations of caregivers. METHODS: The study was conducted on a sample of 476 caregivers of patients with dementia participated in the Clinical Research Center for Dementia of South Korea (CREDOS). We examined the moderating effect of each of the three dimensions of religiosity/spirituality (organizational religious activity, ORA; non-organizational religious activity, NORA; intrinsic religiosity, IR) on the relationship between activities of daily living (ADL) of patients with dementia and caregiving burden and depressive symptoms of caregivers, using a series of hierarchical regression analyses. In addition, these analyses were conducted according to the religious affiliations of the caregivers. RESULTS: ORA, NORA, and IR of religiosity/spirituality alleviated the effect of ADL of patients on caregiving burden. ORA and IR moderated the relationship between ADL of patients and depressive symptoms of caregivers. These moderating effects of religiosity on caregiving outcomes were different according to various religious groups. CONCLUSION: We have identified religiosity/spirituality as a protective factor for caregivers of patients with dementia. The sub-dimensions of religiosity as moderators were different by religious affiliations of caregivers. Further studies are needed to investigate the specific religiosity-related factors which could positively impact the mental health of the caregivers of patients with dementia by religions.