Traditional Korean diet high in one-carbon nutrients increases global DNA methylation: implication for epigenetic diet.

PURPOSE: DNA methylation is a major epigenetic phenomenon through which diet affects health and disease. This study aimed to determine the epigenetic influence of the traditional Korean diet (K-diet) on global DNA methylation via one-carbon metabolism. METHODS: A crossover study was conducted on 52 women. Two diets, a K-diet, high in plant foods and low in calories and animal fat, and a control diet, similar to the diet currently consumed in Korea, were provided to all subjects alternately for 4 weeks with a 4-week washout period. Clinical parameters were measured before and after each dietary intervention. Nutrient intake was calculated by using a computer-aided nutritional analysis program. One-carbon metabolites in the serum and global DNA methylation in peripheral mononuclear cells were determined using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: The K-diet group consumed more folate (669.9 ± 6.7 µg vs. 502.7 ± 3.0, p < 0.001), B6, B12, serine, and choline, and less methionine (992.6 ± 63 vs. 1048.3 mg ± 34.1, p < 0.0001) than the control group did. In the K-diet group, the increment of plasma 5-methyltetrahydrofolate (0.08 µg/mL ± 0.11 vs 0.02 ± 0.10, p < 0.009) and decrement of L-homocysteine (- 70.7 ± 85.0 vs - 39.3 ± 69.4, p < 0.0168) were greater than those of the control group. Global DNA methylation was significantly increased in the K-diet group (6.70 ± 3.02% to 9.45 ± 3.69, p < 0.0001) but not in the control group. CONCLUSIONS: A K-diet high in one-carbon nutrients can enhance the global DNA methylation status, suggesting an epigenetic mechanism by which the K-diet conveys health effects. Trial registration Korean Clinical Trial Registry (trial number: KCT0005340, 24/08/2020, retrospectively registered).

Assessment of the occurrence of the second generation of Mythimna loreyi Duponchel (Lepidoptera: Noctuidae) using temperature-dependent developmental and oviposition models.

A significant crop pest, Mythimna loreyi, migrates annually to Korea and has been frequently observed in rice and corn fields. However, the phenology of this pest, particularly in relation to its ecological interactions and host crop seasons in Korea, remains poorly understood. This study aims to clarify the timing of the second generation of M. loreyi in Korea to enhance pest management strategies. To achieve this, we developed temperature-dependent models for developmental and ovipositional rates, studying these processes across five constant temperatures (15, 20, 25, 30, and 35°C). Our models, which showed a high correlation with observed data (r2 ≥ 0.93), include a theoretical approach that combines the developmental variation of immatures with the necessary degree-days for 50% egg laying and complete egg development. These predictions allow for the forecasting of the second generation's occurrence, with relatively small deviations (one to three days) observed at two different field sites. The insights from this study are critical for both understanding the ecology of M. loreyi and for informing practical management decisions, such as optimal placement of barriers to prevent immigration and strategies for controlling local populations.

Are sporadic colorectal cancers in young patients distinct from those in elderly patients?

AIM: The aim of this study was to compare the clinicopathological and oncological characteristics of sporadic colorectal cancer (CRC) between young and elderly patients without any genetic mutations that cause hereditary CRC. METHOD: In this cross-sectional, retrospective study conducted at three tertiary referral hospitals, we enrolled 1599 patients with CRC who underwent surgery between January 2010 and December 2017, including 157 young patients (age ≤ 40 years; yCRC) and 1442 elderly patients (age ≥ 70 years; eCRC). The clinicopathological and oncological outcomes were compared between the two groups. RESULTS: The median age at diagnosis was 37 years in the yCRC group (range 33.0-39.2 years) and 76 years in the eCRC group (range 72.0-79.0 years). The yCRC group did not present with advanced stages at diagnosis compared with the eCRC group, and the distribution of tumour stages was similar between the two groups. Microsatellite instability (MSI) testing revealed no difference in the frequency of tumours with high MSI (7.8% in yCRC, 5.8% in eCRC), and the frequency of mutations in the KRAS, NRAS and BRAF genes was also similar. The 3-year overall survival was better in the yCRC group than in the eCRC group (97.4% vs. 83.5%, p < 0.001); however, no such difference was observed in cancer-specific survival. CONCLUSION: Genetically proven sporadic CRCs did not differ significantly between young and elderly patients in terms of tumour stage, tumour location and various molecular features. CLINICAL TRIAL REGISTRATION NUMBER: The study was retrospectively registered with Clinical Trials.gov (no. NCT05601609).

High vegetable consumption and regular exercise are associated with better quality of life in patients with gout.

Background/Aims: The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. Methods: We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. Results: The study included 232 patients. 'Gout concern overall' scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and 'well-being during attack' scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the 'well-being during attack' and 'gout concern during attack' scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the 'gout concern overall' and 'gout concern during attack' scores (p = 0.04 and p = 0.002, respectively). Conclusions: Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

A study of the effect of testing for diversification of healthcare waste sterilization and crushing facilities.

This study conducted sterilization testing under different conditions using different strains for sterilization and crushing, the intermediate healthcare waste treatment phase, and proposed strategies for diversifying corresponding facilities in addition to promoting their installation. Five indicator microorganisms were selected to test the sterilization efficiency of steam, microwave, and chemical methods. Steam sterilization testing was conducted in accordance with legal and technological standards, microwave testing was carried out according to the legal standard, and chemical sterilization employed three typical compounds. Steam and microwave sterilization achieved 99.9999 % inactivation rates for all five strains under both conditions used; whereas under the chemical sterilization analyses, sodium hypochlorite (1000 ppm) failed to meet the inactivation requirement of the fungal strain Candida albicans, requiring further investigation. Based on these findings, this study presents strategies for diversifying sterilization·crushing facilities and promoting their installation.

A shared mechanism of multidrug resistance in laboratory-evolved uropathogenic Escherichia coli.

The emergence of multidrug-resistant bacteria poses a significant threat to human health, necessitating a comprehensive understanding of their underlying mechanisms. Uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections, is frequently associated with multidrug resistance and recurrent infections. To elucidate the mechanism of resistance of UPEC to beta-lactam antibiotics, we generated ampicillin-resistant UPEC strains through continuous exposure to low and high levels of ampicillin in the laboratory, referred to as Low AmpR and High AmpR, respectively. Whole-genome sequencing revealed that both Low and High AmpR strains contained mutations in the marR, acrR, and envZ genes. The High AmpR strain exhibited a single additional mutation in the nlpD gene. Using protein modeling and qRT-PCR analyses, we validated the contributions of each mutation in the identified genes to antibiotic resistance in the AmpR strains, including a decrease in membrane permeability, increased expression of multidrug efflux pump, and inhibition of cell lysis. Furthermore, the AmpR strain does not decrease the bacterial burden in the mouse bladder even after continuous antibiotic treatment in vivo, implicating the increasing difficulty in treating host infections caused by the AmpR strain. Interestingly, ampicillin-induced mutations also result in multidrug resistance in UPEC, suggesting a common mechanism by which bacteria acquire cross-resistance to other classes of antibiotics.

Liquid Chromatography/Tandem Mass Spectrometry Analysis of Sophora flavescens Aiton and Protective Effects against Alcohol-Induced Liver Injury and Oxidative Stress in Mice.

In this study, we investigated the hepatoprotective effects of an ethanol extract of Sophora flavescens Aiton (ESF) on an alcohol-induced liver disease mouse model. Alcoholic liver disease (ALD) was caused by the administration of ethanol to male C57/BL6 mice who were given a Lieber-DeCarli liquid diet, including ethanol. The alcoholic fatty liver disease mice were orally administered ESF (100 and 200 mg/kg bw/day) or silymarin (50 mg/kg bw/day), which served as a positive control every day for 16 days. The findings suggest that ESF enhances hepatoprotective benefits by significantly decreasing serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), markers for liver injury. Furthermore, ESF alleviated the accumulation of triglyceride (TG) and total cholesterol (TC), increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), and improved serum alcohol dehydrogenase (ADH) activity in the alcoholic fatty liver disease mice model. Cells and organisms rely on the Kelch-like ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) system as a critical defensive mechanism in response to oxidative stress. Therefore, Nrf2 plays an important role in ALD antioxidant responses, and its level is decreased by increased reactive oxidation stress (ROS) in the liver. ESF increased Nrf2, which was decreased in ethanol-damaged livers. Additionally, four polyphenol compounds were identified through a qualitative analysis of the ESF using LC-MS/MS. This study confirmed ESF's antioxidative and hangover-elimination effects and suggested the possibility of using Sophora flavescens Aiton (SF) to treat ALD.

Ziziphus jujuba Miller Ethanol Extract Restores Disrupted Intestinal Barrier Function via Tight Junction Recovery and Reduces Inflammation.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by the disruption of the intestinal barrier. The intestinal barrier is maintained by tight junctions (TJs), which sustain intestinal homeostasis and prevent pathogens from entering the microbiome and mucosal tissues. Ziziphus jujuba Miller (Z. jujuba) is a natural substance that has been used in traditional medicine as a therapy for a variety of diseases. However, in IBD, the efficacy of Z. jujuba is unknown. Therefore, we evaluated ZJB in Caco2 cells and a dextran sodium sulfate (DSS)-induced mouse model to demonstrate its efficacy in IBD. Z. jujuba extracts were prepared using 70% ethanol and were named ZJB. ZJB was found to be non-cytotoxic and to have excellent antioxidant effects. We confirmed its anti-inflammatory properties via the down-regulation of inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). To evaluate the effects of ZJB on intestinal barrier function and TJ improvement, the trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran 4 kDa (FITC-Dextran 4) permeability were assessed. The TEER value increased by 61.389% and permeability decreased by 27.348% in the 200 µg/mL ZJB group compared with the 50 ng/mL IL-6 group after 24 h. Additionally, ZJB alleviated body weight loss, reduced the disease activity index (DAI) score, and induced colon shortening in 5% DSS-induced mice; inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were down-regulated in the serum. TJ proteins, such as Zonula occludens (ZO)-1 and occludin, were up-regulated by ZJB in an impaired Caco2 mouse model. Additionally, according to the liquid chromatography results, in tandem with mass spectrometry (LC-MS/MS) analysis, seven active ingredients were detected in ZJB. In conclusion, ZJB down-regulated inflammatory factors, protected intestinal barrier function, and increased TJ proteins. It is thus a safe, natural substance with the potential to be used as a therapeutic agent in IBD treatment.

HIGH PLOIDY2-mediated SUMOylation of transcription factor ARR1 controls two-component signaling in Arabidopsis.

Cytokinins regulate plant growth, development, and responses to environmental stresses such as cold via phosphorelay from cytokinin receptors to the ARABIDOPSIS RESPONSE REGULATORs (ARRs). However, the molecular mechanisms underlying the activation of type-B ARR transcriptional activity in Arabidopsis (Arabidopsis thaliana) remain unclear. Here, we show that the E3 SUMO ligase HIGH PLOIDY2 SUMOylates ARR1, a type-B ARR, at K236, triggering its activation. Cold- or cytokinin-induced phosphorylation of ARR1 at D89 is crucial for its interaction with HPY2. Lysine 236 is critical for ARR1's transactivation without compromising its DNA-binding ability, while D89 is crucial for ARR1's binding to target gene promoters. Cytokinin enhances ARR1's chromatin binding, but cold does not. ARR1 K236 plays a critical role in promoting histone H3 acetylation in response to both cytokinin and cold without affecting chromatin binding. The K236R mutation in ARR1 reduces target gene expression and alters cytokinin and cold response phenotypes. This study unveils a mechanism of ARR1 activation wherein phosphorylated ARR1 interacts with HPY2 and binds to chromatin in response to cytokinin. Cold triggers a phosphorelay targeting chromatin-bound ARR1. HPY2 then catalyzes ARR1 SUMOylation at K236, enhancing histone H3 acetylation and leading to transcriptional activation of ARR1 in response to both cold and cytokinin.

Discovery of (-)-epigallocatechin gallate, a novel olfactory receptor 2AT4 agonist that regulates proliferation and apoptosis in leukemia cells.

Olfactory receptors (ORs), the largest family of G protein-coupled receptors (GPCRs), are ectopically expressed in cancer cells and are involved in cellular physiological processes, but their function as anticancer targets is still potential. OR2AT4 is expressed in leukemia cells, influencing the proliferation and apoptosis, yet the limited number of known OR2AT4 agonists makes it challenging to fully generalize the receptor's function. In this study, we aimed to identify new ligands for OR2AT4 and to investigate their functions and mechanisms in K562 leukemia cells. After producing the recombinant OR2AT4 protein, immobilizing it on a surface plasmon resonance chip, and conducting screening to confirm binding activity using 258 chemicals, five novel OR2AT4 ligands were discovered. As a result of examining changes in intracellular calcium by five ligands in OR2AT4-expressing cells and K562 cells, (-)-epigallocatechin gallate (EGCG) was identified as an OR2AT4 agonist in both cells. EGCG reduced the viability of K562 cells and induced apoptosis in K562 cells. EGCG increased the expression of cleaved caspase 3/8 and had no effect on the expression of Bax and Bcl-2, indicating that it induced apoptosis through the extrinsic pathway. Additionally, the initiation of the extrinsic apoptosis pathway in EGCG-induced K562 cells was due to the activation of OR2AT4, using an OR2AT4 antagonist. This study highlights the potential of EGCG as an anti-cancer agent against leukemia and OR2AT4 as a target, making it a new anti-cancer drug.

A mobile app to predict and manage behavioral and psychological symptoms of dementia: Development, usability, and users' acceptability.

Objective: Non-pharmacological interventions are considered the first-line treatment for behavioral and psychological symptoms of dementia (BPSD); however, traditional approaches have shown only small effect sizes. Mobile technology offers an opportunity to improve BPSD assessment and management in people living with dementia (PLWD). We aimed (1) to develop a mobile application (app) featuring a real-time BPSD diary, machine-learning-based BPSD prediction, and individualized non-pharmacological care programs, including therapeutic use of music and reminiscent content, and (2) to test its usability, acceptability, and preliminary efficacy among PLWD and caregivers. Methods: An Android-based app was developed through the following three phases: (1) needs assessment, (2) software development and initial testing with experts, and (3) beta-testing with end users who were dyads of PLWD and caregivers. The preliminary efficacy, usability, and acceptability of the app were assessed using validated BPSD questionnaires and face-to-face interviews with the dyads. Logs of the dyads' program participation (i.e., types, time, and duration), BPSD diaries, and engagement levels of PLWD were also collected through the app. Results: Five dyads created BPSD diaries (range: 22-48) over 3 weeks. Overall, the BPSD symptoms decreased after the beta-testing period. Each dyad participated in the care programs for 106-204 min, during which music alone was most frequently used. Engagement levels ranged from 3.38 to 4.94 (out of 5). Conclusions: The app was deemed usable, acceptable, and feasible for PLWD and caregivers. The upgraded app will be further tested and can be easily implemented at home or in the community.

Isoeugenol Inhibits Adipogenesis in 3T3-L1 Preadipocytes with Impaired Mitotic Clonal Expansion.

Isoeugenol (IEG), a natural component of clove oil, possesses antioxidant, anti-inflammatory, and antibacterial properties. However, the effects of IEG on adipogenesis have not yet been elucidated. Here, we showed that IEG blocks adipogenesis in 3T3-L1 cells at an early stage. IEG inhibits lipid accumulation in adipocytes in a concentration-dependent manner and reduces the expression of mature adipocyte-related factors including PPARγ, C/EBPα, and FABP4. IEG treatment at different stages of adipogenesis showed that IEG inhibited adipocyte differentiation by suppressing the early stage, as confirmed by lipid accumulation and adipocyte-related biomarkers. The early stage stimulates growth-arrested preadipocytes to enter mitotic clonal expansion (MCE) and initiates their differentiation into adipocytes by regulating cell cycle-related factors. IEG arrested 3T3-L1 preadipocytes in the G0/G1 phase of the cell cycle and attenuated cell cycle-related factors including cyclinD1, CDK6, CDK2, and cyclinB1 during the MCE stage. Furthermore, IEG suppresses reactive oxygen species (ROS) production during MCE and inhibits ROS-related antioxidant enzymes, including superoxide dismutase1 (SOD1) and catalase. The expression of cell proliferation-related biomarkers, including pAKT and pERK1/2, was attenuated by the IEG treatment of 3T3-L1 preadipocytes. These findings suggest that it is a potential therapeutic agent for the treatment of obesity.

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.

AI analytics can be used as imaging biomarkers for predicting invasive upgrade of ductal carcinoma in situ.

OBJECTIVES: To evaluate whether the quantitative abnormality scores provided by artificial intelligence (AI)-based computer-aided detection/diagnosis (CAD) for mammography interpretation can be used to predict invasive upgrade in ductal carcinoma in situ (DCIS) diagnosed on percutaneous biopsy. METHODS: Four hundred forty DCIS in 420 women (mean age, 52.8 years) diagnosed via percutaneous biopsy from January 2015 to December 2019 were included. Mammographic characteristics were assessed based on imaging features (mammographically occult, mass/asymmetry/distortion, calcifications only, and combined mass/asymmetry/distortion with calcifications) and BI-RADS assessments. Routine pre-biopsy 4-view digital mammograms were analyzed using AI-CAD to obtain abnormality scores (AI-CAD score, ranging 0-100%). Multivariable logistic regression was performed to identify independent predictive mammographic variables after adjusting for clinicopathological variables. A subgroup analysis was performed with mammographically detected DCIS. RESULTS: Of the 440 DCIS, 117 (26.6%) were upgraded to invasive cancer. Three hundred forty-one (77.5%) DCIS were detected on mammography. The multivariable analysis showed that combined features (odds ratio (OR): 2.225, p = 0.033), BI-RADS 4c or 5 assessments (OR: 2.473, p = 0.023 and OR: 5.190, p < 0.001, respectively), higher AI-CAD score (OR: 1.009, p = 0.007), AI-CAD score ≥ 50% (OR: 1.960, p = 0.017), and AI-CAD score ≥ 75% (OR: 2.306, p = 0.009) were independent predictors of invasive upgrade. In mammographically detected DCIS, combined features (OR: 2.194, p = 0.035), and higher AI-CAD score (OR: 1.008, p = 0.047) were significant predictors of invasive upgrade. CONCLUSION: The AI-CAD score was an independent predictor of invasive upgrade for DCIS. Higher AI-CAD scores, especially in the highest quartile of ≥ 75%, can be used as an objective imaging biomarker to predict invasive upgrade in DCIS diagnosed with percutaneous biopsy. CRITICAL RELEVANCE STATEMENT: Noninvasive imaging features including the quantitative results of AI-CAD for mammography interpretation were independent predictors of invasive upgrade in lesions initially diagnosed as ductal carcinoma in situ via percutaneous biopsy and therefore may help decide the direction of surgery before treatment. KEY POINTS: • Predicting ductal carcinoma in situ upgrade is important, yet there is a lack of conclusive non-invasive biomarkers. • AI-CAD scores-raw numbers, ≥ 50%, and ≥ 75%-predicted ductal carcinoma in situ upgrade independently. • Quantitative AI-CAD results may help predict ductal carcinoma in situ upgrade and guide patient management.

Pulmonary function characteristics in children with suspected asthma: implications for asthma diagnosis.

BACKGROUND: In children suspected of asthma, diagnosis is confirmed via variable expiratory airflow limitation. However, there is no single gold standard test for diagnosing asthma. OBJECTIVE: This study aimed to evaluate the pulmonary function characteristics in children suspected of asthma without bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR). METHODS: We utilized two separate real-world retrospective observational cohorts of children who underwent both spirometry and bronchial provocation testing for asthma. Spirometry parameters were collected and compared between definite asthma, probable asthma, and non-asthma groups. The original cohort comprised 1199 children who visited the Severance Hospital (Seoul, Korea) between January 2017 and December 2019. The external cohort included 105 children who visited the Gangnam Severance Hospital between January 2019 and December 2019. RESULTS: Probable asthma accounted for 16.8% and 32.4% of the original and external cohorts, respectively. This group showed a significantly higher FeNO level and prevalence of allergic sensitization. Baseline forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75), and FEF75 showed stepwise decrements from non-asthma, probable asthma, to definite asthma patients (P < 0.001). The probable asthma group showed significantly higher odds of abnormal FEV1/FVC (OR, 2.24 [95%CI, 1.43-3.52])and FEF25-75 (2.05 [1.13-3.73]) than the non-asthma group and lower odds of abnormal FEV1(0.05 [0.01-0.19]),FEV1 /FVC (0.27 [0.18-0.41]), FEF25-75 (0.17 [0.11-0.28]), and FEF75 (0.14 [0.08-0.24]) compared to the definite asthma group. The external cohort was consistent with the original cohort. CONCLUSION: We show evidence of airway dysfunction in children for whom a high clinical suspicion of asthma exists without evidence of BDR and BHR. Repeated pulmonary function tests that closely monitor for subtle lung function impairments and active utilization of additional tests, such as allergic screening and FeNO, should be considered to close the gap in diagnosing asthma.

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.

Effects of Growth Hormone-Releasing Hormone (GHRH) Plasmid Treatment on the Reproductive Productivity of Sows in Primiparous and Multiparous Sow Breeds.

The effect of growth hormone-releasing hormone (GHRH) plasmid treatment on sow reproductive performance was examined. Forty pregnant sows (three-way crossbreed: Landrace × Yorkshire × Duroc) at 85 days of gestation were included in the study and consisted of twenty primiparous and twenty multiparous sows (third parity). Sows were randomly assigned to the control and treatment groups. The treatment group received 5 mg dose of GHRH plasmid injection via electroporation, whereas the control group received a phosphate buffer solution. Reproductive indicators, including serum insulin-like growth factor-1 (IGF-1) concentration and weaned piglet data, were assessed. In the GHRH plasmid-treated group, serum IGF-1 concentration significantly increased compared with that in the control group, a trend observed in primiparous and multiparous sows. The key indicator of reproductive performance, litter size, showed that for control primiparous sows (C-PS), it was 10.90 ± 0.99 kg, while for control multiparous sows (C-MS), it was 14.00 ± 0.67 kg. Furthermore, for primiparous sows treated with GHRH plasmid (G-PS), the litter size was 11.60 ± 0.97 kg, and for multiparous sows treated with GHRH plasmid (G-MS), it was 14.00 ± 0.82 kg. The GHRH plasmid-treated group also exhibited a higher number of total births and surviving piglet numbers, along with a decrease in stillborn piglets; however, there was no significant difference in birth weight. The results suggest that GHRH plasmid treatment can enhance the reproductive performance of sows.

Recent Advances in Lateral Flow Assays for Viral Protein Detection with Nanomaterial-Based Optical Sensors.

Controlling the progression of contagious diseases is crucial for public health management, emphasizing the importance of early viral infection diagnosis. In response, lateral flow assays (LFAs) have been successfully utilized in point-of-care (POC) testing, emerging as a viable alternative to more traditional diagnostic methods. Recent advancements in virus detection have primarily leveraged methods such as reverse transcription-polymerase chain reaction (RT-PCR), reverse transcription-loop-mediated isothermal amplification (RT-LAMP), and the enzyme-linked immunosorbent assay (ELISA). Despite their proven effectiveness, these conventional techniques are often expensive, require specialized expertise, and consume a significant amount of time. In contrast, LFAs utilize nanomaterial-based optical sensing technologies, including colorimetric, fluorescence, and surface-enhanced Raman scattering (SERS), offering quick, straightforward analyses with minimal training and infrastructure requirements for detecting viral proteins in biological samples. This review describes the composition and mechanism of and recent advancements in LFAs for viral protein detection, categorizing them into colorimetric, fluorescent, and SERS-based techniques. Despite significant progress, developing a simple, stable, highly sensitive, and selective LFA system remains a formidable challenge. Nevertheless, an advanced LFA system promises not only to enhance clinical diagnostics but also to extend its utility to environmental monitoring and beyond, demonstrating its potential to revolutionize both healthcare and environmental safety.

Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways.

PURPOSE: The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature. METHODS: C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells. RESULTS: The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice. CONCLUSION: These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.

Identification of Peucedanum japonicum Thunb. extract components and their protective effects against dexamethasone-induced muscle atrophy.

BACKGROUND: Peucedanum japonicum Thunb. (PJ) is a vegetable widely consumed in East Asia and is known to have anticancer and anti-inflammatory effects. However, the effect of PJ on muscle atrophy remains elusive. PURPOSE: This study aimed to investigate the effect of PJ and its active compound on dexamethasone (DEX)-induced muscle atrophy. METHODS: We performed qualitative and quantitative analysis of PJ using ultra-performance liquid chromatography-mass spectrometry tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. The efficacy of PJ and its main compound 4-caffeoylquinic acid (CQA) on muscle atrophy was evaluated in DEX-induced myotube atrophy and DEX-induced muscle atrophy in mouse myoblasts (C2C12) and C57BL/6 mice, in vitro and in vivo, respectively. RESULTS: The UPLC-MS/MS and HPLC data showed that the concentration of 4-CQA in PJ was 18.845 mg/g. PJ and 4-CQA treatments significantly inhibited DEX-induced myotube atrophy by decreasing protein synthesis and glucocorticoid translocation to the nucleus in C2C12 myotubes. In addition, PJ enhanced myogenesis by upregulating myogenin and myogenic differentiation 1 in C2C12 cells. PJ supplementation effectively increased muscle function and mass, downregulated atrogenes, and decreased proteasome activity in C57BL/6 mice. Additionally, PJ effectively decreased the nuclear translocation of forkhead transcription factor 3 alpha by inhibiting glucocorticoid receptor. CONCLUSION: Overall, PJ and its active compound 4-CQA alleviated skeletal muscle atrophy by inhibiting protein degradation. Hence, our findings present PJ as a potential novel pharmaceutical candidate for the treatment of muscle atrophy.