Exercise-induced signaling activation by Chrysanthemum zawadskii and its active compound, linarin, ameliorates age-related sarcopenia through Sestrin 1 regulation.

BACKGROUND: Exercise is an effective strategy to prevent sarcopenia, but high physical inactivity in the elderly requires alternative therapeutic approaches. Exercise mimetics are therapeutic compounds that simulate the beneficial effects of exercise on skeletal muscles. However, the toxicity and adverse effects of exercise mimetics raise serious concerns. PURPOSE: We aimed to search novel plant-based alternatives to activate exercise induced-signaling. METHODS: We used open databases and luciferase assays to identify plant-derived alternatives to activate exercise-induced signaling and compared its efficacy to mild intensity continuous training (MICT) in aged C57BL/6 mice. The nineteen-month-old mice were either fed an experimental diet supplemented with the isolated alternative or subjected to MICT for up to 21 mo of age. RESULTS: Our analysis revealed that Chrysanthemum zawadskii Herbich var latillobum (Maxim.) Kitamura (CZH), a medicinal plant rich in linarin, is a novel activator of peroxisome proliferator-activated receptor δ (PPARδ) and estrogen-related receptor γ (ERRγ), key regulators of exercise-induced positive effects on muscles. CZH supplementation ameliorated the loss of muscle function and mass, and increased PPARδ and ERRγ expression in mouse muscles. CZH also improved mitochondrial functions and proteostasis in aged mice, similar to MICT. Furthermore, CZH and linarin induced the activation of Sestrin 1, a key mediator of exercise benefits, in muscle. Silencing Sestrin 1 negated the increase in myogenesis and mitochondrial respiration by CZH and linarin in primary myoblasts from old mice. CONCLUSION: Our findings suggest the potential of CZH as a novel plant-derived alternative to activate exercise-induced signaling for preventing sarcopenia in sedentary older adults. This could offer a safer therapeutic option for sarcopenia treatment.

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.

Low-dose daily folic acid (400 µg) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial.

BACKGROUND: Folic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. OBJECTIVE: The objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. METHODS: In this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 µg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. RESULTS: Among 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 µg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 µg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). CONCLUSIONS: Folate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption. This trial was registered at clinicaltrials.gov as NCT03421483.

Extracellular Vesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells Suppress RANKL-Induced Osteoclast Differentiation via miR122-5p.

Researchers are increasingly interested in cell therapy using mesenchymal stem cells (MSCs) as an alternative remedy for osteoporosis, with fewer side effects. Thus, we isolated and characterized extracellular vesicles (EVs) from human adipose tissue-derived MSCs (hMSCs) and investigated their inhibitory effects on RANKL-induced osteoclast differentiation. Purified EVs were collected from the supernatant of hMSCs by tangential flow filtration. Characterization of EVs included typical evaluation of the size and concentration of EVs by nanoparticle tracking analysis and morphology analysis using transmission electron microscopy. hMSC-EVs inhibited RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by EV treatment of osteoclasts. In addition, EVs decreased RANKL-induced phosphorylation of p38 and JNK and expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. To elucidate which part of the hMSC-EVs plays a role in the inhibition of osteoclast differentiation, we analyzed miRNA profiles in hMSC-EVs. The results showed that has-miR122-5p was present at significantly high read counts. Overexpression of miR122-5p in BMDMs significantly inhibited RANKL-induced osteoclast differentiation and induced defects in F-actin ring formation and bone resorption. Our results also revealed that RANKL-induced phosphorylation of p38 and JNK and osteoclast-specific gene expression was decreased by miR122-5p transfection, which was consistent with the results of hMSC-EVs. These findings suggest that hMSC-EVs containing miR122-5p inhibit RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and could be a preventive candidate for destructive bone diseases.

Gut microbial change after administration of Lacticaseibacillus paracasei AO356 is associated with anti-obesity in a mouse model.

Introduction: The status of an impaired gut microbial community, known as dysbiosis, is associated with metabolic diseases such as obesity and insulin resistance. The use of probiotics has been considered an effective approach for the treatment and prevention of obesity and related gut microbial dysbiosis. The anti-obesity effect of Lacticaseibacillus paracasei AO356 was recently reported. However, the effect of L. paracasei AO356 on the gut microbiota has not yet been identified. This study aimed to elucidate the effect of L. paracasei AO356 on gut microbiota and ensure its safety for use as a probiotic. Methods: Oral administration of L. paracasei AO356 (107 colony-forming units [CFU]/mg per day, 5 days a week, for 10 weeks) to mice fed a high-fat diet significantly suppressed weight gain and fat mass. We investigated the composition of gut microbiota and explored its association with obesity-related markers. Results: Oral administration of L. paracasei AO356 significantly changed the gut microbiota and modified the relative abundance of Lactobacillus, Bacteroides, and Oscillospira. Bacteroides and Oscillospira were significantly related to the lipid metabolism pathway and obesity-related markers. We also confirmed the safety of L. paracasei AO356 using antibiotics resistance, hemolysis activity, bile salt hydrolase activity, lactate production, and toxicity tests following the safety assessment guidelines of the Ministry of Food and Drug Safety (MFDS). Discussion: This study demonstrated that L. paracasei AO356 is not only associated with an anti-obesity effect but also with changes in the gut microbiota and metabolic pathways related to obesity. Furthermore, the overall safety assessment seen in this study could increase the potential use of new probiotic materials with anti-obesity effects.

Artemisia gmelinii Extract Attenuates Particulate Matter-Induced Neutrophilic Inflammation in a Mouse Model of Lung Injury.

Particulate matter (PM) induces and augments oxidative stress and inflammation, leading to respiratory diseases. Although Artemisia gmelinii Weber ex Stechm has antioxidant and anti-inflammatory effects, there are no reports on whether Artemisia gmelinii extract (AGE) regulates lung inflammation in a PM-induced model. Thus, we investigated the protective effects of AGE using a PM-induced mouse lung inflammation model. AGE significantly decreased the expression of inflammatory chemokines, neutrophil extracellular trap formation, and the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Furthermore, AGE attenuated lung inflammation through the suppression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, while promoting the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway in lung tissues. Concordant with these observations, AGE suppressed inflammatory cytokines, chemokines, reactive oxygen species, NETosis, myeloperoxidase, and neutrophil elastase by decreasing the mRNA expression of High mobility group box 1, Runt-related transcription factor 1, and Kruppel-like factor 6 in differentiated HL-60 cells. In summary, our data demonstrated that AGE suppresses PM-induced neutrophil infiltration, lung damage, and pulmonary inflammation by suppressing NF-κB/MAPK signaling pathways and enhancing the NRF2/HO-1 signaling pathway. These findings suggest that AGE administration is an effective approach for preventing and treating PM-induced respiratory inflammation.

Potential of a bivalent vaccine for broad protection against enterovirus 71 and coxsackie virus 16 infections causing hand, foot, and mouth disease.

Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection that is mainly caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16). As there are no specific therapeutics for HFMD, the development of a bivalent vaccine is required to cover a broad range of infections. In this study, the effectiveness of novel monovalent and bivalent vaccines targeting EV71 C4a and CVA16 was investigated for their ability to prevent viral infections in neonatal human scavenger receptor class B member 2 (hSCARB2) transgenic mice. As hSCARB2 serves as a key viral receptor for EV71, these transgenic mice are susceptible to EV71 strains and facilitate viral binding, internalization, and uncoating processes. Antisera prepared by vaccine immunization were transferred to 2-day-old hSCARB2 transgenic mice, which were then infected with EV71 C4a or CVA16 virus. The antisera generated by each monovalent or bivalent vaccine effectively protected against EV71 C4a and CVA16 infections. The examination of tissue damage and viral contents in various organs indicated that both monovalent and bivalent antisera reduced EV71 C4a viral load in the brainstem, and no significant tissue damage was observed. During CVA16 infection, the monovalent and bivalent antisera significantly reduced viral contents in both the brainstem and muscles. These results suggest that passive immunity by monovalent and bivalent antisera can effectively protect against EV71 C4a and CVA16 infections. Thus, the development of a bivalent vaccine that can provide broad protection against both CV and EV infections may be a promising strategy in preventing HFMD.

Selective ensemble methods for deep learning segmentation of major vessels in invasive coronary angiography.

BACKGROUND: Invasive coronary angiography (ICA) is a primary imaging modality that visualizes the lumen area of coronary arteries for diagnosis and interventional guidance. In the current practice of quantitative coronary analysis (QCA), semi-automatic segmentation tools require labor-intensive and time-consuming manual correction, limiting their application in the catheterization room. PURPOSE: This study aims to propose rank-based selective ensemble methods that improve the segmentation performance and reduce morphological errors that limit fully automated quantification of coronary artery using deep-learning segmentation of ICA. METHODS: Two selective ensemble methods proposed in this work integrated the weighted ensemble approach with per-image quality estimation. The segmentation outcomes from five base models with different loss functions were ranked either by mask morphology or estimated dice similarity coefficient (DSC). The final output was determined by imposing different weights according to the ranks. The ranking criteria based on mask morphology were formulated from empirical insight to avoid frequent types of segmentation errors (MSEN), while the estimation of DSCs was performed by comparing the pseudo-ground truth generated from a meta-learner (ESEN). Five-fold cross-validation was performed with the internal dataset of 7426 coronary angiograms from 2924 patients, and prediction model was externally validated with 556 images of 226 patients. RESULTS: The selective ensemble methods improved the segmentation performance with DSCs up to 93.07% and provided a better delineation of coronary lesion with local DSCs of up to 93.93%, outperforming all individual models. Proposed methods also minimized the chances of mask disconnection in the most narrowed regions to 2.10%. The robustness of the proposed methods was also evident in the external validation. Inference time for major vessel segmentation was approximately one-sixth of a second. CONCLUSION: Proposed methods successfully reduced morphological errors in the predicted masks and were able to enhance the robustness of the automatic segmentation. The results suggest better applicability of real-time QCA-based diagnostic methods in routine clinical settings.

Microplastic contamination in groundwater of rural area, eastern part of Korea.

Microplastics (MPs) are emerging contaminants in agricultural regions owing to the widespread use of plastics in farming activities. Groundwater has a vital role in farming activities, and it can be contaminated by MPs, fragmented from plastic products used in agricultural activities. Following an appropriate sampling protocol, this study investigated the distribution of MPs in shallow to deep aquifers (well depths: 3-120 m) and cave water of an agricultural region in Korea. Our investigation found that MPs contamination can penetrate up to the deep bedrock aquifer. The abundance of MPs was lower during the wet season (0.014-0.554 particles/L) than during the dry season (0.042-1.026 particles/L), which may be attributed to the dilution effect of precipitation in the groundwater. The abundance of MPs increased as the MPs size decreased at all sampling points, and size ranges were 20.3-869.6 and 20.3-673.0 µm in the dry and wet seasons, respectively. Our findings showed lower MPs abundance compared to previous studies, and we inferred that it might be due to differences in groundwater sampling volume, low agricultural intensity, and the non-application of sludge fertilizers. Our findings suggest that repeated and long-term investigations are needed to identify better the factors that influence the results of MPs distribution in groundwater, including sampling methods and hydrogeological and hydrological conditions.

A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil.

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

Intranasal immunization with curdlan induce Th17 responses and enhance protection against enterovirus 71.

Mucosal surfaces are in contact with the external environment and protect the body from infection by various microbes. To prevent infectious diseases at the first line of defense, the establishment of pathogen-specific mucosal immunity by mucosal vaccine delivery is needed. Curdlan, a 1,3-ß-glucan has a strong immunostimulatory effect when delivered as a vaccine adjuvant. Here, we investigated whether intranasal administration of curdlan and antigen (Ag) could induce sufficient mucosal immune responses and protect against viral infections. Intranasal co-administration of curdlan and OVA increased OVA-specific IgG and IgA Abs in both serum and mucosal secretions. In addition, intranasal co-administration of curdlan and OVA induced the differentiation of OVA-specific Th1/Th17 cells in the draining lymph nodes. To investigate the protective immunity of curdlan against viral infection, intranasal co-administration of curdlan with recombinant VP1 of EV71 C4a was administered and showed enhanced protection against enterovirus 71 in a passive serum transfer model using neonatal hSCARB2 mice, although intranasal administration of VP1 plus curdlan increased VP1-specific helper T cells responses but not mucosal IgA. Next, Mongolian gerbils were intranasally immunized with curdlan plus VP1, and they had effective protection against EV71 C4a infection, while decreasing viral infection and tissue damage by inducing Th17 responses. These results indicated that intranasal curdlan with Ag improved Ag-specific protective immunity by enhancing mucosal IgA and Th17 against viral infection. Our results suggest that curdlan is an advantageous candidate as a mucosal adjuvant and delivery vehicle for the development of mucosal vaccines.

Deep-Learning Segmentation of Urinary Stones in Noncontrast Computed Tomography.

Background: Noncontrast CT (NCCT) relies on labor-intensive examinations of CT slices to identify urolithiasis in the urinary tract, and, despite the use of deep-learning algorithms, false positives remain. Materials and Methods: A total of 410 NCCT axial scans from patients undergoing surgical treatment for urolithiasis were used for model development. The deep learning model was customized to combine a urolithiasis segmentation with per-slice classification for screening. Prediction models of the axial, coronal, and sagittal views were trained, and an additive model with an intersection of the coronal and sagittal predictions added to the axial outcome was introduced. Automated quantification of clinical metrics was evaluated in three-dimensional models of urinary stones. Results: The axial model detected 88.92% of urinary stones and produced a dice similarity coefficient of 87.56% in the urolithiasis segmentation. For urolithiasis (>5 mm), the sensitivity of the axial model reached 95.10%. False positives were reduced to 0.34 per patient using an ensemble of individual models. The additive model improved the sensitivity to 90.97% by detecting more small urolithiasis (<5 mm). All clinical metrics of size, long-axis diameter, volume, mean stone density, stone heterogeneity index, and skin-to-stone distance showed a strong correlation of R2 > 0.964. Conclusions: The proposed system could reduce the burden on the physician for imaging diagnosis and help determine treatment strategies for urinary stones through automated quantification of clinical metrics with high accuracy and reproducibility.

Microplastic contamination in groundwater on a volcanic Jeju Island of Korea.

Microplastic (MPs) contamination in groundwater has received massive attention since plastic waste has been released directly into the environment. This study investigates MPs contamination in groundwater on the Jeju volcanic Island, Korea. To the best of our knowledge, this is the first study to identify MPs in groundwater from volcanic islands. A total of 21 sites were sampled for groundwater wells and springs in July and September (2021). Sampling was performed without cross-contamination through quality assurance and quality control. The results showed that MPs abundance ranged from 0.006 to 0.192 particles/L in groundwater samples. Additionally, MPs were detected in deep groundwater wells where the groundwater level was 143 m below ground surface. Eight MPs polymer types, including polypropylene, polyethylene, polyethylene terephthalate, polyvinyl chloride, polystyrene, polyamide, acrylonitrile butadiene styrene, and polyurethane, were detected using Micro-Fourier Transform Infrared Spectroscopy (µ-FT-IR). Most of the detected MPs size ranged from 20 to 100 µm, accounting for 95% of the total. Fragments and fiber shaped MPs were detected, with the majority of them being fragmented in groundwater samples. The concentrations of MPs and major ions in groundwater showed a positive correlation. A negative correlation was observed between MPs concentration and topographic elevation (r = -0.59, p = 0.01). The source of MPs contamination is most likely attributed to agricultural activities, such as plastic mulching and greenhouses, which account for most of the land use in the study area. In this study, MPs entered the aquifer through the soil at the surface and seeped through cracks in fractured rock on basalt with sealed groundwater wells. This study takes 500 L of samples to prevent sample bias, reveal plastic contamination in groundwater, and indicating the characteristics and sources of contaminated plastics.

Bulb of Lilium longiflorum Thunb Extract Fermented with Lactobacillus acidophilus Reduces Inflammation in a Chronic Obstructive Pulmonary Disease Model.

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is caused by repeated exposure to harmful matter, such as cigarette smoke. Although Lilium longiflorum Thunb (LLT) has anti-inflammatory effects, there is no report on the fermented LLT bulb extract regulating lung inflammation in COPD. Thus, we investigated the protective effect of LLT bulb extract fermented with Lactobacillus acidophilus 803 in COPD mouse models induced by cigarette smoke extract (CSE) and porcine pancreas elastase (PPE). Oral administration of the fermented product (LS803) suppressed the production of inflammatory mediators and the infiltration of immune cells involving neutrophils and macrophages, resulting in protective effects against lung damage. In addition, LS803 inhibited CSE- and LPS-induced IL-6 and IL-8 production in airway epithelial H292 cells as well as suppressed PMA-induced formation of neutrophil extracellular traps in HL-60 cells. In particular, LS803 significantly repressed the elevated IL-6 and MIP-2 production after CSE and LPS stimulation by suppressing the activity of the nuclear factor kappa-light-chain-enhancer of activated B (NFκB) in mouse peritoneal macrophages. Therefore, our results suggest that the fermented product LS803 is effective in preventing and alleviating lung inflammation.

Remnant cholesterol, low-density lipoprotein cholesterol, and incident cardiovascular disease among Koreans: a national population-based study.

AIMS: The synergistic association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident cardiovascular disease (CVD) in various subgroups of Koreans was investigated. METHODS AND RESULTS: Using the national health insurance data, we included subjects aged between 40 and 70 years without a history of CVD and at least two health screenings between 2009 and 2011. The subjects were divided into four groups by LDL-C and remnant-C levels. The primary outcome was CVD, which occurred between 2014 and 2017. Among 3 686 034 (45.6% women) subjects, 144 004 cardiovascular events occurred. Individuals in both high LDL-C and high remnant-C [hazard ratio (HR) 1.266, 95% confidence interval (CI) 1.243-1.289; 7.9%], high LDL-C only (HR 1.098, 95% CI 1.083-1.113; 21.2%), and high remnant-C only groups (HR 1.102, 95% CI 1.087-1.118; 19.1%) had higher risks of CVD than those in the reference group (LDL-C < 3.4 mmol/L and remnant-C < 0.8 mmol/L; 51.8%). A continuous and linear increase in CVD risk was found in those with higher remnant-C levels after adjustment for several confounders, including LDL-C levels. The association of remnant-C ≥ 0.8 mmol/L with an increased CVD risk was consistent across various strata. CONCLUSIONS: Combined high remnant-C and LDL-C levels confer a higher CVD risk than that individually. Elevated remnant-C values independent of LDL-C levels were associated with a risk of incident CVD. Remnant cholesterol levels in addition to LDL-C levels are important considerations in risk stratification for the primary prevention of CVD.

Since remnant-C has recently emerged as a potential risk factor for CVD, the synergistic association of LDL-C and remnant-C with CVD has been investigated among 3 686 034 Koreans (45.6% women) without preceding CVD using nationwide population-based big data. Remnant cholesterol remained proportional to the risk of incident CVD after adjusting for multiple variables, including LDL-C levels.Low-density lipoprotein cholesterol and remnant-C synergistically contributed to incident CVD.

Impact of the ultra-long 48 mm drug-eluting stent on procedural and clinical outcomes in patients with diffuse long coronary artery disease.

BACKGROUND: Diffuse coronary artery disease (CAD) is a prognostic factor after percutaneous coronary intervention (PCI) and requires multiple overlapping stent implantations. HYPOTHESIS: We investigated the impact of ultra-long 48 mm drug-eluting stent (DES) on procedural and clinical outcomes in real-world practice. METHODS: Patients who underwent DES implantation for a lesion length of >40 mm were selected from a prospective registry between 2019 and 2021. Patients treated with one or more ultra-long 48 mm DES were in the ultra-long DES group (n = 221). The others comprised the conventional DES group (n = 428). Procedural and clinical outcomes were compared after propensity score matching (PSM). The primary endpoint was a device-oriented composite outcome (DOCO) consisting of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization at 1-year follow-up. RESULTS: After PSM, 158 matched pairs of patients showed no differences in the baseline clinical and angiographic characteristics. The stent delivery failure rate, the use of guide-extension catheter or anchor balloon technique, and the procedural success rate were similar for both groups. Approximately two-thirds of lesions could be treated with one DES in the ultra-long DES group. At 1-year follow-up, the DOCO was similar for both groups (2.5% vs. 0.6%, p = .168). CONCLUSIONS: In daily clinical practice, ultra-long DES implantation is as safe and effective as multiple overlapping conventional DES implants in treating diffuse long CAD. However, ultra-long DES can reduce the number of stents. (Trial Registration: ClinicalTrials.gov Identifier: NCT02038127).

The targeted anti-Salmonella bacteriophage attenuated the inflammatory response of laying hens challenged with Salmonella Gallinarum.

Fowl typhoid is a severe disease caused by Salmonella Gallinarum with considerable mortality and morbidity in laying hen farms. The current study has focused on controlling the infection in laying hens using anti-Salmonella spp. bacteriophage. The treatments included, PC, without challenge; NC, S. Gallinarum challenged (SGC); B5, 5 mg bacteriophage/kg + SGC; B10, 10 mg bacteriophage/kg + SGC. The Salmonella shedding, inflammatory responses, and gene expression of pro-inflammatory cytokines, toll-like receptor (TLR), and heat shock protein (HSP) in the jejunum, liver, and thigh muscle were tested in laying hens. Supplementation of bacteriophage reduced the abundance of S. Gallinarum in the excreta at d 3, 7, and 14. The abundance of S. Gallinarum was lower in the B10 than the B5 at d 7. Supplementation of bacteriophage decreased the abundance of S. Gallinarum in the oviduct, spleen, and cecum at d 14. The laying hens in the NC group showed an increased relative spleen weight compared with the PC and B10 treatments. Among the SGC treatments, the NC treatment showed higher gene expressions of IL-4 compared with the B5, higher gene expressions of interferon (IFNγ), TLR4, and tumor necrosis factor-α (TNF-α) compared with the B5 and B10, and higher gene expressions of HSP27 compared with the B10 in the jejunum. Dietary supplementation of B10 decreased the mRNA expressions of TLR4 and TNF-α compared with the B5 treatment in the jejunum. The NC treatment showed the highest gene expressions of HSP27, TLR4, and TNF-α in the liver. Dietary supplementation of B10 showed lower mRNA expressions of HSP27 compared with the B5 treatment in the liver. Moreover, the IFNγ and HSP27 were upregulated in the NC treatment compared with the B5 and B10 in the muscle. In conclusion, it can be suggested that bacteriophage is an effective supplement to control S. Gallinarum infection in laying hens and possibly lower horizontal contaminations in laying hen flocks.

Clinical and Echocardiographic Predictors for the Presence of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Patients with Carbon Monoxide Poisoning.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI) reflects the burden of myocardial damage in carbon monoxide (CO) poisoning. This study aimed to identify the clinical and echocardiographic parameters that can predict myocardial LGE on CMRI in CO poisoning. This prospective observational study included patients who presented with acute CO poisoning and elevated troponin I and underwent echocardiography and CMRI to identify myocardial damage at a tertiary university hospital between August 2017 and May 2019 and August 2020 and July 2022. Based on the CMRI findings, participants were categorized into LGE and non-LGE groups. The median age of the 155 patients was 51.0 years, and 98 (63.2%) were males. Median times from emergency department arrival to either CMRI or echocardiography were 3.0 days each. The LGE group included 99 (63.9%) patients with LGE positivity on CMRIs. Time from rescue to hyperbaric oxygen therapy >4 h (odds ratio (OR): 3.31, 95% confidence interval (CI): 1.28-8.56, p = 0.01); serum lactate levels >2 mmol/L (OR: 2.62, 95% CI: 1.20-5.73, p = 0.02); and left ventricular global longitudinal strain >-16% (OR: 2.95, 95% CI: 1.35-6.47, p = 0.007) were significant predictors of LGE positivity. The area under the curve of these predictors was 0.711. Our prediction model, which combines the clinical parameters with left ventricular global longitudinal strain, may be helpful in the early detection of LGE positivity.

Castor Oil Plant (Ricinus communis L.) Leaves Improve Dexamethasone-Induced Muscle Atrophy via Nrf2 Activation.

Skeletal muscle atrophy is characterized by reduced muscle function and size. Oxidative stress contributes to muscle atrophy but can be treated with antioxidants. This study investigated the antioxidant activity of a castor oil plant leaf (Ricinus communis L.) extract (RC) and its effects on muscle atrophy. Rutin was identified as the major compound among the thirty compounds identified in RC via LC-MS/MS and was found to inhibit dexamethasone (DEX)-induced muscle atrophy and mitochondrial oxidative stress. Rutin-rich RC showed DPPH and ABTS radical scavenging activities and efficiently reduced the DEX-induced myotube atrophy and mitochondrial oxidative damage in C2C12 cells. RC supplementation prevented the loss of muscle function and muscle mass in DEX-administered mice and ameliorated DEX-induced oxidative stress via Nrf2 signaling. Taken together, both RC and rutin ameliorated muscle atrophy and helped in maintaining redox homeostasis; hence, rutin-rich RC could be a promising functional food that is beneficial for muscle health.

Deep-learning segmentation of ultrasound images for automated calculation of the hydronephrosis area to renal parenchyma ratio.

PURPOSE: We investigated the feasibility of measuring the hydronephrosis area to renal parenchyma (HARP) ratio from ultrasound images using a deep-learning network. MATERIALS AND METHODS: The coronal renal ultrasound images of 195 pediatric and adolescent patients who underwent pyeloplasty to repair ureteropelvic junction obstruction were retrospectively reviewed. After excluding cases without a representative longitudinal renal image, we used a dataset of 168 images for deep-learning segmentation. Ten novel networks, such as combinations of DeepLabV3+ and UNet++, were assessed for their ability to calculate hydronephrosis and kidney areas, and the ensemble method was applied for further improvement. By dividing the image set into four, cross-validation was conducted, and the segmentation performance of the deep-learning network was evaluated using sensitivity, specificity, and dice similarity coefficients by comparison with the manually traced area. RESULTS: All 10 networks and ensemble methods showed good visual correlation with the manually traced kidney and hydronephrosis areas. The dice similarity coefficient of the 10-model ensemble was 0.9108 on average, and the best 5-model ensemble had a dice similarity coefficient of 0.9113 on average. We included patients with severe hydronephrosis who underwent renal ultrasonography at a single institution; thus, external validation of our algorithm in a heterogeneous ultrasonography examination setup with a diverse set of instruments is recommended. CONCLUSIONS: Deep-learning-based calculation of the HARP ratio is feasible and showed high accuracy for imaging of the severity of hydronephrosis using ultrasonography. This algorithm can help physicians make more accurate and reproducible diagnoses of hydronephrosis using ultrasonography.