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Diarrhea, a common gastrointestinal symptom in health problems, is highly associated with gut dysbiosis. The purpose of this study is to demonstrate the effect of multistrain probiotics (Sensi-Biome) on diarrhea from the perspective of the microbiome-neuron axis. Sensi-Biome (Lactiplantibacillus plantarum, Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, Streptococcus thermophilus, Bifidobacterium bifidum, and Lactococcus lactis) was administered in a 4% acetic acid-induced diarrhea rat model at concentrations of 1 × 108 (G1), 1 × 109 (G2), and 1 × 1010 CFU/0.5 mL (G3). Diarrhea-related parameters, inflammation-related cytokines, and stool microbiota analysis by 16S rRNA were evaluated. A targeted and untargeted metabolomics approach was used to analyze the cecum samples using liquid chromatography and orbitrap mass spectrometry. The stool moisture content (p < 0.001), intestinal movement rate (p < 0.05), and pH (p < 0.05) were significantly recovered in G3. Serotonin levels were decreased in the multistrain probiotics groups. The inflammatory cytokines, serotonin, and tryptophan hydroxylase expression were improved in the Sensi-Biome groups. At the phylum level, Sensi-Biome showed the highest relative abundance of Firmicutes. Short-chain fatty acids including butyrate, iso-butyrate, propionate, and iso-valeric acid were significantly modified in the Sensi-Biome groups. Equol and oleamide were significantly improved in the multistrain probiotics groups. In conclusion, Sensi-Biome effectively controls diarrhea by modulating metabolites and the serotonin pathway.
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Personalized probiotic regimens, taking into account individual characteristics such as stool patterns, have the potential to alleviate gastrointestinal disorders and improve gut health while avoiding the variability exhibited among individuals by conventional probiotics. This study aimed to explore the efficacy of personalized probiotic interventions in managing distinct stool patterns (constipation and diarrhea) by investigating their impact on the gut microbiome and gastrointestinal symptoms using a prospective, randomized, double-blind, placebo-controlled clinical trial design. This research leverages the multi-strain probiotic formulas, Consti-Biome and Sensi-Biome, which have previously demonstrated efficacy in alleviating constipation and diarrhea symptoms, respectively. Improvement in clinical symptoms improvement and compositional changes in the gut microbiome were analyzed in participants with predominant constipation or diarrhea symptoms. Results indicate that tailored probiotics could improve constipation and diarrhea by promoting Erysipelotrichaceae and Lactobacillaceae, producers of short-chain fatty acids, and regulating inflammation and pain-associated taxa. These findings suggest the potential of tailored probiotic prescriptions and emphasize the need for personalized therapeutic approaches for digestive disorders. Clinical trial registration: https://cris.nih.go.kr/cris/index/index.do, identifier KCT0009111.
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Background@#Posterior femoral condylar osteophytes were frequently observed in patients with the ultra-congruent (UC) deepdish design prosthesis. Therefore, the purpose of the present study was to verify the clinical relevance of osteophyte formation in the UC design. @*Methods@#From March 2014 to February 2018, a comparative study was conducted on 96 knees using the UC design. They were divided into 2 groups (group 1: osteophyte +, group 2: osteophyte –). Intraoperative findings, indirect femoral rollback assessment using 30° flexion and active full flexion lateral radiographs, serial change of the osteophyte, and outcomes were compared. @*Results@#The mean follow-up period was 49.35 ± 3.47 months in group 1 and 47.52 ± 3.37 months in group 2. Posterior component coverage was significantly different between the groups: group 1 exhibited more underhang and group 2 exhibited more overhang (p = 0.022). On the indirect assessment of the femoral rollback, there was a statistically significant difference in deep flexion and change in distance (p < 0.001 and p < 0.001, respectively). There was no statistical difference between the 2 groups in the American Knee Society knee and function score, and group 2 showed significant improvement in pain compared to group 1 in Western Ontario and McMaster University Arthritis Index pain score (p = 0.029). @*Conclusions@#Posterior condylar osteophyte formation was related to posterior impingement. It was more frequently observed in the underhang of the femoral component and insufficient femoral rollback. In addition, it changed with time and caused negative effects, including a gradual decrease in flexion and more pain.
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Objective@#Giant cell arteritis (GCA) is a large-vessel vasculitis that primarily affects elderly individuals. However, data regarding Korean patients with GCA are scarce owing to its extremely low prevalence in East Asia. This study aimed to investigate the clinical characteristics of Korean patients with GCA and their outcomes, focusing on relapse. @*Methods@#The medical records of 27 patients with GCA treated at three tertiary hospitals between 2007 and 2022 were retrospectively reviewed. @*Results@#Seventeen (63.0%) patients were females, and the median age at diagnosis was 75 years. Large vessel involvement (LVI) was detected in 12 (44.4%) patients, and polymyalgia rheumatica (PMR) was present in 14 (51.9%) patients. Twelve (44.4%) patients had fever at onset. The presence of LVI or concurrent PMR at diagnosis was associated with a longer time to normalization of the C-reactive protein level (p=0.039) or erythrocyte sedimentation rate (p=0.034). During follow-up (median: 33.8 months), four (14.8%) patients experienced relapse. Kaplan-Meier analyses showed that relapse was associated with visual loss (p=0.008) and the absence of fever (p=0.004) at onset, but not with LVI or concurrent PMR. @*Conclusion@#Concurrent PMR and LVI were observed in approximately half of Korean patients with GCA, and the elapsed time to normalization of inflammatory markers in these patients was longer. The relapse rate in Korean GCA is lower than that in Western countries, and afebrile patients or patients with vision loss at onset have a higher risk of relapse, suggesting that physicians should carefully monitor patients with these characteristics.
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A 4-month-old intact male Sapsaree dog was referred due to a history of postprandial regurgitation following consumption of solid food. Thoracic radiography revealed focal leftward displacement of the thoracic trachea at T1 to T4 vertebrae levels. Barium contrast radiography revealed focal dilation of the cranial thoracic esophagus at the heart base level. Persistent right aortic arch (PRAA) with an aberrant left subclavian artery branching from the patent ductus arteriosus was diagnosed by computed tomography angiography (CTA). Although barium contrast radiography can presumptive diagnose PRAA, CTA should be considered for identifying additional vascular anomalies, specific types, and surgical planning.
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Constipation is one of the most common gastrointestinal (GI) disorders worldwide. The use of probiotics to improve constipation is well known. In this study, the effect on loperamide-induced constipation by intragastric administration of probiotics Consti-Biome mixed with SynBalance® SmilinGut (Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050; Roelmi HPC), L. plantarum UALp-05 (Chr. Hansen), Lactobacillus acidophilus DDS-1 (Chr. Hansen), and Streptococcus thermophilus CKDB027 (Chong Kun Dang Bio) to rats was evaluated. To induce constipation, 5 mg/kg loperamide was intraperitoneally administered twice a day for 7 days to all groups except the normal control group. After inducing constipation, Dulcolax-S tablets and multi-strain probiotics Consti-Biome were orally administered once a day for 14 days. The probiotics were administered 0.5 mL at concentrations of 2 × 108 CFU/mL (G1), 2 × 109 CFU/mL (G2), and 2 × 1010 CFU/mL (G3). Compared to the loperamide administration group (LOP), the multi-strain probiotics not only significantly increased the number of fecal pellets but also improved the GI transit rate. The mRNA expression levels of serotonin- and mucin-related genes in the colons that were treated with the probiotics were also significantly increased compared to levels in the LOP group. In addition, an increase in serotonin was observed in the colon. The cecum metabolites showed a different pattern between the probiotics-treated groups and the LOP group, and an increase in short-chain fatty acids was observed in the probiotic-treated groups. The abundances of the phylum Verrucomicrobia, the family Erysipelotrichaceae and the genus Akkermansia were increased in fecal samples of the probiotic-treated groups. Therefore, the multi-strain probiotics used in this experiment were thought to help alleviate LOP-induced constipation by altering the levels of short-chain fatty acids, serotonin, and mucin through improvement in the intestinal microflora.
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Objectives@#. To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH). @*Methods@#. In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy. @*Results@#. The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393). @*Conclusion@#. HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH.
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The higher the use of nonsteroidal anti-inflammatory drugs (NSAIDs), the more reports of adverse drug reactions, especially in children than in adults. As patients with fever take several NSAIDs alternatively, suspected symptoms allergic to drugs with different chemical structures are also experienced in the clinical field. This is because it appears not only through immunological mechanisms but also through cross-intolerant reactions. Therefore, when hypersensitivity to one or more NSAIDs is present, it is important to distinguish between the 2 mechanisms for future treatment planning. Although it is difficult to distinguish between the 2 mechanisms by clinical history, drug provocation test with aspirin is helpful in diagnosis. A 4-year-old patient who had urticaria/angioedema and shortness of breath after taking ibuprofen and acetaminophen visited Kangwon National University Hospital for a treatment plan using antipyretics and/or analgegics forward. We propose a diagnosis and treatment protocol for such patients with a brief literature review.
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Background@#Deltoid function critically influences the results of reverse total shoulder arthroplasty (RTSA), and spontaneous deltoid attrition tears are frequently detected in cuff tear arthropathy (CTA) patients; however, the clinical impacts of these tears on RTSA outcomes are undetermined. Our aim was to determine the effect of spontaneous deltoid attrition tears on postoperative outcomes after RTSA without an additional deltoid procedure. @*Methods@#Seventy-two patients who underwent RTSA for CTA with preoperative magnetic resonance imaging (MRI) and a minimum clinical follow-up of 1 year (mean, 32 months) were retrospectively reviewed in the study. Patients with a history of previous shoulder surgery or injury were excluded. The presence and location of deltoid attrition tears were determined in preoperative MRI. Propensity score matching (1:1) was performed to construct tear and no-tear groups. Finally, 21 patients, matched with respect to age, sex, hand dominance, symptom duration, medical comorbidity (obesity, diabetes mellitus, and coronary artery disease), Hamada grade, and implant type, were assigned to each group. Clinical outcomes (functional scores, isometric power, and range of motion) in the two groups were compared. @*Results@#Deltoid attrition tears were detected in 21 of the 72 enrolled cases (29.1%). Anterolateral deltoid was the most frequent location and no tear was detected in the posterior deltoid. The tear rate increased with disease severity (Hamada G2, 4.8%; G3, 23.8%; > G4, 71.4%). No pre- or postoperative clinical variables differed significantly between the tear and no tear groups. @*Conclusions@#Deltoid attrition tears were detected in 29% of CTA patients who underwent RTSA. The most common site was the anterolateral region and tear prevalence tended to increase with CTA progression. However, RTSA was found to provide satisfactory outcomes regardless of the presence of a deltoid attrition tear.
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Background@#There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM). @*Methods@#This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics. @*Results@#Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without. @*Conclusion@#We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.
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Purpose@#This study aimed to assess disease characteristics and outcomes of transition in patient care among adolescent patients with inflammatory bowel disease (IBD). @*Materials and Methods@#Data from patients younger than 18 years who were diagnosed with IBD (Crohn’s disease, ulcerative colitis, or intestinal Behçet’s disease) were investigated. We categorized the patients into two groups: transition IBD group (Group A, diagnosed in pediatric care followed by transfer to/attendance in adult IBD care) and non-transition group (Group B, diagnosed and followed up in pediatric care or adult IBD care without transfer). @*Results@#Data from a total of 242 patients [Group A (n=29, 12.0%), Group B (n=213, 88.0%)] were analyzed. A significantly higher number of patients was diagnosed at an earlier age in Group A than in Group B (p<0.001). Group A patients had more severe disease in terms of number of disease flare ups (p=0.011) and frequency of bowel-related complications (p<0.001). Multiple linear regression analysis showed that Group B patients had more medical non-compliance than Group A patients (β=2.31, p=0.018). After transition, IBD-related admission frequency, emergency admission frequency, disease flare frequency, and medical non-compliance were significantly improved. @*Conclusion@#The transition IBD group had more severe disease. Medical non-compliance was lower in the transition IBD group.Clinical outcomes improved after transition.
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Background@#We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians. @*Methods@#We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hoursight, >5 to 7 hoursight (reference), and >7 hoursight. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex. @*Results@#During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 hight had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hoursight group in non-obese individuals, men, and those aged 7 hoursight group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively). @*Conclusion@#This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.
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Background@#Recent studies raise concerns that arthroscopic meniscectomy (AM) for degenerative tear may be detrimental to the maintenance of the joint structure. This study was performed to examine the rate of total knee replacement (TKR) among patients with knee osteoarthritis (OA) who underwent AM for meniscal tears and compare this rate with those who did not. @*Methods@#A retrospective cohort study was conducted using the National Health Insurance Database of South Korea. Among knee OA patients aged 50–79, those who were treated with AM due to meniscal damage from 2007 to 2009 were selected as the AM group while those not treated with AM despite the presence of meniscal damage were selected as control group. Both were matched based on a propensity score and followed-up until the earliest occurrence of:TKR, death, or 10 years. Cox proportional hazards models were used to compare the outcome. @*Results@#A total of 36,974 patients were included in AM groups and non-AM group after 1:1 matching. TKR occurred in 9.62% and 7.64% in AM and non-AM groups with the average duration after meniscectomy of 5.88 ± 2.77 and 5.50 ± 2.94 years, respectively. After adjustment for baseline confounders, the TKR rate in the AM group was calculated to be 25% higher than that in the non-AM group (subdistribution hazard ratio, 1.25; 95% confidence interval, 1.16–1.34). The mortality rate was 5.20%, which did not significantly differ between groups. @*Conclusion@#OA patients who underwent AM for the meniscal injury had higher incidence of TKR up to 10 years of follow-up than the non-operated group. The greater TKR utilization observed in patients undergoing AM merits caution when treating OA patients with meniscal injury.
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Background@#National reference standards for anti-HIV-1 antibody are needed to evaluate the performance and maintain the quality control of anti-HIV-1 antibody assays. The aim of this study was to prepare a mixed-titer performance panel and assess its suitability as a national reference standard for anti-HIV-1 antibody according to stability, collaboration, and other studies. @*Methods@#Nineteen serum samples from different HIV patients were obtained, along with 15 units of fresh frozen plasma samples with negative anti-HIV-1 antibody results. Ten anti-HIV-1 antibody-positive candidate standards and two negative candidate standards were prepared based on the reactivity in the Alinity i HIV Ag/Ab combo assay (Abbott Laboratories, Wiesbaden, Germany). A collaborative study was conducted across eight laboratories using five anti-HIV-1 antibody assays. Real-time and accelerated stability were evaluated to assess the long-term stability. @*Results@#In the collaborative study, results of all five anti-HIV-1 antibody assays were positive for all 10 candidate standards prepared using HIV patient samples. The CV of each assay for every candidate standard was within 10%, except for one assay result. No real-time and accelerated stability change trend was observed at −70°C or −20°C, supporting that the reference standards were maintained in a stable state at −70°C for long-term storage. @*Conclusions@#The overall results suggest that the 12 candidate standards could serve as national reference standards for anti-HIV-1 antibody.
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Background@#G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress. @*Methods@#Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium. @*Results@#In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner. @*Conclusion@#GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.
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Despite various strategies to address sticking failure in stainless steels (STSs), difficulties in understanding its fundamental mechanisms hinder precise solutions during STS fabrication. This study investigated the effect of chromium (Cr) content on the microstructures and failure modes of oxide scales under a tensile load, simulating the hot-rolling process. The dynamic, real-time behavior of crack initiation, propagation, and interfacial delamination in the oxide scales under tension was analyzed using an in situ scanning electron microscopy (SEM) tensile test. With a high Cr content, iron (Fe) oxide and chromium(III) oxide (Cr2O3) form a layered structure, which is delaminated along the interfaces between the thin Cr2O3 layer and the bulk after perpendicular cracking. The saturated crack densities obtained from in situ SEM provide interfacial strength, while the elastic modulus and hardness obtained from nanoindentation provide vertical fracture strength. In combination with an ex situ elemental image analysis, the in situ SEM results reveal three different failure modes of the four different STSs. The results confirm that sticking failure is more likely to occur as the Cr content increases.
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Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.
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Objective@#This study aims to identify the usefulness of voice function in early screening for dysphagia. We sought to evaluate if screening tests through the functions of production and quality of voice were correlated with aspiration in dysphagic patients. @*Methods@#This study involved 55 participants who were referred to videofluoroscopic swallowing study (VFSS) for suspected dysphagia. Blinded examiners rated the voice production function (MVI, MPT) using a portable instrument and evaluated the quality of voice (jitter, shimmer, NHR) using Visi-pitch. Swallowing functions were also evaluated by utilizing the penetration-aspiration scale (PAS), American Speech-Language-Hearing Association (ASHA), National Outcome Measurement System (NOMS) swallowing scale and VDS. The patients were divided into two groups, the penetration group, and the aspiration group according to the PAS score. The difference in variables was analyzed using the Mann-Whitney U test between the two groups. The relationship between voice parameters and swallow-related parameters was determined using the Spearman correlation coefficient. In addition, the cut-off, sensitivity, and specificity of meaningful variables in silent aspiration were analyzed using the ROC curve analysis. @*Results@#The functions of production and quality of voice were found to be significantly different between the penetration and aspiration groups (P＜.000). The PAS score was correlated with all parameters of the functions of production and quality of voice (P＜.001). VDS was correlated with MVI, ASHA was correlated with MVI, and Shimmer (P＜.001). The meaningful variables for silent aspiration were jitter and shimmer. @*Conclusion@#Through a clinical screening test, it may be possible to predict the difference between penetration and aspiration through the functions of production and quality of voice.
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Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.
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Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.