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This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate synthase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in serum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment significantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, enhanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This approach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.
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Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as ß-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications.
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To prevent pesticides from exceeding maximum residue limits (MRLs) in crops during export and shipment, it is necessary to manage residue levels during the pre-harvest stages. Therefore, the Republic of Korea establishes pre-harvest residue limits (PHRLs) per crop and pesticide. This study was conducted to set PHRLs for penthiopyrad and tebufenpyrad in angelica leaves, where the exceedance rates of MRLs are expected to be high. The LOQ of the analytical method used was 0.01 mg/kg and it demonstrated good linearity, with a correlation coefficient of 0.999 or higher within the quantitation range of 0.005 to 0.5 mg/kg. The recovery and storage stability accuracy values were in the range of 94.5-111.1%, within the acceptable range (70-120%, RSD ≤ 20%). The matrix effect for both pesticides was in the medium-to-strong range, and it did not significantly impact the quantitative results as a matrix-matched calibration method was employed. Using the validated method, residue concentrations of penthiopyrad 20 (%) EC and tebufenpyrad 10 (%) EC were analyzed. Both pesticides exhibited a decreasing residue trend over time. In Fields 1-3 and their integrated results, the biological half-life was within 2.6-4.0 days for penthiopyrad and 3.0-4.2 days for tebufenpyrad. The minimum value of the regression coefficient in the dissipation curve regression equation was selected as the dissipation constant. The selected dissipation constants for penthiopyrad in Fields 1-3 and their integration were 0.1221, 0.2081, 0.2162, and 0.1960. For tebufenpyrad, the dissipation constants were 0.1451, 0.0960, 0.1725, and 0.1600, respectively. The dissipation constant was used to calculate PHRL per field. Following the principles of the PHRL proposal process, residue levels (%) on PHI dates relative to MRLs were calculated, and fields for proposing PHRLs were selected. For penthiopyrad, since the residue level (%) was less than 20%, the PHRL for Field 3 with the largest dissipation constant was proposed. For tebufenpyrad, as the residue level (%) exceeded 80%, the PHRL proposal could not established. It is deemed necessary to reassess the MRL and 'guidelines for safe use' for tebufenpyrad in angelica leaves.
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Atopic dermatitis (AD) is the most common form of chronic skin inflammation with diverse clinical variants. Historically, various AD phenotypes have been grouped together without considering their heterogeneity. This approach has resulted in a lack of phenotype- and endotype-adapted therapeutic strategies. Comprehensive insights into AD pathogenesis have enabled precise medicinal approach for AD. These efforts aimed to redefine the endophenotype of AD and develop various biomarkers for diverse purposes. Among these endeavours, efforts are underway to elucidate the mechanisms (and related biomarkers) that lead to the emergence and progression of atopic diseases originating from AD (e.g., atopic march). This review focuses on diverse AD phenotypes and calls for a definition of endophenotypes. While awaiting scientific validation, these biomarkers ensure predicting disease onset and trajectory and tailoring therapeutic strategies for the future.
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Biomarcadores , Dermatite Atópica , Fenótipo , Dermatite Atópica/diagnóstico , Dermatite Atópica/etiologia , Humanos , Endofenótipos , AnimaisRESUMO
Proneural genes play a crucial role in neuronal differentiation. However, our understanding of the regulatory mechanisms governing proneural genes during neuronal differentiation remains limited. RFX4, identified as a candidate regulator of proneural genes, has been reported to be associated with the development of neuropsychiatric disorders. To uncover the regulatory relationship, we utilized a combination of multi-omics data, including ATAC-seq, ChIP-seq, Hi-C, and RNA-seq, to identify RFX4 as an upstream regulator of proneural genes. We further validated the role of RFX4 using an in vitro model of neuronal differentiation with RFX4 knock-in and a CRISPR-Cas9 knock-out system. As a result, we found that RFX4 directly interacts with the promoters of POU3F2 and NEUROD1. Transcriptomic analysis revealed a set of genes associated with neuronal development, which are highly implicated in the development of neuropsychiatric disorders, including schizophrenia. Notably, ectopic expression of RFX4 can drive human embryonic stem cells toward a neuronal fate. Our results strongly indicate that RFX4 serves as a direct upstream regulator of proneural genes, a role that is essential for normal neuronal development. Impairments in RFX4 function could potentially be related to the development of various neuropsychiatric disorders. However, understanding the precise mechanisms by which the RFX4 gene influences the onset of neuropsychiatric disorders requires further investigation through human genetic studies.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Proteínas de Homeodomínio , Neurônios , Fatores do Domínio POU , Fatores de Transcrição de Fator Regulador X , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Perfilação da Expressão Gênica , Regiões Promotoras Genéticas , RNA-Seq , Diferenciação Celular , Proteínas de Homeodomínio/genética , Fatores do Domínio POU/genética , Fatores de Transcrição de Fator Regulador X/genéticaRESUMO
BACKGROUND/AIMS: Epicardial adipose tissue (EAT) shares pathophysiological properties with other visceral fats and potentially triggers local inflammation. However, the association of EAT with cardiovascular disease (CVD) is still debatable. The study aimed to observe the changes and associations in EAT and risk factors over time, as well as to investigate whether EAT was associated with CVD. METHODS: A total of 762 participants from Seoul National University Hospital (SNUH) and SNUH Gangnam Center were included in this study. EAT was measured using coronary computed tomography angiography. RESULTS: Baseline EAT level was positively associated with body mass index (BMI), calcium score, atherosclerotic cardiovascular disease (ASCVD) 10-year risk score, glucose, triglycerides (TG)/high-density lipoprotein (HDL), but not with total cholesterol, low-density lipoprotein (LDL). At follow-up, EAT levels increased in all groups, with low EAT groups demonstrating a significant increase in EAT per year. Change in EAT was associated with a change in BMI, TG/HDL, and glucose, while changes in LDL, calcium score, and ASCVD 10-year risk score were not associated. Although calcium score and ASCVD 10-year risk score were associated with CVD events, baseline information of EAT, baseline EAT/body surface area, or EAT change was not available. CONCLUSION: Metabolic risks, e.g., BMI, TG/HDL, and glucose, were associated with EAT change per year, whereas classical CVD risks, e.g., LDL, calcium score, and ASCVD 10-year risk score, were not. The actual CVD event was not associated with EAT volume, warranting future studies combining qualitative assessments with quantitative ones.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Humanos , Angiografia por Tomografia Computadorizada/efeitos adversos , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Tecido Adiposo Epicárdico , Cálcio , Pericárdio/diagnóstico por imagem , Fatores de Risco , Triglicerídeos , Glucose , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária/métodosRESUMO
OBJECTIVE: In this study, we aimed to evaluate the usability single nucleotide polymorphisms (SNPs) for parentage testing of horse breeds in Korea. METHODS: The genotypes of 93 horse samples (38 Thoroughbred horses, 17 Jeju horses, 20 Quarter horses, and 18 American miniature horses) were determined using 15 microsatellite (Ms) markers (AHT4, AHT5, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG10, LEX3, and VHL20) and 101 SNP markers. RESULTS: Paternity tests were performed using 15 Ms markers and 101 SNP markers in Thoroughbred horses and Quarter horses. AHT5, ASB2, ASB17, ASB23, CA425, HMS7, HTG10, and LEX3 did not follow Mendelian inheritance in Thoroughbred horses, whereas in Quarter horses, only AHT4, ASB2, and HMS2 showed Mendelian inheritance, consequently, paternity was not established. Meanwhile, 31 markers, including MNEc_2_2_ 2_98568918_BIEC2_502451, in Thoroughbred horses, and 30 markers, including MNEc_ 2_30_7430735_BIEC2_816793, in Quarter horses did not conform with Mendelian inheritance and therefore, could not be used for establishing parentage. CONCLUSION: The possibility of replacing Ms markers with SNP markers for paternity testing in horses was confirmed. However, further research using more samples is necessary.
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Osteoarthritis is one of the leading conditions that promote the consumption of these dietary supplements. Chondroitin sulfate, glucosamine, and methylsulfonylmethane are among the prominent alternative treatments for osteoarthritis. In this study, these dietary supplements were incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes, and the formation of marker metabolites was measured to investigate their inhibitory potential on cytochrome P450 enzyme activities. The results revealed no significant inhibitory effects on seven CYPs, consistent with established related research data. Therefore, these substances are anticipated to have a low potential for cytochrome P450-mediated drug interactions with osteoarthritis medications that are likely to be co-administered. However, given the previous reports of interaction cases involving glucosamine, caution is advised regarding dietary supplement-drug interactions.
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Glucosamina , Osteoartrite , Humanos , Glucosamina/farmacologia , Sulfatos de Condroitina/uso terapêutico , Suplementos Nutricionais , Osteoartrite/tratamento farmacológico , Interações Medicamentosas , Sistema Enzimático do Citocromo P-450RESUMO
BACKGROUND: Though antenatal magnesium sulfate (MgSO4) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised. METHODS: We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24-31 weeks. RESULTS: Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18-24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group. CONCLUSION: Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.
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Fármacos Neuroprotetores , Nascimento Prematuro , Lactente , Humanos , Gravidez , Feminino , Recém-Nascido , Sulfato de Magnésio/uso terapêutico , Nascimento Prematuro/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Cuidado Pré-Natal , Recém-Nascido de muito Baixo PesoRESUMO
Cooperative spectrum sensing (CSS) involves multiple secondary users (SUs) reporting primary user (PU) channel sensing states to the fusion center (FC). However, the high overheads associated with multi-user CSS impose power limitations that limit its usefulness in unmanned aerial vehicle (UAV) networks. To address this challenge, we propose a virtual CSS, where a single UAV conducts CSS while following a circular flight trajectory in the air. The novelty of our approach is presenting a working frame structure for the UAV flight, including sensing and data transmission periods with further division of the sensing time into mini-sensing slots. In the virtual CSS, UAV performs local sensing decisions in each mini-slot and accumulates them for a final decision. The proposed virtual CSS scheme exploits sequential decision fusion (SDF), which sequentially adds individual mini-slot decisions. Additionally, we leverage machine learning (ML), employing AdaBoost ensembling classifier (ENC), to inspect flight conditions and reconfigure mini-slot periods dynamically for both traditional decision fusion (TDF) and our proposed SDF schemes. Furthermore, we identify an optimal decision threshold (ODT) for the proposed SDF, enabling the comparison of sequential results with an adjustable threshold through majority voting. This novel approach results in energy efficiency and improved throughput for virtual CSS using SDF, surpassing the performance of TDF, which relies on collecting entire mini-slot reports for its final decision. Simulation results demonstrate the effectiveness of the proposed SDF following the ENCODT (SDF-ENCODT) scheme compared to existing techniques from the literature. We explore varying levels of UAV flight velocities, moving radius, detection probability demand, and channel signal-to-noise ratio (SNR), reinforcing the significance of our contribution. Our research highlights the motivation to address spectrum scarcity in UAV communication by proposing an innovative virtual CSS scheme based on SDF. The proposed approach enhances spectrum utilization, overcomes power limitations, and substantially improves CSS for UAV networks.
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Comunicação , Dispositivos Aéreos não Tripulados , Simulação por Computador , Hidrolases , CogniçãoRESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis, cause, and treatment have been extensively studied. The association of AD with Th2 cytokines is well known; therefore, the analysis of this association is crucial for the diagnosis and treatment of AD. This study aimed to present a new method for measuring protein biomarkers in patients with AD, before and after treatment, using minimally invasive microneedles. MATERIALS AND METHODS: First, hyaluronic acid-loaded microneedle patches (HA-MNs) for skin sample collection were fabricated. Next, after Institutional Review Board approval, 20 patients with AD were recruited and skin samples were taken before and after treatment using four different sampling techniques: (1) tape stripping, (2) hydrocolloid patches, (3) hollow microneedles, and (4) HA-MNs. Lastly, proteins were isolated from the collected samples, and AD-related biomarkers were analyzed by enzyme-linked immunosorbent assay. RESULTS: Proteins were successfully extracted from the skin samples collected by tape stripping, hydrocolloid patches, and HA-MNs, except hollow microneedles. Interleukin (IL)-4, IL-13, and interferon-γ were detected in the HA-MNs only. By comparing the biomarker level correlation before and after treatment and the improvement score of the patients, we observed a significant negative correlation between IL-4 and IL-13 with an improvement in AD symptoms. CONCLUSION: Overall, our results verified that HA-MNs can be used to effectively analyze protein levels of biomarkers from skin metabolites of patients with AD and can be applied to monitor the treatment progress of patients with AD in a minimally invasive manner.
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Dermatite Atópica , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/patologia , Interleucina-13/metabolismo , Pele/patologia , Citocinas/metabolismo , Biomarcadores/metabolismoRESUMO
House dust mite (HDM) is the most common allergen exacerbating atopic dermatitis (AD), and allergen-specific immunotherapy (AIT) using HDM exhibited significant improvements in previous studies. Alopecia can occur as a complication of AD. Alopecia totalis (AT), a severe form of alopecia areata (AA), does not respond well to treatment and the chance of full recovery is less than 10%. For extensive hair loss, topical immunotherapy such as diphenylcyclopropenone (DPCP) is used as the first-line treatment. However, since DPCP is a kind of contact allergen, it has the potential to exacerbate AD. A 38-year-old man with AD and AA visited our clinic with symptoms worsening from 3 months ago. Although taking oral methylprednisolone (8 mg/day) and cyclosporine (100 mg/day) for 3 months, he has lost over 90% of his hair and the Eczema Area and Severity Index (EASI) was 43. Total serum immunoglobulin E (IgE) levels were 4454 kU/L (normal <100 kU/L) and the specific IgE levels for Dermatophagoides pteronyssinus and Dermatophagoides farinae following ImmunoCAP® were 20.8 and 37.4 kU/L, respectively. This patient did not respond well to previous treatment and was reluctant to use long-term steroids, so subcutaneous AIT using HDM was administered along with oral cyclosporine (100 mg/day). Topical tacrolimus was also applied to the AD lesions throughout the body. To reduce itching, nonsedative antihistamines were used if necessary. Hair loss was almost completely improved 1 year after the AIT initiation and the skin lesions of AD also improved (EASI 2.4). The specific IgE levels for D. pteronyssinus and D. farinae were 3.73 and 7.16 kU/L, respectively. Herein, we report a patient with promising results following AIT for AT with severe AD. In severe alopecic patients with AD refractory to conventional treatment, including immunosuppressants, AIT could be considered as a treatment option.
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Alopecia em Áreas , Ciclosporinas , Dermatite Atópica , Masculino , Humanos , Adulto , Dermatite Atópica/complicações , Dermatite Atópica/terapia , Alopecia em Áreas/complicações , Alopecia em Áreas/terapia , Dessensibilização Imunológica/métodos , Alérgenos , Imunoglobulina ERESUMO
Oxidative stress plays a key role in the pathogenesis of neuronal injury, including ischemia. Ras-related nuclear protein (RAN), a member of the Ras superfamily, involves in a variety of biological roles, such as cell division, proliferation, and signal transduction. Although RAN reveals antioxidant effect, its precise neuroprotective mechanisms are still unclear. Therefore, we investigated the effects of RAN on HT-22 cell which were exposed to H2O2-induced oxidative stress and ischemia animal model by using the cell permeable Tat-RAN fusion protein. We showed that Tat-RAN transduced into HT-22 cells, and markedly inhibited cell death, DNA fragmentation, and reactive oxygen species (ROS) generation under oxidative stress. This fusion protein also controlled cellular signaling pathways, including mitogen-activated protein kinases (MAPKs), NF-κB, and apoptosis (Caspase-3, p53, Bax and Bcl-2). In the cerebral forebrain ischemia animal model, Tat-RAN significantly inhibited both neuronal cell death, and astrocyte and microglia activation. These results indicate that RAN significantly protects against hippocampal neuronal cell death, suggesting Tat-RAN will help to develop the therapies for neuronal brain diseases including ischemic injury.
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Lesões Encefálicas , Isquemia Encefálica , Fármacos Neuroprotetores , Animais , Peróxido de Hidrogênio/farmacologia , Proteína ran de Ligação ao GTP/metabolismo , Proteína ran de Ligação ao GTP/farmacologia , Hipocampo/metabolismo , Isquemia/metabolismo , Estresse Oxidativo , Isquemia Encefálica/metabolismo , Apoptose , Produtos do Gene tat/genética , Produtos do Gene tat/metabolismo , Produtos do Gene tat/farmacologia , Modelos Animais de Doenças , Lesões Encefálicas/metabolismo , Fármacos Neuroprotetores/farmacologiaRESUMO
Background: Oxidative stress is considered as one of the main causes of Parkinson's disease (PD), however the exact etiology of PD is still unknown. Although it is known that Proviral Integration Moloney-2 (PIM2) promotes cell survival by its ability to inhibit formation of reactive oxygen species (ROS) in the brain, the precise functional role of PIM2 in PD has not been fully studied yet. Objective: We investigated the protective effect of PIM2 against apoptosis of dopaminergic neuronal cells caused by oxidative stress-induced ROS damage by using the cell permeable Tat-PIM2 fusion protein in vitro and in vivo. Methods: Transduction of Tat-PIM2 into SH-SY5Y cells and apoptotic signaling pathways were determined by Western blot analysis. Intracellular ROS production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. PD animal model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and protective effects were examined using immunohistochemistry. Results: Transduced Tat-PIM2 inhibited the apoptotic caspase signaling and reduced the production of ROS induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells. Furthermore, we confirmed that Tat-PIM2 transduced into the substantia nigra (SN) region through the blood-brain barrier and this protein protected the Tyrosine hydroxylase-positive cells by observation of immunohistostaining. Tat-PIM2 also regulated antioxidant biomolecules such as SOD1, catalase, 4-HNE, and 8-OHdG which reduce the formation of ROS in the MPTP-induced PD mouse model. Conclusion: These results indicated that Tat-PIM2 markedly inhibited the loss of dopaminergic neurons by reducing ROS damage, suggesting that Tat-PIM2 might be a suitable therapeutic agent for PD.
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Despite the increasing presence of social robots (SRs) in Human-Robot Interaction, there are few studies that quantify these interactions and explore children's attitudes by analyzing real-time data as they communicate with SRs. Therefore, we attempted to explore the interaction between pediatric patients and SRs by analyzing the interaction log collected from real-time. This study is a retrospective analysis of data collected in a prospective study conducted on 10 pediatric cancer patients at tertiary hospitals in Korea. Using the Wizard of Oz method, we collected the interaction log during the interaction between pediatric cancer patients and the robot. Out of the collected data, 955 sentences from the robot and 332 sentences from the children were available for analysis, except for the logs that were missing due to environmental errors. we analyzed the delay time from saving the interaction log and the sentence similarity of the interaction log. The interaction log delay time between robot and child was 5.01 seconds. And the child's delay time averaged 7.2 seconds, which was longer than the robot's delay time of 4.29 seconds. Additionally, as a result of analyzing the sentence similarity of the interaction log, the robot (97.2%) was higher than the children (46.2%). The results of the sentiment analysis of the patient's attitude toward the robot were 73% neutral, 13.59% positive, and 12.42% negative. The observational evaluations of pediatric psychological experts identified curiosity (n=7, 70.0%), activity (n=5, 50.0%), passivity (n=5, 50.0%), sympathy (n=7, 70.0%), concentration (n=6, 60.0%), high interest (n=5, 50.0%), positive attitude (n=9, 90.0%), and low interaction initiative (n=6, 60.0%). This study made it possible to explore the feasibility of interaction with SRs and to confirm differences in attitudes toward robots according to child characteristics. To increase the feasibility of human-robot interaction, measures such as improving the completeness of log records by enhancing the network environment are required.
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Neoplasias , Robótica , Humanos , Criança , Estudos Prospectivos , Estudos Retrospectivos , AtitudeRESUMO
This study aimed to prove that deep learning can be effectively used for identifying various equine facial expressions as welfare indicators. In this study, a total of 749 horses (healthy: 586 and experiencing pain: 163) were investigated. Moreover, a model for recognizing facial expressions based on images and their classification into four categories, i.e., resting horses (RH), horses with pain (HP), horses immediately after exercise (HE), and horseshoeing horses (HH), was developed. The normalization of equine facial posture revealed that the profile (99.45%) had higher accuracy than the front (97.59%). The eyes-nose-ears detection model achieved an accuracy of 98.75% in training, 81.44% in validation, and 88.1% in testing, with an average accuracy of 89.43%. Overall, the average classification accuracy was high; however, the accuracy of pain classification was low. These results imply that various facial expressions in addition to pain may exist in horses depending on the situation, degree of pain, and type of pain experienced by horses. Furthermore, automatic pain and stress recognition would greatly enhance the identification of pain and other emotional states, thereby improving the quality of equine welfare.
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Food insecurity refers to the uncertain availability of or limited access to nutritious food. Poor diets prevalent among food insecure populations may incite an inflammatory state and subsequently negatively affect skeletal muscle metabolism. To examine the inflammatory mechanistic potential of the association between food insecurity and the risk of low muscle strength, we analyzed cross-sectional data from 8624 adults aged ≥20 years from the Korean National Health and Nutrition Examination Survey 2014-2015. Household food security status was assessed using an 18-item food security survey module. The inflammatory potential of diets was estimated by the dietary inflammation index (DII). Low muscle strength was ascertained using hand grip strength. In the multivariable-adjusted model, greater food insecurity was significantly associated with a higher DII score and risk of low muscle strength. The multivariable-adjusted mean difference (95% confidence interval) on the DII, comparing the "moderate-to-severe" food insecurity group with the "food secure" group, was 0.43 (0.06-0.80) (P-trend: <0.001) and the odds ratio (95% confidence intervals) of low muscle strength for the same comparison groups was 2.06 (1.07-3.96) (P-trend: 0.005). Our results suggest that individuals with greater food insecurity may be susceptible to diets with greater inflammatory potential, which may contribute to a loss of muscle strength.
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Abastecimento de Alimentos , Força da Mão , Adulto , Humanos , Inquéritos Nutricionais , Estudos Transversais , Dieta , Inflamação , Força Muscular , Insegurança AlimentarRESUMO
Introduction & objectives: Head and neck dermatitis (HND) is a refractory phenotype of atopic dermatitis (AD) and can be a therapeutic challenge due to lack of responsiveness to conventional treatments. Previous studies have suggested that the microbiome and fungiome may play a role in inducing HND, but the underlying pathogenic mechanisms remain unknown. This study aimed to determine the link between HND and fungiome and to examine the contribution of Malassezia furfur. Materials and methods: To identify the effect of the sensitization status of M. furfur on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of M. furfur, human keratinocytes and dermal endothelial cells were cultured with M. furfur and treated with Th2 cytokines. The downstream effects of various cytokines, including inflammation and angiogenesis, were investigated by real-time quantitative PCR. To identify the association between changes in lipid composition and M. furfur sensitization status, D-squame tape stripping was performed. Lipid composition was evaluated by focusing on ceramide species using liquid chromatography coupled with tandem mass spectrometry. Results: Increased sensitization to M. furfur was observed in patients with HND. Additionally, sensitization to M. furfur was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with M. furfur produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/M. furfur co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-ß, TNF-α, and IL-1ß levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, M. furfur growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including Cutibacterium acnes, were not inhibited. Conclusions: Under decreased levels of ceramide in AD patients with HND, M. furfur would proliferate, which may enhance pro-inflammatory cytokine levels, angiogenesis, and tissue remodeling. Thus, it plays a central role in the pathogenesis of HND in AD.
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Dermatite Atópica , Malassezia , Humanos , Malassezia/fisiologia , Células Endoteliais , Interleucina-4 , Citocinas , Ceramidas , LipídeosRESUMO
Glutathione S-transferase pi (GSTpi) is a member of the GST family and plays many critical roles in cellular processes, including anti-oxidative and signal transduction. However, the role of anti-oxidant enzyme GSTpi against dopaminergic neuronal cell death has not been fully investigated. In the present study, we investigated the roles of cell permeable Tat-GSTpi fusion protein in a SH-SY5Y cell and a Parkinson's disease (PD) mouse model. In the 1-methyl-4-phenylpyridinium (MPP+)-exposed cells, Tat-GSTpi protein decreased DNA damage and reactive oxygen species (ROS) generation. Furthermore, this fusion protein increased cell viability by regulating MAPKs, Bcl-2, and Bax signaling. In addition, Tat-GSTpi protein delivered into the substantia nigra (SN) of mice brains protected dopaminergic neuronal cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Our results indicate that the Tat-GSTpi protein inhibited cell death from MPP+- and MPTP-induced damage, suggesting that it plays a protective role during the loss of dopaminergic neurons in PD and that it could help to identify the mechanism responsible for neurodegenerative diseases, including PD.
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Brown adipose tissue (BAT) plays a pivotal role in maintaining body temperature and energy homeostasis. BAT dysfunction is associated with impaired metabolic health. Here, we show that Ssu72 phosphatase is essential for mRNA translation of genes required for thermogenesis in BAT. Ssu72 is found to be highly expressed in BAT among adipose tissue depots, and the expression level of Ssu72 is increased upon acute cold exposure. Mice lacking adipocyte Ssu72 exhibit cold intolerance during acute cold exposure. Mechanistically, Ssu72 deficiency alters cytosolic mRNA translation program through hyperphosphorylation of eIF2α and reduces translation of mitochondrial oxidative phosphorylation (OXPHOS) subunits, resulting in mitochondrial dysfunction and defective thermogenesis in BAT. In addition, metabolic dysfunction in Ssu72-deficient BAT returns to almost normal after restoring Ssu72 expression. In summary, our findings demonstrate that cold-responsive Ssu72 phosphatase is involved in cytosolic translation of key thermogenic effectors via dephosphorylation of eIF2α in brown adipocytes, providing insights into metabolic benefits of Ssu72.