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The transient receptor potential ankyrin 1 (TRPA1) channel plays a pivotal role in the respiratory and gastrointestinal tracts. Within the respiratory system, TRPA1 exhibits diverse distribution patterns across key cell types, including epithelial cells, sensory nerves, and immune cells. Its activation serves as a frontline sensor for inhaled irritants, triggering immediate protective responses, and influencing airway integrity. Furthermore, TRPA1 has been implicated in airway tissue injury, inflammation, and the transition of fibroblasts, thereby posing challenges in conditions, such as severe asthma and fibrosis. In sensory nerves, TRPA1 contributes to nociception, the cough reflex, and bronchoconstriction, highlighting its role in both immediate defense mechanisms and long-term respiratory reflex arcs. In immune cells, TRPA1 may modulate the release of pro-inflammatory mediators, shaping the overall inflammatory landscape. In the gastrointestinal tract, the dynamic expression of TRPA1 in enteric neurons, epithelial cells, and immune cells underscores its multifaceted involvement. It plays a crucial role in gut motility, visceral pain perception, and mucosal defense mechanisms. Dysregulation of TRPA1 in both tracts is associated with various disorders such as asthma, Chronic Obstructive Pulmonary Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Disease. This review emphasizes the potential of TRPA1 as a therapeutic target and discusses the efficacy of TRPA1 antagonists in preclinical studies and their promise for addressing respiratory and gastrointestinal conditions. Understanding the intricate interactions and cross-talk of TRPA1 across different cell types provides insight into its versatile role in maintaining homeostasis in vital physiological systems, offering a foundation for targeted therapeutic interventions.
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Subungual abscesses are rare, and information about them through imaging findings is lacking. Carbon dioxide laser drainage and antibiotics are effective treatment strategies for subungual abscesses. We report a case of a 47-year-old male healthcare worker with a subungual abscess that improved after manual drainage alone. Ultrasound and magnetic resonance images showed a tumor (with blood flow) between the nail plate and distal phalanx. Culture tests revealed Staphylococcus aureus. The patient's symptoms resolved quickly and the nail returned to normal after 4 months. This is possibly the first report of a subungual abscess with ultrasound and magnetic resonance imaging findings.
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BACKGROUND: Interstitial lung disease (ILD) related to rheumatoid arthritis (RA) is among the leading causes of death and an essential prognostic factor. There is only limited evidence for the safety of anti-rheumatic drugs for patients with RA-ILD. The aim of this study is to investigate the safety and efficacy of Janus kinase inhibitors (JAKis) by comparing it with abatacept (ABT) in patients with RA-ILD. METHODS: This single centre, retrospective nested case-control study enrolled patients with RA-ILD treated with JAKi or ABT. To determine the safety of the two drugs for existing ILD, we compared their drug persistency, incidence rates of pulmonary complications, and change of chest computed tomography (CT) image. For their efficacy as RA treatment, disease activity scores and prednisolone (PSL)-sparing effect were compared. We performed propensity score matching to match the groups' patient characteristics. RESULTS: We studied 71 patients with RA-ILD (ABT, n = 45; JAKi, n = 26). At baseline, the JAKi group had longer disease duration, longer duration of past bDMARD or JAKi use and higher usual interstitial pneumonia rate. After propensity score matching, no significant differences in patient characteristics were found between the two groups. No significant difference in the drug persistency rate for the first 2 years (ABT, 61.9%; JAKi, 42.8%; P = 0.256) was observed between the two matched groups. The incidence rate of pulmonary complications did not differ significantly between the two groups (P = 0.683). The CT score did not change after the treatment for the ABT group (Ground-glass opacities (GGO): P = 0.87; fibrosis: P = 0.78), while the GGO score significantly improved for the JAKi group (P = 0.03), although the number was limited (ABT: n = 7; JAKi: n = 8). The fibrosis score of the JAKi group did not change significantly.(P = 0.82). Regarding the efficacy for RA, a significant decrease in disease activity scores after the 1-year treatment was observed in both groups, and PSL dose was successfully tapered, although no significant differences were observed between the two drugs. CONCLUSIONS: JAKi is as safe and effective as ABT for patients with RA-ILD. JAKi can be a good treatment option for such patients.
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BACKGROUND Remimazolam has the advantage of better hemodynamic stability compared with other anesthetics. We compared the effects of remimazolam and sevoflurane on cerebral oxygenation, intracranial pressure, and intraoperative hemodynamic parameters during mild hypercapnia in patients undergoing laparoscopy in the Trendelenburg position. MATERIAL AND METHODS Sixty-two patients (20-65 years old) scheduled for gynecological laparoscopy were randomly allocated to either the remimazolam (n=31) or sevoflurane (n=31) group. Respiratory and hemodynamic parameters and regional cerebral oxygen saturation (rSO2) were recorded. Intracranial pressure was measured using the optic nerve sheath diameter (ONSD). RESULTS The change over time in rSO2 did not differ between groups (P=0.056). The change in ONSD over time showed a significant intergroup difference (P=0.002). ONSD significantly changed over time (P=0.034) in the sevoflurane group but not in the remimazolam group (P=0.115). The changes in mean arterial pressure and heart rate over time showed significant intergroup differences (P=0.045 and 0.031, respectively). The length of stay and the use of rescue antiemetics and analgesics in the postanesthetic care unit were significantly lower in the remimazolam group than in the sevoflurane group (P=0.023, 0.038, and 0.018, respectively). CONCLUSIONS Remimazolam can provide a favorable hemodynamic profile and attenuate the increase in ONSD during gynecological laparoscopy compared with sevoflurane anesthesia during lung-protective ventilation with mild hypercapnia. Remimazolam can provide faster and better postoperative recovery than sevoflurane anesthesia.
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Anestesia , Laparoscopia , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Sevoflurano/farmacologia , Pressão Intracraniana , Hipercapnia , PulmãoRESUMO
OBJECTIVE: To investigate the influence of nutritional status on severe infection complications in patients with rheumatoid arthritis (RA). METHODS: This retrospective cohort study on 2108 patients with RA evaluated the prognostic nutritional index (PNI) as an index of nutritional status. Patients were classified into the high or low PNI group according to the cutoff PNI value (45.0). Based on propensity score matching analysis, 360 patients in each group were selected for comparing the incidence of serious infection, clinical findings, and PNI scores. RESULTS: The incidence of infection was significantly higher in the low PNI group than in the high PNI group (p < 0.001). The occurrence rate of infectious complication at 104 weeks was significantly higher in the low PNI (<45.0) group than in the high PNI group (p < 0.001). The incidence of infection was particularly high in elderly patients (≥65 years) with a low PNI, but the incidence in elderly patients with a high PNI was similar to that in nonelderly patients with a high PNI. CONCLUSIONS: Patients with RA and malnutrition had a higher incidence of severe infection; thus, evaluating and managing nutritional status is necessary for the appropriate and safe treatment of elderly patients with RA.
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Artrite Reumatoide , Avaliação Nutricional , Humanos , Idoso , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Artrite Reumatoide/complicaçõesRESUMO
Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.
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Gluconeogênese , Fígado , Coativadores de Receptor Nuclear , Ácido Pirúvico , Animais , Colforsina/metabolismo , Colforsina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Gluconeogênese/genética , Glucose/metabolismo , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coativadores de Receptor Nuclear/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ácido Pirúvico/metabolismoRESUMO
Advanced maternal age (AMA) is a growing trend world-wide and is traditionally defined as childbearing in women over 35 years of age. The purpose of our study was to determine the maternal age group within the Korean population, in which the risk of early neonatal mortality is increased. Korean birth and mortality data from 2011 to 2015 were used to estimate the influence of maternal age on the risk of early neonatal mortality. A Poisson regression was used for the analysis of multiple clinical variables such as year of delivery, maternal age, gestational age, infant gender, birth weight, multiple birth, parity, and socioeconomic variables. Furthermore, a generalized additive model was used to determine the maternal age at which the risk for neonatal mortality increases. We included 2,161,908 participants and found that 49.4% of mothers were 30-34 years of age at delivery. The proportion of mothers aged 35 and above increased over the 5-year analysis period. A maternal age lower than 29 years or higher than 40 years was associated with a relatively higher risk of early neonatal mortality. The trend and magnitude of the age-related risk on early neonatal mortality were independent of maternal socioeconomic factors such as living in an obstetrically underserved area, education level, and employment status. Furthermore, we showed that the risk for early neonatal mortality was higher until the maternal age of 28. However, there were no significant changes in the risk between the age of 35 and 40 years. According to recent national-wide data, age-related risk for early neonatal mortality is only apparent for mothers ≥ 40 years old whereas, age between 35 and 39 are not at increased risk for early neonatal mortality, despite being classified as AMA.
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Mortalidade Infantil/tendências , Idade Materna , Adulto , Peso ao Nascer , Estudos de Coortes , Bases de Dados Factuais , Feminino , Idade Gestacional , Humanos , Lactente , Paridade , Gravidez , Gravidez Múltipla , República da Coreia/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
Clusterin (CLU) is a heterodimeric glycoprotein involved in a range of biological processes. We investigated the function of CLU as a novel regulator of adipogenesis. CLU expression increased during 3T3-L1 preadipocyte differentiation. CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa). Conversely, knockdown of CLU attenuated adipogenesis and reduced transcript levels of Pparg and Cebpa. However, the promoter activities of both the Pparg and the Cebpa gene were not affected by alteration of CLU expression on its own. Additionally, the protein level of Krüppel-like factor 5 (KLF5), an upstream transcription factor of Pparg and Cebpa involved in adipogenic differentiation, was upregulated by CLU overexpression, although the mRNA level of Klf5 was not altered by changes in the expression level of CLU. Cycloheximide chase assay showed that the increased level of KLF5 by CLU overexpression was due to decreased degradation of KLF5 protein. Interestingly, CLU increased the stability of KLF5 by decreasing KLF5 ubiquitination. CLU inhibited the interaction between KLF5 and F-box/WD repeat-containing protein 7, which is an E3 ubiquitin ligase that targets KLF5. The adipogenic role of CLU was also addressed in mesenchymal stem cells (MSCs) and Clu-/- mouse embryonic fibroblasts (MEFs). Furthermore, CLU enhanced KLF5-mediated transcriptional activation of both the Cebpa and the Pparg promoter. Taken together, these results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5.
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Adipócitos/fisiologia , Diferenciação Celular/genética , Clusterina/genética , Fatores de Transcrição Kruppel-Like/genética , Células 3T3-L1 , Adipogenia/genética , Animais , Linhagem Celular , Fibroblastos/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , Ativação Transcricional/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/genéticaRESUMO
The recent advancements in computer vision have opened new horizons for deploying biometric recognition algorithms in mobile and handheld devices. Similarly, iris recognition is now much needed in unconstraint scenarios with accuracy. These environments make the acquired iris image exhibit occlusion, low resolution, blur, unusual glint, ghost effect, and off-angles. The prevailing segmentation algorithms cannot cope with these constraints. In addition, owing to the unavailability of near-infrared (NIR) light, iris recognition in visible light environment makes the iris segmentation challenging with the noise of visible light. Deep learning with convolutional neural networks (CNN) has brought a considerable breakthrough in various applications. To address the iris segmentation issues in challenging situations by visible light and near-infrared light camera sensors, this paper proposes a densely connected fully convolutional network (IrisDenseNet), which can determine the true iris boundary even with inferior-quality images by using better information gradient flow between the dense blocks. In the experiments conducted, five datasets of visible light and NIR environments were used. For visible light environment, noisy iris challenge evaluation part-II (NICE-II selected from UBIRIS.v2 database) and mobile iris challenge evaluation (MICHE-I) datasets were used. For NIR environment, the institute of automation, Chinese academy of sciences (CASIA) v4.0 interval, CASIA v4.0 distance, and IIT Delhi v1.0 iris datasets were used. Experimental results showed the optimal segmentation of the proposed IrisDenseNet and its excellent performance over existing algorithms for all five datasets.
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Recent developments in intelligence surveillance camera systems have enabled more research on the detection, tracking, and recognition of humans. Such systems typically use visible light cameras and images, in which shadows make it difficult to detect and recognize the exact human area. Near-infrared (NIR) light cameras and thermal cameras are used to mitigate this problem. However, such instruments require a separate NIR illuminator, or are prohibitively expensive. Existing research on shadow detection in images captured by visible light cameras have utilized object and shadow color features for detection. Unfortunately, various environmental factors such as illumination change and brightness of background cause detection to be a difficult task. To overcome this problem, we propose a convolutional neural network-based shadow detection method. Experimental results with a database built from various outdoor surveillance camera environments, and from the context-aware vision using image-based active recognition (CAVIAR) open database, show that our method outperforms previous works.
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The neuronal nitric oxide synthase (nNOS) specific inhibitor, 7-nitroindazole (7-NI), and the nitric oxide (NO) donor (S-nitroso-N-acetylpenicillarnine, SNAP) were used to study the role of NO in polychlorinated biphenyl (PCB: Aroclor 1254)-induced cytotoxicity in the immortalized dopaminergic cell line (CATH.a cells), derived from the central nervous system of mice. Treatment of the dopaminergic cells with various concentrations of Aroclor 1254 (0.5-10 microg/ml), a commercial PCB mixture, showed significant cytotoxicity as evaluated by lactate dehydrogenase (LDH) release and assessment of cell viability, depending on the concentration used. We also observed that Aroclor 1254 treatment reduced the level of nNOS expression. Furthermore, the cytotoxicity of Aroclor 1254 was augmented by 10 microM of 7-NI, which alone did not produce cytotoxicity, while it was protected by treatment with SNAP. Depending on the concentrations of Aroclor 1254 used, intracellular dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations were significantly decreased. Therefore, these results suggest that PCBs have the potential for dopaminergic neurotoxicity, which may be related with the PCBs-mediated alteration of NO production originating from nNOS at least in part.