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1.
Medicine (Baltimore) ; 103(18): e38044, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701299

ABSTRACT

BACKGROUND: Despite laparoscopic cholecystectomy (LC) is a commonly performed operation under ambulatory setting, significant postoperative pain is still a major concern. The ultrasound-guided subcostal approach of transversus abdominis plane (sTAP) blocks and wound infiltration (WI) are both widely practiced techniques to reduce postoperative pain in patients undergoing LC. Although these methods have been shown to relieve postoperative pain effectively, the relative analgesic efficacy between ultrasound-guided sTAP blocks and WI is not well known. METHODS: We searched PubMed, EMBASE, and CENTRAL to identify all randomized controlled trials (RCTs) comparing ultrasound-guided sTAP block versus WI for postoperative pain control in adult patients undergone LC. The search was performed until May 2023. Primary outcome was defined as 24-hour cumulative opioid consumption. Secondary outcomes were postoperative pain scores and the incidence of postoperative nausea and vomiting (PONV). RESULTS: Finally, 6 RCTs were included, and data from 314 participants were retrieved. Postoperative 24-hour opioid consumption was significantly lower in ultrasound-guided sTAP group than in the WI group with a mean difference of -6.67 (95% confidence interval: -9.39 to - 3.95). The ultrasound-guided sTAP group also showed significantly lower pain scores. Incidence of PONV did not significantly differ between the 2 groups. CONCLUSIONS: We conclude that there is low to moderate evidence to advocate that ultrasound-guided sTAP block has better analgesic effects than WI in patients undergoing LC. Further trials are needed with robust methodology and clearly defined outcomes.


Subject(s)
Abdominal Muscles , Cholecystectomy, Laparoscopic , Nerve Block , Pain, Postoperative , Ultrasonography, Interventional , Humans , Pain, Postoperative/prevention & control , Pain, Postoperative/etiology , Nerve Block/methods , Cholecystectomy, Laparoscopic/methods , Cholecystectomy, Laparoscopic/adverse effects , Ultrasonography, Interventional/methods , Abdominal Muscles/innervation , Randomized Controlled Trials as Topic , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use
2.
J Hazard Mater ; 472: 134445, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38701727

ABSTRACT

The prevalence of microplastic (MP) contamination has become a significant environmental concern due to its pervasive nature and persistent effects. While sediments are considered major repositories for MPs, information on their spatial distribution within these matrices is insufficient. This research examined both the horizontal and vertical presence of MPs in the sediments surrounding Lake Paldang in South Korea, alongside a comprehensive evaluation of the physicochemical characteristics of the samples obtained. The total content of MPs varied from 2.15 to 122.2 particles g-1. The average contents of MPs on surface sediments were 40.47, 34.14, 5.01, and 8.19 particles g-1 in north mainstream (NM), south mainstream (SM), tributary (TB), and Tributary catchment (TC) based on Sonae Island, Gyeongan stream, respectively. The most abundant MP types were polyethylene (PE), polytetrafluoroethylene (PTFE), and polypropylene (PP), accounting for more than 70% of the total MPs. The most abundant sizes of MPs were within 45-100 µm. At all sediment depths, polymers were distributed in the order PE, PP, and polyester in NM, SM, and TC, respectively, whereas PTFE mainly occurred in the surface layer. MPs distribution also exhibited seasonal variation as larger inflows and flow rates varied with season.

3.
J Yeungnam Med Sci ; 41(2): 128-133, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38311803

ABSTRACT

Aortic dissection in pregnant patients results in an inpatient mortality rate of 8.6%. Owing to the pronounced mortality rate and speed at which aortic dissections progress, efficient early detection methods are crucial. Here, we highlight the importance of early chest computed tomography (CT) for differentiating aortic dissection from pulmonary embolism in pregnant patients with dyspnea. We present the unique case of a 38-year-old pregnant woman with elevated D-dimer and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, initially suspected of having a pulmonary embolism. Initial transthoracic echocardiography did not indicate aortic dissection. Surprisingly, after an emergency cesarean section, a chest CT scan revealed a DeBakey type I aortic dissection, indicating a diagnostic error. Our findings emphasize the need for early chest CT in pregnant patients with dyspnea and elevated D-dimer and NT-proBNP levels. This case report highlights the critical importance of considering both aortic dissection and pulmonary embolism in the differential diagnosis of such cases, which will inform future clinical practice.

4.
J Prev Med Public Health ; 57(1): 18-27, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38327013

ABSTRACT

OBJECTIVES: This study investigated the association between exacerbated economic hardship during the coronavirus disease 2019 (COVID-19) pandemic and changes in the health behaviors of Korean adolescents. METHODS: We analyzed data from the 2021 Korea Youth Risk Behavior Survey and included 44 908 students (22 823 boys and 22 085 girls) as study subjects. The dependent variables included changes in health behaviors (breakfast habits, physical activity, and alcohol use) that occurred during the COVID-19 pandemic. The aggravation of economic hardship by COVID-19 and the subjective economic status of the family were used as exposure variables. Multiple logistic regression analysis was utilized to calculate the prevalence odds ratios (PORs). RESULTS: Severe exacerbation of a family's economic hardship due to COVID-19 was negatively associated with the health behaviors of adolescents, including increased breakfast skipping (POR, 1.85; 95% confidence interval [CI], 1.55 to 2.21 for boys and POR, 1.56; 95% CI, 1.27 to 1.92 for girls) and decreased physical activity (POR, 1.37; 95% CI, 1.19 to 1.57 for boys and POR, 1.38; 95% CI, 1.19 to 1.60 for girls). These negative changes in health behaviors were further amplified when combined with a low subjective family economic status. CONCLUSIONS: The experience of worsening household hardship can lead to negative changes in health behavior among adolescents. It is crucial to implement measures that address the economic challenges that arise from stressful events such as COVID-19 and to strive to improve the lifestyles of adolescents under such circumstances.


Subject(s)
Adolescent Behavior , COVID-19 , Male , Female , Humans , Adolescent , Cross-Sectional Studies , Pandemics , Financial Stress , Adolescent Health , COVID-19/epidemiology , Health Behavior , Risk-Taking , Republic of Korea/epidemiology
5.
J Vet Sci ; 24(5): e73, 2023 Sep.
Article in English | MEDLINE | ID: mdl-38031652

ABSTRACT

BACKGROUND: Highly pathogenic avian influenza virus (HPAIV) is considered a global threat to both human health and the poultry industry. MicroRNAs (miRNA) can modulate the immune system by affecting gene expression patterns in HPAIV-infected chickens. OBJECTIVES: To gain further insights into the role of miRNAs in immune responses against H5N1 infection, as well as the development of strategies for breeding disease-resistant chickens, we characterized miRNA expression patterns in tracheal tissues from H5N1-infected Ri chickens. METHODS: miRNAs expression was analyzed from two H5N1-infected Ri chicken lines using small RNA sequencing. The target genes of differentially expressed (DE) miRNAs were predicted using miRDB. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then conducted. Furthermore, using quantitative real-time polymerase chain reaction, we validated the expression levels of DE miRNAs (miR-22-3p, miR-146b-3p, miR-27b-3p, miR-128-3p, miR-2188-5p, miR-451, miR-205a, miR-203a, miR-21-3p, and miR-200a-3p) from all comparisons and their immune-related target genes. RESULTS: A total of 53 miRNAs were significantly expressed in the infection samples of the resistant compared to the susceptible line. Network analyses between the DE miRNAs and target genes revealed that DE miRNAs may regulate the expression of target genes involved in the transforming growth factor-beta, mitogen-activated protein kinase, and Toll-like receptor signaling pathways, all of which are related to influenza A virus progression. CONCLUSIONS: Collectively, our results provided novel insights into the miRNA expression patterns of tracheal tissues from H5N1-infected Ri chickens. More importantly, our findings offer insights into the relationship between miRNA and immune-related target genes and the role of miRNA in HPAIV infections in chickens.


Subject(s)
Influenza A Virus, H5N1 Subtype , Influenza A virus , Influenza in Birds , MicroRNAs , Humans , Animals , Chickens/genetics , Chickens/metabolism , Influenza A Virus, H5N1 Subtype/genetics , Influenza in Birds/genetics , Trachea/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Influenza A virus/genetics
6.
Dev Comp Immunol ; 149: 104921, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37611883

ABSTRACT

MicroRNAs play crucial roles in immune-related pathways in host animals. In this study, we aimed to investigate the systemic biological function of gga-miR-26a-5p, a chicken miRNA, in the immune responses to HPAIV H5N1 infection in the Vietnamese Ri chicken line. Our results showed a significant downregulation in gga-miR-26a expression in the lung tissue of Ri chickens during HPAIV H5N1 infection. Overexpression of gga-miR-26a and the reporter construct, either containing the wildtype or mutant melanoma differentiation-associated protein 5 (MDA5) 3' untranslated region (3' UTR)-luciferase, into a chicken fibroblast cell line, revealed that gga-miR-26a can act as a direct translational repressor of MDA5 by targeting the 3' UTRs. Additionally, miR-26a negatively regulated the expression of the signaling molecules related to the MDA5 signaling pathway, including MDA5, mitochondrial antiviral-signaling (MAVS), interferon regulatory factor 7 (IRF7), p38 mitogen-activated protein kinases, and nuclear factor-kappa B (NF-κB). Moreover, downstream of the IRF7 and NF-κB signaling pathway, the proinflammatory cytokines such as IL-1ß, IFN-γ, IFN-α, IFN-ß, and the interferon-stimulated gene (Mx1) were, likewise, downregulated by the overexpression of gga-miR-26a. These findings suggest that gga-miR-26a-5p serves as an important regulator in the MDA5 signaling pathway and antiviral response. Overall, our results contribute to an improved understanding of the biological functions of gga-miR-26a-5p, alongside the mechanisms underlying the MDA5 signaling pathway, and the antiviral response to HPAIV-H5N1 infection in chickens.

7.
Br J Pharmacol ; 180(23): 3059-3070, 2023 12.
Article in English | MEDLINE | ID: mdl-37501600

ABSTRACT

BACKGROUND AND PURPOSE: Pruritic dermatitis is a disease with a considerable unmet need for treatment and appears to present with not only epidermal but also peripheral neuronal complications. Here, we propose a novel pharmacological modulation targeting both peripheral dorsal root ganglion (DRG) sensory neurons and skin keratinocytes. GPR35 is an orphan G-protein-coupled receptor expressed in DRG neurons and has been predicted to downregulate neuronal excitability when activated. Modulator information is currently increasing for GPR35, and pamoic acid (PA), a salt-forming agent for drugs, has been shown to be an activator solely specific for GPR35. Here, we investigated its effects on dermatitic pathology. EXPERIMENTAL APPROACH: We confirmed GPR35 expression in peripheral neurons and tissues. The effect of PA treatment was pharmacologically evaluated in cultured cells in vitro and in in vivo animal models for acute and chronic pruritus. KEY RESULTS: Local PA application mitigated acute non-histaminergic itch and, consistently, obstructed DRG neuronal responses. Keratinocyte fragmentation under dermatitic simulation was also dampened following PA incubation. Chronic pruritus in 1-chloro-2,4-dinitrobenzene and psoriasis models were also moderately but significantly reversed by the repeated applications of PA. Dermatitic scores in the 1-chloro-2,4-dinitrobenzene and psoriatic models were also improved by its application, indicating that it is beneficial for mitigating disease pathology. CONCLUSION AND IMPLICATIONS: Our findings suggest that pamoic acid activation of peripheral GPR35 can contribute to the improvement of pruritus and its associated diseases.


Subject(s)
Dermatitis , Dinitrochlorobenzene , Animals , Dinitrochlorobenzene/metabolism , Dinitrochlorobenzene/pharmacology , Pruritus/drug therapy , Pruritus/metabolism , Skin/metabolism , Dermatitis/metabolism , Ganglia, Spinal/metabolism
8.
Anal Chem ; 95(36): 13478-13487, 2023 09 12.
Article in English | MEDLINE | ID: mdl-37523497

ABSTRACT

Label-free optical diffraction tomography provides three-dimensional imaging of cells and organelles, along with their refractive index (RI) and volume. These physical parameters are valuable for quantitative and accurate analysis of the subcellular microenvironment and its connections to intracellular biological properties. In biological and biochemical cell analysis, various invasive cell manipulations are used, such as temperature change, chemical fixation, live cell staining with fluorescent dye, and gene overexpression of exogenous proteins. However, it is not fully understood how these various manipulations affect the physicochemical properties of different organelles. In this study, we investigated the impact of these manipulations on the cellular properties of single HeLa cells. We found that after cell fixation and an increase in temperature, the RI value of organelles, such as the nucleus and cytoplasm, significantly decreased overall. Interestingly, unlike the cell nuclei, cytoplasmic RI values were hardly detected after membrane permeation, indicating that only intracytoplasmic components were largely lost. Additionally, our findings revealed that the expression of GFP and GFP-tagged proteins significantly increased the RI values of organelles in living cells compared to the less effective RI changes observed with chemical fluorescence staining for cell organelles. The result demonstrates that distinct types of invasive manipulations can alter the microenvironment of organelles in different ways. Our study sheds new light on how chemical and genetic manipulations affect organelles.


Subject(s)
Cell Nucleus , Organelles , Humans , HeLa Cells , Cytoplasm , Cytosol/chemistry , Tomography/methods
9.
Environ Pollut ; 333: 122119, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37385358

ABSTRACT

Fipronil (FIL) use is currently regulated in several countries due to its specific toxicity to bees. This study investigated the possible developmental toxicities as well as the acute toxicities of FIL, fipronil sulfide (FIL-SI), and fipronil sulfone (FIL-SO) to zebrafish (Danio rerio) embryos. At concentrations up to 5000 µg L-1, FIL- and FIL-SI-treated embryos exhibited significant mortality at 96 h postfertilization. Body length was significantly shortened with increasing concentrations in FIL- and FIL-SI-treated embryos. However, FIL-SO-treated embryos exhibited low mortality with high hatching rates. Body length was also significantly shortened in FIL-SO-treated embryos. Regarding the number of intersegmental vessels (ISVs), all chemical-treated embryos showed high ISV numbers with increasing concentrations of each chemical. FIL and FIL-SI induced abnormal heart formation with heart dysfunction in embryos, whereas FIL-SO did not induce any difference in heart development compared with the control. Abnormal heart formation may be related to the upregulation of nppa responsible for the expression of natriuretic peptides in embryos. Embryonic acetylcholinesterase activity was decreased gradually according to the increase in FIL and FIL-SI concentrations, whereas FIL-SO did not cause any change in enzyme activity. Il-1ß responsible for the occurrence of injury or infection was highly upregulated in FIL-SI- and FIL-SO-treated embryos. Therefore, reduction to FIL-SI may be associated with FIL toxicity, whereas oxidation to FIL-SO may be a detoxification route in the environment.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/metabolism , Acetylcholinesterase/metabolism , Water Pollutants, Chemical/metabolism , Embryo, Nonmammalian
10.
Ecotoxicol Environ Saf ; 258: 114995, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37167734

ABSTRACT

Piperlongumine (PL) and piperine (PP) are alkaloids presented in long pepper (Piper longum), and they exhibit various biological activities, especially anti-cancer properties. With these regards, they are considered as future medicines with high potential. Even they are exposed to humans such a long time, their potential toxicities in the environment have not been studied. Therefore, their ecological toxicities were assessed using zebrafish embryos. PP showed low mortality and no abnormal phenotype up to 10 µM. However, PL exhibited strong acute toxicity at the concentration of 5-10 µM ranges, and abnormal development were frequently found in the range of 1-2.5 µM with pericardial and yolk sac edemas. In transgenic zebrafish embryos, PL induced an increase in the number of intersegmental vessels and delayed the early-stage development. PL treatment affected heart formation and heart rate. The presence of PL induced the expression of cytokines, inflammatory markers, and inflammasome in the embryos. The PL treatment changed the mRNA levels of the ER stress and apoptosis-related genes. In addition, ROS production was observed during early-stage development of PL-treated zebrafish embryos. These results indicate that developing PL as a medicine would require extremely meticulous strategies to prevent potential toxicity.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Humans , Animals , Zebrafish/metabolism , Embryo, Nonmammalian , Pericardium , Liver , Water Pollutants, Chemical/metabolism
11.
Environ Pollut ; 327: 121537, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37003586

ABSTRACT

Trifloxystrobin (TFS) is one of the extensively used strobilurin fungicides, which is composed of four enantiomers and its active form is E,E-TFS. In this study, we assess the acute toxicity of four enantiomers, E,E-, E,Z-, Z,E-, and Z,Z-TFS in zebrafish (Danio rerio) embryos. Among the four enantiomers, only E,E-TFS was found to be acutely toxic, with an estimated LC50 value of 0.68 mg/L. Treatment with E,E-TFS resulted in various phenotypic changes in the embryos, including pericardial and yolk-sac edema, spine curvature, and blood pooling. And it shortened the whole body length in the treated embryos by increasing the total intersegmental vessel numbers using a Tg(fli1a:EGFP) zebrafish line. Further study using Tg(cmlc2:EGFP) zebrafish line revealed that E,E-TFS treatment was associated with cardiac malformations, a failure of heart function, and a lowered heartbeat rate at the concentration of 0.25 mg/L. Also, the differential gene expression analysis identified significant down-regulation of vmhc and cacna1c genes encoding ventricular myosin heavy chain and calcium voltage-gated channel subunit alpha 1C, which are crucial for heart development. These results suggest the need for regular monitoring of E,E-TFS enantiomers after field application and further research into their potential chronic effects on environmental organisms.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/genetics , Strobilurins , Stereoisomerism , Embryo, Nonmammalian , Water Pollutants, Chemical/toxicity
12.
Environ Pollut ; 325: 121450, 2023 May 15.
Article in English | MEDLINE | ID: mdl-36940914

ABSTRACT

Combined toxicity can occur in the environment according to the combination of single substances, and the combination works additively or in a synergistic or antagonistic mode. In our study, 3,5,6-trichloro-2-pyridinol (TCP) and 2-(bromomethyl)naphthalene (2-BMN) were used to measure combined toxicity in zebrafish (Danio rerio) embryos. As the lethal concentration (LC) values were obtained through single toxicity, the lethal effects at all combinational concentrations were considered synergistic by the Independent Action model. At 96 hpf, the combined toxicity of TCP LC10 + 2-BMN LC10, the lowest combinational concentration, resulted in high mortality, strong inhibition of hatching, and various morphological changes in zebrafish embryos. Combined treatment resulted in the downregulation of cyp1a, leading to reduced detoxification of the treated chemicals in embryos. These combinations may enhance endocrine-disrupting properties via upregulation of vtg1 in embryos, and inflammatory responses and endoplasmic reticulum stress were found to upregulate il-ß, atf4, and atf6. These combinations might induce severe abnormal cardiac development in embryos via downregulation of myl7, cacna1c, edn1, and vmhc expression, and upregulation of the nppa gene. Therefore, the combined toxicity of these two chemicals was observed in zebrafish embryos, which proves that similar substances can exhibit stronger combined toxicity than single toxicity.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/physiology , Pyridones , Naphthalenes/toxicity , Heart , Embryo, Nonmammalian , Water Pollutants, Chemical/pharmacology
13.
Foods ; 12(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36900442

ABSTRACT

Regulation of melanin production via the MC1R signaling pathway is a protective mechanism of the skin of living organisms against exposure to ultraviolet rays. The discovery of human skin-whitening agents has been one of the most intense pursuits of the cosmetic industry. The MC1R signaling pathway is activated by its agonist, alpha-melanocyte stimulating hormone (α-MSH), and mainly regulates melanogenesis. Here, we evaluated the antimelanogenic activities of curcumin (CUR) and its two derivatives, dimethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), in B16F10 mouse melanoma cells and zebrafish embryos. CUR and BDMC reduced the α-MSH-induced melanin production in B16F10 cells and also downregulated the expression of the melanin-production-related genes Tyr, Mitf, Trp-1, and Trp-2. Moreover, the biological activity of these two compounds against melanogenesis was confirmed in in vivo experiments using zebrafish embryos. However, the highest concentration of CUR (5 µM) resulted in slight malformations in zebrafish embryos, as indicated by acute toxicity tests. In contrast, DMC did not show any biological activity in vitro or in vivo. Conclusively, BDMC is a strong candidate as a skin-whitening agent.

14.
Ecotoxicol Environ Saf ; 253: 114654, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36801540

ABSTRACT

Pymetrozine (PYM) is worldwide used to control sucking insect pests in rice-cultivated fields and it is degraded into various metabolites including 3-pyridinecarboxaldehyde (3-PCA). These two pyridine compounds were used to determine their impacts on aquatic environments, particularly on the aquatic animal model zebrafish (Danio rerio). PYM did not show acute toxicities in terms of lethality, hatching rate, and phenotypic changes in zebrafish embryos in the tested ranges up to a concentration of 20 mg/L. 3-PCA exhibited acute toxicity with LC50 and EC50 values of 10.7 and 2.07 mg/L, respectively. 3-PCA treatment caused phenotypic changes including pericardial edema, yolk sac edema, hyperemia, and curved spine, at a concentration of 10 mg/L after 48 h of exposure. Abnormal cardiac development was observed in 3-PCA-treated zebrafish embryos at a concentration of 5 mg/L with reduced heart function. In a molecular analysis, cacna1c, encoding a voltage-dependent calcium channel, was significantly down-regulated in the 3-PCA-treated embryos, indicating synaptic and behavioral defects. Hyperemia and incomplete intersegmental vessels were observed in 3-PCA-treated embryos. Based on these results, it is necessary to generate scientific information on the acute and chronic toxicity of PYM and its metabolites with regular monitoring of their residues in aquatic environments.


Subject(s)
Hyperemia , Water Pollutants, Chemical , Animals , Zebrafish/metabolism , Embryo, Nonmammalian/metabolism , Hyperemia/metabolism , Heart , Water Pollutants, Chemical/analysis
15.
J Hazard Mater ; 443(Pt A): 130141, 2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36241498

ABSTRACT

Phosphine (PH3) is an ideal fumigant alternative on methyl bromide (MB) as MB has been classified as an ozone-depleting substance. However, several challenges limit its efficient use in crop production, including the emergence of PH3-resistant insect pests and the incidence of phytotoxic effects on nursery plants. Therefore, this study aims to elucidate the mechanism underlying PH3 phytotoxicity in plants using transcriptomic techniques. Fumigation with 2 g/m3 PH3 induced phytotoxic effects in A. thaliana, as evidenced by a decrease in growth and vegetation indices compared to the control group. Transcriptomic analysis revealed that PH3 fumigation phytotoxicity responses in A. thaliana involve genes related to hypoxia stress and energy metabolism. Additionally, pretreatment with ethylene induced pre-adaptation to hypoxia under light conditions during fumigation effectively suppressed the phytotoxic effects of PH3 in A. thaliana by increasing the expression of hypoxia-adaptive genes. Moreover, the phytotoxicity of PH3 was also confirmed in pumpkin (Cucurbita moschata Duch.), and was dependent on light. Overall, our findings showed that fumigation under light conditions and ethylene pretreatment could be used to minimize PH3-induced phytotoxic effects in plants.


Subject(s)
Arabidopsis , Cucurbita , Phosphines , Arabidopsis/genetics , Transcriptome , Phosphines/toxicity , Hypoxia , Energy Metabolism , Ethylenes
16.
Neurotherapeutics ; 20(1): 325-337, 2023 01.
Article in English | MEDLINE | ID: mdl-36352334

ABSTRACT

The function of peripheral nociceptors is frequently tuned by the action of G protein-coupled receptors (GPRs) that are expressed in them, which contribute to pain alteration. Expanding new information on such GPRs and predicting their potential outcomes can help to construct new analgesic strategies based on their modulations. In this context, we attempted to present a new GPR not yet acknowledged for its pain association. Gpr83 exhibits relatively high expressions in the peripheral nervous system compared to other tissues when we mined and reconstructed Gene Expression Omnibus (GEO) metadata, which we confirmed using immunohistochemistry on murine dorsal root ganglia (DRG). When Gpr83 expression was silenced in DRG, neuronal and behavioral nociception were all downregulated. Pathologic pain in hind paw inflammation and chemotherapy-induced peripheral neuropathy were also alleviated by this Gpr83 knockdown. Dependent on exposure time, the application of a known endogenous Gpr83 ligand PEN showed differential effects on nociceptor responses in vitro. Localized PEN administration mitigated pain in vivo, probably following Gq/11-involved GPR downregulation caused by the relatively constant exposure. Collectively, this study suggests that Gpr83 action contributes to the tuning of peripheral pain sensitivity and thus indicates that Gpr83 can be among the potential GPR targets for pain modulation.


Subject(s)
Ganglia, Spinal , Nociceptors , Pain Threshold , Pain , Receptors, G-Protein-Coupled , Animals , Mice , Ganglia, Spinal/chemistry , Ganglia, Spinal/metabolism , Neurons/metabolism , Nociceptors/metabolism , Pain/genetics , Pain/metabolism , Pain Threshold/physiology , Receptors, G-Protein-Coupled/analysis , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Nociception/physiology
17.
Sci Rep ; 12(1): 19423, 2022 Nov 12.
Article in English | MEDLINE | ID: mdl-36371420

ABSTRACT

P-type ternary switch devices are crucial elements for the practical implementation of complementary ternary circuits. This report demonstrates a p-type ternary device showing three distinct electrical output states with controllable threshold voltage values using a dual-channel dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]-thiophene-graphene barristor structure. To obtain transfer characteristics with distinctively separated ternary states, novel structures called contact-resistive and contact-doping layers were developed. The feasibility of a complementary standard ternary inverter design around 1 V was demonstrated using the experimentally calibrated ternary device model.

18.
PLoS One ; 17(11): e0277527, 2022.
Article in English | MEDLINE | ID: mdl-36449449

ABSTRACT

With a cluster of commodity hardware, how can we efficiently find all connected components of an enormous graph containing hundreds of billions of nodes and edges? The problem of finding connected components has been used in various applications such as pattern recognition, reachability indexing, graph compression, graph partitioning, and random walk. Several studies have been proposed to efficiently find connected components in various environments. Most existing single-machine and distributed-memory algorithms are limited in scalability as they have to load all data generated during the process into the main memory; they require expensive machines with vast memory capacities to handle large graphs. Several MapReduce algorithms try to handle large graphs by exploiting distributed storage but fail due to data explosion problems, which is a phenomenon that significantly increases the size of data as the computation proceeds. The latest MapReduce algorithms resolve the problem by proposing two distinguishing star-operations and executing them alternately, while the star-operations still cause massive network traffic as a star-operation is a distributed operation that connects each node to its smallest neighbor. In this paper, we unite the two star-operations into a single operation, namely UniStar, and propose UniCon, a new distributed algorithm for finding connected components in enormous graphs using UniStar. The partition-aware processing of UniStar effectively resolves the data explosion problems. We further optimize UniStar by filtering dispensable edges and exploiting a hybrid data structure. Experimental results with a cluster of 10 cheap machines each of which is equipped with Intel Xeon E3-1220 CPU (4-cores at 3.10GHz), 16GB RAM, and 2 SSDs of 1TB show that UniCon is up to 13 times faster than competitors on real-world graphs. UniCon succeeds in processing a tremendous graph with 129 billion edges, which is up to 4096 times larger than graphs competitors can process.

19.
Biochem Biophys Res Commun ; 627: 97-102, 2022 10 30.
Article in English | MEDLINE | ID: mdl-36030658

ABSTRACT

A nuclear serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) is a critical regulator of development and DNA damage response. HIPK2 can induce apoptosis under cellular stress conditions and thus its protein level is maintained low by constant proteasomal degradation. In the present study, we present evidence that TNF receptor-associated factor 2 (TRAF2) regulates the protein stability of HIPK2. Overexpression of TRAF2 decreased while its knockdown increased the HIPK2 protein level. The TRAF2-mediated decrease in HIPK2 protein expression was blocked by proteasomal inhibitor. In addition, TRAF2 decreased the protein half-life of HIPK2. We found that HIPK2 and TRAF2 co-immunoprecipitated. Interestingly, the co-immunoprecipitation was reduced while HIPK2 protein level increased following TNFα treatment, suggesting TNFα induced dissociation of TRAF2 from HIPK2 to accumulate HIPK2. Inhibition of HIPK2 partially suppressed TNFα-induced cell death, indicating that the accumulated HIPK2 may contribute to the TNFα-induced cell death. Our results suggest that TRAF2 can regulate proapoptotic function of HIPK2 by promoting proteasomal degradation.


Subject(s)
Protein Serine-Threonine Kinases , Tumor Necrosis Factor-alpha , Apoptosis , Protein Serine-Threonine Kinases/genetics , Protein Stability , TNF Receptor-Associated Factor 2/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Ubiquitin-Protein Ligases/metabolism
20.
J Pharmacopuncture ; 25(2): 138-144, 2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35837147

ABSTRACT

Cervical spondylotic myelopathy (CSM) is common in elderly people and severe CSM patients are recommended to receive surgery. However, in some cases, surgery may fail to improve the patients' symptoms. An 80-year-old man diagnosed with CSM complained of right hemiplegia and right arm and leg pain with the presence of a Foley catheter, despite treatment with laminectomy and laminoplasty. Acupuncture, bee venom pharmacopuncture, and herbal medicine were administered for 129 days. As a result, manual muscle testing (MMT) and the Modified Barthel Index (MBI) improved, the pain in his right arm and leg decreased, and he was able to urinate by himself. This case report implies that integrative Korean medicine (IKM) can be an option for patients suffering from muscular weakness resulting from myelopathy.

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