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1.
FASEB J ; 34(10): 13445-13460, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32816366

RESUMEN

We investigated the effect of chitinase-3-like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1-mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.


Asunto(s)
Proteína 1 Similar a Quitinasa-3 , Diabetes Mellitus/metabolismo , Glucosa/metabolismo , Músculo Esquelético , Proteínas Quinasas Activadas por AMP/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Línea Celular , Proteína 1 Similar a Quitinasa-3/sangre , Proteína 1 Similar a Quitinasa-3/fisiología , Estudios de Asociación Genética , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Mioblastos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas
2.
Pain Pract ; 21(8): 836-842, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33973363

RESUMEN

OBJECTIVES: Transforaminal epidural steroid injection (TFESI) is widely used to manage lumbosacral radicular pain due to herniated lumbar disc (HLD). OBJECTIVES: We evaluated the long-term outcomes of TFESI in patients with lumbosacral radicular pain due to an HLD by the location, type, and size of the HLD. METHODS: In total, 114 patients who received the initial TFESI at least 4 years ago completed a telephone interview. We investigated the presence of radicular pain, degree of current pain, current pain medications and TFESIs, additional TFESIs, progression to surgery, and trouble in performing daily life activities and occupational job duties. We classified the included patients by the location, type, and size of the HLD, and evaluated whether these factors affected the long-term outcomes of TFESI. RESULTS: At least 4 years after the initial TFESI, radicular pain was completely resolved in 45% of the patients. However, 30% patients were on oral painkillers or repetitive TFESIs or had undergone surgery and 15% had difficulty in performing daily life activities and occupational job duties. A larger number of patients with extruded lumbar disc herniation required additional TFESIs than those with protruded lumbar disc herniation. Apart from this, the outcomes did not significantly differ by the location, type, and size of the HLD. CONCLUSIONS: Our findings provide useful information to clinicians managing radicular pain due to HLD.


Asunto(s)
Desplazamiento del Disco Intervertebral , Dolor de la Región Lumbar , Radiculopatía , Humanos , Inyecciones Epidurales , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/tratamiento farmacológico , Dolor de la Región Lumbar/tratamiento farmacológico , Vértebras Lumbares , Radiculopatía/tratamiento farmacológico , Esteroides , Resultado del Tratamiento
3.
FASEB J ; 33(12): 14825-14840, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31670977

RESUMEN

ATPase inhibitory factor 1 (IF1) is an ATP synthase-interacting protein that suppresses the hydrolysis activity of ATP synthase. In this study, we observed that the expression of IF1 was up-regulated in response to electrical pulse stimulation of skeletal muscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake via AMPK in skeletal muscle cells and primary cultured myoblasts. Reactive oxygen species and Rac family small GTPase 1 (Rac1) function in the upstream and downstream of AMPK, respectively, in IF1-mediated glucose uptake. In diabetic animal models, the administration of recombinant IF1 improved glucose tolerance and down-regulated blood glucose level. In addition, IF1 inhibits ATP hydrolysis by ß-F1-ATPase in plasma membrane, thereby increasing extracellular ATP and activating the protein kinase B (Akt) pathway, ultimately leading to glucose uptake. Thus, we suggest that IF1 is a novel myokine and propose a mechanism by which AMPK and Akt contribute independently to IF1-mediated improvement of glucose tolerance impairment. These results demonstrate the importance of IF1 as a potential antidiabetic agent.-Lee, H. J., Moon, J., Chung, I., Chung, J. H., Park, C., Lee, J. O., Han, J. A., Kang, M. J., Yoo, E. H., Kwak, S.-Y., Jo, G., Park, W., Park, J., Kim, K. M., Lim, S., Ngoei, K. R. W., Ling, N. X. Y., Oakhill, J. S., Galic, S., Murray-Segal, L., Kemp, B. E., Mantzoros, C. S., Krauss, R. M., Shin, M.-J., Kim, H. S. ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways.


Asunto(s)
Glucosa/metabolismo , Mioblastos/metabolismo , Proteínas/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Adenosina Trifosfato/metabolismo , Adulto , Animales , Línea Celular , Células Cultivadas , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas/metabolismo , Proteínas/genética , Proteínas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Recombinantes/uso terapéutico , Proteína Inhibidora ATPasa
4.
Int J Neurosci ; 129(12): 1189-1191, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31307259

RESUMEN

Purpose/Aim: Macroglossia is a rare condition, especially in patients with motor neuron disease. In this case report, we describe a patient with macroglossia in the early stages of motor neuron disease. Case report: A 62-year-old woman presented with macroglossia in the early stages of motor neuron disease. She was referred to the department of physical medicine and rehabilitation of a university hospital for rehabilitation with the diagnosis of motor neuron disease, most likely primary lateral sclerosis. Her speech was incomprehensible, and she also showed significant sialorrhea and had difficulty in chewing large solid food. Her tongue was enlarged on examination, and she could not close her mouth fully. No other possible causes of macroglossia were found. She showed nocturnal hypercapnia on overnight capnography examination coupled with desaturation, which was believed to result from the macroglossia. After commencing non-invasive ventilation with pressure control mode, follow-up overnight capnography revealed EtCO2 values within the normal range. Conclusions: To the best of our knowledge, this is the first report of macroglossia in PLS. Further study would be needed to ascertain the pathogenesis of this phenomenon.


Asunto(s)
Macroglosia/complicaciones , Enfermedad de la Neurona Motora/complicaciones , Femenino , Humanos , Macroglosia/patología , Macroglosia/fisiopatología , Persona de Mediana Edad , Enfermedad de la Neurona Motora/patología , Enfermedad de la Neurona Motora/fisiopatología
5.
Biochem Biophys Res Commun ; 499(3): 655-661, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29604272

RESUMEN

Adipokines, a group of proteins including leptin, visfatin, resistin, and adiponectin, are produced by adipocytes. Among adipokines, resistin is implicated in insulin resistance and inflammatory response modulation. Mucus hypersecretion has been greatly linked to airway diseases, such as asthma, chronic obstructive pulmonary disease, and rhinosinusitis. Increasing evidence has indicated that adipokines, such as leptin and visfatin, play important regulatory roles in various biological processes involved in mucus secretion. However, the effects of resistin on mucin expression in human airway epithelial cells, as well as the underlying mechanisms, have not been investigated yet. We showed that resistin affected mucin expression in human airway epithelial cells via the mitogen-activated protein kinase/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Resistin increased MUC5AC and MUC5B expression in NCI-H292 and primary human nasal epithelial cells. Additionally, it significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and NF-κB. ERK1/2 and p38 specific inhibitors significantly attenuated resistin-induced MUC5AC/5B expression; however, NF-κB inhibitor reduced resistin-induced MUC5AC, but not MUC5B, expression. Knockdown of ERK1, ERK2, and p38 by ERK1, ERK2, and p38 small interfering RNA (siRNA), respectively, significantly blocked resistin-induced MUC5AC and MUC5B mRNA expression. In addition, NF-κB siRNA attenuated resistin-induced MUC5AC, but not MUC5B, expression. These results suggested that resistin induced MUC5AC and MUC5B expression via activation of different signaling pathways in human airway epithelial cells.


Asunto(s)
Células Epiteliales/metabolismo , Mucina 5AC/genética , Mucina 5B/genética , Nariz/citología , Resistina/farmacología , Regulación hacia Arriba/genética , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mucina 5AC/metabolismo , Mucina 5B/metabolismo , FN-kappa B/metabolismo , Regulación hacia Arriba/efectos de los fármacos
6.
Endocr J ; 65(9): 881-891, 2018 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-29937467

RESUMEN

Vitamin D deficiency affects >60% of the Korean population. Recent reports in Caucasian, African American, and Chinese populations indicate an association between vitamin D status and related single nucleotide polymorphisms (SNPs), but specific associations differ among study populations. We investigated the relationship between five SNPs involved in the vitamin D metabolic pathway (DHCR7 rs12785878, GC rs2282679, CYP2R1 rs12794714, CYP2R1 rs10741657, and CYP24A1 rs6013897) and serum 25-hydroxyvitamin D [25(OH)D] status in Koreans using the Korea National Health and Nutrition Examination Survey, a nationwide database. Whether the association was modified by demographic and lifestyle factors, including sex, body mass index (BMI), smoking status, drinking status, physical activity, and sun exposure, were also investigated. The results showed the serum level of 25(OH)D was associated with rs12785878, rs2282679, and rs12794714 genotypes, but not with rs10741657 or rs6013897. The genetic risk score (GRS) calculated by summing the number of alleles of these 5 SNPs was associated with low circulating levels of 25(OH)D. However, the negative association between 25(OH)D and GRS was modified by obesity and sun exposure. Specifically, negative associations between 25(OH)D and GRS were present in adults with lower BMI (<25 kg/m2) and longer sun exposure time (≥2 h/day). In conclusion, common variants of vitamin D-related SNPs are associated with vitamin D status in Koreans, and this genetic effect was masked when BMI ≥25 kg/m2 or sun exposure <2 h/day. Additionally, seasonal variation must be considered in future studies among Koreans.


Asunto(s)
Redes y Vías Metabólicas/genética , Polimorfismo de Nucleótido Simple , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/genética , Vitamina D/análogos & derivados , Adulto , Colestanotriol 26-Monooxigenasa/genética , Estudios Transversales , Familia 2 del Citocromo P450/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , República de Corea/epidemiología , Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Proteína de Unión a Vitamina D/genética
7.
Ann Nutr Metab ; 70(2): 122-131, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28346913

RESUMEN

BACKGROUND/AIMS: Low socioeconomic status (SES) is linked to higher incidence/mortality of cardiovascular disease, but emerging evidence inconsistently reported that education level, a proxy for SES, is related to cardiovascular risk and metabolic syndrome (MetS) in Koreans. Furthermore, limited information is available on whether dietary components would mediate the relationship between education level and cardiovascular risk. We hypothesized that selected food consumption mediates the association between education level and MetS prevalence. METHODS: Data from the Korea National Health and Nutritional Examination Survey (2008-2011) were included in cross-sectional analyses (n = 11,029, 30-64 years). The possible mediating effect of selected food groups (fruits, raw vegetables, red meat, milk, and soft drinks) on the association between education level and MetS was tested using a multiple mediation model. RESULTS: Education level was negatively associated with MetS prevalence. The association between lower education level and higher MetS prevalence was partially mediated by selected food consumption (lower intakes of fruit, red meat and milk; higher intakes of vegetable and soft drink) after adjusted for covariates. Gender also modified the association between education level and MetS prevalence that was more prominent in women than in men. CONCLUSIONS: Selected food consumption substantially contributes to the association between education level and MetS in Korean adults, especially among women.


Asunto(s)
Pueblo Asiatico , Enfermedades Cardiovasculares/epidemiología , Dieta , Escolaridad , Síndrome Metabólico/epidemiología , Adulto , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Prevalencia , República de Corea , Factores de Riesgo
8.
Biomacromolecules ; 17(3): 1160-9, 2016 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-26905040

RESUMEN

Exendin-4 (EX4), a glucagon-like peptide-1 receptor (GLP-1R) agonist that regulates blood glucose levels, has been used in the management of type-2 diabetes mellitus. EX4 can be PEGylated to improve its antidiabetic effects by enhancing its stability and extending the circulation half-life. Here, to determine whether PEGylated EX4 is effective for the treatment of sepsis, C-terminal thiol-specific PEGylated EX4s with linear maleimide-PEG-2K, -5K, -20K and trimeric maleimide-PEG-50K (hereafter referred to as EX4-2K, EX4-5K, EX4-20K, and EX4-50K, respectively) were prepared, and their antiseptic responses were investigated. These PEGylated EX4s reduced cecal ligation and puncture (CLP)-induced organ injury by decreasing hyperpermeability, and suppressing interactions between leukocytes and endothelial cells. The binding avidity and stability of EX4-50K toward GLP-1R were superior to that of wild-type EX4, as was the circulation half-life of EX4-50K. In addition, the antiseptic effects of EX4-50K were superior to those of other PEGylated EX4s, which may be attributed to enhanced proteolytic stability, longer circulation half-life, and higher receptor-binding affinity of EX4-50K due to its trimeric PEG structure. Therefore, EX4-50K may decrease CLP-induced septic mortality in vivo. There are currently neither effective preventatives against nor treatment options for sepsis; our results show that EX4-50K has the potential to treat sepsis.


Asunto(s)
Antibacterianos/química , Péptidos/química , Polietilenglicoles/química , Sepsis/tratamiento farmacológico , Ponzoñas/química , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Exenatida , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Masculino , Maleimidas/química , Ratones , Ratones Endogámicos C57BL , Péptidos/farmacología , Péptidos/uso terapéutico , Unión Proteica , Estabilidad Proteica , Ponzoñas/farmacología , Ponzoñas/uso terapéutico
9.
Biochim Biophys Acta ; 1840(6): 2042-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24576671

RESUMEN

BACKGROUND: Endangered plant species are a vital resource for exploring novel drug prototypes. A Korean endangered plant Rhododendron brachycarpum G. Don is a broad-leaved shrub native to northern Korea and central Japan. The high mobility group box 1 protein (HMGB1) could be a specific target for the discovery of novel antiseptic agents. METHODS: Gauge-invariant atomic orbital (GIAO) NMR chemical shift calculations were applied for investigation of stereochemical details with accuracy improved by application of DP4 analysis. In vitro antiseptic mechanisms were investigated utilizing immunofluorescence staining, ELISA and cell-cell adhesion assay. Cecal ligation and puncture (CLP) operation was employed to evaluate in vivo potential alleviating severe sepsis and septic shock. RESULTS: The first bicyclic megastigmane glucoside rhododendroside A (1) along with known megastigmane glucosides (2-5) were isolated from the leaves of R. brachycarpum. The structure of 1 was established by NMR analysis as well as comparison of the experimental chemical shifts with those of computed values employing DP4 application. In the CLP operation model that simulates severe sepsis, rhododendroside A (1) improved the survival rate up to 60%. CONCLUSIONS: Our results exhibit that R. brachycarpum may produce a unique scaffold that is developed into a drug lead mitigating HMGB1-induced vascular pro-inflammatory stimuli and thus alleviating severe sepsis and related manifestations. GENERAL SIGNIFICANCE: Discovery of new drug leads would warrant conservation efforts of endangered species.


Asunto(s)
Ciclohexanonas/uso terapéutico , Descubrimiento de Drogas , Glucósidos/uso terapéutico , Proteína HMGB1/antagonistas & inhibidores , Norisoprenoides/uso terapéutico , Rhododendron/química , Sepsis/tratamiento farmacológico , Animales , Permeabilidad Capilar/efectos de los fármacos , Proteína HMGB1/fisiología , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Hojas de la Planta/química
10.
Biochem Biophys Res Commun ; 459(4): 662-7, 2015 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-25769950

RESUMEN

High mobility group box 1 (HMGB1) was recently shown to be an important extracellular mediator of severe vascular inflammatory disease, sepsis. Lysozyme (LYZ) has been shown to bind to bacterial lipopolysaccharide (LPS) and have a potential for playing a role in the therapy of inflammatory diseases. However, the effect of LYZ on HMGB1-induced septic response has not been investigated. Moreover, PEGylation effects on the antiseptic activity of LYZ are not known. Here, we show, for the first time, the anti-septic effects of PEGylated LYZ (PEG-LYZ) in HMGB1-mediated inflammatory responses in vitro and in vivo. Among four mono-PEGylated LYZs with different PEGylation sites (N-terminus, Lys(13), Lys(33), and Lys(97)), N-terminally PEGylated LYZ showed the highest activity. Subsequently, among three N-terminally PEGylated LYZs prepared with aldehyde-activated PEGs of 5, 10, and 20 kDa, 5 kDa-PEG-conjugated LYZ (P5-K(1)-LYZ) showed the highest antiseptic activity. The data showed that P5-K(1)-LYZ post-treatment effectively suppressed LPS-mediated release of HMGB1. P5-K(1)-LYZ also inhibited HMGB1-mediated hyperpermeability in human endothelial cells. Furthermore, P5-K(1)-LYZ reduced the cecal ligation and puncture (CLP)-induced release of HMGB1 and septic mortality. Collectively, these results suggest P5-K(1)-LYZ as a candidate therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.


Asunto(s)
Muramidasa/química , Polietilenglicoles/química , Animales , Endotelio/metabolismo , Humanos , Ratones
11.
Biochem Biophys Res Commun ; 459(4): 650-4, 2015 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-25757907

RESUMEN

Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, has been reported to attenuate myocardial ischemia and reperfusion injury and inflammatory or oxidative responses. The expression level of secretory group IIA phospholipase A2 (sPLA2-IIA) is elevated in inflammatory diseases. Lipopolysaccharide (LPS) upregulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Here, EX4 was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mice. Pre-treatment of cells or mice with EX4 inhibited LPS-induced sPLA2-IIA expression and activity. Additionally, EX4 suppressed LPS-induced activation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2. Therefore, these results show that EX4 inhibited LPS-induced expression of sPLA2-IIA by suppressing cPLA2 and ERK 1/2.


Asunto(s)
Péptidos/fisiología , Animales , Exenatida , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Fosfolipasas A2 , Ponzoñas
13.
Bioorg Med Chem Lett ; 25(22): 5367-71, 2015 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-26410076

RESUMEN

Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, a new caffeoyl glucoside (1) and two known caffeoylated compounds (2 and 3) were isolated from the fruits of Nandina domestica Thunb. (Berberidaceae). The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses. At 20 µM, 1 and 2 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer in a dose-dependent manner suggesting that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders.


Asunto(s)
Berberidaceae/química , Ácidos Cafeicos/química , Endotelio/efectos de los fármacos , Frutas/química , Glucósidos/química , Lipopolisacáridos , Extractos Vegetales/farmacología , Animales , Ácidos Cafeicos/farmacología , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Endotelio/inmunología , Glucósidos/farmacología , Humanos , Inflamación/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/química
14.
Toxicol Appl Pharmacol ; 281(1): 30-8, 2014 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-25223693

RESUMEN

Inhibition of high mobility group box 1 (HMGB1) protein and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, three structurally related polyphenols found in the Chinese herb Huang Qui, baicalin (BCL), baicalein (BCN), and wogonin (WGN), were examined for their effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. According to our data, BCL, BCN, and WGN inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. BCL, BCN, and WGN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with BCL, BCN, and WGN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that BCL, BCN, and WGN could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway.


Asunto(s)
Permeabilidad Capilar/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Flavanonas/farmacología , Flavonoides/farmacología , Proteína HMGB1/antagonistas & inhibidores , Animales , Permeabilidad Capilar/fisiología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Relación Dosis-Respuesta a Droga , Proteína HMGB1/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología
15.
Inflamm Res ; 63(9): 779-87, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24923846

RESUMEN

AIM AND OBJECTIVE: Fisetin, an active compound isolated from flowering plants in the family Fabaceae, was reported to have antiviral, neuroprotective, and anti-inflammatory effects. Vascular inflammatory processes have been suggested to play key roles in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, we determined the ability of fisetin to suppress vascular inflammatory processes induced by high glucose (HG) in primary human umbilical vein endothelial cells (HUVECs) and mice. METHODS: The effects of fisetin on HG-induced vascular inflammation were determined by measuring vascular permeability, leukocyte adhesion and migration, cell adhesion molecule (CAM) expression levels, reactive oxygen species (ROS) formation, and nuclear factor (NF)-κB activation. RESULTS: HG markedly increased vascular permeability, monocyte adhesion, expressions of CAMs, formation of ROS, and activation of NF-κB. Remarkably, all of the observed vascular inflammatory effects induced by HG were inhibited by pretreatment with fisetin. CONCLUSION: Vascular inflammatory responses induced by HG are critical events underlying the development of diabetic complications; therefore, our results suggest that fisetin possesses significant therapeutic effects against diabetic complications and atherosclerosis.


Asunto(s)
Antiinflamatorios/farmacología , Flavonoides/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Animales , Permeabilidad Capilar/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Línea Celular , Células Cultivadas , Quimiocina CCL2/genética , Selectina E/metabolismo , Flavonoles , Glucosa , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Peróxido de Hidrógeno/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-8/genética , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , ARN Mensajero/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo
16.
J Cosmet Dermatol ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38571374

RESUMEN

BACKGROUND: With the rise in interest and demand for body contouring, beauty devices have continuously developed. Suction can aid in increasing the rate of fat breakdown by inducing a massage-like effect, thereby increasing blood flow. Moreover, radiofrequency (RF) can boost fibroblast activity and help reduce cellulite. In addition, electrical muscle stimulation (EMS) can use electrical stimulation to induce muscle contraction, leading to an athletic, and skin elasticity-increasing effect. AIMS: This study aimed to assess the effects of body contouring, such as cellulite and swelling, in healthy Korean women to objectively prove the efficacy of an at-home beauty device equipped with suction, RF, and EMS functions. METHODS: For 8 weeks, 21 participants used the at-home beauty device 3 days a week on their abdomen, thighs, and left calf. Validity assessments and subjective surveys were conducted at 4 and 8 weeks, including the first visit. RESULTS: The results of the validity assessments revealed that cellulite, swelling, elasticity, femoral skin texture, and dermal density were significantly (p < 0.05) improved in the experimental group compared with those at the baseline. CONCLUSIONS: The results of this study demonstrate that the combination of suction, RF, and EMS function is effective for body skin, fat, and body shape management. For better body-contouring effects, combining the beauty device with regular exercise and healthy eating habits is recommended.

17.
Curr Eye Res ; : 1-9, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771168

RESUMEN

PURPOSE: This study aimed to investigate the effects of l-serine on mitochondrial dysfunction in retinal ganglion cells after exposure to H2O2-induced oxidative stress. METHODS: Retinal ganglion cells obtained from C57BL6 mice (postnatal days 1-4) were purified and cultured. A cell viability assay was performed following exposure to H2O2-induced oxidative stress to assess the cytoprotective effects of l-serine on retinal ganglion cells. Flow cytometry with CellROX Deep Red and MitoSOX dyes was performed to analyze the cytoplasmic and mitochondrial reactive oxygen species levels, respectively. Staining with the fluorescent probe JC-1 was used to detect changes in the mitochondrial membrane potential. The oxygen consumption rate and Bioenergetic Health Index were used to evaluate mitochondrial respiration. RESULTS: H2O2 treatment was found to induce mitochondrial dysfunction in retinal ganglion cells. Pretreatment with l-serine prevented cytotoxicity and significantly increased the viability of retinal ganglion cells following exposure to H2O2-induced oxidative stress (p < .05). l-Serine alleviated reactive oxygen species production in retinal ganglion cells following exposure to H2O2-induced oxidative (p < .05). Further, it successfully mitigated H2O2-induced mitochondrial depolarization in retinal ganglion cells (p < .05) and significantly increased the oxygen consumption rate and Bioenergetic Health Index in retinal ganglion cells following exposure to H2O2-induced oxidative stress (p < .05). CONCLUSION: Pretreatment with l-serine protected retinal ganglion cells from H2O2-induced oxidative stress by improving mitochondrial function. The findings of the present study suggest that l-serine is a potential candidate for treatment of reactive oxygen species-related ocular diseases such as mitochondrial optic neuropathies.

18.
NPJ Biofilms Microbiomes ; 10(1): 19, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38467678

RESUMEN

Lower socioeconomic status (SES) is related to increased incidence and mortality due to chronic diseases in adults. Association between SES variables and gut microbiome variation has been observed in adults at the population level, suggesting that biological mechanisms may underlie the SES associations; however, there is a need for larger studies that consider individual- and neighborhood-level measures of SES in racially diverse populations. In 825 participants from a multi-ethnic cohort, we investigated how SES shapes the gut microbiome. We determined the relationship of a range of individual- and neighborhood-level SES indicators with the gut microbiome. Individual education level and occupation were self-reported by questionnaire. Geocoding was applied to link participants' addresses with neighborhood census tract socioeconomic indicators, including average income and social deprivation in the census tract. Gut microbiome was measured using 16SV4 region rRNA gene sequencing of stool samples. We compared α-diversity, ß-diversity, and taxonomic and functional pathway abundance by SES. Lower SES was significantly associated with greater α-diversity and compositional differences among groups, as measured by ß-diversity. Several taxa related to low SES were identified, especially an increasing abundance of Prevotella copri and Catenibacterium sp000437715, and decreasing abundance of Dysosmobacter welbionis in terms of their high log-fold change differences. In addition, nativity and race/ethnicity have emerged as ecosocial factors that also influence the gut microbiota. Together, these results showed that lower SES was strongly associated with compositional and taxonomic measures of the gut microbiome, and may contribute to shaping the gut microbiota.


Asunto(s)
Etnicidad , Microbioma Gastrointestinal , Adulto , Humanos , Clase Social , Factores Socioeconómicos , Renta
19.
J Yeungnam Med Sci ; 40(2): 123-135, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35618662

RESUMEN

Advances in perinatal and pediatric intensive care and recent advances in mechanical ventilation during the last two decades have resulted in an exponential increase in the number of children undergoing home mechanical ventilation (HMV) treatment. Although its efficacy in chronic respiratory failure is well established, HMV in children is more complex than that in adults, and there are more considerations. This review outlines clinical considerations for HMV in children. The goal of HMV in children is not only to correct alveolar hypoventilation but also to maximize development as much as possible. The modes of ventilation and ventilator settings, including ventilation masks, tubing, circuits, humidification, and ventilator parameters, should be tailored to the patient's individual characteristics. To ensure effective HMV, education for the parent and caregiver is important. HMV continues to change the scope of treatment for chronic respiratory failure in children in that it decreases respiratory morbidity and prolongs life spans. Further studies on this topic with larger scale and systemic approach are required to ensure the better outcomes in this population.

20.
Medicine (Baltimore) ; 102(20): e33860, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37335688

RESUMEN

Prognosis prediction of impaired consciousness is clinically important for establishing therapeutic strategies, determining a rehabilitative goal and functional outcome, and estimating rehabilitative therapy duration. In this study, we investigated the prognosis prediction value of videofluoroscopic swallowing study (VFSS) in recovery of impaired consciousness in stroke patients. Fifty-one patients with impaired consciousness who underwent VFSS during the early stage of stroke between 2017 and 2021 were recruited in this retrospective study. VFSS were performed using modified Logemann protocol, and bonorex was used as the liquid contrast medium. The penetration-aspiration scale (PAS) was graded for all patients, and they were classified into 2 groups depending on the presence of aspiration on liquid material: the aspiration-positive group with a PAS score ≥ 6, and the aspiration-negative group with a PAS score < 6. The coma recovery scale-revised (CRS-R) was used to evaluate patients' conscious state at the time of VFSS and 3 months after. Statistical analysis was performed using independent t test and Pearson's correlation. The increase in total CRS-R score from time of VFSS to 3 months later was greater in aspiration-negative group than in aspiration-positive group (P < .05). A moderate negative correlation was observed between liquid PAS score and the increase in total CRS-R score (r = -0.499, P < .05). Among 6 CRS-R subscales, a strong negative correlation was observed between liquid PAS score and the communication score increase (r = -0.563, P < .05), while moderate negative correlations were detected between liquid PAS score and the increases in auditory (r = -0.465, P < .05), motor (r = -0.372, P < .05), oromotor (r = -0.426, P < .05), and arousal (r = -0.368, P < .05) scores. We observed that patients without aspiration on videofluoroscopic swallowing study showed better recovery of impaired consciousness, and the degree of penetration and aspiration had a predictive value for impaired consciousness prognosis in the early stage of stroke.


Asunto(s)
Trastornos de Deglución , Accidente Cerebrovascular , Humanos , Deglución , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Estudios Retrospectivos , Estado de Conciencia , Pronóstico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Coma
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