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1.
Cancer Sci ; 115(6): 1936-1947, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38590281

RESUMO

The immunoglobulin superfamily (IgSF) is one of the largest families of cell-surface molecules involved in various cell-cell interactions, including cancer-stromal interactions. In this study, we undertook a comprehensive RT-PCR-based screening for IgSF molecules that promote experimental lung metastasis in mice. By comparing the expression of 325 genes encoding cell-surface IgSF molecules between mouse melanoma B16 cells and its highly metastatic subline, B16F10 cells, we found that expression of the immunoglobulin superfamily member 3 gene (Igsf3) was significantly enhanced in B16F10 cells than in B16 cells. Knockdown of Igsf3 in B16F10 cells significantly reduced lung metastasis following intravenous injection into C57BL/6 mice. IGSF3 promoted adhesion of B16F10 cells to vascular endothelial cells and functioned as a homophilic cell adhesion molecule between B16F10 cells and vascular endothelial cells. Notably, the knockdown of IGSF3 in either B16F10 cells or vascular endothelial cells suppressed the transendothelial migration of B16F10 cells. Moreover, IGSF3 knockdown suppressed the extravasation of B16F10 cells into the lungs after intravenous injection. These results suggest that IGSF3 promotes the metastatic potential of B16F10 cells in the lungs by facilitating their adhesion to vascular endothelial cells.


Assuntos
Endotélio Vascular , Neoplasias Pulmonares , Melanoma Experimental , Animais , Humanos , Camundongos , Adesão Celular , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Técnicas de Silenciamento de Genes , Imunoglobulinas/metabolismo , Imunoglobulinas/genética , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Melanoma Experimental/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL
2.
J Neurophysiol ; 129(1): 211-219, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36541608

RESUMO

We previously demonstrated that accurate regulation of isometric contraction (IC) of jaw-closing muscles to counteract the ramp load applied to the jaw in the jaw-opening direction is achieved through the calibration between the two sensations arising from muscle spindles (MSs) and periodontal mechanoreceptors (PMRs). However, it remains unclear whether this calibration mechanism accurately works at any jaw positions, i.e., any vertical dimensions of occlusion (VDO). In the present study, we examined the effects of altering VDO on the IC of the masseter muscles in complete dentulous and edentulous subjects. At a VDO higher than the original VDO (O-VDO), the root mean square (RMS) of masseter EMG activity increased more steeply with a load increase, resulting in an over-counteraction. The regression coefficient of the load-RMS relationship significantly increased as the VDO was increased, suggesting that the overestimation became more pronounced with the VDO increases. Consistently also in the edentulous subjects, at a higher VDO than the O-VDO, a steeper increase in the RMS emerged with a delay in response to the same ramp load whereas a similar steeper increase was seen surprisingly even at a lower VDO. Thus, the edentulous subjects displayed a delayed overestimation of the ramp load presumably due to less and slowly sensitive mucous membrane mechanoreceptor (MMR) in alveolar ridge compared with the PMR. Taken together, the accurate calibration between the two sensations arising from MSs and PMRs/MMRs can be done only at the O-VDO, suggesting that the O-VDO is the best calibration point for performing accurate IC.NEW & NOTEWORTHY Since 1934, the vertical dimension of occlusion (VDO) in edentulous individuals has been anatomically determined mostly by referring to the resting jaw position. However, such a static method is not always accurate. Considering the dynamic nature of clenching/mastication, it is desirable to determine VDO dynamically. We demonstrate that VDO can be accurately determined by measuring masseter EMG during the voluntary isometric contraction of jaw-closing muscles exerted against the ramp load in the jaw-opening direction.


Assuntos
Contração Isométrica , Músculo Masseter , Humanos , Músculo Masseter/fisiologia , Contração Isométrica/fisiologia , Dimensão Vertical , Eletromiografia , Fusos Musculares , Contração Muscular , Músculos da Mastigação/fisiologia
3.
Biochem Biophys Res Commun ; 673: 29-35, 2023 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-37356142

RESUMO

BACKGROUND: The development of effective therapies and biomarkers for pancreatic cancer is an unmet clinical need. To address this, we have developed an easy-to-use pancreatic cancer rat animal model via pancreas-targeted hydrodynamic gene delivery of human pancreatic cancer-related genes. Our study aimed to determine the molecular similarity between the pancreatic tumor in the rat model and human pancreatic cancer. METHODS: KRASG12D gene-expressing plasmid was delivered to the pancreas of wild type rats via pancreas-targeted hydrodynamic gene delivery as previously reported. Tissue samples were collected at 5 weeks after the first gene delivery. The tumors developed in the rats were assessed for the expression of oncogenic proteins that are involved in human pancreatic cancer development. RESULTS: The development of a tumor mimicking pancreatic ductal adenocarcinoma was confirmed. The expression levels of Cyclin D1, c-Jun, IL-33, and Zip4 proteins in the tumor were immunohistochemically assessed and the correlation of the proteins was confirmed. The expression pattern showed similarity to that of surgically resected human pancreatic cancer tissues. CONCLUSIONS: Our study findings showing a similar pattern of oncogenic protein expression in novel KRASG12D gene-induced rat pancreatic cancer model and human pancreatic cancer will be useful for establishing novel tumor markers and therapeutic options for pancreatic cancer.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animais , Ratos , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/metabolismo , Pâncreas/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas
4.
Opt Express ; 31(16): 26135-26144, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710481

RESUMO

We demonstrate a propagation-based phase-contrast imaging method for full-field X-ray microscopy based on advanced Kirkpatrick-Baez (AKB) mirrors to achieve high-contrast observations of weak phase objects and correct field curvature aberrations. Through a demonstration performed at SPring-8, the phase contrast of weak phase objects such as polystyrene spheres and chemically fixed cells was successfully observed with high sensitivity (∼0.03 rad). Furthermore, the field of view of the AKB mirrors was expanded to the full area of the obtained images (25 × 30 µm) by correcting the field curvature aberration using reconstructed complex wavefields.

5.
Phys Rev Lett ; 131(16): 163201, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37925726

RESUMO

X-ray diffraction of silicon irradiated with tightly focused femtosecond x-ray pulses (photon energy, 11.5 keV; pulse duration, 6 fs) was measured at various x-ray intensities up to 4.6×10^{19} W/cm^{2}. The measurement reveals that the diffraction intensity is highly suppressed when the x-ray intensity reaches of the order of 10^{19} W/cm^{2}. With a dedicated simulation, we confirm that the observed reduction of the diffraction intensity can be attributed to the femtosecond change in individual atomic scattering factors due to the ultrafast creation of highly ionized atoms through photoionization, Auger decay, and subsequent collisional ionization. We anticipate that this ultrafast reduction of atomic scattering factor will be a basis for new x-ray nonlinear techniques, such as pulse shortening and contrast variation x-ray scattering.

6.
Inorg Chem ; 62(47): 19270-19278, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37948849

RESUMO

Atomic arrangement in Cu-Pd alloy nanoparticles (NPs) has been reported to influence the catalytic activity, but they have yet to be studied in detail. Unlike previous studies, where the B2 structure Cu-Pd NPs are obtained by heat treating the A1 structure, this study reports the one-pot direct syntheses of A1- and B2-structured Cu-Pd NPs using an alcohol reduction method. The alcohol reduction technique facilitates the kinetic control of the reduction reaction by selecting the appropriate alcohol type and complexing agent to delay the reduction of easily reducible metallic elements to realize control over the reduction kinetics for coreduction. Different formation mechanisms for A1- and B2-structured CuPd NPs were confirmed by in situ ultraviolet-visible (UV-vis) measurements and morphological and structural analyses of samples withdrawn during the reaction. Finally, the direct formation of single-phase B2-structured Cu-Pd NPs with an average diameter of 18.6 ± 7.6 nm was realized using tri-n-octyl phosphine as a complexing agent. The noticeable crystal structural dependence of the electrocatalytic CO2 reduction reaction properties of A1- and B2-structured CuPd NPs was demonstrated.

7.
J Clin Biochem Nutr ; 72(3): 207-214, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37251962

RESUMO

Coenzyme Q10 is an important component of the mitochondrial electron transfer chain. A supercomplex of mitochondrial electron transfer system proteins exists. This complex also contains coenzyme Q10. The concentrations of coenzyme Q10 in tissues decrease with age and pathology. Coenzyme Q10 is given as a supplement. It is unknown whether coenzyme Q10 is transported to the supercomplex. We develop a method for measuring coenzyme Q10 in the mitochondrial respiratory chain supercomplex in this study. Blue native electrophoresis was used to separate mitochondrial membranes. Electrophoresis gels were cut into 3 mm slices. Hexane was used to extract coenzyme Q10 from this slice, and HPLC-ECD was used to analyze coenzyme Q10. Coenzyme Q10 was found in the gel at the same site as the supercomplex. Coenzyme Q10 at this location was thought to be coenzyme Q10 in the supercomplex. We discovered that 4-nitrobenzoate, a coenzyme Q10 biosynthesis inhibitor, reduced the amount of coenzyme Q10 both within and outside the supercomplex. We also observed that the addition of coenzyme Q10 to cells increased the amount of coenzyme Q10 in the supercomplex. It is expected to analysis coenzyme Q10 level in supercomplex in various samples by using this novel method.

8.
Biochem Biophys Res Commun ; 625: 116-121, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35952608

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is linked with various cardiovascular complications, which often lead to poor prognostic outcomes. To develop a standard therapy for NAFLD and to urgently address its complications, the current study aimed to investigate the mechanisms of NAFLD-related heart disease and the therapeutic effects of drugs targeting various metabolic pathways. METHODS: To explore the mechanism of NAFLD-related heart disease, a medaka model of high-fat diet-induced NAFLD was utilized. The gross structural, histological, and inflammatory changes in the myocardium were evaluated in a time-dependent manner. In addition, the therapeutic effects of medicines used for NAFLD treatment including, selective peroxisome proliferator-activated receptor α modulator (SPPARMα, pemafibrate), sodium-glucose cotransporter 2 (SGLT2) inhibitor (tofogliflozin), and statin (pitavastatin), and their combinations on heart pathology were evaluated. To determine the mechanisms underlying the therapeutic effects, the expression of genes related to liver inflammation was assessed via whole transcriptome sequencing analysis. RESULTS: The fish with NAFLD-related heart injury presented with cardiomyocyte hypertrophy, which led to cardiac hypertrophy. This morphological change was caused by the infiltration of inflammatory cells, including macrophages and CD4- and CD8-positive lymphocytes, in the cardiac wall and the expression of transforming growth factor beta 1 in the cardiomyocytes. Further, the livers of the fish had upregulated expressions of senescence-associated secretory phenotype-related genes. Treatment with pemafibrate, tofogliflozin, and pitavastatin reduced these changes and, consequently, cardiomyopathy. CONCLUSION: Our results demonstrated that NAFLD-related heart disease was attributed to the senescence-associated secretory phenotype-induced inflammatory activity in the cardiac wall, which resulted in myocardial hypertrophy. Moreover, the effects of SPPARMα, SGLT2 inhibitor, and statin on NAFLD-related heart disease were evident in the medaka NAFLD model.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hepatopatia Gordurosa não Alcoólica , Oryzias , Animais , Cardiomegalia/patologia , Dieta Hiperlipídica , Glucose/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fígado/metabolismo , Miocárdio/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR alfa/metabolismo , Sódio/metabolismo
9.
Dig Dis Sci ; 66(11): 3960-3967, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33180245

RESUMO

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized. AIM: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease. METHODS: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement. RESULTS: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility. CONCLUSIONS: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO.


Assuntos
Pseudo-Obstrução Intestinal/diagnóstico , Manometria/métodos , Adulto , Doença Crônica , Esôfago/fisiopatologia , Feminino , Humanos , Pseudo-Obstrução Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Pediatr Int ; 63(2): 210-216, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32767483

RESUMO

BACKGROUND: The relationship between uneven occlusal contact and fall risk has been described in elderly participants; however, multiple confounding factors, such as systemic disease or deterioration in vestibular function, have not been well considered. This study aimed to investigate this relationship in pediatric participants at the age of approximately 9-12, where these confounding factors are absent and the replacement of primary molars by permanent ones generally occurs and transiently results in uneven occlusal contact. METHODS: Sixty-five children (36 boys and 29 girls, mean age: 9.5 ± 1.5 years) were enrolled in this study. Participants were asked whether they had experienced at least two falls within the past 1 year. The occlusal contact area ratio was calculated by dividing the greater half (right or left dental arch) by the smaller half (the other half) with U-shaped pressure sensor sheet. The total length and rectangular area of the center of pressure while standing upright for 10 s were measured with a stabilometer and used as postural sway parameters. RESULTS: The occlusal contact area ratio significantly correlated with the postural sway parameters. Comparison between those who had experienced the fall incidences and those who had not after propensity score matching that adjusts their overall physical function revealed that there were no significant differences in the postural sway parameters and occlusal contact area ratio regardless of the history of fall incidence. CONCLUSIONS: Uneven occlusal contact leads to an increase in postural sway in children; however, this may not be associated with fall incidence.


Assuntos
Acidentes por Quedas , Equilíbrio Postural , Idoso , Criança , Feminino , Humanos , Incidência , Masculino
11.
J Oral Rehabil ; 48(12): 1327-1336, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34499760

RESUMO

BACKGROUND: Jaw clenching is considered to reduce head acceleration while receiving a strong impact on the body during sport activities. OBJECTIVE: The present study aimed to clarify the effect of jaw clenching on reduction of head acceleration during a predictable load impact to the body. METHODS: Seven healthy participants were exposed to a predictable load impact with and without jaw clenching. We recorded the electromyographic activity of the masseter (MA) and digastricus (DIG) muscles, occlusal pressure and head acceleration throughout the experiment. RESULTS: When participants were not instructed to clench their jaws, they naturally positioned their jaws without occlusal contact at the time of pendulum impact by co-contracting the jaw opener and closer muscles. When participants were instructed to clench their jaws, neither the activity of the jaw opener muscle nor the head acceleration differed at the time of pendulum impact when compared with when participants were not instructed to clench their jaws. CONCLUSIONS: A slightly distanced jaw position (co-contracting the jaw opener and closer muscles without occlusal contact) might serve inherently safety for reduction of head acceleration during predictable body impact, while jaw clenching does not contribute to reduction of head acceleration in response to pendulum impact more than the distanced jaw position does. Notably, DIG activation to minimise the head acceleration in response to pendulum impact was similar in clenching and no clenching positions. This suggests that DIG may play a crucial role in the reduction of head acceleration, regardless of MA muscle activity.


Assuntos
Arcada Osseodentária , Contração Muscular , Aceleração , Eletromiografia , Humanos , Músculo Masseter , Músculos da Mastigação
12.
J Oral Rehabil ; 48(5): 568-574, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33492675

RESUMO

Neck pain is one of the most common musculoskeletal complaints. Evidence suggests that increased activities of neck and trunk muscles are one of the mechanisms related to neck pain. Jaw clenching and sitting posture may modulate the muscle activity in neck and trunk muscles during typing. The present study aimed to assess the effects of different postural positions and clenching conditions on neck and trunk muscle activities. Thirteen healthy adults (39.8 ± 5.0 years) performed computer typing tasks in four conditions (two postural positions [upright vs slouched] and two jaw clenching conditions [clenching vs non-clenching]). Integrated surface electromyography (iEMG) was measured in sternocleidomastoid (SCM), upper trapezius (uTP) and middle trapezius (mTP) muscles and compared between conditions. The Friedman and Wilcoxon signed-rank tests with Bonferroni's corrections were used to estimate the condition-specific differences in the iEMG data. The statistical significance level was set at 5%. In both postural positions, iEMGSCM was significantly greater under the jaw clenching than under the non-clenching condition (χ2  = 21.700, P < .01). Under both jaw clenching conditions, iEMGuTP was significantly greater in the slouched than in the upright postural position (χ2  = 23.182, P < .01). No significant differences in iEMGmTP were seen across conditions (χ2  = 5.018, P = .10). Sitting posture and jaw clenching appear to influence activities of different muscles.


Assuntos
Postura , Postura Sentada , Adulto , Eletromiografia , Humanos , Contração Muscular , Músculo Esquelético , Músculos do Pescoço
13.
Dent Traumatol ; 33(1): 51-56, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27207582

RESUMO

BACKGROUND: The aim of this study was to investigate the effect of wearing a mouthguard and teeth-clenching on impact to the head and temporomandibular joint (TMJ) during a blow to the jaw. MATERIAL AND METHODS: A custom-made mouthguard was fabricated for five participants. A 4.1-N impact load was applied to the chin with a pendulum. Two acceleration sensors were attached to the forehead and left TMJ. The amplitudes and durations of the accelerations were obtained under five conditions: mouth-open without mouthguard; light teeth-clenching without mouthguard; maximum voluntary clenching (MVC) without mouthguard; mouth-open with mouthguard and MVC with mouthguard. RESULTS: Wearing a mouthguard led to significant decreases in the amplitude (mouth-open with mouthguard vs mouth-open without mouthguard, P = 0.035 at forehead, P = 0.022 at TMJ) and duration (mouth-open with mouthguard vs mouth-open without mouthguard, P = 0.043 at forehead, not significant at TMJ). Similarly, teeth-clenching caused significant decreases in the amplitude (mouth-open without mouthguard vs MVC without mouthguard, P = 0.024 at forehead, P = 0.025 at TMJ) and duration (mouth-open without mouthguard vs MVC without mouthguard, P = 0.033 at forehead, not significant at TMJ). Furthermore, wearing a mouthguard in itself provided an impact reduction effect similar to the combination of teeth-clenching and wearing a mouthguard. CONCLUSIONS: Wearing a mouthguard and/or teeth-clenching reduced the impact to the head and TMJ during a blow to the jaw. However, it should be noted that the findings are the results from a small impact load to the jaw.


Assuntos
Queixo , Traumatismos Craniocerebrais/prevenção & controle , Protetores Bucais , Traumatismos Dentários/prevenção & controle , Ferimentos não Penetrantes/prevenção & controle , Aceleração , Adulto , Força de Mordida , Desenho de Equipamento , Voluntários Saudáveis , Humanos , Masculino
14.
Hepatol Int ; 18(1): 155-167, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37864724

RESUMO

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is involved in the pathology of non-alcoholic fatty liver disease (NAFLD) and ameliorates fatty infiltration in the liver. It is activated by growth hormone (GH); however, the role of GH-IGF-1 axis in NAFLD developmental phase has not been well identified. Therefore, in this study, we focused on the effect of IGF-1 in NAFLD pathology and GH excretion activation from the pituitary gland by peripheral autonomic neural pathways relaying liver-brain-gut pathway and by central neuropeptides. METHODS: GH and IGF-1 levels were assessed in wild-type and melanocortin-4 receptor knockout mice upon the development of diet-induced NAFLD. The contribution of the peripheral autonomic nervous system connecting the liver-brain-gut axis was assessed by its blockade using capsaicin and that of the central nervous system was assessed by the expression of hypothalamic brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRH), which activates GH release from the pituitary gland. RESULTS: In the NAFLD mouse models, the levels of GH and IGF-1 increased (p < .05). Further, hepatic fatty infiltration was suppressed even under peripheral autonomic nervous system blockade (p < .001), which inhibited gastric ghrelin expression. In mice with peripheral autonomic nervous blockade, hypothalamic BDNF and CRH were inhibited (p < .05), resulting in GH and IGF-1 excretion, whereas other neuropeptides of somatostatin and cortistatin showed no changes. These complementary effects were canceled in melanocortin-4 receptor knockout mice, which diminished BDNF and CRH release control. CONCLUSIONS: Our study demonstrates that the release of IGF-1 by the nervous system is a key factor in maintaining the pathological homeostasis of NAFLD, suggesting its therapeutic potential.


Assuntos
Neuropeptídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fator Neurotrófico Derivado do Encéfalo , Peptídeos Semelhantes à Insulina , Receptor Tipo 4 de Melanocortina , Fator de Crescimento Insulin-Like I/metabolismo , Neuropeptídeos/metabolismo , Hormônio do Crescimento/metabolismo , Camundongos Knockout
15.
Sci Rep ; 14(1): 21126, 2024 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256539

RESUMO

The onset and progression mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are being studied. We developed and analyzed a new mouse model of obesity by combining maternal Id-like molecule (Maid) and melanocortin-4 receptor (Mc4r) gene deletions. Four mice, each at 12 and 28 weeks of age, were analyzed for each genotype: Maid gene knockout, Mc4r gene knockout, combined Mc4r and Maid gene knockout, and Mc4r gene knockout with a high-fat diet. Mice with a combined deficiency of Mc4r and Maid gene showed significantly more severe obesity compared to all other genotypes, but no liver fibrosis or a decline in metabolic status were observed. In visceral white adipose tissue, Maid and Mc4r gene knockout mice had fewer CD11c-positive cells and lower mRNA expression of both inflammatory and anti-inflammatory cytokines. Furthermore, Maid and Mc4r gene knockout mice showed lower expression of adipocytokines in visceral white adipose tissue and uncoupling protein-1 in scapular brown adipose tissue. The expression of adipocytokines and uncoupling protein-1 is regulated by sympathetic nerve signaling that contribute severe obesity in Maid and Mc4r gene knockout mice. These mechanisms contribute hyperobesity in Maid and Mc4r gene knockout mice.


Assuntos
Inflamação , Obesidade , Receptor Tipo 4 de Melanocortina , Animais , Masculino , Camundongos , Adipocinas/metabolismo , Adipocinas/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fígado Gorduroso/metabolismo , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Receptor Tipo 4 de Melanocortina/genética , Receptor Tipo 4 de Melanocortina/deficiência , Receptor Tipo 4 de Melanocortina/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
16.
Biol Psychol ; 182: 108637, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37490801

RESUMO

Interoception has been proposed as a factor that influences various psychological processes (Khalsa et al., 2018). Afferent signals from the cardiovascular system vary across cardiac cycle phases. Heartbeat-evoked potentials (HEP) and event-related potentials (ERP) were measured to examine whether interoceptive signals differed between cardiac cycle phases. Simultaneously, participants performed an auditory oddball task in which the timing of the presenting stimulus was synchronized with the heartbeat. Pure tones were presented at 10 ms (late diastole condition), 200 ms (systole condition), or 500 ms after the R wave (diastole condition). Greater HEP amplitudes were observed when the tone was presented during diastole than during systole or late diastole. ERP showed the same tendency: a greater amplitude was observed during diastole than systole or late diastole. These results suggest that the processing of interoception reflected by HEP and exteroception reflected by ERP share attentional resources when both stimuli coincide. When the tone was presented during systole, attention to the internal state decreased compared with when the tone was presented during diastole, and attention was distributed to both exteroception and interoception. Our study suggests that HEP may be considered an indication of a relative amount of resources to process the interoception.


Assuntos
Eletroencefalografia , Interocepção , Humanos , Eletroencefalografia/métodos , Frequência Cardíaca/fisiologia , Potenciais Evocados/fisiologia , Coração/fisiologia , Interocepção/fisiologia
17.
JA Clin Rep ; 9(1): 13, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36897467

RESUMO

BACKGROUND: Anesthetic management of pheochromocytoma and paraganglioma with Fontan circulation is challenging for physicians, with attention to cardiovascular physiology. CASE PRESENTATION: We performed anesthetic management for pheochromocytoma and paraganglioma in three patients with Fontan circulation. We maintained intraoperative central venous pressure at preoperative level under fluid infusion and administrating nitric oxide to decrease pulmonary arterial resistance. We administered noradrenaline or vasopressin if low blood pressure was present despite adequate central venous pressure. Although noradrenaline is prevalent for the case of noradrenaline-secreting tumor especially after resection, we could maintain blood pressure to administrate vasopressin without increasing central venous pressure. Retroperitoneal laparoscopic approach which could avoid intra-abdominal adhesions might be selectable as case 3. CONCLUSIONS: Sophisticated management is required for pheochromocytoma and paraganglioma with Fontan circulation.

18.
Sci Rep ; 13(1): 3484, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36922503

RESUMO

Metal homeostasis is tightly regulated in cells and organisms, and its disturbance is frequently observed in some diseases such as neurodegenerative diseases and metabolic disorders. Previous studies suggest that zinc and iron are necessary for the normal functions of pancreatic ß cells. However, the distribution of elements in normal conditions and the pathophysiological significance of dysregulated elements in the islet in diabetic conditions have remained unclear. In this study, to investigate the dynamics of elements in the pancreatic islets of a diabetic mouse model expressing human islet amyloid polypeptide (hIAPP): hIAPP transgenic (hIAPP-Tg) mice, we performed imaging analysis of elements using synchrotron scanning X-ray fluorescence microscopy and quantitative analysis of elements using inductively coupled plasma mass spectrometry. We found that in the islets, zinc significantly decreased in the early stage of diabetes, while iron gradually decreased concurrently with the increase in blood glucose levels of hIAPP-Tg mice. Notably, when zinc and/or iron were decreased in the islets of hIAPP-Tg mice, dysregulation of glucose-stimulated mitochondrial respiration was observed. Our findings may contribute to clarifying the roles of zinc and iron in islet functions under pathophysiological diabetic conditions.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Humanos , Camundongos , Animais , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Zinco/metabolismo , Ferro/metabolismo , Camundongos Transgênicos , Amiloide/metabolismo , Ilhotas Pancreáticas/metabolismo , Células Secretoras de Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo
19.
J Neurophysiol ; 108(9): 2524-33, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22914653

RESUMO

Spindle Ia afferents may be differentially involved in voluntary isometric contraction, depending on the pattern of synaptic connections in spindle reflex pathways. We investigated how isometric contraction of masseter muscles is regulated through the activity of their muscle spindles that contain the largest number of intrafusal fibers among skeletal muscle spindles by examining the effects of vibration of muscle spindles on the voluntary isometric contraction. Subjects were instructed to hold the jaw at resting position by counteracting ramp loads applied on lower molar teeth. In response to the increasing-ramp load, the root mean square (RMS) of masseter EMG activity almost linearly increased under no vibration, while displaying a steep linear increase followed by a slower increase under vibration. The regression line of the relationship between the load and RMS was significantly steeper under vibration than under no vibration, suggesting that the subjects overestimated the ramp load and excessively counteracted it as reflected in the emergence of bite pressure. In response to the decreasing-ramp load applied following the increasing one, the RMS hardly decreased under vibration unlike under no vibration, leading to a generation of bite pressure even after the offset of the negative-ramp load until the vibration was ceased. Thus the subjects overestimated the increasing rate of the load while underestimating the decreasing rate of the load, due to the vibration-induced illusion of jaw opening. These observations suggest that spindle Ia/II inputs play crucial roles both in estimating the load and in controlling the isometric contraction of masseter muscles in the jaw-closed position.


Assuntos
Ilusões , Contração Isométrica/fisiologia , Músculo Masseter/fisiologia , Fusos Musculares/fisiologia , Vibração , Adulto , Eletromiografia , Feminino , Humanos , Masculino
20.
JA Clin Rep ; 8(1): 94, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36484931

RESUMO

BACKGROUND: Hepatectomy for patients with Fontan circulation consists of high central venous pressure and low pulmonary vascular resistance, and is challenging for physicians. CASE PRESENTATION: We performed anesthetic management for hepatectomy in three patients with Fontan circulation. Massive bleeding and transfusion as well as careful management were needed. Open abdominal surgery had to be conducted instead of laparoscopic surgery for controlling bleeding in one case. We successfully performed general anesthesia using nitric oxide and inotropes while monitoring arterial pressure and central venous pressure in all the cases. CONCLUSIONS: To maintain Fontan circulation during hepatectomy, it is important to manage central venous pressure and ensure appropriate circulatory volume.

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