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1.
Adv Mater ; : e2403647, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708960

RESUMO

The near-infrared (NIR) sensor technology is crucial for various applications such as autonomous driving and biometric tracking. Silicon photodetectors (SiPDs) are widely used in NIR applications; however, their scalability is limited by their crystalline properties. Organic photodetectors (OPDs) have attracted attention for NIR applications owing to their scalability, low-temperature processing, and notably low dark current density (JD), which is similar to that of SiPDs. However, the still high JD (at NIR band) and few measurements of noise equivalent powers (NEPs) pose challenges for accurate performance comparisons. This study addresses these issues by quantitatively characterizing the performance matrix and JD generation mechanism using electron-blocking layers (EBLs) in OPDs. The energy offset at an EBL/photosensitive layer interface determines the thermal activation energy and directly affects JD. A newly synthesized EBL (3PAFBr) substantially enhances the interfacial energy barrier by forming a homogeneous contact owing to the improved anchoring ability of 3PAFBr. As a result, the OPD with 3PAFBr yields a noise current of 852 aA (JD = 12.3 fA/cm2 at V → -0.1 V) and several femtowatt-scale NEPs. To the best of our knowledge, this is an ultralow magnitude of JD in NIR OPDs. This also emphasizes the necessity for quantitative performance characterization. This article is protected by copyright. All rights reserved.

2.
Biogerontology ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548993

RESUMO

Piperine, a dietary phytochemical isolated from the Piper species, has been used as a natural medicine for pain, flu, and fever in ancient China and India. Although the health benefits of piperine have been widely studied, research on its effect on aging is limited. This study aimed to determine whether piperine has the potential to mitigate aging-related changes in the fruit fly (Drosophila melanogaster), which is an excellent model organism for studies on aging. The experiments were conducted using the newly eclosed or 30-day-old D. melanogaster wild-type strain Cantonized-white. Piperine was dissolved in 99% ethanol and added to the sucrose-yeast medium at a final concentration of 10, 35, 70, or 100 µM. The study examined the effects of piperine supplementation on the lifespan of D. melanogaster and other physiological functions, such as fecundity, feeding, lipid content, and resistance to environmental stress. Log-rank tests, Shapiro-Wilk test, F-test, t-test, or Wilcoxon rank sum test were used to analyze the data. Piperine failed to change the lifespan and body weight, but increased the fecundity and decreased the feeding rate in one-week-old flies. However, when piperine was fed to 30-day-old flies, it increased the lifespan of male flies and the fecundity and feeding rate of female flies. These results indicate that piperine can improve the health of aged flies. The findings suggest that piperine has age-dependent and sex-specific anti-aging effects in fruit flies.

3.
Nat Commun ; 15(1): 46, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167804

RESUMO

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.


Assuntos
Longevidade , Receptor 5 Toll-Like , Animais , Camundongos , Flagelina/metabolismo , Mucosa Intestinal/metabolismo , Longevidade/genética , Pulmão/metabolismo
4.
Anaesth Crit Care Pain Med ; 43(2): 101337, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38061682

RESUMO

BACKGROUND: General anaesthesia can immobile patients during interventional neuroradiology to improve image quality. Remimazolam, an ultrashort-acting benzodiazepine, is advantageous for haemodynamic stability. This study compared remimazolam and propofol anaesthesia during neuroradiology procedures regarding intraoperative hypotensive events and rapid recovery. METHODS: This single-masked randomised-controlled study included 76 participants who underwent elective endovascular embolisation in a single centre. Patients were randomised between a continuous remimazolam infusion (n = 38) or a target-controlled propofol infusion group (n = 38). In the remimazolam group, flumazenil (0.2 mg) was administered at the end of the procedure. Phenylephrine was titrated to maintain the mean arterial pressure within ± 20% of the baseline value. The primary outcome was the total phenylephrine dose during the procedure. RESULTS: The total phenylephrine dose was 0.0 [0.0-30.0] µg in the remimazolam group and 30.0 [0.0-205.0] µg in the propofol group (p = 0.001). Hypotensive events were observed in 11 (28.9%) patients in the remimazolam group and 23 (60.5%) patients in the propofol group (p = 0.001). Recovery times to spontaneous breathing, eye-opening, extubation, and orientation were shorter in the remimazolam group than in the propofol group (all p < 0.001). CONCLUSIONS: Remimazolam anaesthesia showed superior haemodynamic stability compared with propofol anaesthesia during neuroradiology procedures. Systematic use of flumazenil enabled rapid recovery from remimazolam anaesthesia. REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry; Registration number: UMIN000047384; URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054046.


Assuntos
Propofol , Humanos , Flumazenil/uso terapêutico , Benzodiazepinas , Anestesia Geral , Fenilefrina/uso terapêutico
5.
Membranes (Basel) ; 13(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38132899

RESUMO

In this study, novel pore-filled anion-exchange membranes (PFAEMs) modified with polypyrrole (PPy) and reduced graphene oxide (rGO) were developed to improve the energy harvesting performance of reverse electrodialysis (RED). The surface-modified PFAEMs were fabricated by varying the contents of PPy and rGO through simple spin coating and chemical/thermal treatments. It was confirmed that the PPy and PPy/rGO layers introduced on the membrane surface did not significantly increase the electrical resistance of the membrane and could effectively control surface characteristics, such as structural tightness, hydrophilicity, and electrostatic repulsion. The PPy/rGO-modified PFAEM showed excellent monovalent ion selectivity, more than four times higher than that of the commercial membrane (AMX, Astom Corp., Tokyo, Japan). This means that the PPy/rGO layer can effectively reduce the permeation of multivalent ions with a high charge intensity and a relatively large hydration radius compared to monovalent ions. The results of evaluating the performance of the surface-modified PFAEMs by applying them to a RED cell revealed that the decrease in potential difference occurring in the membrane was reduced by effectively suppressing the uphill transport of multivalent ions. Consequently, the PPy/rGO-modified membrane exhibited a 5.43% higher power density than the AMX membrane.

6.
Sci Rep ; 13(1): 15314, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37714906

RESUMO

Airway clearance is crucial for successful fiberoptic intubation. We hypothesized that tongue retraction using a McIvor blade could facilitate fiberoptic intubation. This randomized clinical trial aimed to compare intubation time and airway condition between the jaw thrust maneuver and tongue retraction with the McIvor blade during fiberoptic intubation. Ninety-four adult patients scheduled for elective surgery were randomly assigned to one of two groups. During fiberoptic intubation, airway clearance was secured by applying the jaw-thrust maneuver (J group) or by tongue retraction using the McIvor blade (M group). We assessed the total intubation time, number of attempts for tube advancement, and airway clearance at the soft palate and epiglottis levels. The total intubation time was significantly shorter in the M group than in the J group (p = 0.035). The number of attempts to advance the tube was significantly lower in the M group (p = 0.033). Airway clearance at the soft palate level was significantly better in the M group than in the J group (p = 0.027). Retracting the tongue with the McIvor blade demonstrated a better condition for fiberoptic intubation and shortened total intubation time compared with the jaw-thrust maneuver.Clinicalregistiration: CRIS; http://cris.nih.go.kr (KCT0002392) registered 28/07/2017.


Assuntos
Transtornos Respiratórios , Adulto , Humanos , Língua , Procedimentos Cirúrgicos Eletivos , Epiglote , Intubação Intratraqueal
7.
Sci Rep ; 13(1): 12056, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491384

RESUMO

Various techniques have been formulated to reduce pain and ensure early recovery after surgery, as these are major concerns among surgeons, anesthesiologists, and patients. Erector spinae plane block (ESPB), the injection of local anesthetic into the fascial plane, is a simple and novel analgesia technique widely used due to its minimal risk of complications. ESPB has been tried in various surgeries; however, no study has reported its use in colorectal surgery. This study investigated whether ESPB could promote early recovery following laparoscopic colorectal surgery (LCS) by reducing opioid consumption and pain intensity. After randomization into the ESPB or control groups, an ultrasound-guided ESPB was performed at the thoracic 10th-11th level with 40 mL of 0.25% bupivacaine or normal saline. The ESPB group used less fentanyl during the initial 24 h after surgery (P = 0.004) and experienced less pain (P < 0.05 at all-time points) than the control group. The time to the first ambulation and the length of hospital stay were shorter in the ESPB group than in the control group (P = 0.015 and P = 0.008, respectively). In conclusion, ESPB could promote early recovery by reducing opioid consumption and pain intensity in patients receiving LCS.


Assuntos
Anestesia por Condução , Cirurgia Colorretal , Laparoscopia , Bloqueio Nervoso , Humanos , Analgésicos Opioides/uso terapêutico , Deambulação Precoce , Laparoscopia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Ultrassonografia de Intervenção
8.
Int J Clin Pharmacol Ther ; 61(9): 377-385, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37382329

RESUMO

OBJECTIVE: Famotidine, an H2 receptor antagonist (H2RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine. MATERIALS AND METHODS: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses. RESULTS: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (tmax,ss) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUCT,ss) and maximum concentration of drug in plasma in steady state (Cmax,ss) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively. CONCLUSION: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.


Assuntos
Esomeprazol , Gastrite , Humanos , Esomeprazol/farmacocinética , Famotidina/farmacologia , Voluntários Saudáveis , Estudos Cross-Over , Gastrite/diagnóstico , Gastrite/tratamento farmacológico
9.
Aging Dis ; 14(4): 1407-1424, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37163439

RESUMO

The term probiotic refers to bacteria that provide a beneficial effect to the host. Limosilactobacillus reuteri (Lactobacillus reuteri) is a probiotic isolated from human breast milk. Although L. reuteri has antimicrobial and anti-inflammatory activities occasionally linked to anti-aging effects, there are no reports of the effects of L. reuteri on longevity. This study evaluated the anti-aging effects of L. reuteri on the lifespan and physiology of Drosophila melanogaster. L. reuteri increased the mean lifespan of fruit flies significantly without reducing the reproductive output, food intake, or locomotor activity. Furthermore, the data suggested that the longevity effect of L. reuteri is mediated by the reduction of the insulin/IGF-1 signaling pathway and the action of reuterin, an antimicrobial compound produced by L. reuteri. These results show that L. reuteri can be used as a probiotic that acts as a dietary restriction mimetic with anti-aging effects.

10.
Medicina (Kaunas) ; 59(5)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37241179

RESUMO

Background and Objectives: Developing effective treatment outcomes for multidrug-resistant Acinetobacter baumannii (MRAB) infections, with colistin and tigecycline the current frontline therapies, is challenging, because of the risk of renal toxicity and low blood concentrations of active ingredients when administered intravenously. This study aimed to identify the effect of combination therapy using conventional antimicrobial agents that are used for treating drug-resistant bacteria and the additional synergistic effect of four probiotic culture extracts isolated from the human body and Lactobacillus preparations. Materials and Methods: The antimicrobial combination and synergistic effect of adding Lactobacillus extract against 33 strains of A. baumannii isolated from pus, urine, and other specimens submitted to the Department of Laboratory Medicine of a university hospital, located in Gyeonggi-do, Korea, was investigated over a 3-year period between January 2017 and December 2019. Results: Antimicrobial susceptibility tests on bacteria isolated in clinical practice demonstrated that 26 strains (79%) were MRAB, while multi-locus sequence typing indicated that ST191 was the predominant type (45%; n = 15). Checkerboard test results demonstrated that combination therapy using meropenem and colistin had the highest synergistic effect (fractional inhibitory concentration index = 0.5), while the time-kill assay test using Lactobacillus spp. culture extract exhibited an inhibitory effect within 1 h and complete inhibition of MRAB within 3 h. Lactobacillus paracasei exhibited the fastest antimicrobial reactivity and longest sustained antimicrobial activity. Conclusion: These findings provide useful foundational data for an appropriate combination of colistin with other antimicrobial agents for treating MRAB infection in clinical settings, and the use of various probiotic culture extracts to reduce the required dosage, and therefore toxicity of colistin.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colistina/farmacologia , Colistina/uso terapêutico , Tipagem de Sequências Multilocus , Sinergismo Farmacológico , Infecções por Acinetobacter/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla
11.
Iran J Public Health ; 52(12): 2554-2562, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38435776

RESUMO

Background: As the elderly population increases, interest in life satisfaction in old age is increasing. We aimed to verify the relationship between social capital, smartphone use motives, and digital literacy and life satisfaction in Koreans aged 50-69 yr. Methods: The data of 7,521 late-middle-aged and older adults from the 2019 survey on smartphone overdependence conducted by the National Information Society Agency were analyzed by hierarchical multi-regression analysis. Results: A hierarchical multiple regression analysis indicated that income(ß=0.062) and educational background(ß=0.054) were positively related to life satisfaction. Among the smartphone use motives, lifestyle motive(ß=-0.069) was negatively related to life satisfaction. Digital literacy(ß=0.145) and Social capital(ß=0.425) were positively related to life satisfaction. Conclusion: Digital literacy and social capital were positively associated with life satisfaction. In addition, this study considered the effects of lifestyle-based apps, while past studies only focused on communication- and leisure-based smartphone activities as factors influencing life satisfaction in adults in their 50s-60s. This study can provide a theoretical framework for therapeutic interventions to improve life satisfaction in the elderly.

12.
Sci Rep ; 12(1): 22550, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581745

RESUMO

Regulatory T (Treg) cells maintain immune homeostasis by preventing abnormal or excessive immune responses. Histone deacetylase 6 (HDAC6) regulates expression of Foxp3, and thus, Treg cell differentiation; however, its role in Treg cell differentiation is unclear and somewhat controversial. Here, we investigated the role of HDAC6 in TGF-ß-induced murine Treg cells. HDAC6 expression was higher in Treg cells than in other T helper cell subsets. Pharmacological inhibitors of HDAC6 selectively inhibited Treg cell differentiation and suppressive function. A specific HDAC6 inhibitor induced changes in global gene expression by Treg cells. Of these changes, genes related to cell division were prominently affected. In summary, HDAC6 plays an important role in TGF-ß-induced murine Treg cell differentiation by regulating cell proliferation.


Assuntos
Desacetilase 6 de Histona , Linfócitos T Reguladores , Fator de Crescimento Transformador beta , Animais , Camundongos , Diferenciação Celular , Proliferação de Células , Desacetilase 6 de Histona/metabolismo , Fator de Crescimento Transformador beta/metabolismo
13.
Oncoimmunology ; 11(1): 2138152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338147

RESUMO

Adoptive transfer of γδ T cells is a novel immunotherapeutic approach to glioblastoma. Few recent studies have shown the efficacy of γδ T cells against glioblastoma, but no previous studies have identified the ligand-receptor interactions between γδ T cells and glioblastoma cells. Here, we identify those ligand-receptor interactions and provide a basis for using γδ T cells to treat glioblastoma. Vγ9Vδ2 T cells were generated from peripheral blood mononuclear cells of healthy donors using artificial antigen presenting cells. MICA, ULBP, PVR and Nectin-2 expression in 10 patient-derived glioblastoma (PDG) cells were analyzed. The in vitro cytokine secretion from the γδ T cells and their cytotoxicity toward the PDG cells were also analyzed. The in vivo anti-tumor effects were evaluated using a U87 orthotopic xenograft glioblastoma model. Expression of ligands and cytotoxicity of the γδ T cells varied among the PDG cells. IFN-γ and Granzyme B secretion levels were significantly higher when γδ Tcells were co-cultured with high-susceptible PDG cells than when they were co-cultured with low-susceptible PDG cells. Cytotoxicity correlated significantly with the expression levels of DNAM-1 ligands of the PDG cells. Blocking DNAM-1 resulted in a decrease in γδ T cell-mediated cytotoxicity and cytokine secretion. Intratumoral injection of γδ T cells showed anti-tumor effects in an orthotopic mouse model. Allogenic γδ T cells showed potent anti-tumor effects on glioblastoma in a DNAM-1 axis dependent manner. Our findings will facilitate the development of clinical strategies using γδ T cells for glioblastoma treatment.


Assuntos
Glioblastoma , Camundongos , Animais , Humanos , Glioblastoma/terapia , Receptores de Antígenos de Linfócitos T gama-delta , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Ligantes , Linfócitos T , Citocinas
14.
Medicine (Baltimore) ; 101(32): e29279, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35960083

RESUMO

RATIONALE: Epidural blood patch (EBP) is an effective treatment for spontaneous intracranial hypotension (SIH). However, its effectiveness can only be judged through subjective symptom improvement; no objective markers have been reported. Linear indices of ventricular volume on brain computed tomography (CT) may aid the objective evaluation of the effectiveness of EBP in patients with SIH. PATIENT CONCERNS: A 45-year-old man was hospitalized due to a 3-week history of orthostatic headache, dizziness, and neck pain. He had visited a local emergency department at symptom onset. His neurological examination results were normal and vital signs were stable. DIAGNOSES: Brain magnetic resonance imaging (MRI) revealed pachymeningeal enhancement in both convexities with a small subdural hematoma (SDH). Based on the clinical features and MRI findings, he was diagnosed with SIH complicated by SDH. INTERVENTIONS: Non-targeted EBP was performed, first at the lumbar level and subsequently at the thoracic level. Linear indices of ventricular volume, including the Evans' index, frontal-occipital horn ratio, and bicaudate index, were measured through brain CT performed before and after EBP. OUTCOMES: After lumbar EBP, there was no symptom relief or increase in linear indices of ventricular volume on brain CT. In contrast, the patient's symptoms completely resolved and the linear indices of ventricular volume increased after thoracic EBP. LESSONS: The effectiveness of EBP, which is currently evaluated solely based on changes in symptom severity, can be assessed using linear indices of ventricular volume.


Assuntos
Placa de Sangue Epidural , Hipotensão Intracraniana , Placa de Sangue Epidural/efeitos adversos , Placa de Sangue Epidural/métodos , Hematoma Subdural/etiologia , Humanos , Hipotensão Intracraniana/complicações , Hipotensão Intracraniana/diagnóstico por imagem , Hipotensão Intracraniana/terapia , Imageamento por Ressonância Magnética/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/efeitos adversos
15.
Nutrients ; 14(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35458218

RESUMO

The relationship between hearing impairment and nutrition has been extensively investigated; however, few studies have focused on this topic in working-age adults by income level. Herein, we aimed to determine the differences in hearing impairment among working-age adults by income level and identify the nutritional factors that affect hearing loss in various socioeconomic groups. Seven-hundred-and-twenty participants had hearing impairment, while 10,130 had normal hearing. After adjustment for propensity score matching, income and smoking status were identified as significant variables. By assessing the relationship between hearing impairment and nutrient intake by income level using multiple regression analyses, significant nutrients differed for each income category. Carbohydrate and vitamin C levels were significant in the low-income group; protein, fat, and vitamin B1 levels were significant in the middle-income group; and carbohydrates were significant in the high-income group. Income was significantly associated with hearing impairment in working-age adults. The proportion of individuals with hearing impairment increased as income decreased. The association between hearing impairment and nutritional intake also differed by income level. Our findings may enable the establishment of health policies for preventing hearing impairment in working-age adults by income level.


Assuntos
Surdez , Perda Auditiva , Adulto , Estudos Transversais , Ingestão de Alimentos , Perda Auditiva/epidemiologia , Humanos , Renda , Pessoa de Meia-Idade , Inquéritos Nutricionais , República da Coreia/epidemiologia
16.
Cell Metab ; 34(2): 285-298.e7, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35108515

RESUMO

The central nervous system has long been thought to regulate insulin secretion, an essential process in the maintenance of blood glucose levels. However, the anatomical and functional connections between the brain and insulin-producing pancreatic ß cells remain undefined. Here, we describe a functional transneuronal circuit connecting the hypothalamus to ß cells in mice. This circuit originates from a subpopulation of oxytocin neurons in the paraventricular hypothalamic nucleus (PVNOXT), and it reaches the islets of the endocrine pancreas via the sympathetic autonomic branch to innervate ß cells. Stimulation of PVNOXT neurons rapidly suppresses insulin secretion and causes hyperglycemia. Conversely, silencing of these neurons elevates insulin levels by dysregulating neuronal signaling and secretory pathways in ß cells and induces hypoglycemia. PVNOXT neuronal activity is triggered by glucoprivation. Our findings reveal that a subset of PVNOXT neurons form functional multisynaptic circuits with ß cells in mice to regulate insulin secretion, and their function is necessary for the ß cell response to hypoglycemia.


Assuntos
Células Secretoras de Insulina , Animais , Hipotálamo/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Camundongos , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo
17.
Exp Mol Med ; 53(12): 1877-1887, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34876693

RESUMO

BIX01294 (BIX), an inhibitor of the G9a histone methyltransferase, has been reported to have antitumor activity against a variety of cancers. However, the molecular mechanisms underlying its anticancer effects, particularly those against lung cancer, remain unclear. Here, we report that BIX induces apoptotic cell death in EGFR-mutant non-small cell lung cancer (NSCLC) cells but not in their wild-type counterparts. Treatment with BIX resulted in a significant reduction in the EGFR level and inhibition of EGFR signaling only in EGFR-mutant NSCLC cells, leading to apoptosis. BIX also inhibited mitochondrial metabolic function and decreased the cellular energy levels that are critical for maintaining the EGFR level. Furthermore, BIX transcriptionally downregulated the transcription of branched-chain α-keto acid dehydrogenase (BCKDHA), which is essential for fueling the tricarboxylic acid (TCA) cycle. Interestingly, this BCKDHA downregulation was due to inhibition of Jumanji-domain histone demethylases but not the G9a histone methyltransferase. We observed that KDM3A, a Jumonji histone demethylase, epigenetically regulates BCKDHA expression by binding to the BCKDHA gene promoter. BIX exposure also led to a significant decrease in the EGFR level, causing apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Taken together, our current data suggest that BIX triggers apoptosis only in EGFR-mutant NSCLC cells via inhibition of BCKDHA-mediated mitochondrial metabolic function.


Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Azepinas/farmacologia , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Adenocarcinoma de Pulmão/patologia , Apoptose/genética , Biomarcadores , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico , Suscetibilidade a Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Metabolismo Energético , Receptores ErbB/genética , Receptores ErbB/metabolismo , Histona Desmetilases , Humanos , Imuno-Histoquímica , Mitocôndrias/metabolismo , Modelos Biológicos , Inibidores de Proteínas Quinases/farmacologia
18.
J Adolesc ; 93: 10-19, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34626886

RESUMO

INTRODUCTION: Until now, South Korean adolescent suicidal ideation literature has focused mainly on individual-level characteristics. Little is known about the contextual effects of social integration and social regulation on an individual's suicide behavior in South Korea as identified through the use of Durkheim's sociological insights. This study drew on Durkheim's suicide and collective efficacy theories and analyzed the effects of the structural characteristics and collective efficacy of neighborhoods on adolescents' suicidal ideation. METHODS: The data analyzed was from three sources: the 2013 Korean National Survey of the Present Status of Children (n = 1,915; 50.41% girls; mean age = 13.04 years), government census data from the Korea Statistical Information System, and administrative data from the Korea Ministry of Health and Welfare. The Hierarchical Generalized Linear Model was used to investigate the effects of neighborhood structural characteristics and collective efficacy on adolescent suicidal ideation. RESULTS: There were no significant associations between neighborhood characteristics such as concentrated poverty, divorce rate, and residential instability; however, adoles cents' perceptions of collective efficacy in neighborhoods was associated with lower suicidal ideation after accounting for individual adolescent differences. CONCLUSION: The findings provide significant implications for the prevention of suicide in adolescents and suggest that enhancing the collective efficacy of neighborhoods through community-based intervention may be an important target of future suicide prevention strategies in South Korea.


Assuntos
Ideação Suicida , Suicídio , Adolescente , Criança , Humanos , Características da Vizinhança , República da Coreia
19.
Medicine (Baltimore) ; 100(27): e26527, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232187

RESUMO

ABSTRACT: Interscalene block (ISB) is commonly performed for regional anesthesia in shoulder surgery. Ultrasound-guided ISB enables visualization of the local anesthetic spread and a reduction in local anesthetic volume. However, little is known about the appropriate local anesthetic dose for surgical anesthesia without sedation or general anesthesia. The purpose of our study was to evaluate the appropriate local anesthetic volume by comparing intraoperative analgesics and hemodynamic changes in ISB in arthroscopic shoulder surgery.Overall, 1007 patients were divided into groups 1, 2, and 3 according to the following volume of local anesthetics: 10-19, 20-29, and 30-40 mL, respectively. The use of intraoperative analgesics and sedatives, and the reduction in intraoperative maximum blood pressure and heart rate were compared through retrospective analysis.Fentanyl was used in 55.6% of patients in group 1, which was significantly higher than in those groups 2 and 3 (22.3% and 30.7%, respectively); furthermore, it was also higher than those in groups 2 and 3 in dose-specific comparisons (P < .05). The percent of the maximum reduction in intraoperative systolic blood pressure and heart rate in group 3 was significantly higher than those in groups 1 and 2. Ephedrine administration was lower in group 2 than that in other groups (P < .05). The incidence of hypotensive bradycardic events was lowest (9.1%) at the local anesthetic volume of 24 mL as revealed by the quadratic regression analysis (R2 = 0.313, P = .003).Decreasing the local anesthetic volume to less than 20 mL for ultrasound-guided ISB as the sole anesthesia increases the opioid consumption during shoulder arthroscopic surgery. Local anesthetics >30 mL or increased opioid consumption with <20 mL of local anesthetics could increase the risk of cardiovascular instability intraoperatively. Our findings indicate that 24 mL of local anesthetic could be used to lower the incidence of hypotensive bradycardic events.


Assuntos
Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Artroscopia/métodos , Bloqueio do Plexo Braquial/métodos , Artropatias/cirurgia , Dor Pós-Operatória/prevenção & controle , Articulação do Ombro/cirurgia , Anestesia Local , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia de Intervenção
20.
Appl Nurs Res ; 59: 151427, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33947514

RESUMO

BACKGROUND: Advances in immunosuppressive therapeutics and medical technology have improved survival rates after heart transplantation. Although there is a rigorous schedule of outpatient visits and testing to detect early signs of rejection and other complications in the first year after transplantation, repeated unplanned readmissions of heart transplant recipients remains a challenge. OBJECTIVE: This study aimed to compare the effects of specialized nurse-led discharge education, including continuous post-transplant education and counselling, on heart transplant recipients' clinical outcomes, with the effects of existing discharge education. METHODS: Participants were 136 heart transplantation recipients at a university-affiliated hospital in South Korea from November 1, 1994, to November 30, 2018. Participants' electronic medical records were retrospectively analyzed. Participants were grouped according to usual care (n = 25), nurse-led program (n = 66), and nurse-led program with post-discharge education (n = 45). We assessed the number of outpatient visits with clinical problems and days to first unplanned rehospitalization within one year after transplantation. RESULTS: The nurse-led program with post-discharge education was associated with significantly reduced outpatient visits with clinical problems, compared to usual care and the existing nurse-led program. We also found a significantly longer time until first unplanned rehospitalization in the nurse-led program with post-discharge education group, compared to the usual care group. CONCLUSION: This study identified the heart transplantation-specialized nurse-led discharge and subsequent post-discharge education as an effective strategy for positive clinical outcomes within one year after heart transplantation.


Assuntos
Papel do Profissional de Enfermagem , Alta do Paciente , Assistência ao Convalescente , Humanos , Readmissão do Paciente , Estudos Retrospectivos , Transplantados
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