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1.
Nat Commun ; 12(1): 5057, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417449

RESUMO

Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.


Assuntos
MicroRNAs/metabolismo , Proteínas de Ligação a RNA/metabolismo , Regiões 3' não Traduzidas/genética , Sítios de Ligação , Evolução Molecular , Células HeLa , Células Hep G2 , Humanos , MicroRNAs/genética , Conformação de Ácido Nucleico , Ligação Proteica , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Especificidade por Substrato
2.
Nat Commun ; 12(1): 5120, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433827

RESUMO

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infected >200 million people resulting in >4 million deaths. However, temporal landscape of the SARS-CoV-2 translatome and its impact on the human genome remain unexplored. Here, we report a high-resolution atlas of the translatome and transcriptome of SARS-CoV-2 for various time points after infecting human cells. Intriguingly, substantial amount of SARS-CoV-2 translation initiates at a novel translation initiation site (TIS) located in the leader sequence, termed TIS-L. Since TIS-L is included in all the genomic and subgenomic RNAs, the SARS-CoV-2 translatome may be regulated by a sophisticated interplay between TIS-L and downstream TISs. TIS-L functions as a strong translation enhancer for ORF S, and as translation suppressors for most of the other ORFs. Our global temporal atlas provides compelling insight into unique regulation of the SARS-CoV-2 translatome and helps comprehensively evaluate its impact on the human genome.


Assuntos
COVID-19/virologia , Biossíntese de Proteínas , SARS-CoV-2/genética , Transcriptoma , Regulação Viral da Expressão Gênica , Genoma Humano , Humanos , Fases de Leitura Aberta , RNA Viral/genética , RNA Viral/metabolismo , SARS-CoV-2/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
3.
Science ; 373(6553): 443-448, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437118

RESUMO

Clues to a planet's geologic history are contained in its interior structure, particularly its core. We detected reflections of seismic waves from the core-mantle boundary of Mars using InSight seismic data and inverted these together with geodetic data to constrain the radius of the liquid metal core to 1830 ± 40 kilometers. The large core implies a martian mantle mineralogically similar to the terrestrial upper mantle and transition zone but differing from Earth by not having a bridgmanite-dominated lower mantle. We inferred a mean core density of 5.7 to 6.3 grams per cubic centimeter, which requires a substantial complement of light elements dissolved in the iron-nickel core. The seismic core shadow as seen from InSight's location covers half the surface of Mars, including the majority of potentially active regions-e.g., Tharsis-possibly limiting the number of detectable marsquakes.

4.
Pharm Res ; 38(8): 1455-1466, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34398405

RESUMO

PURPOSE: To develop an in vitro culture system for tissue engineering to mimic the in vivo environment and evaluate the applicability of ultrasound and PLGA particle system. METHODS: For tissue engineering, large molecules such as growth factors for cell differentiation should be supplied in a controlled manner into the culture system, and the in vivo microenvironment need to be reproduced in the system for the regulation of cellular function. In this study, portable prototype ultrasound with low intensity was devised and tested for protein release from bovine serum albumin (BSA)-loaded poly(lactic-co-glycolic acid) (PLGA) particles. RESULTS: BSA-loaded PLGA particles were prepared using various types of PLGA reagents and their physicochemical properties were characterized including particle size, shape, or aqueous wetting profiles. The BSA-loaded formulation showed nano-ranged size distribution with optimal physical stability during storage period, and protein release behaviors in a controlled manner. Notably, the application of prototype ultrasound with low intensity influenced protein release patterns in the culture system containing the BSA-loaded PLGA formulation. The results revealed that the portable ultrasound set controlled by the computer could contribute for the protein delivery in the culture medium. CONCLUSIONS: This study suggests that combined application with ultrasound and protein-loaded PLGA encapsulation system could be utilized to improve culture system for tissue engineering or cell regeneration therapy.

5.
Science ; 373(6553): 434-438, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437116

RESUMO

For 2 years, the InSight lander has been recording seismic data on Mars that are vital to constrain the structure and thermochemical state of the planet. We used observations of direct (P and S) and surface-reflected (PP, PPP, SS, and SSS) body-wave phases from eight low-frequency marsquakes to constrain the interior structure to a depth of 800 kilometers. We found a structure compatible with a low-velocity zone associated with a thermal lithosphere much thicker than on Earth that is possibly related to a weak S-wave shadow zone at teleseismic distances. By combining the seismic constraints with geodynamic models, we predict that, relative to the primitive mantle, the crust is more enriched in heat-producing elements by a factor of 13 to 20. This enrichment is greater than suggested by gamma-ray surface mapping and has a moderate-to-elevated surface heat flow.

6.
Science ; 373(6553): 438-443, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437117

RESUMO

A planet's crust bears witness to the history of planetary formation and evolution, but for Mars, no absolute measurement of crustal thickness has been available. Here, we determine the structure of the crust beneath the InSight landing site on Mars using both marsquake recordings and the ambient wavefield. By analyzing seismic phases that are reflected and converted at subsurface interfaces, we find that the observations are consistent with models with at least two and possibly three interfaces. If the second interface is the boundary of the crust, the thickness is 20 ± 5 kilometers, whereas if the third interface is the boundary, the thickness is 39 ± 8 kilometers. Global maps of gravity and topography allow extrapolation of this point measurement to the whole planet, showing that the average thickness of the martian crust lies between 24 and 72 kilometers. Independent bulk composition and geodynamic constraints show that the thicker model is consistent with the abundances of crustal heat-producing elements observed for the shallow surface, whereas the thinner model requires greater concentration at depth.

7.
Rev Sci Instrum ; 92(4): 043549, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243449

RESUMO

A Thomson scattering (TS) system has been utilized to measure the electron temperature and density of the core region of Versatile Experiment Spherical Torus (VEST). Recently, the laser injection system is successfully upgraded adopting the burst laser with the repetition rate of 1 kHz and the energy of 2 J. Furthermore, improved collection optics with additional polychromators and a 32-channel fast digitizer are prepared to observe the fast time evolution of radial profiles. This improvement is essential to study fast phenomena such as internal reconnection event (IRE). We increase the TS signal and reduce the stray light by introducing new filters having better optical properties such as high optical density at 1064 nm, transmission, and reflectance. Moreover, the optimum reverse bias voltages are newly set to make the system operational independent of the background radiation. As a result, 1 kHz radial profiles of the core electron temperature and density are measured for the first time, showing characteristics of IREs in VEST.

8.
J Immunol Res ; 2021: 2183427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307692

RESUMO

Korean mistletoe has anti-inflammatory and antioxidant functions and may be a useful training supplement. We investigated the effect of Korean mistletoe extract (KME) on inflammatory markers after high-intensity exercise by 20 university male rowers (KME group vs. CON group) consuming 110 mL KME/dose (2 times a day over 8 weeks). Blood samples were collected for measurement of serum cytokine levels at baseline, immediately after exercise, and following 30 minutes of recovery. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were used as markers for inflammation. After supplementation, IL-6 and TNF-α levels were significantly lowered in the KME group than in the CON group at baseline, immediately after exercise, and following 30 minutes of recovery. KME can reduce high-strength exercise-induced increases in the levels of serum inflammatory cytokines in active individuals and improve anti-inflammatory functions.

9.
J Clin Med ; 10(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34300205

RESUMO

Patient's cooperation and respiration is necessary in percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We compared the respiratory patterns of dexmedetomidine and propofol sedation during this procedure. Participants were randomly allocated into two groups: the continuous infusions of dexmedetomidine-remifentanil (DR group) or the propofol-remifentanil (PR group). We measured the tidal volume for each patient's respiration during one-minute intervals at five points and compared the standard deviation of the tidal volumes (SDvt) between the groups. Sixty-two patients completed the study. SDvt at 10 min was not different between the groups (DR group, 108.58 vs. PR group, 149.06, p = 0.451). However, SDvt and end-tidal carbon dioxide (EtCO2) level of PR group were significantly increased over time compared to DR group (p = 0.004, p = 0.021; ß = 0.14, ß = -0.91, respectively). Heart rate was significantly decreased during sedation in DR group (p < 0.001, ß = -2.32). Radiologist satisfaction was significantly higher, and the incidence of apnea was lower in DR group (p = 0.010, p = 0.009, respectively). Compared with propofol-remifentanil, sedation using dexmedetomidine-remifentanil provided a lower increase of the standard deviation of tidal volume and EtCO2, and also showed less apnea during RFA of HCC.

10.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071140

RESUMO

THeterogeneous nuclear ribonucleoprotein (HNRNP) A1 is the most abundant and ubiquitously expressed member of the HNRNP protein family. In recent years, it has become more evident that HNRNP A1 contributes to the development of neurodegenerative diseases. However, little is known about the underlying role of HNRNP A1 in cancer development. Here, we report that HNRNP A1 expression is significantly increased in lung cancer tissues and is negatively correlated with the overall survival of patients with lung cancer. Additionally, HNRNP A1 positively regulates vaccinia-related kinase 1 (VRK1) translation via binding directly to the 3' untranslated region (UTR) of VRK1 mRNA, thus increasing cyclin D1 (CCND1) expression by VRK1-mediated phosphorylation of the cAMP response element-binding protein (CREB). Furthermore, HNRNP A1 binding to the cis-acting region of the 3'UTR of VRK1 mRNA contributes to increased lung cancer cell proliferation. Thus, our study unveils a novel role of HNRNP A1 in lung carcinogenesis via post-transcriptional regulation of VRK1 expression and suggests its potential as a therapeutic target for patients with lung cancer.


Assuntos
Ribonucleoproteína Nuclear Heterogênea A1/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/fisiologia , Biossíntese de Proteínas , Proteínas Serina-Treonina Quinases/genética , Regiões 3' não Traduzidas , Sequência de Bases , Sistemas CRISPR-Cas , Ciclo Celular , Linhagem Celular , Ciclina D1/biossíntese , Ciclina D1/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Ribonucleoproteína Nuclear Heterogênea A1/química , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Ligação Proteica , Domínios Proteicos , Mapeamento de Interação de Proteínas , Proteínas Serina-Treonina Quinases/biossíntese , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Regulação para Cima
11.
Sci Rep ; 11(1): 7244, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790305

RESUMO

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.

12.
PLoS Genet ; 17(4): e1009523, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33857133

RESUMO

The comorbid association of autoimmune diseases with cancers has been a major obstacle to successful anti-cancer treatment. Cancer survival rate decreases significantly in patients with preexisting autoimmunity. However, to date, the molecular and cellular profiles of such comorbidities are poorly understood. We used Aicardi-Goutières syndrome (AGS) as a model autoimmune disease and explored the underlying mechanisms of genome instability in AGS-associated-gene-deficient patient cells. We found that R-loops are highly enriched at transcription-replication conflict regions of the genome in fibroblast of patients bearing SAMHD1 mutation, which is the AGS-associated-gene mutation most frequently reported with tumor and malignancies. In SAMHD1-depleted cells, R-loops accumulated with the concomitant activation of DNA damage responses. Removal of R-loops in SAMHD1 deficiency reduced cellular responses to genome instability. Furthermore, downregulation of SAMHD1 expression is associated with various types of cancer and poor survival rate. Our findings suggest that SAMHD1 functions as a tumor suppressor by resolving R-loops, and thus, SAMHD1 and R-loop may be novel diagnostic markers and targets for patient stratification in anti-cancer therapy.


Assuntos
Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes/genética , Instabilidade Genômica/genética , Malformações do Sistema Nervoso/genética , Proteína 1 com Domínio SAM e Domínio HD/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/patologia , Linhagem Celular Tumoral , Dano ao DNA/genética , Replicação do DNA/genética , Fibroblastos/metabolismo , Genoma Humano/genética , Humanos , Mutação/genética , Neoplasias/genética , Neoplasias/terapia , Malformações do Sistema Nervoso/imunologia , Malformações do Sistema Nervoso/patologia , Estruturas R-Loop/genética , Proteína 1 com Domínio SAM e Domínio HD/ultraestrutura , Transcrição Genética/genética , Transfecção
13.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807542

RESUMO

Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have identified disease-causing mutations and accelerated the unveiling of complex molecular pathogenic mechanisms, which may be important for understanding the disease and developing therapeutic strategies. Many disease-related genes encode RNA-binding proteins, and most of the disease-causing RNA or proteins encoded by these genes form aggregates and disrupt cellular function related to RNA metabolism. Disease-related RNA or proteins interact or sequester other RNA-binding proteins. Eventually, many disease-causing mutations lead to the dysregulation of nucleocytoplasmic shuttling, the dysfunction of stress granules, and the altered dynamic function of the nucleolus as well as other membrane-less organelles. As RNA-binding proteins are usually components of several RNA-binding protein complexes that have other roles, the dysregulation of RNA-binding proteins tends to cause diverse forms of cellular dysfunction. Therefore, understanding the role of RNA-binding proteins will help elucidate the complex pathophysiology of ALS. Here, we summarize the current knowledge regarding the function of disease-associated RNA-binding proteins and their role in the dysfunction of membrane-less organelles.


Assuntos
Esclerose Amiotrófica Lateral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Humanos , RNA/metabolismo
14.
Nutrients ; 13(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807269

RESUMO

Unhealthy dietary patterns are associated with obesity in children and adolescents. However, few studies have investigated the relationships between dietary patterns and obesity-related metabolic disorders among Asians. We identified dietary patterns in children and adolescents and examined the associations between these patterns and obesity, insulin resistance, and metabolic syndrome in South Korea. This study is a cross-sectional design. We used baseline data from an intervention study of 435 Korean children and adolescents aged 6-17 years. Insulin resistance was assessed as HOMA-IR ≥ 2.6. Metabolic syndrome was diagnosed by cardiovascular disease risk factor clustering. Dietary intakes were estimated using 3-day food records. Factor analysis was used to obtain dietary patterns, and we examined the associations between dietary patterns and obesity-related markers adjusted for potential covariates. Three dietary patterns were identified as fast food and soda (FFS), white rice and kimchi (WRK), and oil and seasoned vegetable (OSV) patterns. Compared with participants in the lower intake of FFS pattern, those in the top intake were associated with a higher waist circumference (WC) (ß = 1.55), insulin level (ß = 1.25), and body mass index (BMI) (ß = 0.53) and it was positively associated with HOMA-IR ≥ 2.6 (OR = 2.11; 95% CI: 1.227-3.638) (p < 0.05). WRK pattern was associated with lower weight and higher HDL cholesterol, and the OSV pattern was associated with a lower weight, WC, and insulin level (p < 0.05). The FFS pattern showed a positive relation with WC, serum insulin, and BMI, and the other two dietary patterns indicated a preventive effect of those parameters. The FFS pattern was associated with significantly elevated insulin resistance among children and adolescents.


Assuntos
Peso Corporal , Doenças Metabólicas , Adolescente , Glicemia , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade Pediátrica , Fatores de Risco , Circunferência da Cintura
15.
Ann Surg ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33914466

RESUMO

OBJECTIVE: To determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). BACKGROUND: Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. METHODS: Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74/129 without autotransfusion were matched with 74/220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. RESULTS: Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/38.3%/39.7% for non-autotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the two groups in overall recurrence (hazard ratio [HR] = 0.72 [0.43-1.21]), intrahepatic recurrence (HR = 0.70 [0.35-1.40]), and extrahepatic recurrence (HR = 0.82 [0.46-1.47]). Also, there were no significant differences in overall death (HR = 0.57 [0.29-1.12]), HCC-related death (HR = 0.59 [0.29-1.20]), and HCC-unrelated death (HR = 0.48 [0.09-2.65]). CONCLUSION: When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.

16.
Adv Exp Med Biol ; 1310: 211-238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834439

RESUMO

Live cell imaging provides essential information in the investigation of cell biology and related pathophysiology. Refractive index (RI) can serve as intrinsic optical imaging contrast for 3-D label-free and quantitative live cell imaging, and provide invaluable information to understand various dynamics of cells and tissues for the study of numerous fields. Recently significant advances have been made in imaging methods and analysis approaches utilizing RI, which are now being transferred to biological and medical research fields, providing novel approaches to investigate the pathophysiology of cells. To provide insight into how RI can be used as an imaging contrast for imaging of biological specimens, here we provide the basic principle of RI-based imaging techniques and summarize recent progress on applications, ranging from microbiology, hematology, infectious diseases, hematology, and histopathology.


Assuntos
Diagnóstico por Imagem , Refratometria , Testes Diagnósticos de Rotina
17.
Neurol Sci ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33860863

RESUMO

BACKGROUND: Although iron dyshomeostasis is associated with Parkinson's disease (PD) pathogenesis, the relationship between iron deposition and non-motor involvement in PD is not fully understood. In this study, we investigated basal ganglia and extra-basal ganglia system iron contents and their correlation with non-motor symptoms in drug-naïve, early-stage PD patients. METHODS: We enrolled 14 drug-naïve, early-stage PD patients and 12 age/sex-matched normal controls. All participants underwent brain magnetic resonance imaging to obtain the effective transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM). Deep brain structures, including the nucleus accumbens, caudate nucleus, putamen, globus pallidus, thalamus, hippocampus, and amygdala, were delineated using the FSL-FIRST; the substantia nigra, red nucleus, and dentate nucleus were segmented manually. Inter-group differences in R2* and QSM values, as well as their association with clinical parameters of PD, were investigated. RESULTS: Substantia nigra and putamen R2* values were significantly higher in PD patients than in normal controls, despite no significant difference in QSM values. Regarding the non-motor symptom scales, PD sleep scale score negatively correlated with R2* values in the red nucleus and right amygdala, Scales for Outcomes in Parkinson's disease-Autonomic scores were positively correlated with R2* values in the right amygdala and left hippocampus, and cardiovascular sub-score of Non-Motor Symptoms Scale for PD was positively associated with the QSM value in the left hippocampus. CONCLUSION: In this study, iron content in the extra-basal ganglia system was significantly correlated with non-motor symptoms, especially sleep problems and dysautonomia, even in early-stage PD.

18.
Eur J Anaesthesiol ; 38(Suppl 2): S106-S112, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33653982

RESUMO

BACKGROUND: Erector spinae plane block (ESPB) has been reported to manage postoperative pain effectively after various types of surgery. However, there has been a lack of study on the effect of ESPB after liver resection. OBJECTIVES: To investigate the analgesic effects of ESPB on pain control after laparoscopic liver resection compared with conventional pain management. DESIGN: Prospective, randomised controlled study. SETTING: A single tertiary care centre from February 2019 to February 2020. PATIENTS: A total of 70 patients scheduled to undergo laparoscopic liver resection. INTERVENTIONS: In the control group (n = 35), no procedure was performed. In the ESPB group (n = 35), ESPB was performed after induction of general anaesthesia. A total of 40 ml of ropivacaine 0.5% was injected at the T9 level bilaterally. After surgery, intravenous fentanyl patient-controlled analgesia was initiated. Fentanyl and hydromorphone were administered as rescue analgesics. MAIN OUTCOME MEASURES: The primary outcome was the cumulative postoperative opioid consumption at 24 h (morphine equivalent). The secondary outcomes were rescue opioid (fentanyl) dose in the postanaesthesia care unit (PACU) and pain severity at 1, 6, 12, 24, 48 and 72 h, assessed using a numerical rating scale (NRS) score. RESULTS: The median [IQR] postoperative opioid consumption during 24 hours following surgery was 48.2 [17.1] mg in the control group and 45.5 [35.8] mg in the ESPB group (median difference, 4.2 mg; 95% CI, -4.2 to 13.3 mg; P = 0.259). Conversely, rescue opioid in PACU was 5.3 [5.0] mg in the control group and 3.0 [1.5] mg in the ESPB group (median difference, 2.5 mg; 95% CI, 1.0 to 5.0 mg; P < 0.001). There was no significant difference in NRS scores point between the groups at any time. CONCLUSION: ESPB does not provide analgesic effect within 24 h after laparoscopic liver resection. TRIAL REGISTRATION: Clinical Trial Registry of Korea (https://cris.nih.go.kr.), identifier: KCT0003549).


Assuntos
Laparoscopia , Bloqueio Nervoso , Analgesia Controlada pelo Paciente , Humanos , Fígado , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , República da Coreia , Ultrassonografia de Intervenção
19.
Biochem Biophys Res Commun ; 551: 161-167, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33740623

RESUMO

Physiological oxygen concentration (physioxia) ranges from 1 to 8% in human tissues while many researchers cultivate mammalian cells under an atmospheric concentration of 21% (hyperoxia). Oxygen is one of the significant gases which functions in human cells including energy production in mitochondria, metabolism in peroxidase, and transcription of various genes in company with HIF (Hypoxia-inducible factors) in the nucleus. Thus, mammalian cell culture should be deliberated on the oxygen concentration to mimic in vivo physiology. Here, we studied if the cultivation of human skin cells under physiological conditions could affect skin significant genes in barrier functions and dermal matrix formation. We further examined that some representative active ingredients in dermatology such as glycolic acid, gluconolactone, and salicylic acid work in different ways depending on the oxygen concentration. Taken together, we present the importance of oxygen concentration in skin cell culture for proper screening of novel ingredients as well as the mechanistic study of skin cell regulation.


Assuntos
Hidroxiácidos/farmacologia , Oxigênio/farmacologia , Pele , Linhagem Celular , Colágeno Tipo I/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Gluconatos/metabolismo , Glicolatos/metabolismo , Humanos , Queratina-1/genética , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Lactonas/metabolismo , Metaloproteinase 1 da Matriz/genética , Oxigênio/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteínas S100/genética , Ácido Salicílico/metabolismo , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo
20.
ACS Appl Mater Interfaces ; 13(13): 14866-14874, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33759486

RESUMO

Multidrug resistance (MDR) of cancer cells reduces chemotherapeutic efficacy by preventing drug accumulation in the cells through a drug efflux pump and lysosomal sequestration/exocytosis. Herein, to overcome such anticancer resistance, lysosome-targeted self-assembly of perylene diimide (PDI) derivatives is presented as a powerful strategy for effective and selective anticancer therapy. Stimulated by the lysosomal low pH, the amphiphilic PDI derivatives functionalized with amino acids (PDI-AAs) construct fibrous self-assembled structures inside the lysosomes, causing cancer cell apoptosis by lysosomal rupture. In contrast, negligible apoptosis was observed from normal cells by PDI-AA. The agglomerated fibrous assemblies were not removed by lysosomal exocytosis, thereby displaying a 10.7-fold higher anticancer efficacy on MDR cancer cells compared to a doxorubicin chemotherapeutic agent. The MDR-circumventing capability, along with high selectivity toward cancer cells, supports PDI-AAs as potential candidates for the treatment of MDR cancer cells by lysosome-targeted self-assembly.


Assuntos
Aminoácidos/farmacologia , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Imidas/farmacologia , Lisossomos/efeitos dos fármacos , Perileno/análogos & derivados , Aminoácidos/química , Antineoplásicos/química , Linhagem Celular , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Humanos , Imidas/química , Lisossomos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Perileno/química , Perileno/farmacologia
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