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Natural products have successfully treated several diseases using a multi-component, multi-target mechanism. However, a precise mechanism of action (MOA) has not been identified. Systems pharmacology methods have been used to overcome these challenges. However, there is a limitation as those similar mechanisms of similar components cannot be identified. In this study, comparisons of physicochemical descriptors, molecular docking analysis and RNA-seq analysis were performed to compare the MOA of similar compounds and to confirm the changes observed when similar compounds were mixed and used. Various analyses have confirmed that compounds with similar structures share similar MOA. We propose an advanced method for in silico experiments in herbal medicine research based on the results. Our study has three novel findings. First, an advanced network pharmacology research method was suggested by partially presenting a solution to the difficulty in identifying multi-component mechanisms. Second, a new natural product analysis method was proposed using large-scale molecular docking analysis. Finally, various biological data and analysis methods were used, such as in silico system pharmacology, docking analysis and drug response RNA-seq. The results of this study are meaningful in that they suggest an analysis strategy that can improve existing systems pharmacology research analysis methods by showing that natural product-derived compounds with the same scaffold have the same mechanism.
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Produtos Biológicos , Medicamentos de Ervas Chinesas , Plantas Medicinais , Simulação de Acoplamento Molecular , Transcriptoma , Produtos Biológicos/farmacologia , Extratos Vegetais , Medicina Tradicional ChinesaRESUMO
PURPOSE: Remimazolam is often used for perioperative sedation due to its rapid onset and offset. However, the possible association between remimazolam and postoperative delirium (POD) remains undetermined. The present study evaluated whether remimazolam increased the incidence of POD compared with dexmedetomidine in elderly patients undergoing orthopedic surgery of the lower extremities. METHODS: This retrospective study included patients aged ≥ 65 years who had undergone orthopedic surgery of the lower extremities under spinal anesthesia from January 2020 to November 2022 and were sedated with continuous intravenous infusion of dexmedetomidine or remimazolam. The incidence of POD was assessed through a validated comprehensive review process of each patient's medical records. The effect of remimazolam on the occurrence of POD compared with dexmedetomidine was evaluated by propensity score weighted multivariable logistic models. RESULTS: A total of 447 patients were included in the final analysis. The crude incidence of POD within 3 days after surgery was 7.5% (17/226) in the dexmedetomidine group and 11.8% (26/221) in the remimazolam group, increasing to 9.7% (22/226) and 15.8% (35/221), respectively (p = 0.073), within 5 days. The multivariable models showed that, compared with dexmedetomidine, intraoperative sedation with remimazolam significantly increased the occurrence of POD within 3 days (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.31 to 3.82, p = 0.003) and 5 days (OR 2.10, 95% CI 1.32 to 3.40, p = 0.002). CONCLUSION: Compared with dexmedetomidine, remimazolam infusion may be associated with a higher risk of POD in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia.
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Korean diesel particulate matter 20 (KDP20) is a pollutant comprising a complex mixture of carbon and chemical irritants. Although particulate matter and nasal inflammation are strongly associated, the underlying molecular mechanism based on systematic transcriptome analysis remains unknown. In this study, genome-wide gene expression profiles of mouse nasal tissues were determined following exposure to KDP20 for 5 and 10 days and compared with those of the control (n = 4/group). We identified 758 significant differentially expressed genes (DEGs) and classified them as 5-day-specific, 10-day-specific, and common among groups based on their expression patterns. The terms "regulation of alpha-beta T cell differentiation," "macrophage differentiation," and "cell adhesion mediated by integrin" were significantly enriched in each group. Receiver operating characteristic analysis revealed six genes as potential predictive biomarkers. The differential expression of these six genes was validated using quantitative RT-PCR (n = 3/group). Furthermore, a possible mechanism for nasal inflammation was suggested through the binding analysis between metal ions and genes. The genes identified in this study may play important roles in regulating the mechanism of nasal inflammation induced by diesel particles, especially immune cell regulation, and may function as markers for diesel particle-induced nasal inflammation.
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Perfilação da Expressão Gênica , Emissões de Veículos , Camundongos , Animais , Emissões de Veículos/toxicidade , Material Particulado/toxicidade , Transcriptoma , Inflamação/induzido quimicamente , Inflamação/genéticaRESUMO
The myogenic capacity of myoblasts decreases in skeletal muscle with age. In addition to environmental factors, intrinsic factors are important for maintaining the regenerative potential of muscle progenitor cells, but their identities are largely unknown. Here, comparative analysis of microRNA (miRNA) expression profiles in young and old myoblasts uncovered miR-431 as a novel miRNA showing markedly reduced abundance in aged myoblasts. Importantly, elevating miR-431 improved the myogenic capacity of old myoblasts, while inhibiting endogenous miR-431 lowered myogenesis. Bioinformatic and biochemical analyses revealed that miR-431 directly interacted with the 3' untranslated region (UTR) of Smad4 mRNA, which encodes one of the downstream effectors of TGF-ß signaling. In keeping with the low levels of miR-431 in old myoblasts, SMAD4 levels increased in this myoblast population. Interestingly, in an in vivo model of muscle regeneration following cardiotoxin injury, ectopic miR-431 injection greatly improved muscle regeneration and reduced SMAD4 levels. Consistent with the finding that the mouse miR-431 seed sequence in the Smad4 3' UTR is conserved in the human SMAD4 3' UTR, inhibition of miR-431 also repressed the myogenic capacity of human skeletal myoblasts. Taken together, our results suggest that the age-associated miR-431 plays a key role in maintaining the myogenic ability of skeletal muscle with age.
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Diferenciação Celular , MicroRNAs/metabolismo , Desenvolvimento Muscular/genética , Músculo Esquelético/fisiologia , Mioblastos/citologia , Regeneração/genética , Proteína Smad4/genética , Regiões 3' não Traduzidas , Animais , Linhagem Celular , Senescência Celular , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Músculo Esquelético/citologia , Ligação ProteicaRESUMO
Tenebrio molitor larvae (mealworm) is an edible insect and is considered a future food. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a novel method for simultaneous analysis of 353 target analytes was developed and validated. Various sample preparation steps including "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) extraction conditions, number of acetonitrile-hexane partitions, and dispersive-solid phase extraction (dSPE) sorbents were compared, and the optimal conditions were determined. In the established method, 5 g of homogenized mealworms was extracted with acetonitrile and treated with QuEChERS EN 15662 salts. The crude extract was subjected to three rounds of acetonitrile-hexane partitioning, and the acetonitrile layer was cleaned with C18 dSPE. The final solution was matrix-matched and injected into LC-MS/MS (2 µL). For target analytes, the limits of quantitation (LOQs) were ≤10 µg/kg, and the correlation coefficient (r2) of calibration was >0.990. In recovery tests, more than 90% of the pesticides showed an excellent recovery range (70-120%) with relative standard deviation (RSD) ≤20%. For more than 94% of pesticides, a negligible matrix effect (within ±20%) was observed. The analytical method was successfully applied and used for the detection of three urea pesticides in 4 of 11 mealworm samples.
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Cromatografia Líquida/métodos , Resíduos de Praguicidas/análise , Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Tenebrio/efeitos dos fármacos , Acetonitrilas/química , Animais , Calibragem , Insetos Comestíveis , Hexanos/química , Insetos , Larva , Limite de Detecção , Extração em Fase Sólida , Ureia/análiseRESUMO
An effective analytical method was optimized for residues including chlorpyrifos-methyl, deltamethrin, fenoxanil, thiobencarb and fludioxonil in mealworms, the larval form of Tenebrio molitor. They are listed for pest control during wheat cultivation and can be found in wheat-bran feed for growing mealworms in South Korea. Analytes were extracted using acetonitrile and salt packet. Four clean-up methods ((1) MgSO4 + 25 mg PSA + 25 mg C18; (2) MgSO4 + 50 mg PSA + 50 mg C18; (3) EMR-lipidTM tube; and (4) 10 mL n-hexane) were investigated and the method (1) was selected due to its robustness. Low-temperature precipitation of fat and proteins improved the recoveries. Recoveries from the Method (1) were satisfying with 70-120% with <20% relative SD at a spiking level of 0.01 mg/kg. With the simultaneous sample preparation, fenoxanil, thiobencarb and fludioxonil were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and chlorpyrifos-methyl and deltamethrin by gas chromatography tandem mass spectrometry (GC-MS/MS). Quantification limits for LC-MS/MS and GC-MS/MS were 0.5 and 2.5 µg/L, respectively. No pesticides of interest were detected in 30 real samples collected across the nation. However, the data can be provided for establishing maximum residue limits for the pesticides in mealworms in response to the positive list system.
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Cromatografia Gasosa-Espectrometria de Massas/métodos , Resíduos de Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Tenebrio/química , Animais , Clorpirifos/análogos & derivados , Clorpirifos/análise , Clorpirifos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Imidazóis/análise , Imidazóis/isolamento & purificação , Larva/química , Larva/metabolismo , Limite de Detecção , Extração Líquido-Líquido , Nitrilas/análise , Nitrilas/isolamento & purificação , Resíduos de Praguicidas/isolamento & purificação , Piretrinas/análise , Piretrinas/isolamento & purificação , Tenebrio/crescimento & desenvolvimento , Tenebrio/metabolismoRESUMO
Asthma, a heterogeneous disease of the airways, is common around the world, but little is known about the molecular mechanisms underlying the interactions between DNA methylation and gene expression in relation to this disease. The seeds of Descurainia sophia are traditionally used to treat coughs, asthma and edema, but their effects on asthma have not been investigated by multi-omics analysis. We undertook this study to assess the epigenetic effects of ethanol extract of D. sophia seeds (DSE) in an ovalbumin (OVA)-induced mouse model of asthma. We profiled genome-wide DNA methylation by Methyl-seq and characterized the transcriptome by RNA-seq in mouse lung tissue under three conditions: saline control, OVA-induced, and DSE-treated. In total, 1995 differentially methylated regions (DMRs) were identified in association with anti-asthmatic effects, most in promoter and coding regions. Among them, 25 DMRs were negatively correlated with the expression of the corresponding 18 genes. These genes were related to development of the lung, respiratory tube and respiratory system. Our findings provide insights into the anti-asthmatic effects of D. sophia seeds and reveal the epigenetic targets of anti-inflammatory processes in mice.
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Antiasmáticos/farmacologia , Brassicaceae/química , Epigênese Genética/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sementes/química , Animais , Antiasmáticos/química , Asma/tratamento farmacológico , Asma/imunologia , Asma/patologia , Biologia Computacional/métodos , Metilação de DNA , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Camundongos , Ovalbumina/efeitos adversos , Ovalbumina/imunologia , Extratos Vegetais/química , TranscriptomaRESUMO
DNA double-strand breaks (DSBs) are the most severe type of DNA damage and are primarily repaired by non-homologous end joining (NHEJ) and homologous recombination (HR) in the G1 and S/G2 phase, respectively. Although CtBP-interacting protein (CtIP) is crucial in DNA end resection during HR following DSBs, little is known about how CtIP levels increase in an S phase-specific manner. Here, we show that Serpine mRNA binding protein 1 (SERBP1) regulates CtIP expression at the translational level in S phase. In response to camptothecin-mediated DNA DSBs, CHK1 and RPA2 phosphorylation, which are hallmarks of HR activation, was abrogated in SERBP1-depleted cells. We identified CtIP mRNA as a binding target of SERBP1 using RNA immunoprecipitation-coupled RNA sequencing, and confirmed SERBP1 binding to CtIP mRNA in S phase. SERBP1 depletion resulted in reduction of polysome-associated CtIP mRNA and concomitant loss of CtIP expression in S phase. These effects were reversed by reconstituting cells with wild-type SERBP1, but not by SERBP1 ΔRGG, an RNA binding defective mutant, suggesting regulation of CtIP translation by SERBP1 association with CtIP mRNA. These results indicate that SERBP1 affects HR-mediated DNA repair in response to DNA DSBs by regulation of CtIP translation in S phase.
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Proteínas de Transporte/biossíntese , Regulação da Expressão Gênica , Proteínas Nucleares/biossíntese , Biossíntese de Proteínas , Proteínas de Ligação a RNA/metabolismo , Reparo de DNA por Recombinação , Fase S/genética , Regiões 3' não Traduzidas , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Endodesoxirribonucleases , Células HeLa , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/fisiologia , Transdução de SinaisRESUMO
Solution-processed inorganic UV-visible short-wave-infrared photodetectors with light sensitivity from 350 nm to 2000 nm are fabricated using highly monodispersed large PbS NCs. These devices showed detectivity values over 1 × 10(11) Jones from 350 nm to 2000 nm, and a maximum detectivity value of 1.2 × 10(12) Jones at 1800 nm.
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BACKGROUND: Age-related differences in diabetes outcomes are important both for clinical and policy considerations. To clarify the basis of such differences, we investigated patterns of associations for age in relation to hospitalization and glycemic control and examined the role of other factors. METHODS: 4471 patients with diabetes aged 40-79 years were drawn from a retrospectively retrieved National Health Insurance Cohort. Using logistic regression, risk factors measured over the two years (2007-2008) were examined for their associations with hospitalization and poor glycemic control during the last year (2009) of follow-up. RESULTS: Compared to the middle-aged patients, older patients were more likely to have been hospitalized (Adjusted odds ratio (OR(adjusted)) = 1.97(95% CI = 1.28, 3.04) for the oldest group (ages 70-79) vs youngest group (ages 40-49)) but less likely to have poor glycemic control (OR(adjusted) = 0.45 (95% CI = 0.37, 0.56) for the oldest group vs youngest group). Older patients were also less likely to be obese but had more complications, longer duration of diabetes, lower continuity of care, and higher blood pressure and total cholesterol level. The pattern of associations for hospitalization and glycemic control was not uniform across the risk factors, sharing only a few common factors such as the duration of diabetes and blood pressure. In general, poor glycemic control was affected predominantly by metabolic management, while hospitalization was strongly related to functional status (i.e., number of complications) and care quality measures (i.e., continuity of care). CONCLUSION: Hospitalization was higher among the older diabetic patients, despite better glycemic control. Factors were differently associated with the two diabetes-related outcomes, providing more comprehensive risk profiles for hospitalization. The co-existence of improved glycemic control and increased hospitalization among older diabetic patients suggests an extension of a geriatric evaluation to wider functional and comorbidity status.
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Diabetes Mellitus Tipo 2/terapia , Gerenciamento Clínico , Atenção Primária à Saúde/métodos , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Perfusion index (PI) has been used as a surrogate marker of sympathetic blockade. This study evaluated changes in PI of bilateral upper extremity after thoracic paravertebral block (PVB) and intertransverse process block (ITPB). Methods: This pilot study included three groups of patients undergoing elective unilateral pulmonary resection under general anesthesia with PVB (n=11) or ITPB (n=10), or urologic procedures with general anesthesia (control group, n=10). Blockades were performed using 10 mL aliquots of 0.5% ropivacaine administered at T3-4, T5-6, and T7-8 intercostal levels immediately after general anesthesia induction. The PI value of the operating side (PI-O) was divided by the contralateral side (PI-CL), and the relative change to baseline was assessed (relative PI-O/PI-CL), with a 50% increase considered meaningful. Results: In all cases within the PVB and ITPB groups, a significant increase in PI was observed following the blockades. The median (1Q, 3Q) intraoperative relative PI-O/PI-CL values were 0.9 (0.8, 1.4), 2.1 (1.4, 2.5), and 1.4 (0.9, 1.9) in the control, PVB, and ITPB groups (P=0.01), respectively. Pairwise comparison revealed a significant difference only between the control and PVB groups (adjusted P=0.01). While the relative PI-O/PI-CL value in the control group generally remained close to 1, occasional fluctuations exceeding 1.5 were noted. Conclusions: PVB induced a noticeable unilateral increase in upper extremity PI, whereas ITPB tended to result in an inconsistent and lesser degree of increase. Monitoring PI values can serve as an indicator of upper extremity sympathetic blockade, but consideration of potential confounders impacting these observations during surgery is essential. Further research is needed to validate these findings.
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Achaete scute-like 2 (ASCL2), a basic helix-loop-helix transcription factor, plays an essential role in the maintenance of adult intestinal stem cells. However, the function of ASCL2 in gastric cancer (GC) is poorly understood. Therefore, we investigated the roles and regulatory transcription mechanisms of ASCL2 in GC. Gene expression and methylation data analysis showed that ASCL2 was upregulated and hypomethylated in GC tissues. Using real-time RT-PCR and pyrosequencing analysis, we confirmed that ASCL2 was overexpressed and hypomethylated in GC tissues compared to adjacent normal tissues. We then investigated the mechanisms underlying the aberrant expression of ASCL2 in GC and found that treatment with a methylation inhibitor induced ASCL2 expression in GC cell lines. MBD-sequencing assay also revealed hypermethylation of the promoter region of ASCL2 in GC cell lines, which barely expressed the ASCL2 gene. Furthermore, ASCL2 expression levels were inversely correlated with GC patient survival. Ectopic overexpression of ASCL2 showed that ASCL2 increased cell growth and promoted resistance to 5-fluorouracil in GC cells. These results suggest that ASCL2 might play an important role in gastric tumor growth and chemoresistance, and could be a useful prognostic marker for GC patients.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Metilação de DNA , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Regulação para CimaRESUMO
Background: Herbal medicines traditionally target organs for treatment based on medicinal properties, and this theory is widely used for prescriptions. However, the scientific evidence explaining how herbs act on specific organs by biological methods has been still limited. This study used bioinformatic tools to identify the target organ locations of Radix Achyranthis Bidentatae (RAB), a blood-activating herb that nourishes the liver and kidney, strengthens bones, and directs prescription to the lower body. Methods: RAB's active compounds and targets were collected and predicted using databases such as TCMSP, HIT2.0, and BATMAN-TCM. Next, the RAB's target list was analyzed based on two approaches to obtain target organ locations. DAVID and Gene ORGANizer enrichment-based approaches were used to enrich an entire gene list, and the BioGPS and HPA gene expression-based approaches were used to analyze the expression of core genes. Results: RAB's targets were found to be involved in whole blood, blood components, and lymphatic organs across all four tools. Each tool indicated a particular aspect of RAB's target organ locations: DAVID-enriched genes showed a predominance in blood, liver, and kidneys; Gene ORGANizer showed the effect on low body parts as well as bones and joints; BioGPS and HPA showed high gene expression in bone marrow, lymphoid tissue, and smooth muscle. Conclusion: Our bioinformatics-based target organ location prediction can serve as a modern interpretation tool for the target organ location theory of traditional medicine. Future studies should predict therapeutic target organ locations in complex prescriptions rather than single herbs and conduct experiments to verify predictions.
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BACKGROUND: Various regional analgesia techniques are used to reduce postoperative pain in patients undergoing lumbar spine surgery. Traditionally, wound infiltration (WI) with local anesthetics has been widely used by surgeons. Recently, other regional analgesia techniques, such as the erector spinae plane block (ESPB) and thoracolumbar interfascial plane (TLIP) block, are being used for multimodal analgesia. The authors aimed to determine the relative efficacy of these using a network meta-analysis. MATERIALS AND METHODS: The authors searched PubMed, EMBASE, the Cochrane Controlled Library, and Google Scholar databases to identify all randomized controlled trials that compared the analgesic efficacy of the following interventions: ESPB, TLIP block, WI technique, and controls. The primary endpoint was postoperative opioid consumption during the first 24 hours after surgery, while the pain score, estimated postoperatively at three different time periods, was the secondary objective. RESULTS: The authors included 34 randomized controlled trials with data from 2365 patients. TLIP showed the greatest reduction in opioid consumption compared to controls [mean difference (MD) =-15.0 mg; 95% CI: -18.8 to -11.2]. In pain scores, TLIP had the greatest effect during all time periods compared to controls (MD=-1.9 in early, -1.4 in middle, -0.9 in late). The injection level of ESPB was different in each study. When only surgical site injection of ESPB was included in the network meta-analysis, there was no difference compared with TLIP (MD=1.0 mg; 95% CI: -3.6 to 5.6). CONCLUSIONS: TLIP showed the greatest analgesic efficacy after lumbar spine surgery, in terms of postoperative opioid consumption and pain scores, while ESPB and WI are also alternative analgesic options for these surgeries. However, further studies are needed to determine the optimal method of providing regional analgesia after lumbar spine surgery.
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Analgesia , Analgésicos Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Metanálise em Rede , Procedimentos Neurocirúrgicos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controleRESUMO
In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issue in iPSC-based cell therapy, it is essential to selectively remove undifferentiated iPSCs remaining in the iPSC-derived differentiated cell product prior to in vivo transplantation. In this study, we explored whether an ethanol extract of coptidis rhizoma (ECR) exhibited anti-teratoma activity and identified the active components involved in the selective elimination of undifferentiated iPSCs. Transcriptome analysis of iPSCs confirmed that cell death-related pathways were significantly altered by ECR treatment. Our results demonstrate that ECR effectively induced apoptotic cell death and DNA damage in iPSCs, and that reactive oxygen species generation, mitochondrial damage, caspase activation, and p53 activation were involved in ECR-mediated iPSC death. However, in iPSC-derived differentiated cells (iPSC-Diff), reduced cell viability and the DNA damage response were not observed after ECR treatment. We co-cultured iPSCs and iPSC-Diff and found that ECR treatment selectively removed iPSCs, whereas iPSC-Diff remained intact. Prior to in ovo implantation, ECR treatment of a mixed cell culture of iPSCs and iPSC-Diff significantly suppressed iPSC-derived teratoma formation. Among the main components of the ECR, berberine and coptisine showed selective cytotoxicity to iPSCs but not to iPSC-Diff. Together, these results indicate the usefulness of ECRs in preparing safe and effective iPSC-based therapeutic cell products with no risk of teratoma formation.
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Medicamentos de Ervas Chinesas , Células-Tronco Pluripotentes Induzidas , Humanos , Adulto , Células-Tronco Pluripotentes Induzidas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Etanol/farmacologia , Apoptose , Diferenciação CelularRESUMO
STUDY OBJECTIVE: The present study assessed whether costotransverse foramen block (CTFB) is noninferior to thoracic paravertebral block (TPVB) for postoperative analgesia in video-assisted thoracoscopic surgery (VATS) pulmonary resection. DESIGN: Single-center, double-blinded, randomized, non-inferiority trial. SETTING: Operating room and intensive care unit or ward in a tertiary hospital. PATIENTS: Patients aged 20 to 80 years with American Society of Anesthesiology physical status 1 to 3 scheduled for elective VATS pulmonary resection. INTERVENTIONS: Sixty patients were randomly allocated 1:1 to receive CTFB or TPVB using 15 mL aliquots of 0.5% ropivacaine at the T4-5 and T6-7 intercostal levels immediately after the induction of general anesthesia. MEASUREMENTS: The primary outcome was the area under the curve (AUC) of numeric rating scale (NRS, 0 to 10) during 24 h postoperatively (noninferiority limit was 24; NRS 1 per hour). The secondary outcomes included postoperative opioid consumption, rescue analgesic use, postoperative nausea and vomiting, pulmonary function, dermatomal spread of the blockade, and quality of recovery. MAIN RESULTS: Forty-seven patients were included for final analysis. The difference between the mean 24-h AUCs of NRS in the CTFB (34.25 ± 16.30, n = 24) and TPVB (39.52 ± 17.13, n = 23) groups was -5.27 (95% confidence interval [CI], -15.09 to 4.55), with the upper limit of 95% CI being far below the predefined noninferiority margin of 24. There was no significant difference in the dermatomal spread of the blockades between the groups, as both reached the upper and lower most levels of T3 and T7 (median). Additionally, there were no significant differences in other secondary outcomes between the two groups. CONCLUSIONS: The analgesic effect of CTFB was noninferior to that of TPVB during 24 h postoperatively in VATS pulmonary resection. Moreover, CTFB may offer potential safety benefits by keeping the tip of the needle far from the pleura and vascular structure.
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Bloqueio Nervoso , Cirurgia Torácica Vídeoassistida , Humanos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Ropivacaina , Analgésicos Opioides/uso terapêuticoRESUMO
Although previous studies have shown correlation between regional cerebral oxygen saturation (rScO2) and mixed venous oxygen saturation (SvO2), there is a lack of pragmatic information on the clinical applicability of these findings, such as tracking ability. We retrospectively analyzed continuous intraoperative recordings of rScO2 and SvO2 obtained from a pulmonary artery catheter and either of two near-infrared spectroscopy (NIRS) devices (INVOS 5100C, Medtronic; O3, Masimo) during off-pump cardiopulmonary bypass (OPCAB) surgery in adult patients. The ability of rScO2 to track SvO2 was quantitatively evaluated with 5 min interval changes transformed into relative values. The analysis included 176 h of data acquired from 48 subjects (26 and 22 subjects for INVOS and O3 dataset, respectively). The area under ROC of the left-rScO2 for detecting change of SvO2 ≥ 10% in INVOS and O3 datasets were 0.919 (95% CI 0.903-0.936) and 0.852 (95% CI 0.818-0.885). The concordance rates between the interval changes of left-rScO2 and SvO2 in INVOS and O3 datasets were 90.6% and 91.9% with 10% exclusion zone. rScO2 can serve as a noninvasive tool for detecting changes in SvO2 levels, a critical hemodynamic measurement.
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Oxigênio , Espectroscopia de Luz Próxima ao Infravermelho , Adulto , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Saturação de Oxigênio , Estudos Retrospectivos , Oximetria/métodosRESUMO
(1) Background: limited data exist regarding the occurrence of hypotension associated with dexmedetomidine use and its risk factors in the context of intraoperative sedation for patients receiving peripheral nerve blocks. (2) Method: This single-center retrospective study assessed the incidence of hypotension in patients undergoing orthopedic upper extremity surgery with brachial plexus blockade. Patients were classified into three groups: group N (non-sedated), group M (midazolam), and group D (dexmedetomidine), based on their primary intraoperative sedative use. The primary outcome was the incidence of perioperative hypotension, defined as systolic blood pressure (SBP) < 90 mmHg or mean blood pressure (MBP) < 60 mmHg, at a minimum of two recorded time points during the intraoperative period and post-anesthesia care unit stay. Multivariable logistic models for the occurrence of hypotension were constructed for the entire cohort and group D. (3) Results: A total of 2152 cases (group N = 445, group M = 678, group D = 1029) were included in the analysis. The odds ratio for the occurrence of hypotension in group D was 5.68 (95% CI, 2.86 to 11.28) compared with group N. Concurrent use of a beta blocker, longer duration of surgery, and lower preoperative SBP and higher preoperative heart rate were identified as significant risk factors. (4) Conclusions: the increased risk of hypotension and the associated factors should be taken into account before using dexmedetomidine in these cases.
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This supplementary data supports the research article 'Genome-wide DNA methylation profiling reveals candidate biomarkers and probable molecular mechanism of metabolic syndrome' (Baek et al., in press). To obtain these data, 32 participants with metabolic syndrome (MetS) were enrolled in the associated study. We collected peripheral blood mononuclear cells (PBMCs) from 11 patients with MetS and nine controls and compared genome-wide gene expression and DNA methylation signatures. The remaining 12 participants were used for the experimental validation of the candidate groups. We provide the raw, analyzed, and filtered genome-wide DNA methylation data, obtained using the Infinium Human MethylationEPIC BeadChIP array, and whole transcriptome sequencing data (accession number GSE181647). We list the differentially expressed and differentially methylated genes and their biological functions. These data can serve as a basis for screening appropriate epigenetic biomarkers for MetS.
RESUMO
Effective treatments for patients experiencing temperature-related symptoms are limited. The hot and cold effects of traditional herbal medicines have been utilized to treat and manage these symptoms, but their molecular mechanisms are not fully understood. Previous studies with arbitrarily selected herbs and ingredients may have produced biased results. Here, we aim to systematically elucidate the molecular mechanisms of the hot and cold properties of herbal medicines through an unbiased large-scale investigation of herbal ingredients, their target genes, and the transcriptome signatures induced by them. Using data regarding 243 herbs retrieved from two herbal medicine databases, we statistically identify (R)-Linalool, (-)-alpha-pinene, peruviol, (L)-alpha-terpineol, and cymol as five new hot-specific ingredients that share a common target, a norepinephrine transporter. However, no significant ingredients are cold-specific. We also statistically identify 14 hot- and 8 cold-specific new target genes. Pathway enrichment analysis of hot-specific target genes reveals the associated pathways including neurotransmitter reuptake, cold-induced thermogenesis, blood pressure regulation, adrenergic receptor signaling, and cation symporter activity. Cold-specific target genes are associated with the steroid pathway. Transcriptome analysis also shows that hot herbs are more strongly associated with coagulation and synaptic transmission than cold herbs. Our results, obtained from novel connections between herbal ingredients, target genes, and pathways, may contribute to the development of pharmacological treatment strategies for temperature-related pain using medicinal plants.