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The complex etiological factors associated with metabolic dysfunction-associated fatty liver disease (MAFLD), including perturbed iron homeostasis, and the unclear nature by which they contribute to disease progression have resulted in a limited number of effective therapeutic interventions. Here, we report that patients with metabolic dysfunction-associated steatohepatitis (MASH), a pathological subtype of MAFLD, exhibit excess hepatic iron and that it has a strong positive correlation with disease progression. FerroTerminator1 (FOT1) effectively reverses liver injury across multiple MASH models without notable toxic side effects compared with clinically approved iron chelators. Mechanistically, our multi-omics analyses reveal that FOT1 concurrently inhibits hepatic iron accumulation and c-Myc-Acsl4-triggered ferroptosis in various MASH models. Furthermore, MAFLD cohort studies suggest that serum ferritin levels might serve as a predictive biomarker for FOT1-based therapy in MASH. These findings provide compelling evidence to support FOT1 as a promising novel therapeutic option for all stages of MAFLD and for future clinical trials.
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MYC amplification is frequently observed in approximately 50% of human cancers, rendering it a highly desired anticancer target. Given the challenge of direct pharmacological inhibiting of MYC, impairing the interaction of MYC and its key cofactor WDR5 has been proposed as a promising strategy for MYC-driven cancer treatment. Herein, we report the discovery of 5-thiocyanatothiazol-2-amines that disrupt the WDR5-MYC interaction. Hit fragments were initially identified in a fluorescence polarization (FP)-based screening of an in-house library, and structural-activity relationship exploration resulted in the lead compounds 4m and 4o with potent inhibitory activities on WDR5-MYC interaction (K i = 2.4 µM for 4m; K i = 1.0 µM for 4o). These compounds were further validated via differential scanning fluorimetry (DSF) and coimmunoprecipitation (Co-IP). Moreover, 4m and 4o exhibited good cellular activities with the IC50 values at the micromolar level (IC50 = 0.71-7.40 µM) against multiple MYC-driven cancer cell lines. Our findings afforded a potential small molecule blocking the WDR5-MYC interaction.
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Since influenza virus RNA polymerase subunit PAN is a dinuclear Mn2+ dependent endonuclease, metal-binding pharmacophores (MBPs) with Mn2+ coordination has been elucidated as a promising strategy to develop PAN inhibitors for influenza treatment. However, few attentions have been paid to the relationship between the optimal arrangement of the donor atoms in MBPs and anti-influenza A virus (IAV) efficacy. Given that, the privileged hydroxypyridinones fusing a seven-membered lactam ring with diverse side chains, chiral centers or cyclic systems were designed and synthesized. A structure-activity relationship study resulted in a hit compound 16l (IC50 = 2.868 ± 0.063 µM against IAV polymerase), the seven-membered lactam ring of which was fused a pyrrolidine ring. Further optimization of the hydrophobic binding groups on 16l afforded a lead compound (R, S)-16s, which exhibited a 64-fold more potent inhibitory activity (IC50 = 0.045 ± 0.002 µM) toward IAV polymerase. Moreover, (R, S)-16s demonstrated a potent anti-IAV efficacy (EC50 = 0.134 ± 0.093 µM) and weak cytotoxicity (CC50 = 15.35 µM), indicating the high selectivity of (R, S)-16s. Although the lead compound (R, S)-16s exhibited a little weaker activity than baloxavir, these findings illustrated the utility of a metal coordination-based strategy in generating novel MBPs with potent anti-influenza activity.
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Antivirales , Diseño de Fármacos , Endonucleasas , Virus de la Influenza A , Lactamas , Piridonas , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Lactamas/química , Lactamas/farmacología , Lactamas/síntesis química , Relación Estructura-Actividad , Endonucleasas/antagonistas & inhibidores , Endonucleasas/metabolismo , Piridonas/farmacología , Piridonas/química , Piridonas/síntesis química , Virus de la Influenza A/efectos de los fármacos , Estructura Molecular , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Perros , Células de Riñón Canino Madin Darby , AnimalesRESUMEN
Sepsis, critical condition marked by severe organ dysfunction from uncontrolled infection, involves the endothelium significantly. Macrophages, through paracrine actions, play a vital role in sepsis, but their mechanisms in sepsis pathogenesis remain elusive. Objective: We aimed to explore how macrophage-derived exosomes with low miR-141 expression promote pyroptosis in endothelial cells (ECs). Exosomes from THP-1 cell supernatant were isolated and characterized. The effects of miR-141 mimic/inhibitor on apoptosis, proliferation, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed using flow cytometry, CCK-8, and transwell assays. Key pyroptosis-related proteins, including caspase-1, IL-18, IL-1ß, NLR Family Pyrin Domain Containing 3 (NLRP3), ASC, and cleaved-GSDMD, were analyzed via Western blot. The interaction between miR-141 and NLRP3 was studied using RNAhybrid v2.2 and dual-Luciferase reporter assays. The mRNA and protein level of NLRP3 after exosomal miR-141 inhibitor treatment was detected by qPCR and Western blot, respectively. Exosomes were successfully isolated. miR-141 mimic reduced cell death and pyroptosis-related protein expression in HUVECs, while the inhibitor had opposite effects, increasing cell death, and enhancing pyroptosis protein expression. Additionally, macrophage-derived exosomal miR-141 inhibitor increased cell death and pyroptosis-related proteins in HUVECs. miR-141 inhibits NLRP3 transcription. Macrophages facilitate sepsis progression by secreting miR-141 decreased exosomes to activate NLRP3-mediated pyroptosis in ECs, which could be a potentially valuable target of sepsis therapy.
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Exosomas , Células Endoteliales de la Vena Umbilical Humana , Macrófagos , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Sepsis , MicroARNs/genética , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Humanos , Exosomas/metabolismo , Macrófagos/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Sepsis/metabolismo , Sepsis/patología , Células THP-1 , Progresión de la Enfermedad , Animales , RatonesRESUMEN
Given the rapidly aging population, aging-related diseases are becoming an excessive burden on the global healthcare system. Metformin has been shown to be beneficial to many age-related disorders, as well as increase lifespan in preclinical animal models. During the aging process, kidney function progressively declines. Currently, whether and how metformin protects the kidney remains unclear. In this study, among longevity drugs, including metformin, nicotinamide, resveratrol, rapamycin, and senolytics, we unexpectedly found that metformin, even at low doses, exacerbated experimentally-induced acute kidney injury (AKI) and increased mortality in mice. By single-cell transcriptomics analysis, we found that death of renal parenchymal cells together with an expansion of neutrophils occurs upon metformin treatment after AKI. We identified programmed cell death by ferroptosis in renal parenchymal cells and blocking ferroptosis, or depleting neutrophils protects against metformin-induced nephrotoxicity. Mechanistically, upon induction of AKI, ferroptosis in renal parenchymal cells initiates the migration of neutrophils to the site of injury via the surface receptor CXCR4-bound to metformin-iron-NGAL complex, which results in NETosis aggravated AKI. Finally, we demonstrated that reducing iron showed protective effects on kidney injury, which supports the notion that iron plays an important role in metformin-triggered AKI. Taken together, these findings delineate a novel mechanism underlying metformin-aggravated nephropathy and highlight the mechanistic relationship between iron, ferroptosis, and NETosis in the resulting AKI.
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Martynoside (MAR), a bioactive component in several well-known tonic traditional Chinese herbs, exhibits pro-hematopoietic activity during 5-fluorouracil (5-FU) treatment. However, the molecular target and the mechanism of MAR are poorly understood. Here, by adopting the mRNA display with a library of even-distribution (md-LED) method, we systematically examined MAR-protein interactions in vitro and identified the ribosomal protein L27a (RPL27A) as a key cellular target of MAR. Structural and mutational analysis confirmed the specific interaction between MAR and the exon 4,5-encoded region of RPL27A. MAR attenuated 5-FU-induced cytotoxicity in bone marrow nucleated cells, increased RPL27A protein stability, and reduced the ubiquitination of RPL27A at lys92 (K92) and lys94 (K94). Disruption of MAR binding at key residues of RPL27A completely abolished the MAR-induced stabilization. Furthermore, by integrating label-free quantitative ubiquitination proteomics, transcriptomics, and ribosome function assays, we revealed that MAR restored RPL27A protein levels and thus rescued ribosome biogenesis impaired by 5-FU. Specifically, MAR increased mature ribosomal RNA (rRNA) abundance, prevented ribosomal protein degradation, facilitated ribosome assembly, and maintained nucleolar integrity. Collectively, our findings characterize the target of a component of Chinese medicine, reveal the importance of ribosome biogenesis in hematopoiesis, and open up a new direction for improving hematopoiesis by targeting RPL27A.
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Bioensayo , Fluorouracilo , Fluorouracilo/farmacología , Células de la Médula Ósea , CafeínaRESUMEN
Acute kidney injury (AKI) is a global health problem that occurs in a variety of clinical settings. Despite some advances in supportive clinical care, no medicinal intervention has been demonstrated to reliably prevent AKI thus far. Therefore, it is highly necessary to investigate the pathophysiology and mechanisms involved in AKI for the discovery of therapeutics. In the current study, a robust change in the level of renal malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and elevated renal iron levels were observed in murine rhabdomyolysis-induced AKI (RM-AKI), which supports a pathogenic role of labile iron-mediated ferroptosis and provides a chance to utilize iron chelation for RM-AKI prevention. Given that the existing small molecule-based iron chelators did not show promising preventative effects against RM-AKI, we further designed and synthesized a new hydroxypyridinone-based iron chelator to potently inhibit labile iron-mediated ferroptosis. Lead compound AKI-02 was identified, which remarkably protected renal proximal tubular epithelial cells from ferroptosis as well as showed excellent iron chelation ability. Moreover, administration of AKI-02 led to renal function recovery, a result that was substantiated by the decreased contents of BUN and creatinine, as well as the reduced labile iron level and improved histopathology. Thus, our studies highlighted that targeting labile iron-mediated ferroptosis could provide therapeutic benefits against RM-AKI.
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Lesión Renal Aguda , Ferroptosis , Rabdomiólisis , Humanos , Ratones , Animales , Hierro/farmacología , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Rabdomiólisis/complicaciones , Rabdomiólisis/tratamiento farmacológico , Rabdomiólisis/inducido químicamente , Quelantes del Hierro/farmacología , Quelantes del Hierro/uso terapéuticoRESUMEN
The PB2 subunit of influenza virus polymerase has been demonstrated as a promising drug target for anti-influenza therapy. In this work, 7-azaindoles containing aza-ß3- or ß2,3 -amino acids were synthesized possessing a good binding affinity of PB2. The aza-ß-amino acid moieties with diverse size, shape, steric hindrance and configuration were investigated. Then a lead HAA-09 was validated, and the attached aza-ß3-amino acid moiety with acyclic tertiary carbon side chain well occupied in the key hydrophobic cavity of PB2_cap binding domain. Importantly, HAA-09 displays potent polymerase inhibition capacity, low cytotoxicity (selectivity index up to 2915) as well as robust anti-viral activity against A/WSN/33 (H1N1) virus and oseltamivir-resistant H275Y variant. Moreover, HAA-09 exhibited druggability with high plasma stability (t1/2 ≥ 12 h) and no obvious hERG inhibition (IC50 > 10 µM). Also, HAA-09 demonstrated a favorable safety profile when orally administrated in healthy mice at a high dose of 40 mg/kg QD for consecutive 3 days. Besides, in vivo therapeutic efficacy (85.7% survival observed at the day 15 post infection) was demonstrated when HAA-09 was administrated orally at 12.5 mg/kg BID starting 48 h post infection for 9 days. These data support that exploring the interactions between side chains on aza-ß3- or ß2,3 -amino acid moieties and hydrophobic pocket of PB2_cap binding domain is a potential medicinal chemistry strategy for developing potent PB2 inhibitors.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Animales , Ratones , Humanos , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Aminoácidos/farmacología , ARN Polimerasa Dependiente del ARN/metabolismoRESUMEN
Influenza is an acute respiratory infectious disease caused by influenza virus, leading to huge morbidity and mortality in humans worldwide. Despite the availability of antivirals in the clinic, the emergence of resistant strains calls for antivirals with novel mechanisms of action. The PB2 subunit of the influenza A virus polymerase is a promising target because of its vital role in the 'cap-snatching' mechanism. In this review, we summarize the technologies and medicinal chemistry strategies for hit identification, hit-to-lead and lead-to-candidate optimization, and current challenges in PB2 inhibitor development, as well as offering insights for the fight against drug resistance.
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Virus de la Influenza A , Gripe Humana , Antivirales/química , Antivirales/farmacología , Antivirales/uso terapéutico , Humanos , Gripe Humana/tratamiento farmacológico , ARN Polimerasa Dependiente del ARN , Proteínas ViralesRESUMEN
3,4-Hydroxypyridinone (3,4-HOPO) is a vital metal-chelating pharmacophore. However, the efficient synthesis has been a long-standing problem in drug development. In this paper, we report an efficient electrophilic activation of unprotected maltols via reversible covalent bonds between boronic acid and 3-hydroxyl/4-carbonyl. This one-pot reaction proceeded well on a gram scale in water with excellent efficiencies up to 97%. Moreover, taking advantage of the covalent interactions via the transient boronate, most of the previously tough amine donors, including sterically hindered amines, aromatic amines, and amino acids and amino alcohols, were well-tolerated. Importantly, the potential of this strategy in the pharmaceutical industry was highlighted with a successful synthesis of 3,4-HOPOs containing iron-chelating active pharmaceutical ingredients on 10 g and kilogram scales.
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Ácidos Borónicos/química , Piridonas/síntesis química , Pironas/química , Agua/química , Estructura Molecular , Piridonas/químicaRESUMEN
BACKGROUND: Marital status has been reported as an independent prognostic factor in various types of malignancies. However, the association between marital status and outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG) has not been fully explored. To this end, we aimed to investigate the effect of marital status on survival of AGE patients. METHODS: The Surveillance Epidemiology and End Results (SEER) database (2010-2015) was used to extract eligible patients with Siewert type II AEG. Meanwhile, propensity score matching was performed to match 1576 unmarried patients with 1576 married patients. Kaplan-Meier method with log-rank test was used to plot survival curves, univariate and multivariate Cox regression analyses were adopted to investigate the association of marital status with overall survival (OS) and cancer-specific survival (CSS) in AEG patients before and after matching. RESULTS: Multivariate analysis in the unmatched cohort revealed that marital status was an independent prognostic factor in patients with Siewert type II AEG. Unmarried patients had poorer OS (hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.12-1.29, P < .001) and poorer CSS (HR: 1.19, 95% CI: 1.10-1.29, P < .001) than married patients before matching. Additionally, widowed patients had the poorest OS (HR: 1.26, 95% CI: 1.11-1.44, P < .001) and CSS (HR: 1.29, 95% CI: 1.12-1.48, P < .001) compared with married patients. Furthermore, unmarried status remained as an independent prognostic for both OS (HR: 1.20, 95% CI: 1.10-1.31, P < .001) and CSS (HR: 1.18, 95% CI: 1.08-1.30, P < .001) in 1:1 propensity score-matched analysis. Subgroup analysis further revealed that OS and CSS rates were significantly higher in married patients than unmarried ones in most subgroups stratified by different variables. CONCLUSIONS: This population-based study identified that marital status was an independent prognostic indicator for AEG patients. Married AEG patients had better prognosis than their unmarried counterparts.
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Adenocarcinoma/mortalidad , Neoplasias Esofágicas/mortalidad , Estado Civil/estadística & datos numéricos , Anciano , Unión Esofagogástrica , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores de Riesgo , Programa de VERF , Tasa de SupervivenciaRESUMEN
A domino annulation/oxidation of heterocyclic ketene aminals (HKAs) and 2-aminochalcones has been developed for the selective synthesis of poly-substituted benzo[f]imidazo[2,1-a][2,7]naphthyridines and 3-azaheterocyclic substituted 2-arylquinolines. These reactions proceed well under mild conditions without any additives. Plausible mechanisms for such a polycyclic ring system assembly were also proposed. Moreover, benzo[f]imidazo[2,1-a][2,7]naphthyridine 3g displayed a fluorescence effect, demonstrating the potential applications in organic optical materials.
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NaftiridinasRESUMEN
The covalent binding nature of irreversible kinase inhibitors potentially increases the severity of "off-target" toxicity. Based on our continual strategy of chemically tuning the Michael addition acceptors, herein, we further explore the relationship among the electronic nature of Michael addition acceptors and EGFRT790M mutation selectivity as well as "off-target" toxicity balance. By perturbing the electronic nature of acrylamide moiety, compound 8a with a chloro-group at the α-position of the Michael addition acceptor was identified. It was found that 8a retained the excellent EGFR L858R/T790M potency (IC50 = 3.9 nM) and exhibited good anti-proliferative activities against the gefitinib-resistant NCI-H1975 cells (IC50 = 0.75 µM). Moreover, 8a displayed a significant EGFRWT selectivity and much weaker inhibitory activity against non-EGFR dependent SW620 cell and COS7. Preliminary study showed that 8a could arrest NCI-H1975 cells in G0/G1 phase. This work provides a promising chemical tuned strategy for balancing the mutant-EGFR potency and selectivity as well as "off-target" toxicity.
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Antineoplásicos/farmacología , Diseño de Fármacos , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Pirimidinas/síntesis química , Pirimidinas/química , Relación Estructura-ActividadAsunto(s)
Betacoronavirus , Reanimación Cardiopulmonar , Infecciones por Coronavirus/complicaciones , Paro Cardíaco/terapia , Control de Infecciones/organización & administración , Neumonía Viral/complicaciones , Algoritmos , COVID-19 , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Paro Cardíaco/virología , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , SARS-CoV-2RESUMEN
Deferoxamine, deferiprone, and deferasirox are used for the treatment of systemic iron overload, although they possess limitations due to lack of oral activity, lower efficacy, and side effects. These limitations led to a search for an orally active iron chelator with an improved therapeutic index. The lower efficacy of deferiprone is due to rapid glucuronidation, leading to the formation of a nonchelating metabolite. Here, we demonstrate that the influence of metabolism can be reduced by introducing a sacrificial site for glucuronidation. A log P-guided investigation of 20 hydroxpyridinones led to the identification of CN128. The Fe(III) affinity and metal selectivity of CN128 are similar to those of deferiprone, the log P value is more lipophilic, and its iron scavenging ability is superior. Overall, CN128 was demonstrated to be safe in a range of toxicity assessments and is now in clinical trials for the treatment of ß-thalassemia after regular blood transfusion.
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Quelantes del Hierro/administración & dosificación , Quelantes del Hierro/química , Sobrecarga de Hierro/tratamiento farmacológico , Piridonas/administración & dosificación , Piridonas/química , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Cobayas , Humanos , Sobrecarga de Hierro/sangre , Ratones , Ratas , Ratas Sprague-Dawley , Distribución Tisular/efectos de los fármacos , Distribución Tisular/fisiologíaRESUMEN
Despite the initial benefit demonstrated in clinical setting with ALK inhibitors, the challenging resistant mutants (F1174L, L1196M and G1202R) invariably developed. In this work, a series of 2-aminopyridine derivatives were designed and synthesized by C-5 position incorporation of a 2-pyridone moiety and bioisosteric replacement of the C-3 position linkers. Optimization of the 2-aminopyridine derivatives led to the identification of hit 18d displaying a significant growth inhibition against a variety of ALK-addicted cancer cells. Especially in the case of ALK-positive Karpas-299â¯cell, 18d exhibited excellent anti-proliferative potency with an IC50 value of about 40â¯nM. Moreover, 18d demonstrated encouraging activities against wild-type ALK (19â¯nM), ROS1 (2.3â¯nM) as well as challenging crizotinib-resistant ALKL1196M and ALKG1202R mutants with IC50 values of 45â¯nM and 22â¯nM, respectively. Additionally flow cytometric analysis indicates that 18d inhibited Karpas-299â¯cell viability via G1 phase arrest. Taken together, this work provided a promising ALK inhibitor to circumvent the clinical crizotinib-resistant mutants.
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Aminopiridinas , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Crizotinib/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores de Proteínas Quinasas , Piridonas/química , Aminopiridinas/síntesis química , Aminopiridinas/química , Aminopiridinas/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Humanos , Mutación , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
A one-pot approach has been developed for the synthesis of polysubstituted dibenzofuran acrylate derivatives from (E)-2-(2-nitrovinyl)phenols, sulfur ylides, and alkynes. This protocol was carried out under mild reaction condition without any precious catalysts in generally moderate to good yields. Additionally, a plausible mechanism for the transformation was proposed.
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Autofluorescing carboline-fluors were efficiently and rationally developed via a Pictet-Spengler involved one-pot multi-component reaction. The carboline-fluors demonstrate specific targeting towards the endoplasmic reticulum in living cells, and superior sensitivity to commercial ER-Trackers. Importantly, they were also successfully used to visualize changes in the ER during cell apoptosis and ER stress.
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Carbolinas/química , Retículo Endoplásmico/metabolismo , Colorantes Fluorescentes/química , Apoptosis , Supervivencia Celular , Células HeLa , Humanos , Imagen Individual de MoléculaRESUMEN
OBJECTIVE: To explore the resuscitation effect of active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR) on patients with cardiac arrest. METHODS: The patients with cardiac arrest admitted to emergency medical center of Hainan General Hospital from June 2014 to January 2016 were enrolled, who were satisfied with the indication of AACD-CPR and had no contraindication for AACD-CPR, and with 40-150 kg weight and over 16 years old. All of enrolled patients were given mechanical ventilation and conventional drug rescue. At the same time, AACD-CPR was performed with the active abdominal compression-decompression device, the rhythm of abdominal compression-decompression was 100 bmp and the ratio of compression time to lift time was 1:1, the pressure intensity was approximately 50 kg and the lifting intensity was approximately 30 kg. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation (SpO2) and blood lactic acid (Lac) were recorded before and after CPR, and restoration of spontaneous circulation (ROSC) were calculated. RESULTS: Forty-one patients with cardiac arrest were enrolled, with 22 males and 19 females, and the age between 15 years old and 89 years old, with an average (66.5±18.8) years old. The etiologies of cardiac arrest were followed: cardiogenic for 10 cases, non-cardiogenic for 18 cases, and unknown causes for 13 cases. The rate of ROSC in patients with AACD-CPR was 19.5% (8/41). During the resuscitation, the HR, MAP and SpO2 of those patients were significantly improved compared with those index suffering the cardiac arrest [HR (bmp): 67.0 (48.0, 105.0) vs. 0.0 (0.0, 11.5), MAP (mmHg, 1 mmHg = 0.133 kPa): 23.0 (16.0, 37.0) vs. 0.0 (0.0, 0.0), SpO2: 0.79 (0.45, 0.90) vs. 0.00 (0.00, 0.32), all P < 0.01]. During the resuscitation and 0.5 hours after ROSC, the indexes of the ROSC patients were significantly improved compared with those suffering cardiac arrest [HR (bmp): 88.5 (53.8, 105.0), 94.5 (72.5, 129.3) vs. 0.0 (0.0, 17.3); MAP (mmHg): 48.0 (41.3, 66.0), 54.0 (42.0, 72.5) vs. 0.0 (0.0, 0.0); SpO2: 0.74 (0.64, 0.80), 0.89 (0.81, 0.93) vs. 0.00 (0.00, 0.42); all P < 0.05]; in addition, the Lac of patients was not increased in the resuscitation and 0.5 hours after ROSC compared with the status before cardiopulmonary resuscitation (mmol/L: 4.44±1.66, 3.71±1.33 vs. 3.95±1.71, both P > 0.05). Besides, the ROSC rate of patients who suffered cardiac arrest before pre-hospital care or in emergency ward [11.1% (2/18)] were lower than those the patients who suffered cardiac arrest in emergency intensive care unit [EICU, 26.1% (6/23)]; while the cardiac arrest patients who didn't experienced AACD-CPR until they got complications such as thoracic rib fracture after standard cardiopulmonary resuscitation (STD-CPR), the ROSC rate of those patients in pre-hospital care or in emergency ward [10.0% (1/10)] were lower than the ROSC rate of the patients who suffered cardiac arrest in EICU [20.0% (4/20)], but there was no significant difference between the two groups (both P > 0.05). CONCLUSIONS: AACD-CPR is effective in the treatment of sudden cardiac arrest patients with contraindication of chest compression, and makes up for the deficiency of STD-CPR.