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Tumor-associated macrophages constitute the main cell population in the tumor microenvironment and play a crucial role in regulating the microenvironment composition. Emerging evidence has revealed that the metabolic profile determines the tumor-associated macrophage phenotype. Tumor-associated macrophage function is highly dependent on glucose metabolism, with glycolysis being the major metabolic pathway. Recent reports have demonstrated diversity in glucose flux of tumor-associated macrophages and complex substance communication with cancer cells. However, how the glucose flux in tumor-associated macrophages connects with glycolysis to influence tumor progression and the tumor microenvironment is still obscure. Moreover, while the development of single-cell sequencing technology allows a clearer and more accurate classification of tumor-associated macrophages, the metabolic profiles of tumor-associated macrophages from the perspective of single-cell omics has not been well summarized. Here, we review the current state of knowledge on glucose metabolism in tumor-associated macrophages and summarize the metabolic profiles of different tumor-associated macrophage subtypes from the perspective of single-cell omics. Additionally, we describe the current strategies targeting glycolysis in tumor-associated macrophages for cancer therapy.
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Neoplasias , Macrófagos Asociados a Tumores , Humanos , Macrófagos/metabolismo , Neoplasias/patología , Glucólisis , Glucosa/metabolismo , Microambiente TumoralRESUMEN
Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients' miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF.
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MicroARNs , Progesterona , Femenino , Humanos , Fase Luteínica , Estudios Retrospectivos , MicroARNs/genética , Transferencia de Embrión , EndometrioRESUMEN
Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare, lysosomal disorder caused by mutations in a gene encoding iduronate-2-sulfatase (IDS). IDS deficiency results in an accumulation of glycosaminoglycans (GAGs) and secondary accumulations of other lipids in lysosomes. Symptoms of MPS II include a variety of soft and hard tissue problems, developmental delay, and deterioration of multiple organs. Enzyme replacement therapy is an approved treatment for MPS II, but fails to improve neuronal symptoms. Cell-based neuronal models of MPS II disease are needed for compound screening and drug development for the treatment of the neuronal symptoms in MPS II. In this study, three induced pluripotent stem cell (iPSC) lines were generated from three MPS II patient-derived dermal fibroblast cell lines that were differentiated into neural stem cells and neurons. The disease phenotypes were measured using immunofluorescence staining and Nile red dye staining. In addition, the therapeutic effects of recombinant human IDS enzyme, delta-tocopherol (DT), and hydroxypropyl-beta-cyclodextrin (HPBCD) were determined in the MPS II disease cells. Finally, the neural stem cells from two of the MPS II iPSC lines exhibited typical disease features including a deficiency of IDS activity, abnormal glycosaminoglycan storage, and secondary lipid accumulation. Enzyme replacement therapy partially rescued the disease phenotypes in these cells. DT showed a significant effect in reducing the secondary accumulation of lipids in the MPS II neural stem cells. In contrast, HPBCD displayed limited or no effect in these cells. Our data indicate that these MPS II cells can be used as a cell-based disease model to study disease pathogenesis, evaluate drug efficacy, and screen compounds for drug development.
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Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Mucopolisacaridosis II/tratamiento farmacológico , Mucopolisacaridosis II/metabolismo , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , 2-Hidroxipropil-beta-Ciclodextrina/uso terapéutico , Línea Celular , Terapia de Reemplazo Enzimático , Glicosaminoglicanos/metabolismo , Humanos , Iduronato Sulfatasa/uso terapéutico , Células Madre Pluripotentes Inducidas/patología , Metabolismo de los Lípidos/efectos de los fármacos , Modelos Neurológicos , Mucopolisacaridosis II/patología , Células-Madre Neurales/patología , Fenotipo , Proteínas Recombinantes/uso terapéutico , Tocoferoles/uso terapéuticoRESUMEN
PURPOSE: Tension pneumomediastinum is a rare and dangerous complication in children that can be fatal, and timely detection and treatment are critical. The aim of this study was to evaluate the safety and feasibility of computed tomography (CT) imaging-guided parasternal approach drainage for tension pneumomediastinum in children. METHODS: From June 2018 to February 2023, we consecutively enrolled 19 children with tension pneumomediastinum in our institution. A pigtail catheter was inserted into the anterior mediastinum by a CT imaging-guided parasternal approach. The catheter was connected to a negative-pressure water seal bottle to drain the pneumomediastinum. Clinical data and outcomes were summarized. RESULTS: The mean age was 3.1 ± 3.4 years, the mean weight was 15 ± 9.1 kg, the mean procedure time was 11.8 ± 2.4 min, and the drainage time was 6.7 ± 3.4 days. No major complications were identified, such as haemothorax, catheter displacement, or mediastinal infection. Effective drainage was obtained in all patients as assessed by comparing images and ventilatory parameters, and no additional surgical treatment was needed. There was no recurrence during the follow-up, which was more than 2 months. In our data, two children with COVID-19 were discharged from the hospital after effective drainage and other clinical treatment. CONCLUSION: CT-guided parasternal approach drainage is safe, minimally invasive, and effective for children with tension pneumomediastinum.
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Enfisema Mediastínico , Humanos , Niño , Preescolar , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/etiología , Enfisema Mediastínico/terapia , Tomografía Computarizada por Rayos X , Drenaje/efectos adversos , Catéteres/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Congenital diaphragmatic hernia (CDH) is a serious congenital malformation. Given the focus on improving survival in patients with "high-risk" CDH, it is possible that risk factors for low-risk patient with CDH may not be a concern. Left heart failure leads to adverse postoperative outcomes, including the need for extracorporeal membrane oxygenation (ECMO). The purpose of this study was to explore the causes of postoperative left heart failure in the low-risk group. METHODS: A retrospective study was conducted on newborns with congenital diaphragmatic hernia who were surgically treated in our hospital from January 2018 to March 2022. Children at low risk were divided into three groups according to the intraoperative repair conditions. Group A was defined as grade A defects repaired by direct suture. Group B was defined as a grade B defect repaired by mesh. Group C was a grade B defect repaired by high-tension suture. The age, gender, weight, perioperative echocardiography, and follow-up of the patients were statistically analyzed. The risk factors of left ventricular dysfunction after surgery in neonates with low-risk congenital diaphragmatic hernia were analyzed. RESULTS: A total of 52 low-risk children were included in the study. For children in the low-risk group, there was no significant difference between the low-tension repair group and the high-tension repair group in terms of operation time, thoracic tube drainage time, hospital stay, and long-term survival rate. Group A and group B showed good left ventricular function, while group C showed more decreased left ventricular EF and LVFS (LVEF 54.06 ± 10.28, LVFS 26.94 ± 5.83, p < 0.001). On the comparison of measures of left ventricular size, the mean values of left ventricular end-diastolic diameters(LVDD) and left ventricular end-systolic diameters (LVDS) were significantly difference in group C. Univariate analysis showed that LHR, o/e LHR, operation time, and high-tension repair were the influencing factors of left ventricular dysfunction. Multivariate logistic regression analysis identified risk factors for high-tension repair. Severe left heart dysfunction occurred in 2 patients with ECMO requirement in the high-tension repair group, although the difference was not significant. CONCLUSIONS: High-tension repair is a potential cause of left ventricular dysfunction in neonates with low-risk CDH.
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Hernias Diafragmáticas Congénitas , Disfunción Ventricular Izquierda , Niño , Humanos , Recién Nacido , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/cirugía , Estudios Retrospectivos , Factores de Riesgo , Ecocardiografía , Disfunción Ventricular Izquierda/etiologíaRESUMEN
PURPOSE: To evaluate the safety and efficacy of single-direction lobectomy for congenital pulmonary airway malformation (CPAM), especially with incomplete pulmonary fissure (IPF). METHODS: A total of 279 patients who underwent thoracoscopic lobectomy in our hospital from January 2019 to January 2022 were analyzed. Fifty-nine children were identified as the single-direction group, and the details of the surgical application are described. The degree of pulmonary fissure completeness was quantified intraoperatively. Propensity score matching was conducted and another 59 patients who underwent conventional lobectomy were matched as the control group. RESULTS: The median age of the patients was 4.9 months and the mean body weight was 7.7 kg. For patients with complete pulmonary fissure, there were no statistical differences between two groups in terms of operative time, intraoperative blood loss, length of chest tube, and hospital stay. For patients with IPF, there were statistical differences between the single-direction group and the control group in terms of operative times (89.10 ± 7.97 min vs. 97.41 ± 7.51 min, P < 0.001), intraoperative blood loss (10.86 ± 5.36 mL vs. 14.14 ± 6.56 mL P = 0.042), and postoperative complications (P = 0.035). CONCLUSION: IPF increases the operative difficulty of thoracoscopic lobectomy for CPAM, and the single-direction lobectomy technique is an effective and safe treatment for IPF.
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Malformación Adenomatoide Quística Congénita del Pulmón , Neoplasias Pulmonares , Humanos , Niño , Lactante , Pérdida de Sangre Quirúrgica , Puntaje de Propensión , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Pulmón/cirugía , Malformación Adenomatoide Quística Congénita del Pulmón/complicaciones , Malformación Adenomatoide Quística Congénita del Pulmón/cirugía , Neoplasias Pulmonares/cirugía , Tiempo de Internación , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
This study investigated miRNA and cytokine expression changes in peritoneal fluid samples of patients with advanced ovarian cancer (OVCA) after receiving hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS). We collected samples prior to HIPEC, immediately after HIPEC, and 24/48/72 h after CRS from a total of 6 patients. Cytokine levels were assessed using a multiplex cytokine array, and a miRNA PanelChip Analysis System was used for miRNA detection. Following HIPEC, miR-320a-3p, and miR-663-a were found to be immediately down-regulated but increased after 24 h. Further, significant upregulation post-HIPEC and sustained increases in expression were detected in six other miRNAs, including miR-1290, miR-1972, miR-1254, miR-483-5p, miR-574-3p, and miR-574-5p. We also found significantly increased expression of cytokines, including MCP-1, IL-6, IL-6sR, TIMP-1, RANTES, and G-CSF. The changing expression pattern throughout the study duration included a negative correlation in miR-320a-3p and miR-663-a to cytokines including RANTES, TIMP-1, and IL-6 but a positive correlation in miRNAs to cytokines including MCP-1, IL-6sR, and G-CSF. Our study found miRNAs and cytokines in the peritoneal fluid of OVCA patients demonstrated different expression characteristics following CRS and HIPEC. Both changes in expression demonstrated correlations, but the role of HIPEC remains unknown, prompting the need for research in the future.
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Hipertermia Inducida , MicroARNs , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Quimioterapia Intraperitoneal Hipertérmica , Quimiocina CCL5 , Inhibidor Tisular de Metaloproteinasa-1 , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genética , Líquido Ascítico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interleucina-6/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Citocinas/uso terapéutico , MicroARNs/genética , MicroARNs/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Terapia Combinada , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
We performed a single-centre retrospective analysis using data from databases that were prospectively maintained in our centre between January 2019 and September 2021. Patients were divided into two groups based on the degree of pulmonary fissure completeness (PFC), using the fissure development scoring system. Patients with grades 2 or 3 PFC were considered to have incomplete pulmonary fissures and were included in Group A, and patients with grades 0 and 1 were considered to have complete pulmonary fissures and were included in Group B. The differences in demographics, perioperative characteristics and clinic outcomes between the two groups were evaluated. Multivariate logistic regression analysis was performed. A total of 213 patients with congenital lung malformation (CLM) underwent video-assisted thoracoscopic lobectomy. There were 30 patients in Group A and 183 patients in Group B. Our data showed that compared with Group B, Group A had a higher incidence of complications, especially Clavien-Dindo grade II and grade III complications. The degree of PFC was significantly correlated with the length of chest tube drainage and postoperative hospital stay. Multivariate logistic regression analysis showed that the degree of PFC could be used to predict the incidence of postoperative complications.ConclusionsThe degree of PFC is a predictor of the incidence of complications after thoracoscopic lobectomy in children with CLM.
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Enfermedades Pulmonares , Neoplasias Pulmonares , Anomalías del Sistema Respiratorio , Niño , Humanos , Tiempo de Internación , Pulmón/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/cirugía , Neumonectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Anomalías del Sistema Respiratorio/complicaciones , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/efectos adversosRESUMEN
OBJECTIVE: To compare the difference between single-lung ventilation with bronchial occlusion and double-lung ventilation with carbon dioxide artificial pneumothorax for thoracoscopic lobectomy in infants. DESIGN: This was a retrospective study. SETTING: It was done in a teaching hospital. PARTICIPANTS: Between March 2017 and April 2020, a total of 72 infants underwent thoracoscopic lobectomy in the authors' hospital. INTERVENTIONS: Twenty-one patients received single-lung ventilation with bronchial occlusion, and 51 patients received carbon dioxide (CO2) artificial pneumothorax. MEASUREMENTS: The patient data included the endotracheal tube length, surgical exposure, intraoperative blood loss, and surgery duration. The mean arterial pressure (MAP), central venous pressure (CVP) and peak inspiratory pressure (Ppeak), partial pressure of oxygen in arterial blood (PaO2), and partial pressure of carbon dioxide in arterial blood (PaCO2) were measured at four points: time of bilateral lung ventilation before the thoracic surgery (T0), 10 minutes after the surgery started (T1), 30 minutes after the surgery started (T2), 60 minutes after the surgery started (T3), and 10 minutes after the surgery was over (T4). MAIN RESULTS: Compared to artificial pneumothorax, the bronchial occlusion group has the following advantages: the surgical exposure was better, the surgery duration was shorter, there was less intraoperative bleeding, and the duration of tracheal intubation was shorter (p < 0.05); bronchial occlusion resulted in a lower MAP but a higher CVP in infants at T1, T2, and T3 (p < 0.05) than the artificial pneumothorax group and resulted in a lower PaCO2 and higher PaO2 at T2, T3, and T4 (p < 0.05). There was no significant difference in Ppeak between the two groups (p > 0.05). CONCLUSION: Compared with CO2 artificial pneumothorax, bronchial occlusion is more favorable for thoracoscopic lobectomy in infants.
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Ventilación Unipulmonar , Neumotórax Artificial , Neumotórax , Procedimientos Quirúrgicos Torácicos , Humanos , Lactante , Intubación Intratraqueal , Respiración Artificial , Estudios RetrospectivosRESUMEN
Selective synthesis of 4-(sulfonyl)-methyl-1H-pyrazoles and (E)-4,5-dihydro-1H-pyrazoles from N-allenic sulfonylhydrazones with sulfonyl group migrations has been developed. A key feature of these reactions is that the migrations of the sulfonyl groups to different positions can be controlled by changing the Lewis acids.
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Química Orgánica/métodos , Hidrazonas/síntesis química , Pirazoles/síntesis química , Ciclización , Hidrazonas/química , Pirazoles/químicaRESUMEN
BACKGROUND: The identification of the intersegmental plane (ISP) is a crucial step in segmentectomy for children with congenital pulmonary airway malformation (CPAM) due to complex anatomical variations. However, there is very limited literature available on this aspect specifically for infant. In this study, we compared the intravenous indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) imaging method with the modified inflation-deflation method in terms of their perioperative characteristics and summarized our experience. METHODS: From June 2021 to November 2022, the data of 83 patients with CPAM who underwent segmentectomy by video-assisted thoracoscopic surgery were retrospectively reviewed. Twenty-eight patients underwent ICG-guided NIRF method, and 56 patients underwent the modified inflation-deflation method, characteristics and clinical outcomes were compared. RESULTS: The median age of the patients was 4.99 months (4.99 ± 1.51) with a mean body weight of 7.54 kg (7.54 ± 1.99). Both methods could accurately identify the ISP. The time taken to clearly display the ISP was shorter in ICG group than in the modified inflation-deflation group (0.18 ± 0.08 vs. 6.49 ± 1.67 min; P < 0.001), and the surgical duration (61.32 ± 14.28 vs. 88.18 ± 8.03 min; P < 0.001) were significantly shorter in the ICG group too. The two groups exhibited differences in the length of chest tube drainage (1.75 ± 1.24 vs. 2.36 ± 1.54 days; P = 0.072) and the length of hospital stay (4.61 ± 1.75 vs. 5.20 ± 3.07 days; P = 0.078), however, the differences were not statistically significant. There were no significant differences between the two groups in the blood lost and postoperative complications. At a follow-up of more than 1 year after operation, all patients had recovered well without recurrence. CONCLUSIONS: According to our experience, the ICG-guided NIRF method was safe and feasible for infants during thoracoscopic segmentectomy, it can quickly display the ISP and shorten the surgical duration compared with the modified inflation-deflation method.
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Verde de Indocianina , Imagen Óptica , Neumonectomía , Cirugía Torácica Asistida por Video , Humanos , Lactante , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/métodos , Femenino , Masculino , Neumonectomía/métodos , Imagen Óptica/métodos , Malformación Adenomatoide Quística Congénita del Pulmón/cirugía , Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico por imagen , Espectroscopía Infrarroja Corta/métodos , Colorantes/administración & dosificaciónRESUMEN
Using the linear approach to design a controller is still prevalent. The state feedback control (SFC) is applied in this paper to improve the dynamic response of permanent magnet synchronous machine (PMSM) speed regulation systems. First, a third-order augmented system is constructed for the reason that a higher-order system has better disturbance rejection. It can be found through analysis and comparison that the order of the proposed speed controller is increased. The parameters of SFC are selected by utilizing the linear quadratic regulator (LQR), and the influence of matrix Q on dynamic performance is detailed through the Bode diagram. Additionally, considering parametric uncertainties and unmodeled dynamics, a disturbance observer (DOB) using the Luenberger observer is designed to further boost anti-disturbance performance. Finally, plenty of experimental results verify the effectiveness of the proposed methods.
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This paper proposes a composite sliding mode control (SMC) to optimize the tracking performance and the anti-disturbance performance of permanent magnet synchronous machine (PMSM) speed regulation systems. The differential term in the control law can magnify the measurement noise, resulting in more discontinuity. To filter out the high frequency noise and make the control law smoother, the first-order differentiator (FOD) is employed to estimate the speed error and its derivative. Since the feedforward compensation can improve the robustness of the system, a disturbance observer (DOB) based on the sliding mode observer (SMO) is designed to reinforce the dynamic performance under disturbance variation. Under the effect of the feedforward compensation, chattering can be further weakened by decreasing the switching gain appropriately. Finally, the effectiveness of the proposed methods is confirmed by various experimental results.
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BACKGROUND: Video-assisted thoracoscopic surgery is a commonly used procedure for treating congenital pulmonary airway malformation (CPAM) in infants, particularly when performing segmentectomy for segmental lesions. An innovative technique employing near-infrared fluorescence (NIRF) imaging with intravenous indocyanine green (ICG) has been utilized to delineate the intersegmental demarcation during surgery. However, no previous reports have investigated this method's application, specifically in infants. The primary aim of this study was to assess the safety and efficacy of the NIRF imaging with ICG approach in this context. METHODS: Between January 2021 and April 2022, a total of 19 consecutive segmentectomies were conducted using the NIRF imaging with ICG method to precisely identify the intersegmental plane. The results were concurrently compared with those obtained using the modified inflation-deflation technique. Comprehensive imaging and clinical data were gathered and analyzed to assess the safety and accuracy of the NIRF imaging with ICG approach. RESULTS: The study involved infants with a median age of 5.12 months (mean body weight of 8.08 g). All segmentectomies were performed successfully without any ICG-related complications. The mean operating time for the surgeries was 88.47 ± 7.94 minutes. Notably, no intraoperative conversions or significant complications were observed in any of the patients. The average hospital stay after surgery was 4.0 ± 0.82 days. During the follow-up period, extending beyond 1-year of postoperation, all patients exhibited excellent recovery with no cases of recurrence. CONCLUSIONS: Based on our experience, the NIRF imaging with intravenous ICG method proved to be both safe and effective when performing segmentectomy for infants with CPAM. Low doses of ICG did not hinder the accurate identification of the intersegmental plane.
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BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.
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Multisystem inflammatory syndrome in children (MIS-C) is an imperative pediatric inflammatory condition closely linked to COVID-19, which garners substantial attention since the onset of the pandemic. Like Kawasaki illness, this condition is characterized by an overactive immune response, leading to symptoms including pyrexia, cardiac and renal complications. To elucidate the pathogenesis of MIS-C and identify potential biomarkers, we conducted an extensive examination of specific cytokines (IL-6, IL-1ß, IL-6R, IL-10, and TNF-α) and microRNA (miRNA) expression profiles at various intervals (ranging from 3 to 20 days) in the peripheral blood sample of a severely affected MIS-C patient. Our investigation revealed a gradual decline in circulating levels of IL-6, IL-1ß, IL-10, and TNF-α following intravenous immune globulin (IVIG) therapy. Notably, IL-6 exhibited a significant reduction from 74.30 to 1.49 pg./mL, while IL-6R levels remained consistently stable throughout the disease course. Furthermore, we observed an inverse correlation between the expression of hsa-miR-596 and hsa-miR-224-5p and the aforementioned cytokines. Our findings underscore a robust association between blood cytokine and miRNA concentrations and the severity of MIS-C. These insights enhance our understanding of the genetic regulatory mechanisms implicated in MIS-C pathogenesis, offering potential avenues for early biomarker detection and therapy monitoring through miRNA analysis.
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The ultimate aim of nuclear reprogramming is to provide stem cells or differentiated cells from unrelated cell types as a cell source for regenerative medicine. A popular route towards this is transcription factor induction, and an alternative way is an original procedure of transplanting a single somatic cell nucleus to an unfertilized egg. A third route is to transplant hundreds of cell nuclei into the germinal vesicle (GV) of a non-dividing Amphibian meiotic oocyte, which leads to the activation of silent genes in 24â h and robustly induces a totipotency-like state in almost all transplanted cells. We apply this third route for potential therapeutic use and describe a procedure by which the differentiated states of cells can be reversed so that totipotency and pluripotency gene expression are regained. Differentiated cells are exposed to GV extracts and are reprogrammed to form embryoid bodies, which shows the maintenance of stemness and could be induced to follow new directions of differentiation. We conclude that much of the reprogramming effect of eggs is already present in meiotic oocytes and does not require cell division or selection of dividing cells. Reprogrammed cells by oocytes could serve as replacements for defective adult cells in humans.
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Oocitos , Trasplante de Células Madre , Adulto , Animales , Humanos , Núcleo Celular , Anfibios , Reprogramación Celular , MamíferosRESUMEN
A one-pot synthesis of 3,4,5- and 1,3,5-pyrazoles from tertiary propargylic alcohols and para-tolylsulfonohydrazide has been accomplished. The pyrazoles are formed through a four-step cascade sequence, including FeCl3 -catalyzed propargylic substitution, aza-Meyer-Schuster rearrangement, base-mediated 6π electrocyclization, and thermal [1,5] sigmatropic shift. In this reaction, the 3,4,5- and 1,3,5-pyrazoles are produced selectively according to different substituents in the starting alcohols.
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Alquinos/química , Propanoles/química , Pirazoles/síntesis química , Alcoholes/química , Catálisis , Estructura Molecular , Pirazoles/química , EstereoisomerismoRESUMEN
BACKGROUND: Sorafenib is the most widely used systematic therapy drug for treating unresectable Hepatocellular Carcinoma (HCC) but showed dissatisfactory efficacy in clinical applications. OBJECTIVE: We conducted a combinational quantitative small-molecule high-throughput screening (qHTS) to identify potential candidates to enhance the treatment effectiveness of sorafenib. METHODS: First, using a Hep3B human HCC cell line, 7051 approved drugs and bioactive compounds were screened, then the primary hits were tested with/without 0.5 µM sorafenib respectively, the compound has the half maximal Inhibitory Concentration (IC50) shift value greater than 1.5 was thought to have the synergistic effect with sorafenib. Furthermore, the MEK inhibitor PD198306 was selected for the further mechanistic study. RESULTS: 12 effective compounds were identified, including kinase inhibitors targeting MEK, AURKB, CAMK, ROCK2, BRAF, PI3K, AKT and EGFR, and a µ-opioid receptor agonist and a Ltype calcium channel blocker. The mechanistic research of the combination of sorafenib plus PD198306 showed that the two compounds synergistically inhibited MEK-ERK and mTORC1- 4EBP1 and induced apoptosis in HCC cells, which can be attributed to the transcriptional and posttranslational regulation of MCL-1 and BIM. CONCLUSION: Small-molecule qHTS identifies MEK inhibitor PD1938306 as a potent sorafenib enhancer, together with several novel combination strategies that are valuable for further studies.