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BACKGROUND: Compared with intravascular ultrasound guidance, there is limited evidence for optical coherence tomography (OCT) guidance during primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients. AIMS: We investigated the role of OCT in guiding a reperfusion strategy and improving the long-term prognosis of STEMI patients. METHODS: All patients who were diagnosed with STEMI and who underwent pPCI between January 2017 and December 2020 were enrolled and divided into OCT-guided versus angiography-guided cohorts. They had routine follow-up for up to 5 years or until the time of the last known contact. All-cause death and cardiovascular death were designated as the primary and secondary endpoints, respectively. RESULTS: A total of 3,897 patients were enrolled: 2,696 (69.2%) with OCT guidance and 1,201 (30.8%) with angiographic guidance. Patients in the OCT-guided cohort were less often treated with stenting during pPCI (62.6% vs 80.2%; p<0.001). The 5-year cumulative rates of all-cause mortality and cardiovascular mortality in the OCT-guided cohort were 10.4% and 8.0%, respectively, significantly lower than in the angiography-guided cohort (19.0% and 14.1%; both log-rank p<0.001). All 4 multivariate models showed that OCT guidance could significantly reduce 5-year all-cause mortality (hazard ratio [HR] in model 4: 0.689, 95% confidence interval [CI]: 0.551-0.862) and cardiovascular mortality (HR in model 4: 0.692, 95% CI: 0.536-0.895). After propensity score matching, the benefits of OCT guidance were consistent in terms of all-cause mortality (HR: 0.707, 95% CI: 0.548-0.913) and cardiovascular mortality (HR: 0.709, 95% CI: 0.526-0.955). CONCLUSIONS: Compared with angiography alone, OCT guidance may change reperfusion strategies and lead to better long-term survival in STEMI patients undergoing pPCI. Findings in the current observational study should be further corroborated in randomised trials.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Tomografía de Coherencia Óptica , Humanos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/cirugía , Anciano , Estudios de Seguimiento , Resultado del Tratamiento , Angiografía CoronariaRESUMEN
This paper addresses the secure quasi-synchronization issue of heterogeneous complex networks (HCNs) under aperiodic denial-of-service (DoS) attacks with dynamic event-triggered impulsive scheme (ETIS). The heterogeneity of networks and the aperiodic DoS attacks, which hinder communication channels and synchronization goals, present challenges to the analysis of secure quasi-synchronization. The ETIS leverages impulsive control and dynamic event-triggered scheme (ETS) to handle the network heterogeneity and the DoS attacks. We give specific bounds on the attack duration and frequency that the network can endure, and obtain synchronization criteria that relate to event parameters, attack duration, attack frequency, and impulsive gain by the variation of parameter formula and recursive methods. Moreover, we prove that the dynamic ETS significantly reduces the controller updates, saves energy without sacrificing the system decay rate, and prevents the Zeno phenomenon. Finally, we validate our control scheme with a numerical example.
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Background: The biochemical and genetic characteristics of four very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD, are reported and discussed in this article. Methods: Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS), and high-throughput sequencing technology. New variants were analyzed for pathogenicity using bioinformatics software. Swiss-PdbViewer software was used to predict the effect of variants on the structure of the very-long-chain acyl-CoA dehydrogenase (VLCAD) protein. Result: A total of four VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10, and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and the neonatal period, respectively. Seven kinds of variants were detected, including four novel variants. Bioinformatics software revealed that the variants were harmful, and the Swiss-PdbViewer results suggest that variation affects protein conformation. Conclusion: This study identified four novel ACADVL gene variants. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of VLCADD.
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Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are life-threatening diseases. Neutrophil extracellular traps (NETs) play a key role in lung damage. Geranylgeranyl diphosphate synthase (GGPPS) is associated with the development of inflammatory diseases. We aimed to explore the role of GGPPS in NETs formation in ARDS/ALI. First, lung pathological changes in lipopolysaccharide (LPS)-induced ALI mice after myeloid-specific GGPPS deletion were evaluated. The level of NETs formation was analyzed by immunofluorescence, PicoGreen assay and Western blotting. Next, we determined the role of GGPPS in NETs formation and underlying mechanisms using immunofluorescence, flow cytometry, DCFH-DA, and SYTOX GREEN staining in vitro. Finally, the correlation between GGPPS expression incirculating neutrophils and dsDNA levels in plasma was evaluated. Myeloid-specific GGPPS deletion mice showed increased NETs deposition in lung tissue and aggravated histopathological damage of lung tissue. In vitro, GGPPS deficiency in neutrophils resulted in increased NETs formation by Phorbol-12-myristate-13-acetate (PMA), which was reversed by Geranylgeranyl diphosphate (GGPP). In addition, inhibitors blocking protein kinase C (PKC) and NADPH-oxidase (NOX) decreased NETs formation induced by GGPPS deletion. Importantly, GGPPS expression in circulating neutrophils was decreased in ARDS patients compared with the healthy control, and the level of dsDNA in plasma of ARDS patients was negatively correlated with the GGPPS expression. Taken together, GGPPS deficiency in neutrophils aggravates LPS-induced lung injury by promoting NETs formation via PKC/NOX signaling. Thus, neutrophil GGPPS could be a key therapeutic target for ARDS.
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The molecular motion trajectories of silicone rubber foam (SRF) at various vinyl silicone oil viscosities were studied via molecular dynamics (MD) simulation from the perspective of all atomic molecules. The influence of different viscosities of vinyl silicone oil on interaction, compatibility, and aggregation degree of molecules was determined based on the mean square displacement, diffusion coefficient, binding energy, solubility parameter, radial distribution function, and radius of gyration. The mechanical properties of the SRF were also experimentally verified. Results revealed that as the viscosity of vinyl silicone oil increased, the mean square displacement, fractional free volume, diffusion coefficient, and solubility parameter of the system decreased, whereas its larger radius of gyration increased. Moreover, the radial distribution function showed a weaker relative interaction between molecular chains. The calculated binding energy demonstrated that the system had better compatibility at a viscosity of 0.45 Pa s. This study provided a deeper insight into the relation between the viscosity of vinyl silicone oil and mechanical properties of the SRF. As the viscosity of vinyl silicone oil increased, the changing trend in MD simulation results of elastic modulus, shear modulus, bulk modulus, and Poisson's ratio was consistent with the experimental results. The MD simulations can promote theoretical predictions and scientific basis for the design of the SRF with desired performances.
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Pseudomonas aeruginosa is a common opportunistic pathogen. The potential efficacy of phage therapy has attracted the attention of researchers, but efficient gene-editing tools are lacking, limiting the study of their biological properties. Here, we designed a type V CRISPR-Cas12a system for the gene editing of P. aeruginosa phages. We first evaluated the active cutting function of the CRISPR-Cas12a system in vitro and discovered that it had a higher gene-cutting efficiency than the type II CRISPR-Cas9 system in three different P. aeruginosa phages. We also demonstrated the system's ability to precisely edit genes in Escherichia coli phages, Salmonella phages, and P. aeruginosa phages. Using the aforementioned strategies, non-essential P. aeruginosa phage genes can be efficiently deleted, resulting in a reduction of up to 5,215 bp (7.05%). Our study has provided a rapid, efficient, and time-saving tool that accelerates progress in phage engineering.
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Ataxin-2 (ATXN2) was originally discovered in the context of spinocerebellar ataxia type 2 (SCA2), but it has become a key player in various neurodegenerative diseases. This review delves into the multifaceted roles of ATXN2 in human diseases, revealing its diverse molecular and cellular pathways. The impact of ATXN2 on diseases extends beyond functional outcomes; it mainly interacts with various RNA-binding proteins (RBPs) to regulate different stages of post-transcriptional gene expression in diseases. With the progress of research, ATXN2 has also been found to play an important role in the development of various cancers, including breast cancer, gastric cancer, pancreatic cancer, colon cancer, and esophageal cancer. This comprehensive exploration underscores the crucial role of ATXN2 in the pathogenesis of diseases and warrants further investigation by the scientific community. By reviewing the latest discoveries on the regulatory functions of ATXN2 in diseases, this article helps us understand the complex molecular mechanisms of a series of human diseases related to this intriguing protein.
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Background: Radiotherapy has become a standard treatment for chest tumors, but a common complication of radiotherapy is radiation lung injury. Currently, there is still a lack of effective treatment for radiation lung injury. Methods: A mouse model of radioactive lung injury (RILI) was constructed and then treated with different cycles of hydrogen inhalation. Lung function tests were performed to detect changes in lung function.HE staining was used to detect pathological changes in lung tissue. Immunofluorescence staining was used to detect the polarization of macrophages in lung tissue. Immunohistochemistry was used to detect changes in cytokine expression in lung tissues. Western Blot was used to detect the expression of proteins related to the NF-κB signalling pathway. Results: Lung function test results showed that lung function decreased in the model group and improved in the treatment group.HE staining showed that inflammatory response was evident in the model group and decreased in the treatment group. Immunohistochemistry results showed that the expression of pro-inflammatory factors was significantly higher in the model group, and the expression of pro-inflammatory factors was significantly higher in the treatment group. The expression of pro-inflammatory factors in the treatment group was significantly lower than that in the model group, and the expression of anti-inflammatory factors in the treatment group was higher than that in the model group. Immunofluorescence showed that the expression of M1 subtype macrophages was up-regulated in the model group and down-regulated in the treatment group. The expression of M2 subtype macrophages was up-regulated in the treatment group relative to the model group. Western Blot showed that P-NF-κB p65/NF-κB p65 was significantly increased in the model group, and P-NF-κB p65/NF-κB p65 was decreased in the treatment group. Conclusion: Hydrogen therapy promotes macrophage polarization from M1 to M2 subtypes by inhibiting the NF-κB signalling pathway, thereby attenuating the inflammatory response to radiation lung injury.
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Lung cancer (LC) is regarded as a fatal cancer, and insulin-like growth factor 1 (IGF1) and its receptor (IGF1R) have been found to play a key role in regulating tumor glycolytic metabolism. The aim of this study is to investigate LC proliferation regulated by metabolite-mediated IGF1R lactylation. IGF1R was highly expressed in LC tissues and cells, and the effects of IGF1R on protein stability were inhibited by Lactate dehydrogenase A (LDHA) inhibition. Moreover, the tightness of IGF1R binding to IGF1 was also enhanced by exogenous lactic acid but suppressed by LDHA silencing, while cell viability and proliferation were promoted by over-expression of IGF1R. Exogenous lactic acid further exacerbated the effects of the IGF1R gene, while LDHA knocking down reduced the IGF1R-induced malignant behaviors. The IGF1R and exogenous lactic acid were also found to increase extracellular acidification rate (ECAR) and decrease oxygen consumption rate to regulate glycolysis, which was inhibited by LDHA deficiency in LC cells. The study concluded that IGF1R-mediated aggressive behaviors of LC cells were associated with higher levels of IGF1R lactylation. Moreover, lactic acid can improve the protein stability of the IGF1R oncogene, thus promoting glycolysis and generating lactic acid, forming a closed loop. Therefore, targeting IGF1R is envisaged to provide a novel strategy for developing therapeutic agents against LC.
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Dermatitis , Granuloma , Neutrófilos , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Granuloma/diagnóstico , Granuloma/etiología , Granuloma/patología , Femenino , Dermatitis/etiología , Dermatitis/diagnóstico , Dermatitis/patología , Neutrófilos/patología , Neutrófilos/inmunología , Resultado del Tratamiento , Biopsia , Piel/patología , Persona de Mediana EdadRESUMEN
Mutations in dental hypophosphatasia (HPP) have been reported less than those in other types of HPP because the symptoms are mild or the dental lesions are only partial manifestations of other types of HPP. In this case, we observe the clinical manifestation of dental hypoalkaline phosphatase by analyzing the genetic mutation and biochemical parameters in child. The clinical data of the child with odonto HPP were collected and analyzed. The blood samples of the child and his parents were sequenced and verified using Sanger through a specific probe capture and high-throughput second-generation sequencing technology. Major clinical manifestations in the patient were early loss of deciduous teeth, significantly lower serum alkaline phosphatase (ALP) levels, lower active vitamin D, and increased blood phosphorus, but no abnormality was observed in the oral X-ray. Two missense mutations-c.542C>T (p. ser181leu) and c.644 T> C (p.Ile215Thr)-were found in exon 6 of the ALPL gene from the father and mother, respectively. The clinical manifestations of odonto hypophosphatasia were early loss of deciduous teeth and significantly reduced serum ALP levels. Of 2 mutations-c.542C>T (p.ser181leu) and c.644 T> C (p.Ile215Thr)-in the ALPL gene, c.644 T> C (p.Ile215Thr) was a new mutation.
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OBJECTIVE: To determine the association between maternal blood glucose patterns throughout pregnancy and neonatal amino acids and acylcarnitines. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study involving 11,457 singleton pregnant women without preexisting diabetes from the Beijing Birth Cohort Study, along with their neonates born between July 2021 and October 2022 in Beijing, China. Distinct maternal glucose trajectories were identified using a latent class model based on blood glucose levels across the three trimesters, and their association with neonatal circulating metabolites, including 11 amino acids and 33 acylcarnitines, was examined, adjusting for potential confounding factors. RESULTS: Three distinct groups of maternal glucose trajectories were identified: consistent normoglycemia (n = 8,648), mid-to-late gestational hyperglycemia (n = 2,540), and early-onset hyperglycemia (n = 269). Mid-to-late gestational hyperglycemia was associated with decreased levels of amino acids (alanine, arginine, ornithine, and proline) involved in the arginine and proline metabolism and urea cycle pathway, as well as increased levels of C4DC+C5-OH and decreased level of C6DC and C10:1. Early-onset hyperglycemia was associated with elevated levels of free acylcarnitine and C4DC+C5-OH and a decreased level of C10:1, involved in the fatty acid oxidation pathway. However, these associations were primarily observed in male neonates rather than in female neonates. CONCLUSIONS: Our findings revealed a significant link between maternal glucose trajectories throughout pregnancy and neonatal arginine and proline metabolism, urea cycle pathway, and fatty acid oxidation pathway. These results highlight the importance of maintaining optimal blood glucose levels throughout pregnancy to promote healthy neonatal metabolic outcomes.
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Colorectal cancer is the second most prevalent and deadly cancer worldwide. The emergence of immune checkpoint therapy has provided a revolutionary strategy for the treatment of solid tumors. However, less than 5â¯% of colorectal cancer patients respond to immune checkpoint therapy. Thus, it is of great scientific significance to develop "potentiators" for immune checkpoint therapy. In this study, we found that knocking down different DNMT and HDAC isoforms could increase the expression of IFNs in colorectal cancer cells, which can enhance the effectiveness of immune checkpoint therapy. Therefore, the combined inhibition of DNMT and HDAC cloud synergistically enhance the effect of immunotherapy. We found that dual DNMT and HDAC inhibitors C02S could inhibit tumor growth in immunocompetent mice but not in immunocompromised nude mice, which indicates that C02S exerts its antitumor effects through the immune system. Mechanistically, C02S could increase the expression of ERVs, which generated the intracellular levels of dsRNA in tumor cells, and then promotes the expression of IFNs through the RIG-I/MDA5-MAVS signaling pathway. Moreover, C02S increased the immune infiltration of DCs and T cells in microenvironment, and enhanced the efficacy of anti-PD-L1 therapy in MC38 and CT26 mice model. These results confirmed that C02S can activate IFNs through the RIG-I/MDA5-MAVS signaling pathway, remodel the tumor immune microenvironment and enhance the efficacy of immune checkpoint therapy, which provides new evidence and solutions for the development of "potentiator" for colorectal cancer immunotherapy.
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Antígeno B7-H1 , Neoplasias Colorrectales , Inhibidores de Histona Desacetilasas , Inhibidores de Puntos de Control Inmunológico , Microambiente Tumoral , Animales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Humanos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ratones Desnudos , Línea Celular Tumoral , Ratones Endogámicos BALB C , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Femenino , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasas/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genéticaRESUMEN
Background: Sudden cardiac death (SCD) represents the most severe complication of hypertrophic cardiomyopathy (HCM). The risk stratification of SCD in patients with HCM remains a subject of ongoing debate, and the utility of left atrial (LA) and left ventricular (LV) myocardial strain for risk stratification of also SCD remains uncertain. Through use of feature-tracking cardiac magnetic resonance (FT-CMR), this study aimed to investigate the attenuation of LA and LV strain in HCM and to assess their predictive value in SCD. Methods: This retrospective and cross-sectional study included patients with HCM who underwent 3.0 T cardiac magnetic resonance (CMR) at a single institution. Feature-tracking strain analysis was conducted to obtain the strain rate (SR) and LV strain and to evaluate LV function. LA strain was measured during different functional phases including left atrial reservoir strain (LARS), LA conduit strain (LACS), and LA booster strain. All patients were categorized into high- and low-risk groups for SCD as defined by the 2020 American Heart Association/American College HCM implantable cardioverter defibrillator class of recommendation algorithm. Comparison between the two groups was conducted using the independent samples t test and the nonparametric rank sum test. Multivariate logistic regression analysis was performed to further identify the factors influencing SCD risk in HCM. Results: Compared with those in the low-risk group, patients in the high-risk group had lower left ventricular ejection fraction (LVEF), LV stroke volume index (LVSVI), and LA stroke volume index (LASVI) but a higher LV end-systolic volume index (LVESVI), LV maximum wall thickness, and late gadolinium enhancement (LGE) (P<0.001). LV strain, SR, and LA strain all showed significant differences between the high- and low-risk groups (LARS: P=0.04; LACS: P=0.02; all other P values <0.001). The LV global circumferential strain (LVGCS) had a strong negative correlation with LVEF in patients with HCM (r=-0.76; P<0.001). Multivariate analysis showed that LV global radial strain (LVGRS) and LARS could be used for categorizing the patients into the high-risk group [LVGRS: odds ratio (OR) =0.69; 95% confidence interval (CI): 0.55-0.87, P<0.001; LARS: OR =1.39; 95% CI: 1.02-1.90, P=0.03]. The combined LVGRS-LARS model exhibited a superior diagnostic value for high risk of SCD [area under the curve (AUC) =0.95; 95% CI: 0.90-1.00; P<0.001] compared to LARS alone (AUC =0.63; 95% CI: 0.51-0.76; P=0.04). Conclusions: LA and LV strain measured by FT-CMR can accurately identify those patients with HCM at a high risk of SCD. This approach may prove considerably value in guiding early therapeutic intervention with implantable cardioverter-defibrillators (ICDs) to prevent adverse clinical outcomes.
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Phage therapy is gaining momentum as an alternative to antibiotics in the treatment of salmonellosis caused by Salmonella. In this study, a novel Salmonella phage, vB_SalS_JNS02, was isolated successfully from poultry farms in Shandong, China. The biological characteristics of vB_SalS_JNS02 were analysed, which revealed a short latent period of approximately 10 min and a burst size of 110 PFU/cell. Moreover, vB_SalS_JNS02 exhibited remarkable stability across a wide pH range (pH 3-12) and temperatures ranging from 30 to 80°C. Genome sequencing analysis provided valuable insights into the genetic composition of vB_SalS_JNS02, which consists of a double-stranded DNA genome that spans 42,450 base pairs and has a G + C content of 49.4%. Of significant importance, the genomic sequence of vB_SalS_JNS02 did not contain any genes related to lysogenicity, virulence, or antibiotic resistance. The phage's efficacy was evaluated in a larval challenge study. Treatment with the phage resulted in increased survival of Galleria mellonella larvae (100, 70, and 85%) (MOI 0.1) in the prophylactic treatment, co-infection treatment, and remedial treatment experiments, respectively. Another in vivo experiment investigated the potential application of the phage in broiler chickens and revealed that a single oral dose of vB_SalS_JNS02 (108 PFU/mL, 100 µL/chick) administered 3 h after S. enteritidis oral administration provided effective protection. The introduction of bacteriophage not only enhances the production of secretory immunoglobulin A (sIgA), but also induces alterations in the composition of the gut microbial community. Phage therapy increases the relative abundance of beneficial bacteria, which helps to maintain intestinal barrier homeostasis. However, it is unable to fully restore the disrupted intestinal microbiome caused by S. enteritidis infection. Importantly, no significant adverse effects were observed in the animal subjects following oral administration of the phage, and our findings highlight vB_SalS_JNS02 is a hopeful candidate as a promising tool to target Salmonella infections in poultry.
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Pollos , Genoma Viral , Terapia de Fagos , Enfermedades de las Aves de Corral , Salmonelosis Animal , Fagos de Salmonella , Animales , Terapia de Fagos/veterinaria , Fagos de Salmonella/fisiología , Fagos de Salmonella/genética , Enfermedades de las Aves de Corral/terapia , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/virología , Salmonelosis Animal/terapia , Salmonelosis Animal/microbiología , Mariposas Nocturnas/virología , Mariposas Nocturnas/microbiología , China , Larva/microbiología , Larva/virologíaRESUMEN
Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine.
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Macaca fascicularis , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Cordón Umbilical , Animales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Humanos , Cordón Umbilical/citología , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Diferenciación Celular , FemeninoRESUMEN
Halobenzoquinones (HBQs), an emerging unregulated category of disinfection byproduct (DBP) in drinking water, have aroused an increasing concern over their potential health risks. However, the chronic toxicity of HBQs at environmentally relevant concentrations remains largely unknown. Here, the occurrence and concentrations of 13 HBQs in drinking water from a northern megacity in China were examined using ultrahigh performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-MS/MS). Four HBQs, including 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), 2,3,6-trichloro-1,4-benzoquinone (TriCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ), were detected beyond 50% occurrence frequency and at median concentrations from 4 to 50 ng/L. The chronic toxicity of these four HBQs to normal human colon and liver cells (FHC and THLE-2) was investigated at these concentrations. After 90 days of exposure, 2,5-DBBQ and 2,6-DCBQ induced the highest levels of oxidative stress and deoxyribonucleic acid (DNA) damage in colon and liver cells, respectively. Moreover, 2,5-DBBQ and 2,6-DCBQ were also found to induce epithelial-mesenchymal transition (EMT) in normal human liver cells via the extracellular signal regulated kinase (ERK) signaling pathway. Importantly, heating to 100 °C (boiling) was found to efficiently reduce the levels of these four HBQs in drinking water. These results suggested that environmentally relevant concentrations of HBQs could induce cytotoxicity and genotoxicity in normal human cells, and boiling is a highly efficient way of detoxification for HBQs.