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High hyperdiploid karyotype with ≥ 49 chromosomes (which will be referred to as HHK) is rare in acute myeloid leukemia (AML). The European leukemia network (ELN) excluded those harboring only numerical changes (with ≥ 3 chromosome gains) from CK and listed them in the intermediate risk group, while the UK National Cancer Research Institute Adult Leukaemia Working Group classification defined ≥ 4 unrelated chromosome abnormalities as the cutoff for a poorer prognosis. Controversies occurred among studies on the clinical outcome of HHK AML, and their molecular characteristics remained unstudied. We identified 1.31% (133/10,131) HHK cases within our center, among which 48 cases only had numerical changes (NUM), 42 had ELN defined adverse abnormalities (ADV) and 43 had other structural abnormalities (STR). Our study demonstrated that: (1) No statistical significance for overall survival (OS) was observed among three cytogenetic subgroups (NUM, STR and ADV) and HHK AML should be assigned to the adverse cytogenetic risk group. (2) The OS was significantly worse in HHK AML with ≥ 51 chromosomes compared with those with 49-50 chromosomes. (3) The clinical characteristics were similar between NUM and STR group compared to ADV group. The former two groups had higher white blood cell counts and blasts, lower platelet counts, and mutations associated with signaling, while the ADV group exhibited older age, higher chromosome counts, higher percentage of myelodysplastic syndrome (MDS) history, and a dominant TP53 mutation.
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Leucemia Mieloide Aguda , Mutación , Proteína p53 Supresora de Tumor , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/diagnóstico , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Proteína p53 Supresora de Tumor/genética , China/epidemiología , Pronóstico , Adolescente , Adulto Joven , Anciano de 80 o más Años , Aberraciones Cromosómicas , Cariotipo , Tasa de Supervivencia , CariotipificaciónRESUMEN
ABSTRACT: The traditional Chinese herbal prescription Buyang Huanwu decoction (BHD), effectively treats atherosclerosis. However, the mechanism of BHD in atherosclerosis remains unclear. We aimed to determine whether BHD could alleviate atherosclerosis by altering the microbiome-associated metabolic changes in atherosclerotic mice. An atherosclerotic model was established in apolipoprotein E-deficient mice fed high-fat diet, and BHD was administered through gavage for 12 weeks at 8.4 g/kg/d and 16.8 g/kg/d. The atherosclerotic plaque size, composition, serum lipid profile, and inflammatory cytokines, were assessed. Mechanistically, metabolomic and microbiota profiles were analyzed by liquid chromatography-mass spectrometry and 16S rRNA gene sequencing, respectively. Furthermore, intestinal microbiota and atherosclerosis-related metabolic parameters were correlated using Spearman analysis. Atherosclerotic mice treated with BHD exhibited reduced plaque area, aortic lumen occlusion, and lipid accumulation in the aortic root. Nine perturbed serum metabolites were significantly restored along with the relative abundance of microbiota at the family and genus levels but not at the phylum level. Gut microbiome improvement was strongly negatively correlated with improved metabolite levels. BHD treatment effectively slows the progression of atherosclerosis by regulating altered intestinal microbiota and perturbed metabolites.
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Apolipoproteínas E , Aterosclerosis , Dieta Alta en Grasa , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Aterosclerosis/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones , Masculino , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Ratones Endogámicos C57BL , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/patología , Ratones Noqueados , Ratones Noqueados para ApoERESUMEN
Background: Effective monitoring and management are crucial during long-term home noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic chronic obstructive pulmonary disease (COPD). This study investigated the benefit of Internet of Things (IOT)-based management of home NPPV. Methods: This multicenter, prospective, parallel-group, randomized controlled non-inferiority trial enrolled patients requiring long-term home NPPV for hypercapnic COPD. Patients were randomly assigned (1:1), via a computer-generated randomization sequence, to standard home management or IOT management based on telemonitoring of clinical and ventilator parameters over 12 months. The intervention was unblinded, but outcome assessment was blinded to management assignment. The primary outcome was the between-group comparison of the change in health-related quality of life, based on severe respiratory insufficiency questionnaire scores with a non-inferiority margin of -5. This study is registered with Chinese Clinical Trials Registry (No. ChiCTR1800019536). Findings: Overall, 148 patients (age: 72.7 ± 6.8 years; male: 85.8%; forced expiratory volume in 1 s: 0.7 ± 0.3 L; PaCO2: 66.4 ± 12.0 mmHg), recruited from 11 Chinese hospitals between January 24, 2019, and June 28, 2021, were randomly allocated to the intervention group (n = 73) or the control group (n = 75). At 12 months, the mean severe respiratory insufficiency questionnaire score was 56.5 in the intervention group and 50.0 in the control group (adjusted between-group difference: 6.26 [95% CI, 3.71-8.80]; P < 0.001), satisfying the hypothesis of non-inferiority. The 12-month risk of readmission was 34.3% in intervention group compared with 56.0% in the control group, adjusted hazard ratio of 0.56 (95% CI, 0.34-0.92; P = 0.023). No severe adverse events were reported. Interpretation: Among stable patients with hypercapnic COPD, using IOT-based management for home NPPV improved health-related quality of life and prolonged the time to readmission. Funding: Air Liquide Healthcare (Beijing) Co., Ltd.
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Background: Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer's disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods: MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl's/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results: It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion: JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Ratas , Ratones , Animales , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptor Toll-Like 4/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios/uso terapéuticoRESUMEN
Idiopathic hypereosinophilic syndrome (IHES) is a rare disease characterized by causeless persistent hypereosinophilia and eosinophilia-associated end-organ damage. Current treatment modalities don't meet the needs due to adverse events of steroids as first-line therapy and the limited efficacy of second-line treatments, underscoring the need for new therapeutic strategies. Here we presented two cases of IHES with different clinical manifestations that were both refractory to corticosteroids. Patient #1 experienced rashes, cough, pneumonia, and steroid-induced side effects. Patient #2 had severe gastrointestinal symptoms attributed to hypereosinophilia. They both had high levels of serum IgE, didn't respond well to second-line treatments of interferon-α (IFN-α) and imatinib, and Mepolizumab was not accessible. We then innovatively switched to Omalizumab, an anti-IgE monoclonal antibody approved for allergic asthma and chronic idiopathic urticaria. Patient #1 was treated with Omalizumab 600 mg per month for 20 months; his absolute eosinophil count (AEC) decreased significantly and has stabilized at around 1.0×109/L for 17 months, with complete relief from erythra and cough. Patient #2 recovered promptly from severe diarrhea with a sharp drop in AEC after 3 months of treatment with omalizumab at 600 mg per month. Therefore, we concluded that Omalizumab may be a seminal therapeutic strategy for IHES patients who are refractory to corticosteroids, whether as long-term management of AEC or as an urgent intervention to address severe symptoms caused by eosinophilia.
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Ginseng is regarded as the "king of herbs" in China, with its roots and rhizomes used as medicine, and it has a high medicinal value. In order to meet the market demand, the artificial cultivation of ginseng emerged, but different growth environments significantly affect the root morphology of garden ginseng. In this study, we used ginseng cultivated in deforested land (CF-CG) and ginseng cultivated in farmland (F-CG) as experimental materials. These two phenotypes were explored at the transcriptomic and metabolomic levels so as to understand the regulatory mechanism of taproot enlargement in garden ginseng. The results show that, compared with those of F-CG, the thickness of the main roots in CF-CG was increased by 70.5%, and the fresh weight of the taproots was increased by 305.4%. Sucrose, fructose and ginsenoside were significantly accumulated in CF-CG. During the enlargement of the taproots of CF-CG, genes related to starch and sucrose metabolism were significantly up-regulated, while genes related to lignin biosynthesis were significantly down-regulated. Auxin, gibberellin and abscisic acid synergistically regulated the enlargement of the taproots of the garden ginseng. In addition, as a sugar signaling molecule, T6P might act on the auxin synthesis gene ALDH2 to promote the synthesis of auxin and, thus, participate in the growth and development of garden ginseng roots. In summary, our study is conducive to clarifying the molecular regulation mechanism of taproot enlargement in garden ginseng, and it provides new insights for the further exploration of the morphogenesis of ginseng roots.
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Ginsenósidos , Panax , Transcriptoma , Raíces de Plantas/genética , Metabolómica/métodos , Sacarosa/metabolismoRESUMEN
Copper and copper alloys are commonly used in industry due to their excellent mechanical properties, making research on the corrosion resistance of copper of great significance. The corrosion inhibition properties of 2-imidazolidinone and allantoin for copper in 3.5 wt % NaCl were studied by weight loss and electrochemical tests. Changes in the density of the copper corrosion current and the impedance module indicated that 2-imidazolidinone and allantoin exhibited cathodic corrosion inhibitors and a valid protective effect. Meanwhile, the weight loss tests showed that the inhibition efficiency of 2-imidazolidinone and allantoin at 3 mM reached 98.94% and 97.82%, respectively. The surface physiochemical properties were qualitatively and quantitatively studied by using SEM-EDS, XPS, white light interferometry, and contact angle analysis. The interfacial adsorption behavior revealed by QCM, synchrotron radiation micro-infrared, and adsorption isotherm analysis indicated that both imidazole derivatives formed an effective and rigid physical adsorption film and obeyed the Langmuir adsorption model on copper, while both the mass and thickness of the adsorption film formed by 2-imidazolidinone were higher than those of allantoin. This study contributed to an in-depth understanding of the interfacial adsorption behavior and corrosion inhibition ability of 2-imidazolidinone and allantoin and provided guidelines for the design and development of novel heterocycles as potential corrosion inhibitors for copper in marine environments. In particular, copper was used as a corrosion inhibitor in seawater storage and transport equipment.
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Atypical chronic myeloid leukemia (CML) is a rare BCR::ABL1-negative hematopoietic stem cell disease characterized by granulocytic proliferation and granulocytic dysplasia. Due to both the challenging diagnosis and the rarity of atypical CML, comprehensive molecular annotation-based analyses of this disease population have been scarce, and it is currently difficult to identify the optimal treatment for atypical CML. To explore atypical CML genomic landscape and treatment options, we performed a systematic retrospective of the clinical data and outcomes of 31 atypical CML patients. We observed that the molecular landscape of atypical CML was highly heterogeneous, with multiple molecular events driving its pathogenesis. Patients with atypical CML had a low response to current therapies, with an overall response rate (ORR) of 33.3% to hypomethylating agent (HMA)-based therapy. The current treatment strategies, including hematopoietic stem cell transplantation (HSCT), did not improve overall survival (OS) in atypical CML patients, with a median survival of 20 months. Thus, the benefits from HSCT and candidates for HSCT remain to be further evaluated. Acute myeloid leukemia (AML)-like chemotherapy followed by bridging allogeneic HSCT may be an ideal regimen for suitable individuals. The large-scale and prospective clinical studies will help to address the dilemma.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa , Humanos , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/terapia , Estudios Retrospectivos , Estudios Prospectivos , Organización Mundial de la Salud , Biología MolecularRESUMEN
OBJECTIVE: To study the clinical efficacy of acetylcysteine combined with pirfenidone in patients with pulmonary fibrosis (PF). METHODS: A total of 114 PF patients admitted from January 2018 to January 2019 were retrospectively analyzed. Among them, 64 patients treated with acetylcysteine combined with pirfenidone were classified into a research group, and the other 50 treated with acetylcysteine combined with budesonide were assigned into a control group. The clinical efficacy and total effectiveness rate of the two groups were compared after 6 months of therapy. The quality of life (QoL) in the two groups before and after treatment was evaluatedusing Asthma Therapy Assessment Questionnaire for idiopathic pulmonary fibrosis patients (ATAQ-IPF). The 2-year survival of the two groups was compared. Additionally, the incidence of adverse reactions was compared between the two groups. The changes in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), inflammatory factors, and PF markers were compared between the two groups before and after therapy. RESULTS: There were no significant differences in clinical efficacy or total effectiveness rate (all P > 0.05), serum IL-4, INFγ or IL-6 expression (all P > 0.05), as well as FEV1 and FVC levels (all P > 0.05) after therapy between two groups. After therapy, the research group showed significantly lower PCIII and HA levels, lower ATAQ-IPF scores, and lower total incidence of adverse reactions than the control group (all P < 0.05). In addition, a higher 2-year survival rate was observed in the research group than in the control group (P=0.025). CONCLUSION: Acetylcysteine combined with pirfenidone can reduce adverse reactions and improve the QoL and survival time of patients.
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Clematis hexapetala Pall. (1776) is a traditional Chinese medicine belonging to the Ranunculaceae. In this study, the complete chloroplast genome was sequenced through Illumina platform, cp was circular DNA molecule of 159,538 bp in length with a typical quadripartite structure, consisting of four regions: two copies of inverted repeat region (IRs: 31,039 bp), a large single-copy (LSC: 79,333 bp) region, a small single-copy (SSC: 18,127 bp) region. The chloroplast genome encodes a total of 135 genes, including 91 CDS genes, 36 tRNA genes, 8 rRNA genes. Phylogenetic analysis based on complete genes shows that C. hexapetala closely related to C. taeguensis in the genus Clematis. This study improves our comprehension of the chloroplast genome and its phylogenetic relationships within Ranunculaceae.
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The complete chloroplast genome sequence of Clematis mandshurica Ruprecht (1867), a specie of the Ranunculaceae family, and its phylogenetic relationships with other species have been reported in this study. The complete chloroplast genome of C. mandshurica is 159,563 bp in length, including a large single-copy (LSC) region of 79,360 bp, a small single-copy (SSC) region of 18,121 bp, and a pair of identical inverted repeat regions (IRs) of 31,041 bp. The genome encodes a total of 132 genes, including 90 protein-coding genes, 34 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis reveals that C. mandshurica was found to be closest to Clematis taeguensis. The complete chloroplast genome of C. mandshurica contributes to a better understanding of phylogenetic relationships among Clematis species.
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In order to make key decisions more conveniently according to the massive data information obtained, a spatial data mining technology based on a genetic algorithm is proposed, which is combined with the k-means algorithm. The immune principle and adaptive genetic algorithm are introduced to optimize the traditional genetic algorithm, and the K-means, GK, and IGK algorithms are compared and analyzed. The results show that, in two different datasets, the objective functions obtained by the K-means algorithm are 94.05822 and 4.10373 (×106), respectively, while the objective functions obtained by the GK and IGK algorithms are 89.8619 and 3.9088 (×106), respectively. The difference between the three algorithms can also be reflected in the data comparison of the number of iterations. The number of iterations required for k-means to reach the optimal solution is 8.21 and 8.4, respectively, which is the most among the three algorithms, while the number of iterations required for IGK to reach the optimal solution is 5.84 and 4.9, respectively, which is the least. Although the time required for K-means is short, by comparison, the IGK algorithm we use can get the optimal solution in relatively less time.
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Minería de Datos , Multimedia , Algoritmos , Tecnología de la InformaciónRESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive impairment. The pathogenesis of AD is complex, and its susceptibility and development process are affected by age, genetic and epigenetic factors. Recent studies confirmed that gut microbiota (GM) might contribute to AD through a variety of pathways including hypothalamic pituitary adrenal axis and inflflammatory and immune processes. CM formula, herbs, and monomer enjoy unique advantages to treat and prevent AD. Hence, the purpose of this review is to outline the roles of GM and its core metabolites in the pathogenesis of AD. Research progress of CMs regarding the mechanisms of how they regulate GM to improve cognitive impairment of AD is also reviewed. The authors tried to explore new therapeutic strategies to AD based on the regulation of GM using CM.
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Enfermedad de Alzheimer , Microbioma Gastrointestinal , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Sistema Hipotálamo-Hipofisario , Medicina Tradicional China , Sistema Hipófiso-Suprarrenal , Encéfalo/patologíaRESUMEN
N6-methyladenosine (m6A) RNA modification can alter gene expression and function by regulating RNA splicing, stability, translocation, and translation. It is involved in various types of cancer. However, its role in gliomas is not well known. This study aimed to determine the prognostic value of the m6A RNA methylation regulator in gliomas and investigate the underlying mechanisms of the aberrant expression of m6A-related genes.mRNA expression profiles and clinical information of 448 glioma samples were obtained from The Cancer Genome Atlas and cBioportal. The expression of m6A-related genes in normal controls and low-grade glioma and glioblastoma was obtained from Gene Expression Profiling Interactive Analysis. Further, m6A-related gene expression and its relationship with prognosis were obtained through The Chinese Glioma Genome Atlas (CGGA). Multivariate Cox regression analyses were performed, and a nomogram was built with potential risk factors based on a multivariate Cox analysis to predict survival probability. Online tools such as Gene Set Enrichment Analysis, STRING, Cytoscape, and Molecular Complex Detection were applied for bioinformatics analysis and to investigate the underlying mechanisms of the aberrant expression of m6A-related genes. The multivariate Cox regression analysis found that higher expression levels of YTHDC2 and insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3, also called IMP3) were independent negative and positive prognostic factors for overall survival (OS), respectively. Data from the CGGA database showed that IGF2BP3 expression increased when the tumor grade increased. Receiver operating characteristic (ROC) curve was used to evaluate the predictive specificity and sensitivity. The area under the ROC curve indicated that the OS prediction was 0.92 (1-year) and 0.917 (3-years), indicating that m6A-related genes could predict patient survival. In addition, IGF2BP3 was closely related to the shorter survival period of patients. Copy number variation and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of IGF2BP3 in gliomas. Significantly altered genes were identified, and the protein-protein interaction network was constructed. Based on the data presented, our study identified several m6A-related genes, especially IGF2BP3, that could be potential prognostic biomarkers of gliomas. The study unveiled the potential regulatory mechanism of IGF2BP3 in gliomas.
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Myeloproliferative neoplasm (MPN) with PCM1-JAK2 rearrangement is a rare disease with poor prognosis and lacks uniform treatment guidelines. Several studies confirmed the efficacy of ruxolitinib in hematological malignancies with PCM1-JAK2 fusion, but the efficacy is variable. Here, we report two patients diagnosed with MPN with PCM1-JAK2 fusion who were treated with ruxolitinib-based regimen, including the first case of ruxolitinib combined with pegylated interferon (Peg-IFN), and we conduct a literature review. We found that ruxolitinib combined with Peg-IFN is an effective treatment option in the case of poor efficacy of ruxolitinib monotherapy.
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NLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE-/- mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE-/- mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE-/- mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1ß and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.
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Aterosclerosis/prevención & control , Furanos/farmacología , Indenos/farmacología , Macrófagos/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Piroptosis/efectos de los fármacos , Sulfonamidas/farmacología , Animales , Aterosclerosis/genética , Aterosclerosis/inmunología , Modelos Animales de Enfermedad , Furanos/uso terapéutico , Humanos , Indenos/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Noqueados para ApoE , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/inmunología , Sulfonamidas/uso terapéuticoRESUMEN
Odd-skipped related transcription factor 1 (OSR1) is implicated in various pathophysiologic processes, such as embryonic heart and urogenital formation, and functions as a tumour suppressor in diverse tumours. Regardless, the regulatory role and mechanism of OSR1 in acute myeloid leukaemia are scarce. Firstly, the CD34-positive blasts or the normal blasts were isolated from the plasma samples of acute myeloid leukaemia patients or healthy donors, respectively. Expression of OSR1 analysis by western blot and qRT-PCR showed that OSR1 was reduced in CD34-positive blasts and acute myeloid leukaemia cell lines. Secondly, acute myeloid leukaemia cell lines were transfected with pcDNA vector or shRNA for the over-expression or silence of OSR1, respectively. Functional assays demonstrated that ectopic expression of OSR1 decreased cell viability and repressed the proliferation of acute myeloid leukaemia cells, while promoted the cell apoptosis. Silence of OSR1 contributed to the proliferation of acute myeloid leukaemia cells and suppressed the cell apoptosis. Thirdly, over-expression of OSR1 decreased protein expression of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and JNK phosphorylation in the acute myeloid leukaemia cells. Ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of LGR5 and JNK phosphorylation. Lastly, ectopic expression of LGR5 attenuated OSR1 over-expression-induced decrease of cell viability and proliferation in acute myeloid leukaemia cells. In conclusion, OSR1 functioned as a tumour suppressor in acute myeloid leukaemia cells by inhibiting LGR5-mediated activation of JNK signalling.
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Leucemia Mieloide Aguda , Apoptosis/genética , Proliferación Celular/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Sistema de Señalización de MAP QuinasasRESUMEN
The complete chloroplast genome of A. heterotropoides var. mandshuricum reported herein was a circular DNA molecule of 160,262 bp in length. The typical quadripartite structure of the genome consisted of a pair of inverted repeats (IRs) of 27,262 bp separated by a large single-copy (LSC) region of 88,927 bp and a small single-copy region (SSC) of 16,811 bp. The overall GC content of the genome is 38.45%, with 36.7%, 33.1%, and 43.0% in LSC, SSC, IR regions, respectively. The cp genome encoded 125 genes, including 83 protein-coding genes, 34 tRNA genes, and 8 rRNA genes. 138 SSRs were identified in the genome. Phylogenetic anlysis showed the position of A. heterotropoides var. mandshuricum is closely related to A. heterotropoides.
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Background: Aging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated. Objective: To explore the underlying mechanism of how aging aggravates AS advancement. Methods: A young (five-week-old, YM) and aged group (32-week-old, OM) male apoE-/- mice with a high fat diet were used as models, and age-matched male wild-type C57BL/6J (WT) mice were used as controls. AS lesion size, serum lipid profile, cytokines, and gut microbiota-derived LPS were analyzed after 32 weeks of diet intervention. A correlation analysis between the 16S rRNA sequencing of the feces and serum metabolomics profiles was applied to examine the effect of their interactions on AS. Results: ApoE-/- mice developed severe atherosclerosis and inflammation in the aorta compared to the WT groups, and aged apoE-/- mice suffered from a more severe AS lesion than their younger counterparts and had low-grade systemic inflammation. Furthermore, increased levels of serum LPS, decreased levels of SCFAs production, as well as dysfunction of the ileal mucosal barrier were detected in aged mice compared with their younger counterparts. There were significant differences in the intestinal flora composition among the four groups, and harmful bacteria such as Lachnospiraceae_FCS020, Ruminococcaceae_UCG-009, Acetatifactor, Lachnoclostridium and Lactobacillus_gasseri were significantly increased in the aged apoE-/- mice compared with the other groups. Concurrently, metabolomics profiling revealed that components involved in the arachidonic acid (AA) metabolic pathway such as 20-HETE, PGF2α, arachidonic acid, and LTB4 were significantly higher in the aged AS group than in the other groups. This suggested that metabolic abnormalities and disorders of intestinal flora occurred in AS mice. Conclusions: Aging not only altered the gut microbiome community but also substantially disturbed metabolic conditions. Our results confirm that AA metabolism is associated with the imbalance of the intestinal flora in the AS lesions of aged mice. These findings may offer new insights regarding the role of gut flora disorders and its consequent metabolite changed in inflammaging during AS development.
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Aterosclerosis , Disbiosis , Animales , Ácido Araquidónico , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S/genéticaRESUMEN
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible and progressive airflow limitation and encompasses varying degrees of chronic obstructive bronchitis and emphysema. Our previous study showed that Forkhead box protein A2 (FOXA2) is involved in cigarette smoke (CS)-induced squamous metaplasia. However, the contribution of FOXA2 activity to CS-induced cellular senescence and lung inflammation remains largely unknown. Here, we report that FOXA2 was underexpressed in CS-exposed mouse lungs, and decreased expression of FOXA2 was related to cell senescence and inflammation. Subsequent investigation suggested that FOXA2 is an anti-senescence factor in lung that is involved in inflammatory responses. Furthermore, FOXA2 overexpression delayed CSE-induced senescence and inflammation, which correlated with regulation of the p38 and Erk1/2 MAPK signaling pathways by CSE-induced FOXA2 downregulation. Collectivelly, these findings reveal a protective role for FOXA2 as a regulator of cell senescence and inflammation during COPD.