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Acute myeloid leukemia (AML) is a fatal hematologic disease. Diagnosis and proper treatment are important for prognosis. High myeloperoxidase (MPO) expression AML cells are characterized with high levels of hypochlorite (ClO-). In this study, we report a ClO--activated theranostic agent, FNC, for AML therapy. FNC responds to ClO- specifically in high MPO expression AML cells, resulting in bright fluorescence and chlorambucil release. FNC can be used to quickly distinguish high MPO expression AML cells from other cells, including low MPO expression leukemia and activated inflammatory cells. FNC exhibits selective toxicity to highly MPO expression AML cells and can efficiently inhibit tumor growth. Meanwhile, FNC can be used to indicate differentiation through the detection of ClO-.
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Detailed data on safety associated with drug-drug interactions (DDIs) between Linezolid (LZD) and other antibiotics are limited. The aim of this study was to investigate the safety signals related to these DDIs and to provide a reference for clinically related adverse drug event monitoring. Adverse event (AE) information from 1 January 2004 to 16 June 2022 of the target antibiotics including LZD using alone or in combination with LZD was extracted from the OpenVigil FDA data platform for safety signal analysis. The combined risk ratio model, reporting ratio method, Ω shrinkage measure model, and chi-square statistics model were used to analyze the safety signals related to DDIs. Meanwhile, we evaluated the correlation and the influence of sex and age between the drug(s) and the target AE detected. There were 18991 AEs related to LZD. There were 2293, 1726, 4449, 821, 2431, 1053, and 463 AE reports when LZD was combined with amikacin, voriconazole, meropenem, clarithromycin, levofloxacin, piperacillin-tazobactam, and azithromycin, respectively. Except for azithromycin, there were positive safety signals related to DDIs between LZD and these antibiotics. These DDIs might influence the incidence of 13, 16, 7, 7, 6, and 15 types of AEs, respectively, and is associated with higher reporting rates of AEs compared with use alone. Moreover, sex and age might influence the occurrence of AEs. We found that the combinations of LZD and other antibiotics are related to multiple AEs, such as hepatotoxicity, drug resistance and electrocardiogram QT prolonged, but further research is still required to investigate their underlying mechanisms. This study can provide a new reference for the safety monitoring of LZD combined with other antibiotics in clinical practice.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Antibacterianos , Interacciones Farmacológicas , Linezolid , Humanos , Linezolid/efectos adversos , Masculino , Antibacterianos/efectos adversos , Femenino , Persona de Mediana Edad , Adulto , Anciano , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Adolescente , Adulto Joven , Niño , Preescolar , Lactante , Anciano de 80 o más Años , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Monitoreo de Drogas/métodos , Factores de Edad , Recién Nacido , Factores SexualesRESUMEN
High-entropy oxides (HEOs), featuring infinite chemical composition and exceptional physicochemical properties, are attracting much attention. The configurational entropy caused by a component disorder of HEOs is popularly believed to be the main driving force for thermal stability, while the role of vibrational entropy in the thermodynamic landscape has been neglected. In this study, we systematically investigated the vibrational entropy of multicomponent rutile oxides (including Fe0.5Ta0.5O2, Fe0.333Ti0.333Ta0.333O2, Fe0.25Ti0.25Ta0.25Sn0.25O2, and Fe0.21Ti0.21Ta0.21Sn0.21Ge0.16O2) by precise heat capacity measurements. It is found that vibrational entropy gradually decreases with increasing component disorder, beyond what one could expect from an equilibrium thermodynamics perspective. Moreover, all multicomponent rutile oxides exhibit a positive excess vibrational entropy at 298.15 K. Upon examinations of configuration disorder, size mismatch, phase transition, and polyhedral distortions, we demonstrate that the excess vibrational entropy plays a pivotal role in lowering the crystallization temperature of multicomponent rutile oxides. These findings represent the first experimental confirmation of the role of lattice vibrations in the thermodynamic landscape of rutile HEOs. In particular, vibrational entropy could serve as a novel descriptor to guide the predictive design of multicomponent oxide materials.
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It is a long-standing scientific controversy to achieve anti-Kasha-type multiple emissions by tuning the structures at a molecular level. Although it is known that some conjugated structures have excitation-dependent multiple emissions, no all-benzenoid molecules have yet been reported, the emissions of which originate from different excited states. Herein, we report the design of two symmetry-breaking heterogeneous carbon bisnanohoops that in solution become multiple fluorescent emitters with unusual anti-Kasha characteristics. This phenomenon can be spectroscopically and theoretically explained and will find applications in a wide range of sensing and imaging technologies.
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Heat capacity is a fundamental thermodynamic property of a substance. Although heat capacity values and related thermodynamic functions are available for many materials, low-temperature heat capacity measurements, especially for novel materials, can still provide valuable insights for research in physics, chemistry, thermodynamics, and other fields. Reliable low-temperature heat capacity data are typically measured using classical adiabatic calorimeters, which use liquid helium as the refrigerant to provide a cryogenic environment for heat capacity measurements. However, liquid helium is not only expensive but also not easy to obtain, which greatly limits the application of adiabatic calorimetry. In this work, an accurate adiabatic calorimeter equipped with a Gifford-MacMahon refrigerator was designed and constructed for measuring the heat capacity of condensed matter in the temperature range from 4 to 100 K. The Gifford-MacMahon refrigerator was utilized to provide a stable liquid helium-free cryogenic environment. A simple mechanical thermal switch assembly was designed to facilitate switching between the refrigeration mode and the adiabatic measurement mode of the calorimeter. Based on the measurement results of standard reference materials, the optimized repeatability and accuracy of heat capacity measurements were determined to be within 0.8% and 1.5%, respectively. The heat capacity of α-Fe2O3 nanoparticles was also investigated with this device. Furthermore, this adiabatic calorimeter only requires electricity to operate in the liquid helium temperature range, which may significantly advance the research on low-temperature heat capacity based on adiabatic calorimetry.
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Keratin 80 (KRT80) is a filament protein that makes up one of the major structural fibers of epithelial cells, and involved in cell differentiation and epithelial barrier integrity. Here, KRT80 mRNA expression was found to be higher in esophageal cancer than normal epithelium by RT-PCR and bioinformatics analysis (p < .05), opposite to KRT80 methylation (p < .05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in esophageal cancer (p < .05). KRT80 mRNA expression was positively correlated with the differentiation, infiltration of immune cells, and poor prognosis of esophageal cancer (p < .05). KRT80 mRNA expression was positively linked to no infiltration of immune cells, the short survival time of esophageal cancers (p < .05). The differential genes of KRT80 mRNA were involved in fat digestion and metabolism, peptidase inhibitor, and intermediate filament, desosome, keratinocyte differentiation, epidermis development, keratinization, ECM regulator, complement cascade, metabolism of vitamins and co-factor (p < .05). KRT-80-related genes were classified into endocytosis, cell adhesion molecule binding, cadherin binding, cell-cell junction, cell leading edge, epidermal cell differentiation and development, T cell differentiation and receptor complex, plasma membrane receptor complex, external side of plasma membrane, metabolism of amino acids and catabolism of small molecules, and so forth (p < .05). KRT80 knockdown suppressed anti-apoptosis, anti-pyroptosis, migration, invasion, chemoresistance, and lipogenesis in esophageal cancer cells (p < .05), while ACC1 and ACLY overexpression reversed the inhibitory effects of KRT80 on lipogenesis and chemoresistance. These findings indicated that up-regulated expression of KRT80 might be involved in esophageal carcinogenesis and subsequent progression, aggravate aggressive phenotypes, and induced chemoresistance by lipid droplet assembly and ACC1- and ACLY-mediated lipogenesis.
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Resistencia a Antineoplásicos , Neoplasias Esofágicas , Queratinas Tipo II , Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Resistencia a Antineoplásicos/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica , Lipogénesis/genética , ARN Mensajero , Queratinas Tipo II/genética , Queratinas Tipo II/metabolismoRESUMEN
BACKGROUND AND AIMS: Deregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) influences intestinal immune cells and leads to intestinal inflammation. We studied the function of fat mass-and obesity-associated protein (FTO), one of the m6A demethylases, in patients with ulcerative colitis (UC). METHODS: We analysed colon tissues of Ftoflox/flox; Villin-cre mice and their Ftoflox/flox littermates with dextran sulfate sodium (DSS) using real-time PCR and 16s rRNA sequencing. RNA and methylated RNA immunoprecipitation sequencing were used to analyse immunocytes and IECs. Macrophages were treated with conditioned medium of FTO-knockdown MODE-K cells or sphingosine-1-phosphate (S1P) and analysed for gene expression. Liquid chromatograph mass spectrometry identified C16-ceramide. RESULTS: FTO downregulation was identified in our in-house cohort and external cohorts of UC patients. Dysbiosis of gut microbiota, increased infiltration of proinflammatory macrophages, and enhanced differentiation of Th17 cells were observed in Ftoflox/flox;Villin-cre mice under DSS treatment. FTO deficiency resulted in an increase in m6A modification and a decrease in mRNA stability of CerS6, the gene encoding ceramide synthetase, leading to the downregulation of CerS6 and the accumulation of S1P in IECs. Subsequentially, the secretion of S1P by IECs triggered proinflammatory macrophages to secrete serum amyloid A protein 1/3, ultimately inducing Th17 cell differentiation. In addition, through bioinformatic analysis and experimental validation, we identified UC patients with lower FTO expression might respond better to vedolizumab treatment. CONCLUSIONS: FTO downregulation promoted UC by decreasing CerS6 expression, leading to increased S1P accumulation in IECs and aggravating colitis via m6A-dependent mechanisms. Lower FTO expression in UC patients may enhance their response to vedolizumab treatment.
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Colitis Ulcerosa , Colitis , Humanos , Animales , Ratones , Colitis Ulcerosa/metabolismo , ARN Ribosómico 16S/metabolismo , Mucosa Intestinal/metabolismo , Colitis/inducido químicamente , Colitis/genética , Colon/metabolismo , Esfingolípidos/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismoRESUMEN
This paper delves into the problem of correlated time-series forecasting in practical applications, an area of growing interest in a multitude of fields such as stock price prediction and traffic demand analysis. Current methodologies primarily represent data using conventional graph structures, yet these fail to capture intricate structures with non-pairwise relationships. To address this challenge, we adopt dynamic hypergraphs in this study to better illustrate complex interactions, and introduce a novel hypergraph neural network model named CHNN for correlated time series forecasting. In more detail, CHNN leverages both semantic and topological similarities via an interaction model and hypergraph diffusion process, thereby constructing comprehensive collaborative correlation scores that effectively guide spatial message propagation. In addition, it incorporates short-term temporal information to generate efficient spatio-temporal feature maps. Lastly, a long-term temporal module is proposed to generate future predictions utilizing both temporal attention and a gated recurrent network. Comprehensive experiments conducted on four real-world datasets, i.e., Tiingo, Stocktwits, NYC-Taxi, and Social Network demonstrate that the proposed CHNN markedly outperforms a range of benchmark methods.
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AIM: In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular dementia (VD) rat models. BACKGROUND: VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear. OBJECTIVE: The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD. METHODS: The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Student's t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05. RESULTS: AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway. CONCLUSION: This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.
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Demencia Vascular , Enfermedades Neurodegenerativas , Ratas , Animales , Ratones , Demencia Vascular/tratamiento farmacológico , Demencia Vascular/metabolismo , Demencia Vascular/patología , Ratas Sprague-Dawley , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Proteínas Quinasas Activadas por AMP , Cognición , Serina-Treonina Quinasas TORRESUMEN
PURPOSE: To investigate the influences and mechanism of erythropoietin (EPO) on the cognitive function of vascular dementia (VD) rats. METHODS: 1) Spatial memory capacity was assessed by Morris water maze test; 2) Pathological conditions of brain tissues were detected by hematoxylin-eosin (HE) staining; 3) The effect of treatment on apoptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining; 4) Western blotting was used to examine the protein expression in hippocampal neurons. RESULTS: The escape latency and swimming distance in the EPO group were much shorter than those in the Model group on the fifth day. In the spatial exploration test, the time spent in the target quadrant was longer, the number of platform crossings was larger and the swimming speed was higher in the Sham group and EPO group than those in the Model group. The results of HE staining showed that the cells in the hippocampal CA1 region were arranged closely in the Sham group, loosely and disorderly in the Model group but significantly better in the EPO group. Compared with that in the Model group, the number of apoptotic cells in the EPO group was obviously smaller. The results of Western blotting revealed that the expressions of EPO, p-EPOR, p-SHP2, p-TrKB, p-PI3K, p-ERK1/2 and Bcl-2 rose, while the expressions of P22, P47, Caspase-3, Caspase-9 and Bax significantly declined in the EPO group. CONCLUSIONS: EPO can effectively ameliorate the cognitive dysfunction induced by chronic hypoperfusion in VD rats by mediating oxidative stress-related pathways.
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Demencia Vascular , Eritropoyetina , Ratas , Animales , Demencia Vascular/tratamiento farmacológico , Demencia Vascular/metabolismo , Ratas Sprague-Dawley , Eritropoyetina/farmacología , Hipocampo/metabolismo , Apoptosis , CogniciónRESUMEN
Aims: We aimed to investigate changes of fecal short chain fatty acids (SCFAs) and their association with metabolic benefits after sleeve gastrectomy (SG). Specifically, whether pre-surgery SCFAs modify surgical therapeutic effects was determined. Methods: 62 participants with measurements of fecal SCFAs and metabolic indices before and 1, 3, 6 months after SG were included. Changes of fecal SCFAs and their association with post-surgery metabolic benefits were calculated. Then, participants were stratified by medians of pre-surgery fecal SCFAs and modification effects of pre-surgery fecal SCFAs on surgical therapeutic effects were investigated, through calculating interaction of group by surgery. Results: Fecal SCFAs were markedly changed by SG. Changes of propionate and acetate were positively correlated with serum triglycerides and total cholesterol, respectively. Notably, high pre-surgery fecal hexanoate group showed a better effect of SG treatment on lowering body weight (P=0.01), BMI (P=0.041) and serum triglycerides (P=0.031), and low pre-surgery fecal butyrate had a better effect of SG on lowering ALT (P=0.003) and AST (P=0.019). Conclusion: Fecal SCFAs were changed and correlated with lipid profiles improvement after SG. Pre-surgery fecal hexanoate and butyrate were potential modifiers impacting metabolic benefits of SG.
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Caproatos , Ácidos Grasos Volátiles , Humanos , Butiratos , Triglicéridos , GastrectomíaRESUMEN
Three mononuclear compounds formulated as {M[(2-1H-tetrazol-5-yl)pyridine]2(H2O)2} (M = FeII (1), CoII (2), CuII (3)) were reported and synthesized. Their space group is monoclinic, P21/c, revealed by single-crystal X-ray diffraction. Antiferromagnetic interactions exist in Compounds 1, 2 and 3, as evidenced by magnetic and low-temperature heat capacity measurements. In addition, their thermodynamic functions were determined by a relaxation calorimeter, indicating that Compound 1 exhibits a Schottky anomaly in low-temperature heat capacity. This work can provide an important fundamental basis for the research of the thermophysical properties of molecular-based magnetic materials.
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Rice (Oryza sativa) resistance is its ability to resist various stresses, the changes of which have important impacts on O. sativa yield security. However, the responses of O. sativa stress resistance to elevated atmospheric CO2 concentration and temperature are poorly understood. We conducted a field open top-chamber experiment with O. sativa (Nanjing 9108 and Jinxiangyu I) based on the CO2 and temperature automatic control platform. The experimental treatments included ambient CO2 concentration and temperature treatment (CK, control), elevated CO2 concentration treatment (C, CO2 concentration increase of 200 µmol·mol-1 above CK), elevated temperature treatment (T, temperature increase of 2 â above CK) and elevated CO2 concentration and temperature (CT, CO2 concentration increase of 200 µmol·mol-1 and temperature increase of 2 â above CK). At the critical growth stages of O. sativa, we measured superoxide dismutase activity, silica content, total flavanol content, malondialdehyde content, soluble sugar content, proline content, and soluble protein content by cutting the uppermost functional leaves. We obtained the rice stress resistance index (RSRI) by principal component analysis to analyze the differences in the composition of stress resistance indicators under different treatments. Considering the disease resistance of O. sativa, the spike neck blast disease was counted to verify the expression level of RSRI for O. sativa stress resistance at maturity stage. Results showed that at the elongation-booting stage, C and CT treatments significantly reduced the RSRI of Jinxiangyu I by 36.5% and 41.1%, respectively, compared with CK. T treatment significantly decreased the RSRI of the two varieties by 44.9% and 33.8%, respectively. The RSRI explained 71.9%-74.3% of the variation in the spike neck blast disease. Overall, the stress resistance of two O. sativa varieties were adversely affected by elevated temperature at the elongation-booting stage. There was an interactive effect of CO2 concentration and temperature on O. sativa stress resistance. Compared with Nanjing 9108, the stress resistance of Jinxiangyu I was more sensitive to elevated CO2 concentration.
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Dióxido de Carbono , Resistencia a la Enfermedad , Temperatura , Malondialdehído , Hojas de la PlantaRESUMEN
PURPOSE: As a member of the G-protein-coupled receptor 1 family, the G-protein-coupled receptor 176 (GPR176) gene encodes a glycosylated protein made up of 515 amino acids. The current study was performed to evaluate the impact of GPR176 on the clinicopathology and prognosis of oesophageal cancer, as well as uncover its molecular mechanisms. METHODS: Bioinformatics and clinical tissue samples were used to detect the expression and clinicopathological significance of GPR176 in oesophageal cancer. The expression, proliferation, migration and invasion, apoptosis and lipid droplet formation of GPR176 gene in oesophageal cancer were performed as phenotypic readouts. RESULTS: Here, RT-PCR and bioinformatic analyses revealed that GPR176 mRNA expression was significantly higher in oesophageal cancer than in normal mucosa (p < 0.05). GPR176 mRNA expression was associated with low weight and BMI, low T stage, low N and clinicopathological stage, low histological grade and favourable clinical outcome of oesophageal cancer (p < 0.05). The differential genes of GPR176 mRNA were involved in protein digestion and absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others (p < 0.05). GPR176-related genes were classified as being involved in oxidoreductase activity, actin and myosin complexes, lipid localisation and transport, among others (p < 0.05). GPR176 knockdown suppressed proliferation, anti-apoptotic and anti-pyroptotic properties, migration, invasion, chemoresistance and lipid droplet formation in oesophageal cancer cells (p < 0.05), while ACC1 and ACLY overexpression reversed the inhibitory effects of GPR176 silencing on lipid droplet formation and chemoresistance. CONCLUSION: These findings indicated that upregulated expression of GPR176 might be involved in oesophageal carcinogenesis and subsequent progression, aggressiveness, and induced chemoresistance by ACC1- and ACLY-mediated lipogenesis and lipid droplet assembly.
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Neoplasias Esofágicas , Lipogénesis , Humanos , Resistencia a Antineoplásicos/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Proliferación Celular , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , ARN Mensajero/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
One lead genetic risk signal of obesity-the rs1421085 T>C variant within the FTO gene-is reported to be functional in vitro but lacks evidence at an organism level. Here we recapitulate the homologous human variant in mice with global and brown adipocyte-specific variant knock-in and reveal that mice carrying the C-allele show increased brown fat thermogenic capacity and resistance to high-fat diet-induced adiposity, whereas the obesity-related phenotypic changes are blunted at thermoneutrality. Both in vivo and in vitro data reveal that the C-allele in brown adipocytes enhances the transcription of the Fto gene, which is associated with stronger chromatin looping linking the enhancer region and Fto promoter. Moreover, FTO knockdown or inhibition effectively eliminates the increased thermogenic ability of brown adipocytes carrying the C-allele. Taken together, these findings identify rs1421085 T>C as a functional variant promoting brown fat thermogenesis.
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Tejido Adiposo Pardo , Obesidad , Humanos , Animales , Ratones , Tejido Adiposo Pardo/metabolismo , Obesidad/genética , Obesidad/metabolismo , Adipocitos Marrones , Adiposidad/genética , Termogénesis/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismoRESUMEN
Objective: This study delves into the impact of erythropoietin (EPO) on hippocampal neurons and its potential implications for sports performance, fitness, and the cognitive well-being of football players facing vascular cognitive impairment. Methodology: The study employs a comprehensive approach, utilizing a rat model of vascular dementia (VaD) induced by bilateral carotid artery ligation. Exogenous EPO is administered to the VaD rat model. Observations of EPO's influence on hippocampal neurons are made, and in vitro experiments are conducted to validate the specific mechanisms at play, particularly under oxygen/glucose-deprived conditions. Results: The results reveal several noteworthy findings. VaD rats treated with EPO demonstrate significantly shorter escape latency, increased neuronal populations, and enhanced preservation of Nissl bodies in hippocampal subfields, specifically cortical area 1 (CA1) and CA2. Moreover, these rats exhibit a lower count of TUNEL-positive cells compared to the model group, with higher doses of EPO demonstrating more notable improvements in escape latency. Molecular analysis shows that EPO up-regulates key protein expressions, including phosphorylated EPO receptor (p-EPOR), p-phosphatidylinositol 3-kinase (p-PI3K), p-protein kinase B (Akt), and p-cyclic AMP response element binding protein (p-CREB). Simultaneously, it down-regulates expressions of apoptosis- and autophagy-related proteins, such as B-cell lymphoma-2-associated X protein (Bax), cleaved-Caspase 3, cleaved-Caspase 9, light chain 3β (LC3β), Beclin, autophagy-related gene 5 (ATG5), and ATG7. Notably, in vitro experiments confirm the role of the PI3K/AKT pathway in EPO's mechanisms, with implications for cognitive health. (AU)
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Animales , Ratas , Eritropoyetina , Neuronas , Rendimiento Atlético , Disfunción Cognitiva , Atletas , Fútbol , Fosfatidilinositol 3-Quinasas , Estrés OxidativoRESUMEN
RATIONALE: Pheochromocytomas are a group of tumors with high genetic heterogeneity, and the clinical characteristics of rearranged during transfection (RET)-mutated pheochromocytoma with medullary spongiform kidney are rarely studied. The treatment process of 1 patient with bilateral adrenal pheochromocytoma combined with medullary sponge kidney with RET gene mutation in our department was retrospectively analyzed, and the treatment methods for this type of disease were studied and summarized in combination with relevant literature. PATIENT CONCERNS: In this case, the patient was found to have bilateral adrenal masses for 8 years due to physical examination, and intermittent dizziness and discomfort for 2 years. Imaging and related laboratory examinations suggest bilateral adrenal giant pheochromocytoma with bilateral medullary sponge kidney. RET gene testing was performed on the patient and his descendant after signing the informed consent form. DIAGNOSES: The patient was diagnosed with bilateral adrenal pheochromocytoma with a RET proto-oncogene mutation and a bilateral medullary spongy kidney. INTERVISION AND OUTCOMES: After sufficient perioperative preparation, retroperitoneal laparoscopic bilateral adrenal pheochromocytoma resection was performed by stages. The operation was successful, and hormone replacement therapy was performed after the operation, with regular follow-up. Relevant genetic testing revealed that the c.1900T > C: p.C634R mutation was detected in the patient's RET gene, which was a heterozygous missense mutation, and the mutation was also present in the son of his family. A literature analysis found that pheochromocytoma is a tumor with high genetic heterogeneity, and the RET proto-oncogene is a common pathogenic gene for bilateral adrenal pheochromocytoma. Medullary sponging of kidneys is a rare complication of this disease. LESSONS: On the basis of adequate perioperative preparation, surgical resection is the most effective and preferred treatment for this type of disease. Laparoscopic surgery is minimally invasive, safe, and effective by stages. Mutations in the RET proto-oncogene may lead to medullary spongy kidneys in multiple endocrine neoplasia 2.
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Neoplasias de las Glándulas Suprarrenales , Riñón Esponjoso Medular , Neoplasia Endocrina Múltiple Tipo 2a , Feocromocitoma , Neoplasias de la Tiroides , Humanos , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/cirugía , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Estudios Retrospectivos , Proteínas Proto-Oncogénicas c-ret/genética , Proto-Oncogenes Mas , Mutación , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/cirugía , Proto-Oncogenes , Neoplasias de la Tiroides/patologíaRESUMEN
Supramolecular behavior is highly dependent on many factors, including complicated microenvironments and weak interactions. Herein, we describe tuning supramolecular architectures of rigid macrocycles by synergistic effects of their geometric configurations, sizes, and guests. Two paraphenylene-based macrocycles are anchored onto different positions in a triphenylene derivative, resulting in dimeric macrocycles with different shapes and configurations. Interestingly, these dimeric macrocycles show tunable supramolecular interactions with guests. In solid state, a 2 : 1 host-guest complex was observed between 1a and C60/C70, while an unusual 2 : 3 host-guest complex 3C60@(1b)2 can be observed between 1b and C60. This work expands the scope of the synthesis of novel rigid bismacrocycles and provides a new strategy to construct different supramolecular systems.
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OBJECTIVE: The safety and efficacy of drug-eluting balloon on the treatment of intracranial atherosclerotic stenosis (ICAS) remain unclear. Here, we present our observation in a cohort study on the safety and efficacy of rapamycin-eluting balloon for patients with ICAS. METHODS: A total of 80 ICAS patients with stenosis degree of 70-99% were included. All patients were treated with rapamycin-eluting balloon and were followed up for 12 months after operation. RESULTS: All patients were successfully treated, where the mean stenosis severity reduced from 85.1 ± 7.6 to 6 ± 4.9%. 8 patients experienced immediate post-operational complications. Two patients passed away during the first month of the follow-up period. Recurrent ischemic syndrome and angiographic restenosis only appeared 7 days after operation. During later follow-up period, none of the patients had clinical angiographic restenosis or needed target vessel revascularization. CONCLUSION: Our data suggest that intracranial stenting with rapamycin-eluting balloon seems to be safe and effective, although more clinical data are needed to support this notion.
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Reestenosis Coronaria , Stents Liberadores de Fármacos , Arteriosclerosis Intracraneal , Humanos , Estudios de Cohortes , Sirolimus/farmacología , Stents Liberadores de Fármacos/efectos adversos , Constricción Patológica , Stents , Arteriosclerosis Intracraneal/cirugía , Resultado del Tratamiento , Angiografía CoronariaRESUMEN
Autotaxin (ATX), the key enzyme that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC), is involved in tumorigenesis through the ATX-LPA axis and is regarded as a valuable target in tumor therapy. Hypoxia is a major feature of solid tumors and contributes to tumor development with striking alterations in the gene expression profile. Here, we show that hypoxia induces ATX expression in a hypoxia-inducible factor (HIF) 2α-dependent fashion in human colon cancer SW480 cells. HIF-2α is directly bound to specific hypoxia response elements (HREs) in the ATX promoter. Under hypoxic conditions, knockout or inhibition of ATX suppressed the migration of SW480 cells, which could be rescued by the addition of LPA, suggesting that the induction of ATX during hypoxia promotes cancer cell migration through the ATX-LPA axis. Further studies showed that ATX expression was induced by HIF-2α through recruiting p300/CBP, which led to crotonylation but not acetylation of histone H3 in the ATX promoter region during hypoxia. Moreover, elevation of cellular histone crotonylation levels could induce ATX expression under normoxic conditions. In conclusion, our findings reveal that ATX is induced in SW480 cells during hypoxia by histone crotonylation in a HIF-2α-dependent manner, while as a novel mechanism of ATX expression regulation, the upregulation of ATX expression by histone crotonylation is not confined to hypoxia.