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Glioma is the most common malignant tumor of the central nervous system, with EZH2 playing a crucial regulatory role. This study further explores the abnormal expression of EZH2 and its mechanisms in regulating glioma progression. Additionally, it was found that IHMT-337 can potentially be a therapeutic agent for glioma. The prognosis, expression, and localization of EZH2 were determined using bioinformatics, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization. The effects of EZH2 on cell function were assessed using CCK-8 assays, Transwell assays, and wound healing assays. Public databases and RT-qPCR were utilized to identify downstream targets. The mechanisms regulating these downstream targets were elucidated using MS-PCR and WB analysis. The efficacy of IHMT-337 was demonstrated through IC50 measurements, WB analysis, and RT-qPCR. The effects of IHMT-337 on glioma cells in vitro were evaluated using Transwell assays, EdU incorporation assays, and flow cytometry. The potential of IHMT-337 as a treatment for glioma was assessed using a blood-brain barrier (BBB) model and an orthotopic glioma model. Our research confirms significantly elevated EZH2 expression in gliomas, correlating with patient prognosis. EZH2 facilitates glioma proliferation, migration, and invasion alongside promoting SLC12A5 DNA methylation. By regulating SLC12A5 expression, EZH2 activates the WNK1-OSR1-NKCC1 pathway, enhancing its interaction with ERM to promote glioma migration. IHMT-337 targets EZH2 in vitro to inhibit WNK1 activation, thereby suppressing glioma cell migration. Additionally, it inhibits cell proliferation and arrests the cell cycle. IHMT-337 has the potential to cross the BBB and has successfully inhibited glioma progression in vivo. This study expands our understanding of the EZH2-SLC12A5 axis in gliomas, laying a new foundation for the clinical translation of IHMT-337 and offering new insights for precision glioma therapy.
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Proliferación Celular , Proteína Potenciadora del Homólogo Zeste 2 , Glioma , Glioma/metabolismo , Glioma/genética , Glioma/patología , Glioma/tratamiento farmacológico , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Humanos , Animales , Línea Celular Tumoral , Ratones , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto , PronósticoRESUMEN
Antimony (Sb) pollution in aquatic ecosystems has emerged as a critical environmental issue on a global scale, emphasizing the urgent need for cost-effective and user-friendly technologies to remove Sb compounds from water sources. In this study, a novel adsorbent, selenium nanoparticles (SeNPs), was synthesized using the aqueous extract of Psidium guajava L. leaves (AEP) for the purpose of eliminating Sb(III) from aqueous solutions. The biosynthesized SeNPs was characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray fluorescence spectrometer (XRF), Fourier Transform-Infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) analysis techniques. Additionally, the removal efficiency of the SeNPs for Sb(III) was systematic investigated under the effects of SeNPs dose, temperature, pH and re-usability. The results of this study showed that the adsorption data fitted well into pseudo-second order model, while the Sips modeling demonstrated a high adsorption capacity (62.7 mg/g) of SeNPs for Sb(III) ions at 303.15 K from aqueous solution. The exothermic enthalpy change of - 22.59 kJ/mol and negative Gibbs free energy change assured the viability of the adsorption process under the considered temperature conditions. Surface functional groups on SeNPs like carboxyl, amide, hydroxyl, carbonyl, and methylene significantly facilitate the adsorption processes. Furthermore, the removal efficiencies of Sb in the two actual Sb mine wastewater samples were remarkably high, achieving nearly to 100% with 1.5 g/L SeNPs within 48 h. This outcome underscores the potential of SeNPs as a highly promising solution for efficiently remediating Sb from aquatic environments, owing to their cost-effectiveness, ease of regeneration, and rapid uptake capabilities.
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Antimonio , Extractos Vegetales , Psidium , Selenio , Aguas Residuales , Contaminantes Químicos del Agua , Psidium/química , Aguas Residuales/química , Extractos Vegetales/química , Contaminantes Químicos del Agua/química , Antimonio/química , Selenio/química , Adsorción , Nanopartículas/químicaRESUMEN
Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.
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Disbiosis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/microbiología , Disbiosis/metabolismo , Disbiosis/microbiología , Disbiosis/inmunología , Humanos , Ratones , Masculino , Femenino , Animales , Enfermedad del Almacenamiento de Glucógeno Tipo I/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Modelos Animales de Enfermedad , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologíaRESUMEN
Nanotechnology offers a promising and innovative approach to mitigate biotic and abiotic stress in crop production. In this study, the beneficial role and potential detoxification mechanism of biogenic selenium nanoparticles (Bio-SeNPs) prepared from Psidium guajava extracts in alleviating antimony (Sb) toxicity in rice seedlings (Oryza sativa L.) were investigated. The results revealed that exogenous addition of Bio-SeNPs (0.05 g/L) into the hydroponic-cultured system led to a substantial enhancement in rice shoot height (73.3%), shoot fresh weight (38.7%) and dry weight (28.8%) under 50 µM Sb(III) stress conditions. Compared to Sb exposure alone, hydroponic application of Bio-SeNPs also greatly promoted rice photosynthesis, improved cell viability and membrane integrity, reduced reactive oxygen species (ROS) levels, and increased antioxidant activities. Meanwhile, exogenous Bio-SeNPs application significantly lowered the Sb accumulation in rice roots (77.1%) and shoots (35.1%), and reduced its root to shoot translocation (55.3%). Additionally, Bio-SeNPs addition were found to modulate the subcellular distribution of Sb and the expression of genes associated with Sb detoxification in rice, such as OsCuZnSOD2, OsCATA, OsGSH1, OsABCC1, and OsWAK11. Overall, our findings highlight the great potential of Bio-SeNPs as a promising alternative for reducing Sb accumulation in crop plants and boosting crop production under Sb stress conditions.
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Antimonio , Antioxidantes , Regulación de la Expresión Génica de las Plantas , Nanopartículas , Oryza , Selenio , Oryza/efectos de los fármacos , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Oryza/genética , Antimonio/toxicidad , Antioxidantes/metabolismo , Selenio/toxicidad , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Nanopartículas/toxicidad , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Plantones/efectos de los fármacos , Plantones/metabolismo , Plantones/crecimiento & desarrolloRESUMEN
Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodiumâglucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.
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Compuestos de Bencidrilo , Glucósidos , Enfermedad del Almacenamiento de Glucógeno Tipo I , Enfermedades Inflamatorias del Intestino , Niño , Humanos , Masculino , Femenino , Adolescente , Constricción Patológica/complicaciones , Úlcera , Hiperplasia , Estudios Prospectivos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo I/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Proteínas de Transporte de Monosacáridos/genética , Antiportadores/genéticaRESUMEN
Microbial antimony (Sb) oxidation in the root rhizosphere and the formation of iron plaque (IP) on the root surface are considered as two separate strategies to mitigate Sb(III) phytotoxicity. Here, the effect of an Sb-oxidizing bacterium Bacillus sp. S3 on IP characteristics of rice exposed to Sb(III) and its alleviating effects on plant growth were investigated. The results revealed that Fe(II) supply promoted IP formation under Sb(III) stress. However, the formed IP facilitated rather than hindered the uptake of Sb by rice roots. In contrast, the combined application of Fe(II) and Bacillus sp. S3 effectively alleviated Sb(III) toxicity in rice, resulting in improved rice growth and photosynthesis, reduced oxidative stress levels, enhanced antioxidant systems, and restricted Sb uptake and translocation. Despite the ability of Bacillus sp. S3 to oxidize Fe(II), bacterial inoculation inhibited the formation of IP, resulting in a reduction in Sb absorption on IP and uptake into the roots. Additionally, the bacterial inoculum enhanced the transformation of Sb(III) to less toxic Sb(V) in the culture solution, further influencing the adsorption of Sb onto IP. These findings highlight the potential of combining microbial Sb oxidation and IP as an effective strategy for minimizing Sb toxicity in sustainable rice production systems.
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Bacillus , Oryza , Contaminantes del Suelo , Hierro , Antimonio/toxicidad , Raíces de Plantas , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Bacterias , Oxidación-Reducción , Compuestos FerrososRESUMEN
Cardiac function and structure significantly impact nonischemic heart failure (HF) patient outcomes. This study investigated 236 patients (107 nonischemic heart failure, 129 healthy) to assess the relationship between coronary computed tomography angiography (CCTA)-derived parameters and clinical outcomes. Among the nonischemic heart failure patients, 37.3% experienced readmissions. In this group, specific CCTA measurements were identified as significant predictors of readmission: epicardial adipose tissue (CTEAT) at 54.49 cm3 (HR: 1.05; 95% CI: 1.03-1.07; P < 0.001), cardiac muscle mass to lumen volume (CTV/M) at 20% (HR: 0.59; 95% CI: 0.48-0.72; P < 0.001), peri-coronary adipose (CTPCAT) at -64.68 HU (HR: 1.1; 95% CI: 1.03-1.16; P = 0.002) for the right coronary artery, -81.07 HU (HR: 1.3; 95% CI: 1.1-1.53; P = 0.002) for the left anterior descending artery, and -73.42 HU (HR: 1.33; 95% CI: 1.18-1.51; P < 0.001) for the circumflex branch of the left coronary artery. In patients with nonischemic heart failure, increased CTEAT, CTPCAT, and CTV/M independently predicted rehospitalization.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Insuficiencia Cardíaca , Humanos , Angiografía por Tomografía Computarizada/métodos , Readmisión del Paciente , Angiografía Coronaria/métodos , Tomografía Computarizada por Rayos X , Insuficiencia Cardíaca/diagnóstico por imagen , Reserva del Flujo Fraccional Miocárdico/fisiología , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: The study aimed to evaluate the correlation and diagnostic value of liver fat quantification in unenhanced dual-energy CT (DECT) using quantitative magnetic resonance imaging (MRI) mDIXON-Quant sequence as reference standard in patients with breast cancer. METHODS: Patients with breast cancer were prospectively recruited between June 2018 and April 2020. Each patient underwent liver DECT and MRI mDIXON-Quant examination. The DECT-fat volume fraction (FVF) and liver-spleen attenuation differences were compared with the MRI-proton density fat fraction using scatterplots, Bland-Altman plots, and concordance correlation coefficient. Receiver operating characteristic curves were established to determine the diagnostic accuracy of hepatic steatosis by DECT. RESULTS: A total of 216 patients with breast cancer (mean age, 50.08 ± 9.33 years) were evaluated. The DECT-FVF correlated well with MRI-proton density fat fraction ( r2 = 0.902; P < 0.001), which was higher than the difference in liver-spleen attenuation ( r2 = 0.728; P < 0.001). Bland-Altman analysis revealed slight positive bias; the mean difference was 3.986. The DECT-FVF yielded an average concordance correlation coefficient of 0.677, which was higher than the difference of liver-spleen attenuation (-0.544). The DECT-FVF and the difference in liver-spleen attenuation both lead to mild overestimation of hepatic steatosis. The areas under the curve of DECT-FVF (0.956) were higher than the difference in liver-spleen attenuation (0.807) in identifying hepatic steatosis ( P < 0.001). CONCLUSIONS: Dual-energy CT-FVF may serve as a reliable screening and quantitative tool for hepatic steatosis in patients with breast cancer.
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Neoplasias de la Mama , Hígado Graso , Humanos , Adulto , Persona de Mediana Edad , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Protones , Hígado Graso/diagnóstico por imagen , Hígado Graso/patología , Hígado/diagnóstico por imagen , Hígado/patología , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Selenium nanoparticles (SeNPs) have gained significant attention owing to their favorable bioavailability and low toxicity, making them widely applications in the fields of medicine, food and agriculture. In this study, bacterial extracellular polymeric substances (EPS) were used as a novel stabilizer and capping agent to prepare dispersed SeNPs. Results show that EPS-SeNPs presented negative potential (-38 mV), spherical morphologies with average particle size about 100-200 nm and kept stable at room temperature for a long time. X-ray diffraction (XRD) analysis demonstrated that the synthesized nanoparticles were pure amorphous nanoparticles, and X-ray photoelectron spectroscopy (XPS) spectrum showed a spike at 55.6 eV, indicating the presence of zero-valent nanoselenium. Fourier-transform infrared spectroscopy (FTIR) and three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy analysis confirmed proteins and polysaccharides in EPS played a crucial role in the synthesis of EPS-SeNPs. Compared to EPS or sodium selenite (Na2SeO3), EPS-SeNPs showed a relatively moderate result in terms of scavenging free radicals in vitro. In contrast, EPS-SeNPs demonstrated lower toxicity to rice seeds than Na2SeO3. Notably, the exogenous application of EPS-SeNPs effectively alleviated the growth inhibition and oxidative damaged caused by cadmium (Cd), and significantly reduced Cd accumulation in rice plants.
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Nanopartículas , Oryza , Selenio , Selenio/química , Cadmio , Matriz Extracelular de Sustancias Poliméricas , Polisacáridos , Nanopartículas/químicaRESUMEN
BACKGROUND: The effectiveness of surgical interventions, whether direct or indirect, for Moyamoya disease (MMD) remains controversial. This study aims to investigate CT perfusion (CTP) as an objective method to evaluate the outcomes of different surgical modalities for adult MMD. METHODS: The clinical and imaging data of 41 patients who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass and 43 who received encephaloduroarteriosynangiosis (EDAS) were retrospectively analyzed. Intra- and intergroup differences in the Modified Rankin Scale (mRS) score, the change in clinical symptoms, collateral grade, and CTP parameters pre- and postoperatively were compared. RESULTS: The overall level of the change in clinical symptoms in the STA-MCA group was higher than in the EDAS group (p < 0.05). In the operative area, the relative cerebral blood flow (rCBF) was significantly higher whereas the relative time to peak (rTTP) and the relative mean transit time (rMTT) were significantly lower in the STA-MCA and EDAS groups postoperatively than preoperatively (all p < 0.05). In the ipsilateral frontal lobe and basal ganglia, the postoperative rCBF was significantly higher, and the rTTP was significantly lower than the preoperative in the STA-MCA group (all p < 0.05). The postoperative rCBF improvement was higher in each brain area for STA-MCA than in the EDAS group (all p < 0.05). CONCLUSION: Highlighting the utility of CTP, this study demonstrates its effectiveness in assessing postoperative cerebral hemodynamic changes in adult MMD patients. STA-MCA yielded a larger postoperative perfusion area and greater improvement compared to EDAS, suggesting CTP's potential to elucidate symptom variation between two surgical revascularization procedures. CRITICAL RELEVANCE STATEMENT: We analyzed computed tomography perfusion parameters in pre- and postoperative adult Moyamoya disease patients undergoing superficial temporal artery-middle cerebral artery bypass and encephaloduroarteriosynangiosis. Our findings suggest computed tomography perfusion's potential in objectively elucidating symptom variations between these surgical revascularization approaches for MMD. KEY POINTS: ⢠Postoperative perfusion improvement is only confined to the operative area after EDAS. ⢠Besides the operative area, postoperative perfusion in the ipsilateral frontal lobe and basal ganglia was also improved after STA-MCA. ⢠The degree of perfusion improvement in each brain area in the STA-MCA group was generally greater than that in the EDAS group.
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This study aimed to assess the stability of thyme essential oil microcapsules (TEOMs) and their impacts on the antioxidant properties and quality of lamb patties. The results demonstrated that gum Arabic effectively enhanced the stability of phenols within the thyme essential oil (TEO), with an optimal core/wall ratio of 1:8. Substituting TEO with TEOMs in lamb patties led to reductions in the thiobarbituric acid content, carbonyl content, sulfhydryl loss, and protein cross-linking. Additionally, the TEOMs positively influenced the mutton patties' color, texture, microbiological stability, and sensory attributes. These findings substantiate the idea that TEOMs exhibit significant potential as a natural preservative to enhance the quality of mutton patties.
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Solar-driven interfacial evaporation is a highly efficient and ecofriendly technology for producing freshwater. Herein, self-floating plasmon Ag/black TiO2/carbon porous layered foams (Ag-BTCFs) were demonstrated as efficient solar-thermal convectors using freeze-drying cast-molding and high-temperature surface hydrogenation strategies. This all-in-one three-dimensional (3D) cross-linked self-floating porous layered foam material with full-spectrum absorption can fully harvest sunlight (â¼95.45%) and effectively block heat transfer to its sublayer. The synergy of sufficient utilization of absorbed ultraviolet radiation by black TiO2 (b-TiO2), visible light absorption by Ag nanoparticles (Ag NPs) via localized surface plasmon resonance, and near-infrared absorption by layered-amorphous carbon can achieve full-solar-spectrum absorption to concentrate thermal energy. In addition to their synergistic effect, they are conducive to the relaxation of hot electrons when utilizing photogenerated holes to degrade pollutants in domestic wastewater. The steam generation efficiency of Ag-BTCFs is up to 1.79 kg m-2h-1 due to their solar energy conversion efficiency of 81.74% under 1 sun irradiation, which is five times higher than the evaporation rate of pure water. Notably, the material's efficient ion removal rate of 99.80% for solar desalination indicates its high potential for various applications. This strategy provides new insights for fabricating recyclable heat-blocking layer systems against thermal loss to enhance solar steam generation.
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Selenium (Se) has been used to detoxify various heavy metals in plants. However, the effects and underlying mechanisms of exogenous Se application on the toxicity of antimonite [Sb(III)] and antimonate [Sb(V)] in crops are still poorly understood. Therefore, the potential alleviating roles of Se on the plant growth, antioxidant system, uptake and subcellular distribution of Sb, and expression of Sb-related genes were comprehensively investigated in rice seedlings (Oryza sativa L.) under both Sb(III) and Sb(V) stress conditions. The results showed that high concentrations of Sb(III) (100 µM) and Sb(V) (300 µM) caused a significant decrease in plant growth parameters, photosynthetic pigments and relative water content in rice seedlings. In contrast, the addition of Se (20 or 2 µM) improved rice growth, decreased Sb accumulation, and reduced oxidative stress in rice seedlings when exposed to 100 µM Sb(III) and 300 µM Sb(V), respectively. Furthermore, Se application could effectively improve the physiological adaptability of rice seedlings under Sb(III) and Sb(V) stress by regulating enzymatic and non-enzymatic antioxidant systems, Sb subcellular distribution and transcription levels of Sb-related genes, including in antioxidant response (OsCuZnSOD2, OsCATA and OsGSH1), detoxification (OsPCS1, OsPCS2 and OsABCC1) and Sb transport and sequestration (OsLsi1 and OsWAK11). Moreover, we also discovered that the mitigation effect of Se was dose-dependent and depended on Sb valence states. Thus, these findings contribute to our understanding of the mechanisms underlying Se-Sb antagonism in rice, offering a potentially useful method for producing both safe and Se-rich crops.
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Antimonio , Antioxidantes , Oryza , Selenio , Oryza/química , Oryza/fisiología , Antimonio/química , Antimonio/toxicidad , Selenio/química , Antioxidantes/química , Estrés FisiológicoRESUMEN
Sphingolipids, a type of bioactive lipid, play crucial roles within cells, serving as integral components of membranes and exhibiting strong signaling properties that have potential therapeutic implications in anti-cancer treatments. However, due to the diverse group of lipids and intricate mechanisms, sphingolipids still face challenges in enhancing the efficacy of different therapy approaches. In recent decades, mass spectrometry has made significant advancements in uncovering sphingolipid biomarkers and elucidating their impact on cancer development, progression, and resistance. Primary sphingolipids, such as ceramide and sphingosine-1-phosphate, exhibit contrasting roles in regulating cancer cell death and survival. The evasion of cell death is a characteristic hallmark of cancer cells, leading to treatment failure and a poor prognosis. The escape initiates with long-established apoptosis and extends to other programmed cell death (PCD) forms when patients experience chemotherapy, radiotherapy, and/or immunotherapy. Gradually, supportive evidence has uncovered the fundamental molecular mechanisms underlying various forms of PCD leading to the development of innovative molecular, genetic, and pharmacological tools that specifically target sphingolipid signaling nodes. In this study, we provide a comprehensive overview of the sphingolipid biomarkers revealed through mass spectrometry in recent decades, as well as an in-depth analysis of the six main forms of PCD (apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis) in aspects of tumorigenesis, metastasis, and tumor response to treatments. We review the corresponding small-molecule compounds associated with these processes and their potential implications in cancer therapy.
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OBJECTIVES: This study aimed to assess the efficacy of quantitative parameters derived from dual-energy computed tomography (DECT) for the preoperative prediction of early recurrence (ER) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: In total, 78 patients with ESCC who underwent radical esophagectomy and DECT from June 2019 to August 2020 were enrolled in this study. Normalized iodine concentration (NIC) and electron density (Rho) in tumors were measured using arterial and venous phase images, whereas unenhanced images were used to determine the effective atomic number (Zeff). Univariate and multivariate Cox proportional hazards models were used to identify independent risk predictors of ER. Receiver operating characteristic curve analysis was performed using the independent risk predictors. ER-free survival curves were constructed using the Kaplan-Meier method. RESULTS: NIC in the arterial phase (A-NIC; hazards ratio [HR], 3.91; 95% confidence interval [CI], 1.79-8.56; p = 0.001) and pathological grade (PG; HR, 2.69; 95% CI, 1.32-5.49; p = 0.007) were identified as significant risk predictors of ER. The area under the curve of A-NIC for predicting ER in patients with ESCC was not significantly higher than that of PG (0.72 vs. 0.66, p = 0.441). In a stratified survival analysis, patients with high A-NIC or poorly differentiated ESCC had a higher rate of ER than those with low A-NIC or highly/moderately differentiated ESCC. CONCLUSIONS: A-NIC derived from DECT can be used to noninvasively predict preoperative ER in patients with ESCC, with an efficacy comparable to that of pathological grade. CLINICAL RELEVANCE STATEMENT: Preoperative quantitative measurement of dual-energy CT parameters can predict the early recurrence of esophageal squamous cell carcinoma and serve as an independent prognostic factor to guide clinical designation of personalized treatment. KEY POINTS: ⢠Normalized iodine concentration in the arterial phase and pathological grade were independent risk predictors of early recurrence in patients with esophageal squamous cell carcinoma. ⢠Normalized iodine concentration in the arterial phase may be a noninvasive imaging marker for preoperatively predicting early recurrence in patients with esophageal squamous cell carcinoma. ⢠The efficacy of normalized iodine concentration in the arterial phase derived from dual-energy computed tomography for predicting early recurrence is comparable to that of pathological grade.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Yodo , Humanos , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Curva ROC , Tomografía , Estudios RetrospectivosRESUMEN
Small-molecule photothermal agents (PTAs) with intense second near-infrared (NIR-II, 1,000 to 1,700 nm) absorption and high photothermal conversion efficiencies (PCEs) are promising candidates for treating deep-seated tumors such as osteosarcoma. To date, the development of small-molecule NIR-II PTAs has largely relied on fabricating donor-acceptor-donor (D-A-D/D') structures and limited success has been achieved. Herein, through acceptor engineering, a donor-acceptor-acceptor (D-A-A')-structured NIR-II aza-boron-dipyrromethene (aza-BODIPY) PTA (SW8) was readily developed for the 1,064-nm laser-mediated phototheranostic treatment of osteosarcoma. Changing the donor groups to acceptor groups produced remarkable red-shifts of absorption maximums from first near-infrared (NIR-I) regions (~808 nm) to NIR-II ones (~1,064 nm) for aza-BODIPYs (SW1 to SW8). Furthermore, SW8 self-assembled into nanoparticles (SW8@NPs) with intense NIR-II absorption and an ultrahigh PCE (75%, 1,064 nm). This ultrahigh PCE primarily originated from an additional nonradiative decay pathway, which showed a 100-fold enhanced decay rate compared to that shown by conventional pathways such as internal conversion and vibrational relaxation. Eventually, SW8@NPs performed highly efficient 1,064-nm laser-mediated NIR-II photothermal therapy of osteosarcoma via concurrent apoptosis and pyroptosis. This work not only illustrates a remote approach for treating deep-seated tumors with high spatiotemporal control but also provides a new strategy for building high-performance small-molecule NIR-II PTAs.
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Introduction: Functional disorder of the placenta is the principal cause of fetal growth restriction (FGR), usually cured with suitable clinical treatment and good nursing. However, some FGR mothers still give birth to small for gestational age (SGA) babies after treatment. The ineffectiveness of treatment in such a group of patients confused physicians of obstetrics and gynecology. Methods: In this study, we performed a microRNA-messenger RNA integrative analysis of gene expression profiles obtained from Gene Expression Omnibus. Differentially expressed genes were screened and checked using quantitative polymerase chain reaction. Target genes of significantly changed microRNA were screened and enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Function of the obtained microRNA-messenger RNA was evaluated using HTR-8/SVneo trophoblast cells, human umbilical vein endothelial cells, and heterozygote male mice. Result: MiR-155-5p was upregulated (p = 0.001, fold-change = 2.275) in fetal-side placentals. Among the hub genes identified as key targets for miR-155-5p in fetal reprogramming, Smad2 was downregulated (p = 0.002, fold change = 0.426) and negatively correlated with miR-155-5p expression levels (r = -0.471, p < 1.0 E - 04) in fetal-side placental tissues. The miR-155-5p mimic blocks Smad2 expression and suppresses villous trophoblast cell and endothelial cell function (proliferation, migration, and invasion), indicating a close relationship with placental development. Luciferase assays further confirmed the targeting of miR-155-5p to Smad2. Furthermore, Smad2+/- heterozygote male mice were born small with low body weight (p = 0.0281) and fat composition (p = 0.013) in the fourth week post-natal. Discussion: We provide the first evidence of the role of the Smad2/miR-155-5p axis in the placental pathologies of FGR. Our findings elucidate the pathogenesis of FGR and provide new therapeutic targets.
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BACKGROUND: The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic. METHODS: Syngeneic G422TN-GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422TN-GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action. RESULTS: Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422TN) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422TN-tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422TN-mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3+/CD4+/CD8+ T-lymphocytes in G422TN-tumor on the basis of RT/TMZ regimen. CONCLUSION: Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials.
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Glioblastoma , Glioma , Humanos , Animales , Ratones , Glioblastoma/tratamiento farmacológico , Temozolomida/farmacología , Temozolomida/uso terapéutico , Especies Reactivas de Oxígeno , Linfocitos T CD8-positivos , Estrés Oxidativo , Quimioradioterapia , Microambiente TumoralRESUMEN
Persistent postural-perceptual dizzinessï¼PPPDï¼ is the most common chronic vestibular disease, the clinical manifestation is dizziness, unstable and non-rotational dizziness for three months or more. And the symptom is exacerbated by upright posture, active or passive movement, and complex visual stimuli. In addition, PPPD is a functional disease, so routine vestibular function tests and imaging tests are often negative. According to the diagnostic criteria established by the Barany Association, the diagnosis of PPPD often relies on history. This article provides a review of PPPD-related questionnaires.
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Mareo , Enfermedades Vestibulares , Humanos , Mareo/diagnóstico , Vértigo/diagnóstico , Enfermedades Vestibulares/diagnóstico , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The aim of this study is to investigate the radiation dose and image quality of head CT using SPS and OBTCM techniques. METHODS: Three anthropomorphic head phantoms (1-yr-old, 5-yr-old, and adult) were used. Images were acquired using four modes (Default protocol, OBTCM, SPS, and SPS+OBTCM). Absorbed dose to the lens, anterior brain (brain_A), and posterior brain (brain_P) was measured and compared. Image noise and CNR were assessed in the selected regions of interest (ROIs). RESULTS: Compared with that in the Default protocol, the absorbed dose to the lens reduced by up to 28.33%,71.38%, and 71.12% in OBTCM, SPS, and SPS+OBTCM, respectively. The noise level in OBTCM slightly (≤1.45HU) increased than that in Default protocol, and the SPS or SPS+OBTCM mode resulted in a quantitatively small increase (≤2.58HU) in three phantoms. There was no significant difference in CNR of different phantoms under varies scanning modes (pâ>â0.05). CONCLUSIONS: During head CT examinations, the SPS mode can reduce the radiation dose while maintaining image quality. SPS+OBTCM couldn't further effectively reduce the absorbed dose to the lens for 1-yr and 5-yr-old phantoms. Thus, SPS mode in pediatric and SPS+OBTCM mode in adult are better than other modes, and should be used in clinical practice.