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Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.
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RATIONALE: Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of plasma cells, which usually occurs in middle-aged and elderly male patients. Bisphosphonates (BP) are commonly used for the treatment of MM bone disease. Long-time use of BP may cause medication-related osteonecrosis of the jaw (MRONJ). MRONJ occurs in jaw exclusively, and Multiple myeloma can also invade the jaw. The 2 diseases have similar clinical manifestations and imaging findings. This report present a case of MM identified in surgical specimen at the site that had been previously pathologically diagnosed as MRONJ in a patient with MM. PATIENT CONCERNS: A 57-years-old male patient visited our clinic on October 16, 2020 because of gingival swelling and pain in the right mandible for 1 month after extraction of the lower right premolar. The patient had a long-time illness history of multiple myeloma, and received intravenous zoledronic acid treatment. DIAGNOSES: Based on the clinical characteristics, imaging, and pathological findings of sequestrum formation and high inflammatory cell infiltration, the patient was diagnosed with MRONJ. After 1 year, a mandibular osteotomy was performed and pathological analysis showed the presence of necrotic bone and a large number of abnormal plasma cell infiltration, suggesting the presence of MM in the mandible. INTERVENTIONS: The patient was treated with a series of conservative treatments including antibiotic treatment, saline irrigation and laser irradiation, as well as superficial sequestration was. One year later, a mandibular osteotomy was performed. OUTCOMES: For the patient, the symptoms of gingival swelling, pain and discharge disappeared after surgery. LESSONS: These findings suggested MRONJ and MM could occur simultaneously at same site, so patients with MM presenting with symptoms of MRONJ should be screened for concurrent or disease relapse of multiple myeloma to prevent misdiagnosis or inadequate management. Meanwhile, this also suggests long-term inflammatory may lead to invasion of multiple myeloma.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Mieloma Múltiple , Humanos , Masculino , Persona de Mediana Edad , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/cirugía , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos , Mandíbula/cirugía , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Recurrencia Local de Neoplasia/tratamiento farmacológico , Dolor/tratamiento farmacológicoRESUMEN
Ganodermasides E-H (1-4), four new ergosterol derivatives and two known ones (5 and 6) were isolated from the fermentation of the endophytic fungus Epicoccum poae DJ-F in the stems of Euphorbia royleana Boiss. Their structures were elucidated by spectroscopic analysis, including extensive 1D NMR, 2D NMR, and HRESIMS techniques. All the isolated compounds were tested for their vitro antibacterial activity. Compounds 1-6 showed weak inhibitory effects on Staphylococcus epidermidis, Pseudomonas syringae, and Ralstonia solanacearum with MIC values ranging from 0.4 to 3.6 mM.
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Ascomicetos , Euphorbia , Estructura Molecular , Ergosterol , Ascomicetos/química , AntibacterianosRESUMEN
A highly active interface is extremely critical for the catalytic efficiency of an electrocatalyst; however, facilely tailoring its atomic packing characteristics remains challenging. Herein, a simple yet effective strategy is reported to obtain copious high-energy atomic steps at the interface via controlling the solidification behavior of glass-forming metallic liquids. By adjusting the chemical composition and cooling rate, highly faceted FeNi3 nanocrystals are in situ formed in an FeNiB metallic glass (MG) matrix, leading to the creation of order/disorder interfaces. Benefiting from the catalytically active and stable atomic steps at the jagged interfaces, the resultant free-standing FeNi3 nanocrystal/MG composite exhibits a low oxygen-evolving overpotential of 214 mV at 10 mA cm-2 , a small Tafel slope of 32.4 mV dec-1 , and good stability in alkaline media, outperforming most state-of-the-art catalysts. This approach is based on the manipulation of nucleation and crystal growth of the solid-solution nanophases (e.g., FeNi3 ) in glass-forming liquids, so that the highly stepped interface architecture can be obtained due to the kinetic frustration effect in MGs upon undercooling. It is envisaged that the atomic-level stepped interface engineering via the physical metallurgy method can be easily extended to other MG systems, providing a new and generic paradigm for designing efficient yet cost-effective electrocatalysts.
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The role of TELO2-interacting protein 1 (TTI1) in the progression of several types of cancer has been reported recently. The aim of this study was to estimate the expression and potential value of TTI1 in non-small-cell lung cancer (NSCLC) patients. The expression of TTI1 and its prognostic value in NSCLC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. To verify the bioinformatics findings, a tissue microarray containing 160 NSCLC and paired peritumoral tissues from NSCLC patients was analyzed by immunohistochemistry for TTI1. Subsequently, the roles of TTI1 in NSCLC cells were investigated in vivo by establishing xenograft models in nude mice and in vitro by transwell, CCK-8, wound healing, and colony formation assays. In addition, quantitative real-time polymerase chain reaction and western blot were applied to explore the underlying mechanism by which TTI1 promotes tumor progression. Finally, the relationship between TTI1 and Ki67 expression level in NSCLC was probed, and Kaplan-Meier and Cox analyses were performed to assess the prognostic merit of TTI1 and Ki67 in NSCLC patients. We found that the expression of TTI1 was significantly upregulated in NSCLC tissues compared to paired peritumoral tissues, which coincides with the bioinformatics findings from the TCGA and GEO databases. TTI1 was highly expressed in NSCLC patients with large tumors, advanced tumor stage, and lymphatic metastasis. In addition, the prognostic analysis identified TTI1 as an independent indication for poor prognosis of NSCLC patients. In vitro, upregulation of TTI1 in NSCLC cells could facilitate cell invasion, metastasis, viability, and proliferation. Mechanistically, our study verified that TTI1 could regulate mTOR activity, which has a pivotal role in human cancer. Consistently, the expressions of TTI1 and Ki67 had a positive relationship in NSCLC cells and tissues. Notably, patients with overexpression of TTI1 or Ki67 had a shorter overall survival rate and a higher disease-free survival rate compared to patients with low expression of TTI1 or Ki67, and the combination of TTI1 and Ki67 was an independent parameter predicting the prognosis and recurrence of NSCLC patients. We conclude that TTI1 promotes NSCLC cell proliferation, metastasis, and invasion by regulating mTOR activity, and the combination of TTI1 and Ki67 is a valuable molecular biomarker for the survival and recurrence of NSCLC patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Humanos , Ratones , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/patología , Ratones Desnudos , Pronóstico , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Previous studies have confirmed the oncogenic role of HMGB2 in various cancers, but the biological functions of HMGB2-derived circRNAs remain unknown. Thus, we intended to investigate the potential role of HMGB2-derived circRNAs in lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). METHODS: The expression profiles of HMGB2-derived circRNAs in LUAD and LUSC tissues and matched normal tissues were assessed using qRT-PCR. The role of circHMGB2 in the progression of the LUAD and LUSC was determined in vitro by Transwell, CCK-8, flow cytometry and immunohistochemistry assays, as well as in vivo in an immunocompetent mouse model and a humanized mouse model. In addition, in vivo circRNA precipitation assays, luciferase reporter assays and RNA pulldown assays were performed to explore the underlying mechanism by which circHMGB2 promotes anti-PD-1 resistance in the LUAD and LUSC. RESULTS: The expression of circHMGB2 (hsa_circ_0071452) was significantly upregulated in NSCLC tissues, and survival analysis identified circHMGB2 as an independent indicator of poor prognosis in the LUAD and LUSC patients. We found that circHMGB2 exerted a mild effect on the proliferation of the LUAD and LUSC cells, but circHMGB2 substantially reshaped the tumor microenvironment by contributing to the exhaustion of antitumor immunity in an immunocompetent mouse model and a humanized mouse model. Mechanistically, circHMGB2 relieves the inhibition of downstream CARM1 by sponging miR-181a-5p, thus inactivating the type 1 interferon response in the LUAD and LUSC. Moreover, we found that the upregulation of circHMGB2 expression decreased the efficacy of anti-PD-1 therapy, and we revealed that the combination of the CARM1 inhibitor EZM2302 and an anti-PD-1 antibody exerted promising synergistic effects in a preclinical model. CONCLUSION: circHMGB2 overexpression promotes the LUAD and LUSC progression mainly by reshaping the tumor microenvironment and regulating anti-PD-1 resistance in the LUAD and LUSC patients. This study provides a new strategy for the LUAD and LUSC treatment.
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Adenocarcinoma del Pulmón , Carcinoma de Células Escamosas , Neoplasias Pulmonares , MicroARNs , Proteína-Arginina N-Metiltransferasas , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Animales , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteína HMGB2/genética , Humanos , Terapia de Inmunosupresión , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Ratones , MicroARNs/genética , Proteína-Arginina N-Metiltransferasas/genética , ARN Circular/genética , Microambiente TumoralRESUMEN
BACKGROUND: CD8+ T cells play a critical role in the innate antitumour immune response. Recently, CD8+ T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer (NSCLC). However, the molecular biological mechanisms of CD8+ T cell dysfunction in human NSCLC are still unclear. METHODS: The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8+ T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8+ T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined. RESULTS: The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8+ T cells. Furthermore, circUSP7 inhibits CD8+ T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients. CONCLUSIONS: Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8+ T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.
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Linfocitos T CD8-positivos/metabolismo , Resistencia a Antineoplásicos/genética , MicroARNs/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , ARN Circular/genética , Peptidasa Específica de Ubiquitina 7/genética , Adulto , Anciano , Animales , Linfocitos T CD8-positivos/inmunología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Exosomas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Recuento de Linfocitos , Masculino , Ratones , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Interferencia de ARNRESUMEN
SCOPE: Obesity is a common disease worldwide and there is an urgent need for strategies to preventing obesity. METHODS AND RESULTS: The anti-obesity effect and mechanism of Ligilactobacillus salivarius LCK11 (LCK11) is studied using a C57BL/6J male mouse model in which obesity is induced by a high-fat diet (HFD). Results show that LCK11 can prevent HFD-induced obesity, reflected as inhibited body weight gain, abdominal and liver fat accumulation and dyslipidemia. Analysis of its mechanism shows that on the one hand, LCK11 can inhibit food intake through significantly improving the transcriptional and translational levels of peptide YY (PYY) in the rectum, in addition to the eventual serum PYY level; this is attributed to the activation of the toll-like receptor 2/nuclear factor-κB signaling pathway in enteroendocrine L cells by the peptidoglycan of LCK11. On the other hand, LCK11 supplementation effectively reduces the Firmicutes/Bacteroidetes ratio and shifts the overall structure of the HFD-disrupted gut microbiota toward that of mice fed on a low-fat diet; this also contributes to preventing obesity. CONCLUSION: LCK11 shows the potential to be used as a novel probiotic for preventing obesity by both promoting PYY secretion to inhibit food intake and regulating gut microbiota.
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Microbioma Gastrointestinal/fisiología , Lactobacillaceae , Obesidad/prevención & control , Péptido YY/metabolismo , Tejido Adiposo/fisiología , Animales , Fármacos Antiobesidad/farmacología , Dieta Alta en Grasa/efectos adversos , Dislipidemias/microbiología , Dislipidemias/terapia , Ingestión de Alimentos , Células Enteroendocrinas/metabolismo , Intestinos/microbiología , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/microbiología , Probióticos/farmacología , Aumento de PesoRESUMEN
In recent years, circular RNAs (circRNAs) have been increasingly reported to play a crucial role in the proliferation, migration, and invasion of non-small-cell lung cancer (NSCLC) cells. However, the circRNA MET (circMET) oncogenic mechanism that drives NSCLC development and progression remains largely unknown. In this study, the present results demonstrated that circMET expression was significantly higher in NSCLC tissues than in peritumoral tissues using quantitative real-time polymerase chain reaction. Notably, NSCLC patients with a large tumor diameter, poor differentiation and lymphatic metastasis had high RNA levels of circMET. Moreover, high circMET expression served as an independent risk factor for short overall survival (OS) and progression-free survival (PFS) in NSCLC patients. Next, we validated that circMET overexpression can enhance NSCLC cell proliferation, metastasis, and immune evasion in vitro. Mechanistically, our study uncovers that circMET acts as a miR-145-5p sponge to upregulate CXCL3 expression. Collectively, circMET regulates the miR-145-5p/CXCL3 axis and serves as a novel, promising diagnostic and prognostic biomarker in patients with NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Quimiocinas CXC/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas c-met/genética , ARN Circular/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/genética , Quimiocinas CXC/metabolismo , Femenino , Humanos , Evasión Inmune/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-met/metabolismo , ARN Circular/metabolismoRESUMEN
The electronic package interconnects electronic signals from one area to another and package delamination is a serious problem in the configuration of materials. This study focused on decreasing the delamination of the low-profile fine pitch ball grid array (LFBGA) and plastic ball grid array (PBGA) packages in terms of polymer thermal issue, metal bonding and bonding mechanisms. PBGA and LFBGA are a very common type of packaging processes in the electronics industry. The present study dealt first with delamination of the LFBGA packaging, through characterization and determination of physical and chemical properties such as surface roughness, surface energy, and contact angle. The relationship between surface roughness and delamination was verified through various roughness bonding experiments. In addition, the surface energy was determined by measuring the contact angle after cleaning the metal surface of Cu, Ni and Cr with Ar + O2 gas, and, this gas plasma treatment was applied to enhance the adhesive properties. The compositions of the surface were analyzed through an X-ray photoelectron spectroscopy (XPS). Also, the delamination issue between the corner of the heat sink cap and the epoxy resin was observed for delamination of the LFBGA packaging. Further, this study analyzed the PBGA packaging process through the finite element analysis simulation software ANSYS. To improve the heat sink cap delamination issue of the PBGA, a new chamfer design of the corner seat was streamlined to decrease the stress value and delamination. Besides, the simulation results demonstrated that the stress value reduced after increasing the shoulder length. The results implicate that the stress value is inversely proportional to the shoulder width and the chamfer radius. This study demonstrated that the optimization in design was able reduce the delamination phenomena in configuration material.
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High-resolution partial-fluorescence-yield X-ray absorption and resonant X-ray emission spectra were used to characterize the temperature dependence of Sm 4f configurations and orbital/charge degree of freedom in SmB6. The variation of Sm 4f configurations responds well to the formed Kondo gap, below 140 K, and an in-gap state, below 40 K. The topological in-gap state is correlated with the fluctuating population of Sm 4f configurations that arises via carrier transfer between 3d94f6 and 3d94f5 states; both states are partially delocalized, and the mediating 5d orbital plays the role of a transfer path. Complementary results shown in this work thus manifest the importance of configuration fluctuations and orbital delocalization in the topological surface state of SmB6.
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Previous studies have demonstrated that the homoebox C6 (HOXC6) gene is highly expressed in gastric cancer tissues and is associated with the depth of tumor invasion, and is associated with poor prognosis of gastric cancer patients expressing HOXC6. The present study investigated the effect and underlying mechanism of HOXC6 on the proliferation and metastasis of gastric cancer cells in vitro. Reverse transcriptionquantitative polymerase chain (PCR) reaction was used to investigate the expression levels of HOXC6 in different gastric cancer cell lines and the effect of different levels of expression on the proliferation of gastric cancer cells was determined by cell growth curve and plate colony formation. The effect of HOXC6 on the anchorageindependent proliferation of gastric cancer cells was determined by soft agar colony formation assay while the Transwell invasion assay was used to investigate the effect of different levels of HOXC6 expression on the invasive and metastatic abilities of gastric cancer cells. Semiquantitative PCR was used to detect the effect of different levels of HOXC6 expression on the expression of matrix metalloproteinase (MMP)2 and MMP9 in gastric cancer cells. Immunoblotting was used to assess MMP9 signaling in the gastric cancer cells. The HOXC6 gene is highly expressed in the majority of the gastric cancer cell lines. Overexpression of HOXC6 promoted gastric cancer cell proliferation and colony formation ability while HOXC6 downregulation inhibited cell proliferation and clone forming ability. HOXC6 overexpression also enhanced the soft agar colony formation ability of gastric cancer cells while HOXC6 downregulation decreased the colony formation ability. Upregulated HOXC6 increased the migration and invasion abilities of gastric cancer cells while interfering with HOXC6 expression inhibited the migration and invasion of the gastric cancer cells. The expression of MMP9 was enhanced with an upregulation of HOXC6 expression while HOXC6 downregulation lowered MMP9 gene expression levels. Increased expression of HOXC6 in gastric cancer cell lines significantly activated extracellular signalregulated kinase signaling and upregulated MMP9. The HOXC6 gene promotes the proliferation of gastric cancer cells while upregulation of MMP9 promotes migration and invasion of gastric cancer cells.
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Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Metaloproteinasa 9 de la Matriz/genética , Invasividad Neoplásica/genética , Neoplasias Gástricas/genética , Estómago/patología , Regulación hacia Arriba , Línea Celular Tumoral , Proliferación Celular , Mucosa Gástrica/metabolismo , Humanos , Invasividad Neoplásica/patología , Neoplasias Gástricas/patologíaRESUMEN
Through the systematical measurements of δ13C values of samples representing 25 families and 86 C3 herb species along the slope aspects in an alpine meadow, the responses of δ13C va-lues and water use efficiency (WUE) for C3 plants to slope aspect changes and influence of environmental factors were analyzed and main environmental factors related to plant δ13C values change were revealed. Along the north-facing to south-facing slope, soil water content decreased gradually, the soil temperature and light intensity increased gradually, and plant community structure also had corresponding change. The δ13C values of C3 plant species in 5 slope aspects were from -31.19 to -21.8, with an average value of (-27.18±0.13). The average δ13C value was the highest along the south-facing slope, followed by that along the southwest slope, west slope and northwest slope, with the lowest along the north slope during the whole growing season. The difference of δ13C values among the different slope aspects were caused by discrepancy in soil water content, soil temperature and light intensity. Soil water content was the main limiting factor. From north slope to south slope, plant δ13C value increased with the increasing soil temperature, light intensity and the reducing soil water content, which suggested that different species had different strategies to adapt to environmental changes of drought stress in different slope aspects, and water use efficiency was improved gradually in order to adapt to the environment of drought stress.
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Ecosistema , Hojas de la Planta/fisiología , Suelo , Agua/fisiología , Isótopos de Carbono/análisis , Plantas , Estaciones del Año , TemperaturaRESUMEN
Quantitative structural parameters of pyrochlore Nd2Ru2O7, with temperature dependence, have been derived upon fitting XRD and EXAFS data. An anomalous expansion of the lattice parameter and the Ru-O bond length indicates a structural instability at low temperatures; in particular, an increase in the non-thermal term of the mean square fluctuation in the bond length is the evidence for a static disorder of Ru atoms. This static disorder is closely correlated with a decrease in the average Ru-O-Ru bond angle with decreasing temperature, favoring the short-range ferromagnetic coupling in the material. This ferromagnetic coupling formed thus triggered the spin frustration at low temperature when the contradictory constraints of antiferromagnetic interaction act upon the same Ru site in the corner-sharing tetrahedrons of pyrochlore Nd2Ru2O7. This study demonstrates that the spin frustration arising from the competition of ferromagnetic/antiferromagnetic interactions in pyrochlore Nd2Ru2O7 will cause structural instability especially on the atomic scale, which provides a new point of view to help understand its particular magnetic state.
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BACKGROUND: The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles. MATERIAL/METHODS: Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR). RESULTS: Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2-8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges. CONCLUSIONS: The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.
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Reparación del ADN/genética , Regulación de la Expresión Génica/efectos de la radiación , Leucocitos/metabolismo , Animales , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular/metabolismo , Radioisótopos de Cobalto/administración & dosificación , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta en la Radiación , Rayos gamma , Leucocitos/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Serina-Treonina Quinasas/metabolismo , Radiometría/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Supresoras de Tumor/metabolismoRESUMEN
The effects of soy isoflavone (SIF) on insulin sensitivity and adipocytokines in high-fat-diet-induced insulin resistant (IR) rats were studied. Male Sprague Dawley rats (n = 80) were randomly assigned into a basal diet fed group and high-fat diet fed group. The high-fat-diet-induced IR rats were assigned into IR model control group and three SIF-treated groups with different dosages. Thirty days later, the fasting blood glucose, insulin and adipocytokines in serum and mRNA expressions of adipocytokines in perirenal white adipose tissue were measured. The Homeostasis Model Assessment of IR was calculated. The administration of 450 mg kg(-1) d(-1) SIF decreased the body weights and depositions of visceral adipose tissue as well as improved insulin resistance in high-fat-diet-induced IR rats. The mechanisms were associated with SIF regulating the expression of adipocytokines, including adiponectin, leptin, resistin and TNF-alpha. SIF supplements may have favourable effects on insulin resistance in high-fat-diet-induced IR rats.
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Adipoquinas/metabolismo , Grasas de la Dieta/administración & dosificación , Glycine max/química , Resistencia a la Insulina , Insulina/sangre , Isoflavonas/farmacología , Animales , Modelos Animales de Enfermedad , Hipoglucemiantes/farmacología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To explore the effects of soy isoflavone (SIF) on low-grade inflammation in rats with high-fat diet-induced insulin resistance (IR) and explore the mechanisms of SIF in improving insulin sensitivity. METHODS: The rats with high-fat diet-induced IR were randomly divided into one model control group and 3 SIF groups gavaged with SIF water solutions at the doses of 50, 150, and 450 mg/kg, respectively. One month after the treatment, fasting blood glucose (FBG), fasting insulin (FINS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), resistin and adiponectin in the serum were detected by enzymatic method, radioimmunoassay, or enzyme-linked immunosorbent assay. RESULTS: In the 150 and 450 mg/kg SIF groups, fasting body-weights, visceral adipose tissue deposition, FINS, resistin, TNF-alpha in serum, and IR index were lowered in comparison with the model control group, and in 450 mg/kg SIF group, serum IL-6 level was obviously lowered, and adiponectin increased. No differences were found in serum C-reactive protein levels between the 3 SIF groups. CONCLUSION: Soy isoflavone may ameliorate insulin sensitivity by decreasing visceral adipose deposition and adjusting low-grade inflammatory molecules derived from white adipose tissue.
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Proteína C-Reactiva/metabolismo , Glycine max/química , Resistencia a la Insulina , Isoflavonas/farmacología , Factor de Necrosis Tumoral alfa/sangre , Adiponectina/sangre , Animales , Peso Corporal/efectos de los fármacos , Inflamación/sangre , Inflamación/fisiopatología , Insulina/sangre , Interleucina-6/sangre , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Resistina/sangreRESUMEN
OBJECTIVE: To explore the mechanism of Shenqi compound recipe (SQCR) anti-earlier diabetic artherosclerosis in GK rats. METHOD: Four-month specefic pathogen free (SPF) GK rats were divided randomly according to blood glucose level into four groups: model group (5 mL x kg(-1) x d(-1) sterile water), ramipril group (positive control, 1 mg x kg(-1) x d(-1)), SQCR low dosage (0.72 g x kg(-1) x d(-1)) and SQCR high dosage group (2.88 g x kg(-1) x d(-1)) and Wistar rats as normal control group(5 mL x kg(-1) x d(-1) sterile water). GK rats took high-fat diet freely and meanwile were injected N-omega-nitro-L-arginine methyl ester (L-N-AME) intra-peritoneally with the dose of 10 mg x kg(-1) x d(-1) in order to induce earlier diabetic artherosclerosis, while normal control group took regular diet and were injected normal saline intra-peritoneally. In the experiment periods, each group was administrated correspondent substance respectively for 32 d. At the end, sampling blood by abdominal aorta and picking aorta on ice. Determined monocyte chemoattractant protein-1 (MCP-1) concentration by ELISA, messenger ribonucleic acid (mRNA) expression of MCP-1 and peroxisome proliferator-activated receptor gamma (PPARgamma) in aorta by reverse transcriptase PCR (RT-PCR). RESULT: Concentrations of MCP-1 in serum in SQCR low and high dosage groups and the mRNA expression of MCP-1 in SQCR high dosage group were all decreased significantly compared with model group (P < 0.05). The mRNA expression of PPARgamma in SQCR low and high dosage groups all increased compared with model group (P < 0.05 or P < 0.01). CONCLUSION: Inhibiting the mRNA and protein expression of MCP-1 and upregulating the mRNA expression of PPARgamma in aorta might be contribute to SQCR anti-earlier diabetic artherosclerosis in GK rats partly.
Asunto(s)
Aterosclerosis/metabolismo , Quimiocina CCL2/biosíntesis , Diabetes Mellitus Tipo 2/metabolismo , Medicamentos Herbarios Chinos/farmacología , Plantas Medicinales , Animales , Aorta/metabolismo , Astragalus propinquus/química , Aterosclerosis/etiología , Quimiocina CCL2/sangre , Quimiocina CCL2/genética , Diabetes Mellitus Tipo 2/complicaciones , Combinación de Medicamentos , Medicamentos Herbarios Chinos/aislamiento & purificación , Masculino , PPAR gamma/biosíntesis , PPAR gamma/genética , Panax/química , Plantas Medicinales/química , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To assess the effects of soy isoflavone (SIF) on improving insulin reistance (IR) status in IR rats induced by high-fat and high-sugar diet and explore the possible mechanisms. METHODS: IR rats were randomly divided into four groups according to their insulin resistance indices (IRI). The rats in one model control group and three SIF groups were fed via gavage with water solutions containing SIF at doses of 0 mg/ kg x bw, 50 mg/kg x bw, 150 mg/kg x bw, and 450 mg/kg x bw, respectively. After one month, fasting glucose, fasting insulin, resistin in serum, and resistin mRNA in adipocyte around kidney were detected by enzymologic method, radioimmunoassay, enzyme linked immunosorbent assay, and real time RT-PCR, respectively. RESULTS: Comparison between the model control group and the other groups revealed that serum resistin and resistin mRNA expression levels were lower in the 450 mg/kg x bw group, that insulin and IRI levels were lower in the 150 mg/ kg x bw group and 450 mg/kg x bw group, and that no differences in plasma glucose levels existed among the 4 groups. A positive correlation between IRI and serum resistin level (r = 0.355, P < 0.05) was observed. CONCLUSION: These results suggest that soy isoflavone may down-regulate resistin mRNA expression, decrease serum resistin level and enhance insulin sensitivity.
Asunto(s)
Glycine max/química , Resistencia a la Insulina/genética , Isoflavonas/farmacología , Resistina/biosíntesis , Animales , Masculino , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Resistina/sangre , Resistina/genéticaRESUMEN
OBJECTIVE: To explore the effects of soy isoflavone (SIF) on low-grade inflammation in obese rats induced by high-fat diet, and to elucidate mechanisms of SIF in improving insulin sensitivity. METHODS: Obese rats were randomly divided into 4 groups: One model control group and 3 SIF groups that were given water solutions with SIF at 0 mg/(kg x d), 50 mg/(kg x d), 150 mg/(kg x d), and 450 mg/(kg x d), respectively. After one month, fasting glucose, fasting insulin, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, resistin, and adiponectin in serum were detected by enzymic method, radioimmunoassay, and enzyme linked immunosorbent assay, respectively. RESULTS: In the 150 mg/(kg x d) group and 450 mg/(kg x d) group, fasting body-weights, viscera fatty deposition, and contents of insulin, interleukin-6, and tumor necrosis factor-alpha in serum were significantly lower; serum adiponectin levels were significantly higher; and serum resistin levels were significantly lower in the 450 mg/(kg d) group than those of the model control group. There was no difference in serum C-reactive protein levels among the 3 SIF groups. CONCLUSION: Soy isoflavone may improve the insulin sensitivity by decreasing viscera fatty deposition and adjusting low-grade inflammatory molecules derived from white adipose tissues.