29 research outputs found

    Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia-Reperfusion and Cyclosporine A in Mice.

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    Renal ischemia-reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis

    Prognostic and therapeutic implications of iron-related cell death pathways in acute myeloid leukemia

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    Acute myeloid leukemia (AML) is a blood cancer that is diverse in terms of its molecular abnormalities and clinical outcomes. Iron homeostasis and cell death pathways play crucial roles in cancer pathogenesis, including AML. The objective of this study was to examine the clinical significance of genes involved in iron-related cell death and apoptotic pathways in AML, with the intention of providing insights that could have prognostic implications and facilitate the development of targeted therapeutic interventions. Gene expression profiles, clinical information, and molecular alterations were integrated from multiple datasets, including TCGA-LAML and GSE71014. Our analysis identified specific molecular subtypes of acute myeloid leukemia (AML) displaying varying outcomes, patterns of immune cell infiltration, and profiles of drug sensitivity for targeted therapies based on the expression of genes involved in iron-related apoptotic and cell death pathways. We further developed a risk model based on four genes, which demonstrated promising prognostic value in both the training and validation cohorts, indicating the potential of this model for clinical decision-making and risk stratification in AML. Subsequently, Western blot analysis showed that the expression levels of C-Myc and CyclinD1 were significantly reduced after CD4 expression levels were knocked down. The findings underscore the potential of iron-related cell death pathways as prognostic biomarkers and therapeutic targets in AML, paving the way for further research aimed at understanding the molecular mechanisms underlying the correlation between iron balance, apoptosis regulation, and immune modulation in the bone marrow microenvironment

    High-energy, alignment-insensitive, injection-seeded Q-switched Ho:yttrium aluminum garnet single-frequency laser

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    A high-energy, alignment-insensitive, injection-seeded Q-switched Ho:yttrium aluminum garnet (YAG) single-frequency laser is developed. Both the slave Q-switched laser and the seed laser are Ho:YAG ring lasers based on a pair of corner cubic reflectors. The seed laser has an available power of 830 mW at 2096.667 nm. At 100 Hz, the Q-switched Ho:YAG laser provides a single-frequency pulsed output using injection-seeded technology. The 7.3 mJ single-frequency pulse energy from the slave laser has a pulse width of 161.2 ns and is scaled to 33.3 mJ after passing through the Ho:YAG single-pass amplifier. According to the measurement results of the heterodyne beating technique, the single-frequency pulse has a half-width of 4.12 MHz

    Exploring the Influences of Temperature on "H-Shaped" Glycerol Dialkyl Glycerol Tetraethers in a Stratigraphic Context: Evidence From Two Peat Cores Across the Late Quaternary

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    Unusual "H-Shaped" branched and isoprenoidal glycerol monoalkyl glycerol tetraethers (GMGTs, or H-GDGTs) have been found in peat, lake, and ocean sediments. A survey of recent samples from a modern global peat database suggested that there is a relationship between the abundance of H-GDGTs relative to regular GDGTs and temperature. However, this relationship has not been widely explored, including in a historical, stratigraphic or geological context. Here, we report the abundance and distribution of H-iso- and H-brGDGTs in two (Hani and Gushantun) peat cores from northeastern China through the late Quaternary (last 15 kyr) to examine whether the relationship between temperature and the relative abundance of H-GDGTs is preserved downcore. The results indicate that high relative abundances of H-brGDGTs are associated with high (or increasing) reconstructed mean annual air temperature (MAAT(peat)), albeit with considerable divergence in some intervals. On the other hand, high relative abundances of H-isoGDGTs are generally associated with low (or decreasing) MAAT(peat). These findings are partly inconsistent with the observations from the modern database of globally distributed peats, which showed that the abundance of both (br- and iso-) H-GDGTs is positively correlated with temperature. The deviation in the relationship between H-isoGDGTs and temperature suggests that additional factors, for example pH and shifts in archaeal community related to hydrology, exert an influence on the abundance of H-isoGDGTs on the long-term

    Improved Leakage Behavior at High Temperature via Engineering of Ferroelectric Sandwich Structures

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    The leakage behavior of ferroelectric film has an important effect on energy storage characteristics. Understanding and controlling the leakage mechanism of ferroelectric film at different temperatures can effectively improve its wide-temperature storage performance. Here, the structures of a 1 mol% SiO2-doped BaZr0.35Ti0.65O3 (BZTS) layer sandwiched between two undoped BaZr0.35Ti0.65O3 (BZT35) layers was demonstrated, and the leakage mechanism was analyzed compared with BZT35 and BZTS single-layer film. It was found that interface-limited conduction of Schottky (S) emission and the Fowler-Nordheim (F-N) tunneling existing in BZT35 and BZTS films under high temperature and a high electric field are the main source of the increase of leakage current and the decrease of energy storage efficiency at high temperature. Only an ohmic conductive mechanism exists in the whole temperature range of BZT35/BZTS/BZT35(1:1:1) sandwich structure films, indicating that sandwich multilayer films can effectively simulate the occurrence of interface-limited conductive mechanisms and mention the energy storage characteristics under high temperature

    Prolonged cooling interrupted the Bronze Age cultures in northeastern China 3500 years ago

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    The role of climatic change in the social transition in NE China during the Bronze Age is poorly understood due to the lack of reliable climate proxy records. Here we report a 3600-yr-long climate record based on branched glycerol dialkyl glycerol tetraether distributions in the Jinchuan peat core, Northeastern (NE) China. Our record shows a persistent cooling between ca.3.5-3.0 ka, which coincides with the societal transition from a settled to a mobile lifestyle. Comparing existing records suggests that this event represents a hemispherical-scale cooling probably driven by the prolonged El Nino conditions. The low temperatures caused unfavorable conditions for the agriculture-based society during the Lower Xiajiadian period and thus drove people to flee southward into the North China and Central China Plains, leading to a culturally desolated area that was gradually occupied by pastoralists in about 250 years. Our results highlight the need to consider the interplay of climatic dynamics with social upheaval in understanding the evolution of prehistorical civilization in NE Asia
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