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1.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732143

RESUMEN

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.


Asunto(s)
Modelos Animales de Enfermedad , Tratamiento con Ondas de Choque Extracorpóreas , Contracción Muscular , Canales Catiónicos TRPV , Vejiga Urinaria , Animales , Femenino , Ratas , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Vejiga Urinaria/fisiopatología , Vejiga Urinaria/metabolismo , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/metabolismo , Vejiga Urinaria Hiperactiva/fisiopatología , Vejiga Urinaria Hiperactiva/etiología , Ovariectomía , Ratas Sprague-Dawley , Ovario/metabolismo
2.
Sci Rep ; 14(1): 3006, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321094

RESUMEN

The large Weilasituo Sn-polymetallic deposit is a recent exploration discovery in the southern Great Xing'an Range, northeast China. The ore cluster area shows horizontal mineralization zoning, from the inner granite body outward, consisting of high-T Sn-W-Li mineralization, middle-T Cu-Zn mineralization and peripheral low-T Pb-Zn-Ag mineralization. However, the intrinsic genetic relationship between Sn-W-Li mineralization and peripheral vein-type Pb-Zn-Ag-Cu mineralization, the formation mechanism and the deep geological background are still insufficiently understood. Here, we use fluid inclusions, trace elements concentrations in quartz and sphalerite, and H-O isotope studies to determine the genetic mechanism and establish a metallogenic model. Fluid inclusion microthermometry and Laser Raman spectroscopic analysis results demonstrates that the aqueous ore-forming fluids evolved from low-medium salinity, medium-high temperature to low salinity, low-medium temperature fluids. Laser Raman spectroscopic analysis shows that CH4 is ubiquitous in fluid inclusions of all ore stages. Early ore fluids have δ18OH2O (v-SMOW) values from + 5.5 to + 6.2‰ and δD values of approximately - 67‰, concordant with a magmatic origin. However, the late ore fluids shifted toward lower δ18OH2O (v-SMOW) (as low as 0.3‰) and δD values (~ - 136‰), suggesting mixing between external fluids derived from the wall rocks and a contribution from meteoric water. Ti-in-quartz thermometry indicates a magmatic crystallization temperature of around 700 °C at a pressure of 1.5 kbar for the magmatic ore stage. Cathodoluminescence (CL) imaging and trace element analysis of quartz from a hydrothermal vug highlight at least three growth episodes that relate to different fluid pulses; each episode begins with CL-bright, Al-Li-rich quartz, and ends with CL-dark quartz with low Al and Li contents. Quartz from Episode 1 formed from early Sn-(Zn)-rich fluids which were likely derived from the quartz porphyry. Quartz from episodes 2 and 3 formed from Zn-(Sn)-Cu-rich fluid. The early magmatic fluid is characterized by low fS2. The SO2 produced by magma degassing reacted with heated water to form SO42-, causing the shift from low fS2 to high fS2. The SO42- generated was converted to S2- by mixing with CH4-rich, Fe and Zn-bearing external fluid which led to late-stage alteration and dissolution of micas in vein walls, thus promoting crystallization of pyrrhotite, Fe-rich sphalerite and chalcopyrite and inhibiting the precipitation of anhydrite. This study shows that ore formation encompassed multiple episodes involving steadily evolved fluids, and that the addition of external fluids plays an important role in the formation of the later Cu-Zn and Ag-Pb-Zn mineralization in the Weilasituo ore district.

3.
Sci Rep ; 13(1): 19022, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37923778

RESUMEN

Extended duration of normothermic machine perfusion (NMP) provides opportunities to resuscitate suboptimal donor livers. This intervention requires adequate oxygen delivery typically provided by a blood-based perfusion solution. Methaemoglobin (MetHb) results from the oxidation of iron within haemoglobin and represents a serious problem in perfusions lasting > 24 h. We explored the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor livers declined for transplantation: three were perfused without NAC (no-NAC group), and six organs perfused with an initial NAC bolus, followed by continuous infusion (NAC group), with hourly methaemoglobin perfusate measurements. In-vitro experiments examined the impact of NAC (3 mg) on red cells (30 ml) in the absence of liver tissue. The no-NAC group sustained perfusions for an average of 96 (range 87-102) h, universally developing methaemoglobinaemia (≥ 2%) observed after an average of 45 h, with subsequent steep rise. The NAC group was perfused for an average of 148 (range 90-184) h. Only 2 livers developed methaemoglobinaemia (peak MetHb of 6%), with an average onset of 116.5 h. Addition of NAC efficiently limits formation and accumulation of methaemoglobin during NMP, and allows the significant extension of perfusion duration.


Asunto(s)
Trasplante de Hígado , Metahemoglobinemia , Humanos , Trasplante de Hígado/métodos , Acetilcisteína/farmacología , Preservación de Órganos/métodos , Metahemoglobina , Hígado , Perfusión/métodos
4.
Int J Mol Sci ; 24(9)2023 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-37175945

RESUMEN

Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich plasma (PRP) or platelet-poor plasma (PPP) after 12 months of OVX to investigate the therapeutic effects of PRP on OHD-induced OAB. The OVX-treated rats exhibited a decrease in the expression of urothelial barrier-associated proteins, altered hyaluronic acid (hyaluronan; HA) production, and exacerbated bladder pathological damage and interstitial fibrosis through NFƘB/COX-2 signaling pathways, which may contribute to OAB. In contrast, PRP instillation for four weeks regulated the inflammatory fibrotic biosynthesis, promoted cell proliferation and matrix synthesis of stroma, enhanced mucosal regeneration, and improved urothelial mucosa to alleviate OHD-induced bladder hyperactivity. PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-α6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS), reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration.


Asunto(s)
Plasma Rico en Plaquetas , Vejiga Urinaria Hiperactiva , Humanos , Ratas , Femenino , Animales , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Ratas Sprague-Dawley , Ácido Hialurónico/farmacología , Fosfatidilinositol 3-Quinasas , Plasma Rico en Plaquetas/metabolismo
5.
Cell Rep Med ; 4(5): 101026, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37137303

RESUMEN

Recurrent spontaneous miscarriage (RSM) affects 1%-2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. In vivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM.


Asunto(s)
Aborto Espontáneo , Decidua , Embarazo , Humanos , Femenino , Ratones , Animales , Decidua/metabolismo , Ácidos Cetoglutáricos/metabolismo , Aborto Espontáneo/metabolismo , Células Cultivadas , Endometrio/metabolismo
6.
Geobiology ; 21(1): 44-65, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36200974

RESUMEN

Most Neoproterozoic iron formations (NIF) are closely associated with global or near-global "Snowball Earth" glaciations. Increasingly, however, studies indicate that some NIFs show no robust evidence of glacial association. Many aspects of non-glacial NIF genesis, including the paleo-environmental setting, Fe(II) source, and oxidation mechanisms, are poorly understood. Here, we present a detailed case study of the Jiapigou NIF, a major non-glacial NIF within a Neoproterozoic volcano-sedimentary sequence in North Qilian, northwestern China. New U-Pb geochronological data place the depositional age of the Jiapigou NIF at ~600 Ma. Petrographic and geochemical evidence supports its identification as a primary chemical sediment with significant detrital input. Major and trace element concentrations, REE + Y systematics, and εNd (t) values indicate that iron was sourced from mixed seawater and hydrothermal fluids. Iron isotopic values (δ56 Fe = -0.04‰-1.43‰) are indicative of partial oxidation of an Fe(II) reservoir. We infer that the Jiapigou NIF was deposited in a redox stratified water column, where hydrothermally sourced Fe(II)-rich fluids underwent oxidation under suboxic conditions. Lastly, the Jiapigou NIF has strong phosphorous enrichments, which in other iron formations are typically interpreted as signals for high marine phosphate concentrations. This suggests that oceanic phosphorus concentrations could have been enriched throughout the Neoproterozoic, as opposed to simply during glacial intervals.


Asunto(s)
Hierro , Agua de Mar , Hierro/análisis , Océanos y Mares , Planeta Tierra , Fósforo , Compuestos Ferrosos , Sedimentos Geológicos
7.
Chem Commun (Camb) ; 58(98): 13600-13603, 2022 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-36398682

RESUMEN

Through the exchange-extended growth method (EEGM), MOF-on-MOF heteroarchitectures with distinct crystallography were produced and pyrolyzed into hybrid metal oxides. The strong exchange ability of organometallic compounds realized the component reconstruction of the MOF matrix and enhanced the interfacial forces between MOFs, showing an excellent performance in low-temperature catalytic oxidation.


Asunto(s)
Compuestos Organometálicos
8.
J Reprod Immunol ; 151: 103626, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35483213

RESUMEN

Oxygen is vital for the normal function of cells and is transported to all parts of the body through red blood cells in the vasculature. Abnormal oxygen concentrations can lead to many complications, and reestablishing oxygen balance is essential for cell biological functions. Mammalian cells have evolved to adapt to hypoxia and sense oxygen levels during hypoxia to maintain and coordinate different biological responses. The best mechanism for studying the hypoxia response involves hypoxia-inducible factors (HIFs), which control the expression of many hypoxia-inducible genes. Recent studies have found that other epigenetic modifier enzymes and metabolite signaling pathways can also sense dynamic changes in oxygen. The mammalian intrauterine oxygen concentration and the mechanisms controlling oxygen homeostasis affect placental development, structure and function. In this review, we focus on how mammalian cells sense oxygen levels and produce anoxic-dependent adaptive responses and explore the relationship between hypoxia and placental development during early pregnancy.


Asunto(s)
Oxígeno , Placenta , Animales , Femenino , Humanos , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Mamíferos/metabolismo , Oxígeno/metabolismo , Placenta/metabolismo , Placentación/fisiología , Embarazo , Transducción de Señal
9.
ACS Omega ; 6(44): 29596-29608, 2021 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-34778631

RESUMEN

Development of multi-ligand metal-organic frameworks (MOFs) and derived heteroatom-doped composites as efficient non-noble metal-based catalysts is highly desirable. However, rational design of these materials with controllable composition and structure remains a challenge. In this study, novel hierarchical N-doped CuO/Cu composites were synthesized by assembling dual-ligand MOFs via a solvent-induced coordination modulation/low-temperature pyrolysis method. Different from a homogeneous system, our heterogeneous nucleation strategy provided more flexible and cost-effective MOF production and offered efficient direction/shape-controlled synthesis, resulting in a faster reaction and more complete conversion. After pyrolysis, they further transformed to a unique metal/carbon matrix with regular morphology and, as a hot template, guided the orderly generation of metal oxides, eliminating sintering and agglomeration of metal oxides and initiating a synergistic effect between the N-doped metal oxide/metal and carbon matrix. The prepared N-doped CuO/Cu catalysts held unique water resistance and superior catalytic activity (100% CO conversion at 140 °C).

10.
Cell Rep ; 34(7): 108759, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33596418

RESUMEN

As transcription and replication use DNA as substrate, conflicts between transcription and replication can occur, leading to genome instability with direct consequences for human health. To determine how the two processes are coordinated throughout S phase, we characterize both processes together at high resolution. We find that transcription occurs during DNA replication, with transcription start sites (TSSs) not fully replicated along with surrounding regions and remaining under-replicated until late in the cell cycle. TSSs undergo completion of DNA replication specifically when cells enter mitosis, when RNA polymerase II is removed. Intriguingly, G2/M DNA synthesis occurs at high frequency in unperturbed cell culture, but it is not associated with increased DNA damage and is fundamentally separated from mitotic DNA synthesis. TSSs duplicated in G2/M are characterized by a series of specific features, including high levels of antisense transcription, making them difficult to duplicate during S phase.


Asunto(s)
División Celular/genética , Replicación del ADN/genética , Fase G2/genética , ARN/genética , Sitio de Iniciación de la Transcripción/fisiología , Humanos
11.
Blood ; 135(6): 411-428, 2020 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-31794600

RESUMEN

Spontaneous regression is a recognized phenomenon in chronic lymphocytic leukemia (CLL) but its biological basis remains unknown. We undertook a detailed investigation of the biological and clinical features of 20 spontaneous CLL regression cases incorporating phenotypic, functional, transcriptomic, and genomic studies at sequential time points. All spontaneously regressed tumors were IGHV-mutated with no restricted IGHV usage or B-cell receptor (BCR) stereotypy. They exhibited shortened telomeres similar to nonregressing CLL, indicating prior proliferation. They also displayed low Ki-67, CD49d, cell-surface immunoglobulin M (IgM) expression and IgM-signaling response but high CXCR4 expression, indicating low proliferative activity associated with poor migration to proliferation centers, with these features becoming increasingly marked during regression. Spontaneously regressed CLL displayed a transcriptome profile characterized by downregulation of metabolic processes as well as MYC and its downstream targets compared with nonregressing CLL. Moreover, spontaneous regression was associated with reversal of T-cell exhaustion features including reduced programmed cell death 1 expression and increased T-cell proliferation. Interestingly, archetypal CLL genomic aberrations including HIST1H1B and TP53 mutations and del(13q14) were found in some spontaneously regressing tumors, but genetic composition remained stable during regression. Conversely, a single case of CLL relapse following spontaneous regression was associated with increased BCR signaling, CLL proliferation, and clonal evolution. These observations indicate that spontaneously regressing CLL appear to undergo a period of proliferation before entering a more quiescent state, and that a complex interaction between genomic alterations and the microenvironment determines disease course. Together, the findings provide novel insight into the biological processes underpinning spontaneous CLL regression, with implications for CLL treatment.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/genética , Adulto , Anciano , Anciano de 80 o más Años , Proliferación Celular , Femenino , Regulación Leucémica de la Expresión Génica , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunoglobulina M/genética , Antígeno Ki-67/genética , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo de Nucleótido Simple , Receptores CXCR4/genética , Microambiente Tumoral
12.
Sci Rep ; 9(1): 15056, 2019 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-31636318

RESUMEN

Earth's atmosphere experienced a step of profound oxygenation during the Neoproterozoic era, accompanied by diversification of animals. However, during the Cryogenian period (720-635 million years ago) Earth experienced its most severe glaciations which likely impacted marine ecosystems and multicellular life in the oceans. In particular, large volumes of Mn and Fe accumulated during the interglacial intervals of the Cryogenian glaciations, indicating large anoxic marine metal reservoirs. Here we present chromium isotope-, rare earth element-, and redox-sensitive trace element data of sedimentary rocks from the interglacial Datangpo Formation deposited between the Sturtian and Marinoan glaciations in South China, in an attempt to investigate the oxidation state of the oceans and atmosphere. Both the Cr isotope and trace element data indicate mainly anoxic water conditions with cryptic oxic surface water incursions after the Sturtian glaciation. Glacial-fed manganese precipitated as manganese carbonate in anoxic basins, and the non-fractionated δ53Cr record of -0.10 ± 0.06‰ identifies anoxic conditions with a cryptic component of slightly fractionated Cr isotope composition in manganese ore, in line with distinctly fractionated Mo isotope composition. Both the manganese carbonate ore and the black shales exhibit very low redox-sensitive element concentrations. Our study demonstrates that the oxygenation of the seawater, and inferably of the atmosphere, at the beginning of the Cryogenian interglacial interval was much subdued. The post-glacial rebound then allowed the Ediacaran biological diversity.

13.
Sci Bull (Beijing) ; 64(3): 205-212, 2019 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36659619

RESUMEN

Hydrothermal ore deposits at convergent plate boundaries represent extraordinary metal enrichment in the continental crust. They are generally associated with felsic magmatism in extensional settings at high thermal gradients. Although their formation is common during accretionary orogeny, more and more ore deposits have been discovered recently in the collisional orogens of China. Because collisional orogeny was operated in a compressional regime at low thermal gradients, it is not favorable for mobilization of ore-forming elements and thus for the production of hydrothermal ore deposits. Nevertheless, continental collision is generally preceded by oceanic subduction, which enables the preliminary enrichment of ore-forming elements in the mantle wedge due to chemical metasomatism by subducting slab-derived fluids. This gave rise to metal pre-enriched domains in the overriding lithosphere, which may be reactivated by extensional tectonism for hydrothermal mineralization either immediately during accretionary orogeny or at a later time during and after collisional orogeny. It is these tectonic processes that have resulted in the progressive enrichment of ore-forming elements through the geochemical differentiation of the subducting oceanic crust, the metasomatic mantle domains and the mafic juvenile crust, respectively, at different depths. Finally, the reactivation of metal pre-enriched domains by continental rifting in the orogenic lithosphere is the key to the metallogenesis of collisional orogens.

14.
Blood ; 130(2): 156-166, 2017 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-28495793

RESUMEN

The role of deubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation of the p53-dependent DNA damage response (DDR) pathway is well established. Whereas previous studies have mostly focused on the mechanisms underlying how USP7 directly controls p53 stability, we recently showed that USP7 modulates the stability of the DNA damage responsive E3 ubiquitin ligase RAD18. This suggests that targeting USP7 may have therapeutic potential even in tumors with defective p53 or ibrutinib resistance. To test this hypothesis, we studied the effect of USP7 inhibition in chronic lymphocytic leukemia (CLL) where the ataxia telangiectasia mutated (ATM)-p53 pathway is inactivated with relatively high frequency, leading to treatment resistance and poor clinical outcome. We demonstrate that USP7 is upregulated in CLL cells, and its loss or inhibition disrupts homologous recombination repair (HRR). Consequently, USP7 inhibition induces significant tumor-cell killing independently of ATM and p53 through the accumulation of genotoxic levels of DNA damage. Moreover, USP7 inhibition sensitized p53-defective, chemotherapy-resistant CLL cells to clinically achievable doses of HRR-inducing chemotherapeutic agents in vitro and in vivo in a murine xenograft model. Together, these results identify USP7 as a promising therapeutic target for the treatment of hematological malignancies with DDR defects, where ATM/p53-dependent apoptosis is compromised.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Leucemia Linfocítica Crónica de Células B/genética , Reparación del ADN por Recombinación/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteasas Ubiquitina-Específicas/genética , Adenina/análogos & derivados , Animales , Antineoplásicos/farmacología , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Línea Celular Tumoral , Daño del ADN , Resistencia a Antineoplásicos/genética , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Ratones , Ratones Endogámicos NOD , Piperidinas , Cultivo Primario de Células , Pirazoles/farmacología , Pirimidinas/farmacología , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Peptidasa Específica de Ubiquitina 7 , Proteasas Ubiquitina-Específicas/antagonistas & inhibidores , Proteasas Ubiquitina-Específicas/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Oncotarget ; 8(27): 44749-44760, 2017 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-28496009

RESUMEN

Subclonal heterogeneity and clonal selection influences disease progression in chronic lymphocytic leukemia (CLL). It is therefore important that therapeutic decisions are made based on an understanding of the CLL clonal architecture and its dynamics in individual patients. Identification of cytogenetic abnormalities by FISH remains the cornerstone of contemporary clinical practice and provides a simple means for prognostic stratification. Here, we demonstrate that multiplexed-FISH can enhance recognition of CLL subclonal repertoire and its dynamics during disease progression, both in patients and CLL patient-derived xenografts (PDX). We applied a combination of patient-specific FISH probes to 24 CLL cases before treatment and at relapse, and determined putative ancestral relationships between subpopulations with different cytogenetic features. We subsequently established 7 CLL PDX models in NOD/Shi-SCID/IL-2Rγctm1sug/Jic (NOG) mice. Application of multiplexed-FISH to these models demonstrated that all of the identified cytogenetic subpopulations had leukemia propagating activity and that changes in their representation during disease progression could be spontaneous, accelerated by treatment or treatment-induced. We conclude that multiplexed-FISH in combination with PDX models have the potential to distinguish between spontaneous and treatment-induced clonal selection, and therefore provide a valuable tool for the pre-clinical evaluation of novel therapies.


Asunto(s)
Aberraciones Cromosómicas , Evolución Clonal/genética , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Animales , Terapia Combinada , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Xenoinjertos , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/terapia , Masculino , Ratones , Pronóstico , Análisis de la Célula Individual , Resultado del Tratamiento
16.
Int J Comput Assist Radiol Surg ; 11(11): 2105-2110, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27234375

RESUMEN

PURPOSE: Metallic foreign bodies (MFBs) retained in soft tissue may pose potential threats to patient health. Interventional procedures using conventional navigation systems are associated with high rate of radiation exposure. We postulated that the surgical approach visualization and navigation system would offer precise percutaneous localization and linear guidance with reduced radiation dosage and system complexity. METHODS: In total, 76 patients underwent percutaneous MFB extraction with the technique, which consists of: (A) displaying the target spot (here the MFB) on the screen; (B) projecting the laser beam onto the skin surface; (C) indicating the optimal direction and angle of the needle; and (D) guiding the surgical approach until the MFB was extracted. RESULTS: A total of 76 MFBs were successfully extracted with a single operation. No systemic complications were observed. The procedure took between 2 and 11 min, with an average of [Formula: see text] min, demonstrating the characteristics of a normal distribution. The mean size of wound was [Formula: see text] mm. The mean amount of bleeding was [Formula: see text] ml. The number of times the intra-operative fluoroscopy was used ranged from one to four times for a single procedure, with an average of 1.89 ± 0.74. CONCLUSION: The proposed navigation system which combines the laser positioning and navigation techniques seems to be a novel surgical approach of high accuracy and efficiency.


Asunto(s)
Cuerpos Extraños/diagnóstico por imagen , Adolescente , Adulto , Anciano , Dorso , Niño , Preescolar , Femenino , Fluoroscopía/métodos , Cuerpos Extraños/cirugía , Humanos , Imagenología Tridimensional , Extremidad Inferior , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Dosis de Radiación , Cirugía Asistida por Computador/métodos , Extremidad Superior , Adulto Joven
17.
Environ Toxicol ; 29(10): 1134-46, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23364946

RESUMEN

This study evaluated the effects of ß-diketone antibiotics (DKAs) on the development of embryo-larval zebrafish (Danio rerio). When exposure to DKAs, developmental malformations, such as hatching delay, curved body axis, pericardial edema, uninflated swim bladder and yolk sac edema, were observed at 120 h postfertilization (hpf). The estimated 120 hpf nominal concentrations of no observed effect concentration and lowest observed effect concentration for DKAs were 18.75 and 37.50 mg/L, respectively, suggesting that DKAs have much lower toxicity than other persistent pollutants. Following DKA exposure, embryonic heart rates were significantly reduced as compared to the controls at 48 and 60 hpf. The peak bending motion frequency appeared 1 h earlier than in control embryos. The 2.34 and 9.38-mg/L treatment groups had a higher basal swim rate than control groups at 120 hpf in both light and light-to-dark photoperiod experiments. The occurrence of high speed swim rates was enhanced approximately threefold to sevenfold in the 2.34 and 9.38 mg/L treatments compared to the control. Glutathione (GSH) concentrations in the 2.34 and 9.38-mg/L treatments were significantly higher than the control at 72 hpf, suggesting that GSH production was induced at the end of the hatching period. When exposed to DKAs, zebrafish superoxide dismutase enzyme (SOD) activities were significantly inhibited in the early embryonic period, demonstrating that the clearing ability in zebrafish was lower than the generation rate of free radicals. In summary, the combined DKAs were developmentally toxic to zebrafish in their early life stages and had the ability to impair individual behaviors that are of great importance in the assessment of their ecological fitness.


Asunto(s)
Antibacterianos/toxicidad , Embrión no Mamífero/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Pez Cebra/embriología , Animales , Embrión no Mamífero/anomalías , Embrión no Mamífero/fisiología , Glutatión/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Larva/efectos de los fármacos , Larva/fisiología , Superóxido Dismutasa/metabolismo , Pez Cebra/crecimiento & desarrollo , Pez Cebra/fisiología , Proteínas de Pez Cebra/metabolismo
18.
J Fluoresc ; 23(2): 323-31, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23207872

RESUMEN

The interactions between room temperature ionic liquids (RTILs) and weak fluorescent chemicals still remain unclear, which hinders the complete and efficient utilization of these "green" solvents in fluorescent analyses of organic chemicals. Herein, we reported the effects of four RTILs, [C8MIM]BF4, [C14MIM]BF4, [C8MIM]PF6 and [C14MIM]PF6, on fluorescence behavior of 4-tert-octylphenol (4-t-OP). In the fortified concentration range of 0.2-1.0 mM, the quenching effects were increased with increasing concentrations of RTILs. However, no obvious variation of peak shape of 4-t-OP was observed in the quenching process, suggesting no formation of ground-state complex between fluorophores in 4-t-OP and quencher (ionic liquids). As for anion effect, the fluorescence quenching efficiency of 4-t-OP by BF4(-) was greater than PF6(-), but the carbon chain length on the imidazolium ring had no significant relationship with fluorescence intensity of 4-t-OP. Both Ksv values (>1.0 × 10(3) L/mol.s) and the different temperature effects demonstrated that the quenching of 4-t-OP by four RTILs was the presence of dynamic and static quenching mechanism. The FI of dansyl chloride within [C8MIM]BF4 increased nearly 5-fold as compared to the control, showing a sensitizing effect on the strong fluorescent chemicals, while a quenching effect on 4-t-OP belonging to weak fluorescent chemicals. The fluorescence-enhanced amplitude of dansyl chloride in [C8MIM]PF6 was greater than [C8MIM]BF4. The fluorescence quenching of 4-t-OP by [C8MIM]PF6 did not belong to FRET phenomenon because of no overlap of emission spectrum of 4-t-OP and absorption spectrum of [C8MIM]PF6. When 0.6 mM [C8MIM]PF6 in acetonitrile was used as the solvent, the detection limit of 4-t-OP was 3.7 µg/L, and the linearity range was 0.01-0.8 mg/L (R(2) = 0.9990). In summary, these results provide a theoretical foundation for the application of RTILs in weak fluorescent chemicals.


Asunto(s)
Líquidos Iónicos , Fenoles/química , Espectrometría de Fluorescencia/métodos , Transferencia Resonante de Energía de Fluorescencia , Temperatura
19.
J Fluoresc ; 23(1): 103-13, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22948804

RESUMEN

Herein, we report the effects of six different room temperature ionic liquids (RTILs) on fluorescence spectra of 17α-estradiol (EE1) and 17ß-estradiol (E2). The selected RTILs belonged to the compound classes of 1-alkyl-3-methylimidazolium tetrafluoroborate ([C(n)MIM]BF(4)) and 1-alkyl-3-methyl imidazolium hexafluorophosphate ([C(n)MIM]PF(6)). RTILs had a gradual quenching effect on fluorescence intensity (FI) of EE1 and E2, and the quenching process followed the well-known Stern-Volmer theory. The quenching mechanism of EE1 and E2 by RTILs was demonstrated to be dynamic quenching. Additionally, the overall quenching efficiency by [C(n)MIM]BF(4) was higher than [C(n)MIM]PF(6). The increased carbon chain length of RTILs did not lead to obvious differences in FI for EE1 and E2. The quenching efficiency showed irregular trend at three different temperatures (25, 35 and 45 °C). RTILs such as [C(4)MIM]PF(6) had the different fluorescent effects on organic chemicals with different fluorophores. The enhancing effects of [C(4)MIM]PF(6) were observed on strong fluorescence chemicals (dansyl chloride, rhrodamine B, 1,10-phenanthroline, norfloxacin), while quenching effect on weak fluorescence chemicals (EE1 and E2). In theory, these results provide a theoretical foundation for deep insight into their interaction mechanism between RTILs and estradiol.


Asunto(s)
Estradiol/química , Líquidos Iónicos/química , Espectrometría de Fluorescencia , Temperatura
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