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BACKGROUND: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. METHODS: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. RESULTS: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. CONCLUSIONS: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.
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Mieloma Múltiple , Receptores Inmunológicos , Transducción de Señal , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Mieloma Múltiple/genética , Humanos , Ratones , Animales , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , FN-kappa B/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Línea Celular Tumoral , Osteoclastos/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Leukemia stem cells (LSC) require frequent adaptation to maintain their self-renewal ability in the face of longer exposure to cell-intrinsic and cell-extrinsic stresses. However, the mechanisms by which LSC maintain their leukemogenic activities, and how individual LSC respond to stress, remain poorly understood. Here, we found that DNAJC10, a member of HSP40 family, was frequently up-regulated in various types of acute myeloid leukemia (AML) and in LSC-enriched cells. Deficiency of DNAJC10 leads to a dramatic increase in the apoptosis of both human leukemia cell lines and LSC-enriched populations. Although DNAJC10 is not required for normal hematopoiesis, deficiency of Dnajc10 significantly abrogated AML development and suppressed self-renewal of LSC in the MLL-AF9-induced murine leukemia model. Mechanistically, inhibition of DNAJC10 specifically induces endoplasmic reticulum stress and promotes activation of PERK-EIF2α-ATF4 branch of unfolded protein response (UPR). Blocking PERK by GSK2606414 (PERKi) or shRNA rescued the loss of function of DNAJC10 both in vitro and in vivo. Importantly, deficiency of DNAJC10 increased sensitivity of AML cells to daunorubicin (DNR) and cytarabine (Ara-C). These data revealed that DNAJC10 functions as an oncogene in MLL-AF9-induced AML via regulation of the PERK branch of the UPR. DNAJC10 may be an ideal therapeutic target for eliminating LSC, and improving the effectiveness of DNR and Ara-C.
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Leucemia Mieloide Aguda , Animales , Humanos , Ratones , Citarabina , Daunorrubicina , Proteínas del Choque Térmico HSP40/genética , Leucemia Mieloide Aguda/genética , Chaperonas Moleculares/genética , Células Madre , Respuesta de Proteína DesplegadaRESUMEN
This study aimed to validate and compare the anatomical variations of the superior intercostal veins, focusing on their origin, course, anastomoses, and destination. In addition, the results were compared with findings from other relevant studies. Fifty Korean and 16 Chinese adult cadavers were dissected for this study. The superior intercostal veins were dissected and measured. In our study of 66 specimens, the right superior intercostal vein was observed in 92.3% of cases, while the left superior intercostal vein was observed in 50%. The right superior intercostal vein was subdivided into six types based on its composition, which mainly drained the second and third right posterior intercostal veins. Similarly, the left superior intercostal vein was subdivided into eight types, primarily involving the second to fourth left posterior intercostal veins. This detailed anatomical study successfully identified and classified the various morphologic types of the superior intercostal vein and reviewed the clinical significance of this vein. The findings of this study can offer valuable anatomical evidence to physicians, aiding in their understanding and utilization of the superior intercostal vein.
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In recent years, nearly 20 cave sites with rich assemblages of mammalian fossils have been found and excavated in the Chongzuo area, Guangxi Zhuang Autonomous Region, China. Their ages are distributed throughout the entire Pleistocene Epoch. These discoveries have greatly facilitated our understanding of the evolution of the Stegodon-Ailuropoda fauna and the environmental context of human evolution in southern China. Here, we present a preliminary report on a diverse late Middle Pleistocene mammalian fauna from the Yixiantian Cave in southern China, which is a typical representative of the Stegodon-Ailuropoda fauna (sensu lato). The fossil mammals are represented by isolated dental remains only. In 2010 and 2011, two seasons of systematic excavations at the Yixiantian Cave yielded a total of 4,958 identifiable mammalian teeth. They were identified as belonging to 37 species and 6 orders of mammals. In addition, the tooth type of all the teeth representing each species was also determined where possible. A single fragmentary molar was identified as belonging to Gigantopithecus blacki, indicating that its population had declined sharply at this time and was on the brink of extinction. Description of the Yixiantian fauna will not only help better characterize the composition of the Stegodon-Ailuropoda fauna during the late Middle Pleistocene, but also clarify our understanding of the paleoenvironmental context at a time just prior to the extinction of G. blacki.
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Brachiosauridae is a lineage of titanosauriform sauropods that includes some of the most iconic non-avian dinosaurs. Undisputed brachiosaurid fossils are known from the Late Jurassic through the Early Cretaceous of North America, Africa, and Europe, but proposed occurrences outside this range have proven controversial. Despite occasional suggestions that brachiosaurids dispersed into Asia, to date no fossils have provided convincing evidence for a pan-Laurasian distribution for the clade, and the failure to discover brachiosaurid fossils in the well-sampled sauropod-bearing horizons of the Early Cretaceous of Asia has been taken to evidence their genuine absence from the continent. Here we report on an isolated sauropod maxilla from the middle Cretaceous (Albian-Cenomanian) Longjing Formation of the Yanji basin of northeast China. Although the specimen preserves limited morphological information, it exhibits axially twisted dentition, a shared derived trait otherwise known only in brachiosaurids. Referral of the specimen to the Brachiosauridae receives support from phylogenetic analysis under both equal and implied weights parsimony, providing the most convincing evidence to date that brachiosaurids dispersed into Asia at some point in their evolutionary history. Inclusion in our phylogenetic analyses of an isolated sauropod dentary from the same site, for which an association with the maxilla is possible but uncertain, does not substantively alter these results. We consider several paleobiogeographic scenarios that could account for the occurrence of a middle Cretaceous Asian brachiosaurid, including dispersal from either North America or Europe during the Early Cretaceous. The identification of a brachiosaurid in the Longshan fauna, and the paleobiogeographic histories that could account for its presence there, are hypotheses that can be tested with continued study and excavation of fossils from the Longjing Formation.
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BACKGROUND: The phase correction on transcranial focused ultrasound is essential to regulate unwanted focal point shift caused by skull bone aberration. The aim of the current study was to design and investigate the feasibility of a ray-based phase correction toolkit for transcranial focused ultrasound. RESULTS: The peak pressure at focal area was improved by 140.5 ± 7.0% on target I and 134.8 ± 19.1% on target II using proposed phase correction toolkit, respectively. A total computation time of 402.1 ± 24.5 milliseconds was achieved for each sonication. CONCLUSION: The designed ray-based phase correction software can be used as a lightweight toolkit to compensate aberrated phase within clinical environment.
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This study presents the fabrication and characterization of a piezoelectric micromachined ultrasonic transducer (pMUT; radius: 40 µm) using a patterned aluminum nitride (AlN) thin film as the active piezoelectric material. A 20 × 20 array of pMUTs using a 1 µm thick AlN thin film was designed and fabricated on a 2 × 2 mm2 footprint for a high fill factor. Based on the electrical impedance and phase of the pMUT array, the electromechanical coefficient was ~1.7% at the average resonant frequency of 2.82 MHz in air. Dynamic displacement of the pMUT surface was characterized by scanning laser Doppler vibrometry. The pressure output while immersed in water was 19.79 kPa when calculated based on the peak displacement at the resonant frequency. The proposed AlN pMUT array has potential applications in biomedical sensing for healthcare, medical imaging, and biometrics.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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We recently demonstrated that leukocyte Ig-like receptor 4 (LILRB4) expressed by monocytic acute myeloid leukemia (AML) cells mediates T-cell inhibition and leukemia cell infiltration via its intracellular domain. The cytoplasmic domain of LILRB4 contains three immunoreceptor tyrosine-based inhibitory motifs (ITIMs); the tyrosines at positions 360, 412, and 442 are phosphorylation sites. Here, we analyzed how the ITIMs of LILRB4 in AML cells mediate its function. Our in vitro and in vivo data show that Y412 and Y442, but not Y360, of LILRB4 are required for T-cell inhibition, and all three ITIMs are needed for leukemia cell infiltration. We constructed chimeric proteins containing the extracellular domain of LILRB4 and the intracellular domain of LILRB1 and vice versa. The intracellular domain of LILRB4, but not that of LILRB1, mediates T-cell suppression and AML cell migration. Our studies thus defined the unique signaling roles of LILRB4 ITIMs in AML cells.
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Movimiento Celular/inmunología , Tolerancia Inmunológica , Glicoproteínas de Membrana/inmunología , Proteínas de Neoplasias/inmunología , Receptores Inmunológicos/inmunología , Linfocitos T/inmunología , Secuencias de Aminoácidos , Animales , Movimiento Celular/genética , Humanos , Leucemia Mieloide Aguda , Glicoproteínas de Membrana/genética , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Proteínas de Neoplasias/genética , Receptores Inmunológicos/genética , Linfocitos T/patología , Células THP-1RESUMEN
Underwater sensors that detect the distance and direction of acoustic sources are critical for surveillance monitoring and target detection in the water. Here, we propose an axial vector sensor that utilizes a small (~1 cm3) compressive-type piezoelectric accelerometer using piezoelectric single crystals. Initially, finite element analysis (FEA) was used to optimize the structure that comprised piezoelectric Pb(Mb1/3Nb2/3)O3-28%PbTiO3 single crystals on a tungsten seismic mass. The receiving voltage sensitivity (RVS) was enhanced through geometric optimization of the thickness and sensing area of the piezoelectric material and the seismic mass. The estimated maximum RVS of the optimized vector sensor was -212 dB. FEA simulations and practical measurements were used to verify the directivity of the vector sensor design, which exhibited a dipole pattern. The dipole beam pattern was used to obtain cardioid patterns using the simulated and measured results for comparison. The results clearly showed the feasibility of using the proposed piezoelectric single-crystal accelerometer for a compressive-type vector sensor.
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OBJECTIVE: Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss. METHODS: The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age). RESULTS: The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells. CONCLUSION: Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.
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Cóclea/ultraestructura , Pérdida Auditiva/patología , Estereocilios/ultraestructura , Animales , Umbral Auditivo/fisiología , Cadherinas/genética , Proteínas Portadoras/genética , Cóclea/patología , Potenciales Evocados Auditivos del Tronco Encefálico , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Endogámicos NOD , Ratones Endogámicos , Proteínas de Microfilamentos/genética , Microscopía Electrónica de Rastreo , Estereocilios/patología , Factores de TiempoRESUMEN
Fascin2 (FSCN2) is an actin cross-linking protein that is mainly localized in retinas and in the stereocilia of hair cells. Earlier studies showed that a deletion mutation in human FASCIN2 (FSCN2) gene could cause autosomal dominant retinitis pigmentosa. Recent studies have indicated that a missense mutation in mouse Fscn2 gene (R109H) can contribute to the early onset of hearing loss in DBA/2J mice. To explore the function of the gene, Fscn2 was knocked out using TALEN (transcription activator-like effector nucleases) on the C57BL/6J background. Four mouse strains with deletions of 1, 4, 5, and 41 nucleotides in the target region of Fscn2 were developed. F1 heterozygous (Fscn2+/- ) mice carrying the same deletion of 41 nucleotides were mated to generate the Fscn2-/- mice. As a result, the Fscn2-/- mice showed progressive hearing loss, as measured in the elevation of auditory brainstem-response thresholds. The hearing impairment began at age 3 weeks at high-stimulus frequencies and became most severe at age 24 weeks. Moreover, degeneration of hair cells and loss of stereocilia were remarkable in Fscn2-/- mice, as revealed by F-actin staining and scanning electron microscopy. Furthermore, compared to the controls, the Fscn2-/- mice displayed significantly lower electroretinogram amplitudes and thinner retinas at 8, 16, and 24 weeks. These results demonstrate that, in C57BL/6Jmice, Fscn2 is essential for maintaining ear and eye function and that a null mutation of Fscn2 leads to progressive hearing loss and retinal degeneration.
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Proteínas Portadoras/genética , Pérdida Auditiva/genética , Pérdida Auditiva/metabolismo , Homocigoto , Proteínas de Microfilamentos/genética , Mutación , Degeneración Retiniana/genética , Degeneración Retiniana/metabolismo , Nucleasas de los Efectores Tipo Activadores de la Transcripción/metabolismo , Animales , Secuencia de Bases , Biopsia , Recuento de Células , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Electrorretinografía , Expresión Génica , Frecuencia de los Genes , Marcación de Gen , Células Ciliadas Auditivas Externas/metabolismo , Células Ciliadas Auditivas Externas/ultraestructura , Pérdida Auditiva/diagnóstico , Heterocigoto , Ratones , Ratones Endogámicos C57BL , Fenotipo , Degeneración Retiniana/diagnóstico , Eliminación de SecuenciaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. To effectively treat HCC, new molecular targets and therapeutic approaches must be identified. 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate (IMP) cyclohydrolase (ATIC), a bifunctional protein enzyme, catalyzes the last two steps of the de novo purine biosynthetic pathway. Whether ATIC contributes to cancer development remains unclear. METHODS: ATIC mRNA levels in different types of human HCC samples or normal tissues were determined from Gene Expression across Normal and Tumor tissue (GENT) database. The expression level of ATIC in human HCC samples or cell lines were examined by RT-PCR and western blot. Overall survival and disease-free survival of HCC patients in the ATIC low and ATIC high groups were determined by Kaplan-Meier analysis. Effects of ATIC knockdown by lentivirus infection were evaluated on cell-proliferation, cell-apoptosis, colony formation and migration. The mechanisms involved in HCC cells growth, apoptosis and migration were analyzed by western blot and Compound C (C-C) rescue assays. RESULTS: Here, we first demonstrated that expression of ATIC is aberrantly up-regulated in HCC tissues and high level of ATIC is correlated with poor survival in HCC patients. Knockdown of ATIC expression resulted in a dramatic decrease in proliferation, colony formation and migration of HCC cells. We also identified ATIC as a novel regulator of adenosine monophosphate-activated protein kinase (AMPK) and its downstream signaling mammalian target of rapamycin (mTOR). ATIC suppresses AMPK activation, thus activates mTOR-S6 K1-S6 signaling and supports growth and motility activity of HCC cells. CONCLUSION: Taken together, our results indicate that ATIC acts as an oncogenic gene that promotes survival, proliferation and migration by targeting AMPK-mTOR-S6 K1 signaling.
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Adenilato Quinasa/metabolismo , Carcinoma Hepatocelular/patología , Transferasas de Hidroximetilo y Formilo/metabolismo , Neoplasias Hepáticas/patología , Complejos Multienzimáticos/metabolismo , Nucleótido Desaminasas/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Activación Enzimática , Técnicas de Silenciamiento del Gen , Humanos , Transferasas de Hidroximetilo y Formilo/deficiencia , Transferasas de Hidroximetilo y Formilo/genética , Terapia Molecular Dirigida , Complejos Multienzimáticos/deficiencia , Complejos Multienzimáticos/genética , Nucleótido Desaminasas/deficiencia , Nucleótido Desaminasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia ArribaRESUMEN
The development of maternal tolerance to the fetal allograft in critical for the maintenance of the pregnancy, and it is accompanied by the development of a special decidual natural killer (dNK) cell tolerance phenotype. To understand the factors that influence dNK cells during early pregnancy, the present study aimed to identify mesenchymal stem cells (MSCs) from human firsttrimester deciduas, termed decidual MSCs (DMSCs), and to investigate the effect of DMSCs on the regulation of dNK cells via collagen. Decidual samples were collected from women with normal pregnancy that had undergone elective vaginal surgical terminations at 69 weeks gestation. DMSCs derived from human decidual tissues were cultured under differentiation conditions to examine their multipotent differentiation capacities, and the expression of MSCspecific markers, including cluster of differentiation (CD)44, CD73, CD105, CD90, CD34, CD31, CD14, CD45, CD11b and human leukocyte antigenantigen D related, was determined. dNK cells were cocultured with DMSCs in order to examine the effect of DMSCs on the tolerance phenotype of dNK cells. The expression of cell surface molecules, natural cytotoxicity triggering receptor 3 and killer cell immunoglobulinlike receptor (KIR) 2DL1, and the secretion of cytokines, including interferonγ, tumor necrosis factor (TNF)α, interleukin (IL)10, IL4 and perforin, were examined by flow cytometry analysis. To determine whether the regulation of dNK cells by DMSCs was mediated by collagen, DMSCs were pretreated with human recombinant leukocyteassociated immunoglobulinlike receptor (LAIR)2 and transfected with pScoRGFPhP4H to inhibit the interaction between LAIR1 and collagen. The present results demonstrated that collagen produced by DMSCs increased the expression of KIR2DL1 and IL4, decrease the expression of NKp30 and TNFα. In conclusion, the results of the present study demonstrated that DMSCs may be cultured in vitro for prolonged periods, whilst retaining the ability to differentiate into different cell lineages. In addition, DMSCs may modulate the function of dNK cells via the interaction between collagen and LAIR1.
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Colágeno/inmunología , Decidua/citología , Células Asesinas Naturales/inmunología , Células Madre Mesenquimatosas/inmunología , Receptores Inmunológicos/inmunología , Adulto , Diferenciación Celular , Células Cultivadas , Técnicas de Cocultivo , Colágeno/análisis , Citocinas/análisis , Citocinas/inmunología , Decidua/inmunología , Femenino , Humanos , Células Asesinas Naturales/citología , Células Madre Mesenquimatosas/citología , Embarazo , Receptores Inmunológicos/análisis , Adulto JovenRESUMEN
The arterial structure cyclically fluctuates in three-dimensions (3-D) caused by pulsatile blood flow. The evaluation of arterial wall motion and hemodynamics contributes to early diagnosis of carotid atherosclerosis. Ultrasound is one of the most appropriate imaging modalities to evaluate arterial wall motion in real time. Although many previous studies have discussed the mechanical properties of the carotid artery bifurcation (CAB) from the two-dimensional (2-D) view, the spatio-temporal variation of carotid artery geometry in 3-D has not yet been investigated in detail. In this study, the 3-D data set of CAB from rats was acquired using a high spatio-temporal resolution ultrasound imaging system with a 40 MHz probe using mechanical sector scanning. A total of 31 slices of cross-section images were stored and a spoke scan algorithm was implemented to radially scan the lumen area in polar coordinates based on a pre-tracked seed point. The boundary of the arterial lumen was segmented using intensity-threshold-based boundary detection and fitted by polynomial regression. Two operators, who were trained with the same protocol to minimize inter- and intra-operator variability, manually segmented the lumen boundary on systolic and diastolic phase from the gray-scale images. Finally, the 3-D lumen geometries of CAB during one cardiac cycle were constructed based on the segmented lumen boundaries. From this constructed 3-D geometry, we observed that the CAB geometry favorably expanded to the anterior/posterior direction, parallel to the sagittal plane; and the manually segmented geometry also confirmed the asymmetrical change in bifurcation geometry. This is the first study on visualization and quantification on the asymmetrical variation of the CAB geometry of a rat in 3-D during a whole cardiac cycle. This finding may be useful in understanding hemodynamic etiology of various cardiovascular diseases such as arterial stenosis and its complications, and also provides reference information for numerical simulation studies on arterial wall motion.
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Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Común/fisiología , Imagenología Tridimensional , Flujo Pulsátil , Ultrasonografía/métodos , Animales , Automatización , Arteria Carótida Externa/diagnóstico por imagen , Arteria Carótida Externa/fisiología , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/fisiología , Interpretación de Imagen Asistida por Computador , Valor Predictivo de las Pruebas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional , Factores de TiempoRESUMEN
The vascular remodeling process plays an important role in the pathology of hypoxia-induced pulmonary hypertension, and it includes cell proliferation, cell motility, cell synthesis and collagen coagulation. Due to their proliferation and synthesis ability, the adventitial fibroblasts are thought to be critical in the vascular remodeling process initiated in response to hypoxia. However, the factors driving hypoxia-induced fibroblast proliferation and synthesis have yet to be elucidated, and the treatment regimens to treat hypoxia remain ineffective. As forthis study, its purpose was to examine the effects exerted by SB-431542, a small-molecule antagonist of transforming growth factor-ß-receptor, on the proliferation, synthesis and collagen coagulation in cultured adventitial fibroblasts. Another aim of this study was to assess the inhibitory ability of SB-431542 on pulmonary vascular remodeling in chronic hypoxia in vivo.The cell morphology and proliferation of cultured adventitial fibroblasts was assessed by laser confocal microscopy and the MTT assay, respectively. Additionally, collagen synthesis was determined by hydroxyproline chromatography, while the expression of cytokines in adventitial fibroblasts and lung tissues was evaluated by immunohistochemical and reverse transcription PCR analyses. The results indicated that the exposure of cultured fibroblasts to 1% oxygen led to the up regulation of cell proliferation, cell synthesis. In addition, increased expression of cytokines and collagen was detected in vivo in the pulmonary artery adventitia of rats exposed to chronic hypoxia. Conversely, SB-431542 inhibited fibroblast proliferation and synthesis in the process of hypoxia-induced pulmonary hypertension (P < 0.01). Thus, the results suggested that by reducing cell proliferation, cell synthesis of vascular adventitia, small molecule inhibitors of the TGF-ß1 receptors may offer a novel therapy for pulmonary hypertension.
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Benzamidas/farmacología , Dioxoles/farmacología , Fibroblastos/efectos de los fármacos , Hipoxia/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Arteria Pulmonar/patología , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Actinas/antagonistas & inhibidores , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno/biosíntesis , Citocinas/biosíntesis , Regulación hacia Abajo/efectos de los fármacos , Hidroxiprolina/metabolismo , Masculino , Metaloproteinasa 1 de la Matriz/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptor Tipo I de Factor de Crecimiento Transformador betaRESUMEN
We investigated the effects of pyrrolidine dithiocarbamate (PDTC) on intrapulmonary expression of nuclear factor-κB (NF-κB), and apoptosis in rats with severe acute pancreatitis (SAP). We induced SAP, then used immunohistochemistry, TUNEL staining, quantitative PCR assays and western blotting to examine PDTC effects. Treatment with PDTC resulted in interstitial edema and widening of the basement membrane, with swollen mitochondria and aggregation of nuclear chromatin. Expression of NF-κB, Fas, Bcl-2 and TNF-α in lung tissues of SAP rats was increased, with NF-κB, Fas and TNF-α levels maximal after 6 h. PDTC appeared to ameliorate pathological changes, with low levels of NF-κB, Fas, TNF-α, and Caspase-3 mRNA observed and a lower apoptosis index compared with that seen in SAP rats. Expression of NF-κB could be involved in lung tissue apoptosis during SAP. We postulate that PDTC inhibits the activation of NF-κB and apoptosis, effectively alleviating the severity of lung injury.
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Previous analyses of dental size in Gigantopithecus blacki indicated marked sexual dimorphism and a trend towards increasing size through time. These studies were based on a sample of over 700 teeth from five localities excavated prior to 1990. Since then, 12 additional cave sites have been discovered in southern China, yielding hundreds of isolated teeth of G. blacki. Most of these sites are well dated by a combination of biochronology and absolute dating methods, so we now have a much better understanding of the chronology of G. blacki. Here, we reexamine the degree of sexual dimorphism and the question of dental size increase through time in G. blacki based on the expanded collections now available. Our results show that sexual dimorphism is not as marked as indicated in previous studies and confirm earlier analyses suggesting that the postcanine teeth of G. blacki tend to become larger through time from the beginning of the Early Pleistocene to the Middle Pleistocene.
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Evolución Biológica , Diente Canino/anatomía & histología , Hominidae/anatomía & histología , Animales , China , Fósiles , Humanos , Masculino , PaleodontologíaRESUMEN
Visualizing and analyzing the morphological structure of carotid bifurcations are important for understanding the etiology of carotid atherosclerosis, which is a major cause of stroke and transient ischemic attack. For delineation of vasculatures in the carotid artery, ultrasound examinations have been widely employed because of a noninvasive procedure without ionizing radiation. However, conventional 2D ultrasound imaging has technical limitations in observing the complicated 3D shapes and asymmetric vasodilation of bifurcations. This study aims to propose image-processing techniques for better 3D reconstruction of a carotid bifurcation in a rat by using 2D cross-sectional ultrasound images. A high-resolution ultrasound imaging system with a probe centered at 40MHz was employed to obtain 2D transversal images. The lumen boundaries in each transverse ultrasound image were detected by using three different techniques; an ellipse-fitting, a correlation mapping to visualize the decorrelation of blood flow, and the ellipse-fitting on the correlation map. When the results are compared, the third technique provides relatively good boundary extraction. The incomplete boundaries of arterial lumen caused by acoustic artifacts are somewhat resolved by adopting the correlation mapping and the distortion in the boundary detection near the bifurcation apex was largely reduced by using the ellipse-fitting technique. The 3D lumen geometry of a carotid artery was obtained by volumetric rendering of several 2D slices. For the 3D vasodilatation of the carotid bifurcation, lumen geometries at the contraction and expansion states were simultaneously depicted at various view angles. The present 3D reconstruction methods would be useful for efficient extraction and construction of the 3D lumen geometries of carotid bifurcations from 2D ultrasound images.