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1.
Proc Natl Acad Sci U S A ; 117(25): 14299-14305, 2020 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-32513701

RESUMEN

The Lower Cretaceous Huajiying Formation of the Sichakou Basin in northern Hebei Province, northern China contains key vertebrate taxa of the early Jehol Biota, e.g., Protopteryx fengningensis, Archaeornithura meemannae, Peipiaosteus fengningensis, and Eoconfuciusornis zhengi This formation arguably documents the second-oldest bird-bearing horizon, producing the oldest fossil records of the two major Mesozoic avian groups Enantiornithes and Ornithuromorpha. Hence, precisely determining the depositional ages of the Huajiying Formation would advance our understanding of the evolutionary history of the Jehol Biota. Here we present secondary ion mass spectrometry (SIMS) U-Pb zircon analysis results of eight interbedded tuff/tuffaceous sandstone samples from the Huajiying Formation. Our findings, combined with previous radiometric dates, suggest that the oldest enantiornithine and ornithuromorph birds in the Jehol Biota are ∼129-131 Ma, and that the Jehol Biota most likely first appeared at ∼135 Ma. This expands the biota's temporal distribution from late Valanginian to middle Aptian with a time span of about 15 My.


Asunto(s)
Biota , Aves/clasificación , Plomo/química , Silicatos/química , Circonio/química , Animales , Evolución Biológica , China , Fósiles , Geología , Filogenia , Espectrometría de Masa de Ion Secundario
2.
Int J Mol Sci ; 23(22)2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36430328

RESUMEN

Microglia activation, increased IL-6 and decreased TGF-ß were found in depressed patients or in animal models of depression. IL-6 enhances T helper 17 cell differentiation, thereby causing an imbalance between Th17 and Treg cells, which induces neuroinflammation and neuronal dysfunction. However, whether imbalances between IL-6 and TGF-ß and between Th17 and Treg occur in depression and whether depression can be improved upon restoring these imbalances are unknown. Treg promoter IL-2 (1500UI/0.1 mL/day) was used to treat a mouse model of depression induced by chronic unpredictable mild stress (CUMS). The behavior and concentrations of IL-6, TGF-ß, Th17, IL-17A, IL-17Rc, Treg-related factors (helios and STAT5), astrocyte A1 phenotype S100ß, microglia M1 phenotype Iba-1, indoleamine-2,3-dioxygenase (IDO) enzyme, corticosterone (CORT) and neurotransmitters were evaluated. When compared to controls, CUMS reduced sucrose preference, the number of entries into and the time spent in the open arms of the elevated plus maze and the exploration in the "open field", while it increased the immobility time in tail suspension, which was ameliorated by IL-2 treatment. RoRα, S100ß, IL-17A, IL-17Rc, IL-6, Iba-1, IDO enzyme and CORT concentrations were significantly increased, and Helios, FoxP3+, STAT5 and TGF-ß were significantly decreased by CUMS, which were significantly attenuated by IL-2 when compared to the CUMS group. The NE, DA and 5-HT contents and those of their metabolites were decreased by CUMS, which returned to control levels after IL-2 treatment. The study demonstrated that imbalances between IL-6 and TGF-ß and between Th17and Treg occurred in the hippocampus of the depression model. IL-2 attenuated depression- and anxiety-like behaviors and normalized the neurotransmitter concentration and the activity of the IDO enzyme, astrocytes and microglia through restoring both balances, but it did not decrease the CORT concentration.


Asunto(s)
Interleucina-17 , Linfocitos T Reguladores , Animales , Ratones , Corticosterona/metabolismo , Depresión/tratamiento farmacológico , Depresión/etiología , Depresión/metabolismo , Modelos Animales de Enfermedad , Interleucina-17/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Factor de Transcripción STAT5/metabolismo , Linfocitos T Reguladores/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Interleucina-12
3.
Nature ; 521(7550): 70-3, 2015 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-25924069

RESUMEN

The wings of birds and their closest theropod relatives share a uniform fundamental architecture, with pinnate flight feathers as the key component. Here we report a new scansoriopterygid theropod, Yi qi gen. et sp. nov., based on a new specimen from the Middle-Upper Jurassic period Tiaojishan Formation of Hebei Province, China. Yi is nested phylogenetically among winged theropods but has large stiff filamentous feathers of an unusual type on both the forelimb and hindlimb. However, the filamentous feathers of Yi resemble pinnate feathers in bearing morphologically diverse melanosomes. Most surprisingly, Yi has a long rod-like bone extending from each wrist, and patches of membranous tissue preserved between the rod-like bones and the manual digits. Analogous features are unknown in any dinosaur but occur in various flying and gliding tetrapods, suggesting the intriguing possibility that Yi had membranous aerodynamic surfaces totally different from the archetypal feathered wings of birds and their closest relatives. Documentation of the unique forelimbs of Yi greatly increases the morphological disparity known to exist among dinosaurs, and highlights the extraordinary breadth and richness of the evolutionary experimentation that took place close to the origin of birds.


Asunto(s)
Dinosaurios/anatomía & histología , Dinosaurios/clasificación , Fósiles , Alas de Animales/anatomía & histología , Animales , Aves/clasificación , China , Plumas/anatomía & histología , Filogenia
4.
J Cell Biochem ; 121(3): 2343-2353, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31633245

RESUMEN

Local angiogenesis following rotator cuff reconstruction is crucial for tendon-bone healing. The current research on the mechanism underlying angiogenesis that promotes tendon-bone healing is scarce. This study investigates the mechanism underlying vascular endothelial growth factor (VEGF)-Hippo signaling pathway's involvement in tendon-bone healing following rotator cuff reconstruction. Verteporfin, the inhibitor of the Yes-associated protein (YAP), was used to mechanically test and analyze two groups of tensile-failure loads following rotator cuff reconstruction and to detect collagen and angiogenesis-related marker expressions in the tendon. The interaction mechanism of the VEGF-Hippo signaling pathway was assessed using human umbilical vein endothelial cells (HUVECs). The diameter of the supraspinatus tendon reduced following verteporfin treatment. Mechanical tests revealed that verteporfin significantly reduces the tensile-failure load of the supraspinatus tendon. Verteporfin significantly reduces collagen 1 (Col 1), Col 3, Angiopoietin 2, CD31, Von Willebrand factor, CTGF, and CYR61 expressions. In HUVECs, VEGF activates VEGF receptors and inhibits LATS and YAP phosphorylation. YAP is then transferred to the nucleus to further activate downstream pathways. Therefore, verteporfin can inhibit VEGF-induced YAP pathway activation by inhibiting YAP activity. Angiogenesis in tendon-bone healing following rotator cuff reconstruction requires VEGF-Hippo signaling pathway synergy.


Asunto(s)
Huesos/citología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neovascularización Fisiológica , Lesiones del Manguito de los Rotadores/cirugía , Tendones/citología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas , Animales , Huesos/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Osteogénesis , Ratas , Ratas Sprague-Dawley , Procedimientos de Cirugía Plástica/métodos , Lesiones del Manguito de los Rotadores/metabolismo , Lesiones del Manguito de los Rotadores/patología , Tendones/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Proteínas Señalizadoras YAP
5.
Nature ; 463(7284): 1075-8, 2010 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-20107440

RESUMEN

Spectacular fossils from the Early Cretaceous Jehol Group of northeastern China have greatly expanded our knowledge of the diversity and palaeobiology of dinosaurs and early birds, and contributed to our understanding of the origin of birds, of flight, and of feathers. Pennaceous (vaned) feathers and integumentary filaments are preserved in birds and non-avian theropod dinosaurs, but little is known of their microstructure. Here we report that melanosomes (colour-bearing organelles) are not only preserved in the pennaceous feathers of early birds, but also in an identical manner in integumentary filaments of non-avian dinosaurs, thus refuting recent claims that the filaments are partially decayed dermal collagen fibres. Examples of both eumelanosomes and phaeomelanosomes have been identified, and they are often preserved in life position within the structure of partially degraded feathers and filaments. Furthermore, the data here provide empirical evidence for reconstructing the colours and colour patterning of these extinct birds and theropod dinosaurs: for example, the dark-coloured stripes on the tail of the theropod dinosaur Sinosauropteryx can reasonably be inferred to have exhibited chestnut to reddish-brown tones.


Asunto(s)
Aves/anatomía & histología , Color , Dinosaurios/anatomía & histología , Plumas/citología , Fósiles , Melanosomas , Pigmentación , Animales , Aves/clasificación , China , Dinosaurios/clasificación , Extinción Biológica , Plumas/anatomía & histología , Plumas/ultraestructura , Integumento Común/anatomía & histología , Melanosomas/fisiología , Melanosomas/ultraestructura , Filogenia , Pigmentación/fisiología
7.
Drug Dev Ind Pharm ; 42(11): 1772-81, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27032257

RESUMEN

The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box-Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384 ± 21 nm and PDI of 0.172 ± 0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced Cmax (7.42 ± 0.73 versus 3.80 ± 0.66 mg/L) and AUC0 - t (193.61 ± 16.30 versus 91.92 ± 17.95 mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp.


Asunto(s)
Liofilización/métodos , Virus de la Hepatitis B/efectos de los fármacos , Nanopartículas/química , Quercetina/análogos & derivados , Administración Oral , Animales , Disponibilidad Biológica , Virus de la Hepatitis B/química , Quercetina/administración & dosificación , Quercetina/química , Quercetina/farmacología , Ratas , Solubilidad
8.
Surgeon ; 13(4): 218-29, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25547802

RESUMEN

BACKGROUND AND AIM: Pancreatitis is the most common and serious complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Prevention strategies targeting risk factors could be important to reduce the rate of post-ERCP pancreatitis. However, the risk factors for post-ERCP pancreatitis (PEP) are still debated. This systematic review and meta-analysis was performed to identify risk factors for PEP. METHODS: Medline (PubMed and Ovid), Cochrane Central Register of Controlled trials & Database of Systematic Reviews, Embase, Scopus, ScienceDirect, Springer links and WEB OF SCIENCE were searched for published studies in all languages. Inclusion and exclusion criteria were defined a priori. Eighteen probable risk factors were evaluated, and outcomes were expressed in the case of dichotomous variables, as an odds ratio (OR) (with a 95% confidence interval, (CI)). RESULTS: When patient-related risk factors were analyzed, the ORs for female gender was 1.46 (95%CI: 1.30-1.64); for previous pancreatitis 2.03 (95%CI: 1.31-3.14); for previous PEP was 2.90 (95%CI: 1.87-4.48); for Sphincter of Oddi dysfunction (SOD) was 2.04 (95%CI: 1.73-2.33) and for Intraductal papillary mucinous neoplasm (IPMN) was 3.01 (95%CI: 1.34-6.77). Four endoscopy-related factors were confirmed: the OR for difficult cannulation was 3.49 (95%CI: 1.364-8.925); for endoscopic sphincterotomy (EST) it was 1.39 (95%CI: 1.09-1.79); for precut sphincterotomy it was 2.25 (95%CI: 1.70_2.96); and for main pancreatic duct injection it was 1.58 (95%CI: 1.21-2.08). CONCLUSIONS: Female gender, previous pancreatitis, previous PEP, SOD, IPMN, difficult cannulation, EST, precut sphincterotomy and main pancreatic duct injection are risk factors for post-ERCP pancreatitis.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Pancreatitis/etiología , Humanos , Factores de Riesgo
9.
Pak J Med Sci ; 31(5): 1053-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26648985

RESUMEN

OBJECTIVE: To investigate the effect of treatment on prognosis of patients with different timing of early interventional treatment for non-ST segment elevation acute myocardial infarction (NSTEMI). METHODS: Forty two cases above 75 years old, diagnosed with high-risk on NSTEMI, were selected in cardiology department of Xinxiang central hospital. They were randomly divided into two groups: 22 in group A and 20 in group B. Group A was performed PCI surgery within 12 hours after the onset while group B from 12 to 24 hour after the onset. Major adverse cardiovascular events (including death, heart failure readmission rates after ischemia, malignant arrhythmias, again target vessel revascularization) and bleeding data were recorded at the three terms of hospitalization, one month after the onset and six months after the onset. RESULTS: Angina, malignant arrhythmia and heart failure during hospitalization can be reduced after interventional treatment carried out within 12 hours after the onset. Readmission rates after ischemia, heart failure and the incidence of death can be significantly reduced after interventional treatment carried out during 1-6 month after the onset with no significant increase in bleeding rate. CONCLUSION: In the treatment of elderly patients with NSTEMI, early interventional treatment is safe and effective.

10.
Nature ; 455(7216): 1105-8, 2008 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-18948955

RESUMEN

Recent coelurosaurian discoveries have greatly enriched our knowledge of the transition from dinosaurs to birds, but all reported taxa close to this transition are from relatively well known coelurosaurian groups. Here we report a new basal avialan, Epidexipteryx hui gen. et sp. nov., from the Middle to Late Jurassic of Inner Mongolia, China. This new species is characterized by an unexpected combination of characters seen in several different theropod groups, particularly the Oviraptorosauria. Phylogenetic analysis shows it to be the sister taxon to Epidendrosaurus, forming a new clade at the base of Avialae. Epidexipteryx also possesses two pairs of elongate ribbon-like tail feathers, and its limbs lack contour feathers for flight. This finding shows that a member of the avialan lineage experimented with integumentary ornamentation as early as the Middle to Late Jurassic, and provides further evidence relating to this aspect of the transition from non-avian theropods to birds.


Asunto(s)
Dinosaurios/anatomía & histología , Dinosaurios/clasificación , Plumas/anatomía & histología , Fósiles , Animales , China , Historia Antigua , Filogenia
11.
Childs Nerv Syst ; 30(1): 189-91, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23974967

RESUMEN

INTRODUCTION: Rhabdoid meningioma (RM) is rare, and it occurs mainly in children. We report the clinical and pathological features of rhabdoid meningioma in a 9-year-old child. MATERIAL AND METHODS: A 9-year-old child with RM presented to our hospital with headache that had persisted for 3 days. Magnetic resonance imaging of his brain demonstrated supratentorial lesions of the right temporal petrous bone and cisterna magna cyst. He underwent surgery on January 13, 2010. The pathological diagnosis was rhabdoid meningioma (grade III). The patient underwent radiotherapy with 30 Gy/16 fractions delivered to the recurrent tumor after surgery. The patient died in December as a result of complications of recurrent meningioma. CONCLUSION: The accumulated data, including this current case, demonstrate the difficulties in reaching the diagnosis and providing treatment for this disease as a consequence of its low incidence, aggressive nature, and poor treatment options for children with rhabdoid meningioma.


Asunto(s)
Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Tumor Rabdoide/diagnóstico , Niño , Resultado Fatal , Humanos , Masculino , Neoplasias Meníngeas/terapia , Meningioma/terapia , Recurrencia Local de Neoplasia/terapia , Tumor Rabdoide/terapia
12.
Proc Natl Acad Sci U S A ; 108(38): 15904-7, 2011 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-21896733

RESUMEN

The crop is characteristic of seed-eating birds today, yet little is known about its early history despite remarkable discoveries of many Mesozoic seed-eating birds in the past decade. Here we report the discovery of some early fossil evidence for the presence of a crop in birds. Two Early Cretaceous birds, the basal ornithurine Hongshanornis and a basal avian Sapeornis, demonstrate that an essentially modern avian digestive system formed early in avian evolution. The discovery of a crop in two phylogenetically remote lineages of Early Cretaceous birds and its absence in most intervening forms indicates that it was independently acquired as a specialized seed-eating adaptation. Finally, the reduction or loss of teeth in the forms showing seed-filled crops suggests that granivory was possibly one of the factors that resulted in the reduction of teeth in early birds.


Asunto(s)
Evolución Biológica , Aves/anatomía & histología , Buche de las Aves/anatomía & histología , Fósiles , Adaptación Fisiológica , Animales , Aves/clasificación , Aves/fisiología , Huesos/anatomía & histología , China , Buche de las Aves/fisiología , Dieta , Semillas , Especificidad de la Especie
13.
Contemp Oncol (Pozn) ; 18(6): 436-41, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25784844

RESUMEN

AIM OF THE STUDY: To use different beam arrangements and numbers to plan intensity-modulated radiation therapy (IMRT) and investigate their effects on low and high radiation doses delivered to the functional lung, in order to reduce radiation-induced lung damage. MATERIAL AND METHODS: Ten patients with stage I-III non-small cell lung carcinoma (NSCLC) underwent IMRT. Beam arrangements were selected on the basis of orientation and dose-volume histograms to create SPECT-guided IMRT plans that spared the functional lung and maintained target coverage. Four different plans, including CT-7, SPECT-7, SPECT-4, SPECT-5 with different beam arrangements, were used. The differences of conformity index (CI), heterogeneity index (HI) between the plans were analyzed, by using a paired t-test. RESULTS: The seven-beam SPECT (SPECT-7) plan reduced the volume of the functional lung irradiated with at least 20 Gy (FV20) and 30 Gy (FV30) by 26.02% ±15.45% and 14.41% ±16.66%, respectively, as compared to the seven-beam computed tomography (CT-7) plan. The CI significantly differed between the SPECT-7 and SPECT-4 plans and between the SPECT-5 and SPECT-4 plans, but not between the SPECT-5 and SPECT-7 plans. The CIs in the SPECT-5 and SPECT-7 plans were better than that in the SPECT-4 plan. The heterogeneity index significantly differed among the three SPECT plans and was best in the SPECT-7 plan. CONCLUSIONS: The incorporation of SPECT images into IMRT planning for NSCLC greatly affected beam angles and number of beams. Fewer beams and modified beam angles achieved similar or better IMRT quality. The low-dose volumes were lower in SPECT-4.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38963737

RESUMEN

Motion retargeting is an active research area in computer graphics and animation, allowing for the transfer of motion from one character to another, thereby creating diverse animated character data. While this technology has numerous applications in animation, games, and movies, current methods often produce unnatural or semantically inconsistent motion when applied to characters with different shapes or joint counts. This is primarily due to a lack of consideration for the geometric and spatial relationships between the body parts of the source and target characters. To tackle this challenge, we introduce a novel spatially-preserving Skinned Motion Retargeting Network (SMRNet) capable of handling motion retargeting for characters with varying shapes and skeletal structures while maintaining semantic consistency. By learning a hybrid representation of the character's skeleton and shape in a rest pose, SMRNet transfers the rotation and root joint position of the source character's motion to the target character through embedded rest pose feature alignment. Additionally, it incorporates a differentiable loss function to further preserve the spatial consistency of body parts between the source and target. Comprehensive quantitative and qualitative evaluations demonstrate the superiority of our approach over existing alternatives, particularly in preserving spatial relationships more effectively.

15.
Materials (Basel) ; 17(3)2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38591981

RESUMEN

Single-pass isothermal hot compression tests on four medium-Mn steels with different C and Al contents were conducted using a Gleeble-3500 thermal simulation machine at varying deformation temperatures (900-1150 °C) and strain rates (0.01-5 s-1). Based on friction correction theory, the friction of the test stress-strain data was corrected. On this basis, the Arrhenius constitutive model of experimental steels considering Al content and strain compensation and hot processing maps of different experimental steels at a strain of 0.9 were established. Moreover, the effects of C and Al contents on constitutive model parameters and hot processing performance were analyzed. The results revealed that the increase in C content changed the trend of the thermal deformation activation energy Q with the true strain. The Q value of 2C7Mn3Al increased by about 50 KJ/mol compared with 7Mn3Al at a true strain greater than 0.4. In contrast, increasing the Al content from 0 to 1.14 wt.% decreased the activation energy of thermal deformation in the true strain range of 0.4-0.9. Continuing to increase to 3.30 wt.% increased the Q of 7Mn3Al over 7Mn by about 65 KJ/mol over the full strain range. In comparison, 7Mn1Al exhibited the best hot processing performance under the deformation temperature of 975-1125 °C and strain rate of 0.2-5 s-1. This is due to the addition of C element reduces the δ-ferrite volume fraction, which leads to the precipitation of κ-carbides and causes the formation of microcracks; an increase in Al content from 0 to 1.14 wt.% reduces the austenite stability and improves the hot workability, but a continued increase in the content up to 3.30 wt.% results in the emergence of δ-ferrite in the microstructure, which slows down the austenite DRX and not conducive to the hot processing performance.

16.
Adv Sci (Weinh) ; 11(5): e2305439, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38050661

RESUMEN

Photo-assisted uranium reduction from uranium mine wastewater is expected to overcome the competition between impurity ions and U(VI) in the traditional process. Here, B-TiO2 @Co2 P-X S-scheme heterojunction with metal-oxygen-hydrogen (M-O-H) is developed insitu modification for photo-assisted U(VI) (hexavalent uranium) reduction. Relying on the DFT calculation and Hard-Soft-Acid-Base (HSAB) theory, the introduction of metal-oxygen-hydrogen (M-O-H, hard base) metallic bonds in the B-TiO2 @Co2 P-X is found to enhance the hydrophilicity and the capture capability for uranyl ion (hard acid). Accordingly, B-TiO2 @Co2 P-500 hybrid nanosheets exhibit excellent U(VI) reduction ability (>98%) in the presence of competing ions. By self-consistent energy band calculations and in-situ KPFM spectral analysis, the formation of the internal electric field between B-TiO2 and Co2 P at the heterojunction is proven, offering a strong driving force and atomic transportation highway for accelerating the S-scheme charge carriers directed migration and promoting the photocatalytic reduction of uranium. This work provides a valuable route to explore the functionally modified photocatalyst with high-efficiency photoelectron separation for U(VI) reduction.

17.
Mol Cell Oncol ; 11(1): 2309715, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38343433

RESUMEN

Breast cancer was considered as a kind of prone breast tumors with the complicated pathological mechanisms and diverse clinical classifications. In the clinical treatments of HER2-positive tumor patients, HER2 monoclonal antibodies, such as Herceptin, have shown well-defined therapeutic effects. Nevertheless, due to the heterogeneity of breast cancers, drug resistance inevitably appeared during the application of Herceptin. In order to fully understand the immune tolerance status of the tumor microenvironment in the population of sensitive and insensitive patients, this study carried out a series of studies through Luminex cytokines assay, clinicopathological analysis, immunofluorescence, and PCR. The results confirmed that in clinical samples sensitive to Herceptin, there were a large number of macrophages, and the protein expression levels and in situ expression of macrophage-related chemokines and inflammatory mediators are significantly higher than drug-resistant tumor samples. Further studies found that T cell function has a low correlation with tumor growth, and there are obvious obstacles in the process of peripheral blood immune cells entering the tumor microenvironment. In summary, this study provided clues for understanding the clinical drug resistance of HER2 monoclonal antibody and the clinical rational use of drugs and combination drugs.

18.
J Orthop Translat ; 47: 176-190, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39040490

RESUMEN

Background: Osteoarthritis (OA) presents a formidable challenge, characterized by as-yet-unclear mechanical intricacies within cartilage and the dysregulation of bone homeostasis. Our preliminary data revealed the encouraging potential of a Sargassum polysaccharide (SP), in promoting chondrogenesis. The aim of our study is to comprehensively assess the therapeutic effects of SP on OA models and further elucidate its potential mechanism. Methods: The protective effects of SP were initially evaluated in an inflammation-induced human chondrocyte (C28) cell model. CCK-8 assays, Alcian blue staining, RT-qPCR and Western blotting were used to verify the chondrogenesis of SP in vitro. To assess the efficacy of SP in vivo, surgically induced medial meniscus destabilization (DMM) OA rats underwent an 8-week SP treatment. The therapeutic effects of SP in OA rats were comprehensively evaluated using X-ray imaging, micro-computed tomography (µ-CT), histopathological analysis, as well as immunohistochemical and immunofluorescent staining. Following these assessments, we delved into the potential signaling pathways of SP in inflammatory chondrocytes utilizing RNA-seq analysis. Validation of these findings was conducted through RT-qPCR and western blotting techniques. Results: SP significantly enhance the viability of C28 chondrocytes, and increased the secretion of acidic glycoproteins. Moreover, SP stimulated the expression of chondrogenic genes (Aggrecan, Sox9, Col2a1) and facilitated the synthesis of Collagen II protein in C28 inflammatory chondrocytes. In vivo experiments revealed that SP markedly ameliorated knee joint stenosis, alleviated bone and cartilage injuries, and reduced the histopathological scores in the OA rats. µ-CT analysis confirmed that SP lessened bone impairments in the medial femoral condyle and the subchondral bone of the tibial plateau, significantly improving the microarchitectural parameters of the subchondral bone. Histopathological analyses indicated that SP notably enhanced cartilage quality on the surface of the tibial plateau, leading to increased cartilage thickness and area. Immunohistochemistry staining and immunofluorescence staining corroborated these findings by showing a significant promotion of Collagen II expression in OA joints treated with SP. RNA-seq analysis suggest that SP's effects were mediated through the regulation of the ITGß1-PI3K-AKT signaling axis, thereby stimulating chondrogenesis. Verification through RT-qPCR and Western blot analyses confirmed that SP significantly upregulated the expression of ITGß1, p110δ, AKT1, ACAN, and Col2a1. Notably, knock-down of ITGß1 using siRNA in C28 chondrocytes inhibited the expression of ITGß1, p110δ, AKT1, and ACAN. However, these inhibitory effects were not completely reversed by supplemental SP intervention. Conclusions: In summary, our findings reveal that SP significantly enhances chondrogenesis both in vitro and in vivo, alleviating OA progression both in bone and cartilage. The observed beneficial effects are intricately linked to the activation of the ITGß1-PI3K-AKT signaling axis. The translational potential of this article: Our research marks the first instance unveiling the advantageous effects and underlying mechanisms of SP in OA treatment. With its clinical prospects, SP presents compelling new evidence for the advancement of a next-generation polysaccharide drug for OA therapy.

19.
Analyst ; 138(24): 7369-75, 2013 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-24165752

RESUMEN

In human plasma, the total concentration of non-protein binding (NPB) drugs is equal to the free drug concentration because NPB drugs do not or hardly bind to plasma proteins. Thus, centrifuge ultrafiltration (CF-UF) has been used in the determination of the concentration of NPB drugs in human plasma. However, with only a common centrifugation, the recovery and the reproducibility were not as excellent as expected. In addition, we discovered that the values of the volume ratio of ultrafiltrate to sample solution (Vu/Vs) were different and could not be well controlled, which may affect the determination of the drug concentration. The problem also affected the determination of other NBP drugs. In the present work, we used biapenem as a representative drug to study the effect of Vu/Vs on the analysis of NPB drugs concentration in human plasma. The results showed that a Vu/Vs value of less than 0.4 had no effect on the analysis of free drug concentration, while a Vu/Vs value of more than 0.4 was associated with increased recovery rate and overestimation of drug concentration. Therefore, to maintain a Vu/Vs value of less than 0.4 and even at a constant value is the key to accurately determine the concentration of NPB drugs in plasma. Fortunately, with an HFCF-UF device, the Vu/Vs could be well controlled and kept at 0.08 in this study. The recovery rates were almost 100% and the analysis precision was greatly improved. In pharmacokinetics studies, this method was successfully employed to determine the concentration of biapenem with excellent accuracy and reproducibility. HFCF-UF may become a feasible platform for the determination of NPB drugs.


Asunto(s)
Proteínas Sanguíneas/metabolismo , Preparaciones Farmacéuticas/metabolismo , Ultrafiltración/métodos , Cromatografía Líquida de Alta Presión , Humanos , Límite de Detección , Farmacocinética , Unión Proteica , Reproducibilidad de los Resultados
20.
Onkologie ; 36(11): 650-5, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24192769

RESUMEN

BACKGROUND: The aim of this study was to investigate the role of far upstream element-binding protein 1 (FUBP1) in gastric cancer development. PATIENTS AND METHODS: Using immunohistochemistry, we detected FUBP1 expression in 18 chronic superficial gastritis patients, 33 chronic atrophic gastritis patients, 21 moderate and severe gastric dysplasia patients, and 31 gastric cancer patients. FUBP1 mRNA expression in gastric cancer tissue and paraneoplastic tissue was measured with fluorescent quantitative reverse transcription polymerase chain reaction. RESULTS: The FUBP1 expression rates in the chronic atrophic gastritis, moderate and severe dysplasia, and gastric cancer patients were 51.51% (17/33), 76.19% (16/21), and 90.32% (28/31), respectively; these were higher than the expression rate of the chronic superficial gastritis patients (11.11%, 2/18). FUBP1 expression in the gastric cancer patients was significantly higher than that in the chronic atrophic gastritis patients. The relative amount (0.2593 ± 0.1209) of FUBP1 mRNA in the gastric cancer tissue was higher than that in paraneoplastic tissue (0.1969 ± 0.0211) (p < 0.05). There was a statistically significant correlation between overall survival rates and age, sex, lymph node metastasis, and distant metastasis (p < 0.05). CONCLUSION: FUBP1 expression differs among gastric tissues. There is a correlation between overall survival rates and age, sex, lymph node metastasis, and distant metastasis.


Asunto(s)
Biomarcadores de Tumor/metabolismo , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Síndromes Paraneoplásicos/metabolismo , Síndromes Paraneoplásicos/mortalidad , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Proteínas de Unión al ARN , Medición de Riesgo , Tasa de Supervivencia , Regulación hacia Arriba
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