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81.
Mio Yamaguchi Kiyoshi Takagi Koki Narita Yasuhiro Miki Yoshiaki Onodera Minoru Miyashita Hironobu Sasano Takashi Suzuki 《International journal of molecular sciences》2021,22(4)
Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment. 相似文献
82.
Evita Athanasiou Antonios N. Gargalionis Fotini Boufidou Athanassios Tsakris 《International journal of molecular sciences》2021,22(5)
The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases. 相似文献
83.
Yeonsil Moon Changmok Lim Yeahoon Kim Won-Jin Moon 《International journal of molecular sciences》2021,22(6)
The role of the blood–brain barrier (BBB) breakdown has been recognized as being important in Alzheimer’s disease pathogenesis. We aimed to evaluate whether regional BBB integrity differed according to sex and whether differences in BBB integrity changed as a consequence of aging or cognitive decline, using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). In total, 75 participants with normal cognition (NC) or mild cognitive impairment (MCI) underwent cognitive assessments and MRI examination including DCE-MRI. Regional Ktrans was calculated in cortical regions and the Patlak permeability model was used to calculate BBB permeability (Ktrans, min−1). Females had a lower median Ktrans in the cingulate and occipital cortices. In the “older old” group, sex differences in Ktrans were only observed in the occipital cortex. In the MCI group, sex differences in Ktrans were only observed in the occipital cortex. Age was the only predictor of cognitive assessment scores in the male MCI group; however, educational years and Ktrans in the occipital cortex could predict cognitive scores in the female MCI group. Our study revealed that females may have better BBB integrity in cingulate and occipital cortices. We also found that sex-related differences in BBB integrity are attenuated with aging or cognitive decline. 相似文献
84.
Improved Controlled Release and Brain Penetration of the Small Molecule S14 Using PLGA Nanoparticles
Vanesa Nozal Elisa Rojas-Prats Ins Maestro Carmen Gil Daniel I. Perez Ana Martinez 《International journal of molecular sciences》2021,22(6)
Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7’s role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor. 相似文献
85.
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87.
松材病虫病是最紧迫的威胁之一,最近对中国针叶林造成了严重破坏,为了阻止松材病虫病的快速传播,必须在早期准确检测和计数受感染的树木。提出了一种基于密度图的方法,用于从高分辨率航拍图像中估计具有松材病虫病的树木数量,方法引入了阈值分割、形态处理和超像素技术,以最大限度地减少由于建筑物和岩石等相似背景物体引起的误差。实验表明,所提出的方法优于密度学习 算法,平均绝对误差、均方根误差和绝对误差方差分别从21.3、22.2和127.2减少到8.0、11.7和59.6,计数准确率从54.7%提高到81.3%。 相似文献
88.
Dr. Bo Zhou Zhengxi Guo Zhaoxin Lin Prof. Bang-Ping Jiang Prof. Xing-Can Shen 《ChemMedChem》2021,16(6):919-931
Phototherapy, a type of photoresponsive regulation of biological activities, together with additional stimuli-responsive features, offers significant potential for enhancing the precision and efficacy of cancer treatments. To achieve tumor-specific therapeutics, numerous studies have focused on the development of smart phototherapeutic nanomaterials (PNMs) that can respond to endogenous pathological characteristics (e. g., mild acidity, the overproduction of glutathione, the overproduction of hydrogen peroxide, the overexpression of specific surface receptors, etc.) present in the tumor and/or exogenous stimuli. Such responsiveness can effectively improve the physicochemical properties, cellular uptake, tumor-targeting performance, and pharmacokinetic profile of PNMs. Herein, we will systematically discuss recent advances in this field. Moreover, potential challenges and future directions in the development of stimuli-responsive PNMs are also presented to support the development of this emerging cutting-edge research area. 相似文献
89.
Ilaria Zuliani Chiara Lanzillotta Antonella Tramutola Eugenio Barone Marzia Perluigi Serena Rinaldo Alessio Paone Francesca Cutruzzol Francesco Bellanti Matteo Spinelli Francesca Natale Salvatore Fusco Claudio Grassi Fabio Di Domenico 《International journal of molecular sciences》2021,22(7)
The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process. 相似文献
90.
Luis O. Soto-Rojas B. Berenice Campa-Crdoba Charles R. Harrington Andrs Salas-Casas Mario Hernandes-Alejandro Ignacio Villanueva-Fierro Marely Bravo-Muoz Linda Garcs-Ramírez Fidel De La Cruz-Lpez Miguel ngel Ontiveros-Torres Goar Gevorkian Mar Pacheco-Herrero Jos Luna-Muoz 《International journal of molecular sciences》2021,22(7)
Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD. 相似文献