bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination treatment of docetaxel with caffeic acid phenethyl ester suppresses the survival and the proliferation of docetaxel-resistant prostate cancer cells via induction of apoptosis and metabolism interference
Authors: Fu Yu-Ke , Wang Bi-Juan , Tseng Jen-Chih , Huang Shih-Han , Lin Ching-Yu , Kuo Ying-Yu , Hour Tzyh-Chyuan , Chuu Chih-Pin 
Published: February 2022

Abstract
Background
Docetaxel has been approved by USFDA as a first-line treatment for castration-resistant prostate cancer (CRPC) patients. Patients receiving androgen deprivation therapy along with docetaxel result in superior survival, lower serum prostate specific antigen (PSA) level, and better quality of life. However, a significant proportion of these patients ultimately develop resistance to docetaxel within months. Caffeic acid phenethyl ester (CAPE), one of the main bioactive components extracted from the propolis, has been reported to be effective for repressing the tumor growth, the migration and invasion of prostate cancer (PCa) cells, as well as the downstream signaling and stability of androgen receptor (AR). We hence determined if combination treatment of docetaxel with CAPE can suppress the proliferation and the survival of docetaxel-resistant PCa cells.

Methods
We established docetaxel-resistant PC/DX25 and DU/DX50 CRPC cell lines from PC-3 and DU-145 human PCa cells, respectively. Proliferation assay, MTT assay, flow cytometry with Annexin V staining, Comet Assay, and nude mice xenograft model were applied to determine the effects of combination treatment on cell proliferation and survival of the docetaxel-resistant PCa cells. Micro-Western Array (MWA) and qRT-PCR were used to investigate the molecular mechanism lying underneath.

Results
Combination treatment effectively suppressed the proliferation, survival and tumor growth of docetaxel-resistant PCa cells both in vitro and in nude mice. Comet assay and flow cytometry indicated that combination treatment induced apoptosis in docetaxel-resistant PCa cells. MWA and Western blotting assay revealed that combination treatment suppressed protein expression of Bcl-2, AKT2, c-Myc, apoptosis and caspase activation inhibitor (AVEN), pyruvate kinase M2 (PKM2) but increased protein expression of Bax, caspase 3, cytochrome c, glucose-6-phosphate dehydrogenase (G6PD) and acylglycerol kinase (AGK). Overexpression of Bcl-2 in the docetaxel-resistant PCa cells enhanced cell proliferation of docetaxel-resistant PCa cells under combination treatment. Analysis with qRT-PCR suggested that combination treatment decreased cholesterol biosynthesis genes DHCR24 (24-dehydrocholesterol reductase) and LSS (lanosterol synthase) but increased genes involved in glycolysis and TCA cycle.

Conclusions
Combination treatment of docetaxel with CAPE effectively suppressed the proliferation and survival of docetaxel-resistant PCa cells via inhibition of Bcl-2 and c-Myc as well as induction of metabolism interference. Combination treatment can be beneficial for patients with docetaxel-resistant PCa.
B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases
Authors: Joly Sandrine , Mdzomba Julius Baya , Rodriguez Léa , Morin Françoise , Vallières Luc , Pernet Vincent 
Published: February 2022

Abstract
Background
In the field of autoimmune demyelinating diseases, visual impairments have extensively been studied using the experimental autoimmune encephalomyelitis (EAE) mouse model, which is classically induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35–55). However, this model does not involve B cells like its human analogs. New antigens have thus been developed to induce a B cell-dependent form of EAE that better mimics human diseases.

Methods
The present study aimed to characterize the visual symptoms of EAE induced with such an antigen called bMOG. After the induction of EAE with bMOG in C57BL/6J mice, visual function changes were studied by electroretinography and optomotor acuity tests. Motor deficits were assessed in parallel with a standard clinical scoring method. Histological examinations and Western blot analyses allowed to follow retinal neuron survival, gliosis, microglia activation, opsin photopigment expression in photoreceptors and optic nerve demyelination. Disease effects on retinal gene expression were established by RNA sequencing.

Results
We observed that bMOG EAE mice exhibited persistent loss of visual acuity, despite partial recovery of electroretinogram and motor functions. This loss was likely due to retinal inflammation, gliosis and synaptic impairments, as evidenced by histological and transcriptomic data. Further analysis suggests that the M-cone photoreceptor pathway was also affected.

Conclusion
Therefore, by documenting visual changes induced by bMOG and showing similarities to those seen in diseases such as multiple sclerosis and neuromyelitis optica, this study offers a new approach to test protective or restorative ophthalmic treatments.
Cervical non-fusion using biomimetic artificial disc and vertebra complex: technical innovation and biomechanics analysis
Authors: Li Jialiang , OuYang Pengrong , He Xijing , Wei Xinyu , Sun Zhongwei , Dong Hui , Wen Zhijing , Wang Yibin , Gu Pengzhen , Lu Teng , Liu Ning , Li Haopeng 
Published: February 2022

Abstract
Background
Changes in spinal mobility after vertebral fusion are important factors contributing to adjacent vertebral disease (ASD). As an implant for spinal non-fusion, the motion-preserving prosthesis is an effective method to reduce the incidence of ASD, but its deficiencies hamper the application in clinical. This study designs a novel motion-preserving artificial cervical disc and vertebra complex with an anti-dislocation mechanism (MACDVC-AM) and verifies its effect on the cervical spine.

Methods
The MACDVC-AM was designed on the data of healthy volunteers. The finite element intact model, fusion model, and MACDVC-AM model were constructed, and the range of motion (ROM) and stress of adjacent discs were compared. The biomechanical tests were performed on fifteen cervical specimens, and the stability index ROM (SI-ROM) were calculated.

Results
Compared with the intervertebral ROMs of the intact model, the MACDVC-AM model reduced by 28–70% in adjacent segments and increased by 26–54% in operated segments, but the fusion model showed the opposite result. In contrast to the fusion model, the MACDVC-AM model diminished the stress of adjacent intervertebral discs. In biomechanical tests, the MACDVC-AM group showed no significant difference with the ROMs of the intact group (p > 0.05). The SI-ROM of the MACDVC-AM group is negative but close to zero and showed no significant difference with the intact group (p > 0.05).

Conclusions
The MACDVC-AM was successfully designed. The results indicate that the MACDVC-AM can provide physiological mobility and stability, reduce adjacent intervertebral compensatory motion, and alleviate the stress change of adjacent discs, which contributes to protect adjacent discs and reduce the occurrence of ASD.
A complex pheotype in a girl with a novel heterozygous missense variant (p.Ile56Phe) of the GNAS gene
Authors: Cavarzere Paolo , Gastaldi Andrea , Elli Francesca Marta , Gaudino Rossella , Peverelli Erika , Brugnara Milena , Thiele Susanne , Granata Francesca , Mantovani Giovanna , Antoniazzi Franco 
Published: February 2022

Abstract
Background
GNAS is a complex gene that encodes Gsα, a signaling protein that triggers a complex network of pathways. Heterozygous inactivating mutations in Gsα-coding GNAS exons cause hormonal resistance; on the contrary, activating mutations in Gsα result in constitutive cAMP stimulation. Recent research has described a clinical condition characterized by both gain and loss of Gsα function, due to a heterozygous de novo variant of the maternal GNAS allele.

Patients and methods
We describe a girl with a complex combination of clinical signs and a new heterozygous GNAS variant. For the molecular analysis of GNAS gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples. In silico analysis was performed to predict the possible in vivo effect of the detected novel genetic variant. The activity of Gsα protein was in vitro analyzed from samples of erythrocyte membranes, recovered from heparinized blood samples.

Results
We found a new heterozygous missense c.166A > T—(p.Ile56Phe) GNAS variant in exon 2, inherited from the mother that determined a reduced activity of 50% of Gsα protein function. The analysis of her parents showed a 20–25% reduction in Gsα protein activity in the mother and a normal function in the father. Clinically our patient presented a multisystemic disorder characterized by hyponatremia compatible with a nephrogenic syndrome of inappropriate antidiuresis, subclinical hyperthyroidism, subclinical hypercortisolism, precocious thelarche and pubarche and congenital bone abnormalities.

Conclusions
This is the first time that the new variant c.166A > T (p.Ile56Phe) on exon 2 of GNAS gene, originated on maternal allele, has been described as probable cause of a multisystemic disorder. Although the mutation is associated with a reduced activity of the function of Gsα protein, this unusual phenotype on the contrary suggests a mild functional gain.
Optogenetics: implications for Alzheimer’s disease research and therapy
Authors: Mirzayi Parsa , Shobeiri Parnian , Kalantari Amirali , Perry George , Rezaei Nima 
Published: February 2022

AbstractAlzheimer’s disease (AD), a critical neurodegenerative condition, has a wide range of effects on brain activity. Synaptic plasticity and neuronal circuits are the most vulnerable in Alzheimer’s disease, but the exact mechanism is unknown. Incorporating optogenetics into the study of AD has resulted in a significant leap in this field during the last decades, kicking off a revolution in our knowledge of the networks that underpin cognitive functions. In Alzheimer's disease, optogenetics can help to reduce and reverse neural circuit and memory impairments. Here we review how optogenetically driven methods have helped expand our knowledge of Alzheimer's disease, and how optogenetic interventions hint at a future translation into therapeutic possibilities for further utilization in clinical settings. In conclusion, neuroscience has witnessed one of its largest revolutions following the introduction of optogenetics into the field.
YTHDF1 promotes breast cancer progression by facilitating FOXM1 translation in an m6A-dependent manner
Authors: Chen Hengyu , Yu Yuanhang , Yang Ming , Huang Haohao , Ma Shenghui , Hu Jin , Xi Zihan , Guo Hui , Yao Guojie , Yang Liu , Huang Xiaoqing , Zhang Feng , Tan Guanghong , Wu Huangfu , Zheng Wuping , Li Lei 
Published: February 2022

Abstract
Background
N6-methyladenosine (m6A) is the most common post-transcriptional modification at the RNA level. However, the exact molecular mechanisms of m6A epigenetic regulation in breast cancer remain largely unknown and need to be fully elucidated.

Methods
The integrating bioinformatics analyses were used to screen clinical relevance and dysregulated m6A “reader” protein YTHDF1 in breast cancer from TCGA databases, which was further validated in a cohort of clinical specimens. Furthermore, functional experiments such as the CCK-8 assay, EdU assay, wound healing assay, transwell invasion assay and cell cycle assay were used to determine the biological role of YTHDF1 in breast cancer. RIP, m6A-IP, and CLIP assays were used to find the target of YTHDF1 and further verification by RT-qPCR, western blot, polysome profiling assay. The protein–protein interaction between YTHDF1 and FOXM1 was detected via co-immunoprecipitation.

Results
Our study showed that YTHDF1 was overexpressed in breast cancer cells and clinical tissues specimens. At the same time, the high expression level of YTHDF1 was positively correlated with tumor size, lymph node invasion, and distant metastasis in breast cancer patients. YTHDF1 depletion repressed the proliferation, invasion and epithelial-mesenchymal transformation (EMT) and induced G0/G1 phase cell cycle arrest of breast cancer cells in vitro and in vivo. We also demonstrated that FOXM1 is a target of YTHDF1. Through recognizing and binding to the m6A-modified mRNA of FOXM1, YTHDF1 accelerated the translation process of FOXM1 and promoted breast cancer metastasis. Whereas overexpression of FOXM1 in breast cancer cells partially counteracted the tumor suppressed effects caused by YTHDF1 silence, which further verified the regulatory relationship between YTHDF1 and FOXM1.

Conclusion
Our study reveals a novel YTHDF1/FOXM1 regulatory pathway that contributes to metastasis and progression of breast cancer, suggesting that YTHDF1 might be applied as a potential biomarker and therapeutic target. That also advances our understanding of the tumorigenesis for breast cancer from m6A epigenetic regulation.
Looking into the past to build the future: food, memory, and identity in the indigenous societies of Puebla, Mexico
Authors: Lugo-Morin Diosey Ramon 
Published: February 2022

AbstractFood memory has been determinant in the survival of social groups, the causes of its activation are varied (e.g. feelings, identity, need or challenge) and it is transmitted from generation to generation. These interactions have given rise to an ethnic food heritage that responds to cultural processes and territorial specificities. It is in this logic that this study is proposed, which aims to explore the dynamics between food, memory, and identity of two ethnic groups in the state of Puebla in Mexico in a context of health disruption. The experience of these two groups shows how food identity and memory is particularly strategic in the face of adversity, as is currently the case with the COVID-19 pandemic.
A preliminary evaluation of some language aspects in normal bilingual Egyptian kindergarten children
Authors: Aziz Azza A. , Osman Dalia M. , Abdel Hady Aisha F. , Maged Samar 
Published: February 2022

Abstract
Background
Bilingualism is the phenomenon of speaking and understanding two languages. The increased representation of bilingual populations calls for in-depth studies of bilingualism. The aim of this work is to devise an assessment protocol that could help in evaluating some aspects of Arabic and English languages acquired in typically developing bilingual preschool Egyptian children as a preliminary attempt to comprehend the language profiles of both languages in the studied group. The study was conducted on 80 bilingual Egyptian preschool male and female children exposed to both Arabic and English languages. Their age ranged from 4 to 4 years and 11 months from international English schools with regular attendance and of normal Arabic language development. All were subjected to the designed Bilingual English-Arabic semantic test, and narrative assessment and their parents and teachers filled in the questionnaires addressing the variables affecting both languages’ acquisition.

Results
Bilingual English-Arabic Semantic and Narration Tests revealed that children under the study had variable development in some aspects in semantic and narration between both languages and according to their age.

Conclusions
Data gathered from the study can be considered a preliminary nucleus for identification of the bilingual children’s normative data to be able to pick up the cases with language impairment of bilingual children and help in making diagnostic decisions and planning for future intervention.
A case of migration of fractured tracheostomy tube—a case presentation
Authors: Singhal Gaurang , Kumar Pallika , Goel Sachin , Goit Sanjeet , Pathak Anjali 
Published: February 2022

Abstract
Background
Tracheostomy is widely used for securing the airway; however, complications do occur. One such rare complication is a fracture of the tracheostomy tube which presents as a foreign body of the tracheobronchial tree.

Case presentation
We report a case of a 7-year-old child who presented with mild respiratory distress following fracture and migration of non-metallic tracheostomy tube in the airway. Successful removal was done via rigid bronchoscopy under general anaesthesia.

Conclusion
Careful inspection of the tracheostomy tube before placing and appropriate tracheostomy care is the cornerstone to prevent such rare complications associated with a tracheostomy.
Polyethylene terephthalate nanoparticles effect on RAW 264.7 macrophage cells
Authors: Aguilar-Guzmán J. Cristóbal , Bejtka Katarzyna , Fontana Marco , Valsami-Jones Eugenia , Villezcas Anaid Meza , Vazquez-Duhalt Rafael , Rodríguez-Hernández Ana G. 
Published: February 2022

AbstractPlastic pollution is a major environmental concern due to its pervasiveness which continues to increase year on year, as a result of a continuing acceleration in global plastic production and use. Polyethylene terephthalate (PET) is among the most produced plastics, commonly used as food and beverage containers. Once released in the environment, the degradation of plastic materials produces micro-and nano-plastics, with a particular concern about potential toxicological effects if they cross epithelial barriers via inhalation or ingestion. In this work, the effect of PET nanoparticles (PET-NPs) (≤ 250 d.nm) was assayed on mouse macrophages cell line (RAW 264.7) in in vitro experiments. Results showed that PET nanoparticles were easily internalized by the cells, 15 μg/mL of nanoparticles concentration had exhibited effects in cell proliferation and a slightly increased production of Reactive Oxygen Species (ROS), which seems to trigger cell response as foreign particles related to upregulation of PCDH12, IGH-V10, ROBO1 genes, and cell maintenance functions, related to FTSJ2 gene upregulation. Thus, the RAW 264.7 results showed here are useful towards for a preliminary and understanding of the potentially toxic effects related to PET nanoparticles and complementary to other in vitro assays, as the first step into the development of the risk assessment framework.
Morpho-functional comparison of differentiation protocols to create iPSC-derived cardiomyocytes
Authors: Nijak Aleksandra , Simons Eline , Vandendriessche Bert , Van de Sande Dieter , Fransen Erik , Sieliwończyk Ewa , Van Gucht Ilse , Van Craenenbroeck Emeline , Saenen Johan , Heidbuchel Hein , Ponsaerts Peter , Labro Alain J. , Snyders Dirk , De Vos Winnok , Schepers Dorien , Alaerts Maaike , Loeys Bart L. 
Published: February 2022

ABSTRACT
Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) offer an attractive platform for cardiovascular research. Patient-specific iPSC-CMs are very useful for studying disease development, and bear potential for disease diagnostics, prognosis evaluation and development of personalized treatment. Several monolayer-based serum-free protocols have been described for the differentiation of iPSCs into cardiomyocytes, but data on their performance are scarce. In this study, we evaluated two protocols that are based on temporal modulation of the Wnt/β-catenin pathway for iPSC-CM differentiation from four iPSC lines, including two control individuals and two patients carrying an SCN5A mutation. The SCN5A gene encodes the cardiac voltage-gated sodium channel (Nav1.5) and loss-of-function mutations can cause the cardiac arrhythmia Brugada syndrome. We performed molecular characterization of the obtained iPSC-CMs by immunostaining for cardiac specific markers and by expression analysis of selected cardiac structural and ionic channel protein-encoding genes with qPCR. We also investigated cell growth morphology, contractility and survival of the iPSC-CMs after dissociation. Finally, we performed electrophysiological characterization of the cells, focusing on the action potential (AP) and calcium transient (CT) characteristics using patch-clamping and optical imaging, respectively. Based on our comprehensive morpho-functional analysis, we concluded that both tested protocols result in a high percentage of contracting CMs. Moreover, they showed acceptable survival and cell quality after dissociation (&gt;50% of cells with a smooth cell membrane, possible to seal during patch-clamping). Both protocols generated cells presenting with typical iPSC-CM AP and CT characteristics, although one protocol (that involves sequential addition of CHIR99021 and Wnt-C59) rendered iPSC-CMs, which were more accessible for patch-clamp and calcium transient experiments and showed an expression pattern of cardiac-specific markers more similar to this observed in human heart left ventricle samples.
Reprogramming cellular identity in vivo
Authors: Leaman Sydney , Marichal Nicolás , Berninger Benedikt 
Published: February 2022

ABSTRACT
Cellular identity is established through complex layers of genetic regulation, forged over a developmental lifetime. An expanding molecular toolbox is allowing us to manipulate these gene regulatory networks in specific cell types in vivo. In principle, if we found the right molecular tricks, we could rewrite cell identity and harness the rich repertoire of possible cellular functions and attributes. Recent work suggests that this rewriting of cell identity is not only possible, but that newly induced cells can mitigate disease phenotypes in animal models of major human diseases. So, is the sky the limit, or do we need to keep our feet on the ground? This Spotlight synthesises key concepts emerging from recent efforts to reprogramme cellular identity in vivo. We provide our perspectives on recent controversies in the field of glia-to-neuron reprogramming and identify important gaps in our understanding that present barriers to progress.
Assessment of anterior thigh muscle size and fat infiltration using single-slice CT imaging versus automated MRI analysis in adults
Authors: Niklasson Erik , Borga Magnus , Dahlqvist Leinhard Olof , Widholm Per , Andersson Daniel P , Wiik Anna , Holmberg Mats , Brismar Torkel B , Gustafsson Thomas , Lundberg Tommy R 
Published: February 2022

Objectives: We examined the longitudinal and cross-sectional relationship between automated MRI-analysis and single-slice axial CT imaging for determining muscle size and muscle fat infiltration (MFI) of the anterior thigh. Methods: Twenty-two patients completing sex-hormone treatment expected to result in muscle hypertrophy (n = 12) and atrophy (n = 10) underwent MRI scans using 2-point Dixon fat/water-separated sequences and CT scans using a system operating at 120 kV and a fixed flux of 100 mA. At baseline and 12 months after, automated volumetric MRI analysis of the anterior thigh was performed bilaterally, and fat-free muscle volume and MFI were computed. In addition, cross-sectional area (CSA) and radiological attenuation (RA) (as a marker of fat infiltration) were calculated from single slice axial CT-images using threshold-assisted planimetry. Linear regression models were used to convert units. Results: There was a strong correlation between MRI-derived fat-free muscle volume and CT-derived CSA (R = 0.91), and between MRI-derived MFI and CT-derived RA (R = −0.81). The 95% limits of agreement were ±0.32 L for muscle volume and ±1.3% units for %MFI. The longitudinal change in muscle size and MFI was comparable across imaging modalities. Conclusions: Both automated MRI and single-slice CT-imaging can be used to reliably quantify anterior thigh muscle size and MFI. Advances in knowledge: This is the first study examining the intermodal agreement between automated MRI analysis and CT-image assessment of muscle size and MFI in the anterior thigh muscles. Our results support that both CT- and MRI-derived measures of muscle size and MFI can be used in clinical settings.