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Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant human brain tumor. Although comprehensive therapies, including chemotherapy and radiotherapy following surgery, have shown promise in prolonging survival, the prognosis for GBM patients remains poor, with an overall survival rate of only 14.6 months. Chemoresistance is a major obstacle to successful treatment and contributes to relapse and poor survival rates in glioma patients. Therefore, there is an urgent need for novel strategies to overcome chemoresistance and improve treatment outcomes for human glioma patients. Recent studies have shown that the tumor microenvironment plays a key role in chemoresistance. Our study demonstrates that upregulation of HAS2 and subsequent hyaluronan secretion promotes glioma cell proliferation, invasion, and chemoresistance in vitro and in vivo through the c-myc pathway. Targeting HAS2 sensitizes glioma cells to chemotherapeutic agents. Additionally, we found that hypoxia-inducible factor HIF1α regulates HAS2 expression. Together, our findings provide insights into the dysregulation of HAS2 and its role in chemoresistance and suggest potential therapeutic strategies for GBM.
Asunto(s)
Proliferación Celular , Resistencia a Antineoplásicos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteínas Proto-Oncogénicas c-myc , Regulación hacia Arriba , Animales , Humanos , Ratones , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Glioblastoma/patología , Glioblastoma/genética , Glioma/patología , Glioma/metabolismo , Glioma/genética , Hialuronano Sintasas/metabolismo , Hialuronano Sintasas/genética , Ácido Hialurónico/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones Desnudos , Proteínas Proto-Oncogénicas c-myc/metabolismoRESUMEN
Soilless cultivation of potatoes often utilizes organic coconut peat and inorganic vermiculite as growing substrates. The unique microbial communities and physicochemical characteristics inherent to each substrate significantly influence the microecological environment crucial for potato growth and breeding. This study analyzed environmental factors within each substrate and employed Illumina sequencing alongside bioinformatics tools to examine microbial community structures, their correlation with environmental factors, core microbial functions, and the dynamics of microbial networks across various samples. These included pure coconut peat (CP1) and pure vermiculite (V1), substrates mixed with organic fertilizer for three days (CP2 and V2), and three combinations cultivated with potatoes for 50 days (CP3, V3, and CV3-a 1:1 mix of coconut peat and vermiculite with organic fertilizer). Vermiculite naturally hosts a more diverse microbial community. After mixing with fertilizer and composting for 3 days, and 50 days of potato cultivation, fungal diversity decreased in both substrates. Coconut peat maintains higher bacterial diversity and richness compared to vermiculite, harboring more beneficial bacteria and fungi, resulting in a more complex microbial network. However, vermiculite shows lower bacterial diversity and richness, with an accumulation of pathogenic microorganisms. Among the 11 environmental factors tested, water-soluble nitrogen (WSN), total nitrogen (TN), available potassium (AK), total organic carbon (TOC) and air-filled porosity (AFP) were significantly associated with microbial succession in the substrate.The nutritional type composition and interaction patterns of indigenous microorganisms differ between vermiculite and coconut peat. Adding abundant nutrients significantly affects the stability and interaction of the entire microbial community, even post-potato cultivation. When using vermiculite for soilless cultivation, precise control and adjustment of nutrient addition quantity and frequency are essential.
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Hyaluronic acid (HA) is a crucial component of the extracellular matrix, and its level of accumulation is related to the progression of various malignant tumors. In this study, a pan-cancer analysis of the three enzymes called hyaluronan synthases (HAS1, HAS2, and HAS3) that produce HA was performed. The study comprehensively describes the characteristics of HAS1, HAS2, and HAS3 in cancers using public databases and tools, to identify the potential biological pathways involved at the molecular, protein, cellular, and clinical sample levels. The analysis showed that dysregulation of the three genes often occurs in cancer, contributing to cancer progression, metastasis, and prognosis. Overexpression of HAS2 promotes secretion of HA in GBM and enhances cell proliferation and migration. The common and specific functions of HAS in certain diseases have important research implications for the treatment and prognosis of tumors.
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The success of autologous tooth transplantation depends on the activity of the periodontal ligament of the donor tooth. Its activity decreases with a longer exposure time. In order to reduce the exposure time of the donor tooth and quickly prepare the alveolar fossa highly matching with the donor tooth root, the clinical data of cone-beam CT (CBCT) was imported into Mimics 21.0 software in this study to obtain three-dimensional (3D) images of the jaw tissue structure. The images were used to extract the target area and select the target tooth. By analysing the information of the recipient region and the donor region, 3-Matic 13.0 software was used to implant the donor virtual into the target region, and restrictive personalised guidance was designed. Subsequently, the surgical guide template was printed by 3D printing technology, and the alveolar fossa was rapidly prepared in vitro. After the operation, the donor tooth was matched with the complete alveolar cavity using 3-Matic13.0 software. The depth deviation of the prepared alveolar cavity was measured within 2.0 mm, and the width deviation was about 1.0 mm. The maximum width deviation is 2.88 mm due to the tilt of the roots. With a high matching degree to the donor tooth root, it needs further and larger clinical studies. Key Words: CBCT, Tooth autotransplantation, 3D printing technology, Computer-aided imaging, Periodontal ligament.
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Cirugía Asistida por Computador , Diente , Humanos , Trasplante Autólogo/métodos , Cirugía Asistida por Computador/métodos , Diente/diagnóstico por imagen , Raíz del Diente/diagnóstico por imagen , Raíz del Diente/cirugía , Impresión Tridimensional , Diseño Asistido por ComputadoraRESUMEN
This study focused on the biomechanical properties and microstructural changes in dentin of teeth in different age groups after cryopreserved for different durations. Ninety third molars from three age groups (youth group, middle-age group, and elderly group), were collected and randomly divided into three groups according to freezing time at -196 °C (7 days, 30 days, and 90 days). Control group was shored at ordinary temperature. After rewarming, the compressive strength and elastic modulus of the dentin were measured with an electronic universal tester. Scanning electron microscopy was used to evaluate the microstructure of dentin after cryopreservation. After cryopreservation, the compressive strength of the teeth in each experimental group was not significantly different from control group. With the increase of freezing time and age, dentin's elastic modulus showed a decreasing trend. There were statistically significances between the control group and freezing 90d group, freezing 7d and 90d group, youth and middle-aged group, youth and elderly group (P < 0.05). Both freezing time and age factors were significant for the elastic modulus of dentin(Pï¼0.05). There was no interaction effect for age and freezing time. In transverse sections of scanning electron microscopy, the dentinal tubule became narrower, partially occluded, and more easily adhered to impurities in the long freezing time and elderly group. In longitudinal sections, with freezing time and age, the inner wall of the dentinal tubules became rough especially in the aged group cryopreserved for 90 days. No significant microcracks exited in any of the longitudinal sections of dentin.
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Criopreservación , Dentina , Humanos , Anciano , Persona de Mediana Edad , Adolescente , Lactante , Criopreservación/métodos , Dentina/química , Congelación , Microscopía Electrónica de RastreoRESUMEN
Long-term use of olanzapine, an antipsychotic drug, induces hypertriglyceridemia, resulting in a higher risk of cardiovascular disease. However, the effects and underlying mechanisms of short-term use of olanzapine on circulating triglyceride levels remain poorly understood. Here, the role of apolipoprotein A5 (apoA5), a regulator of triglyceride metabolism, was investigated in olanzapine-induced hypertriglyceridemia. Our multi-center clinical study recruited 36 schizophrenia patients who received short-term (8 weeks) of olanzapine. Besides, female C57BL/6J mice were treated with olanzapine (3 mg/kg/day versus 6 mg/kg/day) for 6 weeks. We demonstrated that short-term use of olanzapine increased plasma triglyceride and decreased plasma apoA5 levels in the patients and mice, with a negative correlation between the two factors. However, no obesity was observed in the patients and mice. Interestingly, olanzapine increased hepatic apoA5 protein in the mice, without significant changes in hepatic Apoa5 mRNA. Consistently, in vitro studies indicated that olanzapine increased medium triglyceride levels and decreased medium apoA5 levels in a dose-dependent manner in human HepG2 cells and primary mouse hepatocytes. Whereas the olanzapine treatment increased hepatic apoA5 protein in vitro, without effects on hepatic APOA5 mRNA. Of note, olanzapine increased the co-localization between apoA5 protein and accumulated lipid droplets in hepatocytes, as opposed to at the hepatocellular plasma membrane, in mouse liver as demonstrated by fluorescence staining. Therefore, our study indicated that short-term use of olanzapine induced hypertriglyceridemia due to defects of sorting and secretion of hepatic apoA5.
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Eupatorium fortunei Turcz, a perennial herb of the Asteraceae family, is one of the horticultural and medicinal plants used for curing various diseases and is widely distributed in China and other Asian countries. It possesses antibacterial, antimetastatic, antiangiogenic, and antioxidant properties along with anticancer potential. However, the intrageneric classification and phylogenetic relationships within Eupatorium have long been controversial due to the lack of high-resolution molecular markers, and the complete chloroplast (cp) genome sequencing has not been reported with new evolutionary insights. In the present study, E. fortunei was used as an experimental material, and its genome was sequenced using high-throughput sequencing technology. We assembled the complete cp genome, and a systematic analysis was conducted for E. fortunei, acquiring the correspondence of its NCBI accession number (OK545755). The results showed that the cp genome of E. fortunei is a typical tetrad structure with a total length of 152,401 bp, and the genome encodes 133 genes. Analysis of the complete cp genomes of 20 Eupatorieae shows that the number of simple sequence repeats (SSRs) ranged from 19 to 36 while the number of long sequence repeats was 50 in all cases. Eleven highly divergent regions were identified and are potentially useful for the DNA barcoding of Eupatorieae. Phylogenetic analysis among 22 species based on protein-coding genes strongly supported that E. fortunei is more closely related to Praxelis clematidea and belongs to the same branch. The genome assembly and analysis of the cp genome of E. fortunei will facilitate the identification, taxonomy, and utilization of E. fortunei as well as provide more accurate evidence for the taxonomic identification and localization of Asteraceae plants.
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Asteraceae , Eupatorium , Genoma del Cloroplasto , Eupatorium/genética , Asteraceae/genética , Filogenia , Secuenciación Completa del GenomaRESUMEN
Single-chain variable fragment (scFv) antibodies are the smallest immunoglobulins with high antigen-binding affinity. We have previously reported that fibroblast growth factor 1 played pivotal roles in cancer development and generated a mouse scFv (mscFv1C9) could effectively prohibit cancer cell proliferation in vitro and in vivo. Here, we further humanized this scFv (hscFv1C9) using a structure-guided complementarity determining region grafting strategy. The purified hscFv1C9 maintained similar antigen-binding affinity and specificity as mscFv1C9, and it was capable of inhibiting growth of different tumours in vitro and in vivo. These data strongly suggested that hscFv1C9 has antitumour potentials.
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Neoplasias de la Mama/tratamiento farmacológico , Factor 1 de Crecimiento de Fibroblastos/antagonistas & inhibidores , Glioma/tratamiento farmacológico , Anticuerpos de Cadena Única/farmacología , Secuencia de Aminoácidos/genética , Animales , Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Monoclonales Humanizados/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor 1 de Crecimiento de Fibroblastos/química , Factor 1 de Crecimiento de Fibroblastos/genética , Factor 1 de Crecimiento de Fibroblastos/inmunología , Glioma/genética , Glioma/patología , Xenoinjertos , Humanos , Ratones , Anticuerpos de Cadena Única/inmunologíaRESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the co-Editors-in-Chief. The article plagiarizes a paper that was published in BioMed Research International, Volume 2015 (2015), Article ID 729768, 14 pages, http://dx.doi.org/10.1155/2015/729768. Nearly the entire introduction and sections of the methods, limitations and conclusions duplicate the BioMed Research International paper. One of the conditions of submission of a paper to Archives of Physical Medicine and Rehabilitation is that authors declare explicitly that the paper is an original work and not duplicative of prior work unless that work is cited properly. The duplication in this manuscript is a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter.
RESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the co-Editors-in-Chief. The article plagiarizes a paper that was published in BioMed Research International, Volume 2015 (2015), Article ID 729768, 14 pages, http://dx.doi.org/10.1155/2015/729768. Nearly the entire introduction and sections of the methods, limitations and conclusions duplicate the BioMed Research International paper. One of the conditions of submission of a paper to Archives of Physical Medicine and Rehabilitation is that authors declare explicitly that the paper is an original work and not duplicative of prior work unless that work is cited properly. The duplication in this manuscript is a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter.
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Frequently accidental spill of hazard materials into soil environment posed significant threats to human health and natural environment in China. In this paper, simulated nonaqueous phase liquid (NAPLs) toluene sudden spill in fluvo-aquic soil was performed in a two-dimensional tank to investigate the migration and distribution characteristics of toluene as well as its simulation through STOMP model. Visual observation showed that the horizontal expansion of toluene with concentration > 1 g x kg(-1) and > 20 g x kg(-1) were approximate 2.3 and 3 times the length of the corresponding vertical transportation, respectively. The result revealed that toluene exerted a preferential tendency to lateral spread compared to the vertical migration trends, which may contribute to the impeding effect as a result of the low permeable capacity of soil (permeability coefficient was 0.12 cm x h(-1)). The behavior and fate of toluene in heterogeneous soil layers (combined fluvo-aquic-sand and sand-fluvo-aquic soil layers, respectively) after spill were simulated using STOMP model and the results indicated that the significant difference in relative permeability of interface layer, due to the much higher value of permeability coefficient of sand (29.70 cm x h(-1)) than that of fluvo-aquic soil, played an important role on the redistribution of toluene after its spill into the heterogeneous soil layers. For practical purposes, the results of this study may be beneficial to identify the distribution property of NAPLs in time after its release into the soil environment.