bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulatory Effects of high‐purity β‐glucan on macrophage, natural killer (NK) cells, and T cell mediated factors
Authors: Kwon Han Ol , Lee Minhee , Ha Yejin , Kim Hye Sook , Shim Hyejin , Lee Jeongmin 
Published: November 2023

The present study investigated the immunomodulatory effects of high‐purity β‐glucan on macrophage, natural killer (NK) cells, and T cell mediated factors. High‐purity β‐glucan on cytotoxicity in macrophage was investigated. Using macrophage, cytotoxicity of high‐purity β‐glucan was evaluated by MTT assay. We treated high‐purity β‐glucan at concentrations of 50, 100, 150, 200, and 250 μg/mL in macrophage. High‐purity β‐glucan did not affect the macrophage viability. Phagocytic activity was used zymosan. High‐purity β‐glucan cell was significantly increased as compared with the zymosan. We treated high‐purity β‐glucan to murine NK cells co‐incubated with YAC‐1 cells. High‐purity β‐glucan resulted in a significantly increased activity of Natural killer cell as compared with the control. In addition, treatment of macrophage with high‐purity β‐glucan resulted in a significantly increased activity of T cell mediated cytokines (IL‐2, IL‐12, IFN‐γ, and TNF‐α) levels as compared with the control. In conclusion, high‐purity β‐glucan could enhance immune response through activation of macrophage, NK cell, and T cell mediated factors.Support or Funding InformationThis reserch was financially supported by Korea Institute for Advancement of Technology(KIAT, 20151810) through the research and development for regional industry.
Anti‐Infective and Histogenic Bioscaffold for Bone Defect Repair
Authors: Luo Yangyang , Mills David 
Published: November 2023

The objective of this study was to develop a stable drug delivery platform that is biocompatible, biodegradable and would provide sustained combinatorial drug release for the control of bone infection while simultaneously supporting bone tissue regeneration. Chitosan has been widely used in tissue engineering and in a variety of biomedical applications due to its eco‐friendly and biodegradable properties and it possesses a physiochemistry similar to the extracellular matrix of bone. However, the application of chitosan has been limited by its inherent mechanical weakness. Halloysite nanotubes (HNTs) are a naturally‐occurring aluminosilicate clay with a hollow tubular structure. HNTs are widely used as a bulk filler to materially reinforce a variety of polymer materials from bone cement to rubber. They have also been shown to be a potent nanocontainer for the sustained release of varied bioactive factors. In this study, chitosan and HNTs and chitosan and HNTs, doped with gentamicin and BMP‐2, were combined in different wt./wt. ratios and cross‐linked with tripolyphosphate. The biodegradability, mechanical properties, and surface structure of the hybrid nanocomposites were tested. The ability of the nanocomposites to control bacterial growth while supporting bone tissue formation was also evaluated. Gentamicin was selected as a model drug to evaluate the drug release capability of the chitosan‐HNTs nanocomposites and with release, its effectiveness against E. coli was analyzed through growth inhibition studies. Results indicate that the addition of HNTs to the chitosan hydrogel significantly improved the gels’ mechanical properties, permitting an extended period of drug release, and without a negative affect on drug efficacy. The coatings were capable of inhibiting bacterial growth and osteoblasts cultured on the hydrogel surfaces showed enhanced growth and functionality. Our doped clay/chitosan nanocomposite may overcome the limitations of traditional anti‐bacterial hydrogels and its ability to support bone tissue formation may enable its use in bone defect repair results from osteomyelitis.Support or Funding InformationFunding for this project was provided by the Louisiana Governor's Biotechnology Initiative and Louisiana Board of Regents OPT‐IN program.
Low‐grade Fibromyxoid Sarcoma of the Sigmoid Presenting as Uterine Fibroid
Authors: MENDOZA ALEJANDRO S. , Peng Shi‐Kaung , French Samuel W. 
Published: November 2023

BACKGROUNDLow‐grade fibromyxoid sarcoma(LGFMS) is a rare soft tissue tumor with a slight male predominance. The tumor has a tendency to arise from deep soft tissue of the trunk and lower extremities. Rare cases are reported to arise from the mediastinal and retroperitoneal areas. Its deceptively bland histologic appearance makes this tumor difficult to diagnose. We report a case of low‐grade fibromyxoid sarcoma presenting as uterine fibroid.CASE REPORTThe patient is a 48‐year‐old obese female with a history of hypertension and menometrorrhagia who presented complaining of persistent lower abdominal pain and vaginal bleeding. A transvaginal ultrasound revealed an 8.7 cm uterine fibroid and MRI of the pelvis revealed a 10.6 × 6.9 × 8.1 cm lobulated mass within the mid pelvis. The patient was taken to the operating room for a total abdominal hysterectomy with bilateral salpingo‐oophorectomy for a mass of presumed gynecologic origin. Intraoperatively, a large 12 cm mass located in the pelvis was seen to be arising from the sigmoid colon. A shave biopsy was obtained, abdomen closed, and further staging of the colonic mass ensued. Further tests were negative of metastatic disease. Patient consequently underwent emergent sigmoidectomy due to bowel obstruction. Histologically, the tumor showed a swirling whorled growth pattern with alternating fibrous and myxoid areas. The myxoid area had a low to moderate cellularity composed of bland spindle cells with scant cytoplasm, uniform elongated nuclei, and small inconspicuous nucleoli. The tumor cells stained negative for most muscle, neural and mesenchymal stains but positive for CD99, BCL2 and MUC4 stains.CONCLUSIONLGFMS has a deceptively bland histologic appearance making this tumor difficult to diagnose. CD99 and BCL2 stains will yield 90% positivity. MUC4 stain is highly specific and 100% sensitive for low grade fibromyxoid sarcoma. Molecular study will be 90% positive for t(7;16)(q32–34;p11) FUS‐CREB3L2 fusion gene.Support or Funding InformationWe declare no benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Thermal Manipulation during Mid‐term Broiler Chicken Embryogenesis: Effect on Muscle Growth Factors and Muscle Marker Genes
Authors: Al‐Zghoul Mohammad borhan 
Published: November 2023

Animal productivity for meat consumption is directly related to the cellular and molecular mechanisms regulating skeletal muscle growth and development. Thermal manipulation (TM) during mid and late broiler chicken embryogenesis has been shown to promote muscle development and growth. However, the molecular bases of promoting muscle development and growth are not fully understood. The aim of this study was to investigate the molecular bases of muscle growth and development in broiler chicken subjected to thermal manipulation (39° and 65% for 9, 12 or 18 h) daily during ED 12–18. This included the investigating the changes in mRNA expression levels of muscle marker genes (MyoD, Myogenin, Pax7 and PCNA), and muscle growth factors (IGF‐1, Myostatin and GH) during embryogenesis and at posthatch days 10 and 28. Fertile Cobb strain eggs (n=1500) were divided into four groups. Control group was incubated at 37.8°C and 56% relative humidity (RH), the second group (TM1) was subjected to 39°C daily during (ED 12–18) and 65% relative humidity (RH) for 9 hours. The third group (TM2) was subjected to 39°C daily during (ED 12–18) and 65% (RH) for 12 hours. The fourth group (TM3) was subjected to 39°C daily during (ED 12–18) and 65% (RH) for 18 hours. The body weight (BW) during embryogenesis and at posthatch days (1, 3, 5, 7, 14, 21, 28 and 35) was recorded. mRNA expression levels of muscle marker genes (MyoD, Myogenin, Pax7 and PCNA) and muscle growth factor genes (IGF‐1, Myostatin and GH) during embryonic days 12, 14, 16 and 18 and at the posthatch days 10 and 28 were analyzed using the real time RT‐ PCR. TM resulted in significant increase in the mRNA expression of muscle marker genes and muscle growth factors, which were accompanied by the improvement of muscle mass and body weight at posthatch days 28 and 35 of age.Support or Funding InformationThis project was funded by National Plan for Science, Technology and Innovation (MAARIFAH)‐King Abdulaziz city for Science and Technology‐The king of Saudi Arabia, award number (11‐B10 1805‐06).
Fluorinated Caffeic Acid Phenethyl Ester: a Novel Anti‐osteogenic molecule to Attenuate Excessive Bone Damage during Autoimmune Arthritis
Authors: Holland Lauren , Mula Ramanjaneya VR , Machiah Deepa , Wang Xinyu , Shashidharamurthy Rangaiah 
Published: November 2023

Caffeic Acid Phenethyl Ester (CAPE), an antioxidant flavonoid isolated from hives of honeybee, is reported to exert its anti‐osteogenic function by inhibiting the NF‐kB activation. It also disrupts the microtubule network created by osteoclasts, which would also aid in the attenuation of bone resorption. However, commercially available parental CAPE molecules are highly insoluble and have low stability. Recent studies have shown that a new fluorinated derivative of CAPE (F‐CAPE) exhibited improved NF‐kB inhibition and stability. Herein we have investigated the anti‐osteoclastogenic activity of F‐CAPE using an in vitro osteoclastogenesis model with mouse monocytic cell line (RAW264.7 cells). We observed an increased dose dependent inhibition of receptor activator of nuclear factor kappa‐B ligand (RANKL)‐induced multinuclear tartarate resistant acid phosphatase (TRAP) positive osteoclast formation by F‐CAPE compared to the parental compound. F‐CAPE at 150nM concentration has shown more than 2 fold higher anti‐osteoclastogenic activity compared to CAPE. Western blot analysis revealed that F‐CAPE decreased the expression of c‐Fos and nuclear factor of activated T cells c1 (NFATc1), which are the master regulators during osteoclastogenesis. In addition, F‐CAPE inhibits the NF‐κB signaling pathway, as confirmed by the decreased degradation of IκBα. Our data suggests that F‐CAPE is a highly potent anti‐osteogenic compound and could be a novel therapeutic molecule to attenuate excessive bone degradation during autoimmune arthritisSupport or Funding InformationThis work was supported by the Biomedical sciences graduate research program at Philadelphia College of Osteopathic Medicine – GA Campus and American Heart Association Award (11SDG5710004)
The development and characterization of Cardiolipin‐specific fluorescent protein markers to assess and understand the localization and behavior of Cardiolipin within mitochondrial membranes of yeast cells
Authors: Amouzgar Meelad , Labbé Katherine , Nunnari Jodi , Sarsam Reta , Gonser William 
Published: November 2023

Mitochondria are double‐membrane organelles that generate most of the energy used by cells and play key roles in cellular growth, death and differentiation. Continuous remodeling and redistribution of the mitochondrial membrane structure are critical for integrating organelle physiology with cellular needs. Cardiolipin (CL) is a diphosphotidyl lipid found almost exclusively in bacteria and in the mitochondrial inner membrane of eukaryotes. CL distribution within mitochondrial membranes is important in determining membrane structure, regulating bioenergetic processes, and recruiting factors involved in cell death and mitochondrial dynamics to the outer mitochondrial membrane. However, CL's exact distribution and functional localization within mitochondria is poorly understood because there exists no means for detecting and visualizing CL in live cells. We have developed a CL sensor based on the CL‐binding properties of the “InsertB” domain of Mgm‐1, a yeast mitochondrial inner membrane fusion protein. In in vitro assays, Insert B specifically binds CL‐containing liposomes. In live yeast and mammalian cells, a fluorescent‐tagged Insert B protein forms distinct foci within mitochondria depending on the presence of CL. By making a series of site‐directed mutations in highly conserved regions of Insert B, we are further characterizing the marker's affinity and specificity for CL. We are now using this tool to better understand the localization and behavior of CL‐enriched regions within mitochondrial membranes and its association with mitochondrial function.Support or Funding InformationUC Davis Molecular and Cellular Biology Summer Fellowship for Undergraduate Research. Special thanks to Dr. Katherine Labbé and Dr. Jodi Nunnari.
Gene Expression Profiling of Prion‐Infected Brains: a Novel Disease Signature for Neurodegeneration in Humans
Authors: Vanni Silvia , Barbisin Maura , Moda Fabio , Giaccone Giorgio , Tagliavini Fabrizio , Haïk Stéphane , Deslys Jean‐Philippe , Zanusso Gianluigi , Legname Giuseppe 
Published: November 2023

ObjectivesIn a previous study (Barbisin et al. 2014), we identified a five‐gene signature able to distinguish BSE‐infected macaques (Macaca fascicularis) from healthy ones: in brief, hemoglobin beta (HBB) and alpha2 (HBA2) were down‐regulated in infected monkeys, whereas transthyretin (TTR), apolipoprotein C1 (APOC1) and serpin peptidase inhibitor clade A (SERPINA3) were up‐regulated. The aim of the present work is to investigate whether the gene dysregulation pattern observed in macaques is also a specific gene signature for Creutzfeldt– Jakob disease (CJD) in humans compared to both healthy subjects and other neurodegenerative diseases.MethodsWe collected about 120 samples from frontal cortex of frozen brain tissue, obtained from prion‐infected patients (variant (v)CJD, sporadic (s)CJD, iatrogenic (i)CJD), patients with non‐CJD neurodegenerative disorders (Alzheimer's Disease, Parkinson's Disease, tauopathies) and age‐matched controls). RNA was extracted using TRIzol with PureLink® RNA Mini Kit and on‐column DNase I digestion. Quantity, purity and integrity were checked and only samples with a RIN≥5 were included in the study. Reverse transcription was carried out using Superscript III and qPCR was performed for the selected transcripts, with ACTB, RPL19, GAPDH and B2M as reference genes. In addition, erythrocyte markers expression analysis was performed in order to exclude any relevant blood contamination.ResultsGene expression trend observed in macaques was confirmed in humans, with similar FC values, for four genes. HBA1/2 was down‐regulated in sCJD cases and also in patients affected by non‐CJD neurodegenerative diseases, while APOC1, TTR and SERPINA3 were up‐regulated in CJD patients, but not in patients affected by non‐CJD neurodegenerative diseases. IHC and WB analyses on related proteins are ongoing. We also found a consistent up‐regulation of SERPINA3, in both RML‐infected ScGT1 and ScN2a cell lines.ConclusionsBesides providing important hints on some prion‐specific alterations in CJD, these results suggest that various pathways, such as oxygen and iron homeostasis (HBB, HBA2) and in particular cholesterol and lipids metabolism (APOC1, SERPINA3, TTR) have to be taken into consideration to identifying potential biomarkers and drug targets for prion diseases and other neurodegenerative disorders.Support or Funding InformationFIRB Accordi di programma 2011 “genomica funzionale delle malattie neurodegenerative” (Prot. RBAP11FRE9_001)
Optimizing Human Tissue Fixation for High‐Quality Downstream Analysis Using Real‐Time Fixation Monitoring
Authors: Lerch Melissa , Bauer Daniel R , Chafin David , Theiss Abbey , Otter Michael , Baird Geoffrey S. 
Published: November 2023

Molecular markers are invaluable to characterizing and treating disease. The pathologist routinely uses immunohistochemistry of formalin‐fixed paraffin embedded tissues to determine diagnosis or molecular subtypes in cancer and other diseases. Most markers that have been developed to date are robustly detected after varied fixation conditions. A greater challenge will be to develop diagnostics for more difficult markers, such as phosphoproteins, that are highly labile yet are critical “companion diagnostic” biomarkers that indicate sensitivity to selected chemotherapeutics.. Meeting this challenge with formalin fixation, the standard clinical tissue preservation process, will be difficult because of the overall poor understanding of formalin's ability to preserve all tissue biomarkers. We have demonstrated that labile phosphoproteins are better preserved using a rapid fixation protocol of 2 hours cold formalin followed by 2 hours hot formalin, which allows the cold formalin to penetrate tissue specimens completely while minimizing other enzymatic activity and the subsequent hot formalin step to crosslink the tissue proteins rapidly and thoroughly. To aid in studying this problem as well as to provide a potential metric for assessing fixation, we have invented a real‐time ultrasound time‐of‐flight (TOF) instrument that is capable of monitoring and imaging the critical step in formalin fixation, diffusion of the fixative into tissue, thereby creating a quantifiable quality metric for tissue fixation. This technology has been applied to most human tissues types and tissue from multiple disease states to demonstrate a broad range of diffusion, and thus fixation, behaviors. Our measurements can be converted into tissue diffusivity constants that correlate with the apparent diffusion constant calculated using MRI, despite the differences in the approaches, indicating that our approach is biophysically plausible. Using data collected from TOF analysis of many tissues, we have therefore developed a novel rapid fixation program that will ensure high quality downstream analysis for a broad range of tissues that correspond to the thickness of a full histology cassette (6 mm).Support or Funding InformationFunding was provided by Ventana Medical Systems, Inc. to support this research.
Inhibition of ABC‐Transporters by in silico Identified Small Molecules
Authors: Vogel Pia D , Follit Courtney A. , Nanajakkara Amila K. , Wise John G. 
Published: November 2023

Multidrug resistance (MDR) is a complex phenotype characterized by simultaneous resistance to structurally and functionally dissimilar drugs. MDR is frequently associated with overexpression of transmembrane efflux proteins belonging to the ATP‐binding cassette (ABC) transporter superfamily including P‐glycoprotein (P‐gp), multidrug resistance associated protein (MRP1), and breast cancer resistance protein (BCRP). Normally expressed at tissue barriers, these proteins protect vulnerable cells from xenobiotic attack by pumping a wide range of toxins out of the cell. Unfortunately, this broad substrate range, characteristic of these transporters, poses a major obstacle to the successful chemotherapeutic treatment of cancers as the majority of clinically relevant chemotherapeutic drugs can be effluxed by P‐gp, MRP1, and BCRP. Treatment and prevention of MDR have been studied extensively for decades, and yet, there are still no FDA‐approved treatments available.Using targeted molecular dynamics and massively parallel drug docking studies, we have screened millions of drug‐like molecules and identified thousands novel compounds predicted to inhibit P‐gp by specifically interacting with its ATP binding domain. We have previously shown that of four in silico identified compounds inhibited P‐gp ATP hydrolysis (Brewer, F. K., Follit, C. A., Vogel, P. D., & Wise, J. G. (2014) Molecular Pharmacology, 86(6), 716–726). When tested in cell culture, three of these compounds restored chemotherapeutic sensitivity in a MDR human cancer cell line which overexpresses P‐gp (Follit CA, Brewer FK, Wise JG, Vogel PV (2015) Pharmacology Research & Perspectives 3(5): e00170). In this study, we expand our cell culture screening to evaluate 46 potential inhibitors identified by our in silico screening method and report that over 30% of these compounds restored chemosensitivity in MDR human cancer cell lines. Lead compounds will be further investigated to determine toxicity and specificity. With future chemical optimization, we are working towards developing powerful co‐therapeutics to treat and prevent MDR in human cancers.Support or Funding InformationThis work is supported by NIH NIGMS [Grants R15‐GM094771‐01A1 and R15‐GM094771‐02] to PDV and JGW, SMU University Research Council, SMU Engaged Learning program, the SMU Center for Drug Discovery, Design and Delivery, the Communities Foundation of Texas, and a private gift from Ms. Suzann Ruff of Dallas, Texas.
Fragment‐Based Drug Design with CNS Therapeutic Targets
Authors: Surratt Christopher K. , Pellegrene Kendy A. , Wasko Michael J. , Jean Bernandie K. , Madura Jeffry D. 
Published: November 2023

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug, a process fraught with failure. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high‐throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has more recently been augmented by structure‐based virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment‐based drug design (FBDD), an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for “growing” the lead compound candidate. The objective of this study is to develop monoamine transporter and receptor computational models and employ their relevant ligand binding pockets as enclaves within which novel‐scaffold ligands can be constructed. Homology models of the human serotonin transporter (hSERT) and dopamine transporter (hDAT) proteins were constructed using as template a Drosophila dopamine transporter crystal structure; creation of a D3 dopamine receptor (D3R) model employed a human D3R crystal structure as template. The MedChem Transformations (MCT) module of Molecular Operating Environment 2015.10 software was used for FBDD. Applied to the generated D3R model, the MCT method successfully built using a fragment library the D2/D3 antagonist eticlopride and other potential D3R ligands. MCT places special emphasis on creating synthesizable, nontoxic molecules, suggesting that these hit compounds are viable ligand candidates (to be tested in subsequent in vitro pharmacologic assays). Fragment‐based methods should provide a viable, relatively low‐cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.Support or Funding InformationSupported by NIH grant DA027806.