bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemopreventive Property of Sencha Tea Extracts towards Sensitive and Multidrug-Resistant Leukemia and Multiple Myeloma Cells
Authors: Lu Xiaohua , Saeed Mohamed E. M. , Hegazy Mohamed-Elamir F. , Kampf Christopher J. , Efferth Thomas
Published: July 2020

The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically, sencha-MeOH/H2O extracts induced apoptosis, ROS, and MMP collapse on both CCRF/CEM and KMS-12-BM cells. The analysis with microarray and COMPARE in 53 cell lines of the NCI panel revealed diverse functional groups, including cell morphology, cellular growth and proliferation, cell cycle, cell death, and survival, which were closely associated with anti-tumor effects of sencha tea. It is important to note that PI3K/Akt and NF-κB pathways were the top two dominant networks by ingenuity pathway analysis. We demonstrate here the multifactorial modes of action of sencha tea leading to chemopreventive effects of sencha tea against cancer.
Coarse-Grained Models of RNA Nanotubes for Large Time Scale Studies in Biomedical Applications
Authors: Badu Shyam , Prabhakar Sanjay , Melnik Roderick
Published: July 2020

In order to describe the physical properties of large time scale biological systems, coarse-grained models play an increasingly important role. In this paper we develop Coarse-Grained (CG) models for RNA nanotubes and then, by using Molecular Dynamics (MD) simulation, we study their physical properties. Our exemplifications include RNA nanotubes of 40 nm long, equivalent to 10 RNA nanorings connected in series. The developed methodology is based on a coarse-grained representation of RNA nanotubes, where each coarse bead represents a group of atoms. By decreasing computation cost, this allows us to make computations feasible for realistic structures of interest. In particular, for the developed coarse-grained models with three bead approximations, we calculate the histograms for the bond angles and the dihedral angles. From the dihedral angle histograms, we analyze the characteristics of the links used to build the nanotubes. Furthermore, we also calculate the bead distances along the chains of RNA strands in the nanoclusters. The variations in these features with the size of the nanotube are discussed in detail. Finally, we present the results on the calculation of the root mean square deviations for a developed RNA nanotube to demonstrate the equilibration of the systems for drug delivery and other biomedical applications such as medical imaging and tissue engineering.
Noninvasive Early Disease Diagnosis by Electronic-Nose and Related VOC-Detection Devices
Authors: Wilson Alphus Dan
Published: July 2020

This editorial provides an overview and summary of recent research articles published in Biosensors journal, volumes 9 (2019) and 10 (2020), within the Special Issue “Noninvasive Early Disease Diagnosis”, which focused on recent sensors, biosensors, and clinical instruments developed for the noninvasive early detection and diagnosis of human, animal, and plant diseases or invasive pests. The six research articles included in this Special Issue provide examples of some of the latest electronic-nose (e-nose) and related volatile organic compound (VOC)-detection technologies, which are being tested and developed to improve the effectiveness and efficiency of innovative diagnostic methodologies for the early detection of particular diseases and pest infestations in living hosts, prior to symptom development.
Investigating Influences of Medial Olivocochlear Efferent System on Central Auditory Processing and Listening in Noise: A Behavioral and Event-Related Potential Study
Authors: Rao Aparna , Koerner Tess K. , Madsen Brandon , Zhang Yang
Published: July 2020

This electrophysiological study investigated the role of the medial olivocochlear (MOC) efferents in listening in noise. Both ears of eleven normal-hearing adult participants were tested. The physiological tests consisted of transient-evoked otoacoustic emission (TEOAE) inhibition and the measurement of cortical event-related potentials (ERPs). The mismatch negativity (MMN) and P300 responses were obtained in passive and active listening tasks, respectively. Behavioral responses for the word recognition in noise test were also analyzed. Consistent with previous findings, the TEOAE data showed significant inhibition in the presence of contralateral acoustic stimulation. However, performance in the word recognition in noise test was comparable for the two conditions (i.e., without contralateral stimulation and with contralateral stimulation). Peak latencies and peak amplitudes of MMN and P300 did not show changes with contralateral stimulation. Behavioral performance was also maintained in the P300 task. Together, the results show that the peripheral auditory efferent effects captured via otoacoustic emission (OAE) inhibition might not necessarily be reflected in measures of central cortical processing and behavioral performance. As the MOC effects may not play a role in all listening situations in adults, the functional significance of the cochlear effects of the medial olivocochlear efferents and the optimal conditions conducive to corresponding effects in behavioral and cortical responses remain to be elucidated.
MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy
Authors: Cornel Annelisa M. , Mimpen Iris L. , Nierkens Stefan
Published: July 2020

In recent years, major advances have been made in cancer immunotherapy. This has led to significant improvement in prognosis of cancer patients, especially in the hematological setting. Nonetheless, translation of these successes to solid tumors was found difficult. One major mechanism through which solid tumors can avoid anti-tumor immunity is the downregulation of major histocompatibility complex class I (MHC-I), which causes reduced recognition by- and cytotoxicity of CD8+ T-cells. Downregulation of MHC-I has been described in 40–90% of human tumors, often correlating with worse prognosis. Epigenetic and (post-)transcriptional dysregulations relevant in the stabilization of NFkB, IRFs, and NLRC5 are often responsible for MHC-I downregulation in cancer. The intrinsic reversible nature of these dysregulations provides an opportunity to restore MHC-I expression and facilitate adaptive anti-tumor immunity. In this review, we provide an overview of the mechanisms underlying reversible MHC-I downregulation and describe potential strategies to counteract this reduction in MHC-I antigen presentation in cancer.
EpCAM-Binding DARPins for Targeted Photodynamic Therapy of Ovarian Cancer
Authors: van den Brand Dirk , van Lith Sanne A. M. , de Jong Jelske M. , Gorris Mark A. J. , Palacio-Castañeda Valentina , Couwenbergh Stijn T. , Goldman Mark R. G. , Ebisch Inge , Massuger Leon F. , Leenders William P. J. , Brock Roland , Verdurmen Wouter P. R.
Published: July 2020

Ovarian cancer is the most lethal gynecological malignancy due to late detection associated with dissemination throughout the abdominal cavity. Targeted photodynamic therapy (tPDT) aimed at epithelial cell adhesion molecule (EpCAM), overexpressed in over 90% of ovarian cancer metastatic lesions, is a promising novel therapeutic modality. Here, we tested the specificity and activity of conjugates of EpCAM-directed designed ankyrin repeat proteins (DARPins) with the photosensitizer IRDye 700DX in in vitro and in vivo ovarian cancer models. EpCAM-binding DARPins (Ec1: Kd = 68 pM; Ac2: Kd = 130 nM) and a control DARPin were site-specifically functionalized with fluorophores or IRDye 700DX. Conjugation of anti-EpCAM DARPins with fluorophores maintained EpCAM-specific binding in cell lines and patient-derived ovarian cancer explants. Penetration of DARPin Ec1 into tumor spheroids was slower than that of Ac2, indicative of a binding site barrier effect for Ec1. DARPin-IRDye 700DX conjugates killed EpCAM-expressing cells in a highly specific and illumination-dependent fashion in 2D and 3D cultures. Furthermore, they effectively homed to EpCAM-expressing subcutaneous OV90 xenografts in mice. In conclusion, the high activity and specificity observed in preclinical ovarian cancer models, combined with a high specificity in patient material, warrant a further investigation of EpCAM-targeted PDT for ovarian cancer.
IGF-1R/mTOR Targeted Therapy for Ewing Sarcoma: A Meta-Analysis of Five IGF-1R-Related Trials Matched to Proteomic and Radiologic Predictive Biomarkers
Authors: Amin Hesham M. , Morani Ajaykumar C. , Daw Najat C. , Lamhamedi-Cherradi Salah-Eddine , Subbiah Vivek , Menegaz Brian A. , Vishwamitra Deeksha , Eskandari Ghazaleh , George Bhawana , Benjamin Robert S. , Patel Shreyaskumar , Song Juhee , Lazar Alexander J. , Wang Wei-Lien , Kurzrock Razelle , Pappo Alberto , Anderson Peter M. , Schwartz Gary K. , Araujo Dejka , Cuglievan Branko , Ratan Ravin , McCall David , Mohiuddin Sana , Livingston John A. , Molina Eric R. , Naing Aung , Ludwig Joseph A.
Published: July 2020

Background : Ten to fourteen percent of Ewing sarcoma (ES) study participants treated nationwide with IGF-1 receptor (IGF-1R)-targeted antibodies achieved tumor regression. Despite this success, low response rates and short response durations (approximately 7-weeks) have slowed the development of this therapy. Methods: We performed a meta-analysis of five phase-1b/2 ES-oriented trials that evaluated the anticancer activity of IGF-1R antibodies +/− mTOR inhibitors (mTORi). Our meta-analysis provided a head-to-head comparison of the clinical benefits of IGF-1R antibodies vs. the IGF-1R/mTOR-targeted combination. Available pretreatment clinical samples were semi-quantitatively scored using immunohistochemistry to detect proteins in the IGF-1R/PI3K/AKT/mTOR pathway linked to clinical response. Early PET/CT imaging, obtained within the first 2 weeks (median 10 days), were examined to determine if reduced FDG avidity was predictive of progression-free survival (PFS). Results: Among 56 ES patients treated at MD Anderson Cancer Center (MDACC) with IGF-1R antibodies, our analysis revealed a significant ~two-fold improvement in PFS that favored a combination of IGF-1R/mTORi therapy (1.6 vs. 3.3-months, p = 0.042). Low pIGF-1R in the pretreatment specimens was associated with treatment response. Reduced total-lesion glycolysis more accurately predicted the IGF-1R response than other previously reported radiological biomarkers. Conclusion: Synergistic drug combinations, and newly identified proteomic or radiological biomarkers of IGF-1R response, may be incorporated into future IGF-1R-related trials to improve the response rate in ES patients.
The ATF6-EGF Pathway Mediates the Awakening of Slow-Cycling Chemoresistant Cells and Tumor Recurrence by Stimulating Tumor Angiogenesis
Authors: Cho Jaebeom , Min Hye-Young , Pei Honglan , Wei Xuan , Sim Jeong Yeon , Park Shin-Hyung , Hwang Su Jung , Lee Hyo-Jong , Hong Sungyoul , Shin Young Kee , Lee Ho-Young
Published: July 2020

Slow-cycling cancer cells (SCCs) with a quiescence-like phenotype are believed to perpetrate cancer relapse and progression. However, the mechanisms that mediate SCC-derived tumor recurrence are poorly understood. Here, we investigated the mechanisms underlying cancer recurrence after chemotherapy, focusing on the interplay between SCCs and the tumor microenvironment. We established a preclinical model of SCCs by exposing non-small-cell lung cancer (NSCLC) cells to either the proliferation-dependent dye carboxyfluorescein diacetate succinimidyl ester (CFSE) or chemotherapeutic drugs. An RNA sequencing analysis revealed that the established SCCs exhibited the upregulation of a group of genes, especially epidermal growth factor (EGF). Increases in the number of vascular endothelial growth factor receptor (VEGFR)-positive vascular endothelial cells and epidermal growth factor receptor (EGFR) activation were found in NSCLC cell line- and patient-derived xenograft tumors that progressed upon chemotherapy. EGFR tyrosine kinase inhibitors effectively suppressed the migration and tube formation of vascular endothelial cells. Furthermore, activating transcription factor 6 (ATF6) induced the upregulation of EGF, and its antagonism effectively suppressed these SCC-mediated events and inhibited tumor recurrence after chemotherapy. These results suggest that the ATF6-EGF signaling axis in SCCs functions to trigger the angiogenesis switch in residual tumors after chemotherapy and is thus a driving force for the switch from SCCs to actively cycling cancer cells, leading to tumor recurrence.
Comment on McCarthy, C.; et al. Developing Picornaviruses for Cancer Therapy. Cancers 2019, 11, 685
Authors: Alberts Pēteris
Published: July 2020

I would like to make the following corrections to the publication by McCarthy et al [...]
Prognostic Value of CD200R1 mRNA Expression in Head and Neck Squamous Cell Carcinoma
Authors: Chang Hyun , Lee Yun-Gyoo , Ko Yoon Ho , Cho Jang Ho , Choi Jong-Kwon , Park Keon Uk , Kang Eun Joo , Lee Keun-Wook , Lim Sun Min , Kim Jin-Soo , Lee Hyun Woo , Kim Min Kyoung , Hwang In Gyu , Kim Sangwoo , Nam Byung-Ho , Kim Hye Ryun
Published: July 2020

Immune system dysfunction is associated with head and neck squamous cell carcinoma (HNSCC) development and progression and immune checkpoint inhibitors have demonstrated substantial survival benefits in platinum-refractory HNSCC; therefore, we examined the prognostic value of immune-related gene (IRG) expression in HNSCC. We analyzed the expression of 82 IRGs in 71 patients with HNSCC enrolled in a feasibility study for a prospective HNSCC biomarker-driven umbrella trial (Korean Cancer Study Group TRIUMPH study, NCT03292250). CD200R1 was identified as an independent prognostic factor and validated in GEO and TCGA database. CD2000R1 mRNA expression was found to be an independent favorable prognostic factor in patients with HNSCC. Moreover, CD200R1 was found to affect genes and pathways associated with the immune response, while seven differentially expressed genes (CD8A, DOK2, CX3CR1, TYROBP, CXCL9, CD300LF, IFNG) were associated with CD200R1 expression. Samples with higher CD200R1 expression displayed higher tumor-infiltrating immune cell counts both in silico and in histological analysis. These findings will help in the development of more accurate prognostic tools and suggest CD200R1 modulation as a HNSCC immunotherapy.
A Novel Combination Treatment with Honokiol and Rapamycin Effectively Restricts c-Met-Induced Growth of Renal Cancer Cells, and also Inhibits the Expression of Tumor Cell PD-L1 Involved in Immune Escape
Authors: Sabarwal Akash , Chakraborty Samik , Mahanta Simran , Banerjee Selina , Balan Murugabaskar , Pal Soumitro
Published: July 2020

The mTOR inhibitor Rapamycin has tumor inhibitory properties; and it is also used as an immunosuppressive agent after organ transplantation. However, prolonged Rapamycin treatment re-activates Akt and can promote cancer growth. Honokiol is a natural compound with both anti-tumorigenic and anti-inflammatory properties. Here, we assessed the anti-tumor effects of Rapamycin and Honokiol combination in renal cell carcinoma (RCC). Receptor tyrosine kinase c-Met-mediated signaling plays a major role in RCC growth. We observed that compared with Rapamycin alone, Rapamycin + Honokiol combination can effectively down-regulate c-Met-induced Akt phosphorylation in renal cancer cells; and it markedly inhibited Ras activation and cell proliferation and promoted G1 phase cell cycle arrest. The combination treatment significantly induced ROS generation and cancer cell apoptosis even when c-Met is activated. Importantly, Honokiol, but not Rapamycin, decreased c-Met-induced expression of the co-inhibitory molecule PD-L1, implied in the immune escape of renal cancer cells. In mouse renal cancer cells and Balb/c splenocytes co-culture assay, Rapamycin + Honokiol markedly potentiated immune-cell-mediated killing of cancer cells, possibly through the down-regulation of PD-L1. Together, Honokiol can effectively overcome the limitation of Rapamycin treatment alone; and the combination treatment can markedly restrict the growth of RCC, with particular importance to post-transplantation renal cancer.
Elective Neck Dissection or Sentinel Lymph Node Biopsy in Early Stage Oral Cavity Cancer Patients: The Dutch Experience
Authors: den Toom Inne J. , Boeve Koos , Lobeek Daphne , Bloemena Elisabeth , Donswijk Maarten L. , de Keizer Bart , Klop W. Martin C. , Leemans C. René , Willems Stefan M. , Takes Robert P. , Witjes Max J.H. , de Bree Remco
Published: July 2020

Background: Sentinel lymph node biopsy (SLNB) has been introduced as a diagnostic staging modality for detection of occult metastases in patients with early stage oral cancer. Comparisons regarding accuracy to the routinely used elective neck dissection (END) are lacking in literature. Methods: A retrospective, multicenter cohort study included 390 patients staged by END and 488 by SLNB. Results: The overall sensitivity (84% vs. 81%, p = 0.612) and negative predictive value (NPV) (93%, p = 1.000) were comparable between END and SLNB patients. The END cohort contained more pT2 tumours (51%) compared to the SLNB cohort (23%) (p < 0.001). No differences were found for sensitivity and NPV between SLNB and END divided by pT stage. In floor-of-mouth (FOM) tumours, SLNB had a lower sensitivity (63% vs. 92%, p = 0.006) and NPV (90% vs. 97%, p = 0.057) compared to END. Higher disease-specific survival (DSS) rates were found for pT1 SLNB patients compared to pT1 END patients (96% vs. 90%, p = 0.048). Conclusion: In the absence of randomized clinical trials, this study provides the highest available evidence that, in oral cancer, SLNB is as accurate as END in detecting occult lymph node metastases, except for floor-of-mouth tumours.
Characterization of Glycolysis-Associated Molecules in the Tumor Microenvironment Revealed by Pan-Cancer Tissues and Lung Cancer Single Cell Data
Authors: Wei Jinfen , Huang Kaitang , Chen Zixi , Hu Meiling , Bai Yunmeng , Lin Shudai , Du Hongli
Published: July 2020

Altered metabolism is a hallmark of cancer and glycolysis is one of the important factors promoting tumor development. There is however still a lack of molecular characterization glycolysis and comprehensive studies related to tumor glycolysis in the pan-cancer landscape. Here, we applied a gene expression signature to quantify glycolysis in 9229 tumors across 25 cancer types and 7875 human lung cancer single cells and verified the robustness of signature using defined glycolysis samples from previous studies. We classified tumors and cells into glycolysis score-high and -low groups, demonstrated their prognostic associations, and identified genome and transcriptome molecular features associated with glycolysis activity. We observed that glycolysis score-high tumors were associated with worse prognosis across cancer types. High glycolysis tumors exhibited specific driver genes altered by copy number aberrations (CNAs) in most cancer types. Tricarboxylic acid (TCA) cycle, DNA replication, tumor proliferation and other cancer hallmarks were more active in glycolysis-high tumors. Glycolysis signature was strongly correlated with hypoxia signature in all 25 cancer tissues (r > 0.7) and cancer single cells (r > 0.8). In addition, HSPA8 and P4HA1 were screened out as the potential modulating factors to glycolysis as their expression were highly correlated with glycolysis score and glycolysis genes, which enables future efforts for therapeutic options to block the glycolysis and control tumor progression. Our study provides a comprehensive molecular-level understanding of glycolysis with a large sample data and demonstrates the hypoxia pressure, growth signals, oncogene mutation and other potential signals could activate glycolysis, thereby to regulate cell cycle, energy material synthesis, cell proliferation and cancer progression.
Interleukin-1β and Cancer
Authors: Rébé Cédric , Ghiringhelli François
Published: July 2020

Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene is induced after “priming” of the cells and a second signal is required to allow IL-1β maturation by inflammasome-activated caspase-1. IL-1β is then released and leads to transcription of target genes through its ligation with IL-1R1 on target cells. IL-1β expression and maturation are guided by gene polymorphisms and by the cellular context. In cancer, IL-1β has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration, and metastasis. Moreover, anti-cancer treatments are able to promote IL-1β production by cancer or immune cells, with opposite effects on cancer progression. This raises the question of whether or not to use IL-1β inhibitors in cancer treatment.
Rapid Depletion of Subcutaneous Adipose Tissue during Sorafenib Treatment Predicts Poor Survival in Patients with Hepatocellular Carcinoma
Authors: Imai Kenji , Takai Koji , Miwa Takao , Taguchi Daisuke , Hanai Tatsunori , Suetsugu Atsushi , Shiraki Makoto , Shimizu Masahito
Published: July 2020

The aim of this study was to assess the annualized changes in body composition, including skeletal muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) before, during, and after sorafenib treatment in patients with hepatocellular carcinoma (HCC). This retrospective study evaluated 61 HCC patients treated with sorafenib. Annualized changes (Δ; cm2/m2/year) in skeletal muscle index (SMI), SAT index (SATI), and VAT index (VATI), which were defined as the cross-sectional areas (cm2) of those areas on computed tomography normalized by the square of one’s height (m2), before (pre), during (during), and after (post) sorafenib treatment, were calculated. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion group and the effects of these values on survival were analyzed using the Kaplan-Meier analysis and Cox proportional-hazards model. Annualized depletion rates of SMI (ΔSMIpre: −3.5, ΔSMIduring: −3.5, ΔSMIpost: −8.0) and VATI (ΔVATIpre: −3.2, ΔVATIduring: −2.8, ΔVATIpost: −15.1) accelerated after the cancellation of sorafenib, whereas that of SATI (ΔSATIpre: −4.8, ΔSATIduring; −7.6, ΔSATIpost; −8.0) had already accelerated during sorafenib treatment. Patients with rapid depletion of ΔSATIduring experienced significantly worse survival rates (p < 0.001), and it was an independent predictor of survival (p = 0.009), together with therapeutic effect (p < 0.001). Rapid depletion of SAT during sorafenib treatment can be used to predict survival in patients with HCC.
Mycobacteria-Based Vaccines as Immunotherapy for Non-urological Cancers
Authors: Noguera-Ortega Estela , Guallar-Garrido Sandra , Julián Esther
Published: July 2020

The arsenal against different types of cancers has increased impressively in the last decade. The detailed knowledge of the tumor microenvironment enables it to be manipulated in order to help the immune system fight against tumor cells by using specific checkpoint inhibitors, cell-based treatments, targeted antibodies, and immune stimulants. In fact, it is widely known that the first immunotherapeutic tools as immune stimulants for cancer treatment were bacteria and still are; specifically, the use of Mycobacterium bovis bacillus Calmette-Guérin (BCG) continues to be the treatment of choice for preventing cancer recurrence and progression in non-invasive bladder cancer. BCG and also other mycobacteria or their components are currently under study for the immunotherapeutic treatment of different malignancies. This review focuses on the preclinical and clinical assays using mycobacteria to treat non-urological cancers, providing a wide knowledge of the beneficial applications of these microorganisms to manipulate the tumor microenvironment aiming at tumor clearance.
Ethanol Electrooxidation on Phase- and Morphology-Controlled Ni(OH)2 Microspheres
Authors: Lidasan Jun Jeffri B. , del Rosario Julie Anne D. , Ocon Joey D.
Published: July 2020

The electrooxidation kinetics of ethanol is key to making direct ethanol fuel cells and electrocatalytically reforming ethanol viable technologies for a more sustainable energy conversion. In this study, the electrooxidation of ethanol was investigated on nickel hydroxide (Ni(OH)2) catalysts synthesized using a facile solvothermal method. Variations in the temperature, heating time, and the addition of oleylamine in the precursor enabled the phase and morphology control of the catalysts. X-ray diffraction and scanning electron microscopy show that the addition of oleylamine in the precursor resulted in microspheres with a high surface area, but favored the formation of β-phase Ni(OH)2. Elevated temperatures or prolonged periods of heating in a controlled environment, on the other hand, can lead to the formation of the ethanol oxidation reaction-active α-phase. Among the synthesized catalysts, the α-Ni(OH)2 microspheres with nanoflakes achieved the highest activity for ethanol oxidation with a current density of 24.4 mA cm−2 at 1.55 V (vs. RHE, reversible hydrogen electrode) in cyclic voltammetry tests and stable at 40 mA cm−2 in chronoamperometric tests at the same potential, comparatively higher than other Ni-based catalysts found in the literature. While the overpotential is beyond the useful range for direct ethanol fuel cells, it may be useful for understanding the mechanism of ethanol oxidation reactions on transition metal hydroxides at their oxidizing potential for ethanol electroreforming.
Dry Reforming of Methane over CNT-Supported CeZrO2, Ni and Ni-CeZrO2 Catalysts
Authors: Łamacz Agata , Jagódka Paulina , Stawowy Michalina , Matus Krzysztof
Published: July 2020

In this work, the carbon nanotubes (CNT)-supported nanosized, well-dispersed, CeZrO2 and Ni-CeZrO2 catalysts were obtained and tested for the first time in the reaction of methane dry reforming (DRM). The performance of the hybrid materials was compared with the performance of Ni/CNT catalyst. The mechanism of the DRM reaction and the occurrence of reverse water gas shift reaction (RWGS) and CO2 deoxidation were discussed in terms of catalysts composition. The contribution of RWGS and CO2 deoxidation in the DRM process, demonstrating an increased CO2 consumption when compared to CH4, and H2/CO < 1, varied depending on the catalyst composition, was also studied.
Novel Routes in Transformation of Lignocellulosic Biomass to Furan Platform Chemicals: From Pretreatment to Enzyme Catalysis
Authors: Dedes Grigorios , Karnaouri Anthi , Topakas Evangelos
Published: July 2020

The constant depletion of fossil fuels along with the increasing need for novel materials, necessitate the development of alternative routes for polymer synthesis. Lignocellulosic biomass, the most abundant carbon source on the planet, can serve as a renewable starting material for the design of environmentally-friendly processes for the synthesis of polyesters, polyamides and other polymers with significant value. The present review provides an overview of the main processes that have been reported throughout the literature for the production of bio-based monomers from lignocellulose, focusing on physicochemical procedures and biocatalysis. An extensive description of all different stages for the production of furans is presented, starting from physicochemical pretreatment of biomass and biocatalytic decomposition to monomeric sugars, coupled with isomerization by enzymes prior to chemical dehydration by acid Lewis catalysts. A summary of all biotransformations of furans carried out by enzymes is also described, focusing on galactose, glyoxal and aryl-alcohol oxidases, monooxygenases and transaminases for the production of oxidized derivatives and amines. The increased interest in these products in polymer chemistry can lead to a redirection of biomass valorization from second generation biofuels to chemical synthesis, by creating novel pathways to produce bio-based polymers.
Modeling of Urea Decomposition in Selective Catalytic Reduction (SCR) for Systems of Diesel Exhaust Gases Aftertreatment by Finite Volume Method
Authors: Kuternowski Filip , Staszak Maciej , Staszak Katarzyna
Published: July 2020

This study presents modeling of selective catalytic reduction (SCR) for systems of diesel exhaust gases aftertreatment. The main purpose of this work is to develop the modeling approach that allows accurate prediction of urea–water solution behavior (UWS) in the real diesel exhausts in temperature range 373 K to 873 K. The UWS is a key element of catalytic reduction of diesel NOx which utilizes ammonia as reducing specie. The finite volume method (FVM) extended by the nonrandom two liquids (NRTL) phase equilibrium model was used to perform the calculations. The results obtained were verified with experimental measurements. The comparison show that the NRTL extension introduced in this work allows reproducing the actual process conditions in the diesel exhaust environment. The accuracy of the results permits the model to be used for the design purposes and simulation approaches as well.
Effect of La2O3 as a Promoter on the Pt,Pd,Ni/MgO Catalyst in Dry Reforming of Methane Reaction
Authors: Al-Najar Ali M. A. , Al-Doghachi Faris A. J. , Al-Riyahee Ali A. A. , Taufiq-Yap Yun Hin
Published: July 2020

Pt,Pd,Ni/MgO, Pt,Pd,Ni/Mg0.97La3+0.03O, Pt,Pd,Ni/Mg0.93La3+0.07O, and Pt,Pd,Ni/Mg0.85La3+0.15O (1% of each of the Ni, Pd, and Pt) catalysts were prepared by a surfactant-assisted co-precipitation method. Samples were characterized by the XRD, XPS, XRF, FT-IR, H2-TPR, TEM, the Brunauer–Emmett–Teller (BET) method, and TGA and were tested for the dry reforming of methane (DRM). TEM and thermal gravimetric analysis (TGA) methods were used to analyze the carbon deposition on spent catalysts after 200 h at 900 °C. At a temperature of 900 °C and a 1:1 CH4:CO2 ratio, the tri-metallic Pt,Pd,Ni/Mg0.85La3+0.15O catalyst with a lanthanum promoter showed a higher conversion of CH4 (85.01%) and CO2 (98.97%) compared to the Ni,Pd,Pt/MgO catalysts in the whole temperature range. The selectivity of H2/CO decreased in the following order: Pt,Pd,Ni/Mg0.85La3+0.15O > Pt,Pd,Ni/Mg0.93La3+0.07O > Pt,Pd,Ni/Mg0.97La3+0.03O > Ni,Pd,Pt/MgO. The results indicated that among the catalysts, the Pt,Pd,Ni/Mg0.85La23+0.15O catalyst exhibited the highest activity, making it the most suitable for the dry reforming of methane reaction.
Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo
Authors: Mir Bilal , Goettsch Claudia
Published: July 2020

Extracellular vesicles (EVs) mediate cell-to-cell communication via the transfer of biomolecules locally and systemically between organs. It has been elucidated that the specific EV cargo load is fundamental for cellular response upon EV delivery. Therefore, revealing the specific molecular machinery that functionally regulates the precise EV cargo intracellularly is of importance in understanding the role of EVs in physiology and pathophysiology and conveying therapeutic use. The purpose of this review is to summarize recent findings on the general rules, as well as specific modulator motifs governing EV cargo loading. Finally, we address available information on potential therapeutic strategies to alter cargo loading.
Roles of miR-640 and Zinc Finger Protein 91 (ZFP91) in Angiopoietin-1-Induced In Vitro Angiogenesis
Authors: Harel Sharon , Sanchez-Gonzalez Veronica , Echavarria Raquel , Mayaki Dominique , Hussain Sabah NA
Published: July 2020

Angiopoietin-1 (Ang-1) is a ligand of Tie-2 receptors that promotes angiogenesis. It has been established that regulatory loops exist between angiogenic growth factors and distinct pro or anti-angiogenic miRNAs, but the nature and the roles of Ang-1-regulated miRNAs remain unclear. In this study, we assessed the role of miR-640 in Ang-1-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Exposure to Ang-1 (300 ng/mL) from 6 to 72 h significantly decreased expression of mature miR-640, a response that was mediated by Tie-2 receptors and was also observed in response to Ang-2, the vascular endothelial growth factor, and transforming growth factor β. Increasing miR-640 levels using a mimic inhibited Ang-1-induced cell migration and capillary-like tube formation whereas inhibition of miR-640 enhanced these responses. Pull down assays of biotinylated miR-640 revealed that miR-640 directly targets Zinc Finger Protein 91 (ZFP91), an atypical E3-ubiquitin ligase. Ang-1 exposure induced ZFP91 expression through down-regulation of miR-640. Silencing of ZFP91 significantly inhibited Ang-1-induced cell migration and tube formation. We conclude that Ang-1 upregulates ZFP91 expression through transcriptional down-regulation of miR-640 and that ZFP91 plays important roles in the promotion of Ang-1-induced endothelial cell migration and differentiation.
IL-6 Trans-Signaling in the Brain Influences the Metabolic Phenotype of the 3xTg-AD Mouse Model of Alzheimer’s Disease
Authors: Escrig Anna , Molinero Amalia , Méndez Brenda , Giralt Mercedes , Comes Gemma , Sanchis Paula , Fernández-Gayol Olaya , Giménez-Llort Lydia , Becker-Pauly Christoph , Rose-John Stefan , Hidalgo Juan
Published: July 2020

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes the most prevalent dementia in the elderly people. Obesity and insulin resistance, which may cause major health problems per se, are risk factors for AD, and cytokines such as interleukin-6 (IL-6) have a role in these conditions. IL-6 can signal either through a membrane receptor or by trans-signaling, which can be inhibited by the soluble form of the co-receptor gp130 (sgp130). We have addressed the possibility that blocking IL-6 trans-signaling in the brain could have an effect in the triple transgenic 3xTg-AD mouse model of AD and/or in obesity progression, by crossing 3xTg-AD mice with GFAP-sgp130Fc mice. To serve as control groups, GFAP-sgp130Fc mice were also crossed with C57BL/6JOlaHsd mice. Seventeen-month-old mice were fed a control diet (18% kcal from fat) and a high-fat diet (HFD; 58.4% kcal from fat). In our experimental conditions, the 3xTg-AD model showed a mild amyloid phenotype, which nevertheless altered the control of body weight and related endocrine and metabolic factors, suggestive of a hypermetabolic state. The inhibition of IL-6 trans-signaling modulated some of these traits in both 3xTg-AD and control mice, particularly during HFD, and in a sex-dependent manner. These experiments provide evidence of IL-6 trans-signaling playing a role in the CNS of a mouse model of AD.
Methylation in HOX Clusters and Its Applications in Cancer Therapy
Authors: Paço Ana , de Bessa Garcia Simone Aparecida , Freitas Renata
Published: July 2020

HOX genes are commonly known for their role in embryonic development, defining the positional identity of most structures along the anterior–posterior axis. In postembryonic life, HOX gene aberrant expression can affect several processes involved in tumorigenesis such as proliferation, apoptosis, migration and invasion. Epigenetic modifications are implicated in gene expression deregulation, and it is accepted that methylation events affecting HOX gene expression play crucial roles in tumorigenesis. In fact, specific methylation profiles in the HOX gene sequence or in HOX-associated histones are recognized as potential biomarkers in several cancers, helping in the prediction of disease outcomes and adding information for decisions regarding the patient’s treatment. The methylation of some HOX genes can be associated with chemotherapy resistance, and its identification may suggest the use of other treatment options. The use of epigenetic drugs affecting generalized or specific DNA methylation profiles, an approach that now deserves much attention, seems likely to be a promising weapon in cancer therapy in the near future. In this review, we summarize these topics, focusing particularly on how the regulation of epigenetic processes may be used in cancer therapy.
Nanoceria Particles Are an Eligible Candidate to Prevent Age-Related Macular Degeneration by Inhibiting Retinal Pigment Epithelium Cell Death and Autophagy Alterations
Authors: Tisi Annamaria , Flati Vincenzo , Delle Monache Simona , Lozzi Luca , Passacantando Maurizio , Maccarone Rita
Published: July 2020

Retinal pigment epithelium (RPE) dysfunction and degeneration underlie the development of age-related macular degeneration (AMD), which is the leading cause of blindness worldwide. In this study, we investigated whether cerium oxide nanoparticles (CeO2-NPs or nanoceria), which are anti-oxidant agents with auto-regenerative properties, are able to preserve the RPE. On ARPE-19 cells, we found that CeO2-NPs promoted cell viability against H2O2–induced cellular damage. For the in vivo studies, we used a rat model of acute light damage (LD), which mimics many features of AMD. CeO2-NPs intravitreally injected three days before LD prevented RPE cell death and degeneration and nanoceria labelled with fluorescein were found localized in the cytoplasm of RPE cells. CeO2-NPs inhibited epithelial-mesenchymal transition of RPE cells and modulated autophagy by the down-regulation of LC3B-II and p62. Moreover, the treatment inhibited nuclear localization of LC3B. Taken together, our study demonstrates that CeO2-NPs represent an eligible candidate to counteract RPE degeneration and, therefore, a powerful therapy for AMD.
miR-7 Regulates GLP-1-Mediated Insulin Release by Targeting β-Arrestin 1
Authors: Matarese Alessandro , Gambardella Jessica , Lombardi Angela , Wang Xujun , Santulli Gaetano
Published: July 2020

Glucagon-like peptide-1 (GLP-1) has been shown to potentiate glucose-stimulated insulin secretion binding GLP-1 receptor on pancreatic β cells. β-arrestin 1 (βARR1) is known to regulate the desensitization of GLP-1 receptor. Mounting evidence indicates that microRNAs (miRNAs, miRs) are fundamental in the regulation of β cell function and insulin release. However, the regulation of GLP-1/βARR1 pathways by miRs has never been explored. Our hypothesis is that specific miRs can modulate the GLP-1/βARR1 axis in β cells. To test this hypothesis, we applied a bioinformatic approach to detect miRs that could target βARR1; we identified hsa-miR-7-5p (miR-7) and we validated the specific interaction of this miR with βARR1. Then, we verified that GLP-1 was indeed able to regulate the transcription of miR-7 and βARR1, and that miR-7 significantly regulated GLP-1-induced insulin release and cyclic AMP (cAMP) production in β cells. Taken together, our findings indicate, for the first time, that miR-7 plays a functional role in the regulation of GLP-1-mediated insulin release by targeting βARR1. These results have a decisive clinical impact given the importance of drugs modulating GLP-1 signaling in the treatment of patients with type 2 diabetes mellitus.
Modeling of Cell Nuclear Mechanics: Classes, Components, and Applications
Authors: Hobson Chad M. , Stephens Andrew D.
Published: July 2020

Cell nuclei are paramount for both cellular function and mechanical stability. These two roles of nuclei are intertwined as altered mechanical properties of nuclei are associated with altered cell behavior and disease. To further understand the mechanical properties of cell nuclei and guide future experiments, many investigators have turned to mechanical modeling. Here, we provide a comprehensive review of mechanical modeling of cell nuclei with an emphasis on the role of the nuclear lamina in hopes of spurring future growth of this field. The goal of this review is to provide an introduction to mechanical modeling techniques, highlight current applications to nuclear mechanics, and give insight into future directions of mechanical modeling. There are three main classes of mechanical models—schematic, continuum mechanics, and molecular dynamics—which provide unique advantages and limitations. Current experimental understanding of the roles of the cytoskeleton, the nuclear lamina, and the chromatin in nuclear mechanics provide the basis for how each component is subsequently treated in mechanical models. Modeling allows us to interpret assay-specific experimental results for key parameters and quantitatively predict emergent behaviors. This is specifically powerful when emergent phenomena, such as lamin-based strain stiffening, can be deduced from complimentary experimental techniques. Modeling differences in force application, geometry, or composition can additionally clarify seemingly conflicting experimental results. Using these approaches, mechanical models have informed our understanding of relevant biological processes such as migration, nuclear blebbing, nuclear rupture, and cell spreading and detachment. There remain many aspects of nuclear mechanics for which additional mechanical modeling could provide immediate insight. Although mechanical modeling of cell nuclei has been employed for over a decade, there are still relatively few models for any given biological phenomenon. This implies that an influx of research into this realm of the field has the potential to dramatically shape both future experiments and our current understanding of nuclear mechanics, function, and disease.
Development of Artificial Plasma Membranes Derived Nanovesicles Suitable for Drugs Encapsulation
Authors: Martinelli Carolina , Gabriele Fabio , Dini Elena , Carriero Francesca , Bresciani Giorgia , Slivinschi Bianca , Dei Giudici Marco , Zanoletti Lisa , Manai Federico , Paolillo Mayra , Schinelli Sergio , Azzalin Alberto , Comincini Sergio
Published: July 2020

Extracellular vesicles (EVs) are considered as promising nanoparticle theranostic tools in many pathological contexts. The increasing clinical employment of therapeutic nanoparticles is contributing to the development of a new research area related to the design of artificial EVs. To this aim, different approaches have been described to develop mimetic biologically functional nanovescicles. In this paper, we suggest a simplified procedure to generate plasma membrane-derived nanovesicles with the possibility to efficiently encapsulate different drugs during their spontaneously assembly. After physical and molecular characterization by Tunable Resistive Pulse Sensing (TRPS) technology, transmission electron microscopy, and flow cytometry, as a proof of principle, we have loaded into mimetic EVs the isoquinoline alkaloid Berberine chloride and the chemotherapy compounds Temozolomide or Givinostat. We demonstrated the fully functionality of these nanoparticles in drug encapsulation and cell delivery, showing, in particular, a similar cytotoxic effect of direct cell culture administration of the anticancer drugs. In conclusion, we have documented the possibility to easily generate scalable nanovesicles with specific therapeutic cargo modifications useful in different drug delivery contexts.
Study of Sputtered ZnO:Ga2O3 Films for Energy Harvesting Applications
Authors: Aleksandrova Mariya , Ivanova Tatyana , Hamelmann Frank , Strijkova Velichka , Gesheva Kostadinka
Published: July 2020

Thin films of ZnO:Ga2O3 (ZGO) were deposited by radio frequency (RF) sputtering at voltages of 0.5, 0.9 and 1.1 kV. The films were studied with respect to their suitability in flexible piezoelectric nanogenerators. The analysis of the spectroscopic and microscopic results showed that piezoelectric features were revealed for the films grown at all sputtering voltages, but the most favorable morphology in terms of low roughness was achieved at 1.1 kV. The effect of the sputtering voltage on the films crystallinity and lattice strain was studied. It was found that the increasing sputtering voltage promoted the films crystallization. Additionally, the presence of oxygen vacancies in the piezoelectric films was negligible as it is not a major factor affecting their performance. The electrical measurements of the Ag/ZnO:Ga2O3/Ag harvester on a flexible substrate in the low-frequency range showed a piezoelectric voltage of 414 mV, a current of 10.4 µA and an electric power output of 1.4 µW at a mass load of 100 g. These results were achieved by a simple architecture of a single piezoelectric layer with a relatively small size of 3 cm2 and small piezoelectric film thickness (600 nm) containing lead-free material. It was proven that the sputtered ZGO films are suitable for energy harvesting elements and their performance could be tuned by the sputtering voltage. Another possible application of the proposed device, excluding low-frequency vibrational harvesting, could be a pressure sensor or strain gauge, due to the good linearity of the electrical parameter dependences on the strain.
Enhanced Scratch Performance of Plasma Sprayed Hydroxyapatite Composite Coatings Reinforced with BN Nanoplatelets
Authors: Chen Yao , Ren Jia , Liu Weiwei , Zhao Dong
Published: July 2020

In recent years, research on hydroxyapatite (HA) coatings has been driven by the demands of clinical applications. However, the intrinsic brittleness of HA limits its potential in the use for the load-bearing implant. To improve mechanical properties of the HA coating itself, a HA composite coating reinforced with hexagonal boron nitride nanoplatelets (BNNP) was fabricated using plasma spray, and its scratch behavior was investigated in this research. Typical brittle fractures such as microcracks both in and beyond the residual groove and material chipping were observed in the HA coating, while stronger and tougher BNNP/HA coatings exhibited a dominant role in protecting them from scratch damage through resisting plastic deformation and brittle microfracturing. Moreover, easier grain sliding within a splat and splat sliding at the splat boundaries due to the presence of BNNPs, and the nature porosity at different length scales of the as-sprayed HA composite coatings would provide significant self-lubricating effects to reduce the lateral force during scratching and alleviate the contact damage. Therefore, the addition of BNNPs renders HA coating with low scratch friction and enhanced tolerance to surface damage, which is naturally beneficial for the long-term durability and reliability of the implants.
Chemical Vapor Deposition of IrTe2 Thin Films
Authors: Zhou Rui , Zhao Zhaoyang , Wu Juanxia , Xie Liming
Published: July 2020

Two-dimensional (2D) IrTe2 has a profound charge ordering and superconducting state, which is related to its thickness and doping. Here, we report the chemical vapor deposition (CVD) of IrTe2 films using different Ir precursors on different substrates. The Ir(acac)3 precursor and hexagonal boron nitride (h-BN) substrate is found to yield a higher quality of polycrystalline IrTe2 films. Temperature-dependent Raman spectroscopic characterization has shown the q1/8 phase to HT phase at ~250 K in the as-grown IrTe2 films on h-BN. Electrical measurement has shown the HT phase to q1/5 phase at around 220 K.