bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single-Domain Antibody-Based Anti-PSMA Recombinant Immunotoxin Exhibits Specificity and Efficacy for Prostate Cancer Therapy
Authors: Xing Yutong , Xu Keyuan , Li Shixiong , Cao Li , Nan Yue , Li Qiyu , Li Wenjing , Hong Zhangyong
Published: May 2021

Prostate cancer (PCa) is the second most common cancer in men, causing more than 300,000 deaths every year worldwide. Due to their superior cell-killing ability and the relative simplicity of their preparation, immunotoxin molecules have great potential in the clinical treatment of cancer, and several such molecules have been approved for clinical application. In this study, we adopted a relatively simple strategy based on a single-domain antibody (sdAb) and an improved Pseudomonas exotoxin A (PE) toxin (PE24X7) to prepare a safer immunotoxin against prostate-specific membrane antigen (PSMA) for PCa treatment. The designed anti-PSMA immunotoxin, JVM-PE24X7, was conveniently prepared in its soluble form in an Escherichia coli (E. coli) system, avoiding the complex renaturation process needed for immunotoxin preparation by the conventional strategy. The product was very stable and showed a very strong ability to bind the PSMA receptor. Cytotoxicity assays showed that this molecule at a very low concentration could kill PSMA-positive PCa cells, with an EC50 value (concentration at which the cell viability decreased by 50%) of 15.3 pM against PSMA-positive LNCaP cells. Moreover, this molecule showed very good killing selectivity between PSMA-positive and PSMA-negative cells, with a selection ratio of more than 300-fold. Animal studies showed that this molecule at a very low dosage (5 × 0.5 mg/kg once every three days) completely inhibited the growth of PCa tumors, and the maximum tolerable dose (MTD) was more than 15 mg/kg, indicating its very potent tumor-treatment ability and a wide therapeutic window. Use of the new PE toxin, PE24X7, as the effector moiety significantly reduced off-target toxicity and improved the therapeutic window of the immunotoxin. The above results demonstrate that the designed anti-PSMA immunotoxin, JVM-PE24X7, has good application value for the treatment of PCa.
NtRNF217, Encoding a Putative RBR E3 Ligase Protein of Nicotiana tabacum, Plays an Important Role in the Regulation of Resistance to Ralstonia solanacearum Infection
Authors: Liu Ying , Tang Yuanman , Tan Xi , Ding Wei
Published: May 2021

E3 ubiquitin ligases, the most important part of the ubiquitination process, participate in various processes of plant immune response. RBR E3 ligase is one of the E3 family members, but its functions in plant immunity are still little known. NtRNF217 is a RBR E3 ligase in tobacco based on the sequence analysis. To assess roles of NtRNF217 in tobacco responding to Ralstonia solanacearum, overexpression experiments in Nicotiana tabacum (Yunyan 87, a susceptible cultivar) were performed. The results illuminated that NtRNF217-overexpressed tobacco significantly reduced multiplication of R. solanacearum and inhibited the development of disease symptoms compared with wild-type plants. The accumulation of H2O2 and O2− in NtRNF217-OE plants was significantly higher than that in WT-Yunyan87 plants after pathogen inoculation. The activities of CAT and SOD also increased rapidly in a short time after R. solanacearum inoculation in NtRNF217-OE plants. What is more, overexpression of NtRNF217 enhanced the transcript levels of defense-related marker genes, such as NtEFE26, NtACC Oxidase, NtHIN1, NtHSR201, and NtSOD1 in NtRNF217-OE plants after R. solanacearum inoculation. The results suggested that NtRNF217 played an important role in regulating the expression of defense-related genes and the antioxidant enzymes, which resulted in resistance to R. solanacearum infection.
8a, a New Acridine Antiproliferative and Pro-Apoptotic Agent Targeting HDAC1/DNMT1
Authors: Zhang Qiting , Wang Ziyan , Chen Xinyuan , Qiu Haoxiang , Gu Yifan , Wang Ning , Wang Tao , Wang Ze , Ma Huabin , Zhao Yufen , Zhang Bin
Published: May 2021

Epigenetic therapy using histone deacetylase (HDAC) inhibitors has become an attractive project in new drug development. However, DNA methylation and histone acetylation are important epigenetic ways to regulate the occurrence and development of leukemia. Given previous studies, N-(2-aminophenyl)benzamide acridine (8a), as a histone deacetylase 1 (HDAC1) inhibitor, induces apoptosis and shows significant anti-proliferative activity against histiocytic lymphoma U937 cells. HDAC1 plays a role in the nucleus, which we confirmed by finding that 8a entered the nucleus. Subsequently, we verified that 8a mainly passes through the endogenous (mitochondrial) pathway to induce cell apoptosis. From the protein interaction data, we found that 8a also affected the expression of DNA methyltransferase 1 (DNMT1). Therefore, an experiment was performed to assess the binding of 8a to DNMT1 at the molecular and cellular levels. We found that the binding strength of 8a to DNMT1 enhanced in a dose-dependent manner. Additionally, 8a inhibits the expression of DNMT1 mRNA and its protein. These findings suggested that the anti-proliferative and pro-apoptotic activities of 8a against leukemia cells were achieved by targeting HDAC1 and DNMT1.
Overexpression of MdATG8i Enhances Drought Tolerance by Alleviating Oxidative Damage and Promoting Water Uptake in Transgenic Apple
Authors: Jia Xin , Gong Xiaoqing , Jia Xumei , Li Xianpeng , Wang Yu , Wang Ping , Huo Liuqing , Sun Xun , Che Runmin , Li Tiantian , Zou Yangjun , Ma Fengwang
Published: May 2021

Water deficit adversely affects apple (Malus domestica) productivity on the Loess Plateau. Autophagy plays a key role in plant responses to unfavorable environmental conditions. Previously, we demonstrated that a core apple autophagy-related protein, MdATG8i, was responsive to various stresses at the transcript level. Here, we investigated the function of this gene in the response of apple to severe drought and found that its overexpression (OE) significantly enhanced drought tolerance. Under drought conditions, MdATG8iOE apple plants exhibited less drought-related damage and maintained higher photosynthetic capacities compared with the wild type (WT). The accumulation of ROS (reactive oxygen species) was lower in OE plants under drought stress and was accompanied by higher activities of antioxidant enzymes. Besides, OE plants accumulated lower amounts of insoluble or oxidized proteins but greater amounts of amino acids and flavonoid under severe drought stress, probably due to their enhanced autophagic activities. Particularly, MdATG8iOE plants showed higher root hydraulic conductivity than WT plants did under drought conditions, indicating the enhanced ability of water uptake. In summary, the overexpression of MdATG8i alleviated oxidative damage, modulated amino acid metabolism and flavonoid synthesis, and improved root water uptake, ultimately contributing to enhanced drought tolerance in apple.
The Acidic Brain—Glycolytic Switch in the Microenvironment of Malignant Glioma
Authors: Reuss Anna Maria , Groos Dominik , Buchfelder Michael , Savaskan Nicolai
Published: May 2021

Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct tumor zones of this heterogeneous neoplasm develop their own microenvironment, in which subpopulations of cancer cells communicate. Adaptation to hypoxia in the center of the expanding tumor mass leads to the glycolytic and angiogenic switch, accompanied by upregulation of different glycolytic enzymes, transporters, and other metabolites. These processes render the tumor microenvironment more acidic, remodel the extracellular matrix, and create energy gradients for the metabolic communication between different cancer cells in distinct tumor zones. Escape mechanisms from hypoxia-induced cell death and energy deprivation are the result. The functional consequences are more aggressive and malignant behavior with enhanced proliferation and survival, migration and invasiveness, and the induction of angiogenesis. In this review, we go from the biochemical principles of aerobic and anaerobic glycolysis over the glycolytic switch, regulated by the key transcription factor hypoxia-inducible factor (HIF)-1α, to other important metabolic players like the monocarboxylate transporters (MCTs)1 and 4. We discuss the metabolic symbiosis model via lactate shuttling in the acidic tumor microenvironment and highlight the functional consequences of the glycolytic switch on glioma malignancy. Furthermore, we illustrate regulation by micro ribonucleic acids (miRNAs) and the connection between isocitrate dehydrogenase (IDH) mutation status and glycolytic metabolism. Finally, we give an outlook about the diagnostic and therapeutic implications of the glycolytic switch and the relation to tumor immunity in malignant glioma.
The Impact of High Glucose or Insulin Exposure on S100B Protein Levels, Oxidative and Nitrosative Stress and DNA Damage in Neuron-Like Cells
Authors: Kubis-Kubiak Adriana , Wiatrak Benita , Piwowar Agnieszka
Published: May 2021

Alzheimer’s disease (AD) is attracting considerable interest due to its increasing number of cases as a consequence of the aging of the global population. The mainstream concept of AD neuropathology based on pathological changes of amyloid β metabolism and the formation of neurofibrillary tangles is under criticism due to the failure of Aβ-targeting drug trials. Recent findings have shown that AD is a highly complex disease involving a broad range of clinical manifestations as well as cellular and biochemical disturbances. The past decade has seen a renewed importance of metabolic disturbances in disease-relevant early pathology with challenging areas in establishing the role of local micro-fluctuations in glucose concentrations and the impact of insulin on neuronal function. The role of the S100 protein family in this interplay remains unclear and is the aim of this research. Intracellularly the S100B protein has a protective effect on neurons against the toxic effects of glutamate and stimulates neurites outgrowth and neuronal survival. At high concentrations, it can induce apoptosis. The aim of our study was to extend current knowledge of the possible impact of hyper-glycemia and -insulinemia directly on neuronal S100B secretion and comparison to oxidative stress markers such as ROS, NO and DBSs levels. In this paper, we have shown that S100B secretion decreases in neurons cultured in a high-glucose or high-insulin medium, while levels in cell lysates are increased with statistical significance. Our findings demonstrate the strong toxic impact of energetic disturbances on neuronal metabolism and the potential neuroprotective role of S100B protein.
Small RNA, Transcriptome and Degradome Analysis of the Transgenerational Heat Stress Response Network in Durum Wheat
Authors: Liu Haipei , Able Amanda J. , Able Jason A.
Published: May 2021

Heat stress is a major limiting factor of grain yield and quality in crops. Abiotic stresses have a transgenerational impact and the mechanistic basis is associated with epigenetic regulation. The current study presents the first systematic analysis of the transgenerational effects of post-anthesis heat stress in tetraploid wheat. Leaf physiological traits, harvest components and grain quality traits were characterized under the impact of parental and progeny heat stress. The parental heat stress treatment had a positive influence on the offspring for traits including chlorophyll content, grain weight, grain number and grain total starch content. Integrated sequencing analysis of the small RNAome, mRNA transcriptome and degradome provided the first description of the molecular networks mediating heat stress adaptation under transgenerational influence. The expression profile of 1771 microRNAs (733 being novel) and 66,559 genes was provided, with differentially expressed microRNAs and genes characterized subject to the progeny treatment, parental treatment and tissue-type factors. Gene Ontology and KEGG pathway analysis of stress responsive microRNAs-mRNA modules provided further information on their functional roles in biological processes such as hormone homeostasis, signal transduction and protein stabilization. Our results provide new insights on the molecular basis of transgenerational heat stress adaptation, which can be used for improving thermo-tolerance in breeding.
Management of Acute Lung Injury: Palmitoylethanolamide as a New Approach
Authors: Peritore Alessio Filippo , D’Amico Ramona , Siracusa Rosalba , Cordaro Marika , Fusco Roberta , Gugliandolo Enrico , Genovese Tiziana , Crupi Rosalia , Di Paola Rosanna , Cuzzocrea Salvatore , Impellizzeri Daniela
Published: May 2021

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. Lipopolysaccharide (LPS) is usually used intratracheally to induce ALI in mice. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (um-PEA) in mice subjected to LPS-induced ALI. Histopathological analysis reveals that um-PEA reduced alteration in lung after LPS intratracheal administration. Besides, um-PEA decreased wet/dry weight ratio and myeloperoxidase, a marker of neutrophils infiltration, macrophages and total immune cells number and mast cells degranulation in lung. Moreover, um-PEA could also decrease cytokines release of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and interleukin (IL)-18. Furthermore, um-PEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration. Our study suggested that um-PEA contrasted LPS-induced ALI, exerting its potential role as an adjuvant anti-inflammatory therapeutic for treating lung injury, maybe also by p38/NF-κB pathway.
Tailoring Chitosan/LTA Zeolite Hybrid Aerogels for Anionic and Cationic Dye Adsorption
Authors: Salzano de Luna Martina , Greco Francesco , Pastore Raffaele , Mensitieri Giuseppe , Filippone Giovanni , Aprea Paolo , Mallamace Domenico , Mallamace Francesco , Chen Sow-Hsin
Published: May 2021

Chitosan (CS) is largely employed in environmental applications as an adsorbent of anionic dyes, due to the presence in its chemical structure of amine groups that, if protonated, act as adsorbing sites for negatively charged molecules. Efficient adsorption of both cationic and anionic dyes is thus not achievable with a pristine chitosan adsorbent, but it requires the combination of two or more components. Here, we show that simultaneous adsorption of cationic and anionic dyes can be obtained by embedding Linde Type A (LTA) zeolite particles in a crosslinked CS-based aerogel. In order to optimize dye removal ability of the hybrid aerogel, we target the crosslinker concentration so that crosslinking is mainly activated during the thermal treatment after the fast freezing of the CS/LTA mixture. The adsorption of isotherms is obtained for different CS/LTA weight ratios and for different types of anionic and cationic dyes. Irrespective of the formulation, the Langmuir model was found to accurately describe the adsorption isotherms. The optimal tradeoff in the adsorption behavior was obtained with the CS/LTA aerogel (1:1 weight ratio), for which the maximum uptake of indigo carmine (anionic dye) and rhodamine 6G (cationic dye) is 103 and 43 mg g−1, respectively. The behavior observed for the adsorption capacity and energy cannot be rationalized as a pure superposition of the two components, but suggests that reciprocal steric effects, chemical heterogeneity, and molecular interactions between CS and LTA zeolite particles play an important role.
Interactions among Lacosamide and Second-Generation Antiepileptic Drugs in the Tonic-Clonic Seizure Model in Mice
Authors: Załuska-Ogryzek Katarzyna , Marzęda Paweł , Wróblewska-Łuczka Paula , Florek-Łuszczki Magdalena , Plewa Zbigniew , Bojar Hubert , Zolkowska Dorota , Łuszczki Jarogniew J.
Published: May 2021

Combination therapy with two or three antiseizure medications (ASMs) is sometimes a preferred method of treatment in epilepsy patients. (1) Background: To detect the most beneficial combination among three ASMs, a screen test evaluating in vivo interactions with respect to their anticonvulsant properties, was conducted on albino Swiss mice; (2) Methods: Classification of interactions among lacosamide (LCM) and selected second-generation ASMs (lamotrigine (LTG), pregabalin (PGB), oxcarbazepine (OXC), and topiramate (TPM)) was based on the isobolographic analysis in the mouse maximal electroshock-induced seizure (MES) model. Interactions among LCM and second-generation ASMs were visualized using a polygonogram; (3) Results: In the mouse MES model, synergy was observed for the combinations of LCM + TPM + PGB and LCM + OXC + PGB. Additivity was reported for the other combinations tested i.e., LCM + LTG + TPM, LCM + LTG + PGB, LCM + LTG + OXC, and LCM + OXC + TPM in this seizure model. No adverse effects associated with triple ASM combinations, containing LCM and second-generation ASMs were observed in mice; (4) Conclusions: The combination of LCM + TPM + PGB was the most beneficial combination among the tested in this study, offering synergistic suppression of tonic-clonic seizures in mice subjected to the MES model. Both the isobolographic analysis and polygonogram method can be recommended for experimental epileptology when classifying interactions among the ASMs.
Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies
Authors: Wujak Magdalena , Kozakiewicz Anna , Ciarkowska Anna , Loch Joanna I. , Barwiolek Magdalena , Sokolowska Zuzanna , Budny Marcin , Wojtczak Andrzej
Published: May 2021

Statins are the most effective cholesterol-lowering drugs. They also exert many pleiotropic effects, including anti-cancer and cardio- and neuro-protective. Numerous nano-sized drug delivery systems were developed to enhance the therapeutic potential of statins. Studies on possible interactions between statins and human proteins could provide a deeper insight into the pleiotropic and adverse effects of these drugs. Adenylate kinase (AK) was found to regulate HDL endocytosis, cellular metabolism, cardiovascular function and neurodegeneration. In this work, we investigated interactions between human adenylate kinase isoenzyme 1 (hAK1) and atorvastatin (AVS), fluvastatin (FVS), pravastatin (PVS), rosuvastatin (RVS) and simvastatin (SVS) with fluorescence spectroscopy. The tested statins quenched the intrinsic fluorescence of hAK1 by creating stable hAK1-statin complexes with the binding constants of the order of 104 M−1. The enzyme kinetic studies revealed that statins inhibited hAK1 with significantly different efficiencies, in a noncompetitive manner. Simvastatin inhibited hAK1 with the highest yield comparable to that reported for diadenosine pentaphosphate, the only known hAK1 inhibitor. The determined AK sensitivity to statins differed markedly between short and long type AKs, suggesting an essential role of the LID domain in the AK inhibition. Our studies might open new horizons for the development of new modulators of short type AKs.
Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status
Authors: Florea Alexandru , Mottaghy Felix M. , Bauwens Matthias
Published: May 2021

Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.
Cold Atmospheric Pressure Plasma-Activated Medium Induces Selective Cell Death in Human Hepatocellular Carcinoma Cells Independently of Singlet Oxygen, Hydrogen Peroxide, Nitric Oxide and Nitrite/Nitrate
Authors: Li Yan , Tang Tianyu , Lee Haejune , Song Kiwon
Published: May 2021

Cold atmospheric pressure plasma (CAP) and plasma-activated medium (PAM) induce cell death in diverse cancer cells and may function as powerful anti-cancer agents. The main components responsible for the selective anti-cancer effects of CAP and PAM remain elusive. CAP or PAM induces selective cell death in hepatocellular carcinoma cell lines Hep3B and Huh7 containing populations with cancer stem cell markers. Here, we investigated the major component(s) of CAP and PAM for mediating the selective anti-proliferative effect on Hep3B and Huh7 cells. The anti-proliferative effect of CAP was mediated through the medium; however, the reactive oxygen species scavenger N-acetyl cysteine did not suppress PAM-induced cell death. Neither high concentrations of nitrite or nitrite/nitrate nor a low concentration of H2O2 present in the PAM containing sodium pyruvate affected the viability of Hep3B and Huh7 cells. Inhibitors of singlet oxygen, superoxide anions, and nitric oxide retained the capacity of PAM to induce anti-cancer effects. The anti-cancer effect was largely blocked in the PAM prepared by placing an aluminum metal mesh, but not a dielectric PVC mesh, between the plasma source and the medium. Hence, singlet oxygen, hydrogen peroxide, nitric oxide, and nitrite/nitrate are not the main factors responsible for PAM-mediated selective death in Hep3B and Huh7 cells. Other factors, such as charged particles including various ions in CAP and PAM, may induce selective anti-cancer effects in certain cancer cells.
Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment
Authors: Nakai Tsuyoshi , Yamada Kiyofumi , Mizoguchi Hiroyuki
Published: May 2021

Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes, APP knock-in mice, which were presented with touchscreen-based tasks, were developed to better evaluate the efficacy of candidate therapeutics in mouse models of early-stage AD. This review assesses several AD mouse models from the aspect of biomarkers and cognitive impairment and discusses their potential as tools to provide novel AD therapeutic approaches.
Nanotechnology Facilitated Cultured Neuronal Network and Its Applications
Authors: Singh Satnam , Mishra Sachin , Juha Song , Pramanik Manojit , Padmanabhan Parasuraman , Gulyás Balázs
Published: May 2021

The development of a biomimetic neuronal network from neural cells is a big challenge for researchers. Recent advances in nanotechnology, on the other hand, have enabled unprecedented tools and techniques for guiding and directing neural stem cell proliferation and differentiation in vitro to construct an in vivo-like neuronal network. Nanotechnology allows control over neural stem cells by means of scaffolds that guide neurons to reform synaptic networks in suitable directions in 3D architecture, surface modification/nanopatterning to decide cell fate and stimulate/record signals from neurons to find out the relationships between neuronal circuit connectivity and their pathophysiological functions. Overall, nanotechnology-mediated methods facilitate precise physiochemical controls essential to develop tools appropriate for applications in neuroscience. This review emphasizes the newest applications of nanotechnology for examining central nervous system (CNS) roles and, therefore, provides an insight into how these technologies can be tested in vitro before being used in preclinical and clinical research and their potential role in regenerative medicine and tissue engineering.
Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia
Authors: Estaras Matias , Gonzalez-Portillo Manuel R. , Fernandez-Bermejo Miguel , Mateos Jose M. , Vara Daniel , Blanco-Fernandez Gerardo , Lopez-Guerra Diego , Roncero Vicente , Salido Gines M. , González Antonio
Published: May 2021

In certain diseases of the pancreas, pancreatic stellate cells form an important part of fibrosis and are critical for the development of cancer cells. A hypoxic condition develops within the tumor, to which pancreatic stellate cells adapt and are able to proliferate. The consequence is the growth of the tumor. Melatonin, the product of the pineal gland, is gaining attention as an agent with therapeutic potential against pancreatic cancers. Its actions on tumor cells lead, in general, to a reduction in cell viability and proliferation. However, its effects on pancreatic stellate cells subjected to hypoxia are less known. In this study, we evaluated the actions of pharmacological concentrations of melatonin (1 mM–1 µM) on pancreatic stellate cells subjected to hypoxia. The results show that melatonin induced a decrease in cell viability at the highest concentrations tested. Similarly, the incorporation of BrdU into DNA was diminished by melatonin. The expression of cyclins A and D also was decreased in the presence of melatonin. Upon treatment of cells with melatonin, increases in the expression of major markers of ER stress, namely BIP, phospho-eIF2α and ATF-4, were detected. Modulation of apoptosis was noticed as an increase in caspase-3 activation. In addition, changes in the phosphorylated state of p44/42, p38 and JNK MAPKs were detected in cells treated with melatonin. A slight decrease in the content of α-smooth muscle actin was detected in cells treated with melatonin. Finally, treatment of cells with melatonin decreased the expression of matrix metalloproteinases 2, 3, 9 and 13. Our observations suggest that melatonin, at pharmacological concentrations, diminishes the proliferation of pancreatic stellate cells subjected to hypoxia through modulation of cell cycle, apoptosis and the activation of crucial MAPKs. Cellular responses might involve certain ER stress regulator proteins. In view of the results, melatonin could be taken into consideration as a potential therapeutic agent for pancreatic fibrosis.
Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle
Authors: Yang Tao-Chieh , Liu Shih-Jung , Lo Wei-Lun , Chen Shu-Mei , Tang Ya-Ling , Tseng Yuan-Yun
Published: May 2021

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.
Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour
Authors: Álvarez-Artime Alejandro , García-Soler Belén , Sainz Rosa María , Mayo Juan Carlos
Published: May 2021

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.
Social Media in Communicating about Social and Environmental Issues—Non-Financial Reports in Poland
Authors: Stawicka Ewa , Paliszkiewicz Joanna
Published: May 2021

The main purpose of this article is to analyze the dissemination of social reports among entrepreneurs in order to determine the number of reporting organizations and examples in which Corporate Social Responsibility (CSR) areas enterprises report. We analyze the dissemination of social reports among entrepreneurs in Poland and determine the number of reporting organizations and examples in which CSR companies report. This work is a guide for entrepreneurs in Poland to build strategies and activities for transparency and communicating good practice. One of the research goals was to identify and evaluate communication activities with stakeholders in terms of responsible activities, social and environmental. The data analysis comes from a detailed literature review and the Responsible Business Forum (FOB) Reports database for 2008–2019 in Poland. The results of the survey show that many entrepreneurs in Poland, representing small, medium-sized (SME), and even large enterprises underestimate the importance of socially responsible activities. Entrepreneurs communicate with stakeholders to a limited extent and are not informed about good practices. The vast majority of the surveyed enterprises, especially large ones, prepare social reports, which result from obligation: requirements of Directive 2014/95/EU. The SME sector shows a lack of knowledge and uses individual marketing communication tools to a limited extent, limiting itself to advertising activities (very few companies prepare social reports). The article is a practical tip for enterprises showing the impact of business on changes towards sustainable development. Originality/value lies in the fact that the article presents selected research results on various aspects related to social reporting and communicating social and environmental activities to stakeholders.
Deltamethrin-Mediated Effects on Locomotion, Respiration, Feeding, and Histological Changes in the Midgut of Spodoptera frugiperda Caterpillars
Authors: Vinha Germano Lopes , Plata-Rueda Angelica , Soares Marcus Alvarenga , Zanuncio José Cola , Serrão José Eduardo , Martínez Luis Carlos
Published: May 2021

Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is the main pest of maize crops, and effective methods for pest management are needed. The insecticidal efficacy of deltamethrin was evaluated against S. frugiperda for toxicity, survival, locomotion, anti-feeding, and histological changes in the midgut. Concentration–mortality bioassays confirmed that deltamethrin (LC50 = 3.58 mg mL−1) is toxic to S. frugiperda caterpillars. The survival rate was 99.7% in caterpillars not exposed to deltamethrin, decreasing to 50.3% in caterpillars exposed to LC50, and 0.1% in caterpillars treated with LC90. Spodoptera frugiperda demonstrated reduced mobility on deltamethrin-treated surfaces. Deltamethrin promoted a low respiration rate of S. frugiperda for up to 3 h after insecticide exposure, displaying immobilization and inhibiting food consumption. Deltamethrin induces histological alterations (e.g., disorganization of the striated border, cytoplasm vacuolization, and cell fragmentation) in the midgut, damaging the digestive cells and peritrophic matrix, affecting digestion and nutrient absorption.
Latest Developments in Insect Sex Pheromone Research and Its Application in Agricultural Pest Management
Authors: Rizvi Syed Arif Hussain , George Justin , Reddy Gadi V. P. , Zeng Xinnian , Guerrero Angel
Published: May 2021

Since the first identification of the silkworm moth sex pheromone in 1959, significant research has been reported on identifying and unravelling the sex pheromone mechanisms of hundreds of insect species. In the past two decades, the number of research studies on new insect pheromones, pheromone biosynthesis, mode of action, peripheral olfactory and neural mechanisms, and their practical applications in Integrated Pest Management has increased dramatically. An interdisciplinary approach that uses the advances and new techniques in analytical chemistry, chemical ecology, neurophysiology, genetics, and evolutionary and molecular biology has helped us to better understand the pheromone perception mechanisms and its practical application in agricultural pest management. In this review, we present the most recent developments in pheromone research and its application in the past two decades.
Imaging Techniques for the Study of Fibrosis in Atrial Fibrillation Ablation: From Molecular Mechanisms to Therapeutical Perspectives
Authors: De Sensi Francesco , Penela Diego , Soto-Iglesias David , Berruezo Antonio , Limbruno Ugo
Published: May 2021

Atrial fibrillation (AF) is the most prevalent form of cardiac arrhythmia. It is often related to diverse pathological conditions affecting the atria and leading to remodeling processes including collagen accumulation, fatty infiltration, and amyloid deposition. All these events generate atrial fibrosis, which contribute to beget AF. In this scenario, cardiac imaging appears as a promising noninvasive tool for monitoring the presence and degree of LA fibrosis and remodeling. The aim of this review is to comprehensively examine the bench mechanisms of atrial fibrosis moving, then to describe the principal imaging techniques that characterize it, such as cardiac magnetic resonance (CMR) and multidetector cardiac computed tomography (MDCT), in order to tailor atrial fibrillation ablation to each individual.
Analysis of Copy Number Variations in Solid Tumors Using a Next Generation Sequencing Custom Panel
Authors: Vives-Usano Marta , García Pelaez Beatriz , Román Lladó Ruth , Garzón Ibañez Mónica , Aldeguer Erika , Rodriguez Sonia , Aguilar Andrés , Pons Francesc , Viteri Santiago , Cabrera Carlos , José Catalán Maria , Moya Irene , Gonzalez Cao María , García-Mosquera Juan José , Martinez-Bueno Alejandro , Meshoulam Ekaterina , Jordana Nuria , Berrocal Laura , Rosell Rafael , Molina Miguel Angel , Mayo de las Casas Clara
Published: May 2021

Somatic copy number variations (CNV; i.e., amplifications and deletions) have been implicated in the origin and development of multiple cancers and some of these aberrations are designated targets for therapies. Although FISH is still considered the gold standard for CNV detection, the increasing number of potentially druggable amplifications to be assessed makes a gene-by-gene approach time- and tissue-consuming. Here we investigated the potential of next generation sequencing (NGS) custom panels to simultaneously determine CNVs across FFPE solid tumor samples. DNA was purified from cell lines and FFPE samples and analyzed by NGS sequencing using a 20-gene custom panel in the GeneReader Platform®. CNVs were identified using an in-house algorithm based on the UMI read coverage. Retrospective validation of in-house algorithm to identify CNVs showed 97.1% concordance rate with the NGS custom panel. The prospective analysis was performed in a cohort of 243 FFPE samples from patients arriving at our hospital, which included 74 NSCLC tumors, 148 CRC tumors, and 21 other tumors. Of them, 33% presented CNVs by NGS and in 14 cases (5.9%) the CNV was the only alteration detected. We have identified CNV alterations in about one-third of our cohort, including FGFR1, CDK6, CDK4, EGFR, MET, ERBB2, BRAF, or KRAS. Our work highlights the need to include CNV testing as a part of routine NGS analysis in order to uncover clinically relevant gene amplifications that can guide the selection of therapies.
Environmental Status of Cryptococcus neoformans and Cryptococcus gattii in Colombia
Authors: Serna-Espinosa Briggith-Nathalia , Guzmán-Sanabria Diomedes , Forero-Castro Maribel , Escandón Patricia , Sánchez-Quitian Zilpa Adriana
Published: May 2021

The genus Cryptococcus comprises more than 80 species, including C. neoformans and C. gattii, which are pathogenic to humans, mainly affecting the central nervous system. The two species differ in geographic distribution and environmental niche. C. neoformans has a worldwide distribution and is often isolated from bird droppings. On the contrary, C. gattii is reported in tropical and subtropical regions and is associated with Eucalyptus species. This review aims to describe the distribution of environmental isolates of the Cryptococcus neoformans species complex and the Cryptococcus gattii species complex in Colombia. A systematic investigation was carried out using different databases, excluding studies of clinical isolates reported in the country. The complex of the species of C. gattii is recovered mainly from trees of the genus Eucalyptus spp., while the complex of the species of C. neoformans is recovered mainly from avian excrement, primarily Columba livia (pigeons) excrement. In addition, greater positivity was found at high levels of relative humidity. Likewise, an association was observed between the presence of the fungus in places with little insolation and cold or temperate temperatures compared to regions with high temperatures.
Algorithmic Journalism—Current Applications and Future Perspectives
Authors: Kotenidis Efthimis , Veglis Andreas
Published: May 2021

Journalism, more so than other professions, is entangled with technology in a unique and profoundly impactful way. In this context, the technological developments of the past decades have fundamentally impacted the journalistic profession in more ways than one, opening up new possibilities and simultaneously creating a number of concerns for people working in the media industry. The changes that were brought about by the rise of automation and algorithmic technology can mainly be observed in four distinct fields of application within journalism: automated content production, data mining, news dissemination and content optimization. This article focuses on algorithmic journalism and aims to highlight the ways that algorithmic technology is being utilized within those fields, as well as pointing out the ways in which these developments have altered the way journalism is being exercised in the modern world. The study also discusses challenges related to these technologies that are yet to be addressed, as well as potential future implementations related to algorithmic journalism that have the capacity to improve on the foundation of automation in the news industry.
3′-Methyl-2-oxo-1′,5′-diphenyl-1′,7′-dihydrospiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-6′-carboxylic Acid
Authors: Romo Pablo E. , Insuasty Braulio , Quiroga Jairo , Abonia Rodrigo
Published: May 2021

3′-methyl-2-oxo-1′,5′-diphenyl-1′,7′-dihydrospiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-6′-carboxylic acid was synthesized using diverse conditions. The best reaction condition consisted of using water as solvent under microwave irradiation, affording product in 76% yield.
Constitutive Modeling of the Densification Behavior in Open-Porous Cellular Solids
Authors: Rege Ameya
Published: May 2021

The macroscopic mechanical behavior of open-porous cellular materials is dictated by the geometric and material properties of their microscopic cell walls. The overall compressive response of such materials is divided into three regimes, namely, the linear elastic, plateau and densification. In this paper, a constitutive model is presented, which captures not only the linear elastic regime and the subsequent pore-collapse, but is also shown to be capable of capturing the hardening upon the densification of the network. Here, the network is considered to be made up of idealized square-shaped cells, whose cell walls undergo bending and buckling under compression. Depending on the choice of damage criterion, viz. elastic buckling or irreversible bending, the cell walls collapse. These collapsed cells are then assumed to behave as nonlinear springs, acting as a foundation to the elastic network of active open cells. To this end, the network is decomposed into an active network and a collapsed one. The compressive strain at the onset of densification is then shown to be quantified by the point of intersection of the two network stress-strain curves. A parameter sensitivity analysis is presented to demonstrate the range of different material characteristics that the model is capable of capturing. The proposed constitutive model is further validated against two different types of nanoporous materials and shows good agreement.
Investigation on Crystallization and Magnetic Properties of (Nd, Pr, Ce)2Fe14B/α-Fe Nanocomposite Magnets by Microwave Annealing Treatment
Authors: Wang Zhanyong , Shangguan Changping , Wang Zemin , Wang Tianpeng , Wang Lianbo , Liu Min , Sui Yanli
Published: May 2021

In the present work, the structures and magnetic properties of (Nd, Pr, Ce) 2Fe14B/α-Fe nanocomposite magnets were thoroughly investigated. The microwave annealing was applied to achieve a uniform heating effect and uniform grains. Microwave annealing is more favorable to obtain α-Fe phase than conventional annealing, which leads to the enhanced coercivity of hysteresis loops. The coercivity of nanocomposite magnets was 245 kA/m after annealing at 2000 W for 10 min.
Improving the Properties of Laser-Welded Al–Zn–Mg–Cu Alloy Joints by Aging and Double-Sided Ultrasonic Impact Compound Treatment
Authors: Chen Furong , Liu Chenghao
Published: May 2021

To improve the loose structure and serious porosity of (Al–Zn–Mg–Cu) 7075 aluminum alloy laser-welded joints, aging treatment, double-sided ultrasonic impact treatment (DSUIT), and a combination of aging and DSUIT (A–DSUIT) were used to treat joints. In this experiment, the mechanism of A–DSUIT on the microstructure and properties of welded joints was analyzed. The microstructure of the welded joints was observed using optical microscopy, scanning electron microscopy, and electron backscatter diffraction (EBSD). The hardness and tensile properties of the welded components under the different processes were examined via Vickers hardness test and a universal tensile testing machine. The results showed that, after the aging treatment, the dendritic structure of the welded joints transformed into an equiaxed crystal structure. Moreover, the residual tensile stress generated in the welding process was weakened, and the hardness and tensile strength were significantly improved. After DSUIT, a plastic deformation layer of a certain thickness was generated from the surface downward, and the residual compressive stress was introduced to a certain depth of the joint. However, the weld zone unaffected by DSUIT still exhibited residual tensile stress. The inner microhardness of the joint surface improved; the impact surface hardness was the largest and gradually decreased inward to the weld zone base metal hardness, with a small improvement in the tensile strength. Compared with the single treatment process, the microstructural and mechanical properties of the welded joint after A–DSUIT were comprehensively improved. The microhardness and tensile strength of the welded joint reached 200 HV and 615 MPa, respectively, for an increase of 45.8% and 61.8%, respectively. Observation of the fractures of the tensile specimens under the different treatment processes showed that the fractures before the aging treatment were mainly ductile fractures while those after were mainly brittle fractures. After DSUIT of the welded joints, a clear and dense plastic deformation layer was observed in the fracture of the tensile specimens and effectively improved the tensile properties of the welded joints. Under the EBSD characterization, the larger the residual compressive stress near the ultrasonic impact surface, the smaller the grain diameter and misorientation angle, and the lower the texture strength. Finally, after A–DSUIT, the hardness and tensile properties improved the most.
Down-Shifting in the YAM: Ce3+ + Yb3+ System for Solar Cells
Authors: Fetliński Bartosz , Turczyński Sebastian , Malinowski Michał , Szczepański Paweł
Published: May 2021

In this work, we investigate Ce3+ to Yb3+ energy transfer in Y4Al2O9 (YAM) for potential application in solar spectrum down-converting layers for photovoltaic devices. Photoluminescence properties set, of 10 samples, of the YAM host activated with Ce3+ and Yb3+ with varying concentrations are presented, and the Ce3+ to Yb3+ energy transfer is proven. Measurement of highly non-exponential luminescence decays of Ce3+ 5d band allowed for the calculation of maximal theoretical quantum efficiency, of the expected down-conversion process, equal to 123%. Measurements of Yb3+ emission intensity, in the function of excitation power, confirmed the predominantly single-photon downshifting character of Ce3+ to Yb3+ energy transfer. Favorable location of the Ce3+ 5d bands in YAM makes this system a great candidate for down-converting, and down-shifting, luminescent layers for photovoltaics.