bluuebunny/crossref_metadata_2025 huggingface dataset:
Deletion of the Autism-Associated Protein SHANK3 Abolishes Structural Synaptic Plasticity after Brain Trauma
Authors: Urrutia-Ruiz Carolina , Rombach Daniel , Cursano Silvia , Gerlach-Arbeiter Susanne , Schoen Michael , Bockmann Juergen , Demestre Maria , Boeckers Tobias M.
Published: May 2022

Autism spectrum disorders (ASDs) are characterized by repetitive behaviors and impairments of sociability and communication. About 1% of ASD cases are caused by mutations of SHANK3, a major scaffolding protein of the postsynaptic density. We studied the role of SHANK3 in plastic changes of excitatory synapses within the central nervous system by employing mild traumatic brain injury (mTBI) in WT and Shank3 knockout mice. In WT mice, mTBI triggered ipsi- and contralateral loss of hippocampal dendritic spines and excitatory synapses with a partial recovery over time. In contrast, no significant synaptic alterations were detected in Shank3∆11−/− mice, which showed fewer dendritic spines and excitatory synapses at baseline. In line, mTBI induced the upregulation of synaptic plasticity-related proteins Arc and p-cofilin only in WT mice. Interestingly, microglia proliferation was observed in WT mice after mTBI but not in Shank3∆11−/− mice. Finally, we detected TBI-induced increased fear memory at the behavioral level, whereas in Shank3∆11−/− animals, the already-enhanced fear memory levels increased only slightly after mTBI. Our data show the lack of structural synaptic plasticity in Shank3 knockout mice that might explain at least in part the rigidity of behaviors, problems in adjusting to new situations and cognitive deficits seen in ASDs.
Prenatal Zinc Deficient Mice as a Model for Autism Spectrum Disorders
Authors: Sauer Ann Katrin , Hagmeyer Simone , Grabrucker Andreas M.
Published: May 2022

Epidemiological studies have shown a clear association between early life zinc deficiency and Autism Spectrum Disorders (ASD). In line with this, mouse models have revealed prenatal zinc deficiency as a profound risk factor for neurobiological and behavioral abnormalities in the offspring reminiscent of ASD behavior. From these studies, a complex pathology emerges, with alterations in the gastrointestinal and immune system and synaptic signaling in the brain, as a major consequence of prenatal zinc deficiency. The features represent a critical link in a causal chain that leads to various neuronal dysfunctions and behavioral phenotypes observed in prenatal zinc deficient (PZD) mice and probably other mouse models for ASD. Given that the complete phenotype of PZD mice may be key to understanding how non-genetic factors can modify the clinical features and severity of autistic patients and explain the observed heterogeneity, here, we summarize published data on PZD mice. We critically review the emerging evidence that prenatal zinc deficiency is at the core of several environmental risk factors associated with ASD, being mechanistically linked to ASD-associated genetic factors. In addition, we highlight future directions and outstanding questions, including potential symptomatic, disease-modifying, and preventive treatment strategies.
Newly Emerged Antiviral Strategies for SARS-CoV-2: From Deciphering Viral Protein Structural Function to the Development of Vaccines, Antibodies, and Small Molecules
Authors: Zhang Chunye , Yang Ming
Published: May 2022

Coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe health crisis, causing extraordinary economic disruption worldwide. SARS-CoV-2 is a single-stranded RNA-enveloped virus. The process of viral replication and particle packaging is finished in host cells. Viral proteins, including both structural and nonstructural proteins, play important roles in the viral life cycle, which also provides the targets of treatment. Therefore, a better understanding of the structural function of virus proteins is crucial to speed up the development of vaccines and therapeutic strategies. Currently, the structure and function of proteins encoded by the SARS-CoV-2 genome are reviewed by several studies. However, most of them are based on the analysis of SARS-CoV-1 particles, lacking a systematic review update for SARS-CoV-2. Here, we specifically focus on the structure and function of proteins encoded by SARS-CoV-2. Viral proteins that contribute to COVID-19 infection and disease pathogenesis are reviewed according to the most recent research findings. The structure-function correlation of viral proteins provides a fundamental rationale for vaccine development and targeted therapy. Then, current antiviral vaccines are updated, such as inactive viral vaccines and protein-based vaccines and DNA, mRNA, and circular RNA vaccines. A summary of other therapeutic options is also reviewed, including monoclonal antibodies such as a cross-neutralizer antibody, a constructed cobinding antibody, a dual functional monoclonal antibody, an antibody cocktail, and an engineered bispecific antibody, as well as peptide-based inhibitors, chemical compounds, and clustered regularly interspaced short palindromic repeats (CRISPR) exploration. Overall, viral proteins and their functions provide the basis for targeted therapy and vaccine development.
New Potential Agents for Malignant Melanoma Treatment—Most Recent Studies 2020–2022
Authors: Kozyra Paweł , Krasowska Danuta , Pitucha Monika
Published: May 2022

Malignant melanoma (MM) is the most lethal skin cancer. Despite a 4% reduction in mortality over the past few years, an increasing number of new diagnosed cases appear each year. Long-term therapy and the development of resistance to the drugs used drive the search for more and more new agents with anti-melanoma activity. This review focuses on the most recent synthesized anti-melanoma agents from 2020–2022. For selected agents, apart from the analysis of biological activity, the structure–activity relationship (SAR) is also discussed. To the best of our knowledge, the following literature review delivers the latest achievements in the field of new anti-melanoma agents.
Lupeol Treatment Attenuates Activation of Glial Cells and Oxidative-Stress-Mediated Neuropathology in Mouse Model of Traumatic Brain Injury
Authors: Ahmad Riaz , Khan Amjad , Rehman Inayat Ur , Lee Hyeon Jin , Khan Ibrahim , Kim Myeong Ok
Published: May 2022

Traumatic brain injury (TBI) signifies a major cause of death and disability. TBI causes central nervous system (CNS) damage under a variety of mechanisms, including protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Astrocytes and microglia, cells of the CNS, are considered the key players in initiating an inflammatory response after injury. Several evidence suggests that activation of astrocytes/microglia and ROS/LPO have the potential to cause more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that lupeol provides neuroprotection through modulation of inflammation, oxidative stress, and apoptosis in Aβ and LPS model and neurodegenerative disease. However, the effects of lupeol on apoptosis caused by inflammation and oxidative stress in TBI have not yet been investigated. Therefore, we explored the role of Lupeol on antiapoptosis, anti-inflammatory, and antioxidative stress and its potential mechanism following TBI. In these experiments, adult male mice were randomly divided into four groups: control, TBI, TBI+ Lupeol, and Sham group. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of lupeol against neuroinflammation, oxidative stress, and apoptosis. Lupeol treatment reversed TBI-induced behavioral and memory disturbances. Lupeol attenuated TBI-induced generation of reactive oxygen species/lipid per oxidation (ROS/LPO) and improved the antioxidant protein level, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1) in the mouse brain. Similarly, our results indicated that lupeol treatment inhibited glial cell activation, p-NF-κB, and downstream signaling molecules, such as TNF-α, COX-2, and IL-1β, in the mouse cortex and hippocampus. Moreover, lupeol treatment also inhibited mitochondrial apoptotic signaling molecules, such as caspase-3, Bax, cytochrome-C, and reversed deregulated Bcl2 in TBI-treated mice. Overall, our study demonstrated that lupeol inhibits the activation of astrocytes/microglia and ROS/LPO that lead to oxidative stress, neuroinflammation, and apoptosis followed by TBI.
Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the Drosophila warts (wts) Locus
Authors: Gnocchini Eleonora , Pilesi Eleonora , Schiano Ludovica , Vernì Fiammetta
Published: May 2022

The active form of vitamin B6, pyridoxal 5′-phosphate (PLP), is a cofactor for more than 200 enzymes involved in many metabolic pathways. Moreover, PLP has antioxidant properties and quenches the reactive oxygen species (ROS). Accordingly, PLP deficiency causes chromosome aberrations in Drosophila, yeast, and human cells. In this work, we investigated whether PLP depletion can also cause loss of heterozygosity (LOH) of the tumor suppressor warts (wts) in Drosophila. LOH is usually initiated by DNA breakage in heterozygous cells for a tumor suppressor mutation and can contribute to oncogenesis inducing the loss of the wild-type allele. LOH at the wts locus results in epithelial wts homozygous tumors easily detectable on adult fly cuticle. Here, we found that PLP depletion, induced by two PLP inhibitors, promotes LOH of wts locus producing significant frequencies of wts tumors (~7% vs. 2.3%). In addition, we identified the mitotic recombination as a possible mechanism through which PLP deficiency induces LOH. Moreover, LOH of wts locus, induced by PLP inhibitors, was rescued by PLP supplementation. These data further confirm the role of PLP in genome integrity maintenance and indicate that vitamin B6 deficiency may impact on cancer also by promoting LOH.
Effect of Skin Ion Channel TRPM8 Activation by Cold and Menthol on Thermoregulation and the Expression of Genes of Thermosensitive TRP Ion Channels in the Hypothalamus of Hypertensive Rats
Authors: Voronova Irina P. , Khramova Galina M. , Evtushenko Anna A. , Kozyreva Tamara V.
Published: May 2022

ISIAH (inherited stress-induced arterial hypertension) rats are characterized by high blood pressure and decreased Trpm8 gene expression in the anterior hypothalamus. Thermosensitive ion channel TRPM8 plays a critical role in the transduction of moderately cold stimuli that give rise to cool sensations. In normotensive animals, the activation of skin TRPM8 is known to induce changes in gene expression in the hypothalamus and induce alterations of thermoregulatory responses. In this work, in hypertensive rats, we studied the effects of activation of the peripheral TRPM8 by cooling and by application of a 1% menthol suspension on (1) the maintenance of body temperature balance and (2) mRNA expression of thermosensitive TRP ion channels in the hypothalamus. In these hypertensive animals, (1) pharmacological activation of peripheral TRPM8 did not affect the thermoregulatory parameters either under thermoneutral conditions or during cold exposure; (2) the expression of Trpm8 in the anterior hypothalamus approximately doubled (to the level of normotensive animals) under the influence of (a) slow cooling and (b) at pharmacological activation of the peripheral TRPM8 ion channel. The latter fact seems the quite important because it allows the proposal of a tool for correcting at least some parameters that distinguish a hypertensive state from the normotensive one.
Neu3 Sialidase Activates the RISK Cardioprotective Signaling Pathway during Ischemia and Reperfusion Injury (IRI)
Authors: Piccoli Marco , Coviello Simona , Canali Maria Elena , Rota Paola , La Rocca Paolo , Cirillo Federica , Lavota Ivana , Tarantino Adriana , Ciconte Giuseppe , Pappone Carlo , Ghiroldi Andrea , Anastasia Luigi
Published: May 2022

Coronary reperfusion strategies are life-saving approaches to restore blood flow to cardiac tissue after acute myocardial infarction (AMI). However, the sudden restoration of normal blood flow leads to ischemia and reperfusion injury (IRI), which results in cardiomyoblast death, irreversible tissue degeneration, and heart failure. The molecular mechanism of IRI is not fully understood, and there are no effective cardioprotective strategies to prevent it. In this study, we show that activation of sialidase-3, a glycohydrolytic enzyme that cleaves sialic acid residues from glycoconjugates, is cardioprotective by triggering RISK pro-survival signaling pathways. We found that overexpression of Neu3 significantly increased cardiomyoblast resistance to IRI through activation of HIF-1α and Akt/Erk signaling pathways. This raises the possibility of using Sialidase-3 activation as a cardioprotective reperfusion strategy after myocardial infarction.
Proteomic Profiling and Biomarker Discovery in Colorectal Liver Metastases
Authors: Wong Geoffrey Yuet Mun , Diakos Connie , Hugh Thomas J. , Molloy Mark P.
Published: May 2022

Colorectal liver metastases (CRLM) are the leading cause of death among patients with metastatic colorectal cancer (CRC). As part of multimodal therapy, liver resection is the mainstay of curative-intent treatment for select patients with CRLM. However, effective treatment of CRLM remains challenging as recurrence occurs in most patients after liver resection. Proposed clinicopathologic factors for predicting recurrence are inconsistent and lose prognostic significance over time. The rapid development of next-generation sequencing technologies and decreasing DNA sequencing costs have accelerated the genomic profiling of various cancers. The characterisation of genomic alterations in CRC has significantly improved our understanding of its carcinogenesis. However, the functional context at the protein level has not been established for most of this genomic information. Furthermore, genomic alterations do not always result in predicted changes in the corresponding proteins and cancer phenotype, while post-transcriptional and post-translational regulation may alter synthesised protein levels, affecting phenotypes. More recent advancements in mass spectrometry-based technology enable accurate protein quantitation and comprehensive proteomic profiling of cancers. Several studies have explored proteomic biomarkers for predicting CRLM after oncologic resection of primary CRC and recurrence after curative-intent resection of CRLM. The current review aims to rationalise the proteomic complexity of CRC and explore the potential applications of proteomic biomarkers in CRLM.
Chemogenetic Activation of Astrocytes in the Basolateral Amygdala Contributes to Fear Memory Formation by Modulating the Amygdala–Prefrontal Cortex Communication
Authors: Lei Zhuogui , Xie Li , Li Cheuk Hin , Lam Yuk Yan , Ramkrishnan Aruna Surendran , Fu Zhongqi , Zeng Xianlin , Liu Shu , Iqbal Zafar , Li Ying
Published: May 2022

The basolateral amygdala (BLA) is one of the key brain areas involved in aversive learning, especially fear memory formation. Studies of aversive learning in the BLA have largely focused on neuronal function, while the role of BLA astrocytes in aversive learning remains largely unknown. In this study, we manipulated the BLA astrocytes by expressing the Gq-coupled receptor hM3q and discovered that astrocytic Gq modulation during fear conditioning promoted auditorily cued fear memory but did not affect less stressful memory tasks or induce anxiety-like behavior. Moreover, chemogenetic activation of BLA astrocytes during memory retrieval had no effect on fear memory expression. In addition, astrocytic Gq activation increased c-Fos expression in the BLA and the medial prefrontal cortex (mPFC) during fear conditioning, but not in the home cage. Combining these results with retrograde virus tracing, we found that the activity of mPFC-projecting BLA neurons showed significant enhancement after astrocytic Gq activation during fear conditioning. Electrophysiology recordings showed that activating astrocytic Gq in the BLA promoted spike-field coherence and phase locking percentage, not only within the BLA but also between the BLA and the mPFC. Finally, direct chemogenetic activation of mPFC-projecting BLA neurons during fear conditioning enhanced cued fear memory. Taken together, our data suggest that astrocytes in the BLA may contribute to aversive learning by modulating amygdala–mPFC communication.
Active Compounds in Zingiber officinale as Possible Redox Inhibitors of 5-Lipoxygenase Using an In Silico Approach
Authors: Ley-Martínez Jaqueline Stephanie , Ortega-Valencia Jose Erick , García-Barradas Oscar , Jiménez-Fernández Maribel , Uribe-Lam Esmeralda , Vencedor-Meraz Carlos Iván , Oliva-Ramírez Jacqueline
Published: May 2022

5-Lipoxygenase (5-LOX) converts arachidonic acid to lipidic inflammatory mediators such as leukotrienes (LTs). In diseases such as asthma, LTs contribute to a physiopathology that could be reverted by blocking 5-LOX. Natural products with anti-inflammatory potential such as ginger have been used as nutraceuticals since ancient times. 6-Gingerol and 6-shogaol are the most abundant compounds in the ginger rhizome; they possess anti-inflammatory, antioxidant, and chemopreventive properties. In the present study, 6-gingerol and 6-shogaol structures were analyzed and compared with two commercial 5-LOX inhibitors (zileuton and atreleuton) and with other inhibitor candidates (3f, NDGA, CP 209, caffeic acid, and caffeic acid phenethyl ester (CAPE)). The pharmacokinetics and toxicological properties of 6-gingerol, 6-shogaol, and the other compounds were evaluated. Targeted molecular coupling was performed to identify the optimal catalytic pocket for 5-LOX inhibition. The results showed that 6-gingerol and 6-shogaol follow all of the recommended pharmacokinetic parameters. These compounds could be inhibitors of 5-LOX because they present specific interactions with the residues involved in molecular inhibition. The current study demonstrated the potential of 6-gingerol and 6-shogaol as anti-inflammatory agents that inhibit 5-LOX, as they present a high level of performance in the toxicological analysis and could be catabolized by the cytochrome p450 enzymatic complex; however, 6-gingerol was superior in safety compared to 6-shogaol.
Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts
Authors: Reibring Claes-Göran , El Shahawy Maha , Hallberg Kristina , Harfe Brian D. , Linde Anders , Gritli-Linde Amel
Published: May 2022

BMP signaling is crucial for differentiation of secretory ameloblasts, the cells that secrete enamel matrix. However, whether BMP signaling is required for differentiation of maturation-stage ameloblasts (MA), which are instrumental for enamel maturation into hard tissue, is hitherto unknown. To address this, we used an in vivo genetic approach which revealed that combined deactivation of the Bmp2 and Bmp4 genes in the murine dental epithelium causes development of dysmorphic and dysfunctional MA. These fail to exhibit a ruffled apical plasma membrane and to reabsorb enamel matrix proteins, leading to enamel defects mimicking hypomaturation amelogenesis imperfecta. Furthermore, subsets of mutant MA underwent pathological single or collective cell migration away from the ameloblast layer, forming cysts and/or exuberant tumor-like and gland-like structures. Massive apoptosis in the adjacent stratum intermedium and the abnormal cell-cell contacts and cell-matrix adhesion of MA may contribute to this aberrant behavior. The mutant MA also exhibited severely diminished tissue non-specific alkaline phosphatase activity, revealing that this enzyme’s activity in MA crucially depends on BMP2 and BMP4 inputs. Our findings show that combined BMP2 and BMP4 signaling is crucial for survival of the stratum intermedium and for proper development and function of MA to ensure normal enamel maturation.
NLRP3 Inflammasome Negatively Regulates RANKL-Induced Osteoclastogenesis of Mouse Bone Marrow Macrophages but Positively Regulates It in the Presence of Lipopolysaccharides
Authors: Alam Mohammad Ibtehaz , Mae Megumi , Farhana Fatima , Oohira Masayuki , Yamashita Yasunori , Ozaki Yukio , Sakai Eiko , Yoshimura Atsutoshi
Published: May 2022

In inflammatory bone diseases such as periodontitis, the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome accelerates bone resorption by promoting proinflammatory cytokine IL-1β production. However, the role of the NLRP3 inflammasome in physiological bone remodeling remains unclear. Here, we investigated its role in osteoclastogenesis in the presence and absence of lipopolysaccharide (LPS), a Gram-negative bacterial component. When bone marrow macrophages (BMMs) were treated with receptor activator of nuclear factor-κB ligand (RANKL) in the presence of NLRP3 inflammasome inhibitors, osteoclast formation was promoted in the absence of LPS but attenuated in its presence. BMMs treated with RANKL and LPS produced IL-1β, and IL-1 receptor antagonist inhibited osteoclastogenesis, indicating IL-1β involvement. BMMs treated with RANKL alone produced no IL-1β but increased reactive oxygen species (ROS) production. A ROS inhibitor suppressed apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) speck formation and NLRP3 inflammasome inhibitors abrogated cytotoxicity in BMMs treated with RANKL, indicating that RANKL induces pyroptotic cell death in BMMs by activating the NLRP3 inflammasome via ROS. This suggests that the NLRP3 inflammasome promotes osteoclastogenesis via IL-1β production under infectious conditions, but suppresses osteoclastogenesis by inducing pyroptosis in osteoclast precursors under physiological conditions.
Prebiotics as a Tool for the Prevention and Treatment of Obesity and Diabetes: Classification and Ability to Modulate the Gut Microbiota
Authors: Megur Ashwinipriyadarshini , Daliri Eric Banan-Mwine , Baltriukienė Daiva , Burokas Aurelijus
Published: May 2022

Diabetes and obesity are metabolic diseases that have become alarming conditions in recent decades. Their rate of increase is becoming a growing concern worldwide. Recent studies have established that the composition and dysfunction of the gut microbiota are associated with the development of diabetes. For this reason, strategies such as the use of prebiotics to improve intestinal microbial structure and function have become popular. Consumption of prebiotics for modulating the gut microbiota results in the production of microbial metabolites such as short-chain fatty acids that play essential roles in reducing blood glucose levels, mitigating insulin resistance, reducing inflammation, and promoting the secretion of glucagon-like peptide 1 in the host, and this accounts for the observed remission of metabolic diseases. Prebiotics can be either naturally extracted from non-digestible carbohydrate materials or synthetically produced. In this review, we discussed current findings on how the gut microbiota and microbial metabolites may influence host metabolism to promote health. We provided evidence from various studies that show the ability of prebiotic consumption to alter gut microbial profile, improve gut microbial metabolism and functions, and improve host physiology to alleviate diabetes and obesity. We conclude among other things that the application of systems biology coupled with bioinformatics could be essential in ascertaining the exact mechanisms behind the prebiotic–gut microbe–host interactions required for diabetes and obesity improvement.
Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease?
Authors: Hindle Ashly , Singh Sharda P. , Pradeepkiran Jangampalli Adi , Bose Chhanda , Vijayan Murali , Kshirsagar Sudhir , Sawant Neha A. , Reddy P. Hemachandra
Published: May 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia in older people. AD is associated with the loss of synapses, oxidative stress, mitochondrial structural and functional abnormalities, microRNA deregulation, inflammatory responses, neuronal loss, accumulation of amyloid-beta (Aβ) and phosphorylated tau (p-tau). AD occurs in two forms: early onset, familial AD and late-onset, sporadic AD. Causal factors are still unknown for a vast majority of AD patients. Genetic polymorphisms are proposed to contribute to late-onset AD via age-dependent increases in oxidative stress and mitochondrial abnormalities. Recent research from our lab revealed that reduced levels of Rlip76 induce oxidative stress, mitochondrial dysfunction and synaptic damage, leading to molecular and behavioral phenotypes resembling late-onset AD. Rlip76 is a multifunctional 76 kDa protein encoded by the RALBP1 gene, located on chromosome 18. Rlip is a stress-protective ATPase of the mercapturic acid pathway that couples clathrin-dependent endocytosis with the efflux of glutathione–electrophile conjugates. Rlip is evolutionarily highly conserved across species and is ubiquitously expressed in all tissues, including AD-affected brain regions, the cerebral cortex and hippocampus, where highly active neuronal metabolisms render the cells highly susceptible to intracellular oxidative damage. In the current article, we summarize molecular and cellular features of Rlip and how depleted Rlip may exacerbate oxidative stress, mitochondrial dysfunction and synaptic damage in AD. We also discuss the possible role of Rlip in aspects of learning and memory via axonal growth, dendritic remodeling, and receptor regulation. We conclude with a discussion of the potential for the contribution of genetic polymorphisms in Rlip to AD progression and the potential for Rlip-based therapies.
In Vitro Monitoring of Magnesium-Based Implants Degradation by Surface Analysis and Optical Spectroscopy
Authors: Hassan Hafiz Wajahat , Rahmati Maryam , Barrantes Alejandro , Haugen Håvard Jostein , Mirtaheri Peyman
Published: May 2022

Magnesium (Mg)-based degradable alloys have attracted substantial attention for tissue engineering applications due to their biodegradability and potential for avoiding secondary removal surgeries. However, insufficient data in the existing literature regarding Mg’s corrosion and gas formation after implantation have delayed its wide clinical application. Since the surface properties of degradable materials constantly change after contact with body fluid, monitoring the behaviour of Mg in phantoms or buffer solutions could provide some information about its physicochemical surface changes over time. Through surface analysis and spectroscopic analysis, we aimed to investigate the structural and functional properties of degradable disks. Since bubble formation may lead to inflammation and change pH, monitoring components related to acidosis near the cells is essential. To study the bubble formation in cell culture media, we used a newly developed Mg alloy (based on Mg, zinc, and calcium), pure Mg, and commercially available grade 2 Titanium (Ti) disks in Dulbecco’s Modified Eagle Medium (DMEM) solution to observe their behaviour over ten days of immersion. Using surface analysis and the information from near-infrared spectroscopy (NIRS), we concluded on the conditions associated with the medical risks of Mg alloy disintegration. NIRS is used to investigate the degradation behaviour of Mg-based disks in the cell culture media, which is correlated with the surface analysis where possible.
Iron Mobilization from Ferritin in Yeast Cell Lysate and Physiological Implications
Authors: Smith Gideon L. , Srivastava Ayush K. , Reutovich Aliaksandra A. , Hunter Nathan J. , Arosio Paolo , Melman Artem , Bou-Abdallah Fadi
Published: May 2022

Most in vitro iron mobilization studies from ferritin have been performed in aqueous buffered solutions using a variety of reducing substances. The kinetics of iron mobilization from ferritin in a medium that resembles the complex milieu of cells could dramatically differ from those in aqueous solutions, and to our knowledge, no such studies have been performed. Here, we have studied the kinetics of iron release from ferritin in fresh yeast cell lysates and examined the effect of cellular metabolites on this process. Our results show that iron release from ferritin in buffer is extremely slow compared to cell lysate under identical experimental conditions, suggesting that certain cellular metabolites present in yeast cell lysate facilitate the reductive release of ferric iron from the ferritin core. Using filtration membranes with different molecular weight cut-offs (3, 10, 30, 50, and 100 kDa), we demonstrate that a cellular component >50 kDa is implicated in the reductive release of iron. When the cell lysate was washed three times with buffer, or when NADPH was omitted from the solution, a dramatic decrease in iron mobilization rates was observed. The addition of physiological concentrations of free flavins, such as FMN, FAD, and riboflavin showed about a two-fold increase in the amount of released iron. Notably, all iron release kinetics occurred while the solution oxygen level was still high. Altogether, our results indicate that in addition to ferritin proteolysis, there exists an auxiliary iron reductive mechanism that involves long-range electron transfer reactions facilitated by the ferritin shell. The physiological implications of such iron reductive mechanisms are discussed.
Differential Inflammatory Responses in Cultured Endothelial Cells Exposed to Two Conjugated Linoleic Acids (CLAs) under a Pro-Inflammatory Condition
Authors: Valenzuela Carina A. , Baker Ella J. , Miles Elizabeth A. , Calder Philip C.
Published: May 2022

Conjugated linoleic acid (CLA) isomers have been shown to possess anti-atherosclerotic properties, which may be related to the downregulation of inflammatory pathways in different cell types, including endothelial cells (ECs). However, whether different CLA isomers have different actions is not entirely clear, with inconsistent reports to date. Furthermore, in cell culture studies, CLAs have often been used at fairly high concentrations. Whether lower concentrations of CLAs are able to affect EC responses is not clear. The aim of this study was to evaluate the effects of two CLAs (cis-9, trans-11 (CLA9,11) and trans-10, cis-12 (CLA10,12)) on the inflammatory responses of ECs. ECs (EA.hy926 cells) were cultured under standard conditions and exposed to CLAs (1 to 50 μM) for 48 h. Then, the cells were cultured for a further 6 or 24 h with tumour necrosis factor alpha (TNF-α, 1 ng/mL) as an inflammatory stimulant. ECs remained viable after treatments with 1 and 10 μM of each CLA, but not after treatment with 50 μM of CLA10,12. CLAs were incorporated into ECs in a concentration-dependent manner. CLA10,12 increased the levels of ICAM-1, IL-6, and RANTES in the culture medium, while CLA9,11 had null effects. Both CLAs (1 μM) decreased the appearance of NFκB1 mRNA, but only CLA9,11 maintained this downregulation at 10 μM. CLA10,12 had no effect on THP-1 cell adhesion to ECs while significantly decreasing the percentage of ECs expressing ICAM-1 and also levels of ICAM-1 expression per cell when used at 10 µM. Although CLA9,11 did not have any effect on ICAM-1 cell surface expression, it reduced THP-1 cell adhesion to the EA.hy926 cell monolayer at both concentrations. In summary, CLA10,12 showed some pro-inflammatory effects, while CLA9,11 exhibited null or anti-inflammatory effects. The results suggest that each CLA has different effects in ECs under a pro-inflammatory condition, highlighting the need to evaluate the effects of CLA isomers independently.
Enhanced Extracellular Transfer of HLA-DQ Activates CD3+ Lymphocytes towards Compromised Treg Induction in Celiac Disease
Authors: Hudec Michael , Juříčková Iva , Riegerová Kamila , Ovsepian Saak V. , Černá Marie , O’Leary Valerie Bríd
Published: May 2022

Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) on T lymphocytes. This fundamental mechanism of adaptive immunity has broadened upon recognition of extracellular exosomal MHC, raising awareness of an alternative means for antigen presentation. This study demonstrates that conditioned growth media (CGM) previously exposed to monocyte-derived dendritic cells from CeD significantly downregulates the CD3+ lineage marker of control T cells. Such increased activation was reflected in their elevated IL-2 secretion. Exosome localization motif identification and quantification within HLA-DQA1 and HLA-DQB1 transcripts highlighted their significant prevalence within HLA-DQB1 alleles associated with CeD susceptibility. Flow cytometry revealed the strong correlation between HLA-DQ and the CD63 exosomal marker in T cells exposed to CGM from MoDCs sourced from CeD patients. This resulted in lower concentrations of CD25+ CD127− T cells, suggestive of their compromised induction to T-regulatory cells associated with CeD homeostasis. This foremost comparative study deciphered the genomic basis and extracellular exosomal effects of HLA transfer on T lymphocytes in the context of CeD, offering greater insight into this auto-immune disease.
Picrasidine I Triggers Heme Oxygenase-1-Induced Apoptosis in Nasopharyngeal Carcinoma Cells via ERK and Akt Signaling Pathways
Authors: Ho Hsin-Yu , Chen Ping-Ju , Chuang Yi-Ching , Lo Yu-Sheng , Lin Chia-Chieh , Hsieh Ming-Ju , Chen Mu-Kuan
Published: May 2022

Nasopharyngeal carcinoma (NPC) has a higher incidence in Taiwan than worldwide. Although it is a radiosensitive malignancy, cancer recurrence is still high in the advanced stages because of its ability to induce lymph node metastasis. Picrasidine I from Picrasma quassioides has been reported as a potential drug for targeting multiple signaling pathways. The present study aimed to explore the role of picrasidine I in the apoptosis of NPC cells. Our results show that picrasidine I induced cytotoxic effects in NPC cells and caused cell cycle arrest in the sub-G1, S, and G2/M phases. Western blot analysis further demonstrated that the modulation of apoptosis through the extrinsic and intrinsic pathways was involved in picrasidine I-induced cell death. Downregulation of the ERK1/2 and Akt signaling pathways was also found in picrasidine I-induced apoptosis. Additionally, the apoptosis array showed that picrasidine I significantly increased heme oxygenase-1 (HO-1) expression, which could act as a critical molecule in picrasidine I-induced apoptosis in NPC cells. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets also revealed that the HMOX1 mRNA level (HO-1) is lower in patients with head and neck squamous carcinoma (HNSCC) and NPC than in patients without cancer. Our study indicated that picrasidine I exerts anticancer effects in NPC by modulating HO-1 via the ERK and Akt signaling pathways.
Sophoraflavanone G from Sophora flavescens Ameliorates Allergic Airway Inflammation by Suppressing Th2 Response and Oxidative Stress in a Murine Asthma Model
Authors: Wang Meng-Chun , Huang Wen-Chung , Chen Li-Chen , Yeh Kuo-Wei , Lin Chwan-Fwu , Liou Chian-Jiun
Published: May 2022

Sophoraflavanone G (SG), isolated from Sophora flavescens, has anti-inflammatory and anti-tumor bioactive properties. We previously showed that SG promotes apoptosis in human breast cancer cells and leukemia cells and reduces the inflammatory response in lipopolysaccharide-stimulated macrophages. We investigated whether SG attenuates airway hyper-responsiveness (AHR) and airway inflammation in asthmatic mice. We also assessed its effects on the anti-inflammatory response in human tracheal epithelial cells. Female BALB/c mice were sensitized with ovalbumin, and asthmatic mice were treated with SG by intraperitoneal injection. We also exposed human bronchial epithelial BEAS-2B cells to different concentrations of SG to evaluate its effects on inflammatory cytokine levels. SG treatment significantly reduced AHR, eosinophil infiltration, goblet cell hyperplasia, and airway inflammation in the lungs of asthmatic mice. In the lungs of ovalbumin-sensitized mice, SG significantly promoted superoxide dismutase and glutathione expression and attenuated malondialdehyde levels. SG also suppressed levels of Th2 cytokines and chemokines in lung and bronchoalveolar lavage samples. In addition, we confirmed that SG decreased pro-inflammatory cytokine, chemokine, and eotaxin expression in inflammatory BEAS-2B cells. Taken together, our data demonstrate that SG shows potential as an immunomodulator that can improve asthma symptoms by decreasing airway-inflammation-related oxidative stress.
Efficient Edge-AI Application Deployment for FPGAs
Authors: Kalapothas Stavros , Flamis Georgios , Kitsos Paris
Published: May 2022

Field Programmable Gate Array (FPGA) accelerators have been widely adopted for artificial intelligence (AI) applications on edge devices (Edge-AI) utilizing Deep Neural Networks (DNN) architectures. FPGAs have gained their reputation due to the greater energy efficiency and high parallelism than microcontrollers (MCU) and graphical processing units (GPU), while they are easier to develop and more reconfigurable than the Application Specific Integrated Circuit (ASIC). The development and building of AI applications on resource constraint devices such as FPGAs remains a challenge, however, due to the co-design approach, which requires a valuable expertise in low-level hardware design and in software development. This paper explores the efficacy and the dynamic deployment of hardware accelerated applications on the Kria KV260 development platform based on the Xilinx Kria K26 system-on-module (SoM), which includes a Zynq multiprocessor system-on-chip (MPSoC). The platform supports the Python-based PYNQ framework and maintains a high level of versatility with the support of custom bitstreams (overlays). The demonstration proved the reconfigurabibilty and the overall ease of implementation with low-footprint machine learning (ML) algorithms.
Evaluation of Selected Plant Volatiles as Attractants for the Stick Tea Thrip Dendrothrips minowai in the Laboratory and Tea Plantation
Authors: Xiu Chunli , Zhang Fengge , Pan Hongsheng , Bian Lei , Luo Zongxiu , Li Zhaoqun , Fu Nanxia , Cai Xiaoming , Chen Zongmao
Published: May 2022

The stick tea thrip (Dendrothrips minowai Priesner) is the main pest thrip in tea (Camellia sinensis) plantations in China, and seriously affects the quality and yield of tea. Plant-derived semiochemicals provide an alternative to pheromones as lures and these compounds possess powerful attractiveness. In this study, we selected 20 non-pheromone semiochemicals, including compounds that have been reported to attract other thrips and some volatiles emitted from tea plants as the potential attractant components for D. minowai. In electroantennogram (EAG) assays, 10 synthetic compounds (p-anisaldehyde, 3-methyl butanal, (E)-β-ocimene, farnesene, nonanal, eugenol, (+)-α-pinene, limonene, (−)-α-pinene, and γ-terpinene) elicited significant antennal responses in female D. minowai. In addition, a two-choice H-tube olfactometer bioassay showed that D. minowai displayed significant positive responses to eight compound dilutions (p-anisaldehyde, eugenol, farnesene, methyl benzoate, 3-methyl butanal, (E)-β-ocimene, (−)-α-pinene, and (+)-α-pinene) when compared with the solvent control at both 1 and 2 h. Moreover, γ-terpinene exhibited a significantly deterrent effect on D. minowai. Finally, trap catches of four compounds (p-anisaldehyde, eugenol, farnesene, and 3-methyl butanal, respectively) significantly increase in tea plantations. Among these, the maximum number of D. minowai collected by blue sticky traps baited with p-anisaldehyde was 7.7 times higher than the control. In conclusion, p-anisaldehyde, eugenol, farnesene, and 3-methyl butanal could significantly attract D. minowai in the laboratory and under field conditions, suggesting considerable potential as commercial attractants to control D. minowai populations.
Changes in the Chemical Composition of Edible Grasshoppers (Sphenarium purpurascens) Fed Exclusively with Soy Sprouts or Maize Leaves
Authors: Reyes-Herrera Alicia , Pérez-Carrillo Esther , Amador-Espejo Genaro , Valdivia-Nájar Guillermo , Ibarra-Herrera Celeste C.
Published: May 2022

In recent times, insects have gained attention because of their nutritional characteristics as well as the environmental advantages of their production. In this research, the effect of the diet of grasshoppers (Sphenarium purpurascens) under controlled conditions on their chemical and nutritional content was studied. The insects were divided into two groups: maize leaf-fed grasshoppers (MFG) and soy sprout-fed grasshoppers (SFG). To evaluate the changes in composition, chemical analysis (protein, fiber, fat, ashes, and chitin) was carried out in triplicate according to AOAC procedures, and a Student’s t-test was used to determine any significant differences. The results showed a higher content of crude protein, in vitro protein digestibility percentage, and sum of non-essential amino acids (NEAAs) in the MFG samples compared with the SFG samples. The total dietary fiber, insoluble dietary fiber, soluble dietary fiber, sum of the EAA, non-essential amino acid percentage (EAA%), and biological value percentage (BV%) were higher in the SFG than the MFG, while in the amino acid profile and chitin content, no significant differences were obtained, although an increase in oleic acid in the SFG was observed. In FTIR, a β-sheet appeared in the SFG, which could be related to the low in vitro protein digestibility. The use of a soy sprout diet caused changes in the chemical composition and nutritional content of grasshoppers. This represents an opportunity to improve their nutritional value for commercial interests.
Feeding Behavior of Riptortus pedestris (Fabricius) on Soybean: Electrical Penetration Graph Analysis and Histological Investigations
Authors: Jin Yan , Zhang Wendan , Dong Yumei , Xia Ai
Published: May 2022

Riptortus pedestris (Fabricius) is a major agricultural pest feeding on soybean pods and seeds. The large populations occur during seed maturity stages from pod filling to harvest. Its infestation results in shriveled and dimpled seeds while vegetative structures (leaflet and stem) remain green, known as “Stay Green” syndrome. Additional evidence also demonstrates that soybean pods and seeds are required for Riptortus pedestris development. However, the feeding behavior strategies employed by this stink bug to feed on soybean plants are still not clear. In the present study, the feeding behaviors of R. pedestris on soybean plants were recorded by electropenetrography (EPG), and a waveform library was created for this species. A total of five phases of waveforms—nonprobing, pathway (Rp1), xylem sap ingestion (Rp2), salivation and ingestion (Rp3), and interruption (Rp4)—were identified. Non-probing waveforms Z and NP and pathway (Rp1) were found in all tested plant structures (leaflet, stem, cotyledon, and pods). Waveform Rp2 (xylem sap ingestion, xylem ingestion) was primarily recorded during R. pedestris feeding on leaflets and stems, while Rp3 (salivation/ingestion) was only observed during feeding on cotyledon and pods. Histological examinations confirmed that correlation between Rp2 and stylet tip positioning in the xylem vessel in leaflets and stems. Stylet tips end in the tissues of cotyledon and pods when Rp3 is recorded. Taken together, our results demonstrate that R. pedestris ingests xylem sap from vegetative tissues of soybean (leaflet and stem) via a salivary sheath strategy to obtain water. It mainly acquires nutrients from soybean pods and/or seeds using cell-rupture tactics. This study provided insightful information to understand the field occurrence patterns of “Stay Green” syndrome, which may have important implications for pest control.
Group-Based Physical Activity Interventions Targeting Enjoyment in Older Adults: A Systematic Review
Authors: Creighton Rachel M. , Paradis Kyle F. , Blackburn Nicole E. , Tully Mark A.
Published: May 2022

In previous research, older adults reported they preferred enjoyable exercise programmes. The aim of this systematic review is to identify the components of enjoyable group-based physical activity interventions for older adults. Eleven electronic databases were searched in May 2021. Inclusion criteria were: Community-dwelling, ≥60 years of age, group-based physical activity, controlled intervention studies, designed to promote enjoyment, and included a measure of enjoyment or physical activity. Characteristics of the studies, intervention content, and enjoyment outcomes were extracted. Six studies, involving 1205 participants (Mean = 72.9 years old, 71.3% female, 67% European countries) were included. While enjoyment outcomes (n = 3) appeared to improve, there was wide heterogeneity in measurement tools, making it difficult to compare studies. Enjoyable group-based physical activity for older adults may consist of a supportive instructor and peers, creating a shared positive experience. Components included confidence building through competence, and courage experienced in the company of others. Within a physically supportive environment, older adults have the potential to generate social support to enjoy being physically active together. Future studies should include measures of enjoyment and device-based physical activity. Furthermore, a standardised definition of enjoyable physical activity for older adults is needed to inform the design of future interventions.
Perioperative Fluoroquinolone Treatment Deteriorates Prognosis Following Coronary Artery Bypass Grafting
Authors: Zhang Min , Jian Lijuan , Min Xinping , Li Bowen , Cai Xin , Wang Zhiwei , Hu Zhipeng
Published: May 2022

Background: Former studies have revealed that fluoroquinolone (FQ) can induce aortic expansion and rupture. While FQ is widely used in perioperative anti-infection therapy, its impact on graft patency and patient survival is unknown. Methods: Coronary artery bypass grafting (CABG) data were extracted from the MIMIC-III database. Chi-square tests, Fisher’s exact tests, t-tests, or ANOVAs were used to compare baseline data between groups determined by FQ therapy status, depending on the data type. Propensity score matching was used to establish a balanced cohort. Cox regression was used to investigate the impact of FQ on CABG patient survival, whereas paired t-tests were used to analyze secondary results. Results: Of the 5030 patients who underwent CABG, 937 (18.6%) received oral or intravenous FQ therapy. Using propensity score matching, these 819 patients were successfully matched with 819 controls in a 1:1 ratio. Cox regression showed that FQ significantly decreased survival among CABG patients (HR: 1.62, 95% CI: 1.21–2.15, p = 0.001). Furthermore, FQ usage was associated with longer hospitalization (<0.0001), ICU duration (<0.0001), ventilation period (<0.0001), and duration of vasopressor administration (<0.0001). Conclusions: Perioperative FQ therapy was associated with worse prognosis and a more difficult recovery among patients with CABG.