bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Silicone Enclosure Colour on the Function of Optical Sensors
Authors: Frank Garrett , Askari Shahbaz , Raschdorf Katharina , Khosravi Sadra , Kwon Brian K. , Shadgan Babak
Published: June 2022

The colour of the silicone enclosure of an implantable reflectance-based optical probe plays a critical role in sensor performance. Red-coloured probes that are highly reflective to near-infrared light have been found to increase photodetector power by a factor of 6 for wavelengths between 660 and 950 nm and triple the magnitude of measured cardiac pulsations compared to traditional black probes. The increase in photodetector power and cardiac pulsation magnitude is presumably due to increased spatial range resulting from a higher magnitude of superficial tissue scattering. Conversely, probes with highly absorbent colours such as black and blue result in more stable signals and are expected to have higher spatial resolution and depth of penetration.
Detecting Local Adaptation between North and South European Atlantic Salmon Populations
Authors: Gabián María , Morán Paloma , Saura María , Carvajal-Rodríguez Antonio
Published: June 2022

Pollution and other anthropogenic effects have driven a decrease in Atlantic salmon (Salmo salar) in the Iberian Peninsula. The restocking effort carried out in the 1980s, with salmon from northern latitudes with the aim of mitigating the decline of native populations, failed, probably due to the deficiency in adaptation of foreign salmon from northern Europe to the warm waters of the Iberian Peninsula. This result would imply that the Iberian populations of Atlantic salmon have experienced local adaptation in their past evolutionary history, as has been described for other populations of this species and other salmonids. Local adaptation can occur by divergent selections between environments, favoring the fixation of alleles that increase the fitness of a population in the environment it inhabits relative to other alleles favored in another population. In this work, we compared the genomes of different populations from the Iberian Peninsula (Atlantic and Cantabric basins) and Scotland in order to provide tentative evidence of candidate SNPs responsible for the adaptive differences between populations, which may explain the failures of restocking carried out during the 1980s. For this purpose, the samples were genotyped with a 220,000 high-density SNP array (Affymetrix) specific to Atlantic salmon. Our results revealed potential evidence of local adaptation for North Spanish and Scottish populations. As expected, most differences concerned the comparison of the Iberian Peninsula with Scotland, although there were also differences between Atlantic and Cantabric populations. A high proportion of the genes identified are related to development and cellular metabolism, DNA transcription and anatomical structure. A particular SNP was identified within the NADP-dependent malic enzyme-2 (mMEP-2*), previously reported by independent studies as a candidate for local adaptation in salmon from the Iberian Peninsula. Interestingly, the corresponding SNP within the mMEP-2* region was consistent with a genomic pattern of divergent selection.
Anguillid Eels as a Model Species for Understanding Endocrinological Influences on the Onset of Spawning Migration of Fishes
Authors: Sudo Ryusuke , Yada Takashi
Published: June 2022

Anguillid eels are the iconic example of catadromous fishes, because of their long-distance offshore spawning migrations. They are also a good model for research on the onset mechanisms of migrations to breeding areas, because the migrations begin in inland waters. When eels transform from yellow eels to silver eels, it is called silvering. Silver eels show various synchronous external and internal changes during silvering, that include coloration changes, eye-size increases, and gonadal development, which appear to be pre-adaptations to the oceanic environment and for reproductive maturation. A strong gonadotropic axis activation occurs during silvering, whereas somatotropic and thyrotropic axes are not activated. Among various hormones, 11-ketotestosterone (11-KT) drastically increases during spawning migration onset. Gradual water temperature decreases simulating the autumn migratory season, inducing 11-KT increases. Administration of 11-KT appeared to cause changes related to silvering, such as early-stage oocyte growth and eye enlargement. Moreover, 11-KT may be an endogenous factor that elevates the migratory drive needed for the spawning migration onset. These findings suggested that water temperature decreases cause 11-KT to increase in autumn and this induces silvering and increases migratory drive. In addition, we newly report that 11-KT is associated with a corticotropin-releasing hormone that influences migratory behavior of salmonids. This evidence that 11-KT might be among the most important factors in the spawning migration onset of anguillid eels can help provide useful knowledge for understanding endocrinological mechanisms of the initiation of spawning migrations.
Oxidative Stress Biomarkers and Quality of Life Are Contributing Factors of Muscle Pain and Lean Body Mass in Patients with Fibromyalgia
Authors: dos Santos Jousielle Márcia , Rodrigues Lacerda Ana Cristina , Ribeiro Vanessa Gonçalves César , Scheidt Figueiredo Pedro Henrique , Fonseca Sueli Ferreira , da Silva Lage Vanessa Kelly , Costa Henrique Silveira , Pereira Lima Vanessa , Sañudo Borja , Bernardo-Filho Mário , da Cunha de Sá Caputo Danúbia , Mendonça Vanessa Amaral , Taiar Redha
Published: June 2022

(1) The evidence points to an increase in oxygen reactive species as one of the possible causes of fibromyalgia (FM). In addition, it is plausible that an imbalance in redox markers can be associated with pain amplification and dynapenia in FM patients. The aim of our study was to investigate possible factors associated with muscle pain and lean body mass in FM patients. (2) Methods: This was a quantitative, exploratory and cross-sectional study of 47 patients with FM (53.45 + 7.32 years). We evaluated self-perceptions of muscle pain, lean body mass, body composition, quality of life, sleep quality, depression index, muscle performance and oxidative stress biomarkers. (3) Results: We observed that lower blood levels of antioxidants and poor quality of life explained 21% of the greater muscle pain. In addition, high blood levels of oxidative stress, worse muscle performance and poor quality of life explained 27% of the lower lean mass in patients with FM. (4) Conclusions: Larger amounts of lipid peroxidation and reductions in antioxidant levels, in addition to lower muscle performance and poor life quality, are possible independent contributors to greater muscle pain and lower lean body mass in FM patients.
In Vitro Model of Human Skeletal Muscle Tissue for the Study of Resident Macrophages and Stem Cells
Authors: Hao Dandan , Becker Nils , Mückter Eva , Müller Aline , Pishnamaz Miguel , Bollheimer Leo Cornelis , Hildebrand Frank , Nourbakhsh Mahtab
Published: June 2022

Findings from studies of muscle regeneration can significantly contribute to the treatment of age-related loss of skeletal muscle mass, which may predispose older adults to severe morbidities. We established a human experimental model using excised skeletal muscle tissues from reconstructive surgeries in eight older adults. Muscle samples from each participant were preserved immediately or maintained in agarose medium for the following 5, 9, or 11 days. Immunofluorescence analyses of the structural proteins, actin and desmin, confirmed the integrity of muscle fibers over 11 days of maintenance. Similarly, the numbers of CD80-positive M1 and CD163-positive M2 macrophages were stable over 11 days in vitro. However, the numbers of PAX7-positive satellite cells and MYOD-positive myoblasts changed in opposite ways, suggesting that satellite cells partially differentiated in vitro. Further experiments revealed that stimulation with unsaturated fatty acid C18[2]c (linoleic acid) increased resident M1 macrophages and satellite cells specifically. Thus, the use of human skeletal muscle tissue in vitro provides a direct experimental approach to study the regulation of muscle tissue regeneration by macrophages and stem cells and their responses to therapeutic compounds.
Radiation-Induced Bystander Effect and Cytoplasmic Irradiation Studies with Microbeams
Authors: Zhang Ziqi , Li Kui , Hong Mei
Published: June 2022

Although direct damage to nuclear DNA is considered as the major contributing event that leads to radiation-induced effects, accumulating evidence in the past two decades has shown that non-target events, in which cells are not directly irradiated but receive signals from the irradiated cells, or cells irradiated at extranuclear targets, may also contribute to the biological consequences of exposure to ionizing radiation. With a beam diameter at the micrometer or sub-micrometer level, microbeams can precisely deliver radiation, without damaging the surrounding area, or deposit the radiation energy at specific sub-cellular locations within a cell. Such unique features cannot be achieved by other kinds of radiation settings, hence making a microbeam irradiator useful in studies of a radiation-induced bystander effect (RIBE) and cytoplasmic irradiation. Here, studies on RIBE and different responses to cytoplasmic irradiation using microbeams are summarized. Possible mechanisms related to the bystander effect, which include gap-junction intercellular communications and soluble signal molecules as well as factors involved in cytoplasmic irradiation-induced events, are also discussed.
Comparison between the Impacts of Memory and Arithmetic-Based Dual Tasks on Physical Performance in Women with Fibromyalgia
Authors: Sánchez-Gómez Jesús , Villafaina Santos , Domínguez-Muñoz Francisco Javier , Leon-Llamas Juan Luis , Murillo-Garcia Alvaro , Gusi Narcis
Published: June 2022

Background: Fibromyalgia symptoms have a significant impact on the ability to perform activities of daily living. These activities require the ability to perform two or more tasks at the same time, which is known as a dual task. Purpose: To analyze physical and cognitive performance differences between memory and arithmetic dual tasks. Methods: Twenty-five women with fibromyalgia participated in this study. Participants performed three physical tests (back scratch, arm curl, and 10-step stair) as a single task and under two types of dual task (memory and arithmetic). Results: Differences between the single and dual tasks were observed in the back scratch and the 10-step stair tests using the arithmetic dual-task. Significant differences were only observed for the memory dual-task in the 10-step stair test. In addition, the performance in the back scratch and in the 10-step stair was significantly lower under the arithmetic compared to the memory-based dual task. Furthermore, a significant difference between these two types of dual task was obtained in the dual-task cost of 10-step stair. Regarding cognitive performance, a significantly lower percentage of correct responses was found in the AbDT compared to the MbDT in the 10-step stair test. Conclusions: the AbDT could have a higher impact on physical performance than the MbDT during the back scratch and the 10-step stair tests. The characteristics of the sample, environment, complexity of the motor task, and difficulty of the simultaneous cognitive task may also be relevant for understanding the differences in dual-task interference.
Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding
Authors: Ruan Lu-Yu , Lai Zhen-Zhen , Shi Jia-Wei , Yang Hui-Li , Ye Jiang-Feng , Xie Feng , Qiu Xue-Min , Zhu Xiao-Yong , Li Ming-Qing
Published: June 2022

In patients, endometrial hyperplasia (EH) is often accompanied by abnormal uterine bleeding (AUB), which is prone to release large amounts of heme. However, the role of excess heme in the migration and infiltration of immune cells in EH complicated by AUB remains unknown. In this study, 45 patients with AUB were divided into three groups: a proliferative phase group (n = 15), a secretory phase group (n = 15) and EH (n = 15). We observed that immune cell subpopulations were significantly different among the three groups, as demonstrated by flow cytometry analysis. Of note, there was a higher infiltration of total immune cells and macrophages in the endometrium of patients with EH. Heme up-regulated the expression of heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2) in endometrial epithelial cells (EECs) in vitro, as well as chemokine (e.g., CCL2, CCL3, CCL5, CXCL8) levels. Additionally, stimulation with heme led to the increased recruitment of THP-1 cells in an indirect EEC-THP-1 co-culture unit. These data suggest that sustained and excessive heme in patients with AUB may recruit macrophages by increasing the levels of several chemokines, contributing to the accumulation and infiltration of macrophages in the endometrium of EH patients, and the key molecules of heme metabolism, HO-1 and Nrf2, are also involved in this regulatory process.
Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells
Authors: Luo Shahang , Yang Guanghui , Ye Peng , Cao Nengqi , Chi Xiaoxia , Yang Wen-Hao , Yan Xiuwen
Published: June 2022

Cancer stem cells (CSCs) are a subset of highly tumorigenic cells in tumors. They have enhanced self-renewal properties, are usually chemo-radioresistant, and can promote tumor recurrence and metastasis. They can recruit macrophages into the tumor microenvironment and differentiate them into tumor-associated macrophages (TAMs). TAMs maintain CSC stemness and construct niches that are favorable for CSC survival. However, how CSCs and TAMs interact is not completely understood. An understanding on these mechanisms can provide additional targeting strategies for eliminating CSCs. In this review, we comprehensively summarize the reported mechanisms of crosstalk between CSCs and TAMs and update the related signaling pathways involved in tumor progression. In addition, we discuss potential therapies targeting CSC–TAM interaction, including targeting macrophage recruitment and polarization by CSCs and inhibiting the TAM-induced promotion of CSC stemness. This review also provides the perspective on the major challenge for developing potential therapeutic strategies to overcome CSC-TAM crosstalk.
Neuroprotective Effects of Pharmacological Hypothermia on Hyperglycolysis and Gluconeogenesis in Rats after Ischemic Stroke
Authors: Guan Longfei , Lee Hangil , Geng Xiaokun , Li Fengwu , Shen Jiamei , Ji Yu , Peng Changya , Du Huishan , Ding Yuchuan
Published: June 2022

Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential neuroprotective strategy for stroke, in which the temperature is decreased safely. The present study determined whether neuroprotective PH with chlorpromazine and promethazine (C + P), plus dihydrocapsaicin (DHC) improved glucose metabolism in acute ischemic stroke. A total of 208 adult male Sprague Dawley rats were randomly divided into the following groups: sham, stroke, and stroke with various treatments including C + P, DHC, C + P + DHC, phloretin (glucose transporter (GLUT)-1 inhibitor), cytochalasin B (GLUT-3 inhibitor), TZD (thiazolidinedione, phosphoenolpyruvate carboxykinase (PCK) inhibitor), and apocynin (nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor). Stroke was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 6 or 24 h of reperfusion. Rectal temperature was monitored before, during, and after PH. Infarct volume and neurological deficits were measured to assess the neuroprotective effects. Reactive oxygen species (ROS), NOX activity, lactate, apoptotic cell death, glucose, and ATP levels were measured. Protein expression of GLUT-1, GLUT-3, phosphofructokinase (PFK), lactate dehydrogenase (LDH), PCK1, PCK2, and NOX subunit gp91 was measured with Western blotting. PH with a combination of C + P and DHC induced faster, longer, and deeper hypothermia, as compared to each alone. PH significantly improved every measured outcome as compared to stroke and monotherapy. PH reduced brain infarction, neurological deficits, protein levels of glycolytic enzymes (GLUT-1, GLUT-3, PFK and LDH), gluconeogenic enzymes (PCK1 and PCK2), NOX activity and its subunit gp91, ROS, apoptotic cell death, glucose, and lactate, while raising ATP levels. In conclusion, stroke impaired glucose metabolism by enhancing hyperglycolysis and gluconeogenesis, which led to ischemic injury, all of which were reversed by PH induced by a combination of C + P and DHC.
Bioinformatic Analysis Predicts a Novel Genetic Module Related to Triple Gene and Binary Movement Blocks of Plant Viruses: Tetra-Cistron Movement Block
Authors: Morozov Sergey Y. , Solovyev Andrey G.
Published: June 2022

Previous studies have shown that the RNA genomes of some plant viruses encode two related genetic modules required for virus movement over the host body, containing two or three genes and named the binary movement block (BMB) and triple gene block (TGB), respectively. In this paper, we predict a novel putative-related movement gene module, called the tetra-cistron movement block (TCMB), in the virus-like transcriptome assemblies of the moss Dicranum scoparium and the Antarctic flowering plant Colobanthus quitensis. These TCMBs are encoded by smaller RNA components of putative two-component viruses related to plant benyviruses. Similar to the RNA2 of benyviruses, TCMB-containing RNAs have the 5′-terminal coat protein gene and include the RNA helicase gene which is followed by two small overlapping cistrons encoding hydrophobic proteins with a distant sequence similarity to the TGB2 and TGB3 proteins. Unlike TGB, TCMB also includes a fourth 5′-terminal gene preceding the helicase gene and coding for a protein showing a similarity to the double-stranded RNA-binding proteins of the DSRM AtDRB-like superfamily. Additionally, based on phylogenetic analysis, we suggest the involvement of replicative beny-like helicases in the evolution of the BMB and TCMB movement genetic modules.
What Makes GPCRs from Different Families Bind to the Same Ligand?
Authors: Dankwah Kwabena Owusu , Mohl Jonathon E. , Begum Khodeza , Leung Ming-Ying
Published: June 2022

G protein-coupled receptors (GPCRs) are the largest class of cell-surface receptor proteins with important functions in signal transduction and often serve as therapeutic drug targets. With the rapidly growing public data on three dimensional (3D) structures of GPCRs and GPCR-ligand interactions, computational prediction of GPCR ligand binding becomes a convincing option to high throughput screening and other experimental approaches during the beginning phases of ligand discovery. In this work, we set out to computationally uncover and understand the binding of a single ligand to GPCRs from several different families. Three-dimensional structural comparisons of the GPCRs that bind to the same ligand revealed local 3D structural similarities and often these regions overlap with locations of binding pockets. These pockets were found to be similar (based on backbone geometry and side-chain orientation using APoc), and they correlate positively with electrostatic properties of the pockets. Moreover, the more similar the pockets, the more likely a ligand binding to the pockets will interact with similar residues, have similar conformations, and produce similar binding affinities across the pockets. These findings can be exploited to improve protein function inference, drug repurposing and drug toxicity prediction, and accelerate the development of new drugs.
Vascular Calcification and the Gut and Blood Microbiome in Chronic Kidney Disease Patients on Peritoneal Dialysis: A Pilot Study
Authors: Merino-Ribas Ana , Araujo Ricardo , Pereira Luciano , Campos Joana , Barreiros Luísa , Segundo Marcela A. , Silva Nádia , Costa Carolina F. F. A. , Quelhas-Santos Janete , Trindade Fábio , Falcão-Pires Inês , Alencastre Ines , Dumitrescu Ioana Bancu , Sampaio-Maia Benedita
Published: June 2022

Vascular calcification (VC) is a frequent condition in chronic kidney disease (CKD) and a well-established risk factor for the development of cardiovascular disease (CVD). Gut dysbiosis may contribute to CVD and inflammation in CKD patients. Nonetheless, the role of gut and blood microbiomes in CKD-associated VC remains unknown. Therefore, this pilot study aimed to explore the link between gut and blood microbiomes and VC in CKD patients on peritoneal dialysis (CKD-PD). Our results showed relative changes in specific taxa between CKD-PD patients with and without VC, namely Coprobacter, Coprococcus 3, Lactobacillus, and Eubacterium eligens group in the gut, and Cutibacterium, Pajaroellobacter, Devosia, Hyphomicrobium, and Pelomonas in the blood. An association between VC and all-cause mortality risk in CKD-PD patients was also observed, and patients with higher mortality risk corroborate the changes of Eubacterium eligens in the gut and Devosia genus in the blood. Although we did not find differences in uremic toxins, intestinal translocation markers, and inflammatory parameters among CKD-PD patients with and without VC, soluble CD14 (sCD14), a nonspecific marker of monocyte activation, positively correlated with VC severity. Therefore, gut Eubacterium eligens group, blood Devosia, and circulating sCD14 should be further explored as biomarkers for VC, CVD, and mortality risk in CKD.
Modulating Microglia/Macrophage Activation by CDNF Promotes Transplantation of Fetal Ventral Mesencephalic Graft Survival and Function in a Hemiparkinsonian Rat Model
Authors: Tseng Kuan-Yin , Wu Jui-Sheng , Chen Yuan-Hao , Airavaara Mikko , Cheng Cheng-Yi , Ma Kuo-Hsing
Published: June 2022

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, which leads to the motor control deficits. Recently, cell transplantation is a cutting-edge technique for the therapy of PD. Nevertheless, one key bottleneck to realizing such potential is allogenic immune reaction of tissue grafts by recipients. Cerebral dopamine neurotrophic factor (CDNF) was shown to possess immune-modulatory properties that benefit neurodegenerative diseases. We hypothesized that co-administration of CDNF with fetal ventral mesencephalic (VM) tissue can improve the success of VM replacement therapies by attenuating immune responses. Hemiparkinsonian rats were generated by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats, with/without CDNF administration. Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and small-animal positron emission tomography (PET) coupled with [18F] DOPA or [18F] FE-PE2I, respectively. In addition, transplantation-related inflammatory response was determined by uptake of [18F] FEPPA in the grafted side of striatum. Immunohistochemistry (IHC) examination was used to determine the survival of the grated dopaminergic neurons in the striatum and to investigate immune-modulatory effects of CDNF. The modulation of inflammatory responses caused by CDNF might involve enhancing M2 subset polarization and increasing fractal dimensions of 6-OHDA-treated BV2 microglial cell line. Analysis of CDNF-induced changes to gene expressions of 6-OHDA-stimulated BV2 cells implies that these alternations of the biomarkers and microglial morphology are implicated in the upregulation of protein kinase B signaling as well as regulation of catalytic, transferase, and protein serine/threonine kinase activity. The effects of CDNF on 6-OHDA-induced alternation of the canonical pathway in BV2 microglial cells is highly associated with PI3K-mediated phagosome formation. Our results are the first to show that CDNF administration enhances the survival of the grafted dopaminergic neurons and improves functional recovery in PD animal model. Modulation of the polarization, morphological characteristics, and transcriptional profiles of 6-OHDA-stimualted microglia by CDNF may possess these properties in transplantation-based regenerative therapies.
Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion
Authors: Cordaro Marika , D’Amico Ramona , Fusco Roberta , Peritore Alessio Filippo , Genovese Tiziana , Interdonato Livia , Franco Gianluca , Arangia Alessia , Gugliandolo Enrico , Crupi Rosalia , Siracusa Rosalba , Di Paola Rosanna , Cuzzocrea Salvatore , Impellizzeri Daniela
Published: June 2022

Vascular dementia (VaD) is the second leading cause of dementia. The majority of VaD patients have cognitive abnormalities, which are caused by cerebral hypoperfusion-induced ischemia, endothelial dysfunction, oxidative stress, and neuroinflammation. Natural products are receiving increasing attention for the treatment of neuroinflammatory diseases. The aim of this study was to investigate the molecular pathways underlying the protective effects of fisetin, a flavonoid present in many fruits and vegetables, in a mouse model of VaD induced by repeated ischemia-reperfusion (IR) of the total bilateral carotid artery. Here, we found that VaD caused brain injury, lipid peroxidation, and neuronal death in the hippocampus, as well as astrocyte and microglial activation, and reduced BDNF neurotrophic factor expression together with behavioral alterations. In addition, VaD induced the activation of inflammasome components (NLRP-3, ASC, and caspase 1), and their downstream products (IL-1β and IL-18) release and promote activation of apoptotic cell death. Fisetin attenuated histological injury, malondialdehyde levels, inflammasome pathway activation, apoptosis, as well as increased BDNF expression, reduced astrocyte, microglial activation, and cognitive deficits. In conclusion, the protective effects of fisetin could be due to the inhibition of the ROS-induced activation of NF-κB/NLRP3 inflammasome together with the activation of antioxidant Nrf2/HO-1, suggesting a possible crosstalk between these molecular pathways.
Bromelain Protects Critically Perfused Musculocutaneous Flap Tissue from Necrosis
Authors: Weinzierl Andrea , Harder Yves , Schmauss Daniel , Menger Michael D. , Laschke Matthias W.
Published: June 2022

Bromelain has previously been shown to prevent ischemia-induced necrosis in different types of tissues. In the present study, we, therefore, evaluated for the first time, the tissue-protective effects of bromelain in musculocutaneous flaps in mice. Adult C57BL/6N mice were randomly assigned to a bromelain treatment group and a control group. The animals were treated daily with intraperitoneal injections of 20 mg/kg bromelain or saline (control), starting 1 h before the flap elevation throughout a 10-day observation period. The random-pattern musculocutaneous flaps were raised on the backs of the animals and mounted into a dorsal skinfold chamber. Angiogenesis, nutritive blood perfusion and flap necrosis were quantitatively analyzed by means of repeated intravital fluorescence microscopy over 10 days after surgery. After the last microscopy, the flaps were harvested for additional histological and immunohistochemical analyses. Bromelain reduced necrosis of the critically perfused flap tissue by ~25%. The bromelain-treated flaps also exhibited a significantly higher functional microvessel density and an elevated formation of newly developed microvessels in the transition zone between the vital and necrotic tissues when compared to the controls. Immunohistochemical analyses demonstrated a markedly lower invasion of the myeloperoxidase-positive neutrophilic granulocytes and a significantly reduced number of cleaved caspase 3-positive apoptotic cells in the transition zone of bromelain-treated musculocutaneous flaps. These findings indicate that bromelain prevents flap necrosis by maintaining nutritive tissue perfusion and by suppressing ischemia-induced inflammation and apoptosis. Hence, bromelain may represent a promising compound to prevent ischemia-induced flap necrosis in clinical practice.
Reprogrammed CD8+ T-Lymphocytes Isolated from Bone Marrow Have Anticancer Potential in Lung Cancer
Authors: Skurikhin Evgenii G. , Pershina Olga , Ermakova Natalia , Pakhomova Angelina , Widera Darius , Zhukova Mariia , Pan Edgar , Sandrikina Lubov , Kogai Lena , Kushlinskii Nikolai , Morozov Sergey G. , Kubatiev Aslan , Dygai Alexander
Published: June 2022

CD8+ T-lymphocytes play a key role in antitumor immune response. Patients with lung cancer often suffer from T-lymphocyte dysfunction and low T-cell counts. The exhaustion of effector T-lymphocytes largely limits the effectiveness of therapy. In this study, reprogrammed T-lymphocytes used MEK inhibitors and PD-1 blockers to increase their antitumor activity. Antitumor effects of reprogrammed T-lymphocytes were shown in vitro and in vivo in the Lewis lung carcinoma model. The population of T- lymphocytes with persistent expression of CCR7 was formed as a result of reprogramming. Reprogrammed T-lymphocytes were resistant to apoptosis and characterized by high cytotoxicity against Lewis lung carcinoma (LLC) cells in vitro. Administration of reprogrammed T-lymphocytes to C57BL/6 mice with LLC reduced the number of lung metastases. The antitumor effect resulted from the elimination of tumor cells and cancer stem cells, and the effect of therapy on cytotoxic T-lymphocyte counts. Thus, reprogramming of T-lymphocytes using MEK inhibitors is a promising approach for targeted therapy of lung cancer.
The Impact of Inflammatory Stimuli on Xylosyltransferase-I Regulation in Primary Human Dermal Fibroblasts
Authors: Ly Thanh-Diep , Lindenkamp Christopher , Kara Eva , Schmidt Vanessa , Kleine Anika , Fischer Bastian , Hendig Doris , Knabbe Cornelius , Faust-Hinse Isabel
Published: June 2022

Inflammation plays a vital role in regulating fibrotic processes. Beside their classical role in extracellular matrix synthesis and remodeling, fibroblasts act as immune sentinel cells participating in regulating immune responses. The human xylosyltransferase-I (XT-I) catalyzes the initial step in proteoglycan biosynthesis and was shown to be upregulated in normal human dermal fibroblasts (NHDF) under fibrotic conditions. Regarding inflammation, the regulation of XT-I remains elusive. This study aims to investigate the effect of lipopolysaccharide (LPS), a prototypical pathogen-associated molecular pattern, and the damage-associated molecular pattern adenosine triphosphate (ATP) on the expression of XYLT1 and XT-I activity of NHDF. We used an in vitro cell culture model and mimicked the inflammatory tissue environment by exogenous LPS and ATP supplementation. Combining gene expression analyses, enzyme activity assays, and targeted gene silencing, we found a hitherto unknown mechanism involving the inflammasome pathway components cathepsin B (CTSB) and caspase-1 in XT-I regulation. The suppressive role of CTSB on the expression of XYLT1 was further validated by the quantification of CTSB expression in fibroblasts from patients with the inflammation-associated disease Pseudoxanthoma elasticum. Altogether, this study further improves the mechanistic understanding of inflammatory XT-I regulation and provides evidence for fibroblast-targeted therapies in inflammatory diseases.
The Mediating Effect of Cytokines on the Association between Fungal Sensitization and Poor Clinical Outcome in Asthma
Authors: Lin Ching-Hsiung , Li Yi-Rong , Kor Chew-Teng , Lin Sheng-Hao , Ji Bin-Chuan , Lin Ming-Tai , Chai Woei-Horng
Published: June 2022

Sensitization to fungal allergens is one of the proposed phenotypes in asthma. An association between fungal sensitization and worse clinical outcomes is apparent. Moreover, fungal sensitization in asthma that is associated with different type of immunological mechanism has been reported. How the role of cytokines mediates the association between fungal sensitization and poorer asthmatic outcomes remains unclear. We aimed to determine role of cytokines in the relationship between fungal sensitization and worse clinical outcomes in asthma. Method: We conducted a prospective study to recruit adult patients with asthma. Data including age, sex, height, weight, smoking history, medication, emergency visit and admission, pulmonary function testing result, and Asthma Control Test (ACT) scores were collected. We used the automated BioIC method to measure fungal allergen sIgE in sera. Serum levels of Interleukin (IL) -4, IL-13, IL-6, IL-9, IL-10, IL-17 A, IL-22, Interferon (IFN) -γ, Immunoglobulin E (IgE), Tumor necrosis factor-α (TNF-α), and Transforming growth factor-β (TGF-β) were measured using ELISA. Result: IL-6 and IL-17A had a significant positive correlation between sensitization and most fungi species compared to IgE. Sensitization to Candida albicans had strongly positive association both with IL-6 and IL-17A. However, only IL-17A had significant relationship with ED visit times. The mediation analysis result indicates that IL-17A had a significant positively mediating effect (ME) on the association between Candida albicans and ED visit times. Conclusion: IL-17A is a potential mediator to link Candida albicans sensitization and ED visits for asthma. We suggest that patients with fungal sensitization, such as Candida albicans, have poorer outcomes associated with Th17-mediated immune response rather than Th2.
Immune Response to SARS-CoV-2 Vaccines
Authors: Bellamkonda Navya , Lambe Upendra Pradeep , Sawant Sonali , Nandi Shyam Sundar , Chakraborty Chiranjib , Shukla Deepak
Published: June 2022

COVID-19 vaccines have been developed to confer immunity against the SARS-CoV-2 infection. Prior to the pandemic of COVID-19 which started in March 2020, there was a well-established understanding about the structure and pathogenesis of previously known Coronaviruses from the SARS and MERS outbreaks. In addition to this, vaccines for various Coronaviruses were available for veterinary use. This knowledge supported the creation of various vaccine platforms for SARS-CoV-2. Before COVID-19 there are no reports of a vaccine being developed in under a year and no vaccine for preventing coronavirus infection in humans had ever been developed. Approximately nine different technologies are being researched and developed at various levels in order to design an effective COVID-19 vaccine. As the spike protein of SARS-CoV-2 is responsible for generating substantial adaptive immune response, mostly all the vaccine candidates have been targeting the whole spike protein or epitopes of spike protein as a vaccine candidate. In this review, we have compiled the immune response to SARS-CoV-2 infection and followed by the mechanism of action of various vaccine platforms such as mRNA vaccines, Adenoviral vectored vaccine, inactivated virus vaccines and subunit vaccines in the market. In the end we have also summarized the various adjuvants used in the COVID-19 vaccine formulation.
Rosmarinic Acid Reduces Microglia Senescence: A Novel Therapeutic Approach for the Management of Neuropathic Pain Symptoms
Authors: Borgonetti Vittoria , Galeotti Nicoletta
Published: June 2022

The worldwide incidence of neuropathic pain is around 7–8% and is associated with significant and disabling comorbidities (sleep disturbances, depression, anxiety). It is now known that cellular ageing of microglia contributes to neurodegenerative diseases, mood disorders, and, even if with less evidence, chronic pain. The aim of this work was to investigate in vitro and in vivo the senolytic activity of rosmarinic acid (RA) to be exploited for the management of NP symptoms. BV2 cells were stimulated with LPS 500 ng/mL for 24 h. Treatment with RA 1 µM improved cell viability and reduced IL-1ß release leading to an attenuation of neuroinflammation. We then moved on to test the efficacy of RA in reducing microglial senescence. In our model, BV2 cells were stimulated with LPS 500 ng/mL every 72 h for 4 h/day, over a period of 10 days. RA 1 µM reduced the expression of the β-galactosidase enzyme, reduced the release of senescence-associated secretory phenotype (SASP) factors, increased cell viability, and reduced the presence of nuclear foci of senescence (SAHF), well-known cellular senescence markers. In the Spared Nerve Injury (SNI) model, 28 days from surgery, repeated oral administration of RA 5 mg/kg reduced hyperalgesia and NP-associated symptoms, such as anxiety and depression. A reduction of senescence markers was detected on both hippocampal and spinal samples of SNI-treated mice. This study represents a starting point for investigating the role of microglial senescence as a possible pharmacological target in controlling symptoms related to the more advanced stages of peripheral neuropathy.
Special Issue: Emerging Paradigms in Insulin Resistance
Authors: Collier J. Jason , Burke Susan J.
Published: June 2022

This Biomedicines Special Issue was designed to attract articles that focused on different facets of biology relating to insulin resistance, defined as reduced cellular and organismal response to the insulin hormone, and its underlying mechanisms [...]
Mechanisms Regulating Energy Homeostasis in Plant Cells and Their Potential to Inspire Electrical Microgrids Models
Authors: Suzuki Nobuhiro , Shigaki Shunsuke , Yunose Mai , Putrawisesa Nicholas Raditya , Hogaki Sho , Di Piazza Maria Carmela
Published: June 2022

In this paper, the main features of systems that are required to flexibly modulate energy states of plant cells in response to environmental fluctuations are surveyed and summarized. Plant cells possess multiple sources (chloroplasts and mitochondria) to produce energy that is consumed to drive many processes, as well as mechanisms that adequately provide energy to the processes with high priority depending on the conditions. Such energy-providing systems are tightly linked to sensors that monitor the status of the environment and inside the cell. In addition, plants possess the ability to efficiently store and transport energy both at the cell level and at a higher level. Furthermore, these systems can finely tune the various mechanisms of energy homeostasis in plant cells in response to the changes in environment, also assuring the plant survival under adverse environmental conditions. Electrical power systems are prone to the effects of environmental changes as well; furthermore, they are required to be increasingly resilient to the threats of extreme natural events caused, for example, by climate changes, outages, and/or external deliberate attacks. Starting from this consideration, similarities between energy-related processes in plant cells and electrical power grids are identified, and the potential of mechanisms regulating energy homeostasis in plant cells to inspire the definition of new models of flexible and resilient electrical power grids, particularly microgrids, is delineated. The main contribution of this review is surveying energy regulatory mechanisms in detail as a reference and helping readers to find useful information for their work in this research field.
Tracking Arachis hypogaea Allergen in Pre-Packaged Foodstuff: A Nanodiamond-Based Electrochemical Biosensing Approach
Authors: Freitas Maria , Carvalho André , Nouws Henri P. A. , Delerue-Matos Cristina
Published: June 2022

The present work reports a nanodiamond-based voltammetric immunosensing platform for the analysis of a food allergen (Ara h 1) present in peanuts (Arachis hypogaea). The possibility of the usage of nanodiamonds (d = 11.2 ± 0.9 nm) on screen-printed carbon electrodes (SPCE/ND) in a single-use two-monoclonal antibody sandwich assay was studied. An enhanced electroactive area (~18%) was obtained and the biomolecule binding ability was improved when the 3D carbon-based nanomaterial was used. The antibody-antigen interaction was recognized through the combination of alkaline phosphatase with 3-indoxyl phosphate and silver ions. Linear Sweep Voltammetry (LSV) was applied for fast signal acquisition and scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) support the voltammetric approach and confirm the presence of silver particles on the electrode surface. The proposed immunosensor provided a low limit of detection (0.78 ng·mL−1) and highly precise (RSD < 7.5%) and accurate results. Quantification of Ara h 1 in commercial foodstuffs (e.g., crackers, cookies, protein bars) that refer to the presence of peanuts (even traces) on the product label was successfully achieved. The obtained data were in accordance with recovery results (peanut addition, %) and the foodstuff label. Products with the preventive indication “may contain traces” revealed the presence of peanuts lower than 0.1% (m/m). The method’s results were validated by comparison with an enzyme-linked immunosorbent assay. This allows confident information about the presence of allergens (even at trace levels) that leads to profitable conditions for both industry and consumers.
How Does Lower Limb Respond to Unexpected Balance Perturbations? New Insights from Synchronized Human Kinetics, Kinematics, Muscle Electromyography (EMG) and Mechanomyography (MMG) Data
Authors: Zhu Ringo Tang-Long , Lyu Pei-Zhao , Li Shuai , Tong Cheuk Ying , Ling Yan To , Ma Christina Zong-Hao
Published: June 2022

Making rapid and proper compensatory postural adjustments is vital to prevent falls and fall-related injuries. This study aimed to investigate how, especially how rapidly, the multiple lower-limb muscles and joints would respond to the unexpected standing balance perturbations. Unexpected waist-pull perturbations with small, medium and large magnitudes were delivered to twelve healthy young adults from the anterior, posterior, medial and lateral directions. Electromyographical (EMG) and mechanomyographical (MMG) responses of eight dominant-leg muscles (i.e., hip abductor/adductors, hip flexor/extensor, knee flexor/extensor, and ankle dorsiflexor/plantarflexors) together with the lower-limb joint angle, moment, and power data were recorded. The onset latencies, time to peak, peak values, and/or rate of change of these signals were analyzed. Statistical analysis revealed that: (1) agonist muscles resisting the delivered perturbation had faster activation than the antagonist muscles; (2) ankle muscles showed the largest rate of activation among eight muscles following both anteroposterior and mediolateral perturbations; (3) lower-limb joint moments that complied with the perturbation had faster increase; and (4) larger perturbation magnitude tended to evoke a faster response in muscle activities, but not necessarily in joint kinetics/kinematics. These findings provided insights regarding the underlying mechanism and lower-limb muscle activities to maintain reactive standing balance in healthy young adults.
IL-10 Gene Polymorphisms and IL-10 Serum Levels in Patients with Multiple Sclerosis in Lithuania
Authors: Masilionyte Ugne , Gedvilaite Greta , Kaikaryte Kriste , Vilkeviciute Alvita , Kriauciuniene Loresa , Glebauskiene Brigita , Balnyte Renata , Liutkeviciene Rasa
Published: June 2022

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with features of demyelination and axonal degeneration at a young age. Genetic factors may play an important role in the development of multiple sclerosis. (1) Objective: To investigate IL-10 rs1800871, rs1800872, rs1800896, and IL-10 serum levels in patients with multiple sclerosis. (2) Methods: Our study included patients with multiple sclerosis (n = 127) and healthy volunteers (n = 195). The subjects’ DNA was extracted from peripheral blood leukocytes and genotyped by real-time polymerase chain reaction. The results were analyzed using the program “IBM SPSS Statistics 27.0”. (3) Results: The IL-10 SNPs were analyzed between the MS and control groups; however, no statistically significant results were found. The serum levels of IL-10 in the groups of MS and healthy subjects were not statistically significantly different (median (IQR): 0.828 (1.533) vs. 0.756 (0.528), p = 0.872). (4) Conclusions: IL-10 rs1800871, rs1800872, and rs1800896 and serum IL-10 levels are not likely to be associated with MS development. However, individuals carrying the rare haplotypes of rs1800871, rs1800872, and rs1800896 were associated with increased odds of MS (p = 0.006).
Effects of Music Therapy in the Reduction of Pre-Meal Anxiety in Patients Suffering from Anorexia Nervosa
Authors: Ceccato Enrico , Roveran Cristina
Published: June 2022

Literature reviews appear to indicate that Music Therapy (MT) may instil a sense of empowerment and generate feelings of renewed self-confidence, distracting subjects who follow this type of intervention from negative thoughts and, generally, helping patients suffering from Anorexia Nervosa (AN) to redevelop or rediscover their identity. The purpose of the study reported in this paper is to investigate whether MT proposed before an evening meal is capable of decreasing pre-meal anxiety in adolescents suffering from AN who follow the Day-hospital Treatment Programme at the San Bortolo Hospital of Vicenza (Italy). A total of 24 patients participated voluntarily in once-weekly sessions of group-based MT conducted by a qualified music therapist over a period of six months. Before evening meals on Monday, Tuesday and Wednesday, pre-meal anxiety was measured using a self-report scale, and the MT group session occurred every Wednesday before the evening meal was consumed. MT activities were both active and receptive. It has been found that with respect to Mondays and Tuesdays, pre-meal anxiety was significantly lower on Wednesdays following participation in the MT group. MT is evidently capable of reducing pre-meal anxiety and may be adopted as a supportive element in treatment plans relating to patients with AN in a day-hospital treatment programme.
High Myoinositol on Proton MR Spectroscopy Could Be a Potential Signature of Papillary Tumors of the Pineal Region—Case Report of Two Patients
Authors: Pons-Escoda Albert , Sánchez Fernández Juan Jose , de Vilalta Àlex , Vidal Noemí , Majós Carles
Published: June 2022

Papillary tumor of the pineal region (PTPR) is an uncommon entity in which a presurgical suspicion may be crucial for patient management. Maximal safe neurosurgical resection is of choice when PTPR is suspected, whereas non-surgical approaches can be considered in other tumors of the pineal region, such as pineocytoma or concrete subtypes of germ-cell tumors. In general terms, imaging features of tumors of the pineal region have been reported to be unspecific. Nevertheless, in this report, we describe two pathology-confirmed PTPRs in which presurgical proton MR spectroscopy demonstrated extremely high myoinositol, a pattern which drastically differs from that of other pineal tumors. We hypothesize that this high myoinositol may be related to PTPR’s known ependymal component, and that it could be used as a specific non-invasive diagnostic signature.