bluuebunny/crossref_metadata_2025 huggingface dataset:
Applicability and Psychometric Comparison of the General-Population Viral Anxiety Rating Scales among Healthcare Workers in the COVID-19 Pandemic
Authors: Kim Changnam , Ahmed Oli , Silva Washington Allysson Dantas , Park C. Hyung Keun , Yoo Soyoung , Chung Seockhoon
Published: August 2022

We aimed to explore the reliability and validity of viral anxiety rating scales (developed for the general population) among healthcare workers. In addition, we compared the psychometric properties of rating scales in accordance with the Generalized Anxiety Scale-7 items (GAD-7) during this COVID-19 pandemic. The viral anxiety of 330 healthcare workers was measured with Stress and Anxiety to Viral Epidemics—9 items (SAVE-9), SAVE-6, Coronavirus Anxiety Scale (CAS), Fear of COVID-19 Scale (FCV-19S), and COVID-19 Anxiety Scale (CAS-7). Factor analyses, item response theory, and Rasch model analyses were conducted to confirm the construct validities of the scales and compare the psychometric properties of rating scales. The receiver operating curve (ROC) analysis examined the cutoff scores of rating scales in accordance with a mild degree of generalized anxiety. The SAVE-9, SAVE-6, CAS, FCV-19S, and CAS-7 scales showed good reliability of internal consistency among healthcare workers. Their construct validity and convergent validity of each scale were similarly good. Furthermore, in comparing the psychometric properties of rating scales, we observed that the CAS scale was the most discriminating and difficult among the scales. The CAS and FCV-19S provided more information and were more efficient than the SAVE-9, SAVE-6, and CAS-7 scales when they were used to measure healthcare workers’ viral anxiety. Viral anxiety rating scales can be applied to healthcare workers with good reliability and validity.
Can the Virtual Reality-Based Spatial Memory Test Better Discriminate Mild Cognitive Impairment than Neuropsychological Assessment?
Authors: Park Jin-Hyuck
Published: August 2022

Neuropsychological screening tools for mild cognitive impairment (MCI) have been widely used. However, to date, their sensitivity and specificity still remain unsatisfied. This study aims to investigate whether spatial memory can discriminate MCI better than neuropsychological screening tools. A total of 56 healthy older adults and 36 older adults with MCI participated in this study; they performed a spatial cognitive task based on virtual reality (SCT-VR), the Korean version of the Montreal Cognitive Assessment (MoCA-K), and the Wechsler Adult Intelligence Scale-Revised Block Design Test (WAIS-BDT). The discriminant power was compared between the SCT-VR and the MoCA-K, and the reliability and validity of the SCT-VR were analyzed. The spatial memory, assessed by the SCT-VR, showed better sensitivity and specificity (sensitivity: 0.944; specificity: 0.964) than the MoCA-K (sensitivity: 0.857; specificity: 0.746). The test-retest reliability of the SCT-VR was relatively high (ICCs: 0.982, p < 0.001) and the concurrent validity of the SCT-VR with the MoCA-K (r = −0.587, p < 0.001) and the WAIS-BDT (r = −0.594, p < 0.001) was statistically significant. These findings shed light on the importance of spatial memory as a behavioral marker of MCI. The ecologically validated spatial memory tasks based on VR need to be investigated by neuroscientific studies in the future.
Burnout among Professionals Working in Corrections: A Two Stage Review
Authors: Forman-Dolan Justice , Caggiano Claire , Anillo Isabelle , Kennedy Tom Dean
Published: August 2022

Burnout is a state of emotional, physical, and mental exhaustion often caused by excessive and prolonged stress. Given the emotionally and often physically demanding nature of the work of correctional professionals, they are at substantial risk of suffering the adverse consequences of burnout. We systematically reviewed (Stage 1) the influence of burnout amongst forensic psychologists, psychiatrists, case workers, nurses, and correction officers. Interventions were then reviewed (Stage 2) at the individual and collective level to examine the effectiveness or efficacy of treatments for burnout among professionals working in corrections.
Association of Polymorphism within the Putative miRNA Target Site in the 3′UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder
Authors: Boroń Agnieszka , Śmiarowska Małgorzata , Grzywacz Anna , Chmielowiec Krzysztof , Chmielowiec Jolanta , Masiak Jolanta , Pawłowski Tomasz , Larysz Dariusz , Ciechanowicz Andrzej
Published: August 2022

The study aims at looking into associations between the polymorphism rs6276 that occurs in the putative miRNA target site in the 3′UTR region of the DRD2 gene in patients with substance use disorder (SUD) comorbid with a maniacal syndrome (SUD MANIA). In our study, we did not state any essential difference in DRD2 rs6276 genotype frequencies in the studied samples of SUD MANIA, SUD, and control subjects. A significant result was found for the SUD MANIA group vs. SUD vs. controls on the Neuroticism Scale of NEO FFI test, and DRD2 rs6276 (p = 0.0320) accounted for 1.7% of the variance. The G/G homozygous variants were linked with lower results on the neuroticism scale in the SUD MANIA group because G/G alleles may serve a protective role in the expression of neuroticism in patients with SUD MANIA. So far, there have been no data in the literature on the relationship between the miRSNP rs6276 region in the DRD2 gene and neuroticism (personal traits) in patients with a diagnosis of substance use disorder comorbid with the affective, maniacal type disturbances related to SUD. This is the first report on this topic.
Changes in the Gut Microbiome and Pathologies in Pregnancy
Authors: Gorczyca Kamila , Obuchowska Aleksandra , Kimber-Trojnar Żaneta , Wierzchowska-Opoka Magdalena , Leszczyńska-Gorzelak Bożena
Published: August 2022

Pregnancy is a special period in a woman’s life when her organism undergoes multiple physiological changes so that the fetus has optimal conditions for growth and development. These include modifications in the composition of the microbiome that occur between the first and third trimesters of pregnancy. There is an increase in Akkermansia, Bifidobacterium, and Firmicutes, which have been associated with an increase in the need for energy storage. The growth in Proteobacteria and Actinobacteria levels has a protective effect on both the mother and the fetus via proinflammatory mechanisms. The aim of the study is to review the research on the relationship between the mother’s intestinal microbiome and gestational pathologies. Changes in the maternal gut microbiome is probably one of the mechanisms that occurs in various pregnancy diseases such as preeclampsia, fetal growth restriction, gestational diabetes mellitus, excessive gestational weight gain, and premature birth. For this reason, it seems vital to pay attention to certain interventions that can benefit the affected patients both in the short term, by preventing complications during pregnancy, and in the long term, as one of the mechanisms occurring in various gestational diseases is dysbiosis of the maternal intestinal flora.
Understanding, Trusting, and Applying Scientific Insights to Improve Your Health: A Latent Profile Analysis Approach
Authors: Plohl Nejc , Musil Bojan
Published: August 2022

Various leading causes of death can be prevented or delayed through informed decision-making and lifestyle changes. Previous work has, to some extent, linked such health-promoting behavior (HPB) with variables capturing individuals’ understanding of science, trust in science, and capacity to apply evidence-based information in the health context. However, empirical research on the relationship between scientific knowledge, trust in science, health literacy, and HPB is scarce. Additionally, no study has investigated whether these characteristics interact to form homogeneous, high-risk subgroups of the population. The present online study (N = 705) revealed that trust in science and health literacy were positively related to a wide array of HPBs (e.g., healthy nutrition, physical activity, stress management), while scientific knowledge was only positively associated with COVID-19 vaccination intention. Furthermore, the results of latent profile analyses yielded four subgroups (i.e., low, moderate, and high levels of all three variables and a varied profile exhibiting very low trust in science, low health literacy, and moderate scientific knowledge). The identified subgroups differ significantly in HPB and variables determining profile membership (e.g., political conservatism). Hence, the present study offers some guidance on which groups may be targeted with public health campaigns and how they may be designed.
Impact of LncRNA GAS5 Genetic Variants and the Epidermal Growth Factor Receptor Phenotypes on the Clinicopathological Characteristics of Lung Adenocarcinoma Patients
Authors: Hsieh Ming-Hong , Wu Yi-Liang , Tsao Thomas Chang-Yao , Huang Yi-Wen , Lin Jian-Cheng , Lee Chia-Yi , Hsieh Ming-Ju , Yang Shun-Fa
Published: August 2022

The aim of the current study was to evaluate the combined effect of the single nucleotide polymorphism (SNP) in long non-coding RNA growth arrest-specific 5 (GAS5) and the phenotypes of epidermal growth factor receptor (EGFR) on the clinicopathological characteristics of lung adenocarcinoma. The present study examined the relationship between the GAS5 single-nucleotide polymorphisms (SNPs; rs145204276 Ins/Del, rs55829688 T/C) and the clinicopathological factors in 539 lung adenocarcinoma patients with or without EGFR mutations. We found that the genotype distributions of the two GAS5 SNPs between different EGFR genotypes were similar after adjusting for age, gender and smoking history. The GAS5 SNP rs145204276 Ins/Del + Del/Del illustrated a higher distribution with an advanced tumor stage (p = 0.030), larger tumor T status (p = 0.019), positive lymph node status (p = 0.014) and distal metastases (p = 0.011) in the EGFR wild type group. In the subgroup analysis of the EGFR wild type population, the presence of GAS5 SNP rs145204276 Ins/Del + Del/Del was correlated to an advanced tumor stage (p = 0.014) and distal metastases (p = 0.020) in non-smokers. In conclusion, these data indicate that the GAS5 SNP rs145204276 variant may help predict tumor stage, lymph node metastasis and distal metastases in patients with EGFR wild type lung adenocarcinoma.
The Spatial Disparities of Land-Use Efficiency in Mainland China from 2000 to 2015
Authors: Wang Yunchen , Li Boyan
Published: August 2022

Understanding the sustainable development goal (SDG) 11.3.1-ratio of land consumption rate (LCR) to population growth rate (PGR) is an important prerequisite for planning a guide for sustainable urbanization. However, little is known regarding the degree of accuracy of the estimated LCR due to the inconsistency of data on built-up areas. We extracted four built-up areas, based on inverse S-shaped law and area proportion method, and produced more precise built-up area data (LS_BUA) for the period 2000–2015. Chinese population density data in 2000–2015 was generated based on 26 million points of interest, 19 million roads, other multi-source data, and random forest (RF). Finally, the coupling between LCR and PGR for 340 Chinese cities was calculated during the same period. The results showed that (1) the accuracy of LS_BUA was higher than that of the other built-up area data production methods; (2) the accuracy of test sets in RF exceeded 0.86; (3) the LCR value of mainland China was 0.024 and the PGR value was 0.019 during 2000–2015. The LCR consistently exceeded the PGR and the coordination relationship between LCR and PGR continued to deteriorate. Our research eliminated the difference of SDG 11.3.1 from different data sources and could therefore help decision makers balance land consumption and population growth.
Studying Chromatin Epigenetics with Fluorescence Microscopy
Authors: Stepanov Afanasii I. , Besedovskaia Zlata V. , Moshareva Maria A. , Lukyanov Konstantin A. , Putlyaeva Lidia V.
Published: August 2022

Epigenetic modifications of histones (methylation, acetylation, phosphorylation, etc.) are of great importance in determining the functional state of chromatin. Changes in epigenome underlay all basic biological processes, such as cell division, differentiation, aging, and cancerous transformation. Post-translational histone modifications are mainly studied by immunoprecipitation with high-throughput sequencing (ChIP-Seq). It enables an accurate profiling of target modifications along the genome, but suffers from the high cost of analysis and the inability to work with living cells. Fluorescence microscopy represents an attractive complementary approach to characterize epigenetics. It can be applied to both live and fixed cells, easily compatible with high-throughput screening, and provide access to rich spatial information down to the single cell level. In this review, we discuss various fluorescent probes for histone modification detection. Various types of live-cell imaging epigenetic sensors suitable for conventional as well as super-resolution fluorescence microscopy are described. We also focus on problems and future perspectives in the development of fluorescent probes for epigenetics.
Kinetic Characterization of Cerium and Gallium Ions as Inhibitors of Cysteine Cathepsins L, K, and S
Authors: Novinec Marko , Bembič Primož , Janković Milica , Kisilak Marija , Kljun Jakob , Turel Iztok
Published: August 2022

Heavy metal ions can disrupt biological functions via multiple molecular mechanisms, including inhibition of enzymes. We investigate the interactions of human papain-like cysteine endopeptidases cathepsins L, K, and S with gallium and cerium ions, which are associated with medical applications. We compare these results with zinc and lead, which are known to inhibit thiol enzymes. We show that Ga3+, Ce3+, and Ce4+ ions inhibit all tested peptidases with inhibition constants in the low micromolar range (between 0.5 µM and 10 µM) which is comparable to Zn2+ ions, whereas inhibition constants of Pb2+ ions are one order of magnitude higher (30 µM to 150 µM). All tested ions are linear specific inhibitors of cathepsin L, but cathepsins K and S are inhibited by Ga3+, Ce3+, and Ce4+ ions via hyperbolic inhibition mechanisms. This indicates a mode of interaction different from that of Zn2+ and Pb2+ ions, which act as linear specific inhibitors of all peptidases. All ions also inhibit the degradation of insoluble elastin, which is a common target of these peptidases in various inflammatory diseases. Our results suggest that these ions and their compounds have the potential to be used as cysteine cathepsin inhibitors in vitro and possibly in vivo.
The IRE1α–XBP1s Arm of the Unfolded Protein Response Activates N-Glycosylation to Remodel the Subepithelial Basement Membrane in Paramyxovirus Infection
Authors: Zhao Yingxin , Qiao Dianhua , Skibba Melissa , Brasier Allan R.
Published: August 2022

Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) associated with decreased pulmonary function, asthma, and allergy. Recently, we demonstrated that RSV induces the hexosamine biosynthetic pathway via the unfolded protein response (UPR), which is a pathway controlling protein glycosylation and secretion of the extracellular matrix (ECM). Because the presence of matrix metalloproteinases and matricellular growth factors (TGF) is associated with severe LRTI, we studied the effect of RSV on ECM remodeling and found that RSV enhances the deposition of fibronectin-rich ECM by small airway epithelial cells in a manner highly dependent on the inositol requiring kinase (IRE1α)–XBP1 arm of the UPR. To understand this effect comprehensively, we applied pharmacoproteomics to understand the effect of the UPR on N-glycosylation and ECM secretion in RSV infection. We observe that RSV induces N-glycosylation and the secretion of proteins related to ECM organization, secretion, or proteins integral to plasma membranes, such as integrins, laminins, collagens, and ECM-modifying enzymes, in an IRE1α–XBP1 dependent manner. Using a murine paramyxovirus model that activates the UPR in vivo, we validate the IRE1α–XBP1-dependent secretion of ECM to alveolar space. This study extends understanding of the IRE1α–XBP1 pathway in regulating N-glycosylation coupled to structural remodeling of the epithelial basement membrane in RSV infection.
Ethyl Vinyl Ketone Activates K+ Efflux to Regulate Stomatal Closure by MRP4-Dependent eATP Accumulation Working Upstream of H2O2 Burst in Arabidopsis
Authors: Gong Junqing , Yao Lijuan , Jiao Chunyang , Guo Zhujuan , Li Shuwen , Zuo Yixin , Shen Yingbai
Published: August 2022

Plants regulate stomatal mobility to limit water loss and improve pathogen resistance. Ethyl vinyl ketone (evk) is referred to as a reactive electrophilic substance (RES). In this paper, we found that evk can mediate stomatal closure and that evk-induced stomatal closure by increasing guard cell K+ efflux. To investigate the role of eATP, and H2O2 in evk-regulated K+ efflux, we used Arabidopsis wild-type (WT), mutant lines of mrp4, mrp5, dorn1.3 and rbohd/f. Non-invasive micro-test technology (NMT) data showed that evk-induced K+ efflux was diminished in mrp4, rbohd/f, and dorn1.3 mutant, which means eATP and H2O2 work upstream of evk-induced K+ efflux. According to the eATP content assay, evk stimulated eATP production mainly by MRP4. In mrp4 and mrp5 mutant groups and the ABC transporter inhibitor glibenclamide (Gli)-pretreated group, evk-regulated stomatal closure and eATP buildup were diminished, especially in the mrp4 group. According to qRT-PCR and eATP concentration results, evk regulates both relative gene expressions of MRP4/5 and eATP concentration in rbohd/f and WT group. According to the confocal data, evk-induced H2O2 production was lower in mrp4, mrp5 mutants, which implied that eATP works upstream of H2O2. Moreover, NADPH-dependent H2O2 burst is regulated by DORN1. A yeast two-hybrid assay, firefly luciferase complementation imaging assay, bimolecular fluorescence complementation assay, and pulldown assay showed that the interaction between DORN1 and RBOHF can be realized, which means DORN1 may control H2O2 burst by regulating RBOHF through interaction. This study reveals that evk-induced stomatal closure requires MRP4-dependent eATP accumulation and subsequent H2O2 accumulation to regulate K+ efflux.
Upconversion Nanostructures Applied in Theranostic Systems
Authors: Lu Chao , Joulin Etienne , Tang Howyn , Pouri Hossein , Zhang Jin
Published: August 2022

Upconversion (UC) nanostructures, which can upconvert near-infrared (NIR) light with low energy to visible or UV light with higher energy, are investigated for theranostic applications. The surface of lanthanide (Ln)-doped UC nanostructures can be modified with different functional groups and bioconjugated with biomolecules for therapeutic systems. On the other hand, organic molecular-based UC nanostructures, by using the triplet-triplet annihilation (TTA) UC mechanism, have high UC quantum yields and do not require high excitation power. In this review, the major UC mechanisms in different nanostructures have been introduced, including the Ln-doped UC mechanism and the TTA UC mechanism. The design and fabrication of Ln-doped UC nanostructures and TTA UC-based UC nanostructures for theranostic applications have been reviewed and discussed. In addition, the current progress in the application of UC nanostructures for diagnosis and therapy has been summarized, including tumor-targeted bioimaging and chemotherapy, image-guided diagnosis and phototherapy, NIR-triggered controlled drug releasing and bioimaging. We also provide insight into the development of emerging UC nanostructures in the field of theranostics.
Anesthetics and Cell–Cell Communication: Potential Ca2+-Calmodulin Role in Gap Junction Channel Gating by Heptanol, Halothane and Isoflurane
Authors: Peracchia Camillo
Published: August 2022

Cell–cell communication via gap junction channels is known to be inhibited by the anesthetics heptanol, halothane and isoflurane; however, despite numerous studies, the mechanism of gap junction channel gating by anesthetics is still poorly understood. In the early nineties, we reported that gating by anesthetics is strongly potentiated by caffeine and theophylline and inhibited by 4-Aminopyridine. Neither Ca2+ channel blockers nor 3-isobutyl-1-methylxanthine (IBMX), forskolin, CPT-cAMP, 8Br-cGMP, adenosine, phorbol ester or H7 had significant effects on gating by anesthetics. In our publication, we concluded that neither cytosolic Ca2+i nor pHi were involved, and suggested a direct effect of anesthetics on gap junction channel proteins. However, while a direct effect cannot be excluded, based on the potentiating effect of caffeine and theophylline added to anesthetics and data published over the past three decades, we are now reconsidering our earlier interpretation and propose an alternative hypothesis that uncoupling by heptanol, halothane and isoflurane may actually result from a rise in cytosolic Ca2+ concentration ([Ca2+]i) and consequential activation of calmodulin linked to gap junction proteins.
Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function
Authors: Tasić Danica , Opačić Miloš , Kovačević Sanja , Nikolić Kokić Aleksandra , Dimitrijević Milena , Nikolić Dušan , Vojnović Milutinović Danijela , Blagojević Duško , Djordjevic Ana , Brkljačić Jelena
Published: August 2022

The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate copper metabolism in a way that affects redox homeostasis, thus contributing to progression of metabolic disturbances in the kidney. We determined protein level of copper transporters, chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of superoxide dismutase and decreased metallothionein level, while rendering the level of copper importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi network unaffected. Stress had no effect on renal copper metabolism. The activity and expression of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose, independently of stress, decreased renal copper level, and modulated renal copper metabolism as to preserve vital cellular function including mitochondrial energy production and antioxidative defense, at the expense of intracellular copper storage.
Alginate as a Promising Biopolymer in Drug Delivery and Wound Healing: A Review of the State-of-the-Art
Authors: Abourehab Mohammad A. S. , Rajendran Rahul R. , Singh Anshul , Pramanik Sheersha , Shrivastav Prachi , Ansari Mohammad Javed , Manne Ravi , Amaral Larissa Souza , Deepak A.
Published: August 2022

Biopolymeric nanoparticulate systems hold favorable carrier properties for active delivery. The enhancement in the research interest in alginate formulations in biomedical and pharmaceutical research, owing to its biodegradable, biocompatible, and bioadhesive characteristics, reiterates its future use as an efficient drug delivery matrix. Alginates, obtained from natural sources, are the colloidal polysaccharide group, which are water-soluble, non-toxic, and non-irritant. These are linear copolymeric blocks of α-(1→4)-linked l-guluronic acid (G) and β-(1→4)-linked d-mannuronic acid (M) residues. Owing to the monosaccharide sequencing and the enzymatically governed reactions, alginates are well-known as an essential bio-polymer group for multifarious biomedical implementations. Additionally, alginate’s bio-adhesive property makes it significant in the pharmaceutical industry. Alginate has shown immense potential in wound healing and drug delivery applications to date because its gel-forming ability maintains the structural resemblance to the extracellular matrices in tissues and can be altered to perform numerous crucial functions. The initial section of this review will deliver a perception of the extraction source and alginate’s remarkable properties. Furthermore, we have aspired to discuss the current literature on alginate utilization as a biopolymeric carrier for drug delivery through numerous administration routes. Finally, the latest investigations on alginate composite utilization in wound healing are addressed.
Membrane Internalization Mechanisms and Design Strategies of Arginine-Rich Cell-Penetrating Peptides
Authors: Hao Minglu , Zhang Lei , Chen Pu
Published: August 2022

Cell-penetrating peptides (CPPs) have been discovered to deliver chemical drugs, nucleic acids, and macromolecules to permeate cell membranes, creating a novel route for exogenous substances to enter cells. Up until now, various sequence structures and fundamental action mechanisms of CPPs have been established. Among them, arginine-rich peptides with unique cell penetration properties have attracted substantial scientific attention. Due to the positively charged essential amino acids of the arginine-rich peptides, they can interact with negatively charged drug molecules and cell membranes through non-covalent interaction, including electrostatic interactions. Significantly, the sequence design and the penetrating mechanisms are critical. In this brief synopsis, we summarize the transmembrane processes and mechanisms of arginine-rich peptides; and outline the relationship between the function of arginine-rich peptides and the number of arginine residues, arginine optical isomers, primary sequence, secondary and ternary structures, etc. Taking advantage of the penetration ability, biomedical applications of arginine-rich peptides have been refreshed, including drug/RNA delivery systems, biosensors, and blood-brain barrier (BBB) penetration. Understanding the membrane internalization mechanisms and design strategies of CPPs will expand their potential applications in clinical trials.
The Chemerin/CMKLR1 Axis Is Involved in the Recruitment of Microglia to Aβ Deposition through p38 MAPK Pathway
Authors: Chen Yanqing , Liu Zhen , Gong Ping , Zhang Haibo , Chen Yijun , Yao Songquan , Li Wei , Zhang Yan , Yu Yang
Published: August 2022

The accumulation of microglia around senile plaques is one of the pathological features of Alzheimer’s disease (AD). Chemerin is an adipokine with immune-modulating properties. Our previous study showed that chemokine-like receptor 1 (CMKLR1), the receptor for chemerin, is also a functional receptor of Aβ. However, it remains unclear whether and how the chemerin/CMKLR1 axis affects the migration of microglia. The impact of CMKLR1 on microglial activation and recruitment toward Aβ deposits was examined in APP/PS1 mice mated with CMKLR1 knockout (CMKLR1−/−) mice. CMKLR1 deficiency reduced the number of microglia around Aβ deposits in aged APP/PS1-CMKLR1−/− mice compared with APP/PS1 mice. Chemerin expression was significantly decreased in the hippocampus and cortex of aged APP/PS1 mice compared with WT mice. In vitro assays demonstrated that activation of the chemerin/CMKLR1 axis promoted the migration of primary cultures of microglia and murine microglial N9 cells. Mechanistic studies found that chemerin/CMKLR1 induced polarization and protrusion formation of microglia by promoting the remodeling of actin filaments and microtubules, and Golgi apparatus reorientation. The inhibition of p38 MAPK attenuated the promotion of the chemerin/CMKLR1 axis on microglial migration and polarization. In addition, chemerin inhibited Aβ-induced microglial clustering. The inhibition of p38 MAPK alleviated the suppressive effect of chemerin on Aβ-induced microglial aggregation. Our data indicate that the chemerin/CMKLR1 axis is involved in the migration and recruitment of microglia to senile plaques via the p38 MAPK pathway. Modulation of the chemerin/CMKLR1 axis is a potential new strategy for AD therapy.
The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma
Authors: Chelaru Nicoleta-Raluca , Chiosa Andrei , Sorop Andrei , Spiridon Andreea , Cojocaru Florentina , Domocos Dan , Cucu Dana , Popescu Irinel , Dima Simona-Olimpia
Published: August 2022

Pancreatic adenocarcinoma (PDAC) has low survival rates worldwide due to its tendency to be detected late and its characteristic desmoplastic reaction, which slows the use of targeted therapies. As such, the discovery of new connections between genes and the clinicopathological parameters contribute to the search for new biomarkers or targets for therapy. Transient receptor potential (TRP) channels are promising tools for cancer therapy or markers for PDAC. Therefore, in this study, we selected several genes encoding TRP proteins previously reported in cellular models, namely, Transient Receptor Potential Cation Channel Subfamily V Member 6 (TRPV6), Transient receptor potential ankyrin 1 (TRPA1), and Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), as well as the TRPM8 Channel Associated Factor 1 (TCAF1) and TRPM8 Channel Associated Factor 2 (TCAF2) proteins, as regulatory factors. We analyzed the expression levels of tumors from patients enrolled in public datasets and confirmed the results with a validation cohort of PDAC patients enrolled in the Clinical Institute Fundeni, Romania. We found significantly higher expression levels of TRPA1, TRPM8, and TCAF1/F2 in tumoral tissues compared to normal tissues, but lower expression levels of TRPV6, suggesting that TRP channels have either tumor-suppressive or oncogenic roles. The expression levels were correlated with the tumoral stages and are related to the genes involved in calcium homeostasis (Calbindin 1 or S100A4) or to proteins participating in metastasis (PTPN1). We conclude that the selected TRP proteins provide new insights in the search for targets and biomarkers needed for therapeutic strategies for PDAC treatment.
Welding Fume Instillation in Isolated Perfused Mouse Lungs—Effects of Zinc- and Copper-Containing Welding Fumes
Authors: Krabbe Julia , Kraus Thomas , Krabbe Hanif , Martin Christian , Ziegler Patrick
Published: August 2022

Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors. Isolated perfused mouse lungs (IPLs) were perfused and ventilated for 270 min. Lungs were instilled with saline solution (control), welding fume particle suspension (WFs) or the soluble fraction of the welding fumes (SF-WFs). Bronchoalveolar lavage fluid (BALF) and perfusate samples were analyzed for cytokine levels and lung tissue mRNA expression levels were analyzed via RT-PCR. All lungs instilled with WFs did not complete the experiments due to a fatal reduction in tidal volume. Accordingly, IL-6 and MPO levels were significantly higher in BALF of WF lungs compared to the control. IL-6 and MPO mRNA expression levels were also increased for WFs. Lungs instilled with SF-WFs only showed mild reactions in tidal volume, with BALF and mRNA expression levels not significantly differing from the control. Zinc- and copper-containing welding fume particles adversely affect IPLs when instilled, as evidenced by the fatal loss in tidal volume and increased cytokine expression and secretion. The effects are mainly caused by the particles, not by the soluble fraction.
Neuroprotective and Regenerative Effects of Growth Hormone (GH) in the Embryonic Chicken Cerebral Pallium Exposed to Hypoxic–Ischemic (HI) Injury
Authors: Olivares-Hernández Juan David , Carranza Martha , Balderas-Márquez Jerusa Elienai , Epardo David , Baltazar-Lara Rosario , Ávila-Mendoza José , Martínez-Moreno Carlos G. , Luna Maricela , Arámburo Carlos
Published: August 2022

Prenatal hypoxic–ischemic (HI) injury inflicts severe damage on the developing brain provoked by a pathophysiological response that leads to neural structural lesions, synaptic loss, and neuronal death, which may result in a high risk of permanent neurological deficits or even newborn decease. It is known that growth hormone (GH) can act as a neurotrophic factor inducing neuroprotection, neurite growth, and synaptogenesis after HI injury. In this study we used the chicken embryo to develop both in vitro and in vivo models of prenatal HI injury in the cerebral pallium, which is the equivalent of brain cortex in mammals, to examine whether GH exerts neuroprotective and regenerative effects in this tissue and the putative mechanisms involved in these actions. For the in vitro experiments, pallial cell cultures obtained from chick embryos were incubated under HI conditions (<5% O2, 1 g/L glucose) for 24 h and treated with 10 nM GH, and then collected for analysis. For the in vivo experiments, chicken embryos (ED14) were injected in ovo with GH (2.25 µg), exposed to hypoxia (12% O2) for 6 h, and later the pallial tissue was obtained to perform the studies. Results show that GH exerted a clear anti-apoptotic effect and promoted cell survival and proliferation in HI-injured pallial neurons, in both in vitro and in vivo models. Neuroprotective actions of GH were associated with the activation of ERK1/2 and Bcl-2 signaling pathways. Remarkably, GH protected mature neurons that were particularly harmed by HI injury, but was also capable of stimulating neural precursors. In addition, GH stimulated restorative processes such as the number and length of neurite outgrowth and branching in HI-injured pallial neurons, and these effects were blocked by a specific GH antibody, thus indicating a direct action of GH. Furthermore, it was found that the local expression of several synaptogenic markers (NRXN1, NRXN3, GAP-43, and NLG1) and neurotrophic factors (GH, BDNF, NT-3, IGF-1, and BMP4) were increased after GH treatment during HI damage. Together, these results provide novel evidence supporting that GH exerts protective and restorative effects in brain pallium during prenatal HI injury, and these actions could be the result of a joint effect between GH and endogenous neurotrophic factors. Also, they encourage further research on the potential role of GH as a therapeutic complement in HI encephalopathy treatments.
A New Method of Myostatin Inhibition in Mice via Oral Administration of Lactobacillus casei Expressing Modified Myostatin Protein, BLS-M22
Authors: Sung Dong Kyung , Kim Hyeongseop , Park Sang Eon , Lee Jiwon , Kim Ju-A , Park Young-Chul , Jeon Hong Bae , Chang Jong Wook , Lee Jeehun
Published: August 2022

Myostatin is a member of the transforming growth factor-beta superfamily and is an endogenous negative regulator of muscle growth. This study aimed to determine whether an oral administration of Lactobacillus casei expressing modified human myostatin (BLS-M22) could elicit sufficient levels of myostatin-specific antibody and improve the dystrophic features of an animal model of Duchenne muscular dystrophy (DMD; mdx mouse). BLS-M22 is a recombinant L. casei engineered to harbor the pKV vector and poly-gamma-glutamic acid gene linked to a modified human myostatin gene. Serological analysis showed that anti-myostatin IgG titers were significantly increased, and serum creatine kinase was significantly reduced in the BLS-M22-treated mdx mice compared to the control mice. In addition, treatment of BLS-M22 resulted in a significant increase in body weight and motor function (Rotarod behavior test). Histological analysis showed an improvement in the dystrophic features (fibrosis and muscle hypertrophy) of the mdx mice with the administration of BLS-M22. The circulating antibodies generated after BLS-M22 oral administration successfully lowered serum myostatin concentration. Myostatin blockade resulted in serological, histological, and functional improvements in mdx mice. Overall, the findings suggest the potential of BLS-M22 to treat DMD; however, further clinical trials are essential to ascertain its efficacy and safety in humans.
Evaluation of the Safety and Ochratoxin A Degradation Capacity of Pediococcus pentosaceus as a Dietary Probiotic with Molecular Docking Approach and Pharmacokinetic Toxicity Assessment
Authors: Park Sungkwon , Koo Jinsu , Kim Bosung , Pushparaj Karthika , Malaisamy Arunkumar , Liu Wen-Chao , Balasubramanian Balamuralikrishnan
Published: August 2022

The present study evaluated the properties and ochratoxin A (OTA) degradation capacity of the dietary probiotic Pediococcus pentosaceus BalaMMB-P3, isolated from a milk coagulant. The acidic tolerance of the isolate at pH 2–3 was checked with bile salts. No hemolytic activity was noted, which confirmed the nonpathogenicity of the strain. The isolate was tested in vitro for antibiotic susceptibility, enzymatic activity, bile salts hydrolase activity and antifungal activity against Penicillium verrucosum, Fusarium graminearum and Aspergillus ochraceus. A molecular docking-based OTA toxicity assessment was carried out for multitargeted proteins. The 16S rRNA gene-based phylogenetic assessment identified the strain as P. pentosaceus, and was authenticated in GenBank. The carboxylesterase and glutathione s-transferase enzymes showed active and strong interactions with esters and amide bonds, respectively. The compound exhibited carcinogenic and cytotoxicity effects at an LD50 value of 20 mg/kg. Furthermore, the strain showed a potent ability to reduce OTA and suggested the prospects for utilization in nutritional aspects of food.
Fertility Impairment after Trekking at High Altitude: A Proof of Mechanisms on Redox and Metabolic Seminal Changes
Authors: Verratti Vittore , Mrakic-Sposta Simona , Fusi Jonathan , Sabovic Iva , Franzoni Ferdinando , Pietrangelo Tiziana , Bondi Danilo , Dall’Acqua Stefano , Daniele Simona , Scarfò Giorgia , Di Giulio Camillo , Garolla Andrea
Published: August 2022

Many authors described negative but reversible effects of high-altitude hypoxic exposure on animal and human fertility in terms of sperm concentration, function, and biochemical alterations. The aim of this study was to evaluate the acute and chronic effects of high-altitude exposure on classical sperm parameters, redox status, and membrane composition in a group of travellers. Five healthy Italian males, all lowlanders not accustomed to the altitude, were evaluated after 19 days-trekking through low, moderate, and high altitudes in the Himalayas. Sperm samples were collected before (Pre), 10 days after (Post), and 70 days after the end of the expedition (Follow-up). Sperm concentration, cholesterol and oxysterol membrane content, and redox status were measured. Hypoxic trek led to a significant reduction in sperm concentration (p < 0.001, η2p = 0.91), with a reduction from Pre to Post (71.33 ± 38.81 to 60.65 ± 34.63 × 106/mL) and a further reduction at Follow-up (to 37.13 ± 39.17 × 106/mL). The seminal volume was significantly affected by the hypoxic trek (p = 0.001, η2p = 0.75) with a significant reduction from Pre to Post (2.86 ± 0.75 to 1.68 ± 0.49 mL) and with partial recovery at Follow-up (to 2.46 ± 0.45 mL). Moreover, subjects had an increase in ROS production (+86%), and a decrease in antioxidant capacity (−37%) in the Post period with partial recovery at Follow-up. These results integrated the hormonal response on thyroid function, hypothalamus–pituitary–gonadal axis, and the prolactin/cortisol pathways previously reported. An uncontrolled ROS production, rather than a compromised antioxidant activity, was likely the cause of impaired sperm quality. The reduction in fertility status observed in this study may lie in an evolutionary Darwinian explanation, i.e., limiting reproduction due to the “adaptive disadvantage” offered by the combined stressors of high-altitude hypoxia and daily physical exercise.
Properties of New Composite Materials Based on Hydroxyapatite Ceramic and Cross-Linked Gelatin for Biomedical Applications
Authors: Bartmański Michał , Rościszewska Magda , Wekwejt Marcin , Ronowska Anna , Nadolska-Dawidowska Małgorzata , Mielewczyk-Gryń Aleksandra
Published: August 2022

The main aim of the research was to develop a new biocompatible and injectable composite with the potential for application as a bone-to-implant bonding material or as a bone substitute. A composite based on hydroxyapatite, gelatin, and two various types of commercially available transglutaminase (TgBDF/TgSNF), as a cross-linking agent, was proposed. To evaluate the impacts of composite content and processing parameters on various properties of the material, the following research was performed: the morphology was examined by SEM microscopy, the chemical structure by FTIR spectroscopy, the degradation behavior was examined in simulated body fluid, the injectability test was performed using an automatic syringe pump, the mechanical properties using a nanoindentation technique, the surface wettability was examined by an optical tensiometer, and the cell viability was assayed by MTT and LDH. In all cases, a composite paste was successfully obtained. Injectability varied between 8 and 15 min. The type of transglutaminase did not significantly affect the surface topography or chemical composition. All samples demonstrated proper nanomechanical properties with Young’s modulus and the hardness close to the values of natural bone. BDF demonstrated better hydrophilic properties and structural stability over 7 days in comparison with SNF. In all cases, the transglutaminase did not lead to cell necrosis, but cellular proliferation was significantly inhibited, especially for the BDF agent.
Exposome, Molecular Pathways and One Health: The Invertebrate Caenorhabditis elegans
Authors: von Mikecz Anna
Published: August 2022

Due to its preferred habitats in the environment, the free-living nematode Caenorhabditis elegans has become a realistic target organism for pollutants, including manufactured nanoparticles. In the laboratory, the invertebrate animal model represents a cost-effective tool to investigate the molecular mechanisms of the biological response to nanomaterials. With an estimated number of 22,000 coding genes and short life span of 2–3 weeks, the small worm is a giant when it comes to characterization of molecular pathways, long-term low dose pollutant effects and vulnerable age-groups. Here, we review (i) flows of manufactured nanomaterials and exposition of C. elegans in the environment, (ii) the track record of C. elegans in biomedical research, and (iii) its potential to contribute to the investigation of the exposome and bridge nanotoxicology between higher organisms, including humans. The role of C. elegans in the one health concept is taken one step further by proposing methods to sample wild nematodes and their molecular characterization by single worm proteomics.
Feature Selection and Molecular Classification of Cancer Phenotypes: A Comparative Study
Authors: Zanella Luca , Facco Pierantonio , Bezzo Fabrizio , Cimetta Elisa
Published: August 2022

The classification of high dimensional gene expression data is key to the development of effective diagnostic and prognostic tools. Feature selection involves finding the best subset with the highest power in predicting class labels. Here, we conducted a comparative study focused on different combinations of feature selectors (Chi-Squared, mRMR, Relief-F, and Genetic Algorithms) and classification learning algorithms (Random Forests, PLS-DA, SVM, Regularized Logistic/Multinomial Regression, and kNN) to identify those with the best predictive capacity. The performance of each combination is evaluated through an empirical study on three benchmark cancer-related microarray datasets. Our results first suggest that the quality of the data relevant to the target classes is key for the successful classification of cancer phenotypes. We also proved that, for a given classification learning algorithm and dataset, all filters have a similar performance. Interestingly, filters achieve comparable or even better results with respect to the GA-based wrappers, while also being easier and faster to implement. Taken together, our findings suggest that simple, well-established feature selectors in combination with optimized classifiers guarantee good performances, with no need for complicated and computationally demanding methodologies.
Musculoskeletal Development and Skeletal Pathophysiology’s
Authors: Bradley Elizabeth W.
Published: August 2022

Musculoskeletal (MSK) disorders are one of the leading causes of disability for people of all ages and impart significant socio-economic burdens on society [...]
Mechanism and Utilization of Ogura Cytoplasmic Male Sterility in Cruciferae Crops
Authors: Ren Wenjing , Si Jinchao , Chen Li , Fang Zhiyuan , Zhuang Mu , Lv Honghao , Wang Yong , Ji Jialei , Yu Hailong , Zhang Yangyong
Published: August 2022

Hybrid production using lines with cytoplasmic male sterility (CMS) has become an important way to utilize heterosis in vegetables. Ogura CMS, with the advantages of complete pollen abortion, ease of transfer and a progeny sterility rate reaching 100%, is widely used in cruciferous crop breeding. The mapping, cloning, mechanism and application of Ogura CMS and fertility restorer genes in Brassica napus, Brassica rapa, Brassica oleracea and other cruciferous crops are reviewed herein, and the existing problems and future research directions in the application of Ogura CMS are discussed.
α3β4 Acetylcholine Nicotinic Receptors Are Components of the Secretory Machinery Clusters in Chromaffin Cells
Authors: Villanueva José , Criado Manuel , Giménez-Molina Yolanda , González-Vélez Virginia , Gil Amparo , Gutiérrez Luis Miguel
Published: August 2022

The heteromeric assembly of α3 and β4 subunits of acetylcholine nicotinic receptors (nAChRs) seems to mediate the secretory response in bovine chromaffin cells. However, there is no information about the localization of these nAChRs in relationship with the secretory active zones in this cellular model. The present work presents the first evidence that, in fact, a population of these receptors is associated through the F-actin cytoskeleton with exocytotic machinery components, as detected by SNAP-25 labeling. Furthermore, we also prove that, upon stimulation, the probability to find α3β4 nAChRs very close to exocytotic events increases with randomized distributions, thus substantiating the clear dynamic behavior of these receptors during the secretory process. Modeling on secretory dynamics and secretory component distributions supports the idea that α3β4 nAChR cluster mobility could help with improving the efficiency of the secretory response of chromaffin cells. Our study is limited by the use of conventional confocal microscopy; in this sense, a strengthening to our conclusions could come from the use of super-resolution microscopy techniques in the near future.