bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Landscape Structure on Wildlife–Vehicle Collisions: Geostatistical Analysis on Hot Spot and Habitat Proximity Relations
Authors: Galinskaitė Lina , Ulevičius Alius , Valskys Vaidotas , Samas Arūnas , Busher Peter E. , Ignatavičius Gytautas
Published: January 2022

Vehicle collisions with animals pose serious issues in countries with well-developed highway networks. Both expanding wildlife populations and the development of urbanised areas reduce the potential contact distance between wildlife species and vehicles. Many recent studies have been conducted to better understand the factors that influence wildlife–vehicle collisions (WVCs) and provide mitigation methods. Most of these studies examined road density, traffic volume, seasonal fluctuations, etc. However, in analysing the distribution of WVC, few studies have considered a spatial and significant distance geostatistical analysis approach that includes how different land-use categories are associated with the distance to WVCs. Our study investigated the spatial distribution of agricultural land, meadows and pastures, forests, built-up areas, rivers, lakes, and ponds, to highlight the most dangerous sections of roadways where WVCs occur. We examined six potential ‘hot spot’ distances (5–10–25–50–100–200 m) to evaluate the role different landscape elements play in the occurrence of WVC. The near analysis tool showed that a distance of 10–25 m to different landscape elements provided the most sensitive results. Hot spots associated with agricultural land, forests, as well as meadows and pastures, peaked on roadways in close proximity (10 m), while hot spots associated with built-up areas, rivers, lakes, and ponds peaked on roadways farther (200 m) from these land-use types. We found that the order of habitat importance in WVC hot spots was agricultural land < forests < meadows and pastures < built-up areas < rivers < lakes and ponds. This methodological approach includes general hot-spot analysis as well as differentiated distance analysis which helps to better reveal the influence of landscape structure on WVCs.
Where Maps Lie: Visualization of Perceptual Fallacy in Choropleth Maps at Different Levels of Aggregation
Authors: Beconytė Giedrė , Balčiūnas Andrius , Šturaitė Aurelija , Viliuvienė Rita
Published: January 2022

This paper proposes a method for quantitative evaluation of perception deviations due to generalization in choropleth maps. The method proposed is based on comparison of class values assigned to different aggregation units chosen for representing the same dataset. It is illustrated by the results of application of the method to population density maps of Lithuania. Three spatial aggregation levels were chosen for comparison: the 1 × 1 km statistical grid, elderships (NUTS3), and municipalities (NUTS2). Differences in density class values between the reference grid map and the other two maps were calculated. It is demonstrated that a perceptual fallacy on the municipality level population map of Lithuania leads to a misinterpretation of data that makes such maps frankly useless. The eldership level map is, moreover, also largely misleading, especially in sparsely populated areas. The method proposed is easy to use and transferable to any other field where spatially aggregated data are mapped. It can be used for visual analysis of the degree to which a generalized choropleth map is liable to mislead the user in particular areas.
BMP3 Affects Cortical and Trabecular Long Bone Development in Mice
Authors: Banovac Ivan , Grgurevic Lovorka , Rumenovic Viktorija , Vukicevic Slobodan , Erjavec Igor
Published: January 2022

Bone morphogenetic proteins (BMPs) have a major role in tissue development. BMP3 is synthesized in osteocytes and mature osteoblasts and has an antagonistic effect on other BMPs in bone tissue. The main aim of this study was to fully characterize cortical bone and trabecular bone of long bones in both male and female Bmp3−/− mice. To investigate the effect of Bmp3 from birth to maturity, we compared Bmp3−/− mice with wild-type littermates at the following stages of postnatal development: 1 day (P0), 2 weeks (P14), 8 weeks and 16 weeks of age. Bmp3 deletion was confirmed using X-gal staining in P0 animals. Cartilage and bone tissue were examined in P14 animals using Alcian Blue/Alizarin Red staining. Detailed long bone analysis was performed in 8-week-old and 16-week-old animals using micro-CT. The Bmp3 reporter signal was localized in bone tissue, hair follicles, and lungs. Bone mineralization at 2 weeks of age was increased in long bones of Bmp3−/− mice. Bmp3 deletion was shown to affect the skeleton until adulthood, where increased cortical and trabecular bone parameters were found in young and adult mice of both sexes, while delayed mineralization of the epiphyseal growth plate was found in adult Bmp3−/− mice.
Vitamin D3 Treatment Alters Thyroid Functional Morphology in Orchidectomized Rat Model of Osteoporosis
Authors: Šošić-Jurjević Branka , Trifunović Svetlana , Živanović Jasmina , Ajdžanović Vladimir , Miler Marko , Ristić Nataša , Filipović Branko
Published: January 2022

Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small.
Morphological Characterization and Transcriptome Analysis of New Dwarf and Narrow-Leaf (dnl2) Mutant in Maize
Authors: Han Lulu , Jiang Chenggong , Zhang Wei , Wang Hongwu , Li Kun , Liu Xiaogang , Liu Zhifang , Wu Yujin , Huang Changling , Hu Xiaojiao
Published: January 2022

Lodging is the primary factor limiting high yield under a high plant density. However, an optimal plant height and leaf shape can effectively decrease the lodging risk. Here we studied an ethyl methanesulfonate (EMS)-induced dwarf and a narrow-leaf mutant, dnl2. Gene mapping indicated that the mutant was controlled by a gene located on chromosome nine. Phenotypic and cytological observations revealed that dnl2 showed inhibited cell growth, altered vascular bundle patterning, and disrupted secondary cell wall structure when compared with the wild-type, which could be the direct cause of the dwarf and narrow-leaf phenotype. The phytohormone levels, especially auxin and gibberellin, were significantly decreased in dnl2 compared to the wild-type plants. Transcriptome profiling of the internodes of the dnl2 mutant and wild-type revealed a large number of differentially expressed genes enriched in the cell wall biosynthesis, remodeling, and hormone biosynthesis and signaling pathways. Therefore, we suggest that crosstalk between hormones (the altered vascular bundle and secondary cell wall structure) may contribute to the dwarf and narrow-leaf phenotype by influencing cell growth. These results provide a foundation for DNL2 gene cloning and further elucidation of the molecular mechanism of the regulation of plant height and leaf shape in maize.
A Hot Topic: Cancer Immunotherapy and Natural Killer Cells
Authors: Michel Tatiana , Ollert Markus , Zimmer Jacques
Published: January 2022

Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.
MiR-320-3p Regulates the Proliferation and Differentiation of Myogenic Progenitor Cells by Modulating Actin Remodeling
Authors: Nguyen Mai Thi , Lee Wan
Published: January 2022

Skeletal myogenesis is essential for the maintenance of muscle quality and quantity, and impaired myogenesis is intimately associated with muscle wasting diseases. Although microRNA (miRNA) plays a crucial role in myogenesis and relates to muscle wasting in obesity, the molecular targets and roles of miRNAs modulated by saturated fatty acids (SFA) are largely unknown. In the present study, we investigated the role of miR-320-3p on the differentiation of myogenic progenitor cells. Palmitic acid (PA), the most abundant dietary SFA, suppressed myogenic factors expression and impaired differentiation in C2C12 myoblasts, and these effects were accompanied by CFL2 downregulation and miR-320-3p upregulation. In particular, miR-320-3p appeared to target CFL2 mRNA directly and suppress the expression of CFL2, an essential factor for filamentous actin (F-actin) depolymerization. Transfection of myoblasts with miR-320-3p mimic increased F-actin formation and nuclear translocation of Yes-associated protein 1 (YAP1), a key component of mechanotransduction. Furthermore, miR-320-3p mimic increased myoblast proliferation and markedly impeded the expression of MyoD and MyoG, consequently inhibiting myoblast differentiation. In conclusion, our current study highlights the role of miR-320-3p on CFL2 expression, YAP1 activation, and myoblast differentiation and suggests that PA-inducible miR-320-3p is a significant mediator of muscle wasting in obesity.
Nature-Inspired Effects of Naturally Occurring Trace Element-Doped Hydroxyapatite Combined with Surface Interactions of Mineral-Apatite Single Crystals on Human Fibroblast Behavior
Authors: Tyszka-Czochara Malgorzata , Suder Marzena , Dołhańczuk-Śródka Agnieszka , Rajfur Małgorzata , Grata Katarzyna , Starosta Michał , Jagoda-Pasternak Agnieszka , Kasprzyk Wiktor , Nowak Anna K. , Ahmadzadeh Saeid , Kopeć Dorota , Suryło Piotr , Świergosz Tomasz , Stadnicka Katarzyna M.
Published: January 2022

Innovative engineering design for biologically active hydroxyapatites requires enhancing both mechanical and physical properties, along with biocompatibility, by doping with appropriate chemical elements. Herein, the purpose of this investigation was to evaluate and elucidate the model of naturally occurring hydroxyapatite and the effects of doped trace elements on the function of normal human fibroblasts, representing the main cells of connective tissues. The substrates applied (geological apatites with hexagonal prismatic crystal habit originated from Slyudyanka, Lake Baikal, Russia (GAp) and from Imilchil, The Atlas Mountains, Morocco (YAp)) were prepared from mineral natural apatite with a chemical composition consistent with the building blocks of enamel and enriched with a significant F− content. Materials in the form of powders, extracts and single-crystal plates have been investigated. Moreover, the effects on the function of fibroblasts cultured on the analyzed surfaces in the form of changes in metabolic activity, proliferation and cell morphology were evaluated. Apatite plates were also evaluated for cytotoxicity and immune cell activation capacity. The results suggest that a moderate amount of F− has a positive effect on cell proliferation, whereas an inhibitory effect was attributed to the Cl− concentration. It was found that for (100) GAp plate, fibroblast proliferation was significantly increased, whereas for (001) YAp plate, it was significantly reduced, with no cytotoxic effect and no immune response from macrophages exposed to these materials. The study of the interaction of fibroblasts with apatite crystal surfaces provides a characterization relevant to medical applications and may contribute to the design of biomaterials suitable for medical applications and the evaluation of their bioavailability.
Consequences of COVID-19 for the Pancreas
Authors: Abramczyk Urszula , Nowaczyński Maciej , Słomczyński Adam , Wojnicz Piotr , Zatyka Piotr , Kuzan Aleksandra
Published: January 2022

Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of COVID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ. It appears that diabetes is not only a condition that predisposes a patient to suffer from more severe COVID-19, but it may also develop as a consequence of infection with this virus. Some SARS-CoV-2 inpatients experience acute pancreatitis due to direct infection of the tissue with the virus or due to systemic multiple organ dysfunction syndrome (MODS) accompanied by elevated levels of amylase and lipase. There are also reports that reveal a relationship between the development and treatment of pancreatic cancer and SARS-CoV-2 infection. It has been postulated that evaluation of pancreatic function should be increased in post-COVID-19 patients, both adults and children.
Therapeutic CFTR Correction Normalizes Systemic and Lung-Specific S1P Level Alterations Associated with Heart Failure
Authors: Uhl Franziska E. , Vanherle Lotte , Matthes Frank , Meissner Anja
Published: January 2022

Heart failure (HF) is among the main causes of death worldwide. Alterations of sphingosine-1-phosphate (S1P) signaling have been linked to HF as well as to target organ damage that is often associated with HF. S1P’s availability is controlled by the cystic fibrosis transmembrane regulator (CFTR), which acts as a critical bottleneck for intracellular S1P degradation. HF induces CFTR downregulation in cells, tissues and organs, including the lung. Whether CFTR alterations during HF also affect systemic and tissue-specific S1P concentrations has not been investigated. Here, we set out to study the relationship between S1P and CFTR expression in the HF lung. Mice with HF, induced by myocardial infarction, were treated with the CFTR corrector compound C18 starting ten weeks post-myocardial infarction for two consecutive weeks. CFTR expression, S1P concentrations, and immune cell frequencies were determined in vehicle- and C18-treated HF mice and sham controls using Western blotting, flow cytometry, mass spectrometry, and qPCR. HF led to decreased pulmonary CFTR expression, which was accompanied by elevated S1P concentrations and a pro-inflammatory state in the lungs. Systemically, HF associated with higher S1P plasma levels compared to sham-operated controls and presented with higher S1P receptor 1-positive immune cells in the spleen. CFTR correction with C18 attenuated the HF-associated alterations in pulmonary CFTR expression and, hence, led to lower pulmonary S1P levels, which was accompanied by reduced lung inflammation. Collectively, these data suggest an important role for the CFTR-S1P axis in HF-mediated systemic and pulmonary inflammation.
Engagement of the CXCL12–CXCR4 Axis in the Interaction of Endothelial Progenitor Cell and Smooth Muscle Cell to Promote Phenotype Control and Guard Vascular Homeostasis
Authors: Mause Sebastian F. , Ritzel Elisabeth , Deck Annika , Vogt Felix , Liehn Elisa A.
Published: January 2022

Endothelial progenitor cells (EPCs) are involved in vascular repair and modulate properties of smooth muscle cells (SMCs) relevant for their contribution to neointima formation following injury. Considering the relevant role of the CXCL12–CXCR4 axis in vascular homeostasis and the potential of EPCs and SMCs to release CXCL12 and express CXCR4, we analyzed the engagement of the CXCL12–CXCR4 axis in various modes of EPC–SMC interaction relevant for injury- and lipid-induced atherosclerosis. We now demonstrate that the expression and release of CXCL12 is synergistically increased in a CXCR4-dependent mechanism following EPC–SMC interaction during co-cultivation or in response to recombinant CXCL12, thus establishing an amplifying feedback loop Additionally, mechanical injury of SMCs induces increased release of CXCL12, resulting in enhanced CXCR4-dependent recruitment of EPCs to SMCs. The CXCL12–CXCR4 axis is crucially engaged in the EPC-triggered augmentation of SMC migration and the attenuation of SMC apoptosis but not in the EPC-mediated increase in SMC proliferation. Compared to EPCs alone, the alliance of EPC–SMC is superior in promoting the CXCR4-dependent proliferation and migration of endothelial cells. When direct cell–cell contact is established, EPCs protect the contractile phenotype of SMCs via CXCL12–CXCR4 and reverse cholesterol-induced transdifferentiation toward a synthetic, macrophage-like phenotype. In conclusion we show that the interaction of EPCs and SMCs unleashes a CXCL12–CXCR4-based autoregulatory feedback loop promoting regenerative processes and mediating SMC phenotype control to potentially guard vascular homeostasis.
Emerging Role of Microbiome in the Prevention of Urinary Tract Infections in Children
Authors: Kawalec Anna , Zwolińska Danuta
Published: January 2022

The microbiome of the urinary tract plays a significant role in maintaining health through the impact on bladder homeostasis. Urobiome is of great importance in maintaining the urothelial integrity and preventing urinary tract infection (UTI), as well as promoting local immune function. Dysbiosis in this area has been linked to an increased risk of UTIs, nephrolithiasis, and dysfunction of the lower urinary tract. However, the number of studies in the pediatric population is limited, thus the characteristic of the urobiome in children, its role in a child’s health, and pediatric urologic diseases are not completely understood. This review aims to characterize the healthy urobiome in children, the role of dysbiosis in urinary tract infection, and to summarize the strategies to modification and reshape disease-prone microbiomes in pediatric patients with recurrent urinary tract infections.
An RNA Interference Tool to Silence Genes in Sarcoptes scabiei Eggs
Authors: Fernando Deepani D. , Korhonen Pasi K. , Gasser Robin B. , Fischer Katja
Published: January 2022

In a quest for new interventions against scabies—a highly significant skin disease of mammals, caused by a parasitic mite Sarcoptes scabiei—we are focusing on finding new intervention targets. RNA interference (RNAi) could be an efficient functional genomics approach to identify such targets. The RNAi pathway is present in S. scabiei and operational in the female adult mite, but other developmental stages have not been assessed. Identifying potential intervention targets in the egg stage is particularly important because current treatments do not kill this latter stage. Here, we established an RNAi tool to silence single-copy genes in S. scabiei eggs. Using sodium hypochlorite pre-treatment, we succeeded in rendering the eggshell permeable to dsRNA without affecting larval hatching. We optimised the treatment of eggs with gene-specific dsRNAs to three single-copy target genes (designated Ss-Cof, Ss-Ddp, and Ss-Nan) which significantly and repeatedly suppressed transcription by ~66.6%, 74.3%, and 84.1%, respectively. Although no phenotypic alterations were detected in dsRNA-treated eggs for Ss-Cof and Ss-Nan, the silencing of Ss-Ddp resulted in a 38% reduction of larval hatching. This RNAi method is expected to provide a useful tool for larger-scale functional genomic investigations for the identification of essential genes as potential drug targets.
Hypoxia Marker Carbonic Anhydrase IX Is Present in Abdominal Aortic Aneurysm Tissue and Plasma
Authors: Grossmannova Katarina , Barathova Monika , Belvoncikova Petra , Lauko Viliam , Csaderova Lucia , Tomka Jan , Dulka Tomas , Pastorek Jaromir , Madaric Juraj
Published: January 2022

Abdominal aortic aneurysms (AAA) are a significant cause of premature deaths worldwide. Since there is no specific treatment for reducing AAA progression, it is crucial to understand the pathogenesis leading to aneurysm wall weakening/remodeling and identify new proteins involved in this process which could subsequently serve as novel therapeutic targets. In this study, we analyzed the presence of the hypoxia-related proteins carbonic anhydrase IX (CA IX), hypoxia-inducible factor 1α (HIF-1α), and AKT as the key molecule in the phosphoinositide-3-kinase pathway in the AAA wall. Additionally, we used a blood-based assay to examine soluble CA IX (s-CA IX) levels in the plasma of AAA patients. Using western blotting, we detected CA IX protein in 12 out of 15 AAA tissue samples. Immunohistochemistry staining proved CA IX expression in the media of the aneurysmal wall. Evaluation of phosphorylated (p-AKT) and total AKT showed elevated levels of both forms in AAA compared to normal aorta. Using ELISA, we determined the concentration of s-CA IX >20 pg/mL in 13 out of 15 AAA patients. Results obtained from in silico analysis of CA9 and aneurysm-associated genes suggest a role for CA IX in aneurysmal wall remodeling. Our results prove the presence of hypoxia-related CA IX in AAA tissues and indicate a possible role of CA IX in hypoxia-associated cardiovascular diseases.
The Broad-Spectrum Antiviral Potential of the Amphibian Peptide AR-23
Authors: Chianese Annalisa , Zannella Carla , Monti Alessandra , De Filippis Anna , Doti Nunzianna , Franci Gianluigi , Galdiero Massimiliano
Published: January 2022

Viral infections represent a serious threat to the world population and are becoming more frequent. The search and identification of broad-spectrum antiviral molecules is necessary to ensure new therapeutic options, since there is a limited availability of effective antiviral drugs able to eradicate viral infections, and consequently due to the increase of strains that are resistant to the most used drugs. Recently, several studies on antimicrobial peptides identified them as promising antiviral agents. In detail, amphibian skin secretions serve as a rich source of natural antimicrobial peptides. Their antibacterial and antifungal activities have been widely reported, but their exploitation as potential antiviral agents have yet to be fully investigated. In the present study, the antiviral activity of the peptide derived from the secretion of Rana tagoi, named AR-23, was evaluated against both DNA and RNA viruses, with or without envelope. Different assays were performed to identify in which step of the infectious cycle the peptide could act. AR-23 exhibited a greater inhibitory activity in the early stages of infection against both DNA (HSV-1) and RNA (MeV, HPIV-2, HCoV-229E, and SARS-CoV-2) enveloped viruses and, on the contrary, it was inactive against naked viruses (PV-1). Altogether, the results indicated AR-23 as a peptide with potential therapeutic effects against a wide variety of human viruses.
HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia
Authors: Liu Shiqiang , Fu Pengyu , Ning Kaiting , Wang Rui , Yang Baoqiang , Chen Jiahui , Xu Huiyun
Published: January 2022

Exposure to high altitude environment leads to skeletal muscle atrophy. As a hormone secreted by skeletal muscles after exercise, irisin contributes to promoting muscle regeneration and ameliorating skeletal muscle atrophy, but its role in hypoxia-induced skeletal muscle atrophy is still unclear. Our results showed that 4 w of hypoxia exposure significantly reduced body weight and gastrocnemius muscle mass of mice, as well as grip strength and the duration time of treadmill exercise. Hypoxic treatment increased HIF-1α expression and decreased both the circulation level of irisin and its precursor protein FNDC5 expression in skeletal muscle. In in vitro, CoCl2-induced chemical hypoxia and 1% O2 ambient hypoxia both reduced FNDC5, along with the increase in HIF-1α. Moreover, the decline in the area and diameter of myotubes caused by hypoxia were rescued by inhibiting HIF-1α via YC-1. Collectively, our research indicated that FNDC5/irisin was negatively regulated by HIF-1α and could participate in the regulation of muscle atrophy caused by hypoxia.
Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine
Authors: Furlani Franco , Rossi Arianna , Grimaudo Maria Aurora , Bassi Giada , Giusto Elena , Molinari Filippo , Lista Florigio , Montesi Monica , Panseri Silvia
Published: January 2022

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.
Novel Findings regarding the Bioactivity of the Natural Blue Pigment Genipin in Human Diseases
Authors: Bryś Magdalena , Urbańska Karina , Olas Beata
Published: January 2022

Genipin is an important monoterpene iridoid compound isolated from Gardenia jasminoides J.Ellis fruits and from Genipa americana fruits, or genipap. It is a precursor of a blue pigment which may be attractive alternative to existing food dyes and it possesses various potential therapeutic properties such as anti-cancer, anti-diabetic and hepatoprotective activity. Biomedical studies also show that genipin may act as a neuroprotective drug. This review describes new aspects of the bioactivity of genipin against various diseases, as well as its toxicity and industrial applications, and presents its potential mechanism of action.
Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells
Authors: Jang Sunhee , Kwon Eui-Jong , Lee Jennifer Jooha
Published: January 2022

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.
Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke
Authors: Onose Gelu , Anghelescu Aurelian , Blendea Dan , Ciobanu Vlad , Daia Cristina , Firan Florentina , Oprea Mihaela , Spinu Aura , Popescu Cristina , Ionescu Anca , Busnatu Ștefan , Munteanu Constantin
Published: January 2022

BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that “non-pharmacological” approaches might provide new opportunities for stroke therapy, such as electro-/acupuncture, hyperbaric oxygen therapy, hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic/rehabilitative interventions, described as non-invasive and non-pharmacological.
Psychotropic Drug Effects on Steroid Stress Hormone Release and Possible Mechanisms Involved
Authors: Romanova Zuzana , Hlavacova Natasa , Jezova Daniela
Published: January 2022

There is no doubt that chronic stress accompanied by adrenocortical stress hormone release affects the development and treatment outcome of several mental disorders. Less attention has been paid to the effects of psychotropic drugs on adrenocortical steroids, particularly in clinical studies. This review focuses on the knowledge related to the possible modulation of cortisol and aldosterone secretion under non-stress and stress conditions by antipsychotic drugs, which are being used in the treatment of several psychotic and affective disorders. The molecular mechanisms by which antipsychotic drugs may influence steroid stress hormones include the modulation of central and/or adrenocortical dopamine and serotonin receptors, modulation of inflammatory cytokines, influence on regulatory mechanisms in the central part of the hypothalamic-pituitary axis, inhibition of corticotropin-releasing hormone gene promoters, influencing glucocorticoid receptor-mediated gene transcription, indirect effects via prolactin release, alteration of signaling pathways of glucocorticoid and mineralocorticoid actions. Clinical studies performed in healthy subjects, patients with psychosis, and patients with bipolar disorder suggest that single and repeated antipsychotic treatments either reduce cortisol concentrations or do not affect its secretion. A single and potentially long-term treatment with dopamine receptor antagonists, including antipsychotics, has a stimulatory action on aldosterone release.
Time-Resolved Gene Expression Analysis Monitors the Regulation of Inflammatory Mediators and Attenuation of Adaptive Immune Response by Vitamin D
Authors: Hanel Andrea , Carlberg Carsten
Published: January 2022

Peripheral blood mononuclear cells (PBMCs) belong to the innate and adaptive immune system and are highly sensitive and responsive to changes in their systemic environment. In this study, we focused on the time course of transcriptional changes in freshly isolated human PBMCs 4, 8, 24 and 48 h after onset of stimulation with the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Taking all four time points together, 662 target genes were identified and segregated either by time of differential gene expression into 179 primary and 483 secondary targets or by driver of expression change into 293 direct and 369 indirect targets. The latter classification revealed that more than 50% of target genes were primarily driven by the cells' response to ex vivo exposure than by the nuclear hormone and largely explained its down-regulatory effect. Functional analysis indicated vitamin D’s role in the suppression of the inflammatory and adaptive immune response by down-regulating ten major histocompatibility complex class II genes, five alarmins of the S100 calcium binding protein A family and by affecting six chemokines of the C-X-C motif ligand family. Taken together, studying time-resolved responses allows to better contextualize the effects of vitamin D on the immune system.
Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases
Authors: Saenz-Medina Javier , Muñoz Mercedes , Rodriguez Claudia , Sanchez Ana , Contreras Cristina , Carballido-Rodríguez Joaquín , Prieto Dolores
Published: January 2022

An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. Methods: A non-systematic review has been performed mixing the terms “urolithiasis”, “kidney stone” or “nephrolithiasis” with “cardiovascular disease”, “myocardial infarction”, “stroke”, or “endothelial dysfunction”. Results: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. Conclusions: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.
SYNCRIP Modulates the Epithelial-Mesenchymal Transition in Hepatocytes and HCC Cells
Authors: Riccioni Veronica , Trionfetti Flavia , Montaldo Claudia , Garbo Sabrina , Marocco Francesco , Battistelli Cecilia , Marchetti Alessandra , Strippoli Raffaele , Amicone Laura , Cicchini Carla , Tripodi Marco
Published: January 2022

Heterogeneous nuclear ribonucleoproteins (hnRNPs) control gene expression by acting at multiple levels and are often deregulated in epithelial tumors; however, their roles in the fine regulation of cellular reprogramming, specifically in epithelial–mesenchymal transition (EMT), remain largely unknown. Here, we focused on the hnRNP-Q (also known as SYNCRIP), showing by molecular analysis that in hepatocytes it acts as a “mesenchymal” gene, being induced by TGFβ and modulating the EMT. SYNCRIP silencing limits the induction of the mesenchymal program and maintains the epithelial phenotype. Notably, in HCC invasive cells, SYNCRIP knockdown induces a mesenchymal–epithelial transition (MET), negatively regulating their mesenchymal phenotype and significantly impairing their migratory capacity. In exploring possible molecular mechanisms underlying these observations, we identified a set of miRNAs (i.e., miR-181-a1-3p, miR-181-b1-3p, miR-122-5p, miR-200a-5p, and miR-let7g-5p), previously shown to exert pro- or anti-EMT activities, significantly impacted by SYNCRIP interference during EMT/MET dynamics and gathered insights, suggesting the possible involvement of this RNA binding protein in their transcriptional regulation.
The Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors
Authors: Escandon Paulina , Nicholas Sarah E. , Cunningham Rebecca L. , Murphy David A. , Riaz Kamran M. , Karamichos Dimitrios
Published: January 2022

Keratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. KC onset and progression are attributed to diverse factors that include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study aims to determine the role of corneal stroma sex hormone receptors in KC and their interplay with estrone (E1) and estriol (E3) using our established 3D in vitro model. Healthy cornea stromal cells (HCFs) and KC cornea stromal cells (HKCs), both male and female, were stimulated with various concentrations of E1 and E3. Significant changes were observed between cell types, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ) using Western blot analysis. E1 and E3 stimulations in HCF females showed AR, PR, and ERβ were significantly upregulated compared to HCF males. In contrast, ERα and ERβ had significantly higher expression in HKC’s females than HKC’s males. Our data suggest that the human cornea is a sex-dependent, hormone-responsive tissue that is significantly influenced by E1 and E3. Therefore, it is plausible that E1, E3, and sex hormone receptors are involved in the KC pathobiology, warranting further investigation.
Efficacy of Helicoverpa Armigera Nucleopolyhedrovirus on Soybean for Control of Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) in Arkansas Agriculture
Authors: Black Joseph L. , Lorenz Gus M. , Cato Aaron J. , Bateman Nick R. , Seiter Nicholas J.
Published: January 2022

Helicoverpa armigera nucleopolyhedrovirus (HearNPV) is a naturally occurring virus commercially produced for control of Heliothines, including Helicoverpa zea. One drawback with using this virus for control has been the slower time to mortality compared with synthetic insecticides. However, a new formulation (Heligen®) has anecdotally been thought to result in quicker mortality than previously observed. The objective of this study was to evaluate percent defoliation, the efficacy of HearNPV on mortality for each H. zea larval instar, and the potential for control of a second infestation. Fourteen days after the first infestation, all plants were re-infested with a second instar larva to simulate a second infestation. Helicoverpa armigera nucleopolyhedrovirus was effective at killing 1st–3rd instars, resulting in 99% mortality over 4–6 days. However, 4th and 5th instar mortality only reached 35%. Second infestation larvae died between 3.4 and 3.8 days, significantly faster than the 1st infestation of 2nd instars, which had a mean time to mortality of 4.9 days. An increase in mortality rate is probably due to increasing viral concentrations after viral replication within the first hosts. Final defoliation percentages were significantly smaller in the treated plants versus the untreated plants. Only 3rd and 4th instar larvae caused percent defoliation to exceed the current Arkansas action threshold of 40%. Helicoverpa armigera nucleopolyhedrovirus in the Heligen formulation can control 1st–3rd instars within 4–6 days, while keeping defoliation below the action threshold of 40%.
Isolation of Beauveria Strains and Their Potential as Control Agents for Lema bilineata Germar (Coleoptera: Chrysomelidae)
Authors: Furuie Jason Lee , Stuart Andressa Katiski da Costa , Voidaleski Morgana Ferreira , Zawadneak Maria Aparecida Cassilha , Pimentel Ida Chapaval
Published: January 2022

Lema bilineata Germar (Coleoptera: Chrysomelidae) was recently reported to damage Physalis peruviana crops in Brazil. Given the potential for inflicting damage on other Solanaceae species and the lack of alternatives for controlling this pest, we assessed the pathogenicity of 15 Beauveria isolates against L. bilineata adults in vitro. In addition, three of these isolates were tested for their ovicidal effect against L. bilineata eggs. Fungal strains were isolated from mummified corpses of L. bilineata collected in a non-commercial field in Paraná, Brazil. The isolates were identified as Beauveria bassiana using molecular markers. Lema bilineata adults were susceptible to conidial suspensions of all these isolates at a concentration of 108 conidia mL−1. Deaths caused by fungal extrusion were confirmed. Three strains were found to be more virulent against L. bilineata adults and showed ovicidal effects. This is the first study on entomopathogenic fungi isolated from dead insects collected from P. peruviana crops and tested against L. bilineata carried out in Brazil. The results obtained in the laboratory indicate the high potential of the use of three B. bassiana strains against L. bilineata as a biocontrol agent.
Changes in Biomass and Diversity of Soil Macrofauna along a Climatic Gradient in European Boreal Forests
Authors: Kozlov Mikhail V. , Zverev Vitali , Gusarov Vladimir I. , Korobushkin Daniil I. , Krivosheina Nina P. , Mattila Jaakko , Mutanen Marko , Popova Anna , Prosvirov Alexander S. , Punttila Pekka , Söderman Guy , Stańska Marzena , Taylor Astrid , Vahtera Varpu , Zubrii Natalia A. , Zvereva Elena L.
Published: January 2022

Latitudinal gradients allow insights into the factors that shape ecosystem structure and delimit ecosystem processes, particularly climate. We asked whether the biomass and diversity of soil macrofauna in boreal forests change systematically along a latitudinal gradient spanning from 60° N to 69° N. Invertebrates (3697 individuals) were extracted from 400 soil samples (20 × 20 cm, 30 cm depth) collected at ten sites in 2015–2016 and then weighed and identified. We discovered 265 species living in soil and on the soil surface; their average density was 0.486 g d·w·m−2. The species-level diversity decreased from low to high latitudes. The biomass of soil macrofauna showed no latitudinal changes in early summer but decreased towards the north in late summer. This variation among study sites was associated with the decrease in mean annual temperature by ca 5 °C and with variation in fine root biomass. The biomass of herbivores and fungivores decreased towards the north, whereas the biomass of detritivores and predators showed no significant latitudinal changes. This variation in latitudinal biomass patterns among the soil macrofauna feeding guilds suggests that these guilds may respond differently to climate change, with poorly understood consequences for ecosystem structure and functions.
Hemorrhagic Resuscitation Guided by Viscoelastography in Far-Forward Combat and Austere Civilian Environments: Goal-Directed Whole-Blood and Blood-Component Therapy Far from the Trauma Center
Authors: Lantry James H. , Mason Phillip , Logsdon Matthew G. , Bunch Connor M. , Peck Ethan E. , Moore Ernest E. , Moore Hunter B. , Neal Matthew D. , Thomas Scott G. , Khan Rashid Z. , Gillespie Laura , Florance Charles , Korzan Josh , Preuss Fletcher R. , Mason Dan , Saleh Tarek , Marsee Mathew K. , Vande Lune Stefani , Ayoub Qamarnisa , Fries Dietmar , Walsh Mark M.
Published: January 2022

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy—especially in austere or challenging environments—is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.
Association between Inter-Limb Asymmetries in Lower-Limb Functional Performance and Sport Injury: A Systematic Review of Prospective Cohort Studies
Authors: Guan Yanfei , Bredin Shannon , Taunton Jack , Jiang Qinxian , Wu Nana , Warburton Darren
Published: January 2022

Background: Inter-limb asymmetry in lower-limb functional performance has been associated with increased risk of sport injury; however, findings are not always consistent. Purpose: To conduct a systematic review on whether inter-limb asymmetry in lower-limb functional performance can predict sport injury. Methods: Four electronic databases (MEDLINE, EMBASE, Web of Science, and SportDiscus) were systematically searched for prospective cohort studies reporting the association between inter-limb asymmetry in lower-limb functional performance and sport injury. Results: A total of 28 prospective cohort studies were included in the analyses. Collectively, the findings were highly inconsistent, and a clear statement on the association between each asymmetry and sport injury was difficult. Conclusions: Highly inconsistent findings make it difficult to create clear recommendations on the relationship between the inter-limb asymmetry in lower-limb functional performance (power, muscle flexibility, and dynamic balance) and sport injury. The influence of potential factors (selection of tests/parameters, participant characteristics, definition of injury, and ways of calculating asymmetry) should be considered when using previous findings.