bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial Microorganisms and Water Stress Influence Quercus ilex Seedlings’ Response to Phytophthora cinnamomi Rands
Authors: Cabrera-Puerto Roberto J. , Ruiz-Gómez Francisco J. , Navarro-Cerrillo Rafael M.
Published: April 2023

Root rot affecting holm oak is a cause of high ecological and economic losses in the Iberian Peninsula, highlighting the relevance of developing disease control methods. The aim of this work was to assess the effect of a biological treatment composed of beneficial organisms (Trichoderma complex, T-complex) on holm oak seedlings infected by Phytophthora cinnamomi in two contrasted holm oak ecotypes, one considered highly susceptible (HU) and another considered tolerant to the pathogen (GR). For this purpose, a complete multifactorial test was carried out in a greenhouse, and seedlings were monitored for survival analysis and morphological and physiological attribute evaluation. Mortality began earlier in the susceptible (HU) than in the tolerant (GR) ecotype, and survival showed different trends due to the inoculation with beneficial microorganisms depending on the ecotype of the plants. The tolerant ecotype showed a high survival rate and better response to the treatment with beneficial microorganisms. GLM showed that the main reason for differences between treatments was ecotype, followed by T-complex and irrigation, and a weak interaction between ecotype and P. cinnamomi was found. The linear relationship between photosynthesis (A) and transpiration (Tr) showed an increase in the A/Tr rates for infected and inoculated plants under drought conditions for the GR ecotype. The tolerant ecotype was benefited more by the beneficial microorganism treatment. The understanding of the genetic diversity of Q. ilex and water stress influence on the efficacy of biological treatments against root rot provides useful information to develop environmentally friendly disease control methods to address the holm oak decline.
On Fractional Integral Inequalities of Riemann Type for Composite Convex Functions and Applications
Authors: Vivas-Cortez Miguel , Mukhtar Muzammil , Shabbir Iram , Samraiz Muhammad , Yaqoob Muhammad
Published: April 2023

In this study, we apply fractional calculus on certain convex functions and derive many novel mean-type inequalities by employing fractional calculus and convexity theory. In order to investigate fractional mean inequalities, we first build an identity in this study. Then, with its help, we derive many mean-type inequalities and estimate the error of HH inequality using a generalized version of RL-fractional integrals and certain classes of convex functions. The results obtained are validated by taking specific functions. Many mean-type inequalities that exist in the literature are generalized by the main results of this study.
Fault Slip Tendency Analysis for a Deep-Sea Basalt CO2 Injection in the Cascadia Basin
Authors: Ekpo Johnson Eneanwan , Scherwath Martin , Moran Kate , Dosso Stan E. , Rohr Kristin M.
Published: April 2023

Offshore basalts, most commonly found as oceanic crust formed at mid-ocean ridges, are estimated to offer an almost unlimited reservoir for CO2 sequestration and are regarded as one of the most durable locations for carbon sequestration since injected CO2 will mineralize, forming carbonate rock. As part of the Solid Carbon project, the potential of the Cascadia Basin, about 200 km off the west coast of Vancouver Island, Canada, is investigated as a site for geological CO2 sequestration. In anticipation of a demonstration proposed to take place, it is essential to assess the tendency of geologic faults in the area to slip in the presence of CO2 injection, potentially causing seismic events. To understand the viability of the reservoir, a quantitative risk assessment of the proposed site area was conducted. This involved a detailed characterization of the proposed injection site to understand baseline stress and pressure conditions and identify individual faults or fault zones with the potential to slip and thereby generate seismicity. The results indicate that fault slip potential is minimal (less than 1%) for a constant injection of up to ~2.5 MT/yr. This is in part due to the thickness of the basalt aquifer and its permeability. The results provide a reference for assessing the potential earthquake risk from CO2 injection in similar ocean basalt basins.
Simultaneous Biocementation and Compaction of a Soil to Avoid the Breakage of Cementitious Structures during the Execution of Earthwork Constructions
Authors: Hernández Laura Morales , Garzón Eduardo Garzón , Sánchez-Soto Pedro J. , Morales Enrique Romero
Published: April 2023

This research focuses on the potential for microbial treatment to stabilize compacted soils, which are often utilized in earthwork projects. A silt–clay sand was used to describe a particular kind of soil. The suggested remedy makes use of the soil’s naturally occurring urea and Ca2+, as well as microorganisms introduced to the compaction water. Two alternative initial water-content types were examined: those on the dry side and those close to the ideal Proctor conditions. Bacillaceae microorganisms were used to induce microbial CaCO3 precipitation and improve the hydraulic and mechanical properties of the compacted soil. The samples were biotreated and immediately compacted, so that the precipitation of calcium carbonate during the curing process took place in the contact areas between the particles (biocementation) and in the pore space (bioclogging). A set of techniques were used to study the ageing effects, such as the water-retention curve by dew-points psychrometer, mercury porosimetry intrusion, permeability, ultrasonic pulse velocity, resonant column, and unconfined and tensile-compression tests. During the ageing, it was observed that the bacterial activity consumed water for the hydrolysis of urea and other intermediate reactions to precipitate CaCO3. This process resulted in a retraction of the microstructure and a change in the macrostructure. The bioclogging phenomenon was more evident in the soil microstructure, while the biocementation process was easier to observe in the macrostructure. The suction’s effects on the soil stiffness were studied in detail, and a significant increase was detected. Despite these water-content losses, which caused soil stiffening by increasing the suction, it was still feasible to identify the gradual rise in small-strain stiffness throughout incubation. The unconfined and tensile-compression tests showed a similar progressive increase in terms of peak compressive and peak splitting strength during the incubation. These results are of interest when microbiological treatments are applied in soils to produce cementitious materials, with the present investigation demonstrating a complete study of their geotechnical behaviour.
Management of Low Back Pain: Do Physiotherapists Know the Evidence-Based Guidelines?
Authors: Fourré Antoine , Vanderstraeten Rob , Ris Laurence , Bastiaens Hilde , Michielsen Jozef , Demoulin Christophe , Darlow Ben , Roussel Nathalie
Published: April 2023

Background: Clinical practice guidelines promote bio-psychosocial management of patients suffering from low back pain (LBP). The objective of this study was to examine the current knowledge, attitudes and beliefs of physiotherapists about a guideline-adherent approach to LBP and to assess the ability of physiotherapists to recognise signs of a specific LBP in a clinical vignette. Methods: Physiotherapists were recruited to participate in an online study. They were asked to indicate whether they were familiar with evidence-based guidelines and then to fill in the Health Care Providers’ Pain and Impairment Relationship Scale (HC-PAIRS), Back Pain Attitudes Questionnaire (Back-PAQ), Neurophysiology of Pain Questionnaire (NPQ), as well as questions related to two clinical vignettes. Results: In total, 527 physiotherapists participated in this study. Only 38% reported being familiar with guidelines for the management of LBP. Sixty-three percent of the physiotherapists gave guideline-inconsistent recommendations regarding work. Only half of the physiotherapists recognised the signs of a specific LBP. Conclusions: The high proportion of physiotherapists unfamiliar with guidelines and demonstrating attitudes and beliefs not in line with evidence-based management of LBP is concerning. It is crucial to develop efficient strategies to enhance knowledge of guidelines among physiotherapists and increase their implementation in clinical practice.
Examining Cash Expenditures and Associated HIV-Related Behaviors Using Financial Diaries in Women Employed by Sex Work in Rural Uganda: Findings from the Kyaterekera Study
Authors: Jennings Mayo-Wilson Larissa , Peterson Summer K. , Kiyingi Joshua , Nabunya Proscovia , Sensoy Bahar Ozge , Yang Lyla S. , Witte Susan S. , Ssewamala Fred M.
Published: April 2023

Background: Women employed by sex work (WESW) have a high risk of human immunodeficiency virus (HIV) infection and experience economic barriers in accessing care. However, few studies have described their financial lives and the relationship between expenditures and HIV-related behaviors. Methods: This exploratory study used financial diaries to collect expenditure and income data from WESW in Uganda over 6 months. Data were collected as part of a larger trial that tested the efficacy of an HIV prevention intervention method. Descriptive statistics were used to quantify women’s income, relative expenditures, and negative cash balances. Bivariate and multivariate logistic regressions were used to examine the odds of sexual risk behavior or use of HIV medications for several cash scenarios. Results: A total of 163 WESW were enrolled; the participants mean age was 32 years old. Sex work was the sole source of employment for most WESW (99%); their average monthly income was $62.32. Food accounted for the highest proportion of spending (44%) followed by sex work (20%) and housing expenditures (11%). WESW spent the least on health care (5%). Expenditures accounted for a large but variable proportion of these women’s income (56% to 101%). Most WESW (74%) experienced a negative cash balance. Some also reported high sex work (28%), health care (24%), and education (28%) costs. The prevalence of condomless sex (77%) and sex with drugs/alcohol (70%) was high compared to use of ART/PrEP (Antiretroviral therapy/Pre-exposure prophylaxis) medications (45%). Women’s cash expenditures were not statistically significantly associated with HIV-related behaviors. However, the exploratory study observed a consistent null trend of lower odds of condomless sex (adjusted odds ratio (AOR) = 0.70, 95% confidence interval (CI): 0.28–1.70), sex with drugs/alcohol (AOR = 0.93, 95% CI: 0.42–2.05), and use of ART/PrEP (AOR = 0.80, 95% CI: 0.39–1.67) among women who experienced a negative cash balance versus those who did not. Similar trends were observed for other cash scenarios. Conclusion: Financial diaries are a feasible tool to assess the economic lives of vulnerable women. Despite having paid work, most WESW encountered a myriad of financial challenges with limited spending on HIV prevention. Financial protections and additional income-generating activities may improve their status. More robust research is needed to understand the potentially complex relationship between income, expenditures, and HIV risk among vulnerable sex workers.
Method Development for Detecting Low Level Volatile Organic Compounds (VOCs) among Workers and Residents from a Carpentry Work Shop in a Palestinian Village
Authors: Jodeh Shehdeh , Chakir Abdelkhaleq , Hanbali Ghadir , Roth Estelle , Eid Abdelrahman
Published: April 2023

Volatile organic compounds (VOCs) are considered a major public health concern in industrial location areas. The presence of exposure to (VOCs) has raised concern regarding the health effects caused by chronic human exposure as this will increase cancer diseases in the village. An analytical method has been developed and modified to help us detect 38 VOCs in the blood of 38 volunteers who are related to a carpentry shop at the parts-per-trillion level. To measure and evaluate the potential risk, several devices, such as portable passive monitors and air-collected samples, in addition to blood concentration, were used to study three different occupational groups. Ten of the volunteers are employees at the shop, 10 volunteers live very close to the shop, and 10 of them are students in an elementary school very close to the shop. In this study, we developed an automated analytical method using headspace (HS) together with solid-phase microextraction (SPME) connected to capillary gas chromatography (GC) equipped with quadrupole mass spectrometry (MS). The detection limits for the method used were measured in the range from 0.001 to 0.15 ng/L, using linear calibration curves that have three orders of magnitude. The detected concentrations ranged from 3 ng L−1 for trichloroethene to 91 ng L−1 for toluene and 270 ng L−1 for 2,4-diisocyanate, which was derived from the paint solvents used for the wood in the carpentry shop and the paints on the walls. More than half of all assessed species (80%) had mean concentration values less than 50 ng L−1, which is the maximum allowed for most VOCs. The major chemical types among the compounds quantified will be those we found in our previous study in the surrounding air of a carpentry workshop in Deir Ballout in Palestine, which were toluene diisocyanate and butyl cyanate. Some were found to be highly present air. Most of the measurements were below the guidelines of the World Health Organization (WHO). Despite the fact that this study only involved a small number of smokers, smoking was found to be connected with several blood and breath components. This group includes unsaturated hydrocarbons (1,3-butadiene, 1,3-pentadiene, 2-butene), furans (2,5-dimethylfuran), and acetonitrile. The proposed classification of measured species into systemic (blood-borne) and exogenous volatiles is strictly hypothetical, as some species may have several origins.
Racial Differences in Blood Pressure and Autonomic Recovery Following Acute Supramaximal Exercise in Women
Authors: Bajdek Nicole , Merchant Noelle , Camhi Sarah M. , Yan Huimin
Published: April 2023

Despite the growing popularity of high-intensity anaerobic exercise, little is known about the acute effects of this form of exercise on cardiovascular hemodynamics or autonomic modulation, which might provide insight into the individual assessment of responses to training load. The purpose of this study was to compare blood pressure and autonomic recovery following repeated bouts of acute supramaximal exercise in Black and White women. A convenience sample of twelve White and eight Black young, healthy women were recruited for this study and completed two consecutive bouts of supramaximal exercise on the cycle ergometer with 30 min of recovery in between. Brachial and central aortic blood pressures were assessed by tonometry (SphygmoCor Xcel) at rest and 15-min and 30-min following each exercise bout. Central aortic blood pressure was estimated using brachial pressure waveforms and customized software. Autonomic modulation was measured in a subset of ten participants by heart-rate variability and baroreflex sensitivity. Brachial mean arterial pressure and diastolic blood pressure were significantly higher in Blacks compared to Whites across time (race effect, p = 0.043 and p = 0.049, respectively). Very-low-frequency and low-frequency bands of heart rate variability, which are associated with sympathovagal balance and vasomotor tone, were 22.5% and 24.9% lower, respectively, in Blacks compared to Whites (race effect, p = 0.045 and p = 0.006, respectively). In conclusion, the preliminary findings of racial differences in blood pressure and autonomic recovery following supramaximal exercise warrant further investigations of tailored exercise prescriptions for Blacks and Whites.
Skin Microbiome in Prurigo Nodularis
Authors: Tutka Klaudia , Żychowska Magdalena , Żaczek Anna , Maternia-Dudzik Karolina , Pawełczyk Jakub , Strapagiel Dominik , Lach Jakub , Reich Adam
Published: April 2023

Prurigo nodularis (PN) is a chronic condition characterized by the presence of nodular lesions accompanied by intense pruritus. The disease has been linked to several infectious factors, but data on the direct presence of microorganisms in the lesions of PN are scarce. The aim of this study was to evaluate the diversity and composition of the bacterial microbiome in PN lesions by targeting the region V3-V4 of 16S rRNA. Skin swabs were obtained from active nodules in 24 patients with PN, inflammatory patches of 14 patients with atopic dermatitis (AD) and corresponding skin areas of 9 healthy volunteers (HV). After DNA extraction, the V3-V4 region of the bacterial 16S rRNA gene was amplified. Sequencing was performed using the Illumina platform on the MiSeq instrument. Operational taxonomic units (OTU) were identified. The identification of taxa was carried out using the Silva v.138 database. There was no statistically significant difference in the alpha-diversity (intra-sample diversity) between the PN, AD and HV groups. The beta-diversity (inter-sample diversity) showed statistically significant differences between the three groups on a global level and in paired analyses. Staphylococcus was significantly more abundant in samples from PN and AD patients than in controls. The difference was maintained across all taxonomic levels. The PN microbiome is highly similar to that of AD. It remains unclear whether the disturbed composition of the microbiome and the domination of Staphylococcus in PN lesions may be the trigger factor of pruritus and lead to the development of cutaneous changes or is a secondary phenomenon. Our preliminary results support the theory that the composition of the skin microbiome in PN is altered and justify further research on the role of the microbiome in this debilitating condition.
β-Conglutins’ Unique Mobile Arm Is a Key Structural Domain Involved in Molecular Nutraceutical Properties of Narrow-Leafed Lupin (Lupinus angustifolius L.)
Authors: Lima-Cabello Elena , Escudero-Feliu Julia , Peralta-Leal Andreina , Garcia-Fernandez Pedro , Siddique Kadambot H. M. , Singh Karam B. , Núñez Maria I. , León Josefa , Jimenez-Lopez Jose C.
Published: April 2023

Narrow-leafed lupin (NLL; Lupinus angustifolius L.) has multiple nutraceutical properties that may result from unique structural features of β-conglutin proteins, such as the mobile arm at the N-terminal, a structural domain rich in α-helices. A similar domain has not been found in other vicilin proteins of legume species. We used affinity chromatography to purify recombinant complete and truncated (without the mobile arm domain, tβ5 and tβ7) forms of NLL β5 and β7 conglutin proteins. We then used biochemical and molecular biology techniques in ex vivo and in vitro systems to evaluate their anti-inflammatory activity and antioxidant capacity. The complete β5 and β7 conglutin proteins decreased pro-inflammatory mediator levels (e.g., nitric oxide), mRNA expression levels (iNOS, TNFα, IL-1β), and the protein levels of pro-inflammatory cytokine TNF-α, interleukins (IL-1β, IL-2, IL-6, IL-8, IL-12, IL-17, IL-27), and other mediators (INFγ, MOP, S-TNF-R1/-R2, and TWEAK), and exerted a regulatory oxidative balance effect in cells as demonstrated in glutathione, catalase, and superoxide dismutase assays. The truncated tβ5 and tβ7 conglutin proteins did not have these molecular effects. These results suggest that β5 and β7 conglutins have potential as functional food components due to their anti-inflammatory and oxidative cell state regulatory properties, and that the mobile arm of NLL β-conglutin proteins is a key domain in the development of nutraceutical properties, making NLL β5 and β7 excellent innovative candidates as functional foods.
Galectin-3 as a Marker for Increased Thrombogenicity in COVID-19
Authors: Puccini Marianna , Jakobs Kai , Reinshagen Leander , Friebel Julian , Schencke Philipp-Alexander , Ghanbari Emily , Landmesser Ulf , Haghikia Arash , Kränkel Nicolle , Rauch Ursula
Published: April 2023

Galectin-3 is a beta-galactoside-binding lectin involved in inflammation and lung fibrosis and postulated to enhance thrombosis. In COVID-19, it is considered to be a prognostic marker of severity. The aim of this study was to evaluate whether galectin-3 is associated with thrombogenicity in COVID-19. Patients with moderate-to-severe COVID-19 (COVpos; n = 55) and patients with acute respiratory diseases, but without COVID-19 (COVneg; n = 35), were included in the study. We measured the amount of galectin-3, as well as other platelet and coagulation markers, and correlated galectin-3 levels with these markers of thrombogenicity and with the SOFA Score values. We found that galectin-3 levels, as well as von Willebrand Factor (vWF), antithrombin and tissue plasminogen activator levels, were higher in the COVpos than they were in the COVneg cohort. Galectin-3 correlated positively with vWF, antithrombin and D-dimer in the COVpos cohort, but not in the COVneg cohort. Moreover, galactin-3 correlated also with clinical disease severity, as measured by the SOFA Score. In patients with acute respiratory diseases, galectin-3 can be considered as a marker not only for disease severity, but also for increased hypercoagulability. Whether galectin-3 might be a useful therapeutic target in COVID-19 needs to be assessed in future studies.
The Central Nervous System Source Modulates Microglia Function and Morphology In Vitro
Authors: Pinho Andreia G. , Monteiro Andreia , Fernandes Sara , de Sousa Nídia , Salgado António J. , Silva Nuno A. , Monteiro Susana
Published: April 2023

The regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new information on microglia heterogeneity throughout central nervous system (CNS) regions is being revealed by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on behavior in vitro by applying the same experimental protocol and culture conditions. We analyzed the microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in the spinal-cord-derived glial cultures, presenting different expressions of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-γ. Morphologically, the cortical microglial cells were more complex and presented longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired by the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.
Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment
Authors: Shnayder Natalia A. , Ashkhotov Azamat V. , Trefilova Vera V. , Nurgaliev Zaitun A. , Novitsky Maxim A. , Petrova Marina M. , Narodova Ekaterina A. , Al-Zamil Mustafa , Chumakova Galina A. , Garganeeva Natalia P. , Nasyrova Regina F.
Published: April 2023

Intervertebral disc degeneration (IDD) and associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. With age, IDD progresses, leading to spondylosis, spondylarthrosis, herniated disc, spinal canal stenosis. One of the leading mechanisms in the development of IDD and chronic back pain is an imbalance between pro-inflammatory and anti-inflammatory cytokines. However, classical therapeutic strategies for correcting cytokine imbalance in IDD do not give the expected response in more than half of the cases. The purpose of this review is to update knowledge about new and promising therapeutic strategies based on the correction of the molecular mechanisms of cytokine imbalance in patients with IDD. This review demonstrates that knowledge of the molecular mechanisms of the imbalance between pro-inflammatory and anti-inflammatory cytokines may be a new key to finding more effective drugs for the treatment of IDD in the setting of acute and chronic inflammation.
Decasubstituted Pillar[5]arene Derivatives Containing L-Tryptophan and L-Phenylalanine Residues: Non-Covalent Binding and Release of Fluorescein from Nanoparticles
Authors: Sultanaev Vildan , Yakimova Luidmila , Nazarova Anastasia , Mostovaya Olga , Sedov Igor , Davletshin Damir , Gilyazova Elvina , Bulatov Emil , Li Zhang-Ting , Zhang Dan-Wei , Stoikov Ivan
Published: April 2023

Sensitive systems with controlled release of drugs or diagnostic markers are attractive for solving the problems of biomedicine and antitumor therapy. In this study, new decasubstituted pillar[5]arene derivatives containing L-Tryptophan and L-Phenylalanine residues have been synthesized as pH-responsive drug nanocarriers. Fluorescein dye (Fluo) was loaded into the pillar[5]arene associates and used as a spectroscopic probe to evaluate the release in buffered solutions with pH 4.5, 7.4, and 9.2. The nature of the substituents in the pillar[5]arene structure has a huge influence on the rate of delivering. When the dye was loaded into the associates based on pillar[5]arene derivatives containing L-Tryptophan, the Fluo release occurs in the neutral (pH = 7.4) and alkaline (pH = 9.2) buffered solutions. When the dye was loaded into the associates based on pillar[5]arene with L-Phenylalanine fragments, the absence of release was observed in every pH evaluated. This happens as the result of different packing of the dye in the structure of the associate. This fact was confirmed by different fluorescence mechanisms (aggregation-caused quenching and aggregation-induced emission) and association constants. It was shown that the macrocycle with L-Phenylalanine fragments binds the dye more efficiently (lgKa = 3.92). The experimental results indicate that the pillar[5]arene derivatives with amino acids fragments have a high potential to be used as a pH-responsive drug delivery devices, especially for promoting the intracellular delivering, due to its nanometric size.
SnRNA-Seq of Pancreas Revealed the Dysfunction of Endocrine and Exocrine Cells in Transgenic Pigs with Prediabetes
Authors: Peng Huanqi , Zhang Kaiyi , Miao Jiakun , Yang Yu , Xu Shuang , Wu Tianwen , Tao Cong , Wang Yanfang , Yang Shulin
Published: April 2023

Diabetes poses a significant threat to human health. Exocrine pancreatic dysfunction is related to diabetes, but the exact mechanism is not fully understood. This study aimed to describe the pathological phenotype and pathological mechanisms of the pancreas of transgenic pigs (PIGinH11) that was constructed in our laboratory and to compare it with humans. We established diabetes-susceptible transgenic pigs and subjected them to high-fat and high-sucrose dietary interventions. The damage to the pancreatic endocrine and exocrine was evaluated using histopathology and the involved molecular mechanisms were analyzed using single-nucleus RNA-sequencing (SnRNA-seq). Compared to wild-type (WT) pigs, PIGinH11 pigs showed similar pathological manifestations to type 2 diabetes patients, such as insulin deficiency, fatty deposition, inflammatory infiltration, fibrosis tissue necrosis, double positive cells, endoplasmic reticulum (ER) and mitochondria damage. SnRNA-seq analysis revealed 16 clusters and cell-type-specific gene expression characterization in the pig pancreas. Notably, clusters of Ainar-M and Endocrine-U were observed at the intermediate state between the exocrine and endocrine pancreas. Beta cells of the PIGinH11 group demonstrated the dysfunction with insulin produced and secret decreased and ER stress. Moreover, like clinic patients, acinar cells expressed fewer digestive enzymes and showed organelle damage. We hypothesize that TXNIP that is upregulated by high glucose might play an important role in the dysfunction of endocrine to exocrine cells in PIGinH11 pigs.
Synergistic Effect of QNZ, an Inhibitor of NF-κB Signaling, and Bone Morphogenetic Protein 2 on Osteogenic Differentiation in Mesenchymal Stem Cells through Fibroblast-Induced Yes-Associated Protein Activation
Authors: Huang Fei , Wang Hai , Zhang Ying , Wei Guozhen , Xie Yun , Wu Gui
Published: April 2023

Biomaterials carrying recombinant human bone morphogenetic protein 2 (BMP2) have been developed to enhance bone regeneration in the treatment of bone defects. However, various reports have shown that in the bone repair microenvironment, fibroblasts can inhibit BMP2-induced osteogenic differentiation in mesenchymal stem cells (MSCs). Thus, factors that can target fibroblasts and improve BMP2-mediated osteogenesis should be explored. In this project, we focused on whether or not an inhibitor of the NF-κB signaling pathway, QNZ (EVP4593), could play a synergistic role with BMP2 in osteogenesis by regulating the activity of fibroblasts. The roles of QNZ in regulating the proliferation and migration of fibroblasts were examined. In addition, the effect of QNZ combined with BMP2 on the osteogenic differentiation of MSCs was evaluated both in vitro and in vivo. Furthermore, the detailed mechanisms by which QNZ improved BMP2-mediated osteogenesis through the modulation of fibroblasts were analyzed and revealed. Interestingly, we found that QNZ inhibited the proliferation and migration of fibroblasts. Thus, QNZ could relieve the inhibitory effects of fibroblasts on the homing and osteogenic differentiation of mesenchymal stem cells. Furthermore, biomaterials carrying both QNZ and BMP2 showed better osteoinductivity than did those carrying BMP2 alone both in vitro and in vivo. It was found that the mechanism of QNZ involved reactivating YAP activity in mesenchymal stem cells, which was inhibited by fibroblasts. Taken together, our results suggest that QNZ may be a candidate factor for assisting BMP2 in inducing osteogenesis. The combined application of QNZ and BMP2 in biomaterials may be promising for the treatment of bone defects in the future.
Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats
Authors: Zhang Yu-Xiang , Zhu Yuan-Mei , Yang Xi-Xi , Gao Fei-Fei , Chen Jie , Yu Dong-Yu , Gao Jing-Qi , Chen Zhen-Nan , Yang Jing-Si , Yan Chun-Xia , Huo Fu-Quan
Published: April 2023

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.
Impact of Vitamin D Status Correction on Serum Lipid Profile, Carboxypeptidase N and Nitric Oxide Levels in Saudi Adults
Authors: Yakout Sobhy M. , Abdi Saba , Alaskar Alhanouf H. , Khattak Malak Nawaz Khan , Al-Masri Abeer A. , Al-Daghri Nasser M.
Published: April 2023

This study aimed to determine the impact on the lipid profile, carboxypeptidase N (CPN) and nitric oxide (NOx) associated with vitamin D (VD) status correction among Saudi adults with VD deficiency. A total 111 VD deficient (25(OH)D < 50 nmol/L)) adult Saudis aged 18–50 years old (57 females and 54 males) were enrolled in this 6-month interventional study. They were given 50,000 IU VD weekly for the first 2 months and then twice a month for the next 2 months, followed by 1000 IU daily for the last 2 months. The fasting lipid profile and the blood glucose, VD, NOx and CPN concentrations were measured at baseline and after intervention. Post-supplementation, the median VD was significantly higher (p < 0.001) in females [58.3 (50.6–71.2)] and males [57.8 (51.0–71.8)]. HDL cholesterol significantly increased (p = 0.05) and NOx significantly decreased (p = 0.02) in males post-supplementation. Triglycerides were positively associated with NOx in all subjects before (r = 0.44, p = 0.01) and after (r = 0.37, p = 0.01) VD status correction. There was a significant increase in serum levels of CPN2 (p = 0.02) in all subjects. Furthermore, CPN was inversely correlated with NOx (r = −0.35, p = 0.05) in males post-supplementation. In conclusion, VD status correction reduced serum NOx, particularly in males. The inhibition of NOx synthesis may be responsible for the anti-inflammatory effects of VD supplementation. An inverse association was found between NOx and CPN2.
Evaluating Back-to-Back and Day-to-Day Reproducibility of Cortical GABA+ Measurements Using Proton Magnetic Resonance Spectroscopy (1H MRS)
Authors: Elsaid Sonja , Truong Peter , Sailasuta Napapon , Le Foll Bernard
Published: April 2023

γ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter implicated in neuropsychiatric disorders. The best method for quantifying GABA is proton magnetic resonance spectroscopy (1H MRS). Considering that accurate measurements of GABA are affected by slight methodological alterations, demonstrating GABA reproducibility in healthy volunteers is essential before implementing the changes in vivo. Thus, our study aimed to evaluate the back-to-back (B2B) and day-to-day (D2D) reproducibility of GABA+ macromolecules (GABA+) using a 3 Tesla MRI scanner, the new 32-channel head coil (CHC), and Mescher–Garwood Point Resolved Spectroscopy (MEGA-PRESS) technique with the scan time (approximately 10 min), adequate for psychiatric patients. The dorsomedial pre-frontal cortex/anterior cingulate cortex (dmPFC/ACC) was scanned in 29 and the dorsolateral pre-frontal cortex (dlPFC) in 28 healthy volunteers on two separate days. Gannet 3.1 was used to quantify GABA+. The reproducibility was evaluated by Pearson’s r correlation, the interclass-correlation coefficient (ICC), and the coefficient of variation (CV%) (r/ICC/CV%). For Day 1, B2B reproducibility was 0.59/0.60/5.02% in the dmPFC/ACC and 0.74/0.73/5.15% for dlPFC. For Day 2, it was 0.60/0.59/6.26% for the dmPFC/ACC and 0.54/0.54/6.89 for dlPFC. D2D reproducibility of averaged GABA+ was 0.62/0.61/4.95% for the dmPFC/ACC and 0.58/0.58/5.85% for dlPFC. Our study found excellent GABA+ repeatability and reliability in the dmPFC/ACC and dlPFC.
Mineralocorticoid Receptor Antagonists for Preventing Chronic Kidney Disease Progression: Current Evidence and Future Challenges
Authors: Fujii Wataru , Shibata Shigeru
Published: April 2023

Regulation and action of the mineralocorticoid receptor (MR) have been the focus of intensive research over the past 80 years. Genetic and physiological/biochemical analysis revealed how MR and the steroid hormone aldosterone integrate the responses of distinct tubular cells in the face of environmental perturbations and how their dysregulation compromises fluid homeostasis. In addition to these roles, the accumulation of data also provided unequivocal evidence that MR is involved in the pathophysiology of kidney diseases. Experimental studies delineated the diverse pathological consequences of MR overactivity and uncovered the multiple mechanisms that result in enhanced MR signaling. In parallel, clinical studies consistently demonstrated that MR blockade reduces albuminuria in patients with chronic kidney disease. Moreover, recent large-scale clinical studies using finerenone have provided evidence that the non-steroidal MR antagonist can retard the kidney disease progression in diabetic patients. In this article, we review experimental data demonstrating the critical importance of MR in mediating renal injury as well as clinical studies providing evidence on the renoprotective effects of MR blockade. We also discuss areas of future investigation, which include the benefit of non-steroidal MR antagonists in non-diabetic kidney disease patients, the identification of surrogate markers for MR signaling in the kidney, and the search for key downstream mediators whereby MR blockade confers renoprotection. Insights into these questions would help maximize the benefit of MR blockade in subjects with kidney diseases.
The Anti-Atopic Dermatitis Effects of Mentha arvensis Essential Oil Are Involved in the Inhibition of the NLRP3 Inflammasome in DNCB-Challenged Atopic Dermatitis BALB/c Mice
Authors: Kim So-Yeon , Sapkota Arjun , Bae Young Joo , Choi Seung-Hyuk , Bae Ho Jung , Kim Hyun-Jeong , Cho Ye Eun , Choi Yu-Yeong , An Ju-Yeon , Cho So-Young , Hong Sun Hee , Choi Ji Woong , Park Se Jin
Published: April 2023

The NLRP3 inflammasome is upregulated by various agents, such as nuclear factor-kappa B (NF-κB), lipopolysaccharide (LPS), and adenosine triphosphate (ATP). The NLRP3 inflammasome facilitations the maturation of interleukin (IL)-1β, a proinflammatory cytokine that is critically involved in the pathogenesis of atopic dermatitis (AD). Although the NLRP3 inflammasome clearly exacerbates AD symptoms such as erythema and pruritus, drugs for AD patients targeting the NLRP3 inflammasome are still lacking. Based on the previous findings that Mentha arvensis essential oil (MAEO) possesses strong anti-inflammatory and anti-AD properties through its inhibition of the ERK/NF-κB signaling pathway, we postulated that MAEO might be capable of modulating the NLRP3 inflammasome in AD. The aim of this research was to investigate whether MAEO affects the inhibition of NLRP3 inflammasome activation in murine bone marrow-derived macrophages (BMDMs) stimulated with LPS + ATP in vitro and in a murine model displaying AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in vivo. We found that MAEO inhibited the expression of NLRP3 and caspase-1, leading to the suppression of NLRP3 inflammasome activation and IL-1β production in BMDMs stimulated with LPS + ATP. In addition, MAEO exhibited efficacy in ameliorating AD symptoms in a murine model induced by DNCB, as indicated by the reduction in dermatitis score, ear thickness, transepidermal water loss (TEWL), epidermal thickness, and immunoglobulin E (IgE) levels. Furthermore, MAEO attenuated the recruitment of NLRP3-expressing macrophages and NLRP3 inflammasome activation in murine dorsal skin lesions induced by DNCB. Overall, we provide evidence for the anti-AD effects of MAEO via inhibition of NLRP3 inflammasome activation.
The Contribution of the Nrf2/ARE System to Mechanotransduction in Musculoskeletal and Periodontal Tissues
Authors: Fragoulis Athanassios , Tohidnezhad Mersedeh , Kubo Yusuke , Wruck Christoph Jan , Craveiro Rogerio Bastos , Bock Anna , Wolf Michael , Pufe Thomas , Jahr Holger , Suhr Frank
Published: April 2023

Mechanosensing plays an essential role in maintaining tissue functions. Across the human body, several tissues (i.e., striated muscles, bones, tendons, ligaments, as well as cartilage) require mechanical loading to exert their physiological functions. Contrary, mechanical unloading triggers pathological remodeling of these tissues and, consequently, human body dysfunctions. At the cellular level, both mechanical loading and unloading regulate a wide spectrum of cellular pathways. Among those, pathways regulated by oxidants such as reactive oxygen species (ROS) represent an essential node critically controlling tissue organization and function. Hence, a sensitive balance between the generation and elimination of oxidants keeps them within a physiological range. Here, the Nuclear Factor-E2-related factor 2/Antioxidant response element (Nrf2/ARE) system plays an essential role as it constitutes the major cellular regulation against exogenous and endogenous oxidative stresses. Dysregulations of this system advance, i.a., liver, neurodegenerative, and cancer diseases. Herein, we extend our comprehension of the Nrf2 system to the aforementioned mechanically sensitive tissues to explore its role in their physiology and pathology. We demonstrate the relevance of it for the tissues’ functionality and highlight the imperative to further explore the Nrf2 system to understand the physiology and pathology of mechanically sensitive tissues in the context of redox biology.
Autophagy and SARS-CoV-2-Old Players in New Games
Authors: Ivanova Tsvetomira , Mariienko Yuliia , Mehterov Nikolay , Kazakova Maria , Sbirkov Yordan , Todorova Krassimira , Hayrabedyan Soren , Sarafian Victoria
Published: April 2023

At present it is well-defined that autophagy is a fundamental process essential for cell life but its pro-viral and anti-viral role has been stated out with the COVID pandemic. However, viruses in turn have evolved diverse adaptive strategies to cope with autophagy driven host defense, either by blocking or hijacking the autophagy machinery for their own benefit. The mechanisms underlying autophagy modulation are presented in the current review which summarizes the accumulated knowledge on the crosstalk between autophagy and viral infections, with a particular emphasizes on SARS-CoV-2. The different types of autophagy related to infections and their molecular mechanisms are focused in the context of inflammation. In particular, SARS-CoV-2 entry, replication and disease pathogenesis are discussed. Models to study autophagy and to formulate novel treatment approaches and pharmacological modulation to fight COVID-19 are debated. The SARS-CoV-2—autophagy interplay is presented, revealing the complex dynamics and the molecular machinery of autophagy. The new molecular targets and strategies to treat COVID-19 effectively are envisaged. In conclusion, our finding underline the importance of development new treatment strategies and pharmacological modulation of autophagy to fight COVID-19.
GmTCP and GmNLP Underlying Nodulation Character in Soybean Depending on Nitrogen
Authors: Kim Yunchol , Wang Jinhui , Ma Chao , Jong Cholnam , Jin Myongil , Cha Jinmyong , Wang Jing , Peng Yang , Ni Hejia , Li Haibo , Yang Mingliang , Chen Qingshan , Xin Dawei
Published: April 2023

Soybean is a cereal crop with high protein and oil content which serves as the main source of plant-based protein and oil for human consumption. The symbiotic relationship between legumes and rhizobia contributes significantly to soybean yield and quality, but the underlying molecular mechanisms remain poorly understood, hindering efforts to improve soybean productivity. In this study, we conducted a transcriptome analysis and identified 22 differentially expressed genes (DEGs) from nodule-related quantitative trait loci (QTL) located in chromosomes 12 and 19. Subsequently, we performed functional characterisation and haplotype analysis to identify key candidate genes among the 22 DEGs that are responsive to nitrate. Our findings identified GmTCP (TEOSINTE-BRANCHED1/CYCLOIDEA/PCF) and GmNLP (NIN-LIKE PROTEIN) as the key candidate genes that regulate the soybean nodule phenotype in response to nitrogen concentration. We conducted homologous gene mutant analysis in Arabidopsis thaliana, which revealed that the homologous genes of GmTCP and GmNLP play a vital role in regulating root development in response to nitrogen concentration. We further performed overexpression and gene knockout of GmTCP and GmNLP through hairy root transformation in soybeans and analysed the effects of GmTCP and GmNLP on nodulation under different nitrogen concentrations using transgenic lines. Overexpressing GmTCP and GmNLP resulted in significant differences in soybean hairy root nodulation phenotypes, such as nodule number (NN) and nodule dry weight (NDW), under varying nitrate conditions. Our results demonstrate that GmTCP and GmNLP are involved in regulating soybean nodulation in response to nitrogen concentration, providing new insights into the mechanism of soybean symbiosis establishment underlying different nitrogen concentrations.
An In Vitro Approach to Model EMT in Breast Cancer
Authors: Isert Lorenz , Mehta Aditi , Loiudice Gabriele , Oliva Altea , Roidl Andreas , Merkel Olivia M.
Published: April 2023

During the progression from ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC), cells must overcome the physically restraining basement membrane (BM), which compartmentalizes the epithelium from the stroma. Since the extracellular matrix (ECM) of the epithelial and stromal compartments are biochemically and physically distinct from one another, the progression demands a certain degree of cellular plasticity for a primary tumor to become invasive. The epithelial-to-mesenchymal transition (EMT) depicts such a cell program, equipping cancer cells with features allowing for dissemination from the epithelial entity and stromal invasion at the single-cell level. Here, the reciprocal interference between an altering tumor microenvironment and the EMT phenotype was investigated in vitro. BM-typical collagen IV and stroma-typical collagen I coatings were applied as provisional 2D matrices. Pro-inflammatory growth factors were introduced to improve tissue mimicry. Whereas the growth on coated surfaces only slightly affected the EMT phenotype, the combinatorial action of collagen with growth factor TGF-β1 induced prominent phenotypic changes. However, EMT induction was independent of collagen type, and cellular accessibility for EMT-like changes was strongly cell-line dependent. Summarizing the entire body of data, an EMT-phenotyping model was used to determine cellular EMT status and estimate EMT-like changes. The miR200c-mediated reversion of mesenchymal MDA-MB-231 cells is reflected by our EMT-phenotype model, thus emphasizing its potential to predict the therapeutic efficacy of EMT-targeting drugs in the future.
Proteomic Exploration of Paraoxonase 1 Function in Health and Disease
Authors: Jakubowski Hieronim
Published: April 2023

High-density lipoprotein (HDL) exhibits cardio- and neuro-protective properties, which are thought to be promoted by paraoxonase 1 (PON1), a hydrolytic enzyme associated with an HDL subfraction also enriched with an anticoagulant protein (PROS1) and amyloid beta-transport protein clusterin (CLU, APOJ). Reduced levels of PON1 activity, characterized biochemically by elevated levels of homocysteine (Hcy)-thiolactone, oxidized lipids, and proteins modified by these metabolites in humans and mice, are associated with pathological abnormalities affecting the cardiovascular system (atherothrombosis) and the central nervous system (cognitive impairment, Alzheimer’s disease). The molecular bases of these abnormalities have been largely unknown. Proteomic and metabolic studies over the past decade have significantly contributed to our understanding of PON1 function and the mechanisms by which PON1 deficiency can lead to disease. Recent studies discussed in this review highlight the involvement of dysregulated proteostasis in the pro-oxidative, pro-atherothrombotic, and pro-amyloidogenic phenotypes associated with low PON1 activity.