bluuebunny/crossref_metadata_2025 huggingface dataset:
Physicochemical and Antibacterial Properties of Bioactive Retrograde Filling Materials
Authors: Ashi Tarek , Mancino Davide , Hardan Louis , Bourgi Rim , Zghal Jihed , Macaluso Valentina , Al-Ashkar Sharif , Alkhouri Sleman , Haikel Youssef , Kharouf Naji
Published: October 2022

The purpose of the present study was to evaluate the physicochemical properties and antibacterial activity of three calcium silicate cements. Mineral trioxide aggregate (MTA Biorep “BR”), Biodentine (BD) and Well-Root PT (WR) materials were investigated using scanning electron microscopy (SEM) at 24, 72 and 168 h of immersion in phosphate buffered saline (PBS). The antibacterial activity against Enterococcus faecalis (E. faecalis), the solubility, roughness, pH changes and water contact angle were also analyzed. All results were statistically analyzed using a one-way analysis of variance test. Statistically significant lower pH was detected for BD than WR and BR (p < 0.05). No statistical difference was found among the three materials for the efficacy of kill against E. faecalis (p > 0.05). Good antibacterial activity was observed (kill 50% of bacteria) after 24 h of contact. The wettability and the roughness of BR were higher than for the other cements (p < 0.05). BD was more soluble than WR and BR (p < 0.05). In conclusion, the use of bioceramic cements as retrograde materials may play an important role in controlling bacterial growth and in the development of calcium phosphate surface layer to support healing. Moreover, the premixed cement was easier to use than powder–liquid cement.
Differences in the Visual Performances of Patients with Strabismus, Amblyopia, and Healthy Controls
Authors: Ibrahimi Danjela , Rodríguez-Reséndiz Juvenal , Mendiola-Santibañez Jorge Domingo
Published: October 2022

The aim of this paper is to use the new definition of amblyopia and to define the overall visual performance of healthy controls (HCs), patients with strabismus (PS), and patients with refractive amblyopia (PRA), based on the interaction of selected visual abilities. Method: A total of 398 participants were divided in three groups: HCs, PRA, and PS. Variables such as visual acuity, refractive state, degree of stereopsis, phoria state, magnitude, and type of deviation were analyzed using parametric and non-parametric tests. Results: Binocular visual acuity at near is the unique predictor factor for stereopsis in PRA and PS, while age relates to the amount of binocular visual acuity at near, only for PS with stereopsis. Binocular visual acuity at near and phoria states relate to each other in PRA. Binocular visual acuity at near and far in PS is better than PRA, with no differences in the degree of stereopsis. Stereoblind patients were only found among PS (36%). Only (44.9%) of PS had amblyopia. Exophoria predominated among PRA (69.72%) and HCs (78.87%), while exotropia was the predominant deviation in PS (60.54%). Hyperopia was the predominate refractive error among the groups, HCs (74.65%), PRA (79.82%), and PS (59.85%), followed by astigmatism. Interpretation: HCs perform better than PS and PRA. The visual performance of PS with stereopsis and PRA is similar. Binocular visual acuity at near can predict the degree of stereopsis, and stereoblind patients are exclusively related to strabismus.
Phase Response Curve to Light under Ambulatory Conditions: A Pilot Study for Potential Application to Daylight Saving Time Transitions
Authors: Arguelles-Prieto Raquel , Madrid Juan Antonio , Rol Maria Angeles , Bonmatí-Carrión María Ángeles
Published: October 2022

Several studies have investigated the relationship between daylight saving time (DST) and sleep alterations, psychiatric disorders, cardiovascular events and traffic accidents. However, very few have monitored participants while maintaining their usual lifestyle before and after DST. Considering that DST transitions modify human behavior and, therefore, people’s light exposure patterns, the aim of this study was to investigate the potential effects of DST on circadian variables, considering sleep and, for the first time, the human phase response curve to light. To accomplish this, eight healthy adults (33 ± 11 years old, mean ± SD) were recruited to monitor multivariable circadian markers and light exposure by means of a wearable ambulatory monitoring device: Kronowise®. The following night phase markers were calculated: midpoints of the five consecutive hours of maximum wrist temperature (TM5) and the five consecutive hours of minimum time in movement (TL5), sleep onset and offset, as well as sleep duration and light intensity. TM5 for wrist temperature was set as circadian time 0 h, and the balance between advances and delays considering the phase response curve to light was calculated individually before and after both DST transitions. To assess internal desynchronization, the possible shift in TM5 for wrist temperature and TL5 for time in movement were compared. Our results indicate that the transition to DST seems to force the circadian system to produce a phase advance to adapt to the new time. However, the synchronizing signals provided by natural and personal light exposure are not in line with such an advance, which results in internal desynchronization and the need for longer synchronization times. On the contrary, the transition back to ST, which implies a phase delay, is characterized by a faster adaptation and maintenance of internal synchronization, despite the fact that exposure to natural light would favor a phase advance. Considering the pilot nature of this study, further research is needed with higher sample sizes.
The Effect of Long-Term Moderate Static Magnetic Field Exposure on Adult Female Mice
Authors: Yang Xingxing , Yu Biao , Song Chao , Feng Chuanlin , Zhang Jing , Wang Xinyu , Cheng Guofeng , Yang Rui , Wang Wei , Zhu Yong
Published: October 2022

Because of the high cost and safety of ultra-high magnetic resonance imaging (MRI), its application has certain limitations. Whereas 0.5–3 T MRI has been widely applied in hospitals, static magnetic fields (SMFs) have been shown to improve mice mental health and have anti-tumor potentials. Here, we compared the effects of the upward and downward 150 mT SMF groups with the sham group on C57BL/6J adult female mice. Locomotor and exploratory activity were also measured by behavioral tests, including the open field and elevated plus test. Additionally, physiology, pathology indicators and gut microbiota were examined. We found that 150 mT SMFs long-term exposure enhanced locomotive and exploratory activity of mice, especially the downward 150 mT SMF. Compared with the downward 150 mT SMF group, the movement speed and distance in the center area of the sham group were increased by 65.99% (p < 0.0001) and 68.58% (p = 0.0038), respectively. Moreover, compared to the sham group, downward 150 mT SMF increased the number of entrances to the center area by 67.0% (p = 0.0082) and time in the center area by 77.12% (p = 0.0054). Additionally, we observed that upward 150 mT SMF improved the number of follicles (~2.5 times, p = 0.0325) and uterine glands through increasing the total antioxidant capacity and reducing lipid peroxidation level in mice. Gut microbiome analysis showed that 150 mT SMFs long-term exposure improved the microbiota abundance (Clostridium, Bifidobacterium, Ralstonia and Yaniella) in the genus level, which may affect metabolism, anxiety and behavior in adult female mice. Our results demonstrated that 150 mT SMFs long-term exposure not only had good biosafety, but also improved athletic performance, emotion and the function of ovarian, uterine and gut microbiota abundance in adult female mice, which unraveled the potential of moderate long-term SMF exposure in clinical applications.
Influence of Adiposity on the Gut Microbiota Composition of Arab Women: A Case-Control Study
Authors: Aljazairy Esra’a A. , Al-Musharaf Sara , Abudawood Manal , Almaarik Basmah , Hussain Syed D. , Alnaami Abdullah M. , Sabico Shaun , Al-Daghri Nasser M. , Clerici Mario , Aljuraiban Ghadeer S.
Published: October 2022

Recent evidence has suggested that the gut microbiota is a possible risk factor for obesity. However, limited evidence is available on the association between the gut microbiota composition and obesity markers in the Middle-Eastern region. We aimed to investigate the association between gut microbiota and obesity markers in a case-control study including 92 Saudi women aged 18–25 years, including participants with obesity (case, n = 44) and with normal weight (control, n = 48). Anthropometric, body composition, and biochemical data were collected. The whole-genome shotgun technique was used to analyze the gut microbiota. The Shannon alpha and Bray–Curtis beta diversity were determined. The microbial alpha diversity was significantly associated with only the waist-to-hip ratio (WHR) (p-value = 0.04), while the microbial beta diversity was significantly associated with body mass index (p-value = 0.048), %body fat (p-value = 0.018), and WHR (p-value = 0.050). Specific bacteria at different taxonomic levels, such as Bacteroidetes and Synergistetes, were positively associated with different obesity markers. Alistipes was higher in the control group compared with the case group. The results highlight the association of the gut microbiota with obesity and suggest that the gut microbiota of Saudi women is associated with specific obesity markers. Future studies are needed to determine the role of the identified strains in the metabolism of individuals with obesity.
Lipid-Derived Aldehydes: New Key Mediators of Plant Growth and Stress Responses
Authors: Liang Xin , Qian Ruyi , Wang Dan , Liu Lijuan , Sun Chengliang , Lin Xianyong
Published: October 2022

Aldehydes, derivatives of lipids, are ubiquitously produced through non-enzymatic and enzymatic pathways in higher plants and participate in many physiological and biological processes. Increasing evidence demonstrates that aldehydes are involved in plants response to many abiotic stresses, such as light, drought, heat and nutrient deficiency. In plant cells, endogenously triggered or exogenously applied high concentrations of aldehydes can damage proteins and nucleic acid, disturb redox homeostasis, and consequently inhibit plant growth; therefore, they are considered cytotoxins. Aldehyde levels are also used as biomarkers to evaluate the health status of plants. Further genetic research shows that several enzymes have strong capacities to detoxify these electrophilic aldehydes. Small molecules, such as carnosine and glutathione, also exhibit the ability to scavenge aldehydes, effectively promoting plant growth. Recently, increasing evidence has shown that certain aldehydes at certain concentrations can upregulate survival genes, activate antioxidant responses, increase defense against pathogens and stimulate plant growth. This review summarizes recent studies of lipid-derived aldehydes in higher plants, mainly focusing on the generation pathway, toxic effects, and detoxification strategies. In addition, the signaling effects of aldehydes in plants are also discussed.
Antimicrobial and Methicillin Resistance Pattern of Potential Mastitis-Inducing Staphylococcus aureus and Coagulase-Negative Staphylococci Isolates from the Mammary Secretion of Dairy Goats
Authors: Nelli Aikaterini , Voidarou Chrysoula (Chrysa) , Venardou Brigkita , Fotou Konstantina , Tsinas Anastasios , Bonos Eleftherios , Fthenakis George C. , Skoufos Ioannis , Tzora Athina
Published: October 2022

Staphylococcus spp. is an important mastitis-inducing zoonotic pathogen in goats and is associated with antimicrobial resistance (AMR). The objectives of this study were to determine the prevalence and composition of staphylococci in individual mammary secretion (MS) samples of clinically healthy goats and to evaluate the phenotypic AMR pattern and the presence of methicillin resistance in the Staphylococcus spp. strains. Staphylococcus spp. isolates (n = 101) from the MS samples (n = 220) were identified to species level using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The antimicrobial susceptibility testing included a disk diffusion assay and the determination of the minimum inhibitory concentrations (MIC) of resistant strains (n = 46). Presumptive methicillin-resistant strains (n = 9) were assessed for the presence of mecA, mecC and SCCmec/orfx genes. Staphylococcus spp. isolates were recovered from 45.9% of the MS samples, of which, 72.3% was identified as coagulase-negative staphylococci (CoNS), with the remaining being Staphylococcus aureus. CoNS and S. aureus were most commonly resistant to ampicillin (56.2% and 57.1%, respectively), penicillin (26.0% and 39.3%, respectively), amoxicillin (26 % and 25 %, respectively) and cephalexin (12.3% and 25%, respectively) in the disk diffusion method. CoNS exhibited a broader AMR pattern and a higher percentage of resistant strains than S. aureus in the disk diffusion and MIC methods. Of the nine oxacillin- and cefoxitin-resistant strains, three S. aureus and five CoNS strains carried the mecA gene and, thus, were identified as methicillin-resistant. The mecC gene was not found in any of the studied strains. The presence of AMR and methicillin resistance in caprine S. aureus and CoNS poses a concern for animal and public health.
Health and Environmental Effect of Advanced Materials and Fine Particles
Authors: Yu Il Je
Published: October 2022

With the recent development in material sciences, advanced materials have become terms widely used for new materials [...]
Evaluation of Halophyte Biopotential as an Unused Natural Resource: The Case of Lobularia maritima
Authors: Ben Hsouna Anis , Michalak Monika , Kukula-Koch Wirginia , Ben Saad Rania , ben Romdhane Walid , Zeljković Sanja Ćavar , Mnif Wissem
Published: October 2022

Halophytes are plant species widely distributed in saline habitats, such as beaches, postindustrial wastelands, irrigated lands, salt flats, and others. Excessive salt level, known to limit plant growth, is not harmful to halophytes, which have developed a variety of defense mechanisms allowing them to colonize harsh environments. Plants under stress are known to respond with several morpho-anatomical adaptations, but also to enhance the production of secondary metabolites to better cope with difficult conditions. Owing to these adaptations, halophytes are an interesting group of undemanding plants with a high potential for application in the food and pharmaceutical industries. Therefore, this review aims to present the characteristics of halophytes, describe changes in their gene expression, and discuss their synthesized metabolites of pharmacognostic and pharmacological significance. Lobularia maritima is characterized as a widely spread halophyte that has been shown to exhibit various pharmacological properties in vitro and in vivo. It is concluded that halophytes may become important sources of natural products for the treatment of various ailments and for supplementing the human diet with necessary non-nutrients and minerals. However, extensive studies are needed to deepen the knowledge of their biological potential in vivo, so that they can be introduced to the pharmaceutical and food industries.
Submilligram Level of Beetle Antifreeze Proteins Minimize Cold-Induced Cell Swelling and Promote Cell Survival
Authors: Omori Keiko , Gonzalez Ignacio , Nguyen Cindy , Raminani Shanti N. , Deleon Victor M. , Meza Pedro , Zamalloa Jose , Perez Rachel G. , Gonzalez Nelson , Komatsu Hirotake , Al-Abdullah Ismail H. , Wen Xin
Published: October 2022

Hypothermic (cold) preservation is a limiting factor for successful cell and tissue transplantation where cell swelling (edema) usually develops, impairing cell function. University of Wisconsin (UW) solution, a standard cold preservation solution, contains effective components to suppress hypothermia-induced cell swelling. Antifreeze proteins (AFPs) found in many cold-adapted organisms can prevent cold injury of the organisms. Here, the effects of a beetle AFP from Dendroides canadensis (DAFP-1) on pancreatic β-cells preservation were first investigated. As low as 500 µg/mL, DAFP-1 significantly minimized INS-1 cell swelling and subsequent cell death during 4 °C preservation in UW solution for up to three days. However, such significant cytoprotection was not observed by an AFP from Tenebrio molitor (TmAFP), a structural homologue to DAFP-1 but lacking arginine, at the same levels. The cytoprotective effect of DAFP-1 was further validated with the primary β-cells in the isolated rat pancreatic islets in UW solution. The submilligram level supplement of DAFP-1 to UW solution significantly increased the islet mass recovery after three days of cold preservation followed by rewarming. The protective effects of DAFP-1 in UW solution were discussed at a molecular level. The results indicate the potential of DAFP-1 to enhance cell survival during extended cold preservation.
CircRNAs in Tumor Radioresistance
Authors: Gao Yining , Gao Jiawen , Lin Fei , Wang Ting , Huo Sitong , Wu Jiefang , Zhou Qi , Zhang Chao
Published: October 2022

Circular RNAs (circRNAs) are endogenous, non-coding RNAs, which are derived from host genes that are present in several species and can be involved in the progression of various diseases. circRNAs’ leading role is to act as RNA sponges. In recent years, the other roles of circRNAs have been discovered, such as regulating transcription and translation, regulating host genes, and even being translated into proteins. As some tumor cells are no longer radiosensitive, tumor radioresistance has since become a challenge in treating tumors. In recent years, circRNAs are differentially expressed in tumor cells and can be used as biological markers of tumors. In addition, circRNAs can regulate the radiosensitivity of tumors. Here, we list the mechanisms of circRNAs in glioma, nasopharyngeal carcinoma, and non-small cell lung cancer; further, these studies also provide new ideas for the purposes of eliminating radioresistance in tumors.
Fine-Tuning of mTORC1-ULK1-PP2A Regulatory Triangle Is Crucial for Robust Autophagic Response upon Cellular Stress
Authors: Hajdú Bence , Holczer Marianna , Horváth Gergely , Szederkényi Gábor , Kapuy Orsolya
Published: October 2022

Autophagy-dependent cellular survival is tightly regulated by both kinases and phosphatases. While mTORC1 inhibits autophagy by phosphorylating ULK1, PP2A is able to remove this phosphate group from ULK1 and promotes the key inducer of autophagosome formation. However, ULK1 inhibits mTORC1, mTORC1 is able to down-regulate PP2A. In addition, the active ULK1 promotes PP2A via phosphorylation. We claim that these double-negative (mTORC1 –| PP2A –| mTORC1, mTORC1 –| ULK1 –| mTORC1) and positive (ULK1 -> PP2A -> ULK1) feedback loops are all necessary for the robust, irreversible decision making process between the autophagy and non-autophagy states. We approach our scientific analysis from a systems biological perspective by applying both theoretical and molecular biological techniques. For molecular biological experiments, HEK293T cell line is used, meanwhile the dynamical features of the regulatory network are described by mathematical modelling. In our study, we explore the dynamical characteristic of mTORC1-ULK1-PP2A regulatory triangle in detail supposing that the positive feedback loops are essential to manage a robust cellular answer upon various cellular stress events (such as mTORC1 inhibition, starvation, PP2A inhibition or ULK1 silencing). We confirm that active ULK1 can up-regulate PP2A when mTORC1 is inactivated. By using theoretical analysis, we explain the importance of cellular PP2A level in stress response mechanism. We proved both experimentally and theoretically that PP2A down-regulation (via addition of okadaic acid) might generate a periodic repeat of autophagy induction. Understanding how the regulation of the cell survival occurs with the precise molecular balance of ULK1-mTORC1-PP2A in autophagy, is highly relevant in several cellular stress-related diseases (such as neurodegenerative diseases or diabetes) and might help to promote advanced therapies in the near future, too.
Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity
Authors: Weiergräber Oliver H. , Petrović Dušan , Kislat Andreas , Pattky Martin , Fabig Judith , Batra-Safferling Renu , Schulte am Esch Jan , Hänel Karen , Huhn Carolin , Strodel Birgit , Homey Bernhard , Willbold Dieter
Published: October 2022

Human C-C motif ligand 16 (CCL16) is a chemokine that is distinguished by a large cleavable C-terminal extension of unknown significance. Conflicting data have been reported concerning its tissue distribution and modulation of expression, rendering the biological function of CCL16 enigmatic. Here, we report an integrated approach to the characterisation of this chemokine, including a re-assessment of its expression characteristics as well as a biophysical investigation with respect to its structure and dynamics. Our data indicate that CCL16 is chiefly synthesised by hepatocytes, without an appreciable response to mediators of inflammation, and circulates in the blood as a full-length protein. While the crystal structure of CCL16 confirms the presence of a canonical chemokine domain, molecular dynamics simulations support the view that the C-terminal extension impairs the accessibility of the glycosaminoglycan binding sites and may thus serve as an intrinsic modulator of biological activity.
HBcompare: Classifying Ligand Binding Preferences with Hydrogen Bond Topology
Authors: Tam Justin Z. , Kong Zhaoming , Ahmed Omar , He Lifang , Chen Brian Y.
Published: October 2022

This paper presents HBcompare, a method that classifies protein structures according to ligand binding preference categories by analyzing hydrogen bond topology. HBcompare excludes other characteristics of protein structure so that, in the event of accurate classification, it can implicate the involvement of hydrogen bonds in selective binding. This approach contrasts from methods that represent many aspects of protein structure because holistic representations cannot associate classification with just one characteristic. To our knowledge, HBcompare is the first technique with this capability. On five datasets of proteins that catalyze similar reactions with different preferred ligands, HBcompare correctly categorized proteins with similar ligand binding preferences 89.5% of the time. Using only hydrogen bond topology, classification accuracy with HBcompare surpassed standard structure-based comparison algorithms that use atomic coordinates. As a tool for implicating the role of hydrogen bonds in protein function categories, HBcompare represents a first step towards the automatic explanation of biochemical mechanisms.
Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder
Authors: Milivojevic Verica , Charron Lily , Fogelman Nia , Hermes Gretchen , Sinha Rajita
Published: October 2022

Chronic cocaine use leads to adaptations in stress biology and in neuroactive steroid system. These adaptations are associated with high cocaine craving and increased relapse risk. This study tested whether potentiation of the neuroactive steroid system with the precursor pregnenolone (PREG) affects stress- and cue-induced cocaine craving, anxiety and autonomic response in individuals with cocaine use disorder (CUD). Thirty treatment-seeking individuals (21 Male, 9 Female) with CUD were randomized to placebo (PBO) or supraphysiologic PREG doses of 300 mg or 500 mg per day for 8 weeks. After 2 weeks of treatment, participants were exposed to 5-min personalized guided imagery provocation of stress, cocaine, or neutral/relaxing cues in a 3-day experiment, one condition per day on separate days, in a random, counterbalanced order. Repeated assessment of cocaine craving, anxiety, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were assessed on each day. PREG significantly increased pregnenolone levels compared to PBO. Both PREG doses decreased stress- and cocaine cue-induced craving and reduced both stress- and cue-induced anxiety only in the 500 mg/day group. The 500 mg/day PREG group also displayed decreased stress-induced HR, SBP and DBP. Findings indicate that pregnenolone decreases stress- and cocaine cue-provoked craving and anxiety and reduces stress-induced autonomic arousal in individuals with CUD.
Identification of a Fibroblast-Related Prognostic Model in Glioma Based on Bioinformatics Methods
Authors: Zhang Haofuzi , Huang Yutao , Yang Erwan , Gao Xiangyu , Zou Peng , Sun Jidong , Tian Zhicheng , Bao Mingdong , Liao Dan , Ge Junmiao , Yang Qiuzi , Li Xin , Zhang Zhuoyuan , Luo Peng , Jiang Xiaofan
Published: October 2022

Background: Glioma is the most common primary tumor of the central nervous system with a high lethality rate. This study aims to mine fibroblast-related genes with prognostic value and construct a corresponding prognostic model. Methods: A glioma-related TCGA (The Cancer Genome Atlas) cohort and a CGGA (Chinese Glioma Genome Atlas) cohort were incorporated into this study. Variance expression profiling was executed via the “limma” R package. The “clusterProfiler” R package was applied to perform a GO (Gene Ontology) analysis. The Kaplan–Meier (K–M) curve, LASSO regression analysis, and Cox analyses were implemented to determine the prognostic genes. A fibroblast-related risk model was created and affirmed by independent cohorts. We derived enriched pathways between the fibroblast-related high- and low-risk subgroups using gene set variation analysis (GSEA). The immune infiltration cell and the stromal cell were calculated using the microenvironment cell populations-counter (MCP-counter) method, and the immunotherapy response was assessed with the SubMap algorithm. The chemotherapy sensitivity was estimated using the “pRRophetic” R package. Results: A total of 93 differentially expressed fibroblast-related genes (DEFRGs) were uncovered in glioma. Seven prognostic genes were filtered out to create a fibroblast-related gene signature in the TCGA-glioma cohort training set. We then affirmed the fibroblast-related risk model via TCGA-glioma cohort and CGGA-glioma cohort testing sets. The Cox regression analysis proved that the fibroblast-related risk score was an independent prognostic predictor in prediction of the overall survival of glioma patients. The fibroblast-related gene signature revealed by the GSEA was applicable to the immune-relevant pathways. The MCP-counter algorithm results pointed to significant distinctions in the tumor microenvironment between fibroblast-related high- and low-risk subgroups. The SubMap analysis proved that the fibroblast-related risk score could predict the clinical sensitivity of immunotherapy. The chemotherapy sensitivity analysis indicated that low-risk patients were more sensitive to multiple chemotherapeutic drugs. Conclusion: Our study identified prognostic fibroblast-related genes and generated a novel risk signature that could evaluate the prognosis of glioma and offer a theoretical basis for clinical glioma therapy.
Thioterpenoids as Potential Antithrombotic Drugs: Molecular Docking, Antiaggregant, Anticoagulant and Antioxidant Activities
Authors: Ksenofontov Alexander A. , Bocharov Pavel S. , Antina Elena V. , Shevchenko Oksana G. , Samorodov Aleksandr V. , Gilfanov Ilmir R. , Pavelyev Roman S. , Ostolopovskaya Olga V. , Startseva Valeriya A. , Fedyunina Inna V. , Azizova Zulfiya R. , Gaysin Salavat I. , Pestova Svetlana V. , Izmest’ev Evgeniy S. , Rubtsova Svetlana A. , Khelkhal Mohammed A. , Nikitina Liliya E.
Published: October 2022

Natural monoterpenes and their derivatives are widely considered as effective ingredients for the design and production of new biologically active compounds with high antioxidant, antimicrobial and anti-protozoa properties. In this study, we synthesized two series of thiotherpenoids “sulfide-sulfoxide-sulfone”, with different bicyclic monoterpene skeleton (bornane and pinane) structures. The effect of the obtained compounds on platelet aggregation was investigated by using the molecular docking technique. The obtained data revealed that all the synthesized compounds may act as potential inhibitors of platelet aggregation. Moreover, the studied sulfides have shown high antioxidant activity as revealed by lipid peroxidation (LPO) process inhibition in a non-cellular substrate containing animal lipids. The sulfides were able to inhibit erythrocyte oxidative hemolysis, to reduce the accumulation of secondary LPO products in cells and to prevent the oxidation of native oxyhemoglobin. Additionally, the corresponding sulfones and sulfoxides exhibited insignificant antioxidant activity. However, the sulfides were found to exhibit significant antiaggregant and anticoagulant effects. These findings suggest as well that the sulfides could serve as a leader compound for future research and possible practical applications.
Gender Difference in Lithium-Induced Sodium Current Dysregulation and Ventricular Arrhythmogenesis in Right Ventricular Outflow Tract Cardiomyocytes
Authors: Liu Ching-Han , Chen Yao-Chang , Lu Yen-Yu , Lin Yung-Kuo , Higa Satoshi , Chen Shih-Ann , Chen Yi-Jen
Published: October 2022

Lithium intoxication induces Brugada-pattern ECG, ventricular arrhythmia, and sudden death with the predominant preference for the male over the female gender. This study investigated the mechanisms of gender difference in lithium-induced arrhythmogenesis. The ECG parameters were recorded in male and female rabbits before and after the intravenous administration of lithium chloride (LiCl) (1, 3, 10 mmol/kg). Patch clamps were used to study the sodium current (INa) and late sodium current (INa-late) in the isolated single male and female right ventricular outflow tract (RVOT) cardiomyocytes before and after LiCl. Male rabbits (n = 9) were more prone to developing lithium-induced Brugada-pattern ECG changes (incomplete right bundle branch block, ST elevation and QRS widening) with fatal arrhythmia (66.7% vs. 0%, p = 0.002) than in female (n = 7) rabbits at 10 mmol/kg (but not 1 or 3 mmol/kg). Compared to those in the female RVOT cardiomyocytes, LiCl (100 μM) reduced INa to a greater extent and increased INa-late in the male RVOT cardiomyocytes. Moreover, in the presence of ranolazine (the INa-late inhibitor, 3.6 mg/kg iv loading, followed by a second iv bolus 6.0 mg/kg administered 30 min later, n = 5), LiCl (10 mmol/kg) did not induce Brugada-pattern ECG changes (p < 0.005). The male gender is much predisposed to lithium-induced Brugada-pattern ECG changes with a greater impact on INa and INa-late in RVOT cardiomyocytes. Targeting INa-late may be a potential therapeutic strategy for Brugada syndrome-related ventricular tachyarrhythmia.
Antineoplastic Properties by Proapoptotic Mechanisms Induction of Inula viscosa and Its Sesquiterpene Lactones Tomentosin and Inuviscolide
Authors: Migheli Rossana , Virdis Patrizia , Galleri Grazia , Arru Caterina , Lostia Giada , Coradduzza Donatella , Muroni Maria Rosaria , Pintore Giorgio , Podda Luigi , Fozza Claudio , De Miglio Maria Rosaria
Published: October 2022

Cancer is a complex disease including approximately 200 different entities that can potentially affect all body tissues. Among the conventional treatments, radiotherapy and chemotherapy are most often applied to different types of cancers. Despite substantial advances in the development of innovative antineoplastic drugs, cancer remains one of the most significant causes of death, worldwide. The principal pitfall of successful cancer treatment is the intrinsic or acquired resistance to therapeutic agents. The development of more effective or synergistic therapeutic approaches to improve patient outcomes and minimize toxicity has become an urgent issue. Inula viscosa is widely distributed throughout Europe, Africa, and Asia. Used as a medicinal plant in different countries, I. viscosa has been characterized for its complex chemical composition in order to identify the bioactive compounds responsible for its biological activities, including anticancer effects. Sesquiterpene lactones (SLs) are natural, biologically active products that have attracted considerable attention due to their biological activities. SLs are alkylating agents that form covalent adducts with free cysteine residues within enzymes and key proteins favoring cancer cell cytotoxicity. They are effective inducers of apoptosis in several cancer cell types through different molecular mechanisms. This review focuses on recent advances in the cytotoxic effects of I. viscosa and SLs in the treatment of neoplastic diseases, with a special emphasis on their proapoptotic molecular mechanisms.
Homocysteine, Cognitive Functions, and Degenerative Dementias: State of the Art
Authors: Luzzi Simona , Cherubini Veronica , Falsetti Lorenzo , Viticchi Giovanna , Silvestrini Mauro , Toraldo Alessio
Published: October 2022

There is strong evidence that homocysteine is a risk factor not only for cerebrovascular diseases but also for degenerative dementias. A recent consensus statement renewed the importance and the role of high levels of homocysteine in cognitive decline in several forms of degenerative dementia, such as Alzheimer’s disease. Although the molecular mechanisms by which homocysteine causes cell dysfunction are known, both the impact of homocysteine on specific cognitive functions and the relationship between homocysteine level and non-Alzheimer dementias have been poorly investigated. Most of the studies addressing the impact of hyperhomocysteinemia on dementias have not examined the profile of performance across different cognitive domains, and have only relied on screening tests, which provide a very general and coarse-grained picture of the cognitive status of the patients. Yet, trying to understand whether hyperhomocysteinemia is associated with the impairment of specific cognitive functions would be crucial, as it would be, in parallel, learning whether some brain circuits are particularly susceptible to the damage caused by hyperhomocysteinemia. These steps would allow one to (i) understand the actual role of homocysteine in the pathogenesis of cognitive decline and (ii) improve the diagnostic accuracy, differential diagnosis and prognostic implications. This review is aimed at exploring and revising the state of the art of these two strictly related domains. Suggestions for future research are provided.
Chemopreventive Effects of Oral Pterostilbene in Multistage Carcinogenesis of Skin Squamous Cell Carcinoma Mouse Model Induced by DMBA/TPA
Authors: Surien Omchit , Masre Siti Fathiah , Basri Dayang Fredalina , Ghazali Ahmad Rohi
Published: October 2022

Skin squamous cell carcinoma (SCC) is a type of non-melanoma skin cancer. Pterostilbene is a natural compound proven to exhibit various pharmacological properties, including chemo-preventive effects. This study aimed to explore the chemo-preventive effect of oral pterostilbene during initiation, promotion or continuous on multistage skin SCC mouse models induced by 7,12-Dimethylbenz(a)anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-acetate (TPA). The experimental design consists of five groups of female Institute of Cancer Research (ICR) mice, with two control groups of vehicle and cancer. Three oral pterostilbene groups consisted of orally administered pterostilbene during initiation, promotion, or continuously. Oral pterostilbene significantly reduced the number and volume of tumours. Oral pterostilbene demonstrated less severe skin histology changes compared to the cancer control group, with less pleomorphic in the cells and nuclei, and the basement membrane remained intact. Our results showed fewer invasive tumours in oral PT-treated groups than in cancer groups that displayed mitotic bodies, highly pleomorphic cells and nuclei, and basement membrane invasion. The cell proliferation marker (Ki-67) was reduced in oral pterostilbene-treated groups. Overall, oral pterostilbene is a promising chemo-preventive intervention due to its anti-initiation and anti-promotion on skin carcinogenesis. Thus, the potential molecular mechanisms of oral pterostilbene chemo-prevention agent should be explored.
Regenerative Medicine-Based Treatment for Vitiligo: An Overview
Authors: Bellei Barbara , Papaccio Federica , Picardo Mauro
Published: October 2022

Vitiligo is a complex disorder with an important effect on the self-esteem and social life of patients. It is the commonest acquired depigmentation disorder characterized by the development of white macules resulting from the selective loss of epidermal melanocytes. The pathophysiology is complex and involves genetic predisposition, environmental factors, oxidative stress, intrinsic metabolic dysfunctions, and abnormal inflammatory/immune responses. Although several therapeutic options have been proposed to stabilize the disease by stopping the depigmentation process and inducing durable repigmentation, no specific cure has yet been defined, and the long-term persistence of repigmentation is unpredictable. Recently, due to the progressive loss of functional melanocytes associated with failure to spontaneously recover pigmentation, several different cell-based and cell-free regenerative approaches have been suggested to treat vitiligo. This review gives an overview of clinical and preclinical evidence for innovative regenerative approaches for vitiligo patients.
Modified SqueezeNet Architecture for Parkinson’s Disease Detection Based on Keypress Data
Authors: Bernardo Lucas Salvador , Damaševičius Robertas , Ling Sai Ho , de Albuquerque Victor Hugo C. , Tavares João Manuel R. S.
Published: October 2022

Parkinson’s disease (PD) is the most common form of Parkinsonism, which is a group of neurological disorders with PD-like motor impairments. The disease affects over 6 million people worldwide and is characterized by motor and non-motor symptoms. The affected person has trouble in controlling movements, which may affect simple daily-life tasks, such as typing on a computer. We propose the application of a modified SqueezeNet convolutional neural network (CNN) for detecting PD based on the subject’s key-typing patterns. First, the data are pre-processed using data standardization and the Synthetic Minority Oversampling Technique (SMOTE), and then a Continuous Wavelet Transformation is applied to generate spectrograms used for training and testing a modified SqueezeNet model. The modified SqueezeNet model achieved an accuracy of 90%, representing a noticeable improvement in comparison to other approaches.
Impaired Heat Shock Protein Expression in Activated T Cells in B-Cell Lymphoma
Authors: Albakova Zarema , Mangasarova Yana , Sapozhnikov Alexander
Published: October 2022

Heat shock proteins (HSPs) are molecular chaperones that act in a variety of cellular processes, ensuring protein homeostasis and integrity. HSPs play critical roles in the modulation of various immune cells. However, the role of HSPs in T cell activation is largely unknown. We show that HSPs are upregulated following CD3/CD28 stimulation, suggesting that HSP expression might be regulated via TCR. We found that B-cell lymphoma (BCL) patients have dysregulated expression of intracellular and extracellular HSPs, immune checkpoints PD-1, CTLA-4, and STAT3 in CD3/CD28-activated T cells. Consistent with previous findings, we show that HSP90 inhibition downregulated CD4 and CD8 surface markers in healthy controls and BCL patients. HSP90 inhibition alone or in combination with PD-1 or CTLA-4 inhibitors differentially affected CD4+ and CD8+ T cell degranulation responses when stimulated with allogeneic DCs or CD3/CD28 in BCL patients. Additionally, we showed that HSP90 inhibition does not significantly affect intracellular PD-1 and CTLA-4 expression in CD3/CD28-activated T cells. These findings may provide the basis for the discovery of novel immunological targets for the treatment of cancer patients and improve our understanding of HSP functions in immune cells.
Composition of Challenge Substance in Standardized Antimicrobial Efficacy Testing of Wound Antimicrobials Is Essential to Correctly Simulate Efficacy in the Human Wound Micro-Environment
Authors: Severing Anna-Lena , Borkovic Mia , Stuermer Ewa K. , Rembe Julian-Dario
Published: October 2022

Current standards insufficiently acknowledge the influence of the wound micro-environment on the efficacy of antimicrobial agents. To address this, octenidine/phenoxyethanol, polyhexanide, povidone-iodine, and sodium-hypochloride/hypochlorous acid solutions were submitted to standard-based (DIN-EN-13727) or modified peptide-based challenges and compared to a simulated clinical reference using human acute or chronic wound exudate (AWF/CWF). Antimicrobial efficacy against S. aureus and P. aeruginosa was compared using a quantitative suspension method. Agreement between methods were investigated using Bland-Altman (B&A) analysis. Different substances and challenges demonstrated diverging results, depending on class and concentration of agent and challenge. Highly concentrated antiseptics maintained a high efficacy under complex challenges, while especially chlorine-based irrigation solutions showed a remarkably reduced antimicrobial effect. Composition of challenge substance proved more relevant than pure concentration. Therefore, the current standard challenge conditions did not adequately reflect the wound micro-environment with over- or under-estimating antimicrobial efficacy, whilst the modified peptide-challenge showed a higher level of agreement with simulated realistic conditions (AWF/CWF). The results emphasize that a “one-fits-all” approach is not feasible to generalize antimicrobial efficacy, as certain aspects of the complex micro-environment pose a differing influence on varying agents. Based on these results, revision and target focused adaptation of the current standards should be considered.
Analysis of Kinematic Characteristics of Saanen Goat Spine under Multi-Slope
Authors: Zhang Fu , Cui Xiahua , Wang Shunqing , Sun Haoxuan , Wang Jiajia , Wang Xinyue , Fu Sanling , Guo Zhijun
Published: October 2022

In order to improve the slope movement stability and flexibility of quadruped robot, a theoretical design method of a flexible spine of a robot that was based on bionics was proposed. The kinematic characteristics of the spine were analyzed under different slopes with a Saanen goat as the research object. A Qualisys track manager (QTM) gait analysis system was used to obtain the trunk movement of goats under multiple slopes, and linear time normalization (LTN) was used to calibrate and match typical gait cycles to characterize the goat locomotion gait under slopes. Firstly, the spatial angle changes of cervical thoracic vertebrae, thoracolumbar vertebrae, and lumbar vertebrae were compared and analyzed under 0°, 5°, 10°, and 15° slopes, and it was found that the rigid and flexible coupling structure between the thoraco–lumbar vertebrae played an obvious role when moving on the slope. Moreover, with the increase in slope, the movement of the spine changed to the coupling movement of thoraco–lumbar coordination movement and a flexible swing of lumbar vertebrae. Then, the Gaussian mixture model (GMM) clustering algorithm was used to analyze the changes of the thoraco–lumbar vertebrae and lumbar vertebrae in different directions. Combined with anatomical knowledge, it was found that the motion of the thoraco–lumbar vertebrae and lumbar vertebrae in the goat was mainly manifested as a left–right swing in the coronal plane. Finally, on the basis of the analysis of the maximin and variation range of the thoraco–lumbar vertebrae and lumbar vertebrae in the coronal plane, it was found that the coupling motion of the thoraco–lumbar cooperative motion and flexible swing of the lumbar vertebrae at the slope of 10° had the most significant effect on the motion stability. SSE, R2, adjusted-R2, and RMSE were used as evaluation indexes, and the general equations of the spatial fitting curve of the goat spine were obtained by curve fitting of Matlab software. Finally, Origin software was used to obtain the optimal fitting spatial equations under eight movements of the goat spine with SSE and adjusted-R2 as indexes. The research will provide an idea for the bionic spine design with variable stiffness and multi-direction flexible bending, as well as a theoretical reference for the torso design of a bionic quadruped robot.
Biomimetic Whitening Effect of Polyphosphate-Bleaching Agents on Dental Enamel
Authors: Alshehri Abdullah , Almutairi Basil , Jurado Carlos A. , Afrashtehfar Kelvin I. , Albarrak Shug , Alharbi Asma , Alenazi Alanoud , Nurrohman Hamid , Alshabib Abdulrahman
Published: October 2022

This in vitro study investigated the extrinsic tooth-whitening effect of bleaching products containing polyphosphates on the dental enamel surface compared to 10% carbamide peroxide (CP). Eighty human molars were randomly allocated into four whitening-products groups. Group A (control) was treated with 10% CP (Opalescence). The other groups with non-CP over-the-counter (OTC) products were group B = polyphosphates (iWhiteWhitening-Kit); group C = polyphosphates+fluoride (iWhite-toothpaste); and group D = sodium bicarbonate (24K-Whitening-Pen). L*, a*, b* color-parameters were spectrophotometer-recorded at baseline (T0), one day (T1), and one month (T2) post-treatment. Changes in teeth color (ΔEab) were calculated. Data were analyzed using ANOVA and the Bonferroni test (α = 0.05). Groups A, B, and D showed significant differences in ΔL*&Δa* parameters at T1, but not in Δb* at T0. Group C showed no difference for ΔL*, Δa*, Δb* at T0 and T1. Group A showed differences for ΔL*, Δa*, Δb*, at T2, while groups B, C, and D had no difference in any parameters at T0. At T1, ΔEab values = A > D> B > C (ΔEab = 13.4 > 2.4 > 2.1 > 1.2). At T2, ΔEab values increased = A > B > C > D (ΔEab = 12.2 > 10.6 > 9.2 > 2.4). In conclusion, the 10% CP and Biomimetic polyphosphate extrinsic whitening kit demonstrated the highest color change, while simulated brushing with dark stain toothpaste and a whitening pen demonstrated the lowest color change at both measurement intervals.
Optimizing Mineralization of Bioprinted Bone Utilizing Type-2 Fuzzy Systems
Authors: Sedigh Ashkan , Akbarzadeh-T. Mohammad-R. , Tomlinson Ryan E.
Published: October 2022

Bioprinting is an emerging tissue engineering method used to generate cell-laden scaffolds with high spatial resolution. Bioprinting parameters, such as pressure, nozzle size, and speed, highly influence the quality of the bioprinted construct. Moreover, cell suspension density and other critical biological parameters directly impact the biological function. Therefore, an approximation model that can be used to find the optimal bioprinting parameter settings for bioprinted constructs is highly desirable. Here, we propose a type-2 fuzzy model to handle the uncertainty and imprecision in the approximation model. Specifically, we focus on the biological parameters, such as the culture period, that can be used to maximize the output value (mineralization volume 21.8 mm3 with the same culture period of 21 days). We have also implemented a type-1 fuzzy model and compared the results with the proposed type-2 fuzzy model using two levels of uncertainty. We hypothesize that the type-2 fuzzy model may be preferred in biological systems due to the inherent vagueness and imprecision of the input data. Our numerical results confirm this hypothesis. More specifically, the type-2 fuzzy model with a high uncertainty boundary (30%) is superior to type-1 and type-2 fuzzy systems with low uncertainty boundaries in the overall output approximation error for bone bioprinting inputs.