bluuebunny/crossref_metadata_2025 huggingface dataset:
Work-Related Suicide Exposure, Occupational Burnout, and Coping in Emergency Medical Services Personnel in Poland
Authors: Witczak-Błoszyk Kinga , Krysińska Karolina , Andriessen Karl , Stańdo Jacek , Czabański Adam
Published: January 2022

Work-related suicide exposure may significantly contribute to the risk of burnout in first responders. This study assessed the exposure to suicide, burnout, and coping mechanisms in emergency medical services in Poland, including psychosocial determinants, such as age, gender, and access to psychological support. The level of burnout was assessed using the Link Burnout Questionnaire (LBQ), and coping was measured using the Coping Inventory for Stressful Situations (CISS). Data were analysed using a series of variance analyses and a partial least squares structural equation modelling. The study showed that 98% of emergency medical services personnel reported work-related suicide exposure. The LBQ score indicated symptoms of burnout, in particular relational deterioration, and the CISS showed low levels of emotion-oriented coping. Physicians reported higher levels of psycho-physical exhaustion than paramedics and nurses. Access to psychological support in the workplace was related to lower levels of burnout. Emergency medical services personnel are frequently exposed to suicide, which may be related to the risk of occupational burnout, and coping strategies used in this occupational group are often not optimal. Preventive measures, such as training emergency medical services personnel in regard to effective coping strategies, are needed, and personnel should be encouraged to access mental health services and supports.
“When I Don’t Have a Cigarette It’s Helpful, but It Really Don’t Satisfy:” Qualitative Study of Electronic Nicotine Delivery Systems (ENDS) Use among Low-Income Smokers
Authors: Spears Claire A. , Jones Dina M. , Cottrell-Daniels Cherell , Elahi Hala , Strosnider Courtney , Luong Jackie , Weaver Scott R. , Pechacek Terry F.
Published: January 2022

Background: Little is known about the use of electronic nicotine delivery systems (ENDS) among low-income adult cigarette smokers, who experience severe tobacco-related health disparities. Methods: This study conducted interviews to examine experiences and perceptions associated with ENDS use among predominantly low-income adult smokers (n = 30; mean age 30.2 ± 12.9; 60% male, 46.7% African American, 30% white, 10% more than one race; 76.7% annual household income ≤USD 24,000). Interviews were transcribed verbatim and coded in NVivo 11. Results: Overall, participants reported complementing rather than substituting their smoking with ENDS use (e.g., using ENDS only when smoking is not allowed). Predominant reasons for vaping were convenience, smoking reduction/cessation, stress management, social acceptability, lower long-term costs than smoking, and appealing flavors. Common reasons for not switching to exclusive vaping were that ENDS did not satisfy cigarette cravings and concerns about ENDS health effects. Participants indicated higher likelihood of switching to exclusive ENDS use if the products were more affordable, perceived as substantially less harmful, tasted and felt more like smoking a cigarette, and more effective for reducing cravings. Conclusions: Continued research is needed to maximize any harm reduction potential of ENDS and ensure that these products do not contribute to worsening health disparities.
Characteristics of Plantar Pressure with Foot Postures and Lower Limb Pain Profiles in Taiwanese College Elite Rugby League Athletes
Authors: Chow Tong-Hsien , Chen Yih-Shyuan , Hsu Chin-Chia , Hsu Chin-Hsien
Published: January 2022

Background: This study aimed to explore the differences in the distributions of plantar pressure in static and dynamic states and assess the possible pain profiles in the lower limb between elite rugby league athletes and recreational rugby players. Methods: A cross-sectional study of 51 college elite rugby athletes and 57 recreational rugby players was undertaken. The arch index (AI) and plantar pressure distributions (PPDs) with footprint characteristics were evaluated via the JC Mat. Rearfoot alignment was examined to evaluate the static foot posture. The elite group’s lower-limb pain profiles were examined for evaluating the common musculoskeletal pain areas. Results: The recreational group’s AI values fell into the normal range, whereas the elite group’s arch type fell into the category of the low arch. Results from the elite group were: (1) the PPDs mainly exerted on the entire forefoot and lateral midfoot regions in static standing, and transferred to the forefoot region during the midstance phase of walking; (2) the static rearfoot alignment matched the varus posture pattern; (3) the footprint characteristics illustrated the features of low-arched, supinated, dropped metatarsal heads and dropped cuboid feet; and (4) the phalanx and metatarsophalangeal joints, and the abductor hallucis and abductor digiti minimi of the plantar plate were common musculoskeletal pain areas. Conclusions: Characteristics of higher plantar loads beneath forefoot and midfoot associated with low-arched supinated feet in bipedal static stance could be the traceable features for the foot diagram of elite rugby league athletes. The limb pain profiles of the elite rugby league athletes within this study echoed the literature on rugby injuries, and reflected the features of metatarsophalangeal joint pains and dropped cuboids. The relationships among the low-arched supinated feet, metatarsophalangeal joint pains and cuboid syndrome are worth further studies.
Indoor Air Pollution Increases the Risk of Lung Cancer
Authors: Chen Ke-Cheng , Tsai Shih-Wei , Shie Ruei-Hao , Zeng Chian , Yang Hsiao-Yu
Published: January 2022

(1) Background: Cooking and burning incense are important sources of indoor air pollutants. No studies have provided biological evidence of air pollutants in the lungs to support this association. Analysis of pleural fluid may be used to measure the internal exposure dose of air pollutants in the lung. The objective of this study was to provide biological evidence of indoor air pollutants and estimate their risk of lung cancer. (2) Methods: We analyzed 14 common air pollutants in the pleural fluid of 39 cases of lung adenocarcinoma and 40 nonmalignant controls by gas chromatography-mass spectrometry. (3) Results: When we excluded the current smokers and adjusted for age, the adjusted odds ratios (ORs) were 2.22 (95% confidence interval CI = 0.77–6.44) for habitual cooking at home and 3.05 (95% CI = 1.06–8.84) for indoor incense burning. In females, the adjusted ORs were 5.39 (95% CI = 1.11–26.20) for habitual cooking at home and 6.01 (95% CI = 1.14–31.66) for indoor incense burning. In pleural fluid, the most important exposure biomarkers for lung cancer were naphthalene, ethylbenzene, and o-xylene. (4) Conclusions: Habitual cooking and indoor incense burning increased the risk of lung adenocarcinoma.
To Be or Not to Be a Female Gamer: A Qualitative Exploration of Female Gamer Identity
Authors: Kuss Daria J. , Kristensen Anne Marie , Williams A. Jess , Lopez-Fernandez Olatz
Published: January 2022

The literature on online gaming has generally focused on male gamers and has been dominated by negative aspects of gaming. The present study addresses the gender gap in this field by exploring experiences of female gamers further by unravelling several positive experiences alongside some potentially harmful tendencies connected to gaming, including female gamers’ wishes and ambitions for their future gaming. A total of 20 female adult gamers across Europe were interviewed and results were analysed using thematic analysis. Four main themes were identified: (i) to be or not to be a (female) gamer; (ii) improving social skills and levelling up on mental health; (iii) not always a healthy escape; and (iv) there is more to explore. The present study is one of few empirical studies regarding the construction of self-image, and experiences of female gamers. It has showed participants have a history as gamers from adolescence, but still face problems derived from the stigmatised internal gender self-image. Externally, female gamer stigmatisation may result in sexism, gender violence, harassment, and objectification. Additionally, females may decide against identifying as gamers, engaging in social gaming interaction, or hold back from online gaming in general, thereby missing out on the opportunities for recreation as well as social and psychological benefits that gaming brings. There is, therefore, urgent need for more research and actions to promote change, equity, education, and security for female gamers as well as their male counterparts. Game developers would benefit from understanding this large gamer demographic better and tailoring games for women specifically.
The Adverse Effects of Air Pollution on the Eye: A Review
Authors: Lin Chia-Ching , Chiu Chien-Chih , Lee Po-Yen , Chen Kuo-Jen , He Chen-Xi , Hsu Sheng-Kai , Cheng Kai-Chun
Published: January 2022

Air pollution is inevitably the result of human civilization, industrialization, and globalization. It is composed of a mixture of gases and particles at harmful levels. Particulate matter (PM), nitrogen oxides (NOx), and carbon dioxides (CO2) are mainly generated from vehicle emissions and fuel consumption and are the main materials causing outdoor air pollution. Exposure to polluted outdoor air has been proven to be harmful to human eyes. On the other hand, indoor air pollution from environmental tobacco smoking, heating, cooking, or poor indoor ventilation is also related to several eye diseases, including conjunctivitis, glaucoma, cataracts, and age-related macular degeneration (AMD). In the past 30 years, no updated review has provided an overview of the impact of air pollution on the eye. We reviewed reports on air pollution and eye diseases in the last three decades in the PubMed database, Medline databases, and Google Scholar and discussed the effect of various outdoor and indoor pollutants on human eyes.
History, Socioeconomic Problems and Environmental Impacts of Gold Mining in the Andean Region of Ecuador
Authors: Mestanza-Ramón Carlos , Ordoñez-Alcivar Robinson , Arguello-Guadalupe Carla , Carrera-Silva Katherin , D’Orio Giovanni , Straface Salvatore
Published: January 2022

Mining in Ecuadorian territory comprises three stages of Ecuadorian history: pre-Columbian, colonial, and republican times. In its beginnings, this activity did not have regulations or a legal foundation. The first Mining Law dates back to 1830, and it has been modified until the most recent update in 2009. The Andean region consists of 10 provinces, 9 of which have registered gold concessions, the most important of which are Loja, Azuay, and in recent years, Imbabura and Pichincha, which are the provinces with the highest number of reported concessions. The objective of this study focused on analyzing the historical and current situation of Artisanal and Small-scale Mining (ASGM) and the emergence of large-scale (industrial) mining. For the elaboration of this study, different methodological techniques were used, such as literature review, field interviews, and expert judgment validation. The main findings show that the provinces of Loja, Azuay, Imbabura, and Pichincha are the most conflictive areas in the region due to the impacts caused by mining activities. In socio-economic terms, there are conflicts between inhabitants in favor and against these activities and problems associated with human health. In environmental terms, the findings suggest historical contamination of water sources by heavy metals, which has altered the surrounding aquatic and terrestrial systems. Finally, the study concludes that implementing public policies should be promoted to balance socio-economic and environmental aspects in gold mining activities in the Andean region of Ecuador, strengthening the use of new technologies and education to raise awareness of the serious effects of mining activities.
Effects of Six Weeks of Flywheel Single-Leg Romanian Deadlift Training on Speed, Jumping and Change of Direction Performance
Authors: Morencos Esther , González-Frutos Pablo , Rivera Carlos , Veiga Santiago
Published: January 2022

Several studies have confirmed the efficacy of flywheel training, mainly in the bilateral half-squat exercise. The aim of the present study was to analyze the effects of single-leg Romanian deadlift flywheel training on speed, jumping and change of direction performance. Seventeen young healthy males underwent two periods of 3-week training based on two weekly sessions of 3 sets × 7 repetitions or 4 sets × 7 repetitions of single-leg Romanian deadlifts (0.037 kg/m² moment inertia) with their dominant and non-dominant leg. After the first three weeks of the program, the CMJ, the 10 m, 30 m and total sprint times, as well as the COD-90 test, presented likely substantial beneficial effects and a small decrease in the relationship between the sprint and COD-90 test performance. After the second period of the three-week training, likely detrimental effects were observed in some of the change of direction conditions and an increase in the relationship between the sprint and the COD-180 performance. It could be hypothesized that most of the flywheel training effects reported in the traditional protocols lasting a minimum of 5–6 weeks would occur in the first weeks of training.
Solid-State Preparation of Metal and Metal Oxides Nanostructures and Their Application in Environmental Remediation
Authors: Diaz Carlos , Valenzuela Maria Luisa , Laguna-Bercero Miguel Á.
Published: January 2022

Nanomaterials have attracted much attention over the last decades due to their very different properties compared to those of bulk equivalents, such as a large surface-to-volume ratio, the size-dependent optical, physical, and magnetic properties. A number of solution fabrication methods have been developed for the synthesis of metal and metal oxides nanoparticles, but few solid-state methods have been reported. The application of nanostructured materials to electronic solid-state devices or to high-temperature technology requires, however, adequate solid-state methods for obtaining nanostructured materials. In this review, we discuss some of the main current methods of obtaining nanomaterials in solid state, and also we summarize the obtaining of nanomaterials using a new general method in solid state. This new solid-state method to prepare metals and metallic oxides nanostructures start with the preparation of the macromolecular complexes chitosan·Xn and PS-co-4-PVP·MXn as precursors (X = anion accompanying the cationic metal, n = is the subscript, which indicates the number of anions in the formula of the metal salt and PS-co-4-PVP = poly(styrene-co-4-vinylpyridine)). Then, the solid-state pyrolysis under air and at 800 °C affords nanoparticles of M°, MxOy depending on the nature of the metal. Metallic nanoparticles are obtained for noble metals such as Au, while the respective metal oxide is obtained for transition, representative, and lanthanide metals. Size and morphology depend on the nature of the polymer as well as on the spacing of the metals within the polymeric chain. Noticeably in the case of TiO2, anatase or rutile phases can be tuned by the nature of the Ti salts coordinated in the macromolecular polymer. A mechanism for the formation of nanoparticles is outlined on the basis of TG/DSC data. Some applications such as photocatalytic degradation of methylene by different metal oxides obtained by the presented solid-state method are also described. A brief review of the main solid-state methods to prepare nanoparticles is also outlined in the introduction. Some challenges to further development of these materials and methods are finally discussed.
Exosomal MALAT1 Derived from High Glucose-Treated Macrophages Up-Regulates Resistin Expression via miR-150-5p Downregulation
Authors: Shyu Kou-Gi , Wang Bao-Wei , Fang Wei-Jen , Pan Chun-Ming , Lin Chiu-Mei
Published: January 2022

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in the pathophysiological process associated with diabetes-related complications. The effect of high glucose levels on macrophage-derived exosomal MALAT1 is unknown. Therefore, we investigated the molecular regulatory mechanisms controlling exosomal MALAT1 in macrophages under high glucose treatment and the therapeutic target of macrophage-derived exosomal MALAT1 using a balloon injury model of vascular disease in diabetic rats. High glucose (25 mM) significantly increased MALAT1 expression in macrophage-derived exosomes. MALAT1 suppressed miR-150-5p expression in macrophage-derived exosomes under high-glucose conditions. Silencing MALAT1 using MALAT1 siRNA significantly reversed miR-150-5p expression induced by macrophage-derived exosomes. Macrophage-derived exosomes under high-glucose treatment significantly increased resistin expression in macrophages. Silencing MALAT1 and overexpression of miR-150-5p significantly decreased resistin expression induced by macrophage-derived exosomes. Overexpression of miR-150-5p significantly decreased resistin luciferase activity induced by macrophage-derived exosomes. Macrophage-derived exosome significantly decreased glucose uptake in macrophages and silencing MALAT1, resistin or overexpression of miR-150-5p significantly reversed glucose uptake. Balloon injury to the carotid artery significantly increased MALAT1 and resistin expression and significantly decreased miR-150-5p expression in arterial tissue. Silencing MALAT1 significantly reversed miR-150-5p expression in arterial tissue after balloon injury. Silencing MALAT1 or overexpression of miR-150-5p significantly reduced resistin expression after balloon injury. In conclusion, high glucose up-regulates MALAT1 to suppress miR-150-5p expression and counteracts the inhibitory effect of miR-150-5p on resistin expression in macrophages to promote vascular disease. Macrophage-derived exosomes containing MALAT1 may serve as a novel cell-free approach for the treatment of vascular disease in diabetes mellitus.
Deletion of Specific Conserved Motifs from the N-Terminal Domain of αB-Crystallin Results in the Activation of Chaperone Functions
Authors: Mahalingam Sundararajan , Shankar Goutham , Mooney Brian P. , Singh Kamal , Santhoshkumar Puttur , Sharma Krishna K.
Published: January 2022

Smaller oligomeric chaperones of α-crystallins (αA- and αB-) have received increasing attention due to their improved therapeutic potential in preventing protein aggregating diseases. Our previous study suggested that deleting 54–61 residues from the N-terminal domain (NTD) of αB-crystallin (αBΔ54–61) decreases the oligomer size and increases the chaperone function. Several studies have also suggested that NTD plays a significant role in protein oligomerization and chaperone function. The current study was undertaken to assess the effect of deleting conserved 21–28 residues from the activated αBΔ54–61 (to get αBΔ21–28, Δ54–61) on the structure–function of recombinant αBΔ21–28, Δ54–61. The αBΔ21–28, Δ54–61 mutant shows an 80% reduction in oligomer size and 3- to 25-fold increases in chaperone activity against model substrates when compared to αB-WT. Additionally, the αB∆21–28, ∆54–61 was found to prevent β-amyloid (Aβ1–42) fibril formation in vitro and suppressed Aβ1–42-induced cytotoxicity in ARPE-19 cells in a more effective manner than seen with αB-WT or αB∆54–61. Cytotoxicity and reactive oxygen species (ROS) detection studies with sodium iodate (SI) showed that the double mutant protein has higher anti-apoptotic and anti-oxidative activities than the wild-type or αB∆54–61 in oxidatively stressed cells. Our study shows that the residues 21–28 and 54–61 in αB-crystallin contribute to the oligomerization and modulate chaperone function. The deletion of conserved 21–28 residues further potentiates the activated αBΔ54–61. We propose that increased substrate affinity, altered subunit structure, and assembly leading to smaller oligomers could be the causative factors for the increased chaperone activity of αBΔ21–28, Δ54–61.
Development of Thyroid Hormones and Synthetic Thyromimetics in Non-Alcoholic Fatty Liver Disease
Authors: Zhao Man , Xie Huazhong , Shan Hao , Zheng Zhihua , Li Guofeng , Li Min , Hong Liang
Published: January 2022

Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing liver disease in the world. Despite targeted agents which are needed to provide permanent benefits for patients with NAFLD, no drugs have been approved to treat NASH. Thyroid hormone is an important signaling molecule to maintain normal metabolism, and in vivo and vitro studies have shown that regulation of the 3,5,3’-triiodothyronine (T3)/ thyroid hormone receptor (TR) axis is beneficial not only for metabolic symptoms but also for the improvement of NAFLD and even for the repair of liver injury. However, the non-selective regulation of T3 to TR subtypes (TRα/TRβ) could cause unacceptable side effects represented by cardiotoxicity. To avoid deleterious effects, TRβ-selective thyromimetics were developed for NASH studies in recent decades. Herein, we will review the development of thyroid hormones and synthetic thyromimetics based on TR selectivity for NAFLD, and analyze the role of TR-targeted drugs for the treatment of NAFLD in the future.
Effect of Phosphorus Precursor, Reduction Temperature, and Support on the Catalytic Properties of Nickel Phosphide Catalysts in Continuous-Flow Reductive Amination of Ethyl Levulinate
Authors: Wang Yazhou , Nuzhdin Alexey L. , Shamanaev Ivan V. , Kodenev Evgeny G. , Gerasimov Evgeny Yu. , Bukhtiyarova Marina V. , Bukhtiyarova Galina A.
Published: January 2022

Levulinic acid and its esters (e.g., ethyl levulinate, EL) are platform chemicals derived from biomass feedstocks that can be converted to a variety of valuable compounds. Reductive amination of levulinates with primary amines and H2 over heterogeneous catalysts is an attractive method for the synthesis of N-alkyl-5-methyl-2-pyrrolidones, which are an environmentally friendly alternative to the common solvent N-methyl-2-pyrrolidone (NMP). In the present work, the catalytic properties of the different nickel phosphide catalysts supported on SiO2 and Al2O3 were studied in a reductive amination of EL with n-hexylamine to N-hexyl-5-methyl-2-pyrrolidone (HMP) in a flow reactor. The influence of the phosphorus precursor, reduction temperature, reactant ratio, and addition of acidic diluters on the catalyst performance was investigated. The Ni2P/SiO2 catalyst prepared using (NH4)2HPO4 and reduced at 600 °C provides the highest HMP yield, which reaches 98%. Although the presence of acid sites and a sufficient hydrogenating ability are important factors determining the pyrrolidone yield, the selectivity also depends on the specific features of EL adsorption on active catalytic sites.
Challenging Approach to the Development of Novel Estrogen Receptor Modulators Based on the Chemical Properties of Guaiazulene
Authors: Ohta Kiminori , Kaise Asako , Ogawa Takumi , Endo Yasuyuki
Published: January 2022

Tamoxifen, a therapeutic agent for breast cancer, has been associated with genetic polymorphisms in the metabolism of N,N-dialkylaminoethyl substituent, which plays an important role in the expression of selective estrogen receptor modulator (SERM) activity. To solve this problem, we developed a novel estrogen receptor (ER) modulator, Az-01, on the basis of the aromaticity, dipole moment, and isopropyl group of guaiazulene. Az-01 showed four-fold lower binding affinity for ER than E2 but had similar ER-binding affinity to that of 4-hydroxytamoxifen (4-HOtam). Unlike tamoxifen, Az-01 acted as a partial agonist with very weak estrogenic activity at high concentrations when used alone, and it showed potent anti-estrogenic activity in the presence of E2. The cell proliferation and inhibition activities of Az-01 were specific to ER-expressing MCF-7 cells, and no effect of Az-01 on other cell proliferation signals was observed. These findings are important for the development of new types of SERMs without the N,N-dialkylaminoethyl substituent as a privileged functional group for SERMs.
Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma
Authors: Nanamori Hikaru , Sawada Yu
Published: January 2022

Malignant melanoma is one of the representative skin cancers with unfavorable clinical behavior. Immunotherapy is currently used for the treatment, and it dramatically improves clinical outcomes in patients with advanced malignant melanoma. On the other hand, not all these patients can obtain therapeutic efficacy. To overcome this limitation of current immunotherapy, epigenetic modification is a highlighted issue for clinicians. Epigenetic modification is involved in various physiological and pathological conditions in the skin. Recent studies identified that skin cancer, especially malignant melanoma, has advantages in tumor development, indicating that epigenetic manipulation for regulation of gene expression in the tumor can be expected to result in additional therapeutic efficacy during immunotherapy. In this review, we focus on the detailed molecular mechanism of epigenetic modification in immunotherapy, especially anti-PD-1/PD-L1 antibody treatment for malignant melanoma.
Genome-Wide Identification and Characterization of the Soybean DEAD-Box Gene Family and Expression Response to Rhizobia
Authors: Wang Yongliang , Liao Junwen , Wu Jun , Huang Huimei , Yuan Zhanxin , Yang Wei , Wu Xinying , Li Xia
Published: January 2022

DEAD-box proteins are a large family of RNA helicases that play important roles in almost all cellular RNA processes in model plants. However, little is known about this family of proteins in crops such as soybean. Here, we identified 80 DEAD-box family genes in the Glycine max (soybean) genome. These DEAD-box genes were distributed on 19 chromosomes, and some genes were clustered together. The majority of DEAD-box family proteins were highly conserved in Arabidopsis and soybean, but Glyma.08G231300 and Glyma.14G115100 were specific to soybean. The promoters of these DEAD-box genes share cis-acting elements involved in plant responses to MeJA, salicylic acid (SA), low temperature and biotic as well as abiotic stresses; interestingly, half of the genes contain nodulation-related cis elements in their promoters. Microarray data analysis revealed that the DEAD-box genes were differentially expressed in the root and nodule. Notably, 31 genes were induced by rhizobia and/or were highly expressed in the nodule. Real-time quantitative PCR analysis validated the expression patterns of some DEAD-box genes, and among them, Glyma.08G231300 and Glyma.14G115100 were induced by rhizobia in root hair. Thus, we provide a comprehensive view of the DEAD-box family genes in soybean and highlight the crucial role of these genes in symbiotic nodulation.
Decoding the Phosphatase Code: Regulation of Cell Proliferation by Calcineurin
Authors: Masaki Takahiro , Shimada Midori
Published: January 2022

Calcineurin, a calcium-dependent serine/threonine phosphatase, integrates the alterations in intracellular calcium levels into downstream signaling pathways by regulating the phosphorylation states of several targets. Intracellular Ca2+ is essential for normal cellular physiology and cell cycle progression at certain critical stages of the cell cycle. Recently, it was reported that calcineurin is activated in a variety of cancers. Given that abnormalities in calcineurin signaling can lead to malignant growth and cancer, the calcineurin signaling pathway could be a potential target for cancer treatment. For example, NFAT, a typical substrate of calcineurin, activates the genes that promote cell proliferation. Furthermore, cyclin D1 and estrogen receptors are dephosphorylated and stabilized by calcineurin, leading to cell proliferation. In this review, we focus on the cell proliferative functions and regulatory mechanisms of calcineurin and summarize the various substrates of calcineurin. We also describe recent advances regarding dysregulation of the calcineurin activity in cancer cells. We hope that this review will provide new insights into the potential role of calcineurin in cancer development.
EN1 Regulates Cell Growth and Proliferation in Human Glioma Cells via Hedgehog Signaling
Authors: Chang Jinchun , Guo Chenjia , Li Jianyu , Liang Zhangqian , Wang Yankai , Yu Anliang , Liu Runze , Guo Yuting , Chen Jian , Huang Song
Published: January 2022

Glioblastoma is an aggressive cancer of the nervous system that accounts for the majority of brain cancer-related deaths. Through cross-species transcriptome studies, we found that Engrailed 1 (EN1) is highly expressed in serum-free cultured glioma cells as well as glioma tissues, and increased expression level predicts a worse prognosis. EN1 controls glioma cell proliferation, colony formation, migration, and tumorigenic capacity in vivo. It also influences sensitivity of glioma cells to γ-ray irradiation by regulating intracellular ROS levels. Mechanistically, EN1 influences Hedgehog signaling by regulating the level of Gli1 as well as primary cilia length and the primary cilia transport-related protein TULP3. In conclusion, we demonstrate that EN1 acts as an oncogenic regulator that contributes to glioblastoma pathogenesis and could serve as a diagnostic/prognostic marker and therapeutic target for glioblastoma.
Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations
Authors: Zizmare Laimdota , Boyle Christina N. , Buss Sabrina , Louis Sandrine , Kuebler Laura , Mulay Ketki , Krüger Ralf , Steinhauer Lara , Mack Isabelle , Rodriguez Gomez Manuel , Herfert Kristina , Ritze Yvonne , Trautwein Christoph
Published: January 2022

Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action.
Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway
Authors: Liu Pinduo , Wu Anping , Li Hui , Zhang Jun , Ni Junjun , Quan Zhenzhen , Qing Hong
Published: January 2022

Rab21 is a GTPase protein that is functional in intracellular trafficking and involved in the pathologies of many diseases, such as Alzheimer’s disease (AD), glioma, cancer, etc. Our previous work has reported its interaction with the catalytic subunit of gamma-secretase, PS1, and it regulates the activity of PS1 via transferring it from the early endosome to the late endosome/lysosome. However, it is still unknown how Rab21 protein itself is regulated. This work revealed that Rab21 protein, either endogenously or exogenously, can be degraded by the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. It is further observed that the ubiquitinated Rab21 is increased, but the total protein is unchanged in AD model mice. We further observed that overexpression of Rab21 leads to increased expression of a series of genes involved in the autophagy-lysosome pathway. We speculated that even though the ubiquitinated Rab21 is increased due to the impaired proteasome function in the AD model, the autophagy-lysosome pathway functions in parallel to degrade Rab21 to keep its protein level in homeostasis. In conclusion, understanding the characters of Rab21 protein itself help explore its potential as a target for therapeutic strategy in diseases.
Modulating mTOR Signaling as a Promising Therapeutic Strategy for Atherosclerosis
Authors: Poznyak Anastasia V. , Sukhorukov Vasily N. , Zhuravlev Alexander , Orekhov Nikolay A. , Kalmykov Vladislav , Orekhov Alexander N.
Published: January 2022

For more than a decade, atherosclerosis has been one of the leading causes of death in developed countries. The issue of treatment and prevention of the disease is especially acute. Despite the huge amount of basic and clinical research, a significant number of gaps remain in our understanding of the pathogenesis of atherosclerosis, and only their closure will bring us closer to understanding the causes of the disease at the cellular and molecular levels and, accordingly, to the development of an effective treatment. One of the seemingly well-studied elements of atherogenesis is the mTOR signaling pathway. However, more and more new details are still being clarified. Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well.
Cancer as a Metabolic Disorder
Authors: Gyamfi Jones , Kim Jinyoung , Choi Junjeong
Published: January 2022

Cancer has long been considered a genetic disease characterized by a myriad of mutations that drive cancer progression. Recent accumulating evidence indicates that the dysregulated metabolism in cancer cells is more than a hallmark of cancer but may be the underlying cause of the tumor. Most of the well-characterized oncogenes or tumor suppressor genes function to sustain the altered metabolic state in cancer. Here, we review evidence supporting the altered metabolic state in cancer including key alterations in glucose, glutamine, and fatty acid metabolism. Unlike genetic alterations that do not occur in all cancer types, metabolic alterations are more common among cancer subtypes and across cancers. Recognizing cancer as a metabolic disorder could unravel key diagnostic and treatments markers that can impact approaches used in cancer management.
PEG35 as a Preconditioning Agent against Hypoxia/Reoxygenation Injury
Authors: Teixeira da Silva Rui , Machado Ivo F. , Teodoro João S. , Panisello-Roselló Arnau , Roselló-Catafau Joan , Rolo Anabela P. , Palmeira Carlos M.
Published: January 2022

Pharmacological conditioning is a protective strategy against ischemia/reperfusion injury, which occurs during liver resection and transplantation. Polyethylene glycols have shown multiple benefits in cell and organ preservation, including antioxidant capacity, edema prevention and membrane stabilization. Recently, polyethylene glycol 35 kDa (PEG35) preconditioning resulted in decreased hepatic injury and protected the mitochondria in a rat model of cold ischemia. Thus, the study aimed to decipher the mechanisms underlying PEG35 preconditioning-induced protection against ischemia/reperfusion injury. A hypoxia/reoxygenation model using HepG2 cells was established to evaluate the effects of PEG35 preconditioning. Several parameters were assessed, including cell viability, mitochondrial membrane potential, ROS production, ATP levels, protein content and gene expression to investigate autophagy, mitochondrial biogenesis and dynamics. PEG35 preconditioning preserved the mitochondrial function by decreasing the excessive production of ROS and subsequent ATP depletion, as well as by recovering the membrane potential. Furthermore, PEG35 increased levels of autophagy-related proteins and the expression of genes involved in mitochondrial biogenesis and fusion. In conclusion, PEG35 preconditioning effectively ameliorates hepatic hypoxia/reoxygenation injury through the enhancement of autophagy and mitochondrial quality control. Therefore, PEG35 could be useful as a potential pharmacological tool for attenuating hepatic ischemia/reperfusion injury in clinical practice.
P-Glycoprotein and Androgen Receptor Expression Reveals Independence of Canine Prostate Cancer from Androgen Hormone Stimulation
Authors: Cavalca Alexandre Matheus Baesso , Brandi Andressa , Fonseca-Alves Ricardo Henrique , Laufer-Amorim Renée , Fonseca-Alves Carlos Eduardo
Published: January 2022

Canine prostate cancer (PC) is an aggressive disease, and dogs can be considered comparative models for human PC. In recent years, canine PC has been shown to resemble human castrate-resistant prostate cancer. The influx and efflux of testosterone in prostatic luminal cells are regulated by P-glycoprotein (P-gp). Therefore, human PC generally lacks P-gp expression and maintains the expression of androgen receptors (ARs). However, this co-expression has not previously been investigated in dogs. Therefore, this study aimed to evaluate AR and P-gp co-expression to elucidate these protein patterns in canine prostate samples. We identified AR/P-gp double immunofluorescence co-expression of both proteins in normal luminal cells. However, in canine PC, cells lack AR expression and exhibit increased P-gp expression. These results were confirmed by gene expression analyses. Overall, our results strongly suggest that normal canine prostate testosterone influx may be regulated by P-gp expression, and that during progression to PC, prostatic cells lack AR expression and P-gp overexpress. P-gp expression in canine PC may be related to a phenotype of multiple drug resistance.
Transforming Growth Factor-Beta in Skeletal Muscle Wasting
Authors: Klein Gordon L.
Published: January 2022

Transforming growth factor-beta (TGF-β) is part of a family of molecules that is present in many body tissues and performs many different functions. Evidence has been obtained from mice and human cancer patients with bony metastases and non-metastatic disease, as well as pediatric burn patients, that inflammation leads to bone resorption and release of TGF-β from the bone matrix with paracrine effects on muscle protein balance, possibly mediated by the generation of reactive oxygen species. Whether immobilization, which confounds the etiology of bone resorption in burn injury, also leads to the release of TGF-β from bone contributing to muscle wasting in other conditions is unclear. The use of anti-resorptive therapy in both metastatic cancer patients and pediatric burn patients has been successful in the prevention of muscle wasting, thereby creating an additional therapeutic niche for this class of drugs. The liberation of TGF-β may be one way in which bone helps to control muscle mass, but further investigation will be necessary to assess whether the rate of bone resorption is the determining factor for the release of TGF-β. Moreover, whether different resorptive conditions, such as immobilization and hyperparathyroidism, also involve TGF-β release in the pathogenesis of muscle wasting needs to be investigated.
A Deep Dive into VDAC1 Conformational Diversity Using All-Atom Simulations Provides New Insights into the Structural Origin of the Closed States
Authors: Preto Jordane , Gorny Hubert , Krimm Isabelle
Published: January 2022

The voltage-dependent anion channel 1 (VDAC1) is a crucial mitochondrial transporter that controls the flow of ions and respiratory metabolites entering or exiting mitochondria. As a voltage-gated channel, VDAC1 can switch between a high-conducting “open” state and a low-conducting “closed” state emerging at high transmembrane (TM) potentials. Although cell homeostasis depends on channel gating to regulate the transport of ions and metabolites, structural hallmarks characterizing the closed states remain unknown. Here, we performed microsecond accelerated molecular dynamics to highlight a vast region of VDAC1 conformational landscape accessible at typical voltages known to promote closure. Conformers exhibiting durable subconducting properties inherent to closed states were identified. In all cases, the low conductance was due to the particular positioning of an unfolded part of the N-terminus, which obstructed the channel pore. While the N-terminal tail was found to be sensitive to voltage orientation, our models suggest that stable low-conducting states of VDAC1 predominantly take place from disordered events and do not result from the displacement of a voltage sensor or a significant change in the pore. In addition, our results were consistent with conductance jumps observed experimentally and corroborated a recent study describing entropy as a key factor for VDAC gating.
Quantitative In-Depth Transcriptome Analysis Implicates Peritoneal Macrophages as Important Players in the Complement and Coagulation Systems
Authors: Paivandy Aida , Akula Srinivas , Lara Sandra , Fu Zhirong , Olsson Anna-Karin , Kleinau Sandra , Pejler Gunnar , Hellman Lars
Published: January 2022

To obtain a more detailed picture of macrophage (MΦ) biology, in the current study, we analyzed the transcriptome of mouse peritoneal MΦs by RNA-seq and PCR-based transcriptomics. The results show that peritoneal MΦs, based on mRNA content, under non-inflammatory conditions produce large amounts of a number of antimicrobial proteins such as lysozyme and several complement components. They were also found to be potent producers of several chemokines, including platelet factor 4 (PF4), Ccl6, Ccl9, Cxcl13, and Ccl24, and to express high levels of both TGF-β1 and TGF-β2. The liver is considered to be the main producer of most complement and coagulation components. However, we can now show that MΦs are also important sources of such compounds including C1qA, C1qB, C1qC, properdin, C4a, factor H, ficolin, and coagulation factor FV. In addition, FX, FVII, and complement factor B were expressed by the MΦs, altogether indicating that MΦs are important local players in both the complement and coagulation systems. For comparison, we analyzed human peripheral blood monocytes. We show that the human monocytes shared many characteristics with the mouse peritoneal MΦs but that there were also many major differences. Similar to the mouse peritoneal MΦs, the most highly expressed transcript in the monocytes was lysozyme, and high levels of both properdin and ficolin were observed. However, with regard to connective tissue components, such as fibronectin, lubricin, syndecan 3, and extracellular matrix protein 1, which were highly expressed by the peritoneal MΦs, the monocytes almost totally lacked transcripts. In contrast, monocytes expressed high levels of MHC Class II, whereas the peritoneal MΦs showed very low levels of these antigen-presenting molecules. Altogether, the present study provides a novel view of the phenotype of the major MΦ subpopulation in the mouse peritoneum and the large peritoneal MΦs and places the transcriptome profile of the peritoneal MΦs in a broader context, including a comparison of the peritoneal MΦ transcriptome with that of human peripheral blood monocytes and the liver.
Bilateral Meningioma: A Case Report and Review of the Literature
Authors: Bukovac Anja , Panić Hana , Mrgan Tomislava , Šlaus Nika , Kafka Anja , Njirić Niko , Pećina-Šlaus Nives
Published: January 2022

Here, we present a rarely seen example of bilateral meningiomas exhibiting different malignancy grades, I (meningothelial) and II (atypical), recorded in a 72-year-old patient. The presence of two separated lesions of different grades in a single patient can elucidate meningioma progression. To this end, the involvement of specific protein markers of epithelial to mesenchymal transition (EMT), the process responsible for progression, was tested in both tumors. Protein expression status of specific epithelial (E-cadherin) and mesenchymal markers (N-cadherin, SNAIL&SLUG and TWIST1) was investigated. Furthermore, markers that are connected to Wnt signaling pathway–beta-catenin, GSK3beta and DVL1—were also analyzed. For signs of neurofibromatosis and schwanomatosis genetic testing was performed. Immunohistochemistry evaluated by immunoreactivity score (IRS) was used to determine the signal strengths and proteins’ location. Our results indicated that, in comparison to the grade I tumor, mesenchymal markers SNAIL and SLUG were upregulated in the atypical meningioma. TWIST1, beta-catenin and GSK3beta were upregulated in both grades, while E-cadherin was partially lost. A pronounced cadherin switch could not be established; however, N-cadherin showed widespread tissue presence. Genetic testing did not detect changes of NF2 or SMARCB1 genes denying germline origin of the lesions. The rare presence of two different grades in one patient elucidate previously unknown molecules involved in meningioma progression.
Interrelations between Iron and Vitamin A—Studied Using Systems Approach
Authors: Gutowska Kaja , Formanowicz Dorota , Formanowicz Piotr
Published: January 2022

A deficiency of vitamin A (VAD) and iron is the most common nutritional problem affecting people worldwide. Given the scale of the problem, the interactions between vitamin A and iron levels are widely studied. However, the exact mechanism of the impact of vitamin A on the regulation of iron metabolism remains unclear. An extremely significant issue becomes a better understanding of the nature of the studied biological phenomenon, which is possible by using a systems approach through developing and analyzing a mathematical model based on a Petri net. To study the considered system, the t-cluster analysis, the significance analysis, and the analysis of the average number of transition firings were performed. The used analyses have allowed distinguishing the most important mechanisms (both subprocesses and elementary processes) positively and negatively regulating an expression of hepcidin and allowed to distinguish elementary processes with a higher frequency of occurrence compared to others. The analysis also allowed to resolve doubts about the discrepancy in literature reports, where VAD leads to positive regulation of hepcidin expression or to negative regulation of hepcidin expression. The more detailed analyses have shown that VAD more frequently positively stimulates hepcidin expression and this mechanism is more significant than the mechanism inhibiting hepcidin expression indirectly by VAD.
Spectroscopic Properties of Inorganic Glasses Doped with Pr3+: A Comparative Study
Authors: Pisarska Joanna , Kuwik Marta , Pisarski Wojciech A.
Published: January 2022

The results presented in this communication concern visible and near-IR emission of Pr3+ ions in selected inorganic glasses, i.e., borate-based glass with Ga2O3 and BaO, lead-phosphate glass with Ga2O3, gallo-germanate glass modified by BaO/BaF2, and multicomponent fluoride glass based on InF3. Glasses present several emission bands at blue, reddish orange, and near-infrared spectral ranges, which correspond to 4f–4f electronic transitions of Pr3+. The profiles of emission bands and their relative intensity ratios depend strongly on glass-host. Visible emission of Pr3+ ions is tuned from red/orange for borate-based glass to nearly white light for multicomponent fluoride glass based on InF3. The positions and spectral linewidths for near-infrared luminescence bands at the optical telecommunication window corresponding to the 1G4 → 3H5, 1D2 → 1G4, and 3H4 → 3F3,3F4 transitions of Pr3+ are dependent on glass-host matrices and excitation wavelengths. Low-phonon fluoride glasses based on InF3 and gallo-germanate glasses with BaO/BaF2 are excellent candidates for broadband near-infrared optical amplifiers. Spectroscopic properties of Pr3+-doped glasses are compared and discussed in relation to potential optical applications.