bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Parental Perception of Child’s Physical Fitness on Body Image Satisfaction in Spanish Preschool Children
Authors: Rojo-Ramos Jorge , Mendoza-Muñoz María , Castillo-Paredes Antonio , Galán-Arroyo Carmen
Published: April 2023

It is well known that poor physical fitness is an exponential risk factor in the increase in chronic diseases, not only physical but also psychological. Even in childhood, a critical period of development, the perception of physical fitness plays a fundamental role in the individual’s self-concept of body image. Aim: To find out how self-perceived physical fitness influences self-perceived body image in preschoolers. Methods: 475 preschool pupils were recruited in the schools of Extremadura (Spain). They were administered a sociodemographic questionnaire, the Preschool Physical Fitness Index (IFIS) and the Preschool Body Scale (PBS). Findings: Significant correlations (p < 0.05) were observed between body dissatisfaction and perceived physical fitness (IFIS), being higher in girls. In terms of variables, general fitness (<0.001), cardio-respiratory fitness (<0.001), muscular strength (<0.001), speed/agility (<0.001) and balance (<0.001) have a negative, medium and significant association with body dissatisfaction in girls; however, this association was lower in the case of boys. Conclusions: The influence of physical fitness had a clear impact on self-perceived body image. With better findings on self-perceived physical fitness variables (IFIS) there was less body dissatisfaction (PBS), especially in the female sex. The results also showed that parents who perceived their children to be in poorer physical condition had higher body dissatisfaction. Therefore, it would be interesting for the context involved, particularly parents, to implement strategies to improve positive body image through the promotion of physical education and physical fitness at an early age.
A Mixed-Method Examination of Emerging and Young Adult Cancer Caregivers’ Experiences during the COVID-19 Pandemic
Authors: Kastrinos Amanda , Bacharz Kelsey , Mroz Emily L. , Fisher Carla L. , Applebaum Allison J.
Published: April 2023

Advanced cancer caregivers in emerging and young adulthood (EYACs; ages 18–35) are an understudied yet vulnerable caregiving population. The COVID-19 pandemic created new challenges for advanced cancer caregivers but also created unique contexts from which caregivers sometimes benefited. To understand how the pandemic may have positively and negatively impacted their caregiving and bereavement experiences, we examined EYACs’ experiences of caring for and losing a parent with advanced cancer during the pandemic in comparison to those of EYACs with a parent who died outside the context of the pandemic. Eligible EYACs completed an online survey and semi-structured interview. Quantitative analyses compared responses for pre-pandemic EYACS (n = 14) and pandemic EYACs (n = 26). A thematic analysis of the interview transcripts of pandemic EYACS (n = 14) was conducted. Pandemic EYACs experienced non-significant but higher communal coping, benefit finding, negative emotional experiences, and caregiver strain than pre-pandemic EYACs. Thematic analysis revealed that the pandemic negatively affected EYACs’ caregiving efficacy, personal well-being, interpersonal dynamics, and bereavement; shifts to remote work and schooling were reported as benefits. The findings can inform the design of resources to support EYACs whose parents died during the pandemic and who are navigating the healthcare system today.
Mesoporous Carbon-Based Materials for Enhancing the Performance of Lithium-Sulfur Batteries
Authors: Wang Fangzheng , Han Yuying , Feng Xin , Xu Rui , Li Ang , Wang Tao , Deng Mingming , Tong Cheng , Li Jing , Wei Zidong
Published: April 2023

The most promising energy storage devices are lithium-sulfur batteries (LSBs), which offer a high theoretical energy density that is five times greater than that of lithium-ion batteries. However, there are still significant barriers to the commercialization of LSBs, and mesoporous carbon-based materials (MCBMs) have attracted much attention in solving LSBs’ problems, due to their large specific surface area (SSA), high electrical conductivity, and other unique advantages. The synthesis of MCBMs and their applications in the anodes, cathodes, separators, and “two-in-one” hosts of LSBs are reviewed in this study. Most interestingly, we establish a systematic correlation between the structural characteristics of MCBMs and their electrochemical properties, offering recommendations for improving performance by altering the characteristics. Finally, the challenges and opportunities of LSBs under current policies are also clarified. This review provides ideas for the design of cathodes, anodes, and separators for LSBs, which could have a positive impact on the performance enhancement and commercialization of LSBs. The commercialization of high energy density secondary batteries is of great importance for the achievement of carbon neutrality and to meet the world’s expanding energy demand.
Microtubule Cytoskeletal Network Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders
Authors: Gąssowska-Dobrowolska Magdalena , Czapski Grzegorz A. , Cieślik Magdalena , Zajdel Karolina , Frontczak-Baniewicz Małgorzata , Babiec Lidia , Adamczyk Agata
Published: April 2023

Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder caused by loss-of-function mutations in the tumour suppressors TSC1/TSC2, both of which are negative regulators of the mammalian target of rapamycin (mTOR) kinase. Importantly, mTOR hyperactivity seems to be linked with the pathobiology of autism spectrum disorders (ASD). Recent studies suggest the potential involvement of microtubule (MT) network dysfunction in the neuropathology of “mTORopathies”, including ASD. Cytoskeletal reorganization could be responsible for neuroplasticity disturbances in ASD individuals. Thus, the aim of this work was to study the effect of Tsc2 haploinsufficiency on the cytoskeletal pathology and disturbances in the proteostasis of the key cytoskeletal proteins in the brain of a TSC mouse model of ASD. Western-blot analysis indicated significant brain-structure-dependent abnormalities in the microtubule-associated protein Tau (MAP-Tau), and reduced MAP1B and neurofilament light (NF-L) protein level in 2-month-old male B6;129S4-Tsc2tm1Djk/J mice. Alongside, pathological irregularities in the ultrastructure of both MT and neurofilament (NFL) networks as well as swelling of the nerve endings were demonstrated. These changes in the level of key cytoskeletal proteins in the brain of the autistic-like TSC mice suggest the possible molecular mechanisms responsible for neuroplasticity alterations in the ASD brain.
The Expression Levels of MicroRNAs Differentially Expressed in Sudden Sensorineural Hearing Loss Patients’ Serum Are Unchanged for up to 12 Months after Hearing Loss Onset
Authors: Abgoon Reyhaneh , Wijesinghe Printha , Garnis Cathie , Nunez Desmond A.
Published: April 2023

Sudden sensorineural hearing loss (SSNHL) is an acquired idiopathic hearing loss. Serum levels of small, non-coding RNAs and microRNAs (miRNAs) miR-195-5p/-132-3p/-30a-3p/-128-3p/-140-3p/-186-5p/-375-3p/-590-5p are differentially expressed in SSNHL patients within 28 days of hearing loss onset. This study determines if these changes persist by comparing the serum miRNA expression profile of SSNHL patients within 1 month of hearing loss onset with that of patients 3–12 months after hearing loss onset. We collected serum from consenting adult SSNHL patients at presentation or during clinic follow-up. We matched patient samples drawn 3–12 months after hearing loss onset (delayed group, n = 9 patients) by age and sex to samples drawn from patients within 28 days of hearing loss onset (immediate group, n = 14 patients). We compared the real-time PCR-determined expression levels of the target miRNAs between the two groups. We calculated the air conduction pure-tone-averaged (PTA) audiometric thresholds in affected ears at the initial and final follow-up visits. We undertook inter-group comparisons of hearing outcome status and initial and final PTA audiometric thresholds. There was no significant inter-group difference in miRNA expression level, hearing recovery status and initial and final affected ear PTA audiometric thresholds.
Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer
Authors: Du Yin-Xiao , Mamun Abdullah Al , Lyu Ai-Ping , Zhang Hong-Jie
Published: April 2023

Autophagy is a highly conserved intracellular degradation pathway by which misfolded proteins or damaged organelles are delivered in a double-membrane vacuolar vesicle and finally degraded by lysosomes. The risk of colorectal cancer (CRC) is high, and there is growing evidence that autophagy plays a critical role in regulating the initiation and metastasis of CRC; however, whether autophagy promotes or suppresses tumor progression is still controversial. Many natural compounds have been reported to exert anticancer effects or enhance current clinical therapies by modulating autophagy. Here, we discuss recent advancements in the molecular mechanisms of autophagy in regulating CRC. We also highlight the research on natural compounds that are particularly promising autophagy modulators for CRC treatment with clinical evidence. Overall, this review illustrates the importance of autophagy in CRC and provides perspectives for these natural autophagy regulators as new therapeutic candidates for CRC drug development.
Metabolite Identification of Isopropoxy Benzene Guanidine in Rat Liver Microsomes by Using UHPLC-Q-TOF-MS/MS
Authors: Lu Yixing , Zhang Wanying , Zhang Yongxiang , Wu Sujuan , Ma Minglang , Peng Xianfeng , Zeng Zhenling , Zeng Dongping
Published: April 2023

Isopropoxy benzene guanidine (IBG) is a guanidine derivative with antibacterial activity against multidrug-resistant bacteria. A few studies have revealed the metabolism of IBG in animals. The aim of the current study was to identify potential metabolic pathways and metabolites of IBG. The detection and characterization of metabolites were performed with high-performance liquid chromatography tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). Seven metabolites were identified from the microsomal incubated samples by using the UHPLC-Q-TOF-MS/MS system. The metabolic pathways of IBG in the rat liver microsomes involved O-dealkylation, oxygenation, cyclization, and hydrolysis. Hydroxylation was the main metabolic pathway of IBG in the liver microsomes. This research investigated the in vitro metabolism of IBG to provide a basis for the further pharmacology and toxicology of this compound.
IDO1 Protein Is Expressed in Diagnostic Biopsies from Both Follicular and Transformed Follicular Patients
Authors: Enemark Marie Beck Hairing , Sørensen Emma Frasez , Hybel Trine Engelbrecht , Andersen Maja Dam , Madsen Charlotte , Lauridsen Kristina Lystlund , Honoré Bent , d’Amore Francesco , Plesner Trine Lindhardt , Hamilton-Dutoit Stephen Jacques , Ludvigsen Maja
Published: April 2023

Follicular lymphoma (FL) is a lymphoid neoplasia characterized by an indolent clinical nature. Despite generally favorable prognoses, early progression and histological transformation (HT) to a more aggressive lymphoma histology remain the leading causes of death among FL patients. To provide a basis for possible novel treatment options, we set out to evaluate the expression levels of indoleamine 2,3-dioxygenase 1 (IDO1), an immunoinhibitory checkpoint molecule, in follicular and transformed follicular biopsies. The expression levels of IDO1 were assessed using immunohistochemical staining and digital image analysis in lymphoma biopsies from 33 FL patients without subsequent HT (non-transforming FL, nt-FL) and 20 patients with subsequent HT (subsequently transforming FL, st-FL) as well as in paired high-grade biopsies from the time of HT (transformed FL, tFL). Despite no statistical difference in IDO1 expression levels seen between the groups, all diagnostic and transformed lymphomas exhibited positive expression, indicating its possible role in novel treatment regimens. In addition, IDO1 expression revealed a positive correlation with another immune checkpoint inhibitor, namely programmed death 1 (PD-1). In summary, we report IDO1 expression in all cases of FL and tFL, which provides the grounds for future investigations of anti-IDO1 therapy as a possible treatment for FL patients.
Influence of Ethanol Parametrization on Diffusion Coefficients Using OPLS-AA Force Field
Authors: Zêzere Bruno , Fonseca Tiago V. B. , Portugal Inês , Simões Mário M. Q. , Silva Carlos M. , Gomes José R. B.
Published: April 2023

Molecular dynamics simulations employing the all-atom optimized potential for liquid simulations (OPLS-AA) force field were performed for determining self-diffusion coefficients (D11) of ethanol and tracer diffusion coefficients (D12) of solutes in ethanol at several temperature and pressure conditions. For simulations employing the original OPLS-AA diameter of ethanol’s oxygen atom (σOH), calculated and experimental diffusivities of protic solutes differed by more than 25%. To correct this behavior, the σOH was reoptimized using the experimental D12 of quercetin and of gallic acid in liquid ethanol as benchmarks. A substantial improvement of the calculated diffusivities was found by changing σOH from its original value (0.312 nm) to 0.306 nm, with average absolute relative deviations (AARD) of 3.71% and 4.59% for quercetin and gallic acid, respectively. The new σOH value was further tested by computing D12 of ibuprofen and butan-1-ol in liquid ethanol with AARDs of 1.55% and 4.81%, respectively. A significant improvement was also obtained for the D11 of ethanol with AARD = 3.51%. It was also demonstrated that in the case of diffusion coefficients of non-polar solutes in ethanol, the original σOH=0.312 nm should be used for better agreement with experiment. If equilibrium properties such as enthalpy of vaporization and density are estimated, the original diameter should be once again adopted.
Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria
Authors: Aresta Branco Mafalda S. L. , Gutierrez Cruz Alejandro , Borhani Peikani Mahsa , Mutafova-Yambolieva Violeta N.
Published: April 2023

The urinary bladder requires adequate concentrations of extracellular adenosine 5′-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential for achieving suitable extracellular levels of purine mediators. S-ENTDs, in particular, are released in the bladder suburothelium/lamina propria (LP) in a mechanosensitive manner. Using 1,N6-etheno-ATP (eATP) as substrate and sensitive HPLC-FLD methodology, we evaluated the degradation of eATP to eADP, eAMP and eADO in solutions that were in contact with the LP of ex vivo mouse detrusor-free bladders during filling prior to substrate addition. The inhibition of neural activity with tetrodotoxin and ω-conotoxin GVIA, of PIEZO channels with GsMTx4 and D-GsMTx4 and of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) with PACAP6-38 all increased the distention-induced but not spontaneous release of s-ENTDs in LP. It is conceivable, therefore, that the activation of these mechanisms in response to distention restricts the further release of s-ENTDs and prevents excessive hydrolysis of ATP. Together, these data suggest that afferent neurons, PIEZO channels, PAC1 receptors and s-ENTDs form a system that operates a highly regulated homeostatic mechanism to maintain proper extracellular purine concentrations in the LP and ensure normal bladder excitability during bladder filling.
Human Exposure to Bisphenols, Parabens, and Benzophenones, and Its Relationship with the Inflammatory Response: A Systematic Review
Authors: Peinado Francisco Manuel , Iribarne-Durán Luz María , Artacho-Cordón Francisco
Published: April 2023

Bisphenols, parabens (PBs), and benzophenones (BPs) are widely used environmental chemicals that have been linked to several adverse health effects due to their endocrine disrupting properties. However, the cellular pathways through which these chemicals lead to adverse outcomes in humans are still unclear, suggesting some evidence that inflammation might play a key role. Thus, the aim of this study was to summarize the current evidence on the relationship between human exposure to these chemicals and levels of inflammatory biomarkers. A systematic review of peer-reviewed original research studies published up to February 2023 was conducted using the MEDLINE, Web of Science, and Scopus databases. A total of 20 articles met the inclusion/exclusion criteria. Most of the reviewed studies reported significant associations between any of the selected chemicals (mainly bisphenol A) and some pro-inflammatory biomarkers (including C-reactive protein and interleukin 6, among others). Taken together, this systematic review has identified consistent positive associations between human exposure to some chemicals and levels of pro-inflammatory biomarkers, with very few studies exploring the associations between PBs and/or BPs and inflammation. Therefore, a larger number of studies are required to get a better understanding on the mechanisms of action underlying bisphenols, PBs, and BPs and the critical role that inflammation could play.
G-Protein β-Subunit Gene TaGB1-B Enhances Drought and Salt Resistance in Wheat
Authors: Xiong Xin-Xin , Liu Yang , Zhang Li-Li , Li Xiao-Jian , Zhao Yue , Zheng Yan , Yang Qian-Hui , Yang Yan , Min Dong-Hong , Zhang Xiao-Hong
Published: April 2023

In the hexaploid wheat genome, there are three Gα genes, three Gβ and twelve Gγ genes, but the function of Gβ in wheat has not been explored. In this study, we obtained the overexpression of TaGB1 Arabidopsis plants through inflorescence infection, and the overexpression of wheat lines was obtained by gene bombardment. The results showed that under drought and NaCl treatment, the survival rate of Arabidopsis seedlings’ overexpression of TaGB1-B was higher than that of the wild type, while the survival rate of the related mutant agb1-2 was lower than that of the wild type. The survival rate of wheat seedlings with TaGB1-B overexpression was higher than that of the control. In addition, under drought and salt stress, the levels of superoxide dismutase (SOD) and proline (Pro) in the wheat overexpression of TaGB1-B were higher than that of the control, and the concentration of malondialdehyde (MDA) was lower than that of the control. This indicates that TaGB1-B could improve the drought resistance and salt tolerance of Arabidopsis and wheat by scavenging active oxygen. Overall, this work provides a theoretical basis for wheat G-protein β-subunits in a further study, and new genetic resources for the cultivation of drought-tolerant and salt-tolerant wheat varieties.
Protective Effects of a Jellyfish-Derived Thioredoxin Fused with Cell-Penetrating Peptide TAT-PTD on H2O2-Induced Oxidative Damage
Authors: Wang Bo , Zhang Peipei , Wang Qianqian , Zou Shuaijun , Song Juxingsi , Zhang Fuhai , Liu Guoyan , Zhang Liming
Published: April 2023

Thioredoxin (Trx) plays a critical role in maintaining redox balance in various cells and exhibits anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, whether exogenous Trx can inhibit intracellular oxidative damage has not been investigated. In previous study, we have identified a novel Trx from the jellyfish Cyanea capillata, named CcTrx1, and confirmed its antioxidant activities in vitro. Here, we obtained a recombinant protein, PTD-CcTrx1, which is a fusion of CcTrx1 and protein transduction domain (PTD) of HIV TAT protein. The transmembrane ability and antioxidant activities of PTD-CcTrx1, and its protective effects against H2O2-induced oxidative damage in HaCaT cells were also detected. Our results revealed that PTD-CcTrx1 exhibited specific transmembrane ability and antioxidant activities, and it could significantly attenuate the intracellular oxidative stress, inhibit H2O2-induced apoptosis, and protect HaCaT cells from oxidative damage. The present study provides critical evidence for application of PTD-CcTrx1 as a novel antioxidant to treat skin oxidative damage in the future.
Topical Application of Deglycating Enzymes as an Alternative Non-Invasive Treatment for Presbyopia
Authors: Delanghe Joris R. , Beeckman Jeroen , Beerens Koen , Himpe Jonas , Bostan Nezahat , Speeckaert Marijn M. , Notebaert Margo , Huizing Manon , Van Aken Elisabeth
Published: April 2023

Presbyopia is an age-related vision disorder that is a global public health problem. Up to 85% of people aged ≥40 years develop presbyopia. In 2015, 1.8 billion people globally had presbyopia. Of those with significant near vision disabilities due to uncorrected presbyopia, 94% live in developing countries. Presbyopia is undercorrected in many countries, with reading glasses available for only 6–45% of patients living in developing countries. The high prevalence of uncorrected presbyopia in these parts of the world is due to the lack of adequate diagnosis and affordable treatment. The formation of advanced glycation end products (AGEs) is a non-enzymatic process known as the Maillard reaction. The accumulation of AGEs in the lens contributes to lens aging (leading to presbyopia and cataract formation). Non-enzymatic lens protein glycation induces the gradual accumulation of AGEs in aging lenses. AGE-reducing compounds may be effective at preventing and treating AGE-related processes. Fructosyl-amino acid oxidase (FAOD) is active on both fructosyl lysine and fructosyl valine. As the crosslinks encountered in presbyopia are mainly non-disulfide bridges, and based on the positive results of deglycating enzymes in cataracts (another disease caused by glycation of lens proteins), we studied the ex vivo effects of topical FAOD treatment on the power of human lenses as a new potential non-invasive treatment for presbyopia. This study demonstrated that topical FAOD treatment resulted in an increase in lens power, which is approximately equivalent to the correction obtained by most reading glasses. The best results were obtained for the newer lenses. Simultaneously, a decrease in lens opacity was observed, which improved lens quality. We also demonstrated that topical FAOD treatment results in a breakdown of AGEs, as evidenced by gel permeation chromatography and a marked reduction in autofluorescence. This study demonstrated the therapeutic potential of topical FAOD treatment in presbyopia.
Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer
Authors: Nikolova-Mladenova Boryana , Momekov Georgi , Zhivkova Zvetanka , Doytchinova Irini
Published: April 2023

Despite the significant advancements in complex anticancer therapy, the search for new and more efficient specific anticancer agents remains a top priority in the field of drug discovery and development. Here, based on the structure-activity relationships (SARs) of eleven salicylaldehyde hydrazones with anticancer activities, we designed three novel derivatives. The compounds were tested in silico for drug-likeness, synthesized, and evaluated in vitro for anticancer activity and selectivity on four leukemic cell lines (HL-60, KE-37, K-562, and BV-173), one osteosarcomic cell line (SaOS-2), two breast adenocarcinomic cell lines (MCF-7 and MDA-MB-231), and one healthy cell line (HEK-293). The designed compounds were found to have appropriate drug likeness and showed anticancer activities in all cell lines tested; particularly, two of them exhibited remarkable anticancer activity in nanomolar concentrations on the leukemic cell lines HL-60 and K-562 and the breast cancer MCF-7 cells and extraordinary selectivity for the same cancer lines ranging between 164- and 1254-fold. The study also examined the effects of different substituents on the hydrazone scaffold and found that the 4-methoxy salicylic moiety, phenyl, and pyridinyl rings are the most appropriate for anticancer activity and selectivity of this chemical class.
Isopropoxy Benzene Guanidine Ameliorates Streptococcus suis Infection In Vivo and In Vitro
Authors: Han Ning , Li Jie , Zhao Feifei , Li Yangyang , Wang Jun , Dai Xiaolan , Zeng Dongping , Xiong Wenguang , Zeng Zhenling
Published: April 2023

Streptococcus suis, an encapsulated zoonotic pathogen, has been reported to cause a variety of infectious diseases, such as meningitis and streptococcal-toxic-shock-like syndrome. Increasing antimicrobial resistance has triggered the need for new treatments. In the present study, we found that isopropoxy benzene guanidine (IBG) significantly attenuated the effects caused by S. suis infection, in vivo and in vitro, by killing S. suis and reducing S. suis pathogenicity. Further studies showed that IBG disrupted the integrity of S. suis cell membranes and increased the permeability of S. suis cell membranes, leading to an imbalance in proton motive force and the accumulation of intracellular ATP. Meanwhile, IBG antagonized the hemolysis activity of suilysin and decreased the expression of Sly gene. In vivo, IBG improved the viability of S. suis SS3-infected mice by reducing tissue bacterial load. In conclusion, IBG is a promising compound for the treatment of S. suis infections, given its antibacterial and anti-hemolysis activity.
Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia
Authors: Ardissino Diego , Colletti Alessandro , Pellizzato Marzia , Pagliari Gianna , Di Pierro Francesco , Cravotto Giancarlo
Published: April 2023

The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with β-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention.
Identification of Potential p38γ Inhibitors via In Silico Screening, In Vitro Bioassay and Molecular Dynamics Simulation Studies
Authors: Cheng Zixuan , Bhave Mrinal , Hwang Siaw San , Rahman Taufiq , Chee Xavier Wezen
Published: April 2023

Protein kinase p38γ is an attractive target against cancer because it plays a pivotal role in cancer cell proliferation by phosphorylating the retinoblastoma tumour suppressor protein. Therefore, inhibition of p38γ with active small molecules represents an attractive alternative for developing anti-cancer drugs. In this work, we present a rigorous and systematic virtual screening framework to identify potential p38γ inhibitors against cancer. We combined the use of machine learning-based quantitative structure activity relationship modelling with conventional computer-aided drug discovery techniques, namely molecular docking and ligand-based methods, to identify potential p38γ inhibitors. The hit compounds were filtered using negative design techniques and then assessed for their binding stability with p38γ through molecular dynamics simulations. To this end, we identified a promising compound that inhibits p38γ activity at nanomolar concentrations and hepatocellular carcinoma cell growth in vitro in the low micromolar range. This hit compound could serve as a potential scaffold for further development of a potent p38γ inhibitor against cancer.
Evidence of Spaceflight-Induced Adverse Effects on Photoreceptors and Retinal Function in the Mouse Eye
Authors: Mao Xiaowen , Stanbouly Seta , Holley Jacob , Pecaut Michael , Crapo James
Published: April 2023

The goal of the present study was to characterize acute oxidative damage in ocular structure and retinal function after exposure to spaceflight, and to evaluate the efficacy of an antioxidant in reducing spaceflight-induced changes in the retina. Ten-week-old adult C57BL/6 male mice were flown aboard the ISS on Space-X 24 over 35 days, and returned to Earth alive. The mice received a weekly injection of a superoxide dismutase mimic, MnTnBuOE-2-PyP 5+ (BuOE), before launch and during their stay onboard the ISS. Ground control mice were maintained on Earth under identical environmental conditions. Before the launch, intraocular pressure (IOP) was measured using a handheld tonometer and retinal function was evaluated using electroretinogram (ERG). ERG signals were recorded when the mouse eye was under dark-adapted conditions in response to ultraviolet monochromatic light flashes. Within 20 h after splashdown, IOP and ERG assessments were repeated before euthanasia. There were significant increases in body weight for habitat control groups post-flight compared to pre-flight measurements. However, the body weights were similar among flight groups before launch and after splashdown. The IOP measurements were similar between pre- and post-flight groups with no significant differences between BuOE-treated and saline controls. Immunofluorescence evaluation showed increases in retinal oxidative stress and apoptotic cell death after spaceflight. BuOE treatment significantly decreased the level of the oxidative stress biomarker. ERG data showed that the average amplitudes of the a- and b-wave were significantly decreased (39% and 32% by spaceflight, respectively) compared to that of habitat ground controls. These data indicate that spaceflight conditions induce oxidative stress in the retina, which may lead to photoreceptor cell damage and retinal function impairment.
Glyphosate Interference in Follicular Organization in the Wall Lizard Podarcis siculus
Authors: Rosati Luigi , Chianese Teresa , De Gregorio Vincenza , Verderame Mariailaria , Raggio Anja , Motta Chiara Maria , Scudiero Rosaria
Published: April 2023

Glyphosate (Gly) is a broad-spectrum herbicide widely used thanks to its high efficiency and low toxicity. However, evidence exists of its toxic effects on non-target organisms. Among these, the animals inhabiting agricultural fields are particularly threatened. Recent studies demonstrated that exposure to Gly markedly affected the morphophysiology of the liver and testis of the Italian field lizard Podarcis siculus. The present study aimed to investigate the effects of the herbicide on the female reproductive system of this lizard in order to have a full picture of Gly-induced reproductive impairment. The animals were exposed to 0.05 and 0.5 μg/kg of pure Gly by gavage for 3 weeks. The results demonstrated that Gly, at both doses tested, profoundly interfered with ovarian function. It induced germ cells’ recruitment and altered follicular anatomy by anticipating apoptotic regression of the pyriform cells. It also induced thecal fibrosis and affected oocyte cytoplasm and zona pellucida organizations. At the functional levels, Gly stimulated the synthesis of estrogen receptors, suggesting a serious endocrine-disrupting effect. Overall, the follicular alterations, combined with those found at the level of the seminiferous tubules in males, suggest serious damage to the reproductive fitness of these non-target organisms, which over time could lead to a decline in survival.
Oriented Insertion of ESR-Containing Hybrid Proteins in Proteoliposomes
Authors: Petrovskaya Lada E. , Lukashev Evgeniy P. , Mamedov Mahir D. , Kryukova Elena A. , Balashov Sergei P. , Dolgikh Dmitry A. , Rubin Andrei B. , Kirpichnikov Mikhail P. , Siletsky Sergey A.
Published: April 2023

Microbial rhodopsins comprise a diverse family of retinal-containing membrane proteins that convert absorbed light energy to transmembrane ion transport or sensory signals. Incorporation of these proteins in proteoliposomes allows their properties to be studied in a native-like environment; however, unidirectional protein orientation in the artificial membranes is rarely observed. We aimed to obtain proteoliposomes with unidirectional orientation using a proton-pumping retinal protein from Exiguobacterium sibiricum, ESR, as a model. Three ESR hybrids with soluble protein domains (mCherry or thioredoxin at the C-terminus and Caf1M chaperone at the N-terminus) were obtained and characterized. The photocycle of the hybrid proteins incorporated in proteoliposomes demonstrated a higher pKa of the M state accumulation compared to that of the wild-type ESR. Large negative electrogenic phases and an increase in the relative amplitude of kinetic components in the microsecond time range in the kinetics of membrane potential generation of ESR-Cherry and ESR-Trx indicate a decrease in the efficiency of transmembrane proton transport. On the contrary, Caf-ESR demonstrates a native-like kinetics of membrane potential generation and the corresponding electrogenic stages. Our experiments show that the hybrid with Caf1M promotes the unidirectional orientation of ESR in proteoliposomes.
Does Albumin Predict the Risk of Mortality in Patients with Cardiogenic Shock?
Authors: Schupp Tobias , Behnes Michael , Rusnak Jonas , Ruka Marinela , Dudda Jonas , Forner Jan , Egner-Walter Sascha , Barre Max , Abumayyaleh Mohammad , Bertsch Thomas , Müller Julian , Akin Ibrahim
Published: April 2023

This study investigates the prognostic impact of albumin levels in patients with cardiogenic shock (CS). Intensive care unit (ICU) related mortality in CS patients remains unacceptably high despite improvement concerning the treatment of CS patients. Limited data regarding the prognostic value of albumin in patients with CS is available. All consecutive patients with CS from 2019 to 2021 were included at one institution. Laboratory values were retrieved from the day of disease onset (day 1) and days 2, 3, 4, and 8 thereafter. The prognostic impact of albumin was tested for 30-day all-cause mortality. Moreover, the prognostic performance of albumin decline during ICU treatment was examined. Statistical analyses included univariable t-test, Spearman’s correlation, Kaplan–Meier analyses, multivariable mixed analysis of variance (ANOVA), C-Statistics, and Cox proportional regression analyses. In total, 230 CS patients were included, with an overall all-cause mortality at 30 days of 54%. The median albumin on day 1 was 30.0 g/L. Albumin on day 1 was able to discriminate between 30-day survivors and non-survivors (area under the curve (AUC) 0.607; 0.535–0.680; p = 0.005). CS patients with albumin < 30.0 g/L were associated with an increased risk of 30-day all-cause mortality (63% vs. 46%; log-rank p = 0.016; HR = 1.517; 95% CI 1.063–2.164; p = 0.021), which was demonstrated even after multivariable adjustment. Moreover, a decrease of albumin levels by ≥20% from day 1 to day 3 was accompanied by a higher risk of 30-days all-cause mortality (56% vs. 39%; log-rank p = 0.036; HR = 1.645; 95% CI 1.014–2.669; p = 0.044). Especially when combined with lactate, creatinine, and cardiac troponin I, reliable discrimination of 30-day all-cause mortality was observed, including albumin in CS risk stratification models (AUC = 0.745; 95% CI 0.677–0.814; p = 0.001). In conclusion, low baseline albumin levels as well as a decay of albumin levels during the course of ICU treatment, deteriorate prognostic outcomes in CS patients. The additional assessment of albumin levels may further improve risk stratification in CS patients.
Single Copies of the 5S rRNA Inserted into 45S rDNA Intergenic Spacers in the Genomes of Nototheniidae (Perciformes, Actinopterygii)
Authors: Dyomin Alexander , Galkina Svetlana , Ilina Arina , Gaginskaya Elena
Published: April 2023

In the vast majority of Animalia genomes, the 5S rRNA gene repeats are located on chromosomes outside of the 45S rDNA arrays of the nucleolar organiser (NOR). We analysed the genomic databases available and found that a 5S rDNA sequence is inserted into the intergenic spacer (IGS) between the 45S rDNA repeats in ten species of the family Nototheniidae (Perciformes, Actinopterigii). We call this sequence the NOR-5S rRNA gene. Along with Testudines and Crocodilia, this is the second case of a close association between four rRNA genes within one repetitive unit in deuterostomes. In both cases, NOR-5S is oriented opposite the 45S rDNA. None of the three nucleotide substitutions compared to the canonical 5S rRNA gene influenced the 5S rRNA secondary structure. In transcriptomes of the Patagonian toothfish, we only found NOR-5S rRNA reads in ovaries and early embryos, but not in testis or somatic tissues of adults. Thus, we consider the NOR-5S gene to be a maternal-type 5S rRNA template. The colocalization of the 5S and 45S ribosomal genes appears to be essential for the equimolar production of all four rRNAs in the species that show rDNA amplification during oogenesis. Most likely, the integration of 5S and NOR rRNA genes occurred prior to Nototheniidae lineage diversification.
Localized Cutaneous Nodular Amyloidosis: A Specific Cutaneous Manifestation of Sjögren’s Syndrome
Authors: Llamas-Molina José María , Velasco-Amador Juan Pablo , De la Torre-Gomar Francisco Javier , Carrero-Castaño Alejandro , Ruiz-Villaverde Ricardo
Published: April 2023

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition attributed to plasma cell proliferation and the deposition of immunoglobulin light chains in the skin without association with systemic amyloidosis or hematological dyscrasias. It is not uncommon for patients diagnosed with PLCNA to also suffer from other auto-immune connective tissue diseases, with Sjögren’s syndrome (SjS) showing the strongest association. This article provides a literature review and descriptive analysis to better understand the unique relationship between these two entities. To date, 34 patients with PLCNA and SjS have been reported in a total of 26 articles. The co-existence of PLCNA and SjS has been reported, especially in female patients in their seventh decade of life with nodular lesions on the trunk and/or lower extremities. Acral and facial localization, which is a typical localization of PLCNA in the absence of SjS, seems to be much more unusual in patients with associated SjS.
Novel Isoform DTX3c Associates with UBE2N-UBA1 and Cdc48/p97 as Part of the EphB4 Degradation Complex Regulated by the Autocrine IGF-II/IRA Signal in Malignant Mesothelioma
Authors: Scalia Pierluigi , Merali Carmen , Barrero Carlos , Suma Antonio , Carnevale Vincenzo , Merali Salim , Williams Stephen J.
Published: April 2023

EphB4 angiogenic kinase over-expression in Mesothelioma cells relies upon a degradation rescue signal provided by autocrine IGF-II activation of Insulin Receptor A. However, the identity of the molecular machinery involved in EphB4 rapid degradation upon IGF-II signal deprivation are unknown. Using targeted proteomics, protein–protein interaction methods, PCR cloning, and 3D modeling approaches, we identified a novel ubiquitin E3 ligase complex recruited by the EphB4 C tail upon autocrine IGF-II signal deprivation. We show this complex to contain a previously unknown N-Terminal isoform of Deltex3 E3-Ub ligase (referred as “DTX3c”), along with UBA1(E1) and UBE2N(E2) ubiquitin ligases and the ATPase/unfoldase Cdc48/p97. Upon autocrine IGF-II neutralization in cultured MSTO211H (a Malignant Mesothelioma cell line that is highly responsive to the EphB4 degradation rescue IGF-II signal), the inter-molecular interactions between these factors were enhanced and their association with the EphB4 C-tail increased consistently with the previously described EphB4 degradation pattern. The ATPase/unfoldase activity of Cdc48/p97 was required for EphB4 recruitment. As compared to the previously known isoforms DTX3a and DTX3b, a 3D modeling analysis of the DTX3c Nt domain showed a unique 3D folding supporting isoform-specific biological function(s). We shed light on the molecular machinery associated with autocrine IGF-II regulation of oncogenic EphB4 kinase expression in a previously characterized IGF-II+/EphB4+ Mesothelioma cell line. The study provides early evidence for DTX3 Ub-E3 ligase involvement beyond the Notch signaling pathway.
Insomnia Impairs Both the Pro-BDNF and the BDNF Levels Similarly to Older Adults with Cognitive Decline: An Exploratory Study
Authors: Sánchez-García Sergio , Moreno-Tamayo Karla , Ramírez-Aldana Ricardo , García-Peña Carmen , Medina-Campos Raúl Hernán , García dela Torre Paola , Rivero-Segura Nadia Alejandra
Published: April 2023

Sleep disorders, including insomnia, are common during aging, and these conditions have been associated with cognitive decline in older adults. Moreover, during the aging process, neurotransmitters, neurohormones, and neurotrophins decrease significantly, leading to the impairment of cognitive functions. In this sense, BDNF, the most abundant neurotrophic factor in the human brain, has been suggested as a potential target for the prevention and improvement of cognitive decline during aging; however, the current evidence demonstrates that the exogenous administration of BDNF does not improve cognitive function. Hence, in the present study, we quantified pro-BDNF (inactive) and BDNF (active) concentrations in serum samples derived from older individuals with insomnia and/or cognitive decline. We used linear regression to analyze whether clinical or sociodemographic variables impacted the levels of BNDF concentration. We observed that insomnia, rather than cognitive decline, is significantly associated with BDNF concentration, and these effects are independent of other variables. To our knowledge, this is the first study that points to the impact of insomnia on improving the levels of BDNF during aging and suggests that opportune treatment of insomnia may be more beneficial to prevent cognitive decline during aging.
Innova 2020: A Follow-Up Study of the Fecal Microbiota of Infants Using a Novel Infant Formula between 6 Months and 12 Months of Age
Authors: Plaza-Diaz Julio , Ruiz-Ojeda Francisco Javier , Morales Javier , Martín-Masot Rafael , Climent Eric , Silva Ángela , Martinez-Blanch Juan F. , Enrique María , Tortajada Marta , Ramon Daniel , Alvarez Beatriz , Chenoll Empar , Gil Ángel
Published: April 2023

The World Health Organization recommends exclusive breastfeeding on demand until at least the sixth month of life. Breast milk or infant formula is the infant’s primary food source until the age of one year, followed by the gradual introduction of other foods. During weaning, the intestinal microbiota evolves to a profile close to that of the adult, and its disruption can result in an increased incidence of acute infectious diseases. We aimed to determine whether a novel starting formula (INN) provides gut microbiota compositions more similar to those of breastfed (BF) infants from 6 to 12 months of age compared to a standard formula (STD). This study included 210 infants (70 per group) who completed the intervention until they reached the age of 12 months. In the intervention period, infants were divided into three groups. Group 1 received an INN formula with a lower protein content, a casein to whey protein ratio of approximately 70/30, twice as much docosahexaenoic acid as the STD formula, a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis, BPL1TM HT), and twice as much arachidonic acid as the STD formula contained. The second group received the STD formula, while the third group was exclusively BF for exploratory purposes. In the course of the study, visits were conducted at 6 months and 12 months of age. Compared to the BF and STD groups, the Bacillota phylum levels in the INN group were significantly reduced after 6 months. At the end of 6 months, the alpha diversity indices of the BF and INN groups differed significantly from those of the STD group. At 12 months, the Verrucomicrobiota phylum levels in the STD group were significantly lower than those in the BF and INN groups. Based on the comparison between 6 and 12 months, the Bacteroidota phylum levels in the BF group were significantly higher than those in the INN and STD groups. When comparing the INN group with the BF and STD groups, Clostridium sensu stricto 1 was significantly higher in the INN group. The STD group had higher levels of calprotectin than the INN and BF groups at 6 months. The immunoglobulin A levels in the STD group were significantly lower than those in the INN and BF groups after 6 months. Both formulas had significantly higher levels of propionic acid than the BF group at 6 months. At 6 months, the STD group showed a higher quantification of all metabolic pathways than the BF group. The INN formula group exhibited similar behavior to the BF group, except for the superpathway of phospholipid biosynthesis (E. coli). We hypothesize that the novel INN formula may promote an intestinal microbiota that is more similar to the microbiota of an infant who consumes only human milk before the weaning period.
Intra-Specific Variation in Desiccation Tolerance of Citrus sinensis ‘bingtangcheng’ (L.) Seeds under Different Environmental Conditions in China
Authors: Chen Hongying , Visscher Anne M. , Ai Qin , Yang Lan , Pritchard Hugh W. , Li Weiqi
Published: April 2023

Intra-specific variation in seed storage behaviour observed in several species has been related to different maternal environments. However, the particular environmental conditions and molecular processes involved in intra-specific variation of desiccation tolerance remain unclear. We chose Citrus sinensis ‘bingtangcheng’ for the present study due to its known variability in desiccation tolerance amongst seed lots. Six seed lots of mature fruits were harvested across China and systematically compared for drying sensitivity. Annual sunshine hours and average temperature from December to May showed positive correlations with the level of seed survival of dehydration. Transcriptional analysis indicated significant variation in gene expression between relatively desiccation-tolerant (DT) and -sensitive (DS) seed lots after harvest. The major genes involved in late seed maturation, such as heat shock proteins, showed higher expression in the DT seed lot. Following the imposition of drying, 80% of stress-responsive genes in the DS seed lot changed to the stable levels seen in the DT seed lot prior to and post-desiccation. However, the changes in expression of stress-responsive genes in DS seeds did not improve their tolerance to desiccation. Thus, higher desiccation tolerance of Citrus sinensis ‘bingtangcheng’ seeds is modulated by the maternal environment (e.g., higher annual sunshine hours and seasonal temperature) during seed development and involves stable expression levels of stress-responsive genes.