bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation of Minimally Processed Foods and Ultra-Processed Foods with the Mediterranean Diet Score, Time-Related Meal Patterns and Waist Circumference: Results from a Cross-Sectional Study in University Students
Authors: Detopoulou Paraskevi , Dedes Vassilios , Syka Dimitra , Tzirogiannis Konstantinos , Panoutsopoulos Georgios I.
Published: February 2023

Ultra-processed foods are associated with chronic diseases, cardiometabolic factors and obesity. According to the NOVA system, foods are classified into four categories (from 1 = unprocessed to 4 = ultra-processed foods). The purpose of the present study was to assess the consumption of minimally processed foods (MPF) and ultra-processed foods (UPF) in university students and their relationship with obesity, Mediterranean diet adherence and meal patterns. In total, 346 students (269 women) of the University of Peloponnese participated. A food frequency questionnaire was used, and the MedDietScore was calculated. The % energy contribution of MPF and UPF was calculated. The identification of meal patterns was performed via principal component analysis. Both multivariate regression and Spearman’s correlations were used to measure the association of UPF/MPF consumption with anthropometric indices (body mass index, BMI and waist circumference, WC), Mediterranean diet adherence and early/late meal patterns. UPF and MPF provided 40.7 ± 13.6% and 44.3 ± 11.9% (mean ± standard deviation) of energy intake, respectively. In multi-adjusted linear regression models UPF consumption (% energy) was positively associated with WC in men but it was not related to BMI (total sample, men, women). UPF consumption was negatively related to the MedDietScore (Spearman rho = −0.214, p < 0.001) and an “early eating” pattern (Spearman rho = −0.120, p = 0.029) and positively associated with a “late eating” meal pattern (Spearman rho = 0.190, p = 0.001). MPF consumption was positively associated with the MedDietScore (Spearman rho = 0.309, p < 0.001) and an “early eating” pattern (Spearman rho = 0.240, p < 0.001). In conclusion, UPF consumption was positively related to WC in male university students. Nutritional and sociodemographic correlates of UPF consumption, such as low Mediterranean diet adherence and having a “late eating” pattern serve as a basis to better understand the UPF consumption-central obesity relation in young adults and should be considered in nutrition education programs for young adults.
Influence of Cluster Sets on Mechanical and Perceptual Variables in Adolescent Athletes
Authors: Api Gustavo , Legnani Rosimeide Francisco dos Santos , Foschiera Diogo Bertella , Clemente Filipe Manuel , Legnani Elto
Published: February 2023

Cluster sets (CS) are effective in maintaining performance and reducing perceived effort compared to traditional sets (TRD). However, little is known about these effects on adolescent athletes. The purpose of this study was to compare the effect of CS on the performance of mechanical and perceptual variables in young athletes. Eleven subjects [4 boys (age = 15.5 ± 0.8 years; body mass = 54.3 ± 7.0 kg; body height = 1.67 ± 0.04 m; Back Squat 1RM/body mass: 1.62 ± 0.19 kg; years from peak height velocity [PHV]: 0.94 ± 0.50) and 7 girls (age = 17.2 ± 1.4 years; body mass = 54.7 ± 6.3 kg; body height = 1.63 ± 0.08 m; Back Squat 1RM/body mass: 1.22 ± 0.16 kg; years from PHV: 3.33 ± 1.00)] participated in a randomized crossover design with one traditional (TRD: 3 × 8, no intra-set and 225 s interest rest) and two clusters (CS1: 3 × 2 × 4, one 30 s intra-set and 180 s inter-set rest; and CS2: 3 × 4 × 2, three 30 s intra-set and 90 s inter-set rest) protocols. The subjects were assessed for a Back Squat 1RM for the first meet, then performed the three protocols on three different days, with at least 48 h between them. During experimental sessions, a back squat exercise was performed, and mean propulsive velocity (MPV), power (MPP), and force (MPF) were collected to analyze performance between protocols, together with measures of countermovement jump (CMJ) and perceptual responses through Rating of Perceived Exertion for each set (RPE-Set) and the overall session (S-RPE), and Muscle Soreness (DOMS). The results showed that velocity and power decline (MVD and MPD) were favorable for CS2 (MVD: −5.61 ± 14.84%; MPD: −5.63 ± 14.91%) against TRD (MVD: −21.10 ± 11.88%; MPD: −20.98 ± 11.85%) (p < 0.01) and CS1 (MVD: −21.44 ± 12.13%; MPD: −21.50 ± 12.20%) (p < 0.05). For RPE-Set, the scores were smaller for CS2 (RPE8: 3.23 ± 0.61; RPE16: 4.32 ± 1.42; RPE24: 4.46 ± 1.51) compared to TRD (RPE8: 4.73 ± 1.33; RPE16: 5.46 ± 1.62; RPE24: 6.23 ± 1.97) (p = 0.008), as well as for Session RPE (CS2: 4.32 ± 1.59; TRD: 5.68 ± 1.75) (p = 0.015). There were no changes for jump height (CMJ: p = 0.985), and the difference between time points in CMJ (ΔCMJ: p = 0.213) and muscle soreness (DOMS: p = 0.437) were identified. Our findings suggest that using CS with a greater number of intra-set rests is more efficient even with the total rest interval equalized, presenting lower decreases in mechanical performance and lower perceptual effort responses.
Modulatory Effect of Lifestyle-Related, Environmental and Genetic Factors on Paraoxonase-1 Activity: A Review
Authors: Kunachowicz Dominika , Ściskalska Milena , Kepinska Marta
Published: February 2023

Paraoxonase-1 (PON1) is a calcium-dependent, HDL-bound serum hydrolase active toward a wide variety of substrates. PON1 displays three types of activities, among which lactonase, paraoxonase, arylesterase and phosphotriesterase can be distinguished. Not only is this enzyme a major organophosphate compound detoxifier, but it is also an important constituent of the cellular antioxidant system and has anti-inflammatory and antiatherogenic functions. The concentration and activity of PON1 is highly variable among individuals, and these differences can be both of genetic origin and be a subject of epigenetic regulation. Owing to the fact that, in recent decades, the exposure of humans to an increasing number of different xenobiotics has been continuously rising, the issues concerning the role and activity of PON1 shall be reconsidered with particular attention to growing pharmaceuticals intake, dietary habits and environmental awareness. In the following manuscript, the current state of knowledge concerning the influence of certain modifiable and unmodifiable factors, including smoking, alcohol intake, gender, age and genotype variation on PON1 activity, along with pathways through which these could interfere with the enzyme’s protective functions, is presented and discussed. Since exposure to certain xenobiotics plays a key role in PON1 activity, the influence of organophosphates, heavy metals and several pharmaceutical agents is also specified.
“You’ll Be Chased Away”: Sources, Experiences, and Effects of Violence and Stigma among Gay and Bisexual Men in Kenya
Authors: Lewis Katherine A. , Jadwin-Cakmak Laura , Walimbwa Jeffrey , Ogunbajo Adedotun , Jauregui Juan C. , Onyango Daniel Peter , Moore Darius M. , Johnson Gabriel Lee , Odero Wilson , Harper Gary W.
Published: February 2023

Gay and bisexual men in Kenya face extreme socio-political stigma which manifests in widespread violence and discrimination across socio-ecological levels. We conducted individual in-depth interviews with 60 gay and bisexual men in western and central Kenya. Interview transcripts were thematically analyzed using an inductive, phenomenological approach to qualitatively examine experiences of stigma and violence at the interpersonal and institutional levels. A total of seven primary themes and four sub-themes emerged from the data. At the interpersonal level, participants described stigma and violence from family, friends, and romantic/sexual partners with sub-themes for gay-baiting violence, blackmail, intimate partner violence, and commitment phobia. At the institutional level, participants described stigma and violence from religious, employment, educational, and healthcare institutions. This stigma and violence severely impacted the lives of participants including their mental health, physical health, sexual health, socioeconomic status, and ability to access health-promoting services. These data identify sources of stigma and describe how this stigma manifests in the everyday lives of gay and bisexual men in Kenya. Study findings and quotes from participants highlight the severity of violence, stigma, and discrimination faced by this community and emphasize the need for decriminalization of same-sex sexualities as well as interventions to support health and wellbeing.
The Impact of Childhood Trauma on Problematic Alcohol and Drug Use Trajectories and the Moderating Role of Social Support
Authors: Rogers Christopher J. , Forster Myriam , Sussman Steven , Steinberg Jane , Barrington-Trimis Jessica L. , Grigsby Timothy J. , Unger Jennifer B.
Published: February 2023

Adverse childhood experiences (ACE) have a strong association with alcohol and drug use; however, more research is needed to identify protective factors for this association. The present study assesses the longitudinal impact of ACE on problematic alcohol and drug use and the potential moderating effect of perceived social support. Data (n = 1404) are from a sample of Hispanic youth surveyed in high school through young adulthood. Linear growth curve models assessed the effect of ACE and perceived social support over time on problematic alcohol and drug use. Results indicated youth with ACE (vs. those without ACE) report more problematic alcohol and drug use in adolescence and have increased rates into young adulthood. Additionally, findings suggest that social support in high school may moderate the effects of ACE on problematic use over time. Among youth with high levels of support, the association of ACE with problematic alcohol and drug use was diminished. Although ACE can have a persistent impact on problematic alcohol and drug use from adolescence into adulthood, high social support during adolescence may mitigate the negative effects of ACE, lowering early problematic alcohol and drug use, offering the potential for lasting benefits.
Cyberbullying Involvement and Depression among Elementary School, Middle School, High School, and University Students: The Role of Social Support and Gender
Authors: Wright Michelle F. , Wachs Sebastian
Published: February 2023

One aim of this study was to investigate differences in cyberbullying involvement (i.e., victimization, bystanding, perpetration) across four age groups, including 234 elementary school students (4th and 5th grades; 51% female), 363 middle school students (6th through 8th grades; 53% female), 341 high school students (9th through 12th grade; 51% female), and 371 university students (all four years; 60% female). Another aim was to examine the age group differences in the associations between cyberbullying involvement and depression, as well as the moderating effect of social support from parents and friends. Participants completed questionnaires on cyberbullying involvement, depression, and social support from parents and friends. Findings revealed that middle school students were more often involved in cyberbullying as victims, bystanders, and perpetrators, followed by high school and university students, and elementary school students. High school and university students did not differ on their cyberbullying involvement. Gender moderated these relationships for elementary school students, with boys more often involved in cyberbullying perpetration and victimization than girls. In addition, female university students witnessed cyberbullying more so than males. Social support from parents buffered against the negative effects of cyberbullying involvement on depression across all age groups. Results were similar for social support from friends, but only for middle school and high school students. Gender did not influence the associations among age groups, cyberbullying involvement, and depression. The results have implications for designing prevention and intervention programs and ensuring that such programs consider age.
Equine-Assisted Therapeutic Intervention in Institutionalized Children: Case Studies
Authors: Matias Ana Rita , Santos Graça Duarte , Almeida Nicole
Published: February 2023

A significant number of institutionalized children have behavior problems. Socio-emotional skills are fundamental for their adaptation and success throughout life and are usually weakened in this population. Equine-assisted services (EAS) are a form of therapeutic mediation that facilitates and requires the practitioner’s participation, contributing to the promotion of various psychomotor and socio-emotional dimensions. This study was developed during 17 sessions of EAS with a psychomotor intervention, which took place individually and weekly and lasted approximately 45 min, with three institutionalized children. A quantitative and qualitative assessment was carried out before and after the intervention to study the effects of an EAS intervention on socio-emotional competencies in the three institutionalized children. There was an improvement in skills, with an impact on intrapersonal skills and marked improvement in self-regulation and self-control, in addition to an improvement in the intentionality of movement and adequacy of gesture to the context. This type of intervention underlies a renewed educational and therapeutic approach, contributing to mental health promotion in this population.
Dissolved Organic Phosphorus Removal in Secondary Effluent by Ferrate (VI): Performance and Mechanism
Authors: Zheng Lei , Gao Panpan , Song Yali , Wang Hua , Deng Yang
Published: February 2023

Dissolved organic phosphorus (DOP), which is recalcitrant in municipal wastewater treatment, accounts for 26–81% of dissolved total phosphorus in the effluent. More importantly, the majority of DOP could be bioavailable, potentially threatening the aquatic environment through eutrophication. This study aimed to develop a ferrate (VI)-based advanced treatment to effectively destruct and remove DOP from secondary effluent and use deoxyribonucleic acid (DNA) and adenosine-5’-triphosphate (ATP) as DOP model compounds to explore the relevant mechanisms. The results showed that ferrate (VI) treatment could efficiently destruct and remove 75% of the DOP in secondary effluent from an activated sludge-adopted municipal wastewater treatment plant, under normal operating conditions. Moreover, the coexistence of nitrate, ammonia, and alkalinity barely affected the effectiveness, while the presence of phosphate significantly inhibited DOP removal. The mechanistic study revealed that ferrate (VI)-induced particle adsorption was the dominant way to achieve DOP reduction, rather than oxidating DOP to phosphate and forming precipitation afterward. Meanwhile, DOP molecules could be effectively decomposed into smaller ones by ferrate (VI) oxidation. This study clearly demonstrated that ferrate (VI) treatment could achieve a promising DOP removal from secondary effluent for mitigating the risk of eutrophication in receiving water bodies.
The Application of Hyperspectral Imaging to the Measurement of Pressure Injury Area
Authors: Lee Lin-Lin , Chen Shu-Ling
Published: February 2023

Wound size measurement is an important indicator of wound healing. Nurses measure wound size in terms of length × width in wound healing assessment, but it is easy to overestimate the extent of the wound due to irregularities around it. Using hyperspectral imaging (HIS) to measure the area of a pressure injury could provide more accurate data than manual measurement, ensure that the same tool is used for standardized assessment of wounds, and reduce the measurement time. This study was a pilot cross-sectional study, and a total of 30 patients with coccyx sacral pressure injuries were recruited to the rehabilitation ward after approval by the human subjects research committee. We used hyperspectral images to collect pressure injury images and machine learning (k-means) to automatically classify wound areas in combination with the length × width rule (LW rule) and image morphology algorithm for wound judgment and area calculation. The results calculated from the data were compared with the calculations made by the nursing staff using the length × width rule. The use of hyperspectral images, machine learning, the length × width rule (LW rule), and an image morphology algorithm to calculate the wound area yielded more accurate measurements than did nurses, effectively reduced the chance of human error, reduced the measurement time, and produced real-time data. HIS can be used by nursing staff to assess wounds with a standardized approach so as to ensure that proper wound care can be provided.
Developing a Healthy Environment Assessment Tool (HEAT) to Address Heat-Health Vulnerability in South African Towns in a Warming World
Authors: Wright Caradee Y. , Mathee Angela , Goldstone Cheryl , Naidoo Natasha , Kapwata Thandi , Wernecke Bianca , Kunene Zamantimande , Millar Danielle A.
Published: February 2023

Prolonged exposure to high temperatures can cause heat-related illnesses and accelerate death, especially in the elderly. We developed a locally-appropriate Healthy Environment Assessment Tool, or ‘HEAT’ tool, to assess heat-health risks among communities. HEAT was co-developed with stakeholders and practitioners/professionals from the Rustenburg Local Municipality (RLM), a setting in which heat was identified as a risk in an earlier study. Feedback was used to identify vulnerable groups and settings in RLM, consider opportunities and barriers for interventions, and conceptualize a heat-health vulnerability assessment tool for a heat-resilient town. Using information provided by the RLM Integrated Development Plan, the HEAT tool was applied in the form of eight indicators relating to heat-health vulnerability and resilience and areas were evaluated at the ward level. Indicators included population, poverty, education, access to medical facilities, sanitation and basic services, public transport, recreation/community centres, and green spaces. Out of 45 wards situated in the municipality, three were identified as critical risk (red), twenty-eight as medium-high risk (yellow), and six as low risk (green) in relation to heat-health vulnerability. Short-term actions to improve heat health resilience in the community were proposed and partnerships between local government and the community to build heat health resilience were identified.
Estimating Soil Salinity with Different Levels of Vegetation Cover by Using Hyperspectral and Non-Negative Matrix Factorization Algorithm
Authors: Cao Jianfei , Yang Han , Lv Jianshu , Wu Quanyuan , Zhang Baolei
Published: February 2023

Hyperspectral technology has proven to be an effective method for monitoring soil salt content (SSC). However, hyperspectral estimation capabilities are limited when the soil surface is partially vegetated. This work aimed to (1) quantify the influences of different fraction vegetation coverage (FVC) on SSC estimation by hyperspectra and (2) explore the potential for a non-negative matrix factorization algorithm (NMF) to reduce the influence of various FVCs. Nine levels of mixed hyperspectra were measured from simulated mixed scenes, which were performed by strictly controlling SSC and FVC in the laboratory. NMF was implemented to extract soil spectral signals from mixed hyperspectra. The NMF-extracted soil spectra were used to estimate SSC using partial least squares regression. Results indicate that SSC could be estimated based on the original mixed spectra within a 25.76% FVC (R2cv = 0.68, RMSEcv = 5.18 g·kg−1, RPD = 1.43). Compared with the mixed spectra, NMF extraction of soil spectrum improved the estimation accuracy. The NMF-extracted soil spectra from FVC below 63.55% of the mixed spectra provided acceptable estimation accuracies for SSC with the lowest results of determination of the estimation R2cv = 0.69, RMSEcv = 4.15 g·kg−1, and RPD = 1.8. Additionally, we proposed a strategy for the model performance investigation that combines spearman correlation analysis and model variable importance projection analysis. The NMF-extracted soil spectra retained the sensitive wavelengths that were significantly correlated with SSC and participated in the operation as important variables of the model.
CRISPR-Cas9-Mediated Correction of SLC12A3 Gene Mutation Rescues the Gitelman’s Disease Phenotype in a Patient-Derived Kidney Organoid System
Authors: Lim Sun Woo , Fang Xianying , Cui Sheng , Lee Hanbi , Shin Yoo Jin , Ko Eun Jeong , Lee Kang In , Lee Jae Young , Chung Byung Ha , Yang Chul Woo
Published: February 2023

The aim of this study is to explore the possibility of modeling Gitelman’s disease (GIT) with human-induced pluripotent stem cell (hiPSC)-derived kidney organoids and to test whether gene correction using CRISPR/Cas9 can rescue the disease phenotype of GIT. To model GIT, we used the hiPSC line CMCi002 (CMC-GIT-001), generated using PBMCs from GIT patients with SLC12A3 gene mutation. Using the CRISPR-Cas9 system, we corrected CMC-GIT-001 mutations and hence generated CMC-GIT-001corr. Both hiPSCs were differentiated into kidney organoids, and we analyzed the GIT phenotype. The number of matured kidney organoids from the CMC-GIT-001corr group was significantly higher, 3.3-fold, than that of the CMC-GIT-001 group (12.2 ± 0.7/cm2 vs. 3.7 ± 0.2/cm2, p < 0.05). In qRT-PCR, performed using harvested kidney organoids, relative sodium chloride cotransporter (NCCT) mRNA levels (normalized to each iPSC) were increased in the CMC-GIT-001corr group compared with the CMC-GIT-001 group (4.1 ± 0.8 vs. 2.5 ± 0.2, p < 0.05). Consistently, immunoblot analysis revealed increased levels of NCCT protein, in addition to other tubular proteins markers, such as LTL and ECAD, in the CMC-GIT-001corr group compared to the CMC-GIT-001 group. Furthermore, we found that increased immunoreactivity of NCCT in the CMC-GIT-001corr group was colocalized with ECAD (a distal tubule marker) using confocal microscopy. Kidney organoids from GIT patient-derived iPSC recapitulated the Gitelman’s disease phenotype, and correction of SLC12A3 mutation utilizing CRISPR-Cas9 technology provided therapeutic insight.
Supt16 Haploinsufficiency Impairs PI3K/AKT/mTOR/Autophagy Pathway in Human Pluripotent Stem Cells Derived Neural Stem Cells
Authors: Wang Junwen , Wang Ziyi , Dai Limeng , Zhu Xintong , Guan Xingying , Wang Junyi , Li Jia , Zhang Mao , Bai Yun , Guo Hong
Published: February 2023

The maintenance of neural stem cells (NSCs) plays a critical role in neurodevelopment and has been implicated in neurodevelopmental disorders (NDDs). However, the underlying mechanisms linking defective human neural stem cell self-renewal to NDDs remain undetermined. Our previous study found that Supt16 haploinsufficiency causes cognitive and social behavior deficits by disrupting the stemness maintenance of NSCs in mice. However, its effects and underlying mechanisms have not been elucidated in human neural stem cells (hNSCs). Here, we generated Supt16+/− induced pluripotent stem cells (iPSCs) and induced them into hNSCs. The results revealed that Supt16 heterozygous hNSCs exhibit impaired proliferation, cell cycle arrest, and increased apoptosis. As the RNA-seq analysis showed, Supt16 haploinsufficiency inhibited the PI3K/AKT/mTOR pathway, leading to rising autophagy, and further resulted in the dysregulated expression of multiple proteins related to cell proliferation and apoptotic process. Furthermore, the suppression of Supt16 heterozygous hNSC self-renewal caused by autophagy activation could be rescued by MHY1485 treatment or reproduced in rapamycin-treated hNSCs. Thus, our results showed that Supt16 was essential for hNSC self-renewal and its haploinsufficiency led to cell cycle arrest, impaired cell proliferation, and increased apoptosis of hNSCs by regulating the PI3K/AKT/mTOR/autophagy pathway. These provided a new insight to understand the causality between the Supt16 heterozygous NSCs and NDDs in humans.
Stable Enzymatic Nanoparticles from Nucleases, Proteases, Lipase and Antioxidant Proteins with Substrate-Binding and Catalytic Properties
Authors: Morozova Olga V. , Barinov Nikolay A. , Klinov Dmitry V.
Published: February 2023

Limited membrane permeability and biodegradation hamper the intracellular delivery of the free natural or recombinant enzymes necessary for compensatory therapy. Nanoparticles (NP) provide relative protein stability and unspecific endocytosis-mediated cellular uptake. Our objective was the fabrication of NP from 7 biomedicine-relevant enzymes, including DNase I, RNase A, trypsin, chymotrypsin, catalase, horseradish peroxidase (HRP) and lipase, the analysis of their conformation stability and enzymatic activity as well as possible toxicity for eukaryotic cells. The enzymes were dissolved in fluoroalcohol and mixed with 40% ethanol as an anti-solvent with subsequent alcohol evaporation at high temperature and low pressure. The shapes and sizes of NP were determined by scanning electron microscopy (SEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). Enzyme conformations in solutions and in NP were compared using circular dichroism (CD) spectroscopy. The activity of the enzymes was assayed with specific substrates. The cytotoxicity of the enzymatic NP (ENP) was studied by microscopic observations and by using an MTT test. Water-insoluble ENP of different shapes and sizes in a range 50–300 nm consisting of 7 enzymes remained stable for 1 year at +4 °C without any cross-linking. CD spectroscopy of the ENP permitted us to reveal changes in proportions of α-helixes, β-turns and random coils in comparison with fresh enzyme solutions in water. Despite the minor conformation changes of the proteins in the ENP, the enzymes retained their substrate-binding and catalytic properties. Among the studied bioactive ENP, only DNase NP were highly toxic for 3 cell lines with granulation in 1 day posttreatment, whereas other NP were less toxic (if any). Taken together, the enzymes in the stable ENP retained their catalytic activity and might be used for intracellular delivery.
Microsomal Prostaglandin E Synthase-1 and -2: Emerging Targets in Non-Alcoholic Fatty Liver Disease
Authors: Kotsos Dimitrios , Tziomalos Konstantinos
Published: February 2023

Nonalcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is even more prevalent in obese and diabetic patients. NAFLD, and particularly the more advanced manifestation of the disease, nonalcoholic steatohepatitis (NASH), increases the risk for both liver-related and cardiovascular morbidity. The pathogenesis of NAFLD is complex and multifactorial, with many molecular pathways implicated. Emerging data suggest that microsomal prostaglandin E synthase-1 and -2 might participate in the development and progression of NAFLD. It also appears that targeting these enzymes might represent a novel therapeutic approach for NAFLD. In the present review, we discuss the association between microsomal prostaglandin E synthase-1 and -2 and NAFLD.
Long-Term Soil Drought Limits Starch Accumulation by Altering Sucrose Transport and Starch Synthesis in Sweet Potato Tuberous Root
Authors: Sheng Minfei , Xia Houqiang , Ding Huizi , Pan Dongyu , He Jinping , Li Zongyun , Liu Jingran
Published: February 2023

In this study, the influences of long-term soil drought with three levels [soil-relative water content (SRWC) (75 ± 5)%, as the control; SRWC (55 ± 5)%, mild drought; SRWC (45 ± 5)%, severe drought] were investigated on sucrose-starch metabolism in sweet potato tuberous roots (TRs) by pot experiment. Compared to the control, drought stress increased soluble sugar and sucrose content by 4–60% and 9–75%, respectively, but reduced starch accumulation by 30–66% through decreasing the starch accumulate rate in TRs. In the drought-treated TRs, the inhibition of sucrose decomposition was attributed to the reduced activities of acid invertase (AI) and alkaline invertase (AKI) and the IbA-INV3 expression, rather than sucrose synthase (SuSy), consequently leading to the increased sucrose content in TRs. In addition, starch synthesis was inhibited mainly by reducing ADP-glucose pyrophosphorylase (AGPase), granular starch synthase (GBSS) and starch branching enzyme (SBE) activities in TRs under drought stress, and AGPase was the rate-limiting enzyme. Furthermore, soil drought remarkably up-regulated the IbSWEET11, IbSWEET605, and IbSUT4 expressions in Jishu 26 TRs, while it down-regulated or had no significant differences in Xushu 32 and Ningzishu 1 TRs. These results suggested that the sucrose-loading capability in Jishu 26 TRs were stronger than that in Xushu 32 and Ningzishu 1 TRs. Moreover, IbA-INV3, IbAGPS1, IbAGPS2, IbGBSSI and IbSBEII play important roles in different drought-tolerant cultivars under drought stress.
Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Potential Diagnostic Biomarkers in Autism Spectrum Disorders: A Preliminary Study
Authors: Simone Marta , De Giacomo Andrea , Palumbi Roberto , Palazzo Claudia , Lucisano Giuseppe , Pompamea Francesco , Micella Stefania , Pascali Mara , Gabellone Alessandra , Marzulli Lucia , Giordano Paola , Gargano Concetta Domenica , Margari Lucia , Frigeri Antonio , Ruggieri Maddalena
Published: February 2023

Autism spectrum disorder (ASD) is one of the most common neurodevelopment disorders, characterized by a multifactorial etiology based on the interaction of genetic and environmental factors. Recent evidence supports the neurobiological hypothesis based on neuroinflammation theory. To date, there are no sufficiently validated diagnostic and prognostic biomarkers for ASD. Therefore, we decided to investigate the potential diagnostic role for ASD of two biomarkers well known for other neurological inflammatory conditions: the glial fibrillary acidic protein (GFAP) and the neurofilament (Nfl). Nfl and GFAP serum levels were analyzed using SiMoA technology in a group of ASD patients and in a healthy control group (CTRS), age- and gender-matched. Then we investigated the distribution, frequency, and correlation between serum Nfl and GFAP levels and clinical data among the ASD group. The comparison of Nfl and GFAP serum levels between ASD children and the control group showed a mean value of these two markers significantly higher in the ASD group (sNfL mean value ASD pt 6.86 pg/mL median value ASD pt 5.7 pg/mL; mean value CTRS 3.55 pg/mL; median value CTRS 3.1 pg; GFAP mean value ASD pt 205.7 pg/mL median value ASD pt 155.4 pg/mL; mean value CTRS 77.12 pg/mL; median value CTRS 63.94 pg/mL). Interestingly, we also found a statistically significant positive correlation between GFAP levels and hyperactivity symptoms (p-value <0.001). Further investigations using larger groups are necessary to confirm our data and to verify in more depth the potential correlation between these biomarkers and ASD clinical features, such as the severity of the core symptoms, the presence of associated symptoms, and/or the evaluation of a therapeutic intervention. However, these data not only might shed a light on the neurobiology of ASD, supporting the neuroinflammation and neurodegeneration hypothesis, but they also might support the use of these biomarkers in the early diagnosis of ASD, to longitudinally monitor the disease activity, and even more as future prognostic biomarkers.
A Picrocrocin-Enriched Fraction from a Saffron Extract Affects Lipid Homeostasis in HepG2 Cells through a Non-Statin-like Mode
Authors: Frattaruolo Luca , Marra Federica , Lauria Graziantonio , Siciliano Carlo , Curcio Rosita , Muto Luigina , Brindisi Matteo , Aiello Donatella , Napoli Anna , Fiermonte Giuseppe , Cappello Anna Rita , Fiorillo Marco , Ahmed Amer , Dolce Vincenza
Published: February 2023

Dyslipidemia is a lipid metabolism disorder associated with the loss of the physiological homeostasis that ensures safe levels of lipids in the organism. This metabolic disorder can trigger pathological conditions such as atherosclerosis and cardiovascular diseases. In this regard, statins currently represent the main pharmacological therapy, but their contraindications and side effects limit their use. This is stimulating the search for new therapeutic strategies. In this work, we investigated in HepG2 cells the hypolipidemic potential of a picrocrocin-enriched fraction, analyzed by high-resolution 1H NMR and obtained from a saffron extract, the stigmas of Crocus sativus L., a precious spice that has already displayed interesting biological properties. Spectrophotometric assays, as well as expression level of the main enzymes involved in lipid metabolism, have highlighted the interesting hypolipidemic effects of this natural compound; they seem to be exerted through a non-statin-like mechanism. Overall, this work provides new insights into the metabolic effects of picrocrocin, thus confirming the biological potential of saffron and paving the way for in vivo studies that could validate this spice or its phytocomplexes as useful adjuvants in balancing blood lipid homeostasis.
Molecular Dynamics of Lysine Dendrigrafts in Methanol–Water Mixtures
Authors: Fatullaev Emil I. , Shavykin Oleg V. , Neelov Igor M.
Published: February 2023

The molecular dynamics method was used to study the structure and properties of dendrigrafts of the first and second generations in methanol–water mixtures with various volume fractions of methanol. At a small volume fraction of methanol, the size and other properties of both dendrigrafts are very similar to those in pure water. A decrease in the dielectric constant of the mixed solvent with an increase in the methanol fraction leads to the penetration of counterions into the dendrigrafts and a reduction of the effective charge. This leads to a gradual collapse of dendrigrafts: a decrease in their size, and an increase in the internal density and the number of intramolecular hydrogen bonds inside them. At the same time, the number of solvent molecules inside the dendrigraft and the number of hydrogen bonds between the dendrigraft and the solvent decrease. At small fractions of methanol in the mixture, the dominant secondary structure in both dendrigrafts is an elongated polyproline II (PPII) helix. At intermediate volume fractions of methanol, the proportion of the PPII helix decreases, while the proportion of another elongated β-sheet secondary structure gradually increases. However, at a high fraction of methanol, the proportion of compact α-helix conformations begins to increase, while the proportion of both elongated conformations decreases.
Quercetin 3-O-Galactoside Isolated from Limonium tetragonum Inhibits Melanogenesis by Regulating PKA/MITF Signaling and ERK Activation
Authors: Karadeniz Fatih , Oh Jung Hwan , Seo Youngwan , Yang Jiho , Lee Hyunjung , Kong Chang-Suk
Published: February 2023

Quercetin 3-O-galactoside (Q3G) is a common dietary flavanol that has been shown to possess several bioactivities, including anti-melanogenesis. However, how Q3G exerts its anti-melanogenic effect has not been studied. The current study, therefore aimed to investigate the anti-melanogenesis potential of Q3G and elucidate the underlying action mechanism in α-melanocyte-stimulating hormone (α-MSH)-induced hyperpigmentation model of B16F10 murine melanoma cells. Results showed that α-MSH stimulation significantly increased tyrosinase (TYR) and melanin production, which were significantly downregulated by Q3G treatment. The treatment with Q3G suppressed the transcriptional and protein expressions of melanogenesis-related enzymes TYR, tyrosinase related protein-1 (TRP-1), and TRP-2, along with the melanogenic transcription factor microphthalmia-associated transcription factor (MITF) in B16F10 cells. It was shown that Q3G downregulated MITF expression and suppressed its transcriptional activity by inhibiting the cAMP-dependent protein kinase A (PKA)-mediated activation of CREB and GSK3β. In addition, MAPK-regulated MITF activation signaling was also involved in the inhibition of melanin production by Q3G. The results suggest that the anti-melanogenic properties of Q3G rationalize further studies in vivo to confirm its action mechanism and consequent utilization as a cosmetic ingredient against hyperpigmentation.
PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1
Authors: Wei Xing , Liu Yingxiang , Hao Weijie , Feng Peiwen , Zhang Lei , Xue Hongni , Zhou Qunli , Guo Zekun
Published: February 2023

DNA methylation is an epigenetic modification that plays a vital role in a variety of biological processes, including the regulation of gene expression, cell differentiation, early embryonic development, genomic imprinting, and X chromosome inactivation. PGC7 is a maternal factor that maintains DNA methylation during early embryonic development. One mechanism of action has been identified by analyzing the interactions between PGC7 and UHRF1, H3K9 me2, or TET2/TET3, which reveals how PGC7 regulates DNA methylation in oocytes or fertilized embryos. However, the mechanism by which PGC7 regulates the post-translational modification of methylation-related enzymes remains to be elucidated. This study focused on F9 cells (embryonic cancer cells), which display high levels of PGC7 expression. We found that both knockdown of Pgc7 and inhibition of ERK activity resulted in increased genome-wide DNA methylation levels. Mechanistic experiments confirmed that inhibition of ERK activity led to the accumulation of DNMT1 in the nucleus, ERK phosphorylated DNMT1 at ser717, and DNMT1 Ser717-Ala mutation promoted the nuclear localization of DNMT1. Moreover, knockdown of Pgc7 also caused downregulation of ERK phosphorylation and promoted the accumulation of DNMT1 in the nucleus. In conclusion, we reveal a new mechanism by which PGC7 regulates genome-wide DNA methylation via phosphorylation of DNMT1 at ser717 by ERK. These findings may provide new insights into treatments for DNA methylation-related diseases.
Alginate Oligosaccharides Repair Liver Injury by Improving Anti-Inflammatory Capacity in a Busulfan-Induced Mouse Model
Authors: Hao Yanan , Fang Hanhan , Yan Xiaowei , Shen Wei , Liu Jing , Han Pengfei , Zhao Yong , Zhang Weidong , Feng Yanni
Published: February 2023

Liver diseases are associated with many factors, including medicines and alcoholics, which have become a global problem. It is crucial to overcome this problem. Liver diseases always come with inflammatory complications, which might be a potential target to deal with this issue. Alginate oligosaccharides (AOS) have been demonstrated to have many beneficial effects, especially anti-inflammation. In this study, 40 mg/kg body weight (BW) of busulfan was intraperitoneally injected once, and then the mice were dosed with ddH2O or AOS 10 mg/kg BW every day by oral gavage for five weeks. We investigated AOS as a potential no-side-effect and low-cost therapy for liver diseases. For the first time, we discovered that AOS 10 mg/kg recovered liver injury by decreasing the inflammation-related factors. Moreover, AOS 10 mg/kg could improve the blood metabolites related to immune and anti-tumor effects, and thus, ameliorated impaired liver function. The results indicate that AOS may be a potential therapy to deal with liver damage, especially in inflammatory conditions.
Role of Protein Kinase A Activation in the Immune System with an Emphasis on Lipopolysaccharide-Responsive and Beige-like Anchor Protein in B Cells
Authors: Pérez-Pérez Daniela , Santos-Argumedo Leopoldo , Rodríguez-Alba Juan Carlos , López-Herrera Gabriela
Published: February 2023

Cyclic AMP-dependent protein kinase A (PKA) is a ubiquitous enzymatic complex that is involved in a broad spectrum of intracellular receptor signaling. The activity of PKA depends on A-kinase anchoring proteins (AKAPs) that attach to PKAs close to their substrates to control signaling. Although the relevance of PKA-AKAP signaling in the immune system is evident in T cells, its relevance in B and other immune cells remains relatively unclear. In the last decade, lipopolysaccharide-responsive and beige-like anchor protein (LRBA) has emerged as an AKAP that is ubiquitously expressed in B and T cells, specifically after activation. A deficiency of LRBA leads to immune dysregulation and immunodeficiency. The cellular mechanisms regulated by LRBA have not yet been investigated. Therefore, this review summarizes the functions of PKA in immunity and provides the most recent information regarding LRBA deficiency to deepen our understanding of immune regulation and immunological diseases.
Impact of Salinity on the Energy Transfer between Pigment–Protein Complexes in Photosynthetic Apparatus, Functions of the Oxygen-Evolving Complex and Photochemical Activities of Photosystem II and Photosystem I in Two Paulownia Lines
Authors: Stefanov Martin A. , Rashkov Georgi D. , Yotsova Ekaterina K. , Dobrikova Anelia G. , Apostolova Emilia L.
Published: February 2023

The present study shows the effect of salinity on the functions of thylakoid membranes from two hybrid lines of Paulownia: Paulownia tomentosa x fortunei and Paulownia elongate x elongata, grown in a Hoagland solution with two NaCl concentrations (100 and 150 mM) and different exposure times (10 and 25 days). We observed inhibition of the photochemical activities of photosystem I (DCPIH2 → MV) and photosystem II (H2O → BQ) only after the short treatment (10 days) with the higher NaCl concentration. Data also revealed alterations in the energy transfer between pigment–protein complexes (fluorescence emission ratios F735/F685 and F695/F685), the kinetic parameters of the oxygen-evolving reactions (initial S0-S1 state distribution, misses (α), double hits (β) and blocked centers (SB)). Moreover, the experimental results showed that after prolonged treatment with NaCl Paulownia tomentosa x fortunei adapted to the higher concentration of NaCl (150 mM), while this concentration is lethal for Paulownia elongata x elongata. This study demonstrated the relationship between the salt-induced inhibition of the photochemistry of both photosystems and the salt-induced changes in the energy transfer between the pigment–protein complexes and the alterations in the Mn cluster of the oxygen-evolving complex under salt stress.
Effect of Antihypertensive Drug (Chlorothiazide) on Fibrillation of Lysozyme: A Combined Spectroscopy, Microscopy, and Computational Study
Authors: Altwaijry Nojood , Almutairi Ghaliah S. , Khan Mohd Shahnawaz , Shaik Gouse M. , Alokail Majed S.
Published: February 2023

Amyloid fibrils abnormally accumulate together in the human body under certain conditions, which can result in lethal conditions. Thus, blocking this aggregation may prevent or treat this disease. Chlorothiazide (CTZ) is a diuretic and is used to treat hypertension. Several previous studies suggest that diuretics prevent amyloid-related diseases and reduce amyloid aggregation. Thus, in this study we examine the effects of CTZ on hen egg white lysozyme (HEWL) aggregation using spectroscopic, docking, and microscopic approaches. Our results showed that under protein misfolding conditions of 55 °C, pH 2.0, and 600 rpm agitation, HEWL aggregated as evidenced by the increased turbidity and Rayleigh light scattering (RLS). Furthermore, thioflavin-T, as well as trans electron microscope (TEM) analysis confirmed the formation of amyloid structures. An anti-aggregation effect of CTZ is observed on HEWL aggregations. Circular dichroism (CD), TEM, and Thioflavin-T fluorescence show that both CTZ concentrations reduce the formation of amyloid fibrils as compared to fibrillated. The turbidity, RLS, and ANS fluorescence increase with CTZ increasing. This increase is attributed to the formation of a soluble aggregation. As evidenced by CD analysis, there was no significant difference in α-helix content and β-sheet content between at 10 µM CTZ and 100 µM. A TEM analysis of HEWL coincubated with CTZ at different concentrations validated all the above-mentioned results. The TEM results show that CTZ induces morphological changes in the typical structure of amyloid fibrils. The steady-state quenching study demonstrated that CTZ and HEWL bind spontaneously via hydrophobic interactions. HEWL–CTZ also interacts dynamically with changes in the environment surrounding tryptophan. Computational results revealed the binding of CTZ to ILE98, GLN57, ASP52, TRP108, TRP63, TRP63, ILE58, and ALA107 residues in HEWL via hydrophobic interactions and hydrogen bonds with a binding energy of −6.58 kcal mol−1. We suggest that at 10 µM and 100 μM, CTZ binds to the aggregation-prone region (APR) of HEWL and stabilizes it, thus preventing aggregation. Based on these findings, we can conclude that CTZ has antiamyloidogenic activity and can prevent fibril aggregation.
Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice
Authors: Goeritzer Madeleine , Kuentzel Katharina B. , Beck Sarah , Korbelius Melanie , Rainer Silvia , Bradić Ivan , Kolb Dagmar , Mussbacher Marion , Schrottmaier Waltraud C. , Assinger Alice , Schlagenhauf Axel , Rost René , Gottschalk Benjamin , Eichmann Thomas O. , Züllig Thomas , Graier Wolfgang F. , Vujić Nemanja , Kratky Dagmar
Published: February 2023

Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) to glycerol and one fatty acid. Among the various MG species, MGL also degrades 2-arachidonoylglycerol, the most abundant endocannabinoid and potent activator of the cannabinoid receptors 1 and 2. We investigated the consequences of MGL deficiency on platelet function using systemic (Mgl−/−) and platelet-specific Mgl-deficient (platMgl−/−) mice. Despite comparable platelet morphology, loss of MGL was associated with decreased platelet aggregation and reduced response to collagen activation. This was reflected by reduced thrombus formation in vitro, accompanied by a longer bleeding time and a higher blood volume loss. Occlusion time after FeCl3-induced injury was markedly reduced in Mgl−/− mice, which is consistent with contraction of large aggregates and fewer small aggregates in vitro. The absence of any functional changes in platelets from platMgl−/− mice is in accordance with lipid degradation products or other molecules in the circulation, rather than platelet-specific effects, being responsible for the observed alterations in Mgl−/− mice. We conclude that genetic deletion of MGL is associated with altered thrombogenesis.