bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a Consumer Quality Index for Fresh Plums (Prunus salicina Lindell)
Authors: Crisosto Carlos H.
Published: June 2023

Plums are primarily marketed for fresh consumption, canning, freezing, jam and jelly. Unfortunately, plum consumption has remained steady or declined. Consumers complain about a lack of flavor quality but are willing to pay for higher quality. Thus, absence of flavor and cold storage disorders are the main barriers to consumption. Plum cultivars are sensitive to gel breakdown, flesh browning and ‘off flavors’. Consumer approval and postharvest life are controlled by genotype, quality attributes, harvest date and proper postharvest handling. A consumer quality index (CQI) based on soluble solids concentration (SSC) and minimum firmness is proposed to maximize flavor and postharvest life. In most cases, late harvest increases quality attributes. Our work and industry experience demonstrated that using critical bruising thresholds (CBT) based on minimum firmness measured at harvest acts as a reliable predictor of how late to harvest safely for maximum visual and sensory quality. Plums tolerated late harvest well because of their high tolerance to bruising damage, but suitable postharvest temperature management and selling within the potential postharvest life are required to maintain flavor and avoid the beginning of chilling injury. Thus, to maximize flavor and postharvest life, a CQI based on SSC and minimum firmness measured at consumption is proposed. This article provides guidance on using this CQI, combined with proper postharvest handling techniques, such as correct harvest date determination and temperature management, to maintain quality and increase consumption.
Sport Anxiety, Fear of Negative Evaluation, Stress and Coping as Predictors of Athlete’s Sensitivity to the Behavior of Supporters
Authors: Gabrys Katarzyna , Wontorczyk Antoni
Published: June 2023

The aim of the study was to find predictors of athlete sensitivity to the positive or negative behaviors of supporters and determine a relationship between athletes’ sensitivity to the positive and negative behaviors of supporters and traits such as anxiety and stress or the strategies used to cope with stress. The sample consisted of 171 professional athletes. The study determined three variables that are predictors of athlete sensitivity to the positive behavior of supporters (SPS), i.e., strategies of coping with stress, such as high levels of coachability, confidence and achievement motivation and low levels of freedom from worry (change R2 = 0.15, F of change = 9.78, p of change < 0.001). The predictors of sensitivity to the negative behavior of supporters (SNS) are as follows: a low level of freedom from worry and a high level of fear of negative evaluation (change R2 = 0.31, F of change = 38.56, p of change < 0.001). In the context of the athlete’s position, the predictors of SPS for midfielders are as follows: high level of susceptibility to stress and two strategies of coping with stress, i.e., peaking under pressure and concentration. For forwarders they are as follows: high level of worry and coping with stress via goal-setting, while for defenders, the ways of coping with stress are confidence and achievement motivation. In terms of SNS, for defenders, the predictors are low levels of freedom from worry, coachability, and a high level of fear of negative evaluation. Forwarders, who are sensitive to the negative behavior of supporters, are characterized by a fear of negative evaluation.
Climate Change, Ecological Modernization, and Disaster Management: The Coastal Embankment Project in Southwestern Bangladesh
Authors: Kais Shaikh Mohammad , Islam Md Saidul
Published: June 2023

Climate change, one of the severest environmental threats to humankind, disproportionately affects low-income, developing countries in the Global South. Having no feasible mitigation alternatives, these countries resort to adaptation efforts to address climate perturbations. Climate change adaptation (or resilience) is primarily a localized course of action that depends on individuals, social networks, economies, ecologies, political structures, and the capabilities of all those to work collectively to absorb, learn from, and transform in the face of new realities. With a view to controlling the floods that shattered the life and economy of the then East Pakistan, which is now Bangladesh, during the mid-twentieth century, the coastal embankment project (CEP) was instituted as an adaptation strategy to natural disasters in Southwestern Bangladesh. Based on a qualitative analysis of primary and secondary data, this paper seeks to critically evaluate the efficacy of the CEP in terms of the space for feasible action and ecological modernization. The findings of this research indicate that the CEP has become an unrealistic venture that hinders the growing economic activity of shrimp aquaculture in the area. This paper is expected to contribute to generating further theoretical and empirical discourse on the evaluation of similar development projects around the globe.
Hedonic Risk Preference Associated with High-Risk Behaviors under COVID-19 Pandemic among Medical Students in Japan
Authors: Zeng Zechen , Nawa Nobutoshi , Hirama Chie , Fujiwara Takeo
Published: June 2023

Background: Public health measures to mitigate the spread of COVID-19 have focused on raising awareness and disseminating knowledge. Few considered people’s risk preferences and no measurement was adapted to the context of COVID-19. This study aims (1) to investigate the association between risk preference and risk behaviors and (2) to compare a novel hedonic preference question with traditional risk preference assessment tools in the context of the COVID-19 pandemic among medical students in Japan. Methods: An online survey of fourth-year medical students was conducted. Logistic regression analysis adjusted for gender, age, household income, and the overconfidence effect were performed to investigate the association. Results: We observed significantly higher odds of high-risk behaviors in general risk preference (odds ratio (OR): 4.04; 95% confidence interval (CI): 1.05–15.50) and hedonic preference (OR: 6.58; 95% CI: 1.86–23.28) when adjusted, whereas monetary preference showed no significant association. Concerning specific risky behaviors, hedonic preference were significantly associated with four items after adjusting for covariates (“dine out” (OR: 2.78, 95% CI: 1.13–6.85), “go out” (OR: 4.35, 95% CI: 1.65–11.46), “not practicing safety precautions” (OR: 2.79, 95% CI: 1.11–7.04) and “travel” (OR: 4.36, 95% CI: 1.42–13.44)), and general preference in two (“dine out” (OR: 4.82, 95% CI: 1.66–14.00) and “go out” (OR: 6.48, 95% CI: 2.07–20.24)). Conclusion: Hedonic and general risk preferences were significantly associated with high-risk behaviors during the COVID-19 pandemic. Future application of the novel risk-for-pleasure-seeking preference question is warranted.
Beyond Finding Purpose: Motivating a Translational Science of Purpose Acquisition
Authors: Burrow Anthony L.
Published: June 2023

A broad interest in finding purpose is understandable, as having purpose is situated in notions of “the good life” and is linked in studies to greater health and wellbeing. Yet, the empirical basis for whether purpose is truly findable is inadequate, lacking guidance from theories predicting behavioral capacities that drive its acquisition. If feeling purposeful is as favorable as studies suggest, then more transparent and precise explanations of how it is derived are needed; otherwise, the field risks illuminating this resource while leaving the pathways to it unlit. Here, I call for a translational science of purpose acquisition directed at gathering and disseminating evidence of the processes by which this sense can be cultivated. I introduce a minimal viable framework for integrating basic and applied investigations into purpose by bridging laboratory research, intervention and implementation efforts, community-engaged practices, and policies to accelerate testing and strategies for enhancing this salubrious sense in people’s lives.
The Functional States of the Participants of a Marine Arctic Expedition with Different Levels of Vitamin D in Blood
Authors: Simonova Natalia , Kirichek Maria , Trofimova Anna A. , Korneeva Yana , Trofimova Anna N. , Korobitsyna Rimma , Sorokina Tatiana
Published: June 2023

(1) Background: The vitamin D level in blood is one of the markers of the functional reserves of the human body and can contribute to more successful adaptation in the Arctic. (2) Methods: The study involved 38 participants in the project “Arctic Floating University—2021”. The determination of vitamin D content was carried out at the beginning of the expedition. A dynamic study was carried out for 20 days in the morning and in the evening. The functional state parameters of the participants were assessed using psychophysiological and questionnaire methods. Statistical methods: Mann–Whitney U-test and correlation analysis. (3) Results: It was found that at the beginning of the expedition, the functional state of participants with more severe vitamin D deficiency is characterized by a shorter average duration of RR intervals (p = 0.050) and reduced SDNN values (p = 0.015). The higher the content of vitamin D, the greater increase in speed (r = 0.510), the higher the increase in projective performance (r = 0.485), and the smaller the increase in projective stress (r = −0.334). Significant relationships between the subjective characteristics of functional states and the vitamin D of participants have not been established. (4) Conclusion: With an increase in the severity of vitamin D deficiency in the blood, the adaptive capabilities of participants decrease during an expedition to the Arctic.
Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation Combined with Motor Learning on Motor Function and Grip Force of the Upper Limbs and Activities of Daily Living in Patients with a Subacute Stroke
Authors: Shim Jungwoo , Lee Seungwon
Published: June 2023

Functional paralysis of the upper extremities occurs in >70% of all patients after having a stroke, and >60% showed decreased hand dexterity. A total of 30 patients with a subacute stroke were randomly allocated to either high-frequency repetitive transcranial magnetic stimulation combined with motor learning (n = 14) or sham repetitive transcranial magnetic stimulation combined with motor learning (n = 16). High-frequency repetitive transcranial magnetic stimulation combined with the motor learning group was conducted for 20 min (10 min of high-frequency repetitive transcranial magnetic stimulation and 10 min of motor learning) three times a week for 4 weeks. The sham repetitive transcranial magnetic stimulation combined with the motor learning group received 12 20-min sessions (10 min of sham repetitive transcranial magnetic stimulation and 10 min of motor learning). This was held three times a week for 4 weeks. Upper-limb function (Fugl-Meyer Assessment of the Upper Limbs) and upper-limb dexterity (box and block tests) concerning upper-limb motor function and grip force (hand grip dynamometer), and activities of daily living (Korean version of the modified Barthel index), were measured pre- and post-intervention. In both groups, there were significant improvements in the upper-limb motor function, grip force, and activities of daily living (p < 0.05). Regarding grip force, the high-frequency repetitive transcranial magnetic stimulation combined with the motor learning group improved significantly compared to the sham repetitive transcranial magnetic stimulation combined with the motor learning group (p < 0.05). However, except for grip force, there were no significant differences in the upper-limb motor function or activities of daily living between the groups. These findings suggest that high-frequency repetitive transcranial magnetic stimulation combined with motor learning is more likely to improve grip force than motor learning alone.
Analysis of Inequalities and Inequities in Maternal Mortality in Chocó, Colombia
Authors: Rodríguez Hernández Jorge Martín , Ariza Ruiz Liany Katerine , Castro Barbudo Daniella , Vivas Sánchez Paula , Matallana Gómez María Alexandra , Gómez Hernández Leidy Johanna , Romero Mendoza Lilibeth , Chaparro Narváez Pablo Enrique
Published: June 2023

We used a mixed design study to analyze the inequalities and inequities in Maternal Mortality (MM) for Chocó (Colombia) between 2010–2018. The quantitative component consisted of an analytical ecological design, where proportions, ratios, measures of central tendency and rates ratios, rate difference, Gini and concentration indices were calculated to measure inequalities. The qualitative component had a phenomenological and interpretive approach. One hundred thirty-one women died in Choco between 2010–2018. The Maternal Mortality Ratio was 224/100.000 live births. The Gini coefficient was 0.35, indicating inequality in the distribution of the number of MM with respect to live births. The health service offers have been concentrated in the private sector in urban areas (77%). The exercise of midwifery has played an important role in maternal and perinatal care processes, especially in territories where the State has been absent. Nevertheless, it occurs in complex circumstances such as the armed conflict, lack of transportation routes, and income deficits, affecting the timelines and care quality for these vulnerable groups. MM in Chocó has been a consequence of deficiencies in the health system and weaknesses in its infrastructure (absence of a high level of maternal-perinatal care). This is in addition to the territory’s geographical characteristics, which increase vulnerability and health risks for women and their newborns. In Colombia, as well as in other countries, many maternal and newborn deaths are preventable because their causes are due to social injustices.
The VEGA Tool to Check the Applicability Domain Gives Greater Confidence in the Prediction of In Silico Models
Authors: Danieli Alberto , Colombo Erika , Raitano Giuseppa , Lombardo Anna , Roncaglioni Alessandra , Manganaro Alberto , Sommovigo Alessio , Carnesecchi Edoardo , Dorne Jean-Lou C. M. , Benfenati Emilio
Published: June 2023

A sound assessment of in silico models and their applicability domain can support the use of new approach methodologies (NAMs) in chemical risk assessment and requires increasing the users’ confidence in this approach. Several approaches have been proposed to evaluate the applicability domain of such models, but their prediction power still needs a thorough assessment. In this context, the VEGA tool capable of assessing the applicability domain of in silico models is examined for a range of toxicological endpoints. The VEGA tool evaluates chemical structures and other features related to the predicted endpoints and is efficient in measuring applicability domain, enabling the user to identify less accurate predictions. This is demonstrated with many models addressing different endpoints, towards toxicity of relevance to human health, ecotoxicological endpoints, environmental fate, physicochemical and toxicokinetic properties, for both regression models and classifiers.
S-Nitrosoglutathione (GSNO)-Mediated Lead Detoxification in Soybean through the Regulation of ROS and Metal-Related Transcripts
Authors: Methela Nusrat Jahan , Islam Mohammad Shafiqul , Lee Da-Sol , Yun Byung-Wook , Mun Bong-Gyu
Published: June 2023

Heavy metal toxicity, including lead (Pb) toxicity, is increasing in soils, and heavy metals are considered to be toxic in small amounts. Pb contamination is mainly caused by industrialization (e.g., smelting and mining), agricultural practices (e.g., sewage sludge and pests), and urban practices (e.g., lead paint). An excessive concentration of Pb can seriously damage and threaten crop growth. Furthermore, Pb adversely affects plant growth and development by affecting the photosystem, cell membrane integrity, and excessive production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and superoxide (O2−). Nitric oxide (NO) is produced via enzymatic and non-enzymatic antioxidants to scavenge ROS and lipid peroxidation substrates to protect cells from oxidative damage. Thus, NO improves ion homeostasis and confers resistance to metal stress. In the present study, we investigated the effect of exogenously applied NO and S-nitrosoglutathione in soybean plants Our results demonstrated that exogenously applied NO aids in better growth under lead stress due to its ability in sensing, signaling, and stress tolerance in plants under heavy metal stress along with lead stress. In addition, our results showed that S-nitrosoglutathione (GSNO) has a positive effect on soybean seedling growth under lead-induced toxicity and that NO supplementation helps to reduce chlorophyll maturation and relative water content in leaves and roots following strong bursts under lead stress. GSNO supplementation (200 µM and 100 µM) reduced compaction and approximated the oxidative damage of MDA, proline, and H2O2. Moreover, under plant stress, GSNO application was found to relieve the oxidative damage by reactive oxygen species (ROS) scavenging. Additionally, modulation of NO and phytochelatins (PCS) after prolonged metal reversing GSNO application confirmed detoxification of ROS induced by the toxic metal lead in soybean. In summary, the detoxification of ROS caused by toxic metal concentrations in soybean is confirmed by using NO, PCS, and traditionally sustained concentrations of metal reversing GSNO application.
ETV2 Enhances CXCL5 Secretion from Endothelial Cells, Leading to the Promotion of Vascular Smooth Muscle Cell Migration
Authors: Sun Ningning , Chu Beyongsam , Choi Dong-Hyun , Lim Leejin , Song Heesang
Published: June 2023

Abnormal communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) promotes vascular diseases, including atherogenesis. ETS variant transcription factor 2 (ETV2) plays a substantial role in pathological angiogenesis and the reprogramming of ECs; however, the role of ETV2 in the communication between ECs and VSMCs has not been revealed. To investigate the interactive role of ETV2 in the EC to VSMC phenotype, we first showed that treatment with a conditioned medium from ETV2-overexpressed ECs (Ad-ETV2 CM) significantly increased VSMC migration. The cytokine array showed altered levels of several cytokines in Ad-ETV2 CM compared with those in normal CM. We found that C-X-C motif chemokine 5 (CXCL5) promoted VSMC migration using the Boyden chamber and wound healing assays. In addition, an inhibitor of C-X-C motif chemokine receptor 2 (CXCR2) (the receptor for CXCL5) significantly inhibited this process. Gelatin zymography showed that the activities of matrix metalloproteinase (MMP)-2 and MMP-9 increased in the media of VSMCs treated with Ad-ETV2 CM. Western blotting revealed a positive correlation between Akt/p38/c-Jun phosphorylation and CXCL5 concentration. The inhibition of Akt and p38-c-Jun effectively blocked CXCL5-induced VSMC migration. In conclusion, CXCL5 from ECs induced by ETV2 promotes VSMC migration via MMP upregulation and the activation of Akt and p38/c-Jun.
Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation
Authors: El Malki Khalifa , Wehling Pia , Alt Francesca , Sandhoff Roger , Zahnreich Sebastian , Ustjanzew Arsenij , Wilzius Carolin , Brockmann Marc A. , Wingerter Arthur , Russo Alexandra , Beck Olaf , Sommer Clemens , Ottenhausen Malte , Frauenknecht Katrin B. M. , Paret Claudia , Faber Jörg
Published: June 2023

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2 in a concentration and time-dependent manner and increased the expression of ceramide, ceramide 1-phosphate, sphingosine, and sphingomyelin but not of sphingosine 1-phosphate. Miglustat significantly increased the efficacy of irradiation. Treatment with miglustat according to dose recommendations for patients with Niemann–Pick disease was well tolerated with manageable toxicities. One patient showed a mixed response. In ependymoma, a high concentration of GD2 was found only in the presence of the loss of H3.3K27 trimethylation. In conclusion, treatment with miglustat and, in general, targeting GSL metabolism may offer a new therapeutic opportunity and can be administered in close proximity to radiation therapy. Alterations in H3K27 could be useful to identify patients with a deregulated GSL metabolism.
Targeting the Mannose Receptor with Functionalized Fucoidan/Chitosan Nanoparticles Triggers the Classical Activation of Macrophages
Authors: Serrasqueiro Filipa , Barbosa Ana Isabel , Lima Sofia A. Costa , Reis Salette
Published: June 2023

Understanding how nanoparticles’ properties influence their cellular interactions is a bottleneck for improving the design of carriers. Macrophage polarization governs their active role in solving infections or tissue repair. To unravel the effect of carbohydrate-targeting mannose receptors on the macrophage surface, drug-free fucoidan/chitosan nanoparticles were functionalized using mannose (M) and mannan (Mn). Polyelectrolyte complex nanoparticles were obtained upon chitosan self-assembly using fucoidan. The functionalized nanoparticles were characterized in terms of their physicochemical characteristics, chemical profile, and carbohydrate orientation. The nanoparticles varied in size from 200 to 400 nm, were monodisperse, and had a stable negative zeta potential with a low aggregation tendency. The nonfunctionalized and functionalized nanoparticles retained their properties for up to 12 weeks. Cell viability and internalization studies were performed for all the designed nanoparticles in the THP-1 monocytes and THP-1-differentiated macrophages. The expression of the mannose receptor was verified in both immune cells. The carbohydrate-functionalized nanoparticles led to their activation and the production of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α. Both M- and Mn-coated nanoparticles modulate macrophages toward an M1-polarized state. These findings demonstrate the tailoring of these nanoplatforms to interact and alter the macrophage phenotype in vitro and represent their therapeutic potential either alone or in combination with a loaded drug for future studies.
Hyperoside as a UV Photoprotective or Photostimulating Compound—Evaluation of the Effect of UV Radiation with Selected UV-Absorbing Organic Compounds on Skin Cells
Authors: Moukova Anna , Malina Lukas , Kolarova Hana , Bajgar Robert
Published: June 2023

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.
Advanced Biomaterials for Food Edible Coatings
Authors: Giosafatto C. Valeria L. , Porta Raffaele
Published: June 2023

The aim of this Special Issue is to highlight recent investigations on different biopolymers obtained from renewable sources for use as edible coatings [...]
Molecular-Biology-Driven Frontline Treatment for Chronic Lymphocytic Leukemia: A Network Meta-Analysis of Randomized Clinical Trials
Authors: Rizzuto Andrea , Pirrera Angelo , Gigliotta Emilia , Mancuso Salvatrice , Vullo Candida , Camarda Giulia Maria , Rotolo Cristina , Roppolo Arianna , Spoto Corinne , Gentile Massimo , Botta Cirino , Siragusa Sergio
Published: June 2023

The treatment of chronic lymphocytic leukemia (CLL) currently relies on the use of chemo-immunotherapy, Bruton’s tyrosine kinase inhibitors, or BCL2 inhibitors alone or combined with an anti-CD20 monoclonal antibody. However, the availability of multiple choices for the first-line setting and a lack of direct head-to-head comparisons pose a challenge for treatment selection. To overcome these limitations, we performed a systematic review and a network meta-analysis on published randomized clinical trials performed in the first-line treatment setting of CLL. For each study, we retrieved data on progression-free survival (according to del17/P53 and IGHV status), overall response rate, complete response, and incidence of most frequent grade 3–4 adverse event. We identified nine clinical trials encompassing 11 different treatments, with a total of 5288 CLL patients evaluated. We systematically performed separated network meta-analyses (NMA) to evaluate the efficacy/safety of each regimen in the conditions previously described to obtain the surface under the cumulative ranking curve (SUCRA) score, which was subsequently used to build separated ranking charts. Interestingly, the combination of obinutuzumab with acalabrutinib reached the top of the chart in each sub-analysis performed, with the exception of the del17/P53mut setting, where it was almost on par with the aCD20 mAbs/ibrutinib combination (SUCRA aCD20-ibrutinib and O-acala: 93.5% and 91%, respectively) and of the safety evaluation, where monotherapies (acalabrutinib in particular) gave better results. Finally, considering that NMA and SUCRA work for single endpoints only, we performed a principal component analysis to recapitulate in a cartesian plane the SUCRA profiles of each schedule according to the results obtained in each sub-analysis, confirming again the superiority of aCD20/BTKi or BCL2i combinations in a first-line setting. Overall, here we demonstrated that: (1) a chemotherapy-free regimen, such as the combination of aCD20 with a BTKi or BCL2i, should be the preferred treatment choice despite biological/molecular characteristics (preferred regimen O-acala); (2) there is less and less room for chemotherapy in the first line treatment of CLL.
New Insights into Immunopathology Associated to Bothrops lanceolatus Snake Envenomation: Focus on PLA2 Toxin
Authors: Gabrili Joel J. M. , Pidde Giselle , Magnoli Fabio Carlos , Marques-Porto Rafael , Villas-Boas Isadora Maria , Squaiella-Baptistão Carla Cristina , Silva-de-França Felipe , Burgher François , Blomet Joël , Tambourgi Denise V.
Published: June 2023

The systemic increase in inflammatory mediator levels can induce diverse pathological disorders, including potentially thrombus formation, which may be lethal. Among the clinical conditions in which the formation of thrombi dictates the patient’s prognosis, envenomation by Bothrops lanceolatus should be emphasized, as it can evolve to stroke, myocardial infarction and pulmonary embolism. Despite their life-threatening potential, the immunopathological events and toxins involved in these reactions remain poorly explored. Therefore, in the present study, we examined the immunopathological events triggered by a PLA2 purified from B. lanceolatus venom, using an ex vivo human blood model of inflammation. Our results showed that the purified PLA2 from the venom of B. lanceolatus damages human erythrocytes in a dose dependent way. The cell injury was associated with a decrease in the levels of CD55 and CD59 complement regulators on the cell surface. Moreover, the generation of anaphylatoxins (C3a and C5a) and the soluble terminal complement complex (sTCC) indicates that human blood exposure to the toxin activates the complement system. Increased production of TNF-α, CXCL8, CCL2 and CCL5 followed complement activation. The venom PLA2 also triggered the generation of lipid mediators, as evidenced by the detected high levels of LTB4, PGE2 and TXB2. The scenario here observed of red blood cell damage, dysfunctions of the complement regulatory proteins, accompanied by an inflammatory mediator storm, suggests that B. lanceolatus venom PLA2 contributes to the thrombotic disorders present in the envenomed individuals.
Do Colonic Mucosal Tumor Necrosis Factor Alpha Levels Play a Role in Diverticular Disease? A Systematic Review and Meta-Analysis
Authors: Sabo Cristina Maria , Ismaiel Mohamed , Ismaiel Abdulrahman , Leucuta Daniel-Corneliu , Popa Stefan-Lucian , Grad Simona , Dumitrascu Dan L.
Published: June 2023

Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle–Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI −1.148–2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI −0.883–2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744–30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823–30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.
New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II
Authors: Musri Melina Mara , Venturi Veronica , Ferrer-Cortès Xènia , Romero-Cortadellas Lídia , Hernández Gonzalo , Leoz Pilar , Ricard Andrés María Pilar , Morado Marta , Fernández Valle María del Carmen , Beneitez Pastor David , Ortuño Cabrero Ana , Moreno Gamiz Maite , Senent Peris Leonor , Perez-Valencia Amanda Isabel , Pérez-Montero Santiago , Tornador Cristian , Sánchez Mayka
Published: June 2023

Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones. CDA II is caused by biallelic mutations in the SEC23B gene. In this study, we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel. The newly reported variants in SEC23B include three missenses (p.Thr445Arg, p.Tyr579Cys, and p.Arg701His), one frameshift (p.Asp693GlyfsTer2), and two splicing variants (c.1512-2A>G, and the complex intronic variant c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT in the same allele). Computational analyses of the missense variants indicated a loss of key residue interactions within the beta sheet and the helical and gelsolin domains, respectively. Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation. Reduced SEC23B mRNA expression was only detected in two probands carrying nonsense and frameshift variants; the remaining patients showed either higher gene expression levels or no expression changes at all. The skipping of exons 13 and 14 in the newly reported complex variant c.1512-3delinsTT/c.1512-16_1512-7delACTCTGGAAT results in a shorter protein isoform, as assessed by RT-PCR followed by Sanger sequencing. In this work, we summarize a comprehensive spectrum of SEC23B variants, describe nine new CDA II cases accounting for six previously unreported variants, and discuss innovative therapeutic approaches for CDA II.
Bioactivity Profiling and Quantification of Gastrodin in Gastrodia elata Cultivated in the Field versus Facility via Hyphenated High-Performance Thin-Layer Chromatography
Authors: Mügge Fernanda L. B. , Sim Cheul Muu , Honermeier Bernd , Morlock Gertrud E.
Published: June 2023

Gastrodia elata (Orchidaceae) is native to mountainous areas of Asia and is a plant species used in traditional medicine for more than two thousand years. The species was reported to have many biological activities, such as neuroprotective, antioxidant, and anti-inflammatory activity. After many years of extensive exploitation from the wild, the plant was added to lists of endangered species. Since its desired cultivation is considered difficult, innovative cultivation methods that can reduce the costs of using new soil in each cycle and at the same time avoid contamination with pathogens and chemicals are urgently needed on large scale. In this work, five G. elata samples cultivated in a facility utilizing electron beam-treated soil were compared to two samples grown in the field concerning their chemical composition and bioactivity. Using hyphenated high-performance thin-layer chromatography (HPTLC) and multi-imaging (UV/Vis/FLD, also after derivatization), the chemical marker compound gastrodin was quantified in the seven G. elata rhizome/tuber samples, which showed differences in their contents between facility and field samples and between samples collected during different seasons. Parishin E was also found to be present. Combining HPTLC with on-surface (bio)assays, the antioxidant activity and inhibition of acetylcholinesterase as well as the absence of cytotoxicity against human cells were demonstrated and compared between samples.
Aflatoxin B1 Increases Soluble Epoxide Hydrolase in the Brain and Induces Neuroinflammation and Dopaminergic Neurotoxicity
Authors: Wang Weicang , Wang Yuxin , Wagner Karen M. , Lee Ruth Diana , Hwang Sung Hee , Morisseau Christophe , Wulff Heike , Hammock Bruce D.
Published: June 2023

Parkinson’s disease (PD) is an increasingly common neurodegenerative movement disorder with contributing factors that are still largely unexplored and currently no effective intervention strategy. Epidemiological and pre-clinical studies support the close association between environmental toxicant exposure and PD incidence. Aflatoxin B1 (AFB1), a hazardous mycotoxin commonly present in food and environment, is alarmingly high in many areas of the world. Previous evidence suggests that chronic exposure to AFB1 leads to neurological disorders as well as cancer. However, whether and how aflatoxin B1 contributes to the pathogenesis of PD is poorly understood. Here, oral exposure to AFB1 is shown to induce neuroinflammation, trigger the α-synuclein pathology, and cause dopaminergic neurotoxicity. This was accompanied by the increased expression and enzymatic activity of soluble epoxide hydrolase (sEH) in the mouse brain. Importantly, genetic deletion or pharmacological inhibition of sEH alleviated the AFB1-induced neuroinflammation by reducing microglia activation and suppressing pro-inflammatory factors in the brain. Furthermore, blocking the action of sEH attenuated dopaminergic neuron dysfunction caused by AFB1 in vivo and in vitro. Together, our findings suggest a contributing role of AFB1 to PD etiology and highlight sEH as a potential pharmacological target for alleviating PD-related neuronal disorders caused by AFB1 exposure.
Toxicity of Metal Ions Released from a Fixed Orthodontic Appliance to Gastrointestinal Tract Cell Lines
Authors: Durgo Ksenija , Orešić Sunčana , Rinčić Mlinarić Marijana , Fiket Željka , Jurešić Gordana Čanadi
Published: June 2023

The mechanism of toxicity and cellular response to metal ions present in the environment is still a very current area of research. In this work, which is a continuation of the study of the toxicity of metal ions released by fixed orthodontic appliances, eluates of archwires, brackets, ligatures, and bands are used to test the prooxidant effect, cytotoxicity, and genotoxicity on cell lines of the gastrointestinal tract. Eluates obtained after three immersion periods (3, 7, and 14 days) and with known amounts and types of metal ions were used. Four cell lines—CAL 27 (human tongue), Hep-G2 (liver), AGS (stomach) and CaCo-2 (colon)—were treated with each type of eluate at four concentrations (0.1×, 0.5×, 1.0×, and 2.0×) for 24 h. Most eluates had toxic effects on CAL 27 cells over the entire concentration range regardless of exposure time, while CaCo-2 proved to be the most resistant. In AGS and Hep-G2 cells, all samples tested induced free radical formation, with the highest concentration (2×) causing a decrease in free radicals formed compared to the lowest concentrations. Eluates containing Cr, Mn, and Al showed a slight pro-oxidant effect on DNA (on plasmid φX-174 RF I) and slight genotoxicity (comet assay), but these effects are not so great that the human body could not “resist” them. Statistical analysis of data on chemical composition, cytotoxicity, ROS, genotoxicity, and prooxidative DNA damage shows the influence of metal ions present in some eluates on the toxicity obtained. Fe and Ni are responsible for the production of ROS, while Mn and Cr have a great influence on hydroxyl radicals, which cause single-strand breaks in supercoiled plasmid DNA in addition to the production of ROS. On the other hand, Fe, Cr, Mn, and Al are responsible for the cytotoxic effect of the studied eluates. The obtained results confirm that this type of research is useful and brings us closer to more accurate in vivo conditions.
Tunable Fluorescence via Self-Assembled Switching of AIE-Active Micelle-like Nanoaggregates
Authors: Elsyed Amal Farghal Noreldein , Wong Gah-Lai , Ameen Mohamed , Wu Min-Wei , Chang Cheng-Chung
Published: June 2023

Chemical structures bearing a combination of aggregation-induced emission enhancement (AIEE) and intramolecular charge transfer (ICT) properties attracted the attention of many researchers. Recently, there is an increasing demand to pose tunable AIEE and ICT fluorophores that could present their conformation changes-related emission colors by adjusting the medium polarity. In this study, we designed and synthesized a series of 4-alkoxyphenyl-substituted 1,8-naphthalic anhydride derivatives NAxC using the Suzuki coupling reaction to construct donor–acceptor (D-A)-type fluorophores with alkoxyl substituents of varying carbon chain lengths (x = 1, 2, 4, 6, 12 in NAxC). To explain the observation that molecules with longer carbon chains revealed unusual fluorescence enhancement in water, we study the optical properties and evaluate their locally excited (LE) and ICT states by solvent effects combined with Lippert–Mataga plots. Then, we explored the self-assembly abilities of these molecules in water-organic (W/O) mixed solutions and observed the morphology of its nanostructure using a fluorescence microscope and SEM. The results show that NAxC, x = 4, 6, 12 show different degrees of self-assembly behaviors and corresponding aggregation-induced emission enhancement (AIEE) progresses. At the same time, different nanostructures and corresponding spectral changes can be obtained by adjusting the water ratio in the mixed solution. That is, NAxC compounds present different transitions between LE, ICT and AIEE based on the polarity, water ratio and time changes. We designed NAxC as the structure–activity relationship (SAR) of the surfactant to demonstrate that AIEE comes from the formation of micelle-like nanoaggregates, which causes a restriction of the transfer from the LE state to the ICT state, and micelle formation results in a blue-shift in emission and enhances the intensity in the aggregate state. Among them, NA12C is most likely to form micelles and the most obvious fluorescence enhancement, which will switch over time due to the nano-aggregation transition.
Vista of the Future: Novel Immunotherapy Based on the Human V-Set Immunoregulatory Receptor for Digestive System Tumors
Authors: Chmiel Paulina , Gęca Katarzyna , Michalski Adam , Kłosińska Martyna , Kaczyńska Agnieszka , Polkowski Wojciech P. , Pelc Zuzanna , Skórzewska Magdalena
Published: June 2023

While gastrointestinal tumors remain a multifactorial and prevalent group of malignancies commonly treated surgically in combination with chemotherapy and radiotherapy, advancements regarding immunotherapeutic approaches continue to occur. Entering a new era of immunotherapy focused on overcoming resistance to preceding therapies caused the emergence of new therapeutic strategies. A promising solution surfaces with a V-domain Ig suppressor of T-cell activation (VISTA), a negative regulator of a T-cell function expressed in hematopoietic cells. Due to VISTA’s ability to act as both a ligand and a receptor, several therapeutic approaches can be potentially developed. A broad expression of VISTA was discovered on various tumor-growth-controlling cells, which proved to increase in specific tumor microenvironment (TME) conditions, thus serving as a rationale behind the development of new VISTA-targeting. Nevertheless, VISTA’s ligands and signaling pathways are still not fully understood. The uncertain results of clinical trials suggest the need for future examining inhibitor agents for VISTA and implicating a double immunotherapeutic blockade. However, more research is needed before the breakthrough can be achieved. This review discusses perspectives and novel approaches presented in the current literature. Based on the results of the ongoing studies, VISTA might be considered a potential target in combined therapy, especially for treating gastrointestinal malignancies.
Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer
Authors: Marstrand-Daucé Louis , Lorenzo Diane , Chassac Anaïs , Nicole Pascal , Couvelard Anne , Haumaitre Cécile
Published: June 2023

Adult pancreatic acinar cells show high plasticity allowing them to change in their differentiation commitment. Pancreatic acinar-to-ductal metaplasia (ADM) is a cellular process in which the differentiated pancreatic acinar cells transform into duct-like cells. This process can occur as a result of cellular injury or inflammation in the pancreas. While ADM is a reversible process allowing pancreatic acinar regeneration, persistent inflammation or injury can lead to the development of pancreatic intraepithelial neoplasia (PanIN), which is a common precancerous lesion that precedes pancreatic ductal adenocarcinoma (PDAC). Several factors can contribute to the development of ADM and PanIN, including environmental factors such as obesity, chronic inflammation and genetic mutations. ADM is driven by extrinsic and intrinsic signaling. Here, we review the current knowledge on the cellular and molecular biology of ADM. Understanding the cellular and molecular mechanisms underlying ADM is critical for the development of new therapeutic strategies for pancreatitis and PDAC. Identifying the intermediate states and key molecules that regulate ADM initiation, maintenance and progression may help the development of novel preventive strategies for PDAC.
Therapeutic Benefits of Stem Cells and Exosomes for Sulfur-Mustard-Induced Tissue Damage
Authors: Bosholm Carol Christine , Zhu Hainan , Yu Pengfei , Cheng Kun , Murphy Sean Vincent , McNutt Patrick Michael , Zhang Yuanyuan
Published: June 2023

Sulfur mustard (SM) is a highly toxic chemical agent that causes severe tissue damage, particularly to the eyes, lungs, and skin. Despite advances in treatment, there is a need for more effective therapies for SM-induced tissue injury. Stem cell and exosome therapies are emerging as promising approaches for tissue repair and regeneration. Stem cells can differentiate into multiple cell types and promote tissue regeneration, while exosomes are small vesicles that can deliver therapeutic cargo to target cells. Several preclinical studies demonstrated the potential of stem cell, exosome, or combination therapy for various tissue injury, showing improvements in tissue repairing, inflammation, and fibrosis. However, there are also challenges associated with these therapies, such as the requirement for standardized methods for exosome isolation and characterization, the long-term safety and efficacy and reduced SM-induced tissue injury of these therapies. Stem cell or exosome therapy was used for SM-induced eye and lung injury. Despite the limited data on the use for SM-induced skin injury, this therapy is a promising area of research and may offer new treatment options in the future. In this review, we focused on optimizing these therapies, evaluating their safety and efficacy, and comparing their efficacy to other emerging therapeutic approaches potentially for SM-induced tissue injury in the eye, lung, and skin.
Adaptive Changes in Detoxification Metabolism and Transmembrane Transport of Bombyx mori Malpighian Tubules to Artificial Diet
Authors: Liu Lijing , Zhao Dongchao , Wang Genhong , He Qingxiu , Song Yuwei , Jiang Yulu , Xia Qingyou , Zhao Ping
Published: June 2023

The high adaptability of insects to food sources has contributed to their ranking among the most abundant and diverse species on Earth. However, the molecular mechanisms underlying the rapid adaptation of insects to different foods remain unclear. We explored the changes in gene expression and metabolic composition of the Malpighian tubules as an important metabolic excretion and detoxification organ in silkworms (Bombyx mori) fed mulberry leaf and artificial diets. A total of 2436 differentially expressed genes (DEGs) and 245 differential metabolites were identified between groups, with the majority of DEGs associated with metabolic detoxification, transmembrane transport, and mitochondrial function. Detoxification enzymes, such as cytochrome P450 (CYP), glutathione-S-transferase (GST), and UDP-glycosyltransferase, and ABC and SLC transporters of endogenous and exogenous solutes were more abundant in the artificial diet group. Enzyme activity assays confirmed increased CYP and GST activity in the Malpighian tubules of the artificial diet-fed group. Metabolome analysis showed increased contents of secondary metabolites, terpenoids, flavonoids, alkaloids, organic acids, lipids, and food additives in the artificial diet group. Our findings highlight the important role of the Malpighian tubules in adaptation to different foods and provide guidance for further optimization of artificial diets to improve silkworm breeding.