bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxanthine guanine phosphoribosyl transferases SmHGPRTases functional roles in Schistosoma mansoni
Authors: Batista Izabella Cristina Andrade , Gava Sandra Grossi , Tavares Naiara Clemente , Calzavara-Silva Carlos Eduardo , Mourão Marina Moraes
Published: December 2022

Introduction

Extracellular/environmental stimuli trigger cellular responses to allow Schistosoma sp. parasites adaptation and decide development and survival fate. In this context, signal transduction involving eukaryotic protein kinases (ePKs) has an essential role in regulatory mechanisms. Functional studies had shown the importance of MAPK pathway for Schistosoma mansoni development. In addition, early studies demonstrated that Smp38 MAPK regulates the expression of a large set of genes, among them the hypoxanthine-guanine phosphoribosyl transferase 1 (SmHGPRTase 1, Smp_103560), a key enzyme in the purine salvage pathway that is part of a family comprising five different proteins.

Methods

First, the regulation of this gene family by the MAPKs pathways was experimentally verified using Smp38-predicted specific inhibitors. In silico analysis showed significant differences in the predicted structure and the domain sequence among the schistosomal HGPRTase family and their orthologs in humans. In order to interrogate the HGPRTases (Smp_103560, Smp_148820, Smp_168500, Smp_312580 and Smp_332640, henceforth SmHGPRTase −1, −2, −3, −4, −5) functional roles, schistosomula, sporocysts, and adult worms were knocked-down using specific dsRNAs.

Results

Our results suggest that SmHGPRTases activity has an essential role in sporocysts and schistosomula development since significant differences in viability, size, and/ or shape were observed after the in vitro knockdown. Also, the knockdown of SmHGPRTases in schistosomula influenced the ovary development and egg maturation in female adult worms during mammalian infection. We also observed alterations in the movement of female adult worms knocked-down in vitro. Most of these results were shown when all gene family members were knocked-down simultaneously, suggesting a redundant function among them.

Discussion

Thus, this study helps to elucidate the functional roles of the SmHGPRTase gene family in the S. mansoni life cycle and provides knowledge for future studies required for schistosomiasis treatment and control.
On the effect of hippocampal c-Jun N-terminal kinase inhibition on object recognition memory
Authors: Rossato Janine I. , Radiske Andressa , Gonzalez Maria Carolina , Bevilaqua Lia R. M. , Cammarota Martín
Published: December 2022

c-Jun N-terminal kinase (JNK) phosphorylates the transcription factor c-Jun in response to stress stimuli and contributes to both hippocampal synaptic plasticity and memory processing in mammals. Object recognition memory (ORM) is essential for remembering facts and events. In rodents, ORM consolidation and reconsolidation require a functional hippocampus. However, the possible involvement of hippocampal JNK on ORM processing has not yet been studied. Here we show that when injected into dorsal CA1 5 min, but not 6 h, after training adult male rats in the novel object recognition learning task, the JNK inhibitor SP600125 impaired ORM for at least 7 days without affecting exploratory activity, short-term ORM retention, or the functional integrity of the hippocampus. SP600125 did not hinder ORM retention when given in CA1 after a memory reactivation session carried out 24 h post-training in the presence of the same two objects presented during the training session, but caused time-dependent amnesia when one of the objects presented at training was replaced by a different but behaviorally equivalent novel one. Taken together, our results indicate that hippocampal JNK activity is necessary for ORM consolidation and reconsolidation but not for ORM recall or short-term retention.
Mitochondrial quality control in the brain: The physiological and pathological roles
Authors: Shen Xurui , Sun Peixin , Zhang Hao , Yang Hanting
Published: December 2022

The human brain has high energetic expenses and consumes over 20% of total oxygen metabolism. Abnormal brain energy homeostasis leads to various brain diseases. Among multiple factors that contribute to these diseases, mitochondrial dysfunction is one of the most common causes. Maintenance of mitochondrial integrity and functionality is of pivotal importance to brain energy generation. Mitochondrial quality control (MQC), employing the coordination of multiple mechanisms, is evolved to overcome many mitochondrial defects. Thus, not surprisingly, aberrant mitochondrial quality control results in a wide range of brain disorders. Targeting MQC to preserve and restore mitochondrial function has emerged as a promising therapeutic strategy for the prevention and treatment of brain diseases. Here, we set out to summarize the current understanding of mitochondrial quality control in brain homeostasis. We also evaluate potential pharmaceutically and clinically relevant targets in MQC-associated brain disorders.
Case report: Dramatic response to pralsetinib in an elderly patient with advanced RET-fusion positive papillary thyroid carcinoma
Authors: Nannini Margherita , Repaci Andrea , Ricco Gianluca , Ianni Manuela , Golemi Arber , Maiolo Vincenzo , Ferrari Marco , Natali Filippo , Rizzini Elisa Lodi , Monari Fabio , Solaroli Erica , De Leo Antonio , Maloberti Thais , Pantaleo Maria A. , De Biase Dario , Tallini Giovanni
Published: December 2022

We are recently faced with a progressive evolution of the therapeutic paradigm for radioiodine refractory differentiated thyroid cancer (RAI-R DTC), since the advent of tissue agnostic inhibitors. Thus, tumor genotype assessment is always more relevant and is playing a crucial role into clinical practice. We report the case of an elderly patient with advanced papillary thyroid carcinoma (PTC) harboring RET-CCDC6 fusion with four co-occurring mutations involving PI3KCA, TP53, and hTERT mutations, treated with pralsetinib under a compassionate use program. Despite the high histological grade and the coexistence of aggressive RET co-mutations, an impressive metabolic and structural tumor response has been obtained, together with a patient’s prolonged clinical benefit. A timely comprehensive molecular testing of those cases wild-type for the common thyroid carcinoma BRAF V600E-like and RAS-like driver mutations may uncover actionable gene rearrangements that can be targeted by highly selective inhibitors with great potential benefit for the patients.
DCE-MRI and DWI can differentiate benign from malignant prostate tumors when serum PSA is ≥10 ng/ml
Authors: Sun Hongmei , Du Fengli , Liu Yan , Li Qian , Liu Xinai , Wang Tongming
Published: December 2022

Background

This study investigated the diagnostic utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) parameters for distinguishing between benign and malignant prostate tumors when serum prostate-specific antigen (PSA) level is ≥10 ng/ml.

Methods

Patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with serum PSA ≥10 ng/ml before treatment were recruited. Transrectal ultrasound-guided biopsy or surgery was performed for tumor classification and patients were stratified accordingly into PCa and BPH groups. Patients underwent DCE-MRI and DWI scanning and the transfer constant (Ktrans), rate constant (Kep), fractional volume of the extravascular extracellular space, plasma volume (Vp), and Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) score were determined. The apparent diffusion coefficient (ADC) was calculated from DWI. The diagnostic performance of these parameters was assessed by receiver operating characteristic (ROC) curve analysis, and those showing a significant difference between the PCa and BPH groups were combined into a multivariate logistic regression model for PCa diagnosis. Spearman’s correlation was used to analyze the relationship between Gleason score and imaging parameters.

Results

The study enrolled 65 patients including 32 with PCa and 33 with BPH. Ktrans (P=0.006), Kep (P=0.001), and Vp (P=0.009) from DCE-MRI and ADC (P<0.001) from DWI could distinguish between the 2 groups when PSA was ≥10 ng/ml. PI-RADS score (area under the ROC curve [AUC]=0.705), Ktrans (AUC=0.700), Kep (AUC=0.737), Vp (AUC=0.688), and ADC (AUC=0.999) showed high diagnostic performance for discriminating PCa from BPH. A combined model based on PI-RADS score, Ktrans, Kep, Vp, and ADC had a higher AUC (1.000), with a sensitivity of 0.998 and specificity of 0.999. Imaging markers showed no significant correlation with Gleason score in PCa.

Conclusion

DCE-MRI and DWI parameters can distinguish between benign and malignant prostate tumors in patients with serum PSA ≥10 ng/ml.
Do proton pump inhibitors affect the effectiveness of chemotherapy in colorectal cancer patients? A systematic review with meta-analysis
Authors: Lin Wan-Ying , Wang Shih-Syuan , Kang Yi-No , Porpiglia Andrea S. , Chang Yu , Huang Chin-Hsuan , Bhimani Ronak , Abdul-Lattif Eahab , Azmat Muneeba , Wang Tsu-Hsien , Lin Yu-Shiuan , Chang Yu-Cheng , Chi Kuan-Yu
Published: December 2022

Proton pump inhibitors (PPI), one of the most commonly prescribed medications, carry a myriad of adverse events. For colorectal cancer (CRC) patients, it still remains unclear whether the concurrent use of proton pump inhibitors (PPI) would negatively affect chemotherapy. PubMed, Medline, Embase, and Cochrane Library were searched from inception to 10 June 2022, to identify relevant studies involving CRC patients receiving chemotherapy and reporting comparative survival outcomes between PPI users and non-users. Meta-analyses were performed using random-effects models. We identified 16 studies involving 8,188 patients (PPI = 1,789; non-PPI = 6,329) receiving either capecitabine-based or fluorouracil-based regimens. The overall survival (HR, 1.02; 95% CI, 0.91 to 1.15; I2 = 0%) and progression-free survival (HR, 1.15; 95% CI, 0.98 to 1.35; I2 = 29%) were similar between PPI users and non-users in patients taking capecitabine-based regimens, with low statis-tical heterogeneity. Although the subgroup analysis indicated that early-stage cancer patients taking capecitabine monotherapy with concurrent PPI had a significantly higher disease progression rate (HR, 1.96; 95% CI, 1.21 to 3.16; I2 = 0%) than those who did not use PPIs, both groups had comparable all-cause mortality (HR, 1.31; 95% CI, 0.75 to 2.29; I2 = 0%). On the other hand, there was little difference in both OS and PFS in both early- and end-stage patients taking capecitabine combination therapy between PPI users and non-users. Conversely, the use of concomitant PPI in patients taking fluorouracil-based regimens contributed to a marginally significant higher all-cause mortality (HR, 1.18; 95% CI, 1.00 to 1.40; I2 = 74%), but with high statistical heterogeneity. In conclusion, PPI has little survival influence on CRC patients treated with capecitabine-based regimens, especially in patients taking capecitabine combination therapy. Thus, it should be safe for clinicians to prescribe PPI in these patients. Although patients treated with fluorouracil-based regimens with concomitant PPI trended toward higher all-cause mortality, results were subject to considerable heterogeneity.

Systematic Review Registration: identifier https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022338161
Role of omega-3 fatty acids in the prevention and treatment of cardiovascular Diseases: A consensus statement from the Experts’ Committee Of National Society Of Cardiometabolic Medicine
Authors: Li Jian-Jun , Dou Ke-Fei , Zhou Zhi-Guang , Zhao Dong , Ye Ping , Zhao Jia-Jun , Guo Li-Xin
Published: December 2022

Low-density lipoprotein cholesterol (LDL-C) has been considered as the primary target for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, there are still residual cardiovascular risks in some patients even if LDL-C achieves the target level. Emerging evidence suggestes that elevated triglyceride (TG) level or triglyceride-rich lipoprotein (TRL) cholesterol (TRL-C) is one of the important components of the residual cardiovascular risks. Omega-3 fatty acids have been shown to be one of the effective drugs for reducing TG. However, its efficacy in reducing the risk of ASCVD is inconsistent in large randomized clinical trials. There is lack of consensus among Experts regarding the application of omega-3 fatty acids in cardiovascular diseases including heart failure, arrhythmia, cardiomyopathy, hypertension, and sudden death. Hence, the current consensus will comprehensively and scientifically present the detailed knowledge about the omega-3 fatty acids from a variety of aspects to provide a reference for its management of omega-3 fatty acids application in the Chinese population.
Functional analysis of CqPORB in the regulation of chlorophyll biosynthesis in Chenopodium quinoa
Authors: Li Chao , Ran Minyuan , Liu Jianwei , Wang Xiaoxiao , Wu Qingbing , Zhang Qiang , Yang Jing , Yi Feng , Zhang Heng , Zhu Jian-Kang , Zhao Chunzhao
Published: December 2022

Protochlorophyllide oxidoreductase (POR) plays a key role in catalyzing the light-dependent reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide), and thus promotes the transit from etiolated seedlings to green plants. In this study, by exploring ethyl methanesulfonate (EMS)-mediated mutagenesis in Chenopodium quinoa NL-6 variety, we identified a mutant nl6-35 that displays faded green leaf and reduced chlorophyll (Chl) and carotenoid contents. Bulk segregant analysis (BSA) revealed that a mutation in CqPORB gene is genetically associated with the faded green leaf of the nl6-35 mutant. Further study indicates that the nl6-35 mutant exhibits abnormal grana stacks and compromised conversion of Pchlide to Chlide upon illumination, suggesting the important role of CqPORB in producing photoactive Pchlide. Totally three CqPOR isoforms, including CqPORA, CqPORA-like, and CqPORB are identified in NL-6 variety. Transcriptional analysis shows that the expression of all these three CqPOR isoforms is regulated in light- and development-dependent manners, and in mature quinoa plants only CqPORB isoform is predominantly expressed. Subcellular localization analysis indicates that CqPORB is exclusively localized in chloroplast. Together, our study elucidates the important role of CqPORB in the regulation of Chl biosynthesis and chloroplast development in quinoa.
The Palestinian human right to full Israeli citizenship: Between settler colonialism and a hard place
Authors: Samuel M.T.
Published: December 2022

This article examines the significance of a legal analysis supporting the recognition of a Palestinian human right to Israeli citizenship for the advancement of equality in Israel-Palestine. It does so by assessing the workings of Israeli citizenship in accordance with the theoretical frameworks of the nation-state and settler colonialism and in light of the one-state reality. The article demonstrates the importance of treating the two frameworks as complementary, rather than mutually exclusive, in analyses involving Palestinian rights. It argues that the struggle for Palestinian equality is not only a legal one but also a moral one, the success of which depends upon a nuanced understanding of the functioning of law in settler colonialism.
The impact financial resources on implementation of large-scale electronic health records in the Saudi Arabia's primary healthcare centers: Mixed methods
Authors: Alzghaibi Haitham , Mughal Yasir Hayat , Alkhamees Mohammad , Alasqah Ibrahim , Alhlayl Adel Sulaiman , Alwheeb Mohammed Hamed , Alrehiely Majedah
Published: December 2022

Introduction

There is worldwide demand for the implementation of electronic health systems and a transformation to electronic transactions in healthcare organizations. This move to e-health transformation stems from the perceived positive impact that e-health systems have in improving the quality of healthcare and, in turn, reducing expenses. Despite this, more than half of previous Electronic Health Record System (EHRS) implementation projects have failed due to several barriers and challenges such as cost.

Aim of the study

To evaluate the impact of financial resources (FR) on the implementation of the EHRS in PHCs in SA.

Methods

A mixed methods approach was implemented. SPSS and AMOS-SEM are used to test reliability and validity and hypotheses. Thirty-one (59%) out of 51 policy makers at the MoH filled and returned the questionnaire while 13 policymakers were interviewed using semi-structure interviews.

Results

Results revealed that both measurement model and structural models met the threshold. All scales are found reliable and valid. Furthermore financial resources have positive impact on EHRS implementation. Findings from both studies show that financial resources have a very positive impact to facilitate large-scale EHRs implementation and overcome barriers that may lead to the failure of the project.
A process evaluation of an on-line fall prevention and management program for individuals who use wheelchairs or scooters living with multiple sclerosis
Authors: Van Denend Toni , Peterson Elizabeth W. , McArthur Amy Roder , Yarnot Rebecca , Kish Jacqueline , Steinkellner Sydney , Sandhu Arman , Rice Laura A.
Published: December 2022

Background

Falls and resulting injury are a significant concern for individuals living with multiple sclerosis (MS) that use a wheelchair and/or scooter to support mobility. Effective fall prevention efforts are vital to support the health, wellbeing, and participation for these individuals.

Aims

This study reports the findings from the process evaluation conducted in association with a pilot study evaluating the efficacy of Individualized Reduction of FaLLs-Online (iROLL-O), an online, group fall prevention, and management program specifically designed for community-based people living with multiple sclerosis (pwMS) who are full-time wheelchair or scooter users.

Methods

A mixed-methods process evaluation was conducted, with specific attention to the impact of online delivery on intervention implementation, participant satisfaction, and mechanisms of change (MOC). Multiple data sources were utilized, including post-session and post-intervention participant and trainer feedback forms and participant qualitative interview data. Descriptive analysis was conducted using Microsoft Excel. Close-ended questions were analyzed by examining five-point Likert scale responses. Qualitative interview data was explored using thematic analysis.

Results

Twelve participants and three trainers (one occupational therapist and two physical therapists) contributed to the study. Online delivery did not compromise session fidelity, which averaged 95%. No significant adaptations to the intervention were made during delivery. Participant satisfaction was high at 4.6/5.0. Post-course Trainer Feedback Forms indicate trainer satisfaction with the group dynamic, ability to address unique group needs, and program content. Reach improved with online delivery as transportation barriers were removed and recruitment from a broader geographic area was enabled. Three themes reflecting key MOC emerged from the analysis: group context, motivation for participant engagement, and the multifaceted nature of the program. The COVID-19 pandemic was identified as a contextual factor impacting community participation. Both participants and trainers identified the group dynamic as a strength. The trainers valued the program's flexibility in allowing them to address individual and/or group-specific fall prevention needs.

Conclusion

Feedback from key stakeholders was essential to a meaningful process evaluation. Online delivery supported program implementation, including reach, and resulted in high levels of satisfaction among participants and trainers. Future iterations should aim to uphold the positive group context, recruit, and train skilled interventionists who are licensed as occupational or physical therapists and continue to provide the program's diverse approach to fall prevention and management.
Impact of the COVID-19 pandemic on risk of burn-out syndrome and recovery need among secondary school teachers in Flanders: A prospective study
Authors: De Laet Hannah , Verhavert Yanni , De Martelaer Kristine , Zinzen Evert , Deliens Tom , Van Hoof Elke
Published: December 2022

Background

Due to the COVID-19 pandemic, schools were closed, teachers had to teach from home and after a while, they had to return to the classroom while the pandemic was still on-going. Even before the pandemic, teachers were already more at risk for burn-out syndrome compared to the general population. Furthermore, not much research pertaining to this population has been carried out during the pandemic and so the impact of the pandemic on teachers' risk of burn-out syndrome and recovery need remains unclear. The aim of the current study was to fill this knowledge gap and map out the impact on risk of burn-out syndrome and recovery need at different time points during the pandemic.

Methods and findings

At baseline, 2,167 secondary school teachers in Flanders were included in this prospective study. Questionnaire data were obtained at ten different time points between September 2019 and August 2021. To assess risk of burn-out syndrome and its dimensions, the Utrecht Burn-out Scale for Teachers was administered. Need for recovery was assessed using questions adopted from the Short Inventory to Monitor Psychosocial Hazards. The results revealed an initial positive effect of the first lockdown (Mar/Apr 2020) with a decrease in risk of burn-out syndrome [Odds ratio (OR) Jan/Feb 2020–Mar/Apr 2020 = 0.33, p < 0.001], emotional exhaustion (EMM Jan/Feb 2020–Mar/Apr 2020 = −0.51, p < 0.001), depersonalization (EMM Jan/Feb 2020–Mar/Apr 2020 = −0.13, p < 0.001) and recovery need [Estimated marginal mean (EMM) Jan/Feb 2020–Mar/Apr 2020 = −0.79, p < 0.001]. No significant effect on personal accomplishment was found (p = 0.410). However, as the pandemic went on, higher risk of burn-out syndrome, emotional exhaustion, depersonalization and recovery need, and lower personal accomplishment were observed.

Conclusions

Despite the initial positive impact on risk of burn-out syndrome, its dimensions and recovery need, a negative long-term impact of the COVID-19 pandemic became visible. This study highlights once again the importance for interventions to reduce teachers' risk of burn-out syndrome, especially in such difficult times as a pandemic.
Smoking Ban Law in Chile: Impact in Newborns’ Birth Weight by Women’s Age Groups and by City Population Density
Authors: Valentino Giovanna , Ortigoza Ana , Rodriguez Osiac Lorena , Doberti Tamara , Mullachery Pricila , Nazzal Carolina
Published: December 2022

Objectives: We examined the short-term impact of the Smoking Ban Law (SBL) enacted in Chile in 2013 on low birth weight (LBW) rates in cities and its differential effects by different maternal age groups and city density.

Methods: We included 885,880 live births from 21 Chilean cities of ≥100,000 inhabitants. We examined the smoking and LBW prevalence distribution before and after the SBL. Through Poisson mixed effect models, we determined whether a meaningful change in LBW rate occurred after SBL implementation in the whole sample and stratified by city population density and maternal age group.

Results: LBW prevalence remained stable before and after the SBL implementation (6.1% and 6.3%, respectively), while women’s smoking prevalence had a relative reduction of 25.9% (p < 0.00001). No significant changes in LBW rate occurred after the implementation of SBL in the total sample or stratified by city density tertiles or maternal age groups.

Conclusion: SBL implementation did not show short-term impact on LBW rate in Chile. Further studies need to examine long-term impact of SBL on low birthweight.
Antimicrobial and Antibiofilm Effect of 4,4′-Dihydroxy-azobenzene against Clinically Resistant Staphylococci
Authors: Pérez-Aranda María , Pajuelo Eloísa , Navarro-Torre Salvadora , Pérez-Palacios Patricia , Begines Belén , Rodríguez-Llorente Ignacio D. , Torres Yadir , Alcudia Ana
Published: December 2022

The spread of antibiotic resistance among human and animal pathogens is one of the more significant public health concerns. Moreover, the restrictions on the use of particular antibiotics can limit the options for the treatment of infections in veterinary clinical practice. In this context, searching for alternative antimicrobial substances is crucial nowadays. In this study, 4,4′-dihydroxy-azobenzene (DHAB) was tested for its potential in vitro as an antimicrobial agent against two relevant human and animal pathogens, namely Staphylococcus aureus and Staphylococcus pseudintermedius. The values of minimal inhibitory concentration (MIC) were 64 and 32 mg/L respectively, and they comparable to other azo compounds of probed antimicrobial activity. In addition, the minimal bactericidal concentrations (MCB) were 256 and 64 mg/L. The mechanism by which DHAB produces toxicity in staphylococci has been investigated. DHAB caused membrane damage as revealed by the increase in thiobarbituric acid reactive substances (TBARS) such as malondialdehyde. Furthermore, differential induction of the enzymes peroxidases and superoxide dismutase in S. aureus and S. pseudintermedius suggested their prevalent role in ROS-scavenging due to the oxidative burst induced by this compound in either species. In addition, this substance was able to inhibit the formation of biofilms by both bacteria as observed by colorimetric tests and scanning electron microscopy. In order to assess the relevance of DHAB against clinical strains of MRSA, 10 clinical isolates resistant to either methicillin or daptomycin were assayed; 80% of them gave values of CMI and CMB similar to those of the control S. aureus strain. Finally, cutaneous plasters containing a composite formed by an agar base supplemented with DHAB were designed. These plasters were able to inhibit in vitro the growth of S. aureus and S. pseudintermedius, particularly the later, and this suggests that this substance could be a promising candidate as an alternative to antibiotics in the treatment of animal skin infections, as it has been proven that the toxicity of this substance is very low particularly at a dermal level.
Oxidative Stress-Induced Overactivation of Frog Eggs Triggers Calcium-Dependent Non-Apoptotic Cell Death
Authors: Tokmakov Alexander A. , Morichika Yudai , Teranishi Ryuga , Sato Ken-Ichi
Published: December 2022

Excessive activation of frog eggs (overactivation) is a pathological process that renders eggs unfertilizable. Its physiological inducers are unknown. Previously, oxidative stress was shown to cause time- and dose-dependent overactivation of Xenopus laevis frog eggs. Here, we demonstrate that the oxidative stress-induced egg overactivation is a calcium-dependent phenomenon which can be attenuated in the presence of the selective calcium chelator BAPTA. Degradation of cyclin B2, which is known to be initiated by calcium transient in fertilized or parthenogenetically activated eggs, can also be observed in the overactivated eggs. Decline in mitochondrial membrane potential, ATP depletion and termination of protein synthesis manifest in the eggs within one hour of triggering overactivation. These intracellular events occur in the absence of caspase activation. Furthermore, plasma membrane integrity is compromised in the overactivated eggs, as evidenced by ATP leakage and egg swelling. In sum, our data demonstrate that oxidative stress-induced overactivation of frog eggs causes fast and dramatic disruption of cellular homeostasis, resulting in robust and expedited cell death by a calcium-dependent non-apoptotic mechanism.
Eco-Efficient Quantification of Glucosinolates in Camelina Seed, Oil, and Defatted Meal: Optimization, Development, and Validation of a UPLC-DAD Method
Authors: Meza Salvador , Zhou Yucheng , Chastain Jonathan , Yang Yingying , Cheng Hope Hua , Iassonova Diliara , Rivest Jason , You Hong
Published: December 2022

Camelina sativa (camelina) seed, oil, and defatted meal are widely used for food, animal feed, and other purposes. The accurate quantification of camelina glucosinolates is critical as their functionalities are highly dose-dependent. The classic quantification of glucosinolates in camelina products involves tedious desulfation steps, toxic reagents, and a lengthy instrument time because glucosinolates are easy to degrade and subject to interference in the liquid chromatography. Thus, we developed and validated an eco-efficient UPLC-DAD method for determining glucoarabin (GS9), glucocamelinin (GS10), and homoglucocamelinin (GS11) in camelina seed, oil, and defatted meal. Glucosinolates were extracted using 80% cold methanol to denature myrosinase, and were separated by an HSS T3 column without desulfation. Glucotropaeolin was used as an internal standard to track analyte degradation and loss during sample preparation. The method has shown high precision (relative standard deviations ranging from 4.12% to 6.54%) and accuracy (>94.4% spike recovery) for GS9-11, and all validation parameters passed the industry-consensus AOAC Appendix F criteria. To our best knowledge, this is the first eco-efficient and low-cost analytical method that is validated against strict AOAC criteria for the quantification of intact camelina glucosinolates. The method is suitable to be adopted as a new industrial testing standard to assist in the quality control of camelina products.
Leaves of Cedrela sinensis Attenuate Chronic Unpredictable Mild Stress-Induced Depression-like Behavior via Regulation of Hormonal and Inflammatory Imbalance
Authors: Jeong Hye Rin , Kim Jong Min , Lee Uk , Kang Jin Yong , Park Seon Kyeong , Lee Hyo Lim , Moon Jong Hyun , Kim Min Ji , Go Min Ji , Heo Ho Jin
Published: December 2022

This study aimed to evaluate the protective effects of ethyl acetate fraction from Cedrela sinensis (EFCS) against chronic unpredictable mild stress (CUMS)-induced behavioral dysfunction and stress response in C57BL/6 mice. The physiological compounds of EFCS were identified as rutin, isoquercitrin, ethyl gallate, quercitrin, kaempferol-3-O-rhamnoside, and ethyl digallate, using UPLC-Q-TOF/MSE. To evaluate the neuroprotective effect of EFCS, H2O2− and corticosterone-induced neuronal cell viability was conducted in human neuroblastoma MC-IXC cells. It was found that EFCS alleviated depression-like behavior by conducting the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). EFCS inhibited mitochondrial dysfunction related to neuronal energy metabolism by regulating reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and ATP contents in brain tissue. In addition, the administration of EFCS regulated the stress hormones in serum. EFCS regulated stress-related indicators such as CRF, ACTH, CYP11B1, and BDNF. Moreover, EFCS downregulated the inflammatory responses and apoptosis proteins such as caspase-1, TNF-α, IL-1β, p-JNK, BAX, and p-tau in brain tissues. These results suggest that EFCS might be a potential natural plant material that alleviates CUMS-induced behavior disorder by regulating inflammation in brain tissue against CUMS-induced depression.
Bioprocess Economic Modeling: Decision Support Tools for the Development of Stem Cell Therapy Products
Authors: Salvador William O. S. , Ribeiro Inês A. B. , Nogueira Diogo E. S. , Ferreira Frederico C. , Cabral Joaquim M. S. , Rodrigues Carlos A. V.
Published: December 2022

Over recent years, the field of cell and gene therapy has witnessed rapid growth due to the demonstrated benefits of using living cells as therapeutic agents in a broad range of clinical studies and trials. Bioprocess economic models (BEMs) are fundamental tools for guiding decision-making in bioprocess design, being capable of supporting process optimization and helping to reduce production costs. These tools are particularly important when it comes to guiding manufacturing decisions and increasing the likelihood of market acceptance of cell-based therapies, which are often cost-prohibitive because of high resource and quality control costs. Not only this, but the inherent biological variability of their underlying bioprocesses makes them particularly susceptible to unforeseen costs arising from failed or delayed production batches. The present work reviews important concepts concerning the development of bioprocesses for stem cell therapy products and highlights the valuable role which BEMs can play in this endeavor. Additionally, some theoretical concepts relevant to the building and structuring of BEMs are explored. Finally, a comprehensive review of the existent BEMs so far reported in the scientific literature for stem cell-related bioprocesses is provided to showcase their potential usefulness.
Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma
Authors: Tümen Deniz , Heumann Philipp , Gülow Karsten , Demirci Cagla-Nur , Cosma Lidia-Sabina , Müller Martina , Kandulski Arne
Published: December 2022

Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC. Treatment options for HCC are strictly dependent on tumor staging and liver function, which are structured by the updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, and liver transplantation are valid and curative therapeutic options for early tumor stages. For multifocal and metastatic diseases, systemic therapy is recommended. While Sorafenib had been the standalone HCC first-line therapy for decades, recent developments had led to the approval of new treatment options as first-line as well as second-line treatment. Anti-PD-L1 directed combination therapies either with anti-VEGF directed agents or with anti-CTLA-4 active substances have been implemented as the new treatment standard in the first-line setting. However, data from clinical trials indicate different responses on specific therapeutic regimens depending on the underlying pathogenesis of hepatocellular cancer. Therefore, histopathological examinations have been re-emphasized by current international clinical guidelines in addition to the standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. In this review, we emphasize the current knowledge on molecular pathogenesis of hepatocellular carcinoma. On this occasion, the treatment sequences for early and advanced tumor stages according to the recently updated Barcelona Clinic Liver Cancer classification system and the current algorithm of systemic therapy (first-, second-, and third-line treatment) are summarized. Furthermore, we discuss novel precautional and pre-therapeutic approaches including therapeutic vaccination, adoptive cell transfer, locoregional therapy enhancement, and non-coding RNA-based therapy as promising treatment options. These novel treatments may prolong overall survival rates in regard with quality of life and liver function as mainstay of HCC therapy.
Screening of Potential Plasticizer Alternatives for Their Toxic Effects on Male Germline Stem Cells
Authors: Zhang Xiangfan , Nagano Makoto
Published: December 2022

Plasticizers give flexibility to a wide range of consumer and medical plastic products. Among them, phthalate esters are recognized as endocrine disruptors that target male reproductive functions. With this notion, past studies designed and produced alternative plasticizers that could replace phthalates with limited toxicity to the environment and to male reproductive functions. Here, we focused on one reproductive cell type that was not investigated in past studies—spermatogonial stem cells (SSCs)—and examined in vitro the effects on 22 compounds (seven plasticizers currently in use and 15 newly synthesized potential alternative plasticizers) for their effects on SSCs. Our in vitro compound screening analyses showed that a majority of the compounds examined had a limited level of toxicity to SSCs. Yet, some commercial plasticizers and their derivatives, such as DEHP (di-(2-ethylhexyl) phthalate) and MEHP (mono-(2-ethylhexyl) phthalate), were detrimental at 10−5 to 10−4 M. Among new compounds, some of maleate- and fumarate-derivatives showed toxic effects. In contrast, no detrimental effects were detected with two new compounds, BDDB (1,4 butanediol dibenzoate) and DOS (dioctyl succinate). Furthermore, SSCs that were exposed to BDDB and DOS in vitro successfully established spermatogenic colonies in testes of recipient mice after transplantation. These results demonstrate that SSC culture acts as an effective platform for toxicological tests on SSC function and provide novel information that two new compounds, BDDB and DOS, are alternative plasticizers that do not have significant negative impacts on SSC integrity.
gldc Is Essential for Renal Progenitor Patterning during Kidney Development
Authors: Weaver Nicole E. , Healy Allison , Wingert Rebecca A.
Published: December 2022

The glycine cleavage system (GCS) is a complex located on the mitochondrial membrane that is responsible for regulating glycine levels and contributing one-carbon units to folate metabolism. Congenital mutations in GCS components, such as glycine decarboxylase (gldc), cause an elevation in glycine levels and the rare disease, nonketotic hyperglycinemia (NKH). NKH patients suffer from pleiotropic symptoms including seizures, lethargy, mental retardation, and early death. Therefore, it is imperative to fully elucidate the pathological effects of gldc dysfunction and glycine accumulation during development. Here, we describe a zebrafish model of gldc deficiency that recapitulates phenotypes seen in humans and mice. gldc deficient embryos displayed impaired fluid homeostasis suggesting renal abnormalities, as well as aberrant craniofacial morphology and neural development defects. Whole mount in situ hybridization (WISH) revealed that gldc transcripts were highly expressed in the embryonic kidney, as seen in mouse and human repository data, and that formation of several nephron segments was disrupted in gldc deficient embryos, including proximal and distal tubule populations. These kidney defects were caused by alterations in renal progenitor populations, revealing that the proper function of Gldc is essential for the patterning of this organ. Additionally, further analysis of the urogenital tract revealed altered collecting duct and cloaca morphology in gldc deficient embryos. Finally, to gain insight into the molecular mechanisms underlying these disruptions, we examined the effects of exogenous glycine treatment and observed analogous renal and cloacal defects. Taken together, these studies indicate for the first time that gldc function serves an essential role in regulating renal progenitor development by modulating glycine levels.
SERS-TLC Device for Simultaneous Determination of Sulfamethoxazole and Trimethoprim in Milk
Authors: Soares Frederico Luis Felipe , Junior Benedito Roberto de Alvarenga , Carneiro Renato Lajarim
Published: December 2022

The aim of this work is to develop a device based on thin-layer chromatography coupled with surface-enhanced Raman spectroscopy (TLC-SERS) to analyze sulfamethoxazole (SMX) and trimethoprim (TMP) in commercial milk samples using chemometric tools. Samples were eluted in TLC plates, and a central composite design (CCD) of two factors was performed to optimize the gold nanoparticle dispersion on TLC plates for SERS, aiming at the detection of both drugs at concentrations close to their maximum residual limits (MRLs). Following the optimization, hyperspectral images from the SERS were captured of the TLC plates. Multivariate curve resolution (MCR-ALS) and independent component analysis (ICA) chemometric techniques were used to extract the signals of the analytes. All the samples presented recovery values of 81–128% for TMP. The quantification of SMX was not possible due to SERS suppression by an interferent. However, it was possible to detect SMX at a concentration of two times the MRL (8.0 × 10−7 mol·L−1). The results demonstrate that the TLC-SERS device is a potential tool for the quantification of TMP and the detection of SMX in milk.
Bioelectrical Impedance Analysis-Derived Phase Angle and Body Composition Are Predictors of Health-Related Fitness in Children and Adolescents with Obesity
Authors: Ballarin Giada , Licenziati Maria Rosaria , Alicante Paola , Di Vincenzo Olivia , Valerio Giuliana , Scalfi Luca
Published: December 2022

There is little evidence in children and adolescents with obesity of the relationships between muscle strength/cardiorespiratory fitness (both components of health-related fitness = HRF) and body composition. Body composition and HRF were studied in 281 children and adolescents with obesity to explore their mutual relationship and to identify the predictors of HRF. By performing a bioelectrical impedance analysis (BIA), the fat-free mass (FFM) and percentage of body fat (%BF) were calculated, and the phase angle (PhA) was recorded. Handgrip strength (HGS), the standard broad jump (SBJ), and five broad jumps (FIVEBJ) were considered for the assessment of muscle strength, and the six-minute walking distance (SIXMWD) for cardiorespiratory fitness. The BMI Z-score was slightly higher in boys, and the %BF was higher in girls, with no difference in the FFM. HGS, the SBJ, and FIVEBJ were greater in the male sex. After controlling for sex, HGS was associated with the FFM, and with height, weight, and absolute BMI. On the contrary, the SBJ and FIVEBJ were negatively associated with adiposity, with a weak relationship with the FFM. The SIXMWD was only poorly related to height, the BMI Z-score, and the waist-to-height ratio. These results were confirmed with a multiple regression analysis. HGS, the SBJ, and FIVEBJ were higher in the first compared to the third tertile of the PhA in both sexes. The PhA also remained a consistent predictor of HGS, the SBJ, and FIVEBJ in a multiple regression analysis. In conclusion, the following predictors have been identified for HRF: the FFM for the isometric strength of the upper limbs and adiposity indicators for the SBJ and FIVEBJ. The PhA emerged as a proxy index of muscle strength.
Case Reports and Experts Opinions about Current Use of Leech Therapy in Dermatology and Cosmetology
Authors: Ząbkowska Ewelina , Czerwińska-Ledwig Olga , Bartnicka Magdalena , Piotrowska Anna
Published: December 2022

This article aimed to determine the experts’ opinion on the use of hirudotherapy in cosmetology, to supplement knowledge, and to identify factors that, in the opinion of experts, affect the effectiveness and frequency of use of this method in eliminating skin problems. The study was conducted using the expert interview method. The research tool was a categorized expert interview questionnaire using the CAWI (Computer Assisted Web Interview) technique. Hirudotherapy is one of the oldest healing methods. The mechanism of action is based on the therapeutic properties of bioactive substances isolated from leech saliva. It has been shown to have a wide range of applications in the treatment of numerous diseases in various fields of medicine, including dermatology and cosmetology. Despite its therapeutic properties and effectiveness, hirudotherapy is a rarely used tool in cosmetology. It has been found effective in the treatment of many dermatoses. The most spectacular effects have been observed in the treatment of rosacea, local inflammations, lipomas, skin scars, hard to heal wounds and contusions.
The Contribution of New Breed Purple Wheat (8526-2 and 8529-1) Varieties Wholemeal Flour and Sourdough to Quality Parameters and Acrylamide Formation in Wheat Bread
Authors: Klupsaite Dovilė , Kaminskaite Aura , Rimsa Arnoldas , Gerybaite Agne , Stankaityte Agne , Sileikaite Ausra , Svetlauskaite Elzbieta , Cesonyte Emilija , Urbone Giedre , Pilipavicius Karolis , Vaiginyte Konstancija , Vaisvilaite Marija , Prokopenko Vilte , Stukonyte Giedre , Starkute Vytaute , Zokaityte Egle , Lele Vita , Cernauskas Darius , Mockus Ernestas , Liatukas Zilvinas , Ruzgas Vytautas , Rocha João Miguel , Bartkiene Elena
Published: December 2022

The aim of this study was to evaluate the influence of purple wheat (varieties 8526-2 and 8529-1) wholemeal flour (PWWF) left untreated or fermented with Lactiplantibacillus plantarum No. 135 on the quality parameters of and acrylamide formation in wheat bread. Different quantities (5, 10, 15, and 20%) of PWWF were tested for bread preparation. Acidity, colour characteristics, hardness, enzyme activities, and antioxidant activity of PWWF, as well as bread quality and acrylamide concentration, were analysed. Differences in LAB count and amylolytic and proteolytic enzyme activities between two varieties of non-treated and fermented PWWF were not found. Fermentation increased DPPH-scavenging activity and reduced hardness of both PWWF varieties. A very strong positive correlation was found between total phenolic compound content and antioxidant activity in PWWF (r = 0.816, p = 0.001). In most cases, PWWF addition lowered bread specific volume and mass loss after baking. After 72 h of storage, bread with 5% PWWF showed the lowest hardness. Addition of 15% PWWF to bread increased overall acceptability. Fermentation and wheat variety significantly affected bread crumb a* colour coordinates. Addition of fermented PWWF significantly decreased acrylamide formation in bread (p ≤ 0.0001), and bread with 5% PWWF variety 8526-1 had the lowest acrylamide content. In conclusion, the addition of new-breed PWWF to wheat bread improved certain quality parameters, while PWWF fermented with L. plantarum possessed DPPH-scavenging activity and can be recommended for acrylamide reduction in wheat bread.