bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Effects of Bariatric Surgery on Kidney Functions by Inhibiting Oxidative Stress Responses Through Activating PPARα in Rats With Diabetes
Authors: Jiang Hong-Wei , Zhou Yong , Zhou Pin-Yi , Zhang Tian-Yi , Hu Jing-Yao , Bai Xue-Tao
Published: June 2021

Objective

The aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats.

Methods

We established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague–Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal–jejunal bypass (DJB) surgery group. The food intake and body weight of rats were monitored and the glucose tolerance test (OGTT) test was performed every 2 weeks. The glomerular filtration rate (GFR) and urinary albumin excretion rate (UAFR) were measured to assess renal function. Hematoxylin–eosin (H&E), periodic acid–Schiff (PAS), and Masson staining were used to evaluate renal histopathological changes. TUNEL assay was performed to detect cell apoptosis. The expressions of oxidative stress factors and inflammatory factors in the renal tissues of rats were detected by ELISA. The expressions of PPARα, reactive oxygen species (ROS), and NF-κB were detected by immunofluorescence. For in vitro experiment, HK2 cells cultured with high glucose were treated with PPARα agonist, PPARα antagonist, and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) agonist. The expressions of AMPK/PPARα/NF-κB signaling pathway-related proteins were detected by Western blot.

Results

Bariatric surgery improved the glucose tolerance of DN rats. The GFR was decreased, the promotion of urinary albumin excretion rate (UAER) was inhibited, and the renal injury was alleviated. The extracellular matrix fraction was decreased and the renal function was improved. Meanwhile, bariatric surgery activates PPARα, inhibits ROS release, reduces oxidative stress injury, and reduces renal cell apoptosis. In vitro experiment results showed that the AMPK activator could activate PPARα, downregulate NF-κB, and inhibit inflammatory response. The phosphorylation of AMPK was inhibited by PPARα antagonism.

Conclusion

Bariatric surgery can activate PPARα, inhibit oxidative stress injury, and improve glucose metabolism and renal function in DN rats.
Modulation of Perturbed Cardiac Metabolism in Rats Under High-Altitude Hypoxia by Combination Treatment With L-carnitine and Trimetazidine
Authors: Xie Hebing , Xu Gang , Aa Jiye , Gu Shuhua , Gao Yuqi
Published: June 2021

High-altitude hypoxia has long been recognized as a vital etiology for high-altitude illnesses. High-altitude myocardial injury (HAMI) usually occurs in people who suffered from high-altitude exposure. To date, the molecular mechanism of HAMI remains elusive, which seriously hinders the prevention and treatment of HAMI. L-carnitine and trimetazidine are classic cardiovascular protective medicines. In this study, we used the metabolomic method, based on GC/MS, to explore the changes in metabolites in rats exposed to high-altitude hypoxia and then illustrate the metabolic pathways associated with the modulatory effect of L-carnitine combined with trimetazidine on rats with high-altitude exposure. The results showed that metabolites in the myocardium in rats under high-altitude hypoxia were markedly changed, such as branched-chain amino acids (BCAA, leucine, isoleucine, and valine), taurine, succinic acid, fumaric acid, lactic acid, pyruvic acid, 3-hydroxybutyrate, and docosahexaenoic acid (DHA), while L-carnitine combined with trimetazidine modulated and improved the abnormal changes in energy substances caused by high-altitude hypoxia. L-carnitine mainly promoted the metabolism of fatty acids, while trimetazidine enhanced the glycolysis process. The combined administration of the two components not only increased the metabolism of fatty acids but also promoted aerobic glycolysis. Meanwhile, it contributed to the decrease in the elevation in some of the intermediates of the tricarboxylic acid (TCA) cycle, decrease in the production of 3-hydroxybutyric acid, and relief of the abnormal energy metabolism process in organisms and the cardiac tissue. Our analysis delineates the landscape of the metabolites in the myocardial tissue of rats that were exposed to high altitude. Moreover, L-carnitine combined with trimetazidine can relieve the HAMI through modulated and improved abnormal changes in energy substances caused by high-altitude hypoxia.
Effects of Individual Changes in Training Distribution on Maximal Aerobic Capacity in Well-Trained Cross-Country Skiers: A Follow-Up Study
Authors: Johansen Jan-Michael , Sunde Arnstein , Helgerud Jan , Gjerløw Lars Erik , Støren Øyvind
Published: June 2021

The purpose of this study was to evaluate individual changes in training distribution and the subsequent effects on maximal oxygen uptake (VO2max). The participants were well-trained cross-country skiers who had performed a year with no substantial changes in training prior to this study. Six cross-country skiers, who were participants in a larger previous study, volunteered for a follow-up study. All skiers performed self-motivated changes in training distribution for a new preparation period in this follow-up, generally by more high-intensity training (HIT). All training characteristics were registered from training diaries. During the follow-up period, all skiers performed an incremental VO2max test in February 2020 and August 2020. Training were categorized into three different training periods; (1) February 2019 to February 2020 (P1) representing the training performed prior to the follow-up, (2) February 2020 to July 2020 (P2), and (3) July 2020 to August 2020 (P3). On average, the skiers increased their VO2max by 5.8 ± 5.0% (range: −1.8 to + 10.2%) during the follow-up study compared with the average VO2max during the preceding year. Total training volume increased on average by 10.0 and 25.7% in P2 and P3, respectively, compared with P1. The average volume of HIT was similar between P1 and P2 but increased 62.8% in P3. However, large individual differences in training changes were observed. In conclusion, the present study revealed that individual changes in training distribution generated an increased VO2max in four out of six already well-trained cross-country skiers. Reduced total training volume (three out of six) and increased (four out of six) HIT volume were the most marked changes.
Insights Into Transcriptome Profiles Associated With Wooden Breast Myopathy in Broilers Slaughtered at the Age of 6 or 7 Weeks
Authors: Malila Yuwares , Uengwetwanit Tanaporn , Thanatsang Krittaporn V. , Arayamethakorn Sopacha , Srimarut Yanee , Petracci Massimiliano , Soglia Francesca , Rungrassamee Wanilada , Visessanguan Wonnop
Published: June 2021

Transcriptomes associated with wooden breast (WB) were characterized in broilers at two different market ages. Breasts (Pectoralis major) were collected, 20-min postmortem, from male Ross 308 broilers slaughtered at 6 and 7 weeks of age. The breasts were classified as “non-WB” or “WB” based on palpation hardness scoring (non-WB = no abnormal hardness, WB = consistently hardened). Total RNA was isolated from 16 samples (n = 3 for 6 week non-WB, n = 3 for 6 week WB; n = 5 for 7 week non-WB, n = 5 for 7 week WB). Transcriptome was profiled using a chicken gene expression microarray with one-color hybridization technique, and compared between non-WB and WB samples of the same age. Among 6 week broilers, 910 transcripts were differentially expressed (DE) (false discovery rate, FDR < 0.05). Pathway analysis underlined metabolisms of glucose and lipids along with gap junctions, tight junction, and focal adhesion (FA) signaling as the top enriched pathways. For the 7 week broilers, 1,195 transcripts were identified (FDR < 0.05) with regulation of actin cytoskeleton, mitogen-activated protein kinase (MAPK) signaling, protein processing in endoplasmic reticulum and FA signaling highlighted as the enriched affected pathways. Absolute transcript levels of eight genes (actinin-1 – ACTN1, integrin-linked kinase – ILK, integrin subunit alpha 8 – ITGA8, integrin subunit beta 5 – ITGB5, protein tyrosine kinase 2 – PTK2, paxillin – PXN, talin 1 – TLN1, and vinculin – VCL) of FA signaling pathway were further elucidated using a droplet digital polymerase chain reaction. The results indicated that, in 6 week broilers, ITGA8 abundance in WB was greater than that of non-WB samples (p < 0.05). Concerning 7 week broilers, greater absolute levels of ACTN1, ILK, ITGA8, and TLN1, accompanied with a reduced ITGB5 were found in WB compared with non-WB (p < 0.05). Transcriptional modification of FA signaling underlined the potential of disrupted cell-cell communication that may incite aberrant molecular events in association with development of WB myopathy.
Genome-Wide Analysis of MADS-Box Genes in Foxtail Millet (Setaria italica L.) and Functional Assessment of the Role of SiMADS51 in the Drought Stress Response
Authors: Zhao Wan , Zhang Li-Li , Xu Zhao-Shi , Fu Liang , Pang Hong-Xi , Ma You-Zhi , Min Dong-Hong
Published: June 2021

MADS-box transcription factors play vital roles in multiple biological processes in plants. At present, a comprehensive investigation into the genome-wide identification and classification of MADS-box genes in foxtail millet (Setaria italica L.) has not been reported. In this study, we identified 72 MADS-box genes in the foxtail millet genome and give an overview of the phylogeny, chromosomal location, gene structures, and potential functions of the proteins encoded by these genes. We also found that the expression of 10 MIKC-type MADS-box genes was induced by abiotic stresses (PEG-6000 and NaCl) and exogenous hormones (ABA and GA), which suggests that these genes may play important regulatory roles in response to different stresses. Further studies showed that transgenic Arabidopsis and rice (Oryza sativa L.) plants overexpressing SiMADS51 had reduced drought stress tolerance as revealed by lower survival rates and poorer growth performance under drought stress conditions, which demonstrated that SiMADS51 is a negative regulator of drought stress tolerance in plants. Moreover, expression of some stress-related genes were down-regulated in the SiMADS51-overexpressing plants. The results of our study provide an overall picture of the MADS-box gene family in foxtail millet and establish a foundation for further research on the mechanisms of action of MADS-box proteins with respect to abiotic stresses.
Transcriptome Analysis of Chloris virgata, Which Shows the Fastest Germination and Growth in the Major Mongolian Grassland Plant
Authors: Bolortuya Byambajav , Kawabata Shintaro , Yamagami Ayumi , Davaapurev Bekh-Ochir , Takahashi Fuminori , Inoue Komaki , Kanatani Asaka , Mochida Keiichi , Kumazawa Minoru , Ifuku Kentaro , Jigjidsuren Sodnomdarjaa , Battogtokh Tugsjargal , Udval Gombosuren , Shinozaki Kazuo , Asami Tadao , Batkhuu Javzan , Nakano Takeshi
Published: June 2021

Plants in Mongolian grasslands are exposed to short, dry summers and long, cold winters. These plants should be prepared for fast germination and growth activity in response to the limited summer rainfall. The wild plant species adapted to the Mongolian grassland environment may allow us to explore useful genes, as a source of unique genetic codes for crop improvement. Here, we identified the Chloris virgata Dornogovi accession as the fastest germinating plant in major Mongolian grassland plants. It germinated just 5 h after treatment for germination initiation and showed rapid growth, especially in its early and young development stages. This indicates its high growth potential compared to grass crops such as rice and wheat. By assessing growth recovery after animal bite treatment (mimicked by cutting the leaves with scissors), we found that C. virgata could rapidly regenerate leaves after being damaged, suggesting high regeneration potential against grazing. To analyze the regulatory mechanism involved in the high growth potential of C. virgata, we performed RNA-seq-based transcriptome analysis and illustrated a comprehensive gene expression map of the species. Through de novo transcriptome assembly with the RNA-seq reads from whole organ samples of C. virgata at the germination stage (2 days after germination, DAG), early young development stage (8 DAG), young development stage (17 DAG), and adult development stage (28 DAG), we identified 21,589 unified transcripts (contigs) and found that 19,346 and 18,156 protein-coding transcripts were homologous to those in rice and Arabidopsis, respectively. The best-aligned sequences were annotated with gene ontology groups. When comparing the transcriptomes across developmental stages, we found an over-representation of genes involved in growth regulation in the early development stage in C. virgata. Plant development is tightly regulated by phytohormones such as brassinosteroids, gibberellic acid, abscisic acid, and strigolactones. Moreover, our transcriptome map demonstrated the expression profiles of orthologs involved in the biosynthesis of these phytohormones and their signaling networks. We discuss the possibility that C. virgata phytohormone signaling and biosynthesis genes regulate early germination and growth advantages. Comprehensive transcriptome information will provide a useful resource for gene discovery and facilitate a deeper understanding of the diversity of the regulatory systems that have evolved in C. virgata while adapting to severe environmental conditions.
Engagement in Music-Related Activities During the COVID-19 Pandemic as a Mirror of Individual Differences in Musical Reward and Coping Strategies
Authors: Ferreri Laura , Singer Neomi , McPhee Michael , Ripollés Pablo , Zatorre Robert J. , Mas-Herrero Ernest
Published: June 2021

The COVID-19 pandemic and the measures taken to mitigate its impact (e.g., confinement orders) have affected people's lives in profound ways that would have been unimagable only months before the pandemic began. Media reports from the height of the pandemic's initial international surge frequently highlighted that many people were engaging in music-related activities (from singing and dancing to playing music from balconies and attending virtual concerts) to help them cope with the strain of the pandemic. Our first goal in this study was to investigate changes in music-related habits due to the pandemic. We also investigated whether engagement in distinct music-related activities (singing, listening, dancing, etc.) was associated with individual differences in musical reward, music perception, musical training, or emotional regulation strategies. To do so, we collected detailed (~1 h-long) surveys during the initial peak of shelter-in-place order implementation (May–June 2020) from over a thousand individuals across different Countries in which the pandemic was especially devastating at that time: the USA, Spain, and Italy. Our findings indicate that, on average, people spent more time in music-related activities while under confinement than they had before the pandemic. Notably, this change in behavior was dependent on individual differences in music reward sensitivity, and in emotional regulation strategies. Finally, the type of musical activity with which individuals engaged was further associated with the degree to which they used music as a way to regulate stress, to address the lack of social interaction (especially the individuals more concerned about the risk of contracting the virus), or to cheer themselves up (especially those who were more worried about the pandemic consequences). Identifying which music-related activities have been particularly sought for by the population as a means for coping with such heightened uncertainty and stress, and understanding the individual differences that underlie said propensities are crucial to implementing personalized music-based interventions that aim to reduce stress, anxiety, and depression symptoms.
Evaluating Delivery of a CBT-Based Group Intervention for Schoolchildren With Emotional Problems: Examining the Reliability and Applicability of a Video-Based Adherence and Competence Measure
Authors: Rasmussen Lene-Mari Potulski , Patras Joshua , Handegård Bjørn Helge , Neumer Simon-Peter , Martinsen Kristin Dagmar , Adolfsen Frode , Sund Anne Mari , Martinussen Monica
Published: June 2021

Adherence and competence are essential parts of program fidelity and having adequate measures to assess these constructs is important. The Competence and Adherence Scale for Cognitive Behavioral Therapy (CAS CBT) was developed to evaluate the delivery of cognitive therapies for children with clinical anxiety. The present study is an assessment of the slightly adapted version of the CAS CBT evaluating the delivery of a Cognitive Behavioral Therapy (CBT)-based preventive group intervention: EMOTION: Kids Coping with Anxiety and Depression. This study was part of a Norwegian cluster randomized controlled trial (cRCT) investigating the effectiveness of a transdiagnostic intervention, the EMOTION program—an indicated prevention program targeting anxious and depressive symptoms. The applicability and psychometric properties of the CAS CBT were explored. Results are based on six raters evaluating 239 video-recorded sessions of the EMOTION program being delivered by 68 trained group leaders from different municipal services. Interrater reliability (intraclass correlation coefficients, ICC [3, 1]) indicated fair to good agreement between raters. Internal consistency of the instrument's key domains was calculated using the Omega coefficient which ranged between 0.70 to 0.94. There was a strong association between the two scales Adherence and Competence, and inter-item correlations were high across the items, except for the items rating the adherence to the session goals. Competence and Adherence Scale for Cognitive Behavioral Therapy is a brief measure for use in first-line services, with some promising features for easily assessing program fidelity, but some of the results indicated that the instrument should be improved. Future attention should also be made to adapt the instrument to fit better within a group setting, especially regarding evaluation of session goals. More research on how to adequately evaluate fidelity measures are also warranted.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02340637.
Effects of Supplementation With Antioxidant Agents on Sleep in Autism Spectrum Disorder: A Review
Authors: Zambrelli Elena , Lividini Althea , Spadavecchia Sofia , Turner Katherine , Canevini Maria Paola
Published: June 2021

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition, whose etiology remains poorly understood in most cases. Several genetic, epigenetic and environmental factors have been implicated in ASD pathogenesis and numerous studies have provided evidences for increased levels of oxidative stress and reduced antioxidant capacity in patients with ASD. Recent clinical trials explored supplementation with antioxidant agents as a potential therapeutic strategy for ASD, investigating the impact of this treatment on behavioral symptoms and on most common comorbidities of the disease, including sleep disturbances. Among all medical conditions associated to ASD, sleep problems are highly prevalent and are supposed to be positively related to the severity of the disease. Moreover, studies on animal models support the hypothesis of a relationship between oxidative stress and sleep deprivation. The aim of this review is to summarize the current state of the literature on the effect of antioxidant treatment on sleep disturbances in patients with ASD. Twenty-one articles were included in final synthesis. Of them, 15 studies involved Melatonin, 1 Tryptophan and 5 focused on supplementation with other antioxidant agents (namely Coenzyme Q10, L-Carnosine, Luteolin and Quercetin). Despite the high prevalence of comorbid sleep troubles in ASD, there is a paucity of data on the efficacy of antioxidant agents in those patients. Further research is needed to better define the role of antioxidants agents as adjunctive therapy in the management sleep disorders in children and adolescents affected with ASD.
Relational and Growth Outcomes Following Couples Therapy With MDMA for PTSD
Authors: Wagner Anne C. , Liebman Rachel E. , Mithoefer Ann T. , Mithoefer Michael C. , Monson Candice M.
Published: June 2021

Healing from trauma occurs in a relational context, and the impacts of traumatic experiences that result in post-traumatic stress disorder (PTSD) go beyond the diagnosis itself. To fully understand a treatment for PTSD, understanding its impact on interpersonal, relational, and growth outcomes yields a more fulsome picture of the effects of the treatment. The current paper examines these secondary outcomes of a pilot trial of Cognitive Behavioral Conjoint Therapy (CBCT) for PTSD with MDMA. Six romantic dyads, where one partner had PTSD, undertook a course of treatment combining CBCT for PTSD with two MDMA psychotherapy sessions. Outcomes were assessed at mid-treatment, post-treatment, and 3- and 6-month follow-up. Both partners reported improvements in post-traumatic growth, relational support, and social intimacy. Partners reported reduced behavioral accommodation and conflict in the relationship, and patients with PTSD reported improved psychosocial functioning and empathic concern. These improvements were maintained throughout the follow-up period. These findings suggest that CBCT for PTSD with MDMA has significant effect on relational and growth outcomes in this pilot sample. Improvements in these domains is central to a holistic recovery from traumatic experiences, and lends support to the utility of treating PTSD dyadically.
Does Listening to Music Improve Pain Perception and Anxiety in Patients Undergoing Cystoscopy: A Meta-Analysis
Authors: Chen Guo , Tang Cai , Liu Yuebai , Liu Yuhao , Dai Yi , Yang Luo
Published: June 2021

Objective: To identify the effect of music on outpatient-based cystoscopy.

Methods: We systematically reviewed the effect of music on all reported outpatient for cystoscopy and extracted data from randomized trials from inception to February 3, 2021, with no language restrictions. The analysis was completed via STATA version 14.2.

Results: A total of 27 studies were initially identified, and 6 articles containing 639 patients were included in the final analysis. In terms of post-procedural pain perception, a pooled analysis of 6 articles containing 639 patients showed that music seems to improve discomfort in patients who undergo cystoscopy (WMD: −1.72; 95%CI: −2.37 to −1.07). This improvement remained consistent in patients undergoing flexible cystoscopy (FC) (WMD: −1.18; 95% CI: −1.39 to −0.98) and rigid cystoscopy (RC) (WMD: −2.56; 95% CI: −3.64 to −1.48). The music group also had less post-procedural anxiety than those in no music group during cystoscopy (WMD: −13.33; 95% CI: −21.61 to −5.06), which was in accordance with the result of FC (WMD: −4.82; 95% CI: −6.38 to −3.26) than RC (WMD: −26.05; 95% CI: −56.13 to 4.04). Besides, we detected a significantly lower post-procedural heart rate (HR) in the music group than no music group during cystoscopy (WMD: −4.04; 95% CI: −5.38 to −2.71), which is similar to the results of subgroup analysis for FC (WMD: −3.77; 95% CI: −5.84 to −1.70) and RC (WMD: −4.24; 95% CI: −5.98 to −2.50). A pooled analysis of three trials indicated that patients in the music group had significantly higher post-operative satisfaction visual analog scale (VAS) scores than those in the no-music group during RC. However, there was no significant difference between the music group and no music group regarding post-procedural systolic pressures (SPs) during cystoscopy (WMD: −3.08; 95% CI: −8.64 to 2.49). For male patients undergoing cystoscopy, the music seemed to exert a similar effect on decreasing anxiety and pain, and it might serve as a useful adjunct to increase procedural satisfaction.

Conclusions: These findings indicate that listening to music contributes to the improvement of pain perception, HR, and anxiety feeling during cystoscopy, especially for male patients undergoing RC. Music might serve as a simple, inexpensive, and effective adjunct to sedation during cystoscopy.
Significance of Endogenous Antimicrobial Peptides on the Health of Food Animals
Authors: Fasina Yewande O. , Obanla Temitayo , Dosu George , Muzquiz Sierra
Published: June 2021

Acquired resistance to in-feed antibiotic growth promoters continues to be an imperative problem in the livestock industries, thereby necessitating continuous pursuit for alternatives. Antimicrobial peptides (AMPs) represent a critical part of the host's innate immune system and have been documented to have immunomodulatory activity. Increasing research evidence suggests that in contrast to antibiotics, AMPs exert broad-spectrum antibacterial activity in a manner that reduces bacterial acquisition of resistance genes. This review summarizes current knowledge on the protective effects of endogenous (natural) AMPs in the gastrointestinal tract of food animals. Factors limiting the efficacy of these AMPs were also discussed and mitigating strategies were proposed.
qRobot: A Quantum Computing Approach in Mobile Robot Order Picking and Batching Problem Solver Optimization
Authors: Atchade-Adelomou Parfait , Alonso-Linaje Guillermo , Albo-Canals Jordi , Casado-Fauli Daniel
Published: June 2021

This article aims to bring quantum computing to robotics. A quantum algorithm is developed to minimize the distance traveled in warehouses and distribution centers where order picking is applied. For this, a proof of concept is proposed through a Raspberry Pi 4, generating a quantum combinatorial optimization algorithm that saves the distance travelled and the batch of orders to be made. In case of computational need, the robot will be able to parallelize part of the operations in hybrid computing (quantum + classical), accessing CPUs and QPUs distributed in a public or private cloud. We developed a stable environment (ARM64) inside the robot (Raspberry) to run gradient operations and other quantum algorithms on IBMQ, Amazon Braket (D-Wave), and Pennylane locally or remotely. The proof of concept, when run in the above stated quantum environments, showed the execution time of our algorithm with different public access simulators on the market, computational results of our picking and batching algorithm, and analyze the quantum real-time execution. Our findings are that the behavior of the Amazon Braket D-Wave is better than Gate-based Quantum Computing over 20 qubits, and that AWS-Braket has better time performance than Qiskit or Pennylane.
The Dynamics of Selenium Uptake by Maize (Zea mays L.)
Authors: Płaczek Aldona , Patorczyk-Pytlik Barbara
Published: June 2021

The dynamics of selenium (Se) uptake by two maize varieties (Zea mays L.) were assessed under two selenium doses (0.1 and 0.2 mg kg−1 of soil) applied to the soil. The addition of Se increased the biomass yield of the Se-susceptible variety (Bielik), while significantly decreasing the yield of the Se-resistant variety (Lober), and this suppression was stronger at the higher Se dose. The content and uptake of selenium by maize also increased with the Se dose, and the Bielik variety proved to be more effective. In terms of crop quality for animal nutrition, the optimal Se content (330–365 µg kg−1) was reached after 81 days of vegetation under the lower Se dose only, while the higher treatment led to excessive Se accumulation in maize biomass.
Taxonomy-Focused Natural Product Databases for Carbon-13 NMR-Based Dereplication
Authors: Nuzillard Jean-Marc
Published: June 2021

The recent revival of the study of organic natural products as renewable sources of medicinal drugs, cosmetics, dyes, and materials motivated the creation of general purpose structural databases. Dereplication, the efficient identification of already reported compounds, relies on the grouping of structural, taxonomic and spectroscopic databases that focus on a particular taxon (species, genus, family, order, etc.). A set of freely available python scripts, CNMR_Predict, is proposed for the quick supplementation of taxon oriented search results from the naturaL prOducTs occUrrences database (LOTUS, lotus.naturalproducts.net) with predicted carbon-13 nuclear magnetic resonance data from the ACD/Labs CNMR predictor and DB software (acdlabs.com) to provide easily searchable databases. The database construction process is illustrated using Brassica rapa as a taxon example.
Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells
Authors: Chung Katherine Po Sin , Leung Rainbow Wing Hei , Lee Terence Kin Wah
Published: June 2021

Cancer stem cells (CSCs) within the tumor bulk play crucial roles in tumor initiation, recurrence and therapeutic resistance. In addition to intrinsic regulation, a growing body of evidence suggests that the phenotypes of CSCs are also regulated extrinsically by stromal cells in the tumor microenvironment (TME). Here, we discuss the current knowledge of the interplay between stromal cells and cancer cells with a special focus on how stromal cells drive the stemness of cancer cells and immune evasive mechanisms of CSCs. Knowledge gained from the interaction between CSCs and stromal cells will provide a mechanistic basis for the development of novel therapeutic strategies for the treatment of cancers.
RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer
Authors: Gleizes Antoine , Triki Mouna , Bonnet Sandrine , Baccari Naomi , Jimenez-Dominguez Gabriel , Covinhes Aurélie , Pirot Nelly , Blache Philippe , Yuan Rong , Győrffy Balázs , Cavaillès Vincent , Lapierre Marion
Published: June 2021

RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.
Smart Biosensors for Cancer Diagnosis Based on Graphene Quantum Dots
Authors: Iannazzo Daniela , Espro Claudia , Celesti Consuelo , Ferlazzo Angelo , Neri Giovanni
Published: June 2021

The timely diagnosis of cancer represents the best chance to increase treatment success and to reduce cancer deaths. Nanomaterials-based biosensors containing graphene quantum dots (GQDs) as a sensing platform show great promise in the early and sensitive detection of cancer biomarkers, due to their unique chemical and physical properties, large surface area and ease of functionalization with different biomolecules able to recognize relevant cancer biomarkers. In this review, we report different advanced strategies for the synthesis and functionalization of GQDs with different agents able to selectively recognize and convert into a signal specific cancer biomarkers such as antigens, enzymes, hormones, proteins, cancer related byproducts, biomolecules exposed on the surface of cancer cells and changes in pH. The developed optical, electrochemical and chemiluminescent biosensors based on GQDs have been shown to ensure the effective diagnosis of several cancer diseases as well as the possibility to evaluate the effectiveness of anticancer therapy. The wide linear range of detection and low detection limits recorded for most of the reported biosensors highlight their great potential in clinics for the diagnosis and management of cancer.
Imaging Mass Spectrometry-Based Proteomic Analysis to Differentiate Melanocytic Nevi and Malignant Melanoma
Authors: Casadonte Rita , Kriegsmann Mark , Kriegsmann Katharina , Hauk Isabella , Meliß Rolf R. , Müller Cornelia S. L. , Kriegsmann Jörg
Published: June 2021

The discrimination of malignant melanoma from benign nevi may be difficult in some cases. For this reason, immunohistological and molecular techniques are included in the differential diagnostic toolbox for these lesions. These methods are time consuming when applied subsequently and, in some cases, no definitive diagnosis can be made. We studied both lesions by imaging mass spectrometry (IMS) in a large cohort (n = 203) to determine a different proteomic profile between cutaneous melanomas and melanocytic nevi. Sample preparation and instrument setting were tested to obtain optimal results in term of data quality and reproducibility. A proteomic signature was found by linear discriminant analysis to discern malignant melanoma from benign nevus (n = 113) with an overall accuracy of >98%. The prediction model was tested in an independent set (n = 90) reaching an overall accuracy of 93% in classifying melanoma from nevi. Statistical analysis of the IMS data revealed mass-to-charge ratio (m/z) peaks which varied significantly (Area under the receiver operating characteristic curve > 0.7) between the two tissue types. To our knowledge, this is the largest IMS study of cutaneous melanoma and nevi performed up to now. Our findings clearly show that discrimination of melanocytic nevi from melanoma is possible by IMS.
Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs
Authors: Prete Alessandro , Matrone Antonio , Gambale Carla , Torregrossa Liborio , Minaldi Elisa , Romei Cristina , Ciampi Raffaele , Molinaro Eleonora , Elisei Rossella
Published: June 2021

PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed the newest findings about genetic features of PDTC and ATC, from mutations occurring in DNA to alterations in RNA. Therefore, we describe their tumor microenvironments (both immune and not-immune) and the interactions between tumor and neighboring cells. Finally, we recapitulate how this upcoming evidence are changing the treatment of PDTC and ATC.
Depletion of DNA Polymerase Theta Inhibits Tumor Growth and Promotes Genome Instability through the cGAS-STING-ISG Pathway in Esophageal Squamous Cell Carcinoma
Authors: Li Jian , Ko Josephine Mun-Yee , Dai Wei , Yu Valen Zhuoyou , Ng Hoi Yan , Hoffmann Jean-Sébastien , Lung Maria Li
Published: June 2021

Overexpression of the specialized DNA polymerase theta (POLQ) is frequent in breast, colon and lung cancers and has been correlated with unfavorable clinical outcomes. Here, we aimed to determine the importance and functional role of POLQ in esophageal squamous cell carcinoma (ESCC). Integrated analysis of four RNA-seq datasets showed POLQ was predominantly upregulated in ESCC tumors. High expression of POLQ was also observed in a cohort of 25 Hong Kong ESCC patients and negatively correlated with ESCC patient survival. POLQ knockout (KO) ESCC cells were sensitized to multiple genotoxic agents. Both rH2AX foci staining and the comet assay indicated a higher level of genomic instability in POLQ-depleted cells. Double KO of POLQ and FANCD2, known to promote POLQ recruitment at sites of damage, significantly impaired cell proliferation both in vitro and in vivo, as compared to either single POLQ or FANCD2 KOs. A significantly increased number of micronuclei was observed in POLQ and/or FANCD2 KO ESCC cells. Loss of POLQ and/or FANCD2 also resulted in the activation of cGAS and upregulation of interferon-stimulated genes (ISGs). Our results suggest that high abundance of POLQ in ESCC contributes to the malignant phenotype through genome instability and activation of the cGAS pathway.
Pregnancy Inhibits Mammary Carcinogenesis by Persistently Altering the Hypothalamic–Pituitary Axis
Authors: Subramani Ramadevi , Estrada Adriana , Dixon Madeline , Parada Maria , Rodriguez Sheryl , Pedroza Diego A. , Ramirez Matthew D. , Clift Alexa , Garcia Lilia , Lakshmanaswamy Rajkumar
Published: June 2021

Early full-term pregnancy is known to reduce the lifetime risk of breast cancer. Although the phenomenon of parity-induced protection is well-established, the physiological mechanisms involved in this protection are not clear. Earlier reports have shown that pregnancy results in alterations of hormone levels. How pregnancy affects hypothalamic hormones and how the change, if any, influences breast cancer is not well understood. Seven-week-old female Lewis rats were given N-methyl-N-nitrosourea. Two weeks post carcinogen exposure, a set of females were housed with males to generate the parous rats and another set of rats served as the nulliparous controls. Mammary tumorigenesis was assessed for 9 months. Hypothalamic and pituitary levels of hormones were measured at various timepoints. Further, animals were also challenged with growth hormone and prolactin secretagogues to test the effect of pregnancy on the hypothalamic–pituitary hormonal axis. Persistent alterations in the level of growth hormone-releasing hormone, thyrotropin releasing hormone, dopamine, and somatostatin in the hypothalamus of parous animals was observed. Further, we also observed that pregnancy had a significant effect on the pituitary gland and its response to growth hormone and prolactin secretagogues. Our studies using the rodent model system demonstrate that pregnancy could be reducing the risk of breast cancer by persistently altering the hypothalamic–pituitary axis, which could have implications for breast cancers in humans as well.
Epigenetics of Most Aggressive Solid Tumors: Pathways, Targets and Treatments
Authors: Martinez-Useros Javier , Martin-Galan Mario , Florez-Cespedes Maria , Garcia-Foncillas Jesus
Published: June 2021

Highly aggressive tumors are characterized by a highly invasive phenotype, and they display chemoresistance. Furthermore, some of the tumors lack expression of biomarkers for target therapies. This is the case of small-cell lung cancer, triple-negative breast cancer, pancreatic ductal adenocarcinoma, glioblastoma, metastatic melanoma, and advanced ovarian cancer. Unfortunately, these patients show a low survival rate and most of the available drugs are ineffective. In this context, epigenetic modifications have emerged to provide the causes and potential treatments for such types of tumors. Methylation and hydroxymethylation of DNA, and histone modifications, are the most common targets of epigenetic therapy, to influence gene expression without altering the DNA sequence. These modifications could impact both oncogenes and tumor suppressor factors, which influence several molecular pathways such as epithelial-to-mesenchymal transition, WNT/β–catenin, PI3K–mTOR, MAPK, or mismatch repair machinery. However, epigenetic changes are inducible and reversible events that could be influenced by some environmental conditions, such as UV exposure, smoking habit, or diet. Changes in DNA methylation status and/or histone modification, such as acetylation, methylation or phosphorylation, among others, are the most important targets for epigenetic cancer therapy. Therefore, the present review aims to compile the basic information of epigenetic modifications, pathways and factors, and provide a rationale for the research and treatment of highly aggressive tumors with epigenetic drugs.
Significant Decrease in Annual Cancer Diagnoses in Spain during the COVID-19 Pandemic: A Real-Data Study
Authors: Ruiz-Medina Sofía , Gil Silvia , Jimenez Begoña , Rodriguez-Brazzarola Pablo , Diaz-Redondo Tamara , Cazorla Mireya , Muñoz-Ayllon Marta , Ramos Inmaculada , Reyna Carmen , Bermejo María José , Godoy Ana , Torres Esperanza , Cobo Manuel , Galvez Laura , Rueda Antonio , Alba Emilio , Ribelles Nuria
Published: June 2021

The COVID-19 pandemic has caused a profound change in health organizations at both the primary and hospital care levels. This cross-sectional study aims to investigate the impact of the COVID-19 pandemic in the annual rate of new cancer diagnosis in two university-affiliated hospitals. This study includes all the patients with a pathological diagnosis of cancer attended in two hospitals in Málaga (Spain) during the first year of pandemic. This study population was compared with the patients diagnosed during the previous year 2019. To analyze whether the possible differences in the annual rate of diagnoses were due to the pandemic or to other causes, the patients diagnosed during 2018 and 2017 were also compared. There were 2340 new cancer diagnosis compared to 2825 patients in 2019 which represented a decrease of −17.2% (p = 0.0001). Differences in the number of cancer patients diagnosed between 2018 and 2019 (2840 new cases; 0.5% increase) or 2017 and 2019 (2909 new cases; 3% increase) were not statistically significant. The highest number of patients lost from diagnosis in 2020 was in breast cancer (−26.1%), colorectal neoplasms (−16.9%), and head and neck tumors (−19.8%). The study of incidence rates throughout the first year of the COVID-19 pandemic shows that the diagnosis of new cancer patients has been significantly impaired. Health systems must take the necessary measures to restore pre-pandemic diagnostic procedures and to recover lost patients who have not been diagnosed.
Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes
Authors: Chung Tony K. H. , Doran Graeme , Cheung Tak-Hong , Yim So-Fan , Yu Mei-Yung , Worley Michael J. , Elias Kevin M. , Thorner Aaron R. , Pedamallu Chandra Sekhar , Ojesina Akinyemi I. , Lau Kei-Man , Ducar Matthew D. , Wong Raymond R. Y. , Wang Vivian W. , Nag Anwesha , Wollison Bruce M. , Dalgarno Audrey , Lee Jacqueline H. S. , Yeung Suet-Ying , Wong Lo , Horowitz Neil S. , Davis Michelle R. , Leung Shuk-On A. , Mu Yi , Mok Samuel C. , Chan Paul K. S. , Lawrence Michael S. , Crum Christopher P. , Chiu Rossa W. K. , Berkowitz Ross S. , Wong Yick-Fu
Published: June 2021

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.
An Insight into Pathophysiological Features and Therapeutic Advances on Ependymoma
Authors: Seo Seung-Hee , Paul Shamrat Kumar , Shikder Mita , Khanam Mushira , Ghosh Popy , Hasib Tasnin Al , Ahmed Kazi Ahsan , Sikdar Suranjana , Uddin Md Jamal , Kwon Youngjoo
Published: June 2021

Glial cells comprise the non-sensory parts of the central nervous system as well as the peripheral nervous system. Glial cells, also known as neuroglia, constitute a significant portion of the mammalian nervous system and can be viewed simply as a matrix of neural cells. Despite being the “Nervenkitt” or “glue of the nerves”, they aptly serve multiple roles, including neuron repair, myelin sheath formation, and cerebrospinal fluid circulation. Ependymal cells are one of four kinds of glial cells that exert distinct functions. Tumorigenesis of a glial cell is termed a glioma, and in the case of an ependymal cell, it is called an ependymoma. Among the various gliomas, an ependymoma in children is one of the more challenging brain tumors to cure. Children are afflicted more severely by ependymal tumors than adults. It has appeared from several surveys that ependymoma comprises approximately six to ten percent of all tumors in children. Presently, the surgical removal of the tumor is considered a standard treatment for ependymomas. It has been conspicuously evident that a combination of irradiation therapy and surgery is much more efficacious in treating ependymomas. The main purpose of this review is to present the importance of both a deep understanding and ongoing research into histopathological features and prognoses of ependymomas to ensure that effective diagnostic methods and treatments can be developed.
Simultaneous Expression of Long Non-Coding RNA FAL1 and Extracellular Matrix Protein 1 Defines Tumour Behaviour in Young Patients with Papillary Thyroid Cancer
Authors: Jeong Seonhyang , Lee Seul-Gi , Kim Hyunji , Lee Gibbeum , Park Sunmi , Kim In-Kyu , Lee Jandee , Jo Young-Suk
Published: June 2021

We investigated the regulatory mechanism of FAL1 and unravelled the molecular biological features of FAL1 upregulation in papillary thyroid cancer (PTC). Correlation analyses of FAL1 and neighbouring genes adjacent to chromosome 1q21.3 were performed. Focal amplification was performed using data from copy number alterations in The Cancer Genome Atlas (TCGA) database. To identify putative transcriptional factors, PROMO and the Encyclopaedia of DNA Elements (ENCODE) were used. To validate c-JUN and JUND as master transcription factors for FAL1 and ECM1, gene set enrichment analysis was performed according to FAL1 and ECM1 expression. Statistical analyses of the molecular biological features of FAL1- and ECM1-upregulated PTCs were conducted. FAL1 expression significantly correlated with that of neighbouring genes. Focal amplification of chromosome 1q21.3 was observed in ovarian cancer but not in thyroid carcinoma. However, PROMO suggested 53 transcription factors as putative common transcriptional factors for FAL1 and ECM1 simultaneously. Among them, we selected c-JUN and JUND as the best candidates based on ENCODE results. The expression of target genes of JUND simultaneously increased in FAL1- and ECM1-upregulated PTCs, especially in young patients. The molecular biological features represented RAS-driven PTC and simultaneously enriched immune-related gene sets. FAL1 and ECM1 expression frequently increased simultaneously and could be operated by JUND. The simultaneous upregulation might be a potential diagnostic and therapeutic target for RAS-driven PTC.