bluuebunny/crossref_metadata_2025 huggingface dataset:
Fraction and Number of Unemployed Associated with Self-Reported Low Back Pain: A Nation-Wide Cross-Sectional Study in Japan
Authors: Tomioka Kimiko , Kitahara Teruyo , Shima Midori , Saeki Keigo
Published: October 2021

This study examined a cross-sectional association between self-reported low back pain (LBP) and unemployment among working-age people, and estimated the impact of self-reported LBP on unemployment. We used anonymized data from a nationally representative survey (24,854 men and 26,549 women aged 20–64 years). The generalized estimating equations of the multivariable Poisson regression models stratified by gender were used to estimate the adjusted prevalence ratio (PR) and 95% confidence interval (CI) for unemployment. The population attributable fraction (PAF) was calculated using Levin’s method, with the substitution method for 95% CI estimation. The prevalence of self-reported LBP was 9.0% in men and 11.1% in women. The prevalence of unemployment was 9.3% in men and 31.7% in women. After adjusting for age, socio-economic status, lifestyle habits, and comorbidities, the PR (95% CI) for the unemployment of the LBP group was 1.32 (1.19–1.47) in men and 1.01 (0.96–1.07) in women, compared with the respective non-LBP group. The PAF (95% CI) of unemployment associated with self-reported LBP was 2.8% (1.6%, 4.2%) in men. Because the total population of Japanese men aged 20–64 in 2013 was 36,851 thousand, it was estimated that unemployment in 1037 thousand of the Japanese male working population was LBP-related.
Cigarette Smoking as a Predictor of Male DUI Recidivism
Authors: Terranova Claudio , Forza Giovanni , Beccegato Elena , Ruggeri Angelo , Viel Guido , Viero Alessia , Montisci Massimo
Published: October 2021

This study aimed to investigate the predictors of recidivism in first-time driving under the influence (DUI) offenders, analyzing variables derived from medico-legal and toxicological examinations. The research was structured as a comparative study for the period 2012–2019. DUI offenders with a blood alcohol concentration >0.5 were included in the study. The case group consisted of recidivist offenders, while the comparison group consisted of first-time offenders. Personal data, socioeconomics, and parameters linked to the DUI were compared between the two groups. Significance was determined by chi-square and Mann–Whitney tests. To prevent confounding effects, multivariate binary logistic regression analysis was performed. Our sample encompassed 1678 subjects (196 in the case group, 1482 in the comparison group). Gender, driving license category, education, and tobacco use resulted in significant differences between the groups. In a model including age at DUI, education, and smoking habit as independent variables, higher educational levels (high school, bachelor’s) and older age protected against recidivism, whereas smoking >20 cigarettes/day was an independent risk factor for recidivism. Recidivist offenders have specific characteristics indicating different therapeutic programs and carefulness in driving license regranting. A higher tobacco consumption in recidivists suggests that the use of this substance could influence the risk of DUI for reasons that will need to be explored.
Relationship between Cardiovascular Disease Risk and Neck Circumference Shown in the Systematic Coronary Risk Estimation (SCORE) Risk Model
Authors: Asil Serkan , Murat Ender , Taşkan Hatice , Barış Veysel Özgür , Görmel Suat , Yaşar Salim , Çelik Murat , Yüksel Uygar Çağdaş , Kabul Hasan Kutsi , Barçın Cem
Published: October 2021

Introduction: The most important way to reduce CVD-related mortality is to apply appropriate treatment according to the risk status of the patients. For this purpose, the SCORE risk model is used in Europe. In addition to these risk models, some anthropometric measurements are known to be associated with CVD risk and risk factors. Objectives: This study aimed to investigate the association of these anthropometric measurements, especially neck circumference (NC), with the SCORE risk chart. Methods: This was planned as a cross-sectional study. The study population were classified according to their SCORE risk values. The relationship of NC and other anthropometric measurements with the total cardiovascular risk indicated by the SCORE risk was investigated. Results: A total of 232 patients were included in the study. The patients participating in the study were analysed in four groups according to the SCORE ten-year total cardiovascular mortality risk. As a result, the NC was statistically significantly lower among the SCORE low and moderate risk group than all other SCORE risk groups (low-high and very high 36(3)–38(4) (IQR) p: 0.026, 36(3)–39(4) (IQR) p < 0.001, 36(3)–40(4) (IQR) p < 0.001), (moderate-high and very high 38(4) vs. 39(4) (IQR) p: 0.02, 38(4) vs. 40(4) (IQR) p < 0.001, 39(4) vs. 40(4) (IQR) p > 0.05). NC was found to have the strongest correlation with SCORE than the other anthropometric measurements. Conclusions: Neck circumference correlates strongly with the SCORE risk model which shows the ten-year cardiovascular mortality risk and can be used in clinical practice to predict CVD risk.
Do Parental Perceptions of the Nutritional Quality of School Meals Reflect the Food Environment in Public Schools?
Authors: Martinelli Sarah , Acciai Francesco , Yedidia Michael J. , Ohri-Vachaspati Punam
Published: October 2021

(1) Background: It is unknown whether parents’ perception of school meals, a determinant of student meal participation, align with the nutritional quality of meals served in schools. This study compares the healthfulness of foods offered in schools with parental perception of school meals at those same schools. (2) Method: Parents were asked to rate the healthfulness of school meals at their child’s school. Data on the types of foods offered were collected from public schools in four cities in New Jersey and matched with parent-reported data. Measures were developed to capture the presence of healthy and unhealthy items in the National School Lunch Program and the presence of a la carte offerings as well as vending machines. Multivariable analysis examined the association between parental perceptions of school meals and the school food measures after adjusting for covariates. (3) Results: Measures of the school food environment and parental perceptions were available for 890 pre-K to 12th grade students. No significant associations were observed between parental perceptions and food environment measures when examined one by one or in a comprehensive model. (4) Conclusions: Parents’ perception of the healthfulness of meals served do not align with the nutritional quality of foods offered at schools.
Animal-Assisted Interventions for the Improvement of Mental Health Outcomes in Higher Education Students: A Systematic Review of Randomised Controlled Trials
Authors: Parbery-Clark Charlotte , Lubamba Marvellas , Tanner Louise , McColl Elaine
Published: October 2021

Background: The aim of this systematic review was to evaluate the effectiveness of Animal-Assisted Interventions (AAIs), particularly Animal-Assisted Therapy (AAT) and Animal-Assisted Activity (AAA), in improving mental health outcomes for students in higher education. The number of students in higher education reporting mental health problems and seeking support from universities’ student support services has risen over recent years. Therefore, providing engaging interventions, such as AAIs, that are accessible to large groups of students are attractive. Methods: MEDLINE, PsycINFO, Embase and Cochrane Library were searched from relative inception to end of April 2020. Additionally, a grey literature search was undertaken. Independent screening, data extraction and risk of bias assessment were completed, with varying percentages, by two reviewers. Results: After de-duplication, 6248 articles were identified of which 11 studies were included in the narrative synthesis. The evidence from randomised controlled trials suggests that AAIs could provide short-term beneficial results for anxiety in students attending higher education but with limited evidence for stress, and inconclusive evidence for depression, well-being and mood. For the non-statistically significant results, the studies either did not include a power calculation or were under-powered. Conclusions: Potential emerging evidence for the short-term benefits of AAI for anxiety, and possibly stress, for students in higher education was found.
Association between Relative Handgrip Strength and Chronic Lower Back Pain: A Nationwide Cross-Sectional Analysis of the Korea National Health and Nutrition Examination Survey
Authors: Choi Sungwoo , Nah Sangun , Jang Haedong , Moon Jieun , Han Sangsoo
Published: October 2021

Lower back pain (LBP) is the most common musculoskeletal complaint and significantly reduces the quality of life. Muscle weakness is a major cause of LBP. Handgrip strength (HGS) is widely used to determine general muscle strength. Relative HGS (RHGS) incorporates body mass and provides a more accurate estimation of muscle strength and health status. We analyzed the data from Korea National Health and Nutrition Examination Survey to investigate the association between RHGS and chronic LBP. We identified 14,930 participants and excluded a total of 9553 participants with age < 50 years, with incomplete LBP information, and with incomplete HGS information. We analyzed the data of 5377 participants: 1086 (20.19%) with chronic LBP and 4291 (79.8%) without chronic LBP. Multivariate regression analysis with adjustment for covariates identified an association between weak RHGS and chronic LBP (odds ratio 1.31; CI 1.07–1.61; p = 0.01). This article demonstrated a significant association between RHGS and chronic LBP. Therefore, RHGS should be measured for patients with chronic LBP.
Pharmaceutical Products and Pesticides Toxicity Associated with Microplastics (Polyvinyl Chloride) in Artemia salina
Authors: Albendín María Gemma , Aranda Vanessa , Coello María Dolores , González-Gómez Carmen , Rodríguez-Barroso Rocío , Quiroga José María , Arellano Juana María
Published: October 2021

Pharmaceutical products, as well as insecticides and antimicrobials, have been extensively studied, but knowledge of their effects—especially those caused by their mixtures with microplastics—on aquatic organisms remains limited. However, it should be borne in mind that the state of knowledge on acute and chronic effects in aquatic organisms for pharmaceuticals and pesticides is not similar. In response, this investigation analyzed the presence of microplastics (polyvinyl chloride) and their impacts on the toxicity of chlorpyrifos (an insecticide) and triclosan (an antibacterial) when they coincide in the environment, alongside the two most consumed drugs of their type (hypolipemic and anticonvulsant, respectively), namely simvastatin and carbamazepine, in Artemia salina. LC50 and cholinesterase enzyme activity were calculated to determine the possible neurotoxicity associated with emergent contaminants in the treatments. The LC50 values obtained were 0.006 mg/dm3 for chlorpyrifos, 0.012 mg/dm3 for chlorpyrifos associated with microplastics, 4.979 mg/dm3 for triclosan, 4.957 mg/dm3 for triclosan associated with microplastics, 9.35 mg/dm3 for simvastatin, 10.29 mg/dm3 for simvastatin associated with microplastics, 43.25 mg/dm3 for carbamazepine and 46.50 mg/dm3 for carbamazepine associated with microplastics in acute exposure. These results indicate that the presence of microplastics in the medium reduces toxicity, considering the LC50 values. However, exposure to chlorpyrifos and carbamazepine, both alone and associated with microplastics, showed a decline in cholinesterase activity, confirming their neurotoxic effect. Nevertheless, no significant differences were observed with the biomarker cholinesterase between the toxicant and the toxicant with microplastics.
Executive Functioning in Adults with Down Syndrome: Machine-Learning-Based Prediction of Inhibitory Capacity
Authors: Jojoa-Acosta Mario Fernando , Signo-Miguel Sara , Garcia-Zapirain Maria Begoña , Gimeno-Santos Mercè , Méndez-Zorrilla Amaia , Vaidya Chandan J. , Molins-Sauri Marta , Guerra-Balic Myriam , Bruna-Rabassa Olga
Published: October 2021

The study of executive function decline in adults with Down syndrome (DS) is important, because it supports independent functioning in real-world settings. Inhibitory control is posited to be essential for self-regulation and adaptation to daily life activities. However, cognitive domains that most predict the capacity for inhibition in adults with DS have not been identified. The aim of this study was to identify cognitive domains that predict the capacity for inhibition, using novel data-driven techniques in a sample of adults with DS (n = 188; 49.47% men; 33.6 ± 8.8 years old), with low and moderate levels of intellectual disability. Neuropsychological tests, including assessment of memory, attention, language, executive functions, and praxis, were submitted to Random Forest, support vector machine, and logistic regression algorithms for the purpose of predicting inhibition capacity, assessed with the Cats-and-Dogs test. Convergent results from the three algorithms show that the best predictors for inhibition capacity were constructive praxis, verbal memory, immediate memory, planning, and written verbal comprehension. These results suggest the minimum set of neuropsychological assessments and potential intervention targets for individuals with DS and ID, which may optimize potential for independent living.
Objectively Measured Physical Activity Is Associated with Static Balance in Young Adults
Authors: Zhu Wenfei , Li Yunfeng , Wang Bingqi , Zhao Chenxi , Wu Tongzhou , Liu Tao , Sun Fangjun
Published: October 2021

Purpose: Regular physical activity (PA) strengthens muscles and improves balance and coordination of human body. The aim of this study was to examine whether objectively measured physical activity (PA) and sedentary behaviors were related to static balance in young men and women. Design and setting: Cross-sectional community study. Participants: 86 healthy adults (50% women) aged 21.26 ± 2.11 years. Method: PA variables, including moderate-to-vigorous PA (MVPA), light PA (LPA), sedentary time (SED), and sedentary breaks, were measured by accelerometers on wrist (ActiGraph WGT3X-BT). The static balance was tested in the bipedal stance with eyes open or closed. The movement of the center of pressure, including total sway path length (SP), sway velocity (SV), and sway area (SA), was recorded with a three-dimensional force platform (Kistler 9287CA). The associations between PA (MVPA/LPA/SED/sedentary breaks) and static balance (SP/SV/SA) were analyzed using mixed linear regression analyses, with adjustments for condition (eyes open/closed), sex, age, body mass index (BMI), total device wearing time, and PA*condition. Data were analyzed with SPSS 24.0. Results: Better performance was observed in eyes-open condition (p < 0.05). MVPA was negatively associated with SA (p = 0.030), and SED was positively associated with SA after adjustments, respectively (p = 0.0004). No significance was found in the association of light PA, SED, or sedentary breaks with other static balance variables, respectively (p > 0.05). Conclusion: Increasing MVPA and less SED are associated with lower sway area measured by force platform, indicating more PA may related to better static balance in young adults.
Effects of 16 Weeks of Taekwondo Training on the Cerebral Blood Flow Velocity, Circulating Neurotransmitters, and Subjective Well-Being of Obese Postmenopausal Women
Authors: Lee Yong-Kuk , Cho Su-Youn , Roh Hee-Tae
Published: October 2021

We investigated the effects of Taekwondo training on the body composition, serum lipid profiles, plasma neurotransmitter levels, cerebral blood flow velocities, and subjective well-being of 24 obese postmenopausal women. The women were randomly assigned into the experimental (n = 12) and control (n = 12) groups. The experimental group underwent Taekwondo training five times per week for 16 weeks, while the control group did not. All participants underwent evaluation for the following parameters before and after the intervention: body composition; serum lipid profiles; plasma serotonin and dopamine levels; cerebral blood flow velocities; positive and negative affect schedule (PANAS) scores; satisfaction with life scale (SWLS) scores. After the intervention, it was observed that the weight, body mass index, body fat percentage, total cholesterol, low-density lipoprotein cholesterol, and PANAS-NA (negative affect in the PANAS questionnaire) scores were significantly decreased (p < 0.05)—while the plasma serotonin levels were significantly increased (p < 0.05)—in the experimental group. Conversely, there were no significant changes in the cerebral blood flow velocities (p > 0.05). Taekwondo training can be effective in not only reducing obesity, but also in increasing the circulating neurotransmitters and enhancing the subjective well-being of obese postmenopausal women.
A Study of Differences in Leisure Satisfaction of Leisure Activity Patterns for South Korean Adults
Authors: Ahn Byoung-Wook , Song Won-Ick
Published: October 2021

The purpose of this study was to analyse differences in leisure satisfaction among leisure activity participants according to the type of activity including differences by gender. The study subjects were 448 adult men and women who were participating in leisure activities in Seoul, Gyeonggi, Chungcheong, and Gangwon-do, Korea. Frequency analysis, confirmatory factor analysis, and latent mean analysis were applied to the data collected from the participants. First, the form, measurement, and intercept uniformity were verified to check that the study scale could be used equally with men and women. Second, it showed that leisure satisfaction was higher in sports activity of leisure activity patterns than hobbies, watching, socializing, tourism and games. It is concluded that infrastructure for sports should expand and that policy support is needed to increase leisure satisfaction in other leisure activities.
Translation, Adaptation, and Validation of the L’Échelle d’Interactions Infirmière-Patient-23 for the Portuguese Culture: The Multidimensional Nature of Nursing Care
Authors: Agostinho Paula , Gaspar Filomena , Potra Teresa
Published: October 2021

Nursing care is based on the interaction between nurse and patient. The L’Échelle d’Interactions Infirmière-Patient-23 (EIIP-23) is used to evaluate and understand the perception of nurses about their interventions in the practice of care, to reach better health results. The present study aims to validate the questionnaire EIIP-23 to Portuguese, evaluating its psychometric properties. Methods: This is methodological research for the process of cross-cultural translation and adaptation. Results: The process of cross-cultural translation and adaptation were satisfactory. The committee of experts reached an agreement of more than 90% in the first evaluation for all the items. The internal consistency of the nurse-patient interaction scale 22-PT (NPIS-22-PT) was 0.864. Exploratory and confirmatory factor analyses were carried out in the NPIS-22-PT model, with three factors. The results show that the final factorial solution presents acceptable goodness of fit indexes and adequate convergent validity. Conclusion: The translated version produced a good quality psychometric evaluation, and can be considered a valid, trustworthy, and useful instrument to evaluate the nurse-patient interactions in Portugal. It showed acceptable reliability and validity in psychometric tests. In the context of nursing, the NPIS-22-PT is a relevant instrument.
The M2a Macrophage Phenotype Accompanies Pulmonary Granuloma Resolution in Mmp12 Knock-Out Mice Instilled with Multiwall Carbon Nanotubes
Authors: Ogburn David , Bhalla Sophia , Leffler Nan , Mohan Arjun , Malur Anagha , Malur Achut G. , McPeek Matthew , Barna Barbara P. , Thomassen Mary Jane
Published: October 2021

Sarcoidosis is a chronic disease with unknown etiology and pathophysiology, characterized by granuloma formation. Matrix Metalloproteinase-12 (MMP12) is an elastase implicated in active granulomatous sarcoidosis. Previously, we reported that oropharyngeal instillation of multiwall carbon nanotubes (MWCNT) into C57Bl/6 mice induced sarcoid-like granulomas and upregulation of MMP12. When Mmp12 knock-out (KO) mice were instilled with MWCNT, granuloma formation occurred 10 days post-instillation but subsequently resolved at 60 days. Thus, we concluded that MMP12 was essential to granuloma persistence. The aim of the current study was to identify potential mechanisms of granuloma resolution in Mmp12KO mice. Strikingly, an M2 macrophage phenotype was present in Mmp12KO but not in C57Bl/6 mice. Between 10 and 60 days, macrophage populations in MWCNT-instilled Mmp12KO mice demonstrated an M2c to M2a phenotypic shift, with elevations in levels of IL-13, an M2 subtype-regulating factor. Furthermore, the M2 inducer, Apolipoprotein E (ApoE), and Matrix Metalloproteinase-14 (MMP14), a promoter of collagen degradation, were upregulated in 60-day MWCNT-instilled Mmp12KO mice. In conclusion, alveolar macrophages express two M2 phenotypes in Mmp12KO mice: M2c at 10 days when granulomas form, and M2a at 60 days when granulomas are resolving. Findings suggest that granuloma resolution in 60-day Mmp12KO mice requires an M2a macrophage phenotype.
Inhibition of BIRC2 Sensitizes α7-HPV-Related Cervical Squamous Cell Carcinoma to Chemotherapy
Authors: Lin Chiao-Yun , Wang Chun-Chieh , Wu Ren-Chin , Yang Lan-Yan , Chang Chen-Bin , Pan Yu-Bin , Chao Angel , Lai Chyong-Huey
Published: October 2021

The α7-human papillomavirus (HPV)-related cervical squamous cell carcinoma (SCC) is associated with poor prognosis. We compared the genomic profiles of this disease in a cohort corresponding to the 2001–2014 period with various responses to radiotherapy or concurrent chemoradiation through microRNA (miR) profiling involving miR 4.0 array and human transcriptome array 2.0 analyses. A real-time quantitative polymerase chain reaction was then conducted to identify the predictive biomarkers. A significantly lower expression of miR143-3p in recurrent tumors (p = 0.0309) relative to that in nonrecurrent tumors was observed. The miR143-3p targeted the mRNA expression of the baculoviral inhibitor of the apoptosis protein (IAP) repeat-containing 2 (BIRC2; p = 0.0261). The BIRC2 protein levels (p = 0.0023) were significantly higher in recurrent tumors than in nonrecurrent tumors. Moreover, the miR-143-3p sensitized the response of α7-HPV-related cervical SCC to chemotherapy by targeting BIRC2. A combination of BIRC2-inhibitor LCL161 and topotecan exerted synergistic effects on cancer cells and animal tumor models. In a pooled cohort of α7-HPV-related cervical SCC (including mixed infections with non-α7-HPV) treated between 1993 and 2014, high BIRC2 expression was associated with significantly worse outcomes (cancer-specific survival, hazard ratio (HR) = 1.42, p = 0.008; progression-free survival, HR = 1.64; p = 0.005). Summarily, BIRC2 constitutes a novel prognostic factor and therapeutic target for α7-HPV-related cervical SCC.
RESVEGA, a Nutraceutical Omega-3/Resveratrol Supplementation, Reduces Angiogenesis in a Preclinical Mouse Model of Choroidal Neovascularization
Authors: Courtaut Flavie , Aires Virginie , Acar Niyazi , Bretillon Lionel , Guerrera Ida Chiara , Chhuon Cerina , Pais de Barros Jean-Paul , Olmiere Céline , Delmas Dominique
Published: October 2021

Age-related macular degeneration (AMD) is an eye disease that is characterized by damage to the central part of the retina, the macula, and that affects millions of people worldwide. At an advanced stage, a blind spot grows in the center of vision, severely handicapping patients with this degenerative condition. Despite therapeutic advances thanks to the use of anti-VEGF, many resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether supplementation with Resvega®, a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, a well-known polyphenol in grapes, was able to counteract laser-induced choroidal neovascularization (CNV) in mice. We highlight that Resvega® significantly reduced CNV in mice compared with supplementations containing omega-3 or resveratrol alone. Moreover, a proteomic approach confirmed that Resvega® could counteract the progression of AMD through a pleiotropic effect targeting key regulators of neoangiogenesis in retina cells in vivo. These events were associated with an accumulation of resveratrol metabolites within the retina. Therefore, a supplementation of omega-3/resveratrol could improve the management or slow the progression of AMD in patients with this condition.
A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps
Authors: Briata Irene Maria , Paleari Laura , Rutigliani Mariangela , Petrera Marilena , Caviglia Silvia , Romagnoli Paola , Libera Mauro Dalla , Oppezzi Massimo , Puntoni Matteo , Siri Giacomo , Lazzeroni Matteo , Howells Lynne , Singh Raj , Brown Karen , DeCensi Andrea
Published: October 2021

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4–6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51–1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50–1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.
IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives
Authors: Španko Michal , Strnadová Karolína , Pavlíček Aleš Jan , Szabo Pavol , Kodet Ondřej , Valach Jaroslav , Dvořánková Barbora , Smetana Karel , Lacina Lukáš
Published: October 2021

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.
Proteomics and Nucleotide Profiling as Tools for Biomarker and Drug Target Discovery
Authors: Honoré Bent , Rice Gregory Edward , Vorum Henrik
Published: October 2021

Proteomics has gone through tremendous development during recent decades [...]
Serotonin and Melatonin Biosynthesis in Plants: Genome-Wide Identification of the Genes and Their Expression Reveal a Conserved Role in Stress and Development
Authors: Bhowal Bidisha , Bhattacharjee Annapurna , Goswami Kavita , Sanan-Mishra Neeti , Singla-Pareek Sneh L. , Kaur Charanpreet , Sopory Sudhir
Published: October 2021

Serotonin (Ser) and melatonin (Mel) serve as master regulators of plant growth and development by influencing diverse cellular processes. The enzymes namely, tryptophan decarboxylase (TDC) and tryptamine 5-hydroxylase (T5H) catalyse the formation of Ser from tryptophan. Subsequently, serotonin N-acetyl transferase (SNAT) and acetyl-serotonin methyltransferase (ASMT) form Mel from Ser. Plant genomes harbour multiple genes for each of these four enzymes, all of which have not been identified. Therefore, to delineate information regarding these four gene families, we carried out a genome-wide analysis of the genes involved in Ser and Mel biosynthesis in Arabidopsis, tomato, rice and sorghum. Phylogenetic analysis unravelled distinct evolutionary relationships among these genes from different plants. Interestingly, no gene family except ASMTs showed monocot- or dicot-specific clustering of respective proteins. Further, we observed tissue-specific, developmental and stress/hormone-mediated variations in the expression of the four gene families. The light/dark cycle also affected their expression in agreement with our quantitative reverse transcriptase-PCR (qRT-PCR) analysis. Importantly, we found that miRNAs (miR6249a and miR-1846e) regulated the expression of Ser and Mel biosynthesis under light and stress by influencing the expression of OsTDC5 and OsASMT18, respectively. Thus, this study may provide opportunities for functional characterization of suitable target genes of the Ser and Mel pathway to decipher their exact roles in plant physiology.
Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy
Authors: Sarhadi Virinder Kaur , Daddali Ravindra , Seppänen-Kaijansinkko Riitta
Published: October 2021

Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.
The Effect of Surface-Modified Gold Nanorods on the Early Stage of Embryonic Development and Angiogenesis: Insight into the Molecular Pathways
Authors: Mahmoud Nouf N. , Zakaria Zain Zaki , Kheraldine Hadeel , Gupta Ishita , Vranic Semir , Al-Asmakh Maha , Al Moustafa Ala-Eddin
Published: October 2021

Gold nanorods have been implicated in several biomedical applications. Herein, the effect of two surface-modified gold nanorods on the early stages of embryogenesis and angiogenesis was investigated using avian embryos at three days and their chorioallantoic membrane (CAM) at five days of incubation. We found that gold nanorods (GNR) modified with PEGylated phospholipid moiety show a high mortality rate in embryos after four days of exposure compared to GNR modified with PEGylated cholesterol moiety. Meanwhile, our data revealed that surface modified-GNR significantly inhibit the formation of new blood vessels in the treated CAM model after 48 h of exposure. Moreover, we report that surface-modified GNR significantly deregulate the expression of several genes implicated in cell proliferation, invasion, apoptosis, cellular energy metabolism, and angiogenesis. On the other hand, our data point out that GNR treatments can modulate the expression patterns of JNK1/2/3, NF-KB/p38, and MAPK, which could be the main molecular pathways of the nanorods in our experimental models.
Between Stress and Response: Function and Localization of Mechanosensitive Ca2+ Channels in Herbaceous and Perennial Plants
Authors: Hartmann Félix P. , Tinturier Erwan , Julien Jean-Louis , Leblanc-Fournier Nathalie
Published: October 2021

Over the past three decades, how plants sense and respond to mechanical stress has become a flourishing field of research. The pivotal role of mechanosensing in organogenesis and acclimation was demonstrated in various plants, and links are emerging between gene regulatory networks and physical forces exerted on tissues. However, how plant cells convert physical signals into chemical signals remains unclear. Numerous studies have focused on the role played by mechanosensitive (MS) calcium ion channels MCA, Piezo and OSCA. To complement these data, we combined data mining and visualization approaches to compare the tissue-specific expression of these genes, taking advantage of recent single-cell RNA-sequencing data obtained in the root apex and the stem of Arabidopsis and the Populus stem. These analyses raise questions about the relationships between the localization of MS channels and the localization of stress and responses. Such tissue-specific expression studies could help to elucidate the functions of MS channels. Finally, we stress the need for a better understanding of such mechanisms in trees, which are facing mechanical challenges of much higher magnitudes and over much longer time scales than herbaceous plants, and we mention practical applications of plant responsiveness to mechanical stress in agriculture and forestry.
Water Activity Prediction in Sugar and Polyol Systems Using Theoretical Molecular Descriptors
Authors: Zuorro Antonio
Published: October 2021

Water activity is a key factor in the development of pharmaceutical, cosmetic, and food products. In aqueous solutions of nonelectrolytes, the Norrish model provides a simple and effective way to evaluate this quantity. However, it contains a parameter, known as the Norrish constant, that must be estimated from experimental data. In this study, a new strategy is proposed for the prediction of water activity in the absence of experimental information, based on the use of theoretical molecular descriptors for characterizing the effects of a solute. This approach was applied to the evaluation of water activity in the presence of sugars (glucose, fructose, xylose, sucrose) and polyols (sorbitol, xylitol, glycerol, erythritol). The use of two descriptors related to the constitutional and connectivity properties of the solutes was first investigated. Subsequently, a new theoretical descriptor, named the global information index (G), was developed. By using this index, the water activity curves in the binary systems were reconstructed. The positive results obtained support the proposed strategy, as well as the possibility of including, in a single information index, the main molecular features of a solute that determine its effects on water activity.
Structural and Dynamical Behaviour of Colloids with Competing Interactions Confined in Slit Pores
Authors: Serna Horacio , Góźdź Wojciech T. , Noya Eva G.
Published: October 2021

Systems with short-range attractive and long-range repulsive interactions can form periodic modulated phases at low temperatures, such as cluster-crystal, hexagonal, lamellar and bicontinuous gyroid phases. These periodic microphases should be stable regardless of the physical origin of the interactions. However, they have not yet been experimentally observed in colloidal systems, where, in principle, the interactions can be tuned by modifying the colloidal solution. Our goal is to investigate whether the formation of some of these periodic microphases can be promoted by confinement in narrow slit pores. By performing simulations of a simple model with competing interactions, we find that both the cluster-crystal and lamellar phases can be stable up to higher temperatures than in the bulk system, whereas the hexagonal phase is destabilised at temperatures somewhat lower than in bulk. Besides, we observed that the internal ordering of the lamellar phase can be modified by changing the pore width. Interestingly, for sufficiently wide pores to host three lamellae, there is a range of temperatures for which the two lamellae close to the walls are internally ordered, whereas the one at the centre of the pore remains internally disordered. We also find that particle diffusion under confinement exhibits a complex dependence with the pore width and with the density, obtaining larger and smaller values of the diffusion coefficient than in the corresponding bulk system.
CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis
Authors: Nasiri-Aghdam Maryam , Garcia-Garduño Texali , Jave-Suárez Luis
Published: October 2021

Post-transcriptional modifications to coding and non-coding RNAs are unquestionably a pivotal way in which human mRNA and protein diversity can influence the different phases of a transcript’s life cycle. CELF (CUGBP Elav-like family) proteins are RBPs (RNA-binding proteins) with pleiotropic capabilities in RNA processing. Their responsibilities extend from alternative splicing and transcript editing in the nucleus to mRNA stability, and translation into the cytoplasm. In this way, CELF family members have been connected to global alterations in cancer proliferation and invasion, leading to their identification as potential tumor suppressors or even oncogenes. Notably, genetic variants, alternative splicing, phosphorylation, acetylation, subcellular distribution, competition with other RBPs, and ultimately lncRNAs, miRNAs, and circRNAs all impact CELF regulation. Discoveries have emerged about the control of CELF functions, particularly via noncoding RNAs, and CELF proteins have been identified as competing, antagonizing, and regulating agents of noncoding RNA biogenesis. On the other hand, CELFs are an intriguing example through which to broaden our understanding of the RBP/noncoding RNA regulatory axis. Balancing these complex pathways in cancer is undeniably pivotal and deserves further research. This review outlines some mechanisms of CELF protein regulation and their functional consequences in cancer physiology.
Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Alport Syndrome: A Primer for Clinicians
Authors: Martínez-Pulleiro Raquel , García-Murias María , Fidalgo-Díaz Manuel , García-González Miguel Ángel
Published: October 2021

Alport syndrome is a genetic and hereditary disease, caused by mutations in the type IV collagen genes COL4A3, COL4A4 and COL4A5, that affects the glomerular basement membrane of the kidney. It is a rare disease with an underestimated prevalence. Genetic analysis of population cohorts has revealed that it is the second most common inherited kidney disease after polycystic kidney disease. Renal involvement is the main manifestation, although it may have associated extrarenal manifestations such as hearing loss or ocular problems. The degree of expression of the disease changes according to the gene affected and other factors, known or yet to be known. The pathophysiology is not yet fully understood, although some receptors, pathways or molecules are known to be linked to the disease. There is also no specific treatment for Alport syndrome; the most commonly used are renin–angiotensin–aldosterone system inhibitors. In recent years, diagnosis has come a long way, thanks to advances in DNA sequencing technologies such as next-generation sequencing (NGS). Further research at the genetic and molecular levels in the future will complete the partial vision of the pathophysiological mechanism that we have, and will allow us to better understand what is happening and how to solve it.
Alterations in ACE and ACE2 Activities and Cardiomyocyte Signaling Underlie Improved Myocardial Function in a Rat Model of Repeated Remote Ischemic Conditioning
Authors: Bódi Beáta , Pilz Patrick M. , Mártha Lilla , Lang Miriam , Hamza Ouafa , Fagyas Miklós , Szabó Petra L. , Abraham Dietmar , Tóth Attila , Podesser Bruno K. , Kiss Attila , Papp Zoltán
Published: October 2021

Post-ischemic left ventricular (LV) remodeling and its hypothetical prevention by repeated remote ischemic conditioning (rRIC) in male Sprague–Dawley rats were studied. Myocardial infarction (MI) was evoked by permanent ligation of the left anterior descending coronary artery (LAD), and myocardial characteristics were tested in the infarcted anterior and non-infarcted inferior LV regions four and/or six weeks later. rRIC was induced by three cycles of five-minute-long unilateral hind limb ischemia and five minutes of reperfusion on a daily basis for a period of two weeks starting four weeks after LAD occlusion. Sham operated animals served as controls. Echocardiographic examinations and invasive hemodynamic measurements revealed distinct changes in LV systolic function between four and six weeks after MI induction in the absence of rRIC (i.e., LV ejection fraction (LVEF) decreased from 52.8 ± 2.1% to 50 ± 1.6%, mean ± SEM, p < 0.05) and in the presence of rRIC (i.e., LVEF increased from 48.2 ± 4.8% to 55.2 ± 4.1%, p < 0.05). Angiotensin-converting enzyme (ACE) activity was about five times higher in the anterior LV wall at six weeks than that in sham animals. Angiotensin-converting enzyme 2 (ACE2) activity roughly doubled in post-ischemic LVs. These increases in ACE and ACE2 activities were effectively mitigated by rRIC. Ca2+-sensitivities of force production (pCa50) of LV permeabilized cardiomyocytes were increased at six weeks after MI induction together with hypophosphorylation of 1) cardiac troponin I (cTnI) in both LV regions, and 2) cardiac myosin-binding protein C (cMyBP-C) in the anterior wall. rRIC normalized pCa50, cTnI and cMyBP-C phosphorylations. Taken together, post-ischemic LV remodeling involves region-specific alterations in ACE and ACE2 activities together with changes in cardiomyocyte myofilament protein phosphorylation and function. rRIC has the potential to prevent these alterations and to improve LV performance following MI.
IAF, QGF, and QDF Peptides Exhibit Cholesterol-Lowering Activity through a Statin-like HMG-CoA Reductase Regulation Mechanism: In Silico and In Vitro Approach
Authors: Silva Mariana , Philadelpho Biane , Santos Johnnie , Souza Victória , Souza Caio , Santiago Victória , Silva Jaff , Souza Carolina , Azeredo Francine , Castilho Marcelo , Cilli Eduardo , Ferreira Ederlan
Published: October 2021

In this study, in silico approaches are employed to investigate the binding mechanism of peptides derived from cowpea β-vignin and HMG-CoA reductase. With the obtained information, we designed synthetic peptides to evaluate their in vitro enzyme inhibitory activity. In vitro, the total protein extract and <3 kDa fraction, at 5000 µg, support this hypothesis (95% and 90% inhibition of HMG-CoA reductase, respectively). Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides were predicted to bind to the substrate binding site of HMGCR via HMG-CoAR. In silico, it was established that the mechanism of HMG-CoA reductase inhibition largely entailed mimicking the interactions of the decalin ring of simvastatin and via H-bonding; in vitro studies corroborated the predictions, whereby the HMG-CoA reductase activity was decreased by 69%, 77%, and 78%, respectively. Our results suggest that Ile-Ala-Phe, Gln-Gly-Phe, and Gln-Asp-Phe peptides derived from cowpea β-vignin have the potential to lower cholesterol synthesis through a statin-like regulation mechanism.
Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review
Authors: Kaul Ridhima , Paul Pradipta , Kumar Sanjay , Büsselberg Dietrich , Dwivedi Vivek Dhar , Chaari Ali
Published: October 2021

The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.
Genome Study of a Novel Virulent Phage vB_SspS_KASIA and Mu-like Prophages of Shewanella sp. M16 Provides Insights into the Genetic Diversity of the Shewanella Virome
Authors: Bujak Katarzyna , Decewicz Przemyslaw , Rosinska Joanna M. , Radlinska Monika
Published: October 2021

Shewanella is a ubiquitous bacterial genus of aquatic ecosystems, and its bacteriophages are also isolated from aquatic environments (oceans, lakes, ice, and wastewater). In this study, the isolation and characterization of a novel virulent Shewanella phage vB_SspS_KASIA and the identification of three prophages of its host, Shewanella sp. M16, including a mitomycin-inducible Mu-like siphovirus, vB_SspS_MuM16-1, became the starting point for comparative analyses of phages infecting Shewanella spp. and the determination of their position among the known bacterial viruses. A similarity networking analysis revealed the high diversity of Shewanella phages in general, with vB_SspS_KASIA clustering exclusively with Colwellia phage 9A, with which it forms a single viral cluster composed of two separate viral subclusters. Furthermore, vB_SspS_MuM16-1 presented itself as being significantly different from the phages deposited in public databases, expanding the diversity of the known Mu-like phages and giving potential molecular markers for the identification of Mu-like prophages in bacterial genomes. Moreover, the functional analysis performed for vB_SspS_KASIA suggested that, despite the KASIA host, the M16 strain grows better in a rich medium and at 30 °C the phage replication cycle seems to be optimal in restrictive culture conditions mimicking their natural environment, the Zloty Stok gold and arsenic mine.