bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Childhood Experiences and Chronic Diseases: Identifying a Cut-Point for ACE Scores
Authors: Alhowaymel Fahad M. , Kalmakis Karen A. , Chiodo Lisa M. , Kent Nicole M. , Almuneef Maha
Published: January 2023

Adverse Childhood Experiences (ACEs) contribute to many negative physiological, psychological, and behavioral health consequences. However, a cut-point for adverse childhood experience (ACE) scores, as it pertains to health outcomes, has not been clearly identified. This ambiguity has led to the use of different cut-points to define high scores. The aim of this study is to clarify a cut-point at which ACEs are significantly associated with negative chronic health outcomes. To accomplish this aim, a secondary analysis using data from a cross-sectional study was conducted. The Adverse Childhood Experiences-International Questionnaire (ACE-IQ) was used for data collection. Descriptive statistics, nonparametric regression, and logistic regression analyses were performed on a sample of 10,047 adults. Data from demographic and self-report health measures were included. The results showed that a cut-point of four or more ACEs was significantly associated with increased rates of chronic disease. Participants with at least one chronic disease were almost 3 times more likely (OR = 2.8) to be in the high ACE group. A standardized cut-point for ACE scores will assist in future research examining the impact of high ACEs across cultures to study the effect of childhood experiences on health.
Understanding Mental Health in Developmental Dyslexia: A Scoping Review
Authors: Wilmot Adrienne , Hasking Penelope , Leitão Suze , Hill Elizabeth , Boyes Mark
Published: January 2023

Children with dyslexia are at elevated risk of internalising and externalising mental health concerns. Our aim was to scope the extent and nature of the literature investigating factors which may influence this association. We systematically searched the peer-reviewed and grey literature with no restrictions on the date. We included both qualitative and quantitative studies. Inclusion criteria included: (1) a focus on childhood (≤18 years) reading/learning difficulties; (2) internalising and/or externalising symptoms; and (3) a potentially modifiable third factor (e.g., self-esteem). Ninety-eight studies met the inclusion criteria. We organised the studies according to individual, family, and community-level third factors. Whilst a range of third factors were identified, relatively few researchers tested associations between the third factor and mental health in the context of dyslexia. Furthermore, there was a focus on primary rather than secondary school experience and a reliance, in many cases, on teacher/parent perspectives on children’s mental health. Future researchers are encouraged to explore links between socio-emotional skills, coping strategies, school connectedness, and mental health in the context of dyslexia. Research of this nature is important to assist with the identification of children who are more (or less) at risk of mental health concerns and to inform tailored mental health programs for children with dyslexia.
The Impact of a Six-Year Existing Screening Programme Using the Faecal Immunochemical Test in Flanders (Belgium) on Colorectal Cancer Incidence, Mortality and Survival: A Population-Based Study
Authors: Tran Thuy Ngan , Hoeck Sarah , De Schutter Harlinde , Janssens Sharon , Peeters Marc , Van Hal Guido
Published: January 2023

The faecal immunochemical test (FIT) has been increasingly used for organised colorectal cancer (CRC) screening. We assessed the impact of a six-year existing FIT screening programme in Flanders (Belgium) on CRC incidence, mortality and survival. The Flemish CRC screening programme started in 2013, targeting individuals aged 50–74 years. Joinpoint regression was used to investigate trends of age-standardised CRC incidence and mortality among individuals aged 50–79 years (2004–2019). Their 5-year relative survival was calculated using the Ederer II method. We found that FIT screening significantly reduced CRC incidence, especially that of advanced-stage CRCs (69.8/100,000 in 2012 vs. 51.1/100,000 in 2019), with a greater impact in men. Mortality started to decline in men two years after organised screening implementation (annual reduction of 9.3% after 2015 vs. 2.2% before 2015). The 5-year relative survival was significantly higher in screen-detected (93.8%) and lower in FIT non-participant CRCs (61.9%) vs. FIT interval cancers and CRCs in never-invited cases (67.6% and 66.7%, respectively). Organised FIT screening in Flanders clearly reduced CRC incidence (especially advanced-stage) and mortality (in men, but not yet in women). Survival is significantly better in screen-detected cases vs. CRCs in unscreened people. Our findings support the implementation of FIT organised screening and the continued effort to increase uptake.
How Does Agricultural Mechanization Service Affect Agricultural Green Transformation in China?
Authors: Li Xuelan , Guan Rui
Published: January 2023

Agricultural mechanization service (AMS) is a critical path to achieving agricultural green transformation with smallholders as the mainstay of agricultural production. Based on the panel data of 30 Chinese provinces from 2011 to 2020, this paper measures the AGTFP using the Super-SBM model and examines the effects of different AMS supply agents on AGTFP and spatial spillover effects through the spatial Durbin model. The main conclusions are as follows: First, China’s AGTFP showed a stable growth trend, with the mean value increasing from 0.1990 in 2011 to 0.5590 in 2020. Second, the specialization (SPO) and large-scale (LSO) of AMS supply organizations have significantly positive effect on the AGTFP of the local province. However, SPO has a significantly positive effect on the AGTFP of the neighboring provinces, while LSO has the opposite effect. Third, the specialization of AMS supply individuals (SPI) has significantly negative effect on the AGTFP of the local province. In contrast, the large-scale AMS supply individuals (LSI) has the opposite effect. Furthermore, the spatial spillover effects of both are insignificant. Fourth, the spatial spillover effect of AGTFP shows asymmetry among different regions and indicates that AMS resources flow from non-main grain production and economically developed regions to main grain production and less developed regions. These findings provide helpful policy references for constructing and improving the agricultural mechanization service system and realizing the agricultural green transformation in economies as the mainstay of agricultural production.
Climate Variables Related to the Incidence of Human Leishmaniosis in Montenegro in Southeastern Europe during Seven Decades (1945–2014)
Authors: Medenica Sanja , Miladinović-Tasić Nataša , Stojanović Nikola M. , Lakićević Novak , Rakočević Božidarka
Published: January 2023

Leishmaniosis (or leishmaniasis) is a neglected parasitosis most commonly transmitted by the sandfly bite. Changes in temperature, precipitation, and humidity can greatly affect the vectors and reservoir hosts. This study aimed to determine the association between temperature, air humidity, and weather conditions with the incidence of leishmaniasis in Montenegro during a seven-decade period (1945–2014) and to statistically compare and correlate the obtained data. In the studied period, there were 165 registered cases of leishmaniosis, 96.4%, in the coastal and central region of Montenegro, with an average incidence rate of 0.45/100.000. The visceral form of leishmaniosis predominated (99% of the cases), with only one case of cutaneous disease. Climate factors (average temperature, air humidity, and precipitation) had an impact on the occurrence of leishmaniosis in Montenegro. Air temperature elevated by 1 °C in all regions of Montenegro was significantly correlated with an increased incidence of leishmaniosis, by 0.150 (0.013 to 0.287; p < 0.05). In order to improve prevention and control of this disease, it is also necessary to investigate other factors with a possible impact on the number of cases of this neglected parasitosis.
Primary Validation of the Submandibular Skinfold as an Anthropometric Measurement of Cardiometabolic Risk in People with Intellectual Disabilities
Authors: Ferrero-Hernández Paloma , Farías-Valenzuela Claudio , Ferrari Gerson , Álvarez-Arangua Sebastián , Villalobos-Flores Hans , Valdivia-Moral Pedro
Published: January 2023

The accumulation of body fat is an important cardiometabolic risk factor; however, there is no consensus about which measure is more reliable for the assessment of cardiometabolic risk in people with intellectual disabilities. The aim of the present study was to primarily validate the submandibular skinfold as an anthropometric measurement of cardiometabolic risk in children, adolescents, and adults with intellectual disabilities, using a cross-sectional study made up of 131 people (67.2% men) with mild and moderate intellectual disability. The cardiometabolic risk indicators used were: body mass index (kg/m2), neck circumference (cm), waist circumference (cm), calf circumference (cm) and waist-to-height ratio. Moderate correlations were demonstrated between the submandibular skinfold measure and the anthropometric measurements analyzed in the three age categories, showing the highest correlation (r = 0.70) between the submandibular skinfold and BMI in the adolescent group and waist-to-height ratio in adults. The implementation of the submandibular skinfold measurement is suggested as an easy, fast, and minimally invasive anthropometric measurement as part of the physical and nutritional evaluation for the assessment of cardiometabolic risk in people with intellectual disabilities.
Understanding the Impact of Contemporary Racism on the Mental Health of Middle Class Black Americans
Authors: Hudson Darrell , Collins-Anderson Akilah , Hutson William
Published: January 2023

Evidence from previous research indicates that while socioeconomic status (SES) narrows Black-White health inequities, these inequities do not completely disappear, and in some cases, worsen. Why do Black-White health inequities persist, even when controlling for SES? It is critical to examine how perceptions of unfair treatment, especially those that are nuanced and subtle, affect the mental health of Black Americans with greater levels of SES. This study, using a new sample composed exclusively of college-educated Black Americans, investigated whether experiences related to racism were associated with poorer mental health. Qualtrics provided the sample from their nationwide panelists that met the research criteria. Inclusion criteria included the following: (1) self-identified as Black or African American; (2) at least 24 years old; (3) completed a 4-year college degree or higher. The findings from this study indicated that the effects of unfair treatment are significantly associated with poorer mental health. These findings highlight the insidious nature of contemporary racism as the everyday experiences of unfair treatment have a tremendous effect on depressive symptoms among this sample of college-educated Black Americans. Efforts to simply improve SES among historically marginalized groups will not bring about health equity. Findings from this study indicate that there are mental health costs associated with upward social mobility. It is likely that these costs, particularly the experience of everyday unfair treatment, likely diminish the social, economic and health returns on the human capital.
Poor Sleep Quality in Aging: The Association with Mental Health
Authors: Corbo Ilaria , Forte Giuseppe , Favieri Francesca , Casagrande Maria
Published: January 2023

Sleep disturbances are common in the elderly. A primary sleep disorder can result from the physiological decline of aging; however, secondary sleep problems result from various causes involving physical and mental health. Since little is known about the relationships between sleep quality and mental health in aging, the present study aims to understand how different aspects generally associated with sleep (e.g., psychological and physiological factors, and sleep medication) may predict poor sleep quality in different stages of the lifespan. Therefore, we conducted several analyses (ANOVAs, Pearson correlations, and linear regressions) to test the hypotheses of the study. Accordingly, from a pool of 180 participants (elderly, middle-aged, and young adults), 143 individuals with poor sleep quality were selected. Different predictive patterns in the three groups emerged. Specifically, the use of sleep medication associated with worse sleep conditions is predicted by poor sleep quality in the elderly and by depression in young adults. In contrast, worsening sleep quality is predicted by depression in middle-aged adults. Previous studies focused on the transitions from good to poor sleep quality, while this is the first study to have examined the features of poor sleep quality in aging, highlighting different sleep patterns across the lifespan. This evidence should be considered from a preventive perspective.
Modern Rape Myths: Justifying Victim and Perpetrator Blame in Sexual Violence
Authors: Murray Carol , Calderón Carlos , Bahamondes Joaquín
Published: January 2023

Rape myths are beliefs, stereotypes, and attitudes usually false, widespread, and persistent about rape, victims, and perpetrators. They aim to deny and justify men’s sexual assault against women. This study evaluates the mediating effect of modern rape myths on the relationship between gender system justification and attribution of blame to both victim and perpetrator in a fictional case of sexual violence. A total of 375 individuals residing in Chile, 255 women and 120 men, 19–81 years (M = 37.6 SD = 13.06) participated in the study. Results from a Structural Equation Model show that gender system justification is directly related to the attribution of blame to the victim, showing an indirect relationship throughout the modern rape myth. However, gender system justification and attribution of blame to the aggressor are indirectly related, being mediated by modern rape myths. The study of the relationship between the acceptance of modern rape myths, gender-specific system justification, and victim and aggressor blame for rape is a contribution to understanding beliefs justifying sexual violence against women.
Temporal-Spatial Evolution and Trend Prediction of the Supply Efficiency of Primary Medical Health Service—An Empirical Study Based on Central and Western Regions of China
Authors: Wu Fang , Gu Mingyao , Zhu Chenming , Qu Yingna
Published: January 2023

China has established a comprehensive primary medical health service system, but the development of primary medical health services in the central and western regions is still unbalanced and insufficient. Based on data from 2010 to 2019, this paper constructs a super efficiency Slack-Based Measure model to calculate the supply efficiency of primary medical health services in 20 provinces and cities in central and western China. Using Kernel density estimation and Markov chain analysis, this paper further analyzes the spatial-temporal evolution of the supply efficiency of primary medical health services in central and western China, and also predicts the future development distribution through the limiting distribution of Markov chain to provide a theoretical basis for promoting the sinking of high-quality medical resources to the primary level. The results show that firstly, during the observation period, the center of the Kernel density curve moves to the left, and the main peak value decreases continuously. The main diagonal elements of the traditional Markov transition probability matrix are 0.7872, 0.5172, 0.8353, and 0.7368 respectively, which are significantly larger than other elements. Secondly, when adjacent to low state and high state, it will develop into convergence distributions of 0.7251 and 0.8243. The supply efficiency of primary medical health services in central and western China has the characteristics of high (Ningxia) and low (Shaanxi) aggregation respectively, but the aggregation trend is weakened. Thirdly, the supply efficiency of health services has the stability of keeping its own state unchanged, but the transition of state can still occur. The long-term development of the current trend cannot break the distribution characteristics of the high and low clusters, the efficiency will show a downward trend in the next 10–20 years, and still the problem of uneven long-term development emerges.
Community Health Assessment Tools Adoptable in Nursing Practice: A Scoping Review
Authors: Pazzaglia Chiara , Camedda Claudia , Ugenti Nikita Valentina , Trentin Andrea , Scalorbi Sandra , Longobucco Yari
Published: January 2023

The WHO European Region defined the role of a new central professional for primary care, the Family and Community Nurse (FCN). The introduction of an FCN in the framework of health policies highlights a key role of nurses in addressing the needs of families and communities. A scoping review was conducted in order to identify and describe the available tools which have been adopted for the assessment of community health needs by FCNs. A comprehensive literature review on the Embase, Cochrane Library, PubMed, CINAHL, Scopus and PsycInfo databases was conducted including all studies up to May 2021. A total of 1563 studies were identified and 36 of them were included. The literature review made it possible to identify studies employing twelve different community assessment tools or modalities. Referring to the WHO framework proposed in 2001, some common themes have been identified with an uneven distribution, such as profiling the population, deciding on priorities for action and public healthcare programs, implementing the planned activities, an evaluation of the health outcomes, multidisciplinary activity, flexibility and involving the community. To the best of our knowledge, this work is the first attempt to provide an overview of community assessment tools, keeping the guidance provided by the WHO as a reference.
Is Frailty Diagnosis Important in Patients with COPD? A Narrative Review of the Literature
Authors: Tarazona-Santabalbina Francisco José , Naval Elsa , De la Cámara-de las Heras Juan María , Cunha-Pérez Cristina , Viña José
Published: January 2023

Frailty is prevalent in older adults and is related to a worsening functionality, quality of life, and health outcomes. Though there is an increasing interest in this field, the relationship between frailty and worsening COPD outcomes remains unknown. A narrative review of the literature with studies published between 2018 and 2022 was carried out to address three questions: the prevalence of frailty and other geriatric syndromes in COPD patients, the link between frailty and worsening health outcomes in COPD patients, and the non-pharmacological interventions performed in order to reverse frailty in these patients. A total of 25 articles were selected. Frailty prevalence ranged from 6% and 85.9%, depending on the COPD severity and the frailty measurement tool used. Frailty in COPD patients was related to a high prevalence of geriatric syndromes and to a high incidence of adverse events such as exacerbations, admissions, readmissions, and mortality. One study showed improvements in functionality after physical intervention. In conclusion, the prevalence of frailty is associated with a high incidence of geriatric syndromes and adverse events in COPD patients. The use of frailty screenings and a comprehensive geriatric assessment of COPD patients is advisable in order to detect associated problems and to establish individualized approaches for better outcomes.
Parent-Implemented Telepractice Autism Intervention: A Case Study of Maintenance and Generalization
Authors: Meadan Hedda , Sands Michelle M. , Chung Moon Y.
Published: January 2023

The extent to which people maintain new skills and generalize those skills to new contexts without support are two aspects of intervention research that can be difficult to examine, especially over a sustained period of time and across a variety of contexts. In past research, we have explored teaching parents and caregivers to implement evidence-based communication strategies with their young children with autism who are minimally verbal. When a former research participant contacted us with a request to participate in our project again, four years later and with a different son, we used this as an opportunity to ask questions about her maintenance of the skills in using the targeted strategies, and her generalization of those skills to a different child. Using the data collected with her older son, Ali, and new data collected four years later with her younger son, Rami, we present a case study of this mother. We discuss the implications of the findings on interpreting the efficacy of the telepractice intervention’s programming for generalization, identifying opportunities for refining the intervention, and insights useful for other intervention research.
The Role of Slurry Reflux in a Corn Stalk Continuous Anaerobic Digestion System: Performance and Microbial Community
Authors: Zhao Ling , Gao Yang , Sun Jiaxing , Wang Yanan , Wang Congxin , Yu Shuai , Wang Zhen , Li Jingyang , Liu Ronghou , Kou Wei
Published: January 2023

Slurry reflux is a low-cost slurry reduction technology, which can solve the problem that a large amount of slurry cannot be completely consumed in a biogas plant. Anaerobic digestion (AD) of corn stalks with slurry reflux and non-reflux was compared and evaluated in continuous anaerobic digestion to clarify the effects of slurry reflux on AD with organic loading rate (OLR) variation. It was found that slurry reflux increased cumulative methane production and improved system stability. The average methane yield of the slurry reflux group was 224.19 mL/gVS, which was 41.35% higher than that of the non-reflux group. High-throughput sequencing results showed that slurry reflux increased the microbial community richness. The dominant microorganisms in the reflux group were in phylum Bacteroidetes, which have the capacity to degrade polymers, and Methanothrix, which is an aceticlastic methanogen. The relative abundances of Bacteroidetes and Methanothrix were 32.41% and 41.75%, respectively. Clostridium III and Saccharofermentans, which are related to syntrophic acetate oxidation and hydrolysis, were increased in relative abundance in the slurry reflux system. The increase of the OLR altered the main methane-producing pathway from the acetoclastic methanogenic pathway to the hydrogenotrophic methanogenic pathway in the AD system, and the slurry reflux can delay this trend. This study provided an effective way for the reduction and utilization of slurry in a biogas plant.
Targeting Cancer Stem Cells as the Key Driver of Carcinogenesis and Therapeutic Resistance
Authors: Eid Refaat A. , Alaa Edeen Muhammad , Shedid Eslam M. , Kamal Al Shaimaa S. , Warda Mona M. , Mamdouh Farag , Khedr Sohila A. , Soltan Mohamed A. , Jeon Hee Won , Zaki Mohamed Samir A. , Kim Bonglee
Published: January 2023

The emerging concept of cancer stem cells (CSCs) as the key driver behind carcinogenesis, progression, and diversity has displaced the prior model of a tumor composed of cells with similar subsequently acquired mutations and an equivalent capacity for renewal, invasion, and metastasis. This significant change has shifted the research focus toward targeting CSCs to eradicate cancer. CSCs may be characterized using cell surface markers. They are defined by their capacity to self-renew and differentiate, resist conventional therapies, and generate new tumors following repeated transplantation in xenografted mice. CSCs’ functional capabilities are governed by various intracellular and extracellular variables such as pluripotency-related transcription factors, internal signaling pathways, and external stimuli. Numerous natural compounds and synthetic chemicals have been investigated for their ability to disrupt these regulatory components and inhibit stemness and terminal differentiation in CSCs, hence achieving clinical implications. However, no cancer treatment focuses on the biological consequences of these drugs on CSCs, and their functions have been established. This article provides a biomedical discussion of cancer at the time along with an overview of CSCs and their origin, features, characterization, isolation techniques, signaling pathways, and novel targeted therapeutic approaches. Additionally, we highlighted the factors endorsed as controlling or helping to promote stemness in CSCs. Our objective was to encourage future studies on these prospective treatments to develop a framework for their application as single or combined therapeutics to eradicate various forms of cancer.
The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma
Authors: Gabanella Francesca , Colizza Andrea , Mottola Maria Chiara , Francati Silvia , Blaconà Giovanna , Petrella Carla , Barbato Christian , Greco Antonio , Ralli Massimo , Fiore Marco , Corbi Nicoletta , Ferraguti Giampiero , Corsi Alessandro , Minni Antonio , de Vincentiis Marco , Passananti Claudio , Di Certo Maria Grazia
Published: January 2023

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.
The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression
Authors: Kanno Yosuke
Published: January 2023

Fibrotic diseases, such as systemic sclerosis (SSc), idiopathic pulmonary fibrosis, renal fibrosis and liver cirrhosis are characterized by tissue overgrowth due to excessive extracellular matrix (ECM) deposition. Fibrosis progression is caused by ECM overproduction and the inhibition of ECM degradation due to several events, including inflammation, vascular endothelial dysfunction, and immune abnormalities. Recently, it has been reported that urokinase plasminogen activator (uPA) and its receptor (uPAR), known to be fibrinolytic factors, orchestrate the inflammatory response, vascular homeostasis, and immune homeostasis system. The uPA/uPAR system may show promise as a potential therapeutic target for fibrotic diseases. This review considers the role of the uPA/uPAR system in the progression of fibrotic diseases.
Association between HLA DNA Variants and Long-Term Response to Anti-TNF Drugs in a Spanish Pediatric Inflammatory Bowel Disease Cohort
Authors: Salvador-Martín Sara , Zapata-Cobo Paula , Velasco Marta , Palomino Laura M. , Clemente Susana , Segarra Oscar , Sánchez Cesar , Tolín Mar , Moreno-Álvarez Ana , Fernández-Lorenzo Ana , Pérez-Moneo Begoña , Loverdos Inés , Navas López Victor Manuel , Millán Antonio , Magallares Lorena , Torres-Peral Ricardo , García-Romero Ruth , Pujol-Muncunill Gemma , Merino-Bohorquez Vicente , Rodríguez Alejandro , Salcedo Enrique , López-Cauce Beatriz , Marín-Jiménez Ignacio , Menchén Luis , Laserna-Mendieta Emilio , Lucendo Alfredo J. , Sanjurjo-Sáez María , López-Fernández Luis A.
Published: January 2023

The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.
Pharmacokinetic and Permeation Studies in Rat Brain of Natural Compounds Led to Investigate Eugenol as Direct Activator of Dopamine Release in PC12 Cells
Authors: Pavan Barbara , Bianchi Anna , Botti Giada , Ferraro Luca , Valerii Maria Chiara , Spisni Enzo , Dalpiaz Alessandro
Published: January 2023

Eugenol, cinnamaldehyde and D-limonene, the main components of natural essential oils, are endowed with antioxidant and anti-inflammatory properties which allow them to induce beneficial effects on intestinal, cardiac and neuronal levels. In order to characterize their pharmacokinetic profiles and aptitude to permeate in the central nervous system after intravenous and oral administration to rats, new analytical procedures, easily achievable with HPLC-UV techniques, were developed. The terminal half-lives of these compounds range from 12.4 ± 0.9 (D-limonene) and 23.1 ± 1.6 min (cinnamaldehyde); their oral bioavailability appears relatively poor, ranging from 4.25 ± 0.11% (eugenol) to 7.33 ± 0.37% (cinnamaldehyde). Eugenol evidences a marked aptitude to permeate in the cerebrospinal fluid (CSF) of rats following both intravenous and oral administrations, whereas cinnamaldehyde appears able to reach the CSF only after intravenous administration; limonene is totally unable to permeate in the CSF. Eugenol was therefore recruited for in vitro studies of viability and time-/dose-dependent dopamine release in neuronal differentiated PC12 cells (a recognized cellular model mimicking dopaminergic neurons), evidencing its ability to increase cell viability and to induce dopamine release according to a U-shaped time-course curve. Moreover, concentration-response data suggest that eugenol may induce beneficial effects against Parkinson’s disease after oral administration.
Pressure Tuning Studies of Four-Stranded Nucleic Acid Structures
Authors: Smeller László
Published: January 2023

Four-stranded folded structures, such as G-quadruplexes and i-motifs in the genome, have attracted a growing interest nowadays since they have been discovered in the telomere and in several oncogene promoter regions. Their biological relevance is undeniable since their existence in living cells has been observed. In vivo they take part in the regulation of gene expression, in vitro they are used in the analytical biochemistry. They are attractive and promising targets for cancer therapy. Pressure studies can reveal specific aspects of the molecular processes. Pressure tuning experiments allow the determination of the volumetric parameters of the folded structures and of the folding–unfolding processes. Here, we review the thermodynamic parameters with a special focus on the volumetric ones, which were determined using pressure tuning spectroscopic experiments on the G-quadruplex and i-motif nucleic acid forms.
Changes in Serum Protein–Peptide Patterns in Atopic Children Allergic to Plant Storage Proteins
Authors: Packi Kacper , Matysiak Joanna , Matuszewska Eliza , Bręborowicz Anna , Matysiak Jan
Published: January 2023

Next to cow’s milk and eggs, plant foods, i.e., legumes, tree nuts and cereal grains, most often sensitise atopic children. Storage proteins constitutes the most relevant protein fraction of plant foods, causing primary sensitisation. They exhibit strong allergenic properties and immunogenicity. Our goal was to analyse sensitisation to 26 plant storage proteins in a group of 76 children aged 0–5 years with chronic symptoms of atopic dermatitis using Allergy Explorer ALEX2 and to discover changes in serum protein–peptide patterns in allergic patients with the use of MALDI-TOF-MS. We reported that 25% of children were allergic to 2S albumins, 19.7% to 7S globulins, 13.2% to 11S globulins and 1.3% to cereal prolamins. The most common allergenic molecules were Ara h 1 (18.4%), Ara h 2 (17.1%), Ara h 6 (15.8%) and Ara h 3 (11.8%) from peanuts, and the mean serum sIgE concentrations in allergic patients were 10.93 kUA/L, 15.353 kUA/L, 15.359 kUA/L and 9.038 kUA/L, respectively. In children allergic to storage proteins compared to the other patients (both allergic and non-allergic), the cell cycle control protein 50A, testis-expressed sequence 13B, DENN domain-containing protein 5A and SKI family transcriptional corepressor 2 were altered. Our results indicate that the IgE-mediated allergy to storage proteins is a huge problem in a group of young, atopic children, and show the potential of proteomic analysis in the prediction of primary sensitisation to plant foods. It is the next crucial step for understanding the molecular consequences of allergy to storage proteins.
Irisin Modulates Inflammatory, Angiogenic, and Osteogenic Factors during Fracture Healing
Authors: Oranger Angela , Zerlotin Roberta , Buccoliero Cinzia , Sanesi Lorenzo , Storlino Giuseppina , Schipani Ernestina , Kozloff Kenneth Michael , Mori Giorgio , Colaianni Graziana , Colucci Silvia , Grano Maria
Published: January 2023

Bone fractures are a widespread clinical event due to accidental falls and trauma or bone fragility; they also occur in association with various diseases and are common with aging. In the search for new therapeutic strategies, a crucial link between irisin and bone fractures has recently emerged. To explore this issue, we subjected 8-week-old C57BL/6 male mice to tibial fracture, and then we treated them with intra-peritoneal injection of r-Irisin (100 µg/kg/weekly) or vehicle as control. At day 10 post fracture, histological analysis showed a significant reduced expression of inflammatory cytokines as tumor necrosis factor-alpha (TNFα) (p = 0.004) and macrophage inflammatory protein-alpha (MIP-1α) (p = 0.015) in the cartilaginous callus of irisin-treated mice compared to controls, supporting irisin’s anti-inflammatory role. We also found increased expressions of the pro-angiogenic molecule vascular endothelial growth factor (VEGF) (p = 0.002) and the metalloproteinase MMP-13 (p = 0.0006) in the irisin-treated mice compared to the vehicle ones, suggesting a myokine involvement in angiogenesis and cartilage matrix degradation processes. Moreover, the bone morphogenetic protein (BMP2) expression was also upregulated (p = 0.002). Taken together, our findings suggest that irisin can contribute to fracture repair by reducing inflammation and promoting vessel invasion, matrix degradation, and bone formation, supporting its possible role as a novel molecule for fracture treatment.
Gliflozins Have an Anti-Inflammatory Effect on Renal Proximal Tubular Epithelial Cells in a Diabetic and Inflammatory Microenvironment In Vitro
Authors: Koch Benjamin , Fuhrmann Dominik C. , Schubert Ralf , Geiger Helmut , Speer Thimoteus , Baer Patrick C.
Published: January 2023

Inflammation is intimately involved in the pathogenesis of diabetic kidney disease. Inhibition of SGLT-2 by a specific class of drugs, gliflozins, has been shown to reduce inflammation and attenuate the progression of diabetic nephropathy, in addition to its main effect of inhibiting renal glucose reabsorption. We used highly purified human renal proximal tubular epithelial cells (PTCs) as an in vitro model to study the cellular response to a diabetic (high glucose) and inflammatory (cytokines) microenvironment and the effect of gliflozins. In this context, we investigated the influence of SGLT-2 inhibition by empa- and dapagliflozin (500 nM) on the expression of pro-inflammatory factors (IL-1β, IL-6, TNF-α, MCP-1, and ICAM-1). The results clearly indicate an anti-inflammatory effect of both gliflozins. Although induced expression of the four cytokines was only slightly attenuated, there was a clear effect on the expression of the adhesion molecule ICAM-1, a master regulator of cellular responses in inflammation and injury resolution. The induced expression of ICAM-1 mRNA was significantly reduced by approximately 13.5% by empagliflozin and also showed an inhibitory trend with dapagliflozin. However, induced ICAM-1 protein expression was significantly inhibited from 24.71 ± 1.0 ng/mL to 18.81 ± 3.9 (empagliflozin) and 19.62 ± 2.1 ng/mL (dapagliflozin). In conclusion, an additional anti-inflammatory effect of empa- and dapagliflozin in therapeutically observed concentrations was demonstrated in primary human PTCs in vitro.
Comprehensive Analysis and Functional Verification of the Pinus massoniana NBS-LRR Gene Family Involved in the Resistance to Bursaphelenchus xylophilus
Authors: Xie Yini , Liu Bin , Gao Kai , Zhao Yunxiao , Li Wenhua , Deng Lili , Zhou Zhichun , Liu Qinghua
Published: January 2023

Pinus massoniana Lamb. is a crucial timber and resin conifer in China, but its plantation industry is threatened by outbreaks of pine wilt disease (PWD) caused by Bursaphelenchus xylophilus (pinewood nematode; PWN). However, as of yet, there is no comprehensive analysis of NBS-LRR genes in P. massoniana involved in its defense against PWN. In this study, 507 NBS genes were identified in the transcriptome of resistant and susceptible P. masoniana inoculated with the PWN. The phylogenetic analysis and expression profiles of resistant and susceptible P. massoniana revealed that the up-regulated PmNBS-LRR97 gene was involved in conferring resistance to PWN. The results of real-time quantitative PCR (qRT-PCR) showed that PmNBS-LRR97 was significantly up-regulated after PWN infection, especially in the stems. Subcellular localization indicated that PmNBS-LRR97 located to the cell membrane. PmNBS-LRR97 significantly activated the expression of reactive oxygen species (ROS)-related genes in P. massoniana. In addition, the overexpression of PmNBS-LRR97 was capable of promoting the production of ROS, aiding in plant growth and development. In summary, PmNBS-LRR97 participates in the defense response to PWN and plays an active role in conferring resistance in P. massoniana. This finding provides new insight into the regulatory mechanism of the R gene in P. massoniana.
Increased Serum Levels of Tumor Necrosis Factor-like Ligand 1A in Atopic Dermatitis
Authors: Hisamoto Teruyoshi , Suga Hiraku , Yoshizaki-Ogawa Asako , Sato Shinichi , Yoshizaki Ayumi
Published: January 2023

Atopic dermatitis (AD) is a common chronic skin disease with pruritus, affecting 5–20% of the population in developed countries. Though its cause varies from genetic polymorphisms to the environmental factors, the T-helper (Th) 2 inflammation is one of the main characteristic pathoses. TNF superfamily ligand A (TL1A) is a recently discovered cytokine, which is released by various immune cells and reported to have an ability to stimulate Th1, Th2, and Th17 responses. Its association was investigated in chronic inflammatory disease, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, its role on AD is unclear. To elucidate the association of TL1A in AD, we measured the serum TL1A levels in AD patients and healthy controls and performed the immunohistochemistry of TL1A. The result showed that the serum TL1A levels were higher in AD patients than healthy controls, and they positively correlated with the serum immunoglobulin E levels, serum Lactate dehydrogenase, and the number of eosinophils in peripheral blood. The immunohistochemistry of TL1A also showed TL1A expression in epithelium of AD samples. Because previous studies indicate TL1A has a certain role as an inflammation enhancer in Th2 and/or Th17 polarized disease, TL1A in AD may also has a role as an inflammation generator.
Characterisation of the Paternal Influence on Intergenerational Offspring Cardiac and Brain Lipid Homeostasis in Mice
Authors: Furse Samuel , Morgan Hannah L. , Koulman Albert , Watkins Adam J.
Published: January 2023

There is growing evidence that poor paternal diet at the time of conception increase the risk of offspring developing a range of non-communicable metabolic diseases, such as obesity, diabetes and cardiovascular disease, in adulthood. We hypothesise that a paternal low protein–high carbohydrate diet perturbs offspring tissue lipid abundance through both sperm and seminal plasma-mediated mechanisms. To test our hypothesis, we fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. We generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using high resolution mass-spectrometry, we found that offspring derived from either LPD sperm or seminal fluid displayed perturbed cardiac and brain lipid abundance from just three weeks of age, typically associated with the altered abundance of tissue triglycerides. We also observed the differential sex-specific patterns of lipids between the control and experimental offspring’s hearts and brains. These observations indicate that poor paternal diet at the time of conception affects offspring cardiac and brain lipid profiles in an age-, sex- and generation-specific manner.
Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy
Authors: Wang Ling , Wang Binquan , Wu Chunyan , Wang Jie , Sun Mingkuan
Published: January 2023

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, the prevalence of autism spectrum disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for autism have emerged. As a result, neurobehavioral abnormalities, neurobiological alterations in ASD, and the development of novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss the development of multiple animal models of ASD to contribute to the disease mechanisms of ASD, as well as new studies from multiple disciplines to assess the behavioral pathology of ASD. In addition, we summarize and highlight the mechanistic advances regarding gene transcription, RNA and non-coding RNA translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation and neural loop abnormalities in autism to provide a theoretical basis for the next step of precision therapy. Furthermore, we review existing autism therapy tactics and limits and present challenges and opportunities for translating multidisciplinary knowledge of ASD into clinical practice.
Using a Network-Based Analysis Approach to Investigate the Involvement of S. aureus in the Pathogenesis of Granulomatosis with Polyangiitis
Authors: Rowland Gregory , Kronbichler Andreas , Smith Rona , Jayne David , van der Graaf Piet H. , Chelliah Vijayalakshmi
Published: January 2023

Chronic nasal carriage of Staphylococcus aureus (SA) has been shown to be significantly higher in GPA patients when compared to healthy subjects, as well as being associated with increased endonasal activity and disease relapse. The aim of this study was to investigate SA involvement in GPA by applying a network-based analysis (NBA) approach to publicly available nasal transcriptomic data. Using these data, our NBA pipeline generated a proteinase 3 (PR3) positive ANCA associated vasculitis (AAV) disease network integrating differentially expressed genes, dysregulated transcription factors (TFs), disease-specific genes derived from GWAS studies, drug–target and protein–protein interactions. The PR3+ AAV disease network captured genes previously reported to be dysregulated in AAV associated. A subnetwork focussing on interactions between SA virulence factors and enriched biological processes revealed potential mechanisms for SA’s involvement in PR3+ AAV. Immunosuppressant treatment reduced differential expression and absolute TF activities in this subnetwork for patients with inactive nasal disease but not active nasal disease symptoms at the time of sampling. The disease network generated identified the key molecular signatures and highlighted the associated biological processes in PR3+ AAV and revealed potential mechanisms for SA to affect these processes.
Role of NF-κB Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells
Authors: Cippitelli Marco , Stabile Helena , Kosta Andrea , Petillo Sara , Lucantonio Lorenzo , Gismondi Angela , Santoni Angela , Fionda Cinzia
Published: January 2023

Nuclear factor-κB (NF-κB) transcription factors play a key role in the pathogenesis of multiple myeloma (MM). The survival, proliferation and chemoresistance of malignant plasma cells largely rely on the activation of canonical and noncanonical NF-κB pathways. They are triggered by cancer-associated mutations or by the autocrine and paracrine production of cytokines and growth factors as well as direct interaction with cellular and noncellular components of bone marrow microenvironment (BM). In this context, NF-κB also significantly affects the activity of noncancerous cells, including mesenchymal stromal cells (MSCs), which have a critical role in disease progression. Indeed, NF-κB transcription factors are involved in inflammatory signaling that alters the functional properties of these cells to support cancer evolution. Moreover, they act as regulators and/or effectors of pathways involved in the interplay between MSCs and MM cells. The aim of this review is to analyze the role of NF-κB in this hematologic cancer, focusing on NF-κB-dependent mechanisms in tumor cells, MSCs and myeloma–mesenchymal stromal cell crosstalk.
Long Noncoding RNAs and Cancer Stem Cells: Dangerous Liaisons Managing Cancer
Authors: Ciafrè Silvia Anna , Russo Monia , Michienzi Alessandro , Galardi Silvia
Published: January 2023

Decades of research have investigated the mechanisms that lead to the origin of cancer, striving to identify tumor-initiating cells. These cells, also known as cancer stem cells, are characterized by the ability to self-renew, to give rise to differentiated tumor populations, and on a larger scale, are deemed responsible not only for tumor initiation but also for recurrent tumors, often resistant to chemotherapy and radiotherapy. Long noncoding RNAs are RNA molecules longer than 200 nt, lacking the ability to code for proteins, with recognized roles as fine regulators of gene expression. They can exert these functions through a variety of mechanisms, acting at almost all steps of gene expression, from modulation of the epigenetic state of chromatin to modulation of protein stability. In all cases, lncRNAs do not work alone, but they always interact with other RNA molecules, either coding or non-coding, or with protein factors. In this review, we summarize the latest results obtained about the involvement of lncRNAs in the initiating cells of several types of tumors, and highlight the different mechanisms through which they work, while discussing how the modulation of a lncRNA can affect several aspects of tumor onset and progression.