bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Network Correlates of Mental Health among Rural-to-Urban Migrants in China
Authors: Wang Wenqing
Published: October 2021

Internal rural-to-urban migrants in China are facing a high risk of mental disorders. Previous research on mental health correlates and predictors among this population focused on individual-level characteristics, neglecting network-level indicators, and migrant–urbanite intergroup relationship. A cross-sectional survey was conducted in Beijing, China from December 2018 to January 2019. A convenience sample of 420 rural-to-urban migrants completed the Chinese 12-item General Health Questionnaire and reported their relationship with urbanites in the past six months. Multivariate linear regression models were used to test the association of the inter-hukou network with migrant mental health. Two indicators of the inter-hukou network were significantly associated with migrant mental health. Migrants were more mentally healthy if their proportion of weak ties in the inter-hukou network was no less than 50%. The more social support migrants received from the inter-hukou network, the better their mental health was. Meanwhile, there was a significant interaction effect between social support and sex, indicating that the same level of social support better protected the mental health of female migrants. Results suggest the importance of social network factors and migrant–urbanite ties for migrant mental health. Future efforts may need to mobilize and facilitate the inter-hukou network to improve migrant mental health.
Artificial Intelligence and Computer Vision in Low Back Pain: A Systematic Review
Authors: D’Antoni Federico , Russo Fabrizio , Ambrosio Luca , Vollero Luca , Vadalà Gianluca , Merone Mario , Papalia Rocco , Denaro Vincenzo
Published: October 2021

Chronic Low Back Pain (LBP) is a symptom that may be caused by several diseases, and it is currently the leading cause of disability worldwide. The increased amount of digital images in orthopaedics has led to the development of methods related to artificial intelligence, and to computer vision in particular, which aim to improve diagnosis and treatment of LBP. In this manuscript, we have systematically reviewed the available literature on the use of computer vision in the diagnosis and treatment of LBP. A systematic research of PubMed electronic database was performed. The search strategy was set as the combinations of the following keywords: “Artificial Intelligence”, “Feature Extraction”, “Segmentation”, “Computer Vision”, “Machine Learning”, “Deep Learning”, “Neural Network”, “Low Back Pain”, “Lumbar”. Results: The search returned a total of 558 articles. After careful evaluation of the abstracts, 358 were excluded, whereas 124 papers were excluded after full-text examination, taking the number of eligible articles to 76. The main applications of computer vision in LBP include feature extraction and segmentation, which are usually followed by further tasks. Most recent methods use deep learning models rather than digital image processing techniques. The best performing methods for segmentation of vertebrae, intervertebral discs, spinal canal and lumbar muscles achieve Sørensen–Dice scores greater than 90%, whereas studies focusing on localization and identification of structures collectively showed an accuracy greater than 80%. Future advances in artificial intelligence are expected to increase systems’ autonomy and reliability, thus providing even more effective tools for the diagnosis and treatment of LBP.
Moving Forward: Understanding Correlates of Physical Activity and Sedentary Behaviour during COVID-19—An Integrative Review and Socioecological Approach
Authors: Knight Rachel L. , McNarry Melitta A. , Sheeran Liba , Runacres Adam W. , Thatcher Rhys , Shelley James , Mackintosh Kelly A.
Published: October 2021

Population-level physical activity (PA) and sedentary time/behaviour estimates represent a significant public health issue exacerbated by restrictions enforced to control COVID-19. This integrative review interrogated available literature to explore the pandemic’s impact on correlates of such behaviours in adults (≥18 years). Five electronic databases were systematically searched in January 2021. Data extracted from 64 articles were assessed for risk-of-bias using the Mixed Methods Assessment Tool, with correlates identified, coded, and themed via thematic analysis. A socioecological model of during-pandemic PA was conceptualized and mapped to the Capability, Opportunity, Motivation, and Behaviour (COM-B) model of behaviour change mechanisms, which illustrates influences over five levels: Individual (biological)—general health; Individual (psychological)—mental health, cognition, motivation, and behaviour; Social—domestic situation, sociodemographic factors, support, and lifestyle choices; Environmental—resources and area of residence; and Policy—COVID-19-related rules. For sedentary time/behaviour, individual level factors, namely general and mental health, may be important correlates. Neither age or sex were clearly correlated with either behaviour. As we transition into a new normal, understanding which behaviour mechanisms could effectively challenge physical inactivity is essential. Targeting capability on a psychological level may facilitate PA and limit sedentary time/behaviour, whereas, on a physical level, maximizing PA opportunities could be crucial.
Informal Payments by Patients in Central and Eastern Europe during the COVID-19 Pandemic: An Institutional Perspective
Authors: Horodnic Adrian V. , Williams Colin C. , Drugă Răzvan Ionuț , Incaltarau Cristian
Published: October 2021

Confronted with a global pandemic, public healthcare systems are under pressure, making access to healthcare services difficult for patients. This provides fertile ground for using illegal practices such as informal payments to gain access. This paper aims to evaluate the use of informal payments by patients during the COVID-19 pandemic and the institutions that affect the prevalence of this practice. Various measurements of formal and informal institutions are here investigated, namely the acceptability of corruption, the level of trust, transparency, and performance of the healthcare system. To do so, a logistic regression of 10,859 interviews with patients conducted across 11 Central and Eastern Europe countries in October–December 2020 is employed. The finding is that there are large disparities between countries in the prevalence of informal payments, and that the practice is more likely to occur where there are poorer formal and informal institutions, namely higher acceptability of corruption, lower trust in authorities, lower perceived transparency in handling the COVID-19 pandemic, difficult access to, and poor quality of, healthcare services, and higher mortality rates due to the COVID-19 pandemic. These findings suggest that policy measures for tackling informal payments need to address the current state of the institutional environment.
Association between Breastfeeding Attitudes and Postpartum Depression among Mothers with Premature Infants during COVID-19 Pandemic
Authors: Yahya Noor Fairuzi Suhana , Teng Nur Islami Mohd Fahmi , Shafiee Najwa , Juliana Norsham
Published: October 2021

Breastfeeding is the best form of feeding for premature infants. However, mothers with premature delivery are frequently reported to be depressed, and this has been especially the case during the Coronavirus Disease-2019 (COVID-19) pandemic. We aimed to measure the level of breastfeeding attitude and its association with postpartum depression among mothers with premature infants in the Neonatal Intensive Care Unit (NICU) during the COVID-19 pandemic. A total of 248 mothers with a premature infant were observed in this cross-sectional study from the chosen NICUs of government hospitals in Selangor, Malaysia. The Iowa Infant Feeding Attitude Score (IIFAS) and the Edinburgh Postnatal Depression Scale, along with sociodemographic questionnaires, were used to obtain information on the mothers’ attitudes towards breastfeeding and the risk of postpartum depression. A higher percentage of mothers had a positive attitude towards breastfeeding (64.9%), with a mean IIFAS score of 66.30 ± 6.92. Meanwhile, about 27% of mothers with premature infants were reported to have high risk of depressive symptoms. Mothers with a high risk of depression were less likely to have a positive attitude towards breastfeeding (OR 0.37, 95% CI 0.199, 0.675) as compared to mothers with a low risk of depression (p < 0.01). We found that there is an association between the risk of depression and the attitude towards breastfeeding. Early identification of maternal mental health problems should be addressed to ensure the willingness of mothers to continue breastfeeding.
Gender Self-Perception and Psychological Distress in Healthcare Students during the COVID-19 Pandemic
Authors: Rodríguez-Roca Beatriz , Subirón-Valera Ana Belén , Gasch-Gallén Ángel , Calatayud Estela , Gómez-Soria Isabel , Marcén-Román Yolanda
Published: October 2021

The aim of this study was to analyze university Health Sciences students’ self-perception regarding gender stereotypes, and to explore whether there was any association between gender stereotypes and clinical/socio-demographic variables. Methods: This cross-sectional study was conducted with a sample of 252 university students who completed a self-administrated online questionnaire (18.3% males, 81.7% females). We evaluated the self-perception of gender stereotypes as determined using the BSRI-12 questionnaire and explored the association of this measure with the impact of perceived stress measured using a modified scale (PSS-10-C) as well as anxiety and depression according to scores on the Goldberg scale (GADS). Results: According to the students’ self-perception of gender stereotypes, 24.9% self-perceived themselves as feminine, 20.1% as masculine, 24.9% as androgynous, and 30% as undifferentiated. The degree determines self-identification with gender stereotypes. Nursing and Occupational Therapy are studied mostly by women, 28.4% and 45%, respectively, while Physiotherapy is studied mainly by men (71.2%). Females indicated more anxiety (75.7%) and depression (81.7%) than males (52.9% and 67.3%, respectively). In contrast, males developed more stress (88.5%) than females (74.1%). Conclusions: University degree, anxiety, depression, and stress determined self-identification with gender stereotypes. The results of this study indicate that gender roles influence the possibility of developing mental disorders and should be taken into account in future studies.
Air Quality in a Dental Clinic during Er:YAG Laser Usage for Cavity Preparation on Human Teeth—An Ex-Vivo Study
Authors: Karveli Angeliki , Tzoutzas Ioannis G. , Raptis Panagiotis Ioannis , Tzanakakis Emmanouil-George C. , Farmakis Eleftherios Terry R. , Helmis Constantinos G.
Published: October 2021

Chemical air pollution in dental clinics consists of the emission of gases and particulate matter (PM), both generated by dental equipment and tooth tissues. One basic application of Erbium Laser devices is cavity preparation on human teeth due to its strong affinity to water and hydroxyapatite. The objective of this study was the evaluation of indoor air quality during the application of an Er:YAG laser, as a dentin removal instrument, in a Dental Clinic. Particulate Matter (PM) was measured using the standard method of EN legislation. In order to measure total Volatile Organic compounds (VOCs), a portable monitor was used. In the first experiment, PM10 and PM2.5 concentrations were increased by approximately 10 and 15 times, respectively. From the second experiment it can be concluded that neither of the measured particle concentrations exceeded the recommended indoor limit values while windows were open, although laser influence was still detectable. Within the limitations applied herein, it was found that Er:YAG laser activity for hard dental tissue removal was associated with high PM and TVOCs concentration values in the working environment, under insufficient or no ventilation. Physical ventilation in the aforementioned setting proved to be an important key factor in improving air quality, as both PM and TVOCs concentrations decreased significantly.
Social Physique Anxiety Scale: Psychometric Evaluation and Development of a Chinese Adaptation
Authors: Jin Jiahui , Fung Sai-fu
Published: October 2021

The Social Physique Anxiety Scale (SPAS) is a popular measure of individual anxiety related to body image. This study assessed the psychometric properties of the 12-, 9-, 8- and 7-item versions of the SPAS. Two cross-sectional studies recruited 466 Chinese university students. Study 1 (n = 273) evaluated the construct validity and internal consistency of the SPAS. Study 2 (n = 193) further assessed the construct validity, factorial validity, internal consistency, convergent validity and divergent validity of the SPAS. The results indicated that none of the existing SPAS versions possess good psychometric properties suitable for the Chinese student population. In short, a new 7-item version of the SPAS that is more suitable for measuring social physique anxiety among Chinese university students. The implications of our results and future research directions are discussed.
Anemia among Men in Malaysia: A Population-Based Survey in 2019
Authors: Awaluddin S Maria , Shahein Nik Adilah , Che Abdul Rahim Norsyamlina , Mohd Zaki Nor Azian , Nasaruddin Nur Hamizah , Saminathan Thamil Arasu , Alias Nazirah , Ganapathy Shubash Shander , Ahmad Noor Ani
Published: October 2021

This study aimed to determine the prevalence of anemia and factors associated with anemia among men in Malaysia. The researchers used data from the 2019 National Health and Morbidity Survey (NHMS). The hemoglobin levels of men aged 15 years and above who gave their consent was measured using the HemoCue® Hb 201+ System©. The majority of them (87.2%) were men aged 15–59 years, referred to as the younger age group in this study. The prevalence of anemia among men was 12.6% (95% confidence interval (CI): 10.9, 14.5). The prevalence was higher among older men (30.7%; 95% CI: 26.6, 35.1) than younger men (10.0%; 95% CI: 8.2, 12.2). Anemia among men was associated with older age (adjusted odds ratios (aOR) = 3.1; 95% CI: 2.1, 4.4) and those with diabetes (aOR = 1.5; 95% CI: 1.2, 2.1) via a logistic regression analysis. In conclusion, older men were more affected by anemia than younger men in this study. Anemia among older men in Malaysia is at the level of moderate to severe public health significance. The likelihood of developing anemia is increased among older men with diabetes compared to older men without diabetes. These often-overlooked issues among men need to be detected and treated early in order to prevent complications and improve their quality of life.
Effect of Different Exercise Types on the Cross-Sectional Area and Lumbar Lordosis Angle in Patients with Flat Back Syndrome
Authors: Kim Won-Moon , Seo Yong-Gon , Park Yun-Jin , Cho Han-Su , Lee Chang-Hee
Published: October 2021

Flat back syndrome (FBS) is a sagittal imbalance wherein the normal spinal curvature is reduced. This study aimed to compare the effects of different exercise programs on the cross-sectional area (CSA) of the lumbar muscles, lumbar lordosis angle (LLA), lumbar disability, and flexibility in patients with FBS. Thirty-six females with flexible FBS were randomly allocated to the corrective exercise group (CEG, n = 12), resistance exercise group (REG, n = 12), and physical therapy group (PTG, n = 12). CEG and REG patients participated in a 12-week exercise intervention for 60 min three times per week. The CSA, LLA, Oswestry disability index (ODI), and sit-and-reach test were measured before and after intervention. CSA showed a significant difference between groups (p < 0.01), with CEG and REG demonstrating a significant increase (p < 0.05 and p < 0.05, respectively). LLA showed a significant difference between groups (p < 0.001); CEG showed a higher increase than did REG (p < 0.01) and PTG (p < 0.001). ODI also showed a significant difference between groups (p < 0.001), being lower in CEG than in REG (p < 0.001) and PTG (p < 0.001). Lumbar flexibility significantly improved in all groups, albeit with a significant difference (p < 0.001). Although corrective and resistance exercise programs effectively improve these parameters, corrective exercise is superior to other interventions for patients with FBS.
Clustering of Physical Activity, Diet and Sedentary Behavior among Youth from Low-, Middle-, and High-Income Countries: A Scoping Review
Authors: Mello Gabrielli Thais de , Lopes Marcus Vinicius Veber , Minatto Giseli , Costa Rafael Martins da , Matias Thiago Sousa , Guerra Paulo Henrique , Filho Valter Cordeiro Barbosa , Silva Kelly Samara
Published: October 2021

Background: The interaction between physical activity (PA), diet, and sedentary behavior (SB) plays an important role on health-related outcomes. This scoping review (Prospero CRD42018094826) aims to identify and appraise clusters of PA, diet, and SB among youth (0–19 years) according to country income. Methods: Five databases were searched. Fifty-seven articles met the inclusion criteria. Results: Fifty-five cluster types were identified, with greater variety in high-income than lower income countries. The most prevalent profiles were “High SB and consumption of sugar, salt, and beverages (SSB)” (n = 17) and “High PA” (n = 13–5), both of which presented in all income countries. The healthiest profile, “High PA and fruit and vegetables (F&V); Low SB and SSB” (n = 12), was present in upper-middle and high-income countries, while the unhealthiest “Low PA and F&V; High SB and SSB” (n = 6) was present only in high-income countries. Conclusions: High SB and unhealthy diet (SSB) were more prevalent in clusters, mainly in high-income countries. The results support the need for multi-component actions targeting more than one behavior at the same time.
Conserved Structure and Evolution of DPF Domain of PHF10—The Specific Subunit of PBAF Chromatin Remodeling Complex
Authors: Chugunov Anton O. , Potapova Nadezhda A. , Klimenko Natalia S. , Tatarskiy Victor V. , Georgieva Sofia G. , Soshnikova Nataliya V.
Published: October 2021

Transcription activation factors and multisubunit coactivator complexes get recruited at specific chromatin sites via protein domains that recognize histone modifications. Single PHDs (plant homeodomains) interact with differentially modified H3 histone tails. Double PHD finger (DPF) domains possess a unique structure different from PHD and are found in six proteins: histone acetyltransferases MOZ and MORF; chromatin remodeling complex BAF (DPF1–3); and chromatin remodeling complex PBAF (PHF10). Among them, PHF10 stands out due to the DPF sequence, structure, and functions. PHF10 is ubiquitously expressed in developing and adult organisms as four isoforms differing in structure (the presence or absence of DPF) and transcription regulation functions. Despite the importance of the DPF domain of PHF10 for transcription activation, its structure remains undetermined. We performed homology modeling of the human PHF10 DPF domain and determined common and distinct features in structure and histone modifications recognition capabilities, which can affect PBAF complex chromatin recruitment. We also traced the evolution of DPF1–3 and PHF10 genes from unicellular to vertebrate organisms. The data reviewed suggest that the DPF domain of PHF10 plays an important role in SWI/SNF-dependent chromatin remodeling during transcription activation.
Identification of Salicylates in Willow Bark (Salix Cortex) for Targeting Peripheral Inflammation
Authors: Antoniadou Kyriaki , Herz Corinna , Le Nguyen Phan Khoi , Mittermeier-Kleßinger Verena Karolin , Förster Nadja , Zander Matthias , Ulrichs Christian , Mewis Inga , Hofmann Thomas , Dawid Corinna , Lamy Evelyn
Published: October 2021

Salix cortex-containing medicine is used against pain conditions, fever, headaches, and inflammation, which are partly mediated via arachidonic acid-derived prostaglandins (PGs). We used an activity-guided fractionation strategy, followed by structure elucidation experiments using LC-MS/MS, CD-spectroscopy, and 1D/2D NMR techniques, to identify the compounds relevant for the inhibition of PGE2 release from activated human peripheral blood mononuclear cells. Subsequent compound purification by means of preparative and semipreparative HPLC revealed 2′-O-acetylsalicortin (1), 3′-O-acetylsalicortin (2), 2′-O-acetylsalicin (3), 2′,6′-O-diacetylsalicortin (4), lasiandrin (5), tremulacin (6), and cinnamrutinose A (7). In contrast to 3 and 7, compounds 1, 2, 4, 5, and 6 showed inhibitory activity against PGE2 release with different potencies. Polyphenols were not relevant for the bioactivity of the Salix extract but salicylates, which degrade to, e.g., catechol, salicylic acid, salicin, and/or 1-hydroxy-6-oxo-2-cycohexenecarboxylate. Inflammation presents an important therapeutic target for pharmacological interventions; thus, the identification of relevant key drugs in Salix could provide new prospects for the improvement and standardization of existing clinical medicine.
Mitochondrial and Plastid Genomes of the Monoraphid Diatom Schizostauron trachyderma
Authors: Górecka Ewa , Gastineau Romain , Davidovich Nikolai A. , Davidovich Olga I. , Ashworth Matt P. , Sabir Jamal S. M. , Lemieux Claude , Turmel Monique , Witkowski Andrzej
Published: October 2021

We provide for the first time the complete plastid and mitochondrial genomes of a monoraphid diatom: Schizostauron trachyderma. The mitogenome is 41,957 bp in size and displays two group II introns in the cox1 gene. The 187,029 bp plastid genome features the typical quadripartite architecture of diatom genomes. It contains a group II intron in the petB gene that overlaps the large single-copy and the inverted repeat region. There is also a group IB4 intron encoding a putative LAGLIDADG homing endonuclease in the rnl gene. The multigene phylogenies conducted provide more evidence of the proximity between S. trachyderma and fistula-bearing species of biraphid diatoms.
Perineuronal Nets in the Prefrontal Cortex of a Schizophrenia Mouse Model: Assessment of Neuroanatomical, Electrophysiological, and Behavioral Contributions
Authors: Sultana Razia , Brooks Charles Brady , Shrestha Amita , Ogundele Olalekan Michael , Lee Charles Chulsoo
Published: October 2021

Schizophrenia is a neurodevelopmental disorder whose etiopathogenesis includes changes in cellular as well as extracellular structures. Perineuronal nets (PNNs) associated with parvalbumin-positive interneurons (PVs) in the prefrontal cortex (PFC) are dysregulated in schizophrenia. However, the postnatal development of these structures along with their associated neurons in the PFC is unexplored, as is their effects on behavior and neural activity. Therefore, in this study, we employed a DISC1 (Disruption in Schizophrenia) mutation mouse model of schizophrenia to assess these developmental changes and tested whether enzymatic digestion of PNNs in the PFC affected schizophrenia-like behaviors and neural activity. Developmentally, we found that the normal formation of PNNs, PVs, and colocalization of these two in the PFC, peaked around PND 22 (postnatal day 22). However, in DISC1, mutation animals from PND 0 to PND 60, both PNNs and PVs were significantly reduced. After enzymatic digestion of PNNs with chondroitinase in adult animals, the behavioral pattern of control animals mimicked that of DISC1 mutation animals, exhibiting reduced sociability, novelty and increased ultrasonic vocalizations, while there was very little change in other behaviors, such as working memory (Y-maze task involving medial temporal lobe) or depression-like behavior (tail-suspension test involving processing via the hypothalamic pituitary adrenal (HPA) axis). Moreover, following chondroitinase treatment, electrophysiological recordings from the PFC exhibited a reduced proportion of spontaneous, high-frequency firing neurons, and an increased proportion of irregularly firing neurons, with increased spike count and reduced inter-spike intervals in control animals. These results support the proposition that the aberrant development of PNNs and PVs affects normal neural operations in the PFC and contributes to the emergence of some of the behavioral phenotypes observed in the DISC1 mutation model of schizophrenia.
Trimethylamine n-Oxide (TMAO) Modulates the Expression of Cardiovascular Disease-Related microRNAs and Their Targets
Authors: Díez-Ricote Laura , Ruiz-Valderrey Paloma , Micó Víctor , Blanco-Rojo Ruth , Tomé-Carneiro João , Dávalos Alberto , Ordovás José M. , Daimiel Lidia
Published: October 2021

Diet is a well-known risk factor of cardiovascular diseases (CVDs). Some microRNAs (miRNAs) have been described to regulate molecular pathways related to CVDs. Diet can modulate miRNAs and their target genes. Choline, betaine, and l-carnitine, nutrients found in animal products, are metabolized into trimethylamine n-oxide (TMAO), which has been associated with CVD risk. The aim of this study was to investigate TMAO regulation of CVD-related miRNAs and their target genes in cellular models of liver and macrophages. We treated HEPG-2, THP-1, mouse liver organoids, and primary human macrophages with 6 µM TMAO at different timepoints (4, 8, and 24 h for HEPG-2 and mouse liver organoids, 12 and 24 h for THP-1, and 12 h for primary human macrophages) and analyzed the expression of a selected panel of CVD-related miRNAs and their target genes and proteins by real-time PCR and Western blot, respectively. HEPG-2 cells were transfected with anti-miR-30c and syn-miR-30c. TMAO increased the expression of miR-21-5p and miR-30c-5p. PER2, a target gene of both, decreased its expression with TMAO in HEPG-2 and mice liver organoids but increased its mRNA expression with syn-miR-30c. We concluded that TMAO modulates the expression of miRNAs related to CVDs, and that such modulation affects their target genes.
Synergistic Action of Antimicrobial Lung Proteins against Klebsiella pneumoniae
Authors: Fraile-Ágreda Víctor , Cañadas Olga , Weaver Timothy E. , Casals Cristina
Published: October 2021

As key components of innate immunity, lung antimicrobial proteins play a critical role in warding off invading respiratory pathogens. Lung surfactant protein A (SP-A) exerts synergistic antimicrobial activity with the N-terminal segment of the SP-B proprotein (SP-BN) against Klebsiella pneumoniae K2 in vivo. However, the factors that govern SP-A/SP-BN antimicrobial activity are still unclear. The aim of this study was to identify the mechanisms by which SP-A and SP-BN act synergistically against K. pneumoniae, which is resistant to either protein alone. The effect of these proteins on K. pneumoniae was studied by membrane permeabilization and depolarization assays and transmission electron microscopy. Their effects on model membranes of the outer and inner bacterial membranes were analyzed by differential scanning calorimetry and membrane leakage assays. Our results indicate that the SP-A/SP-BN complex alters the ultrastructure of K. pneumoniae by binding to lipopolysaccharide molecules present in the outer membrane, forming packing defects in the membrane that may favor the translocation of both proteins to the periplasmic space. The SP-A/SP-BN complex depolarized and permeabilized the inner membrane, perhaps through the induction of toroidal pores. We conclude that the synergistic antimicrobial activity of SP-A/SP-BN is based on the capability of this complex, but not either protein alone, to alter the integrity of bacterial membranes.
Reversal Activity and Toxicity of Heparin-Binding Copolymer after Subcutaneous Administration of Enoxaparin in Mice
Authors: Swieton Justyna , Miklosz Joanna , Yusa Shin-Ichi , Szczubialka Krzysztof , Pawlak Dariusz , Mogielnicki Andrzej , Kalaska Bartlomiej
Published: October 2021

Uncontrolled bleeding after enoxaparin (ENX) is rare but may be life-threatening. The only registered antidote for ENX, protamine sulfate (PS), has 60% efficacy and can cause severe adverse side effects. We developed a diblock copolymer, heparin-binding copolymer (HBC), that reverses intravenously administered heparins. Here, we focused on the HBC inhibitory activity against subcutaneously administered ENX in healthy mice. BALB/c mice were subcutaneously injected with ENX at the dose of 5 mg/kg. After 110 min, vehicle, HBC (6.25 and 12.5 mg/kg), or PS (5 and 10 mg/kg) were administered into the tail vein. The blood was collected after 3, 10, 60, 120, 360, and 600 min after vehicle, HBC, or PS administration. The activities of antifactors Xa and IIa and biochemical parameters were measured. The main organs were collected for histological analysis. HBC at the lower dose reversed the effect of ENX on antifactor Xa activity for 10 min after antidote administration, whereas at the higher dose, HBC reversed the effect on antifactor Xa activity throughout the course of the experiment. Both doses of HBC completely reversed the effect of ENX on antifactor IIa activity. PS did not reverse antifactor Xa activity and partially reversed antifactor IIa activity. HBC modulated biochemical parameters. Histopathological analysis showed changes in the liver, lungs, and spleen of mice treated with HBC and in the lungs and heart of mice treated with PS. HBC administered in an appropriate dose might be an efficient substitute for PS to reverse significantly increased anticoagulant activity that may be connected with major bleeding in patients receiving ENX subcutaneously.
Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
Authors: Chang Kai-Wei , Zhang Xiang , Lin Shih-Chao , Lin Yu-Chao , Li Chia-Hsiang , Akhrymuk Ivan , Lin Sheng-Hao , Lin Chi-Chien
Published: October 2021

Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.
Cardiomyocyte Dysfunction in Inherited Cardiomyopathies
Authors: Hassoun Roua , Budde Heidi , Mügge Andreas , Hamdani Nazha
Published: October 2021

Inherited cardiomyopathies form a heterogenous group of disorders that affect the structure and function of the heart. Defects in the genes encoding sarcomeric proteins are associated with various perturbations that induce contractile dysfunction and promote disease development. In this review we aimed to outline the functional consequences of the major inherited cardiomyopathies in terms of myocardial contraction and kinetics, and to highlight the structural and functional alterations in some sarcomeric variants that have been demonstrated to be involved in the pathogenesis of the inherited cardiomyopathies. A particular focus was made on mutation-induced alterations in cardiomyocyte mechanics. Since no disease-specific treatments for familial cardiomyopathies exist, several novel agents have been developed to modulate sarcomere contractility. Understanding the molecular basis of the disease opens new avenues for the development of new therapies. Furthermore, the earlier the awareness of the genetic defect, the better the clinical prognostication would be for patients and the better the prevention of development of the disease.
Cytosolic Phospholipase A2 Is Required for Fexofenadine’s Therapeutic Effects against Inflammatory Bowel Disease in Mice
Authors: Zhao Xiangli , Liu Ronghan , Chen Yuehong , Hettinghouse Aubryanna , Liu Chuanju
Published: October 2021

Inflammatory Bowel Disease (IBD) is an autoimmune condition with complicated pathology and diverse clinical signs. TNFα is believed to play a crucial role in the pathogenesis of IBD. We recently identified fexofenadine, a well-known antagonist of histamine H1 receptor, as a novel inhibitor of TNFα signaling. Additionally, cytosolic phospholipase A2 (cPLA2) was isolated as a binding target of fexofenadine, and fexofenadine-mediated anti-TNF activity relied on cPLA2 in vitro. The objective of this study is to determine whether fexofenadine is therapeutic against chemically-induced murine IBD model and whether cPLA2 and/or histamine H1 receptor is important for fexofenadine’s anti-inflammatory activity in vivo by leveraging various genetically modified mice and chemically induced murine IBD models. Both dextran sulfate sodium- and 2, 4, 6-trinitrobenzene sulfonic acid-induced murine IBD models revealed that orally delivered fexofenadine was therapeutic against IBD, evidenced by mitigated clinical symptoms, decreased secretions of the proinflammatory cytokine IL-6 and IL-1β, lowered intestinal inflammation, and reduced p-p65 and p-IĸBα. Intriguingly, Fexofenadine-mediated protective effects against IBD were lost in cPLA2 deficient mice but not in histamine H1 receptor-deficient mice. Collectively, these findings demonstrate the therapeutic effects of over-the-counter drug Fexofenadine in treating DSS-induced IBD murine and provide first in vivo evidence showing that cPLA2 is required for fexofenadine’s therapeutic effects in murine IBD model and probably other inflammatory and autoimmune diseases as well.
Paracetamol (Acetaminophen) and the Developing Brain
Authors: Bührer Christoph , Endesfelder Stefanie , Scheuer Till , Schmitz Thomas
Published: October 2021

Paracetamol is commonly used to treat fever and pain in pregnant women, but there are growing concerns that this may cause attention deficit hyperactivity disorder and autism spectrum disorder in the offspring. A growing number of epidemiological studies suggests that relative risks for these disorders increase by an average of about 25% following intrauterine paracetamol exposure. The data analyzed point to a dose–effect relationship but cannot fully account for unmeasured confounders, notably indication and genetic transmission. Only few experimental investigations have addressed this issue. Altered behavior has been demonstrated in offspring of paracetamol-gavaged pregnant rats, and paracetamol given at or prior to day 10 of life to newborn mice resulted in altered locomotor activity in response to a novel home environment in adulthood and blunted the analgesic effect of paracetamol given to adult animals. The molecular mechanisms that might mediate these effects are unknown. Paracetamol has diverse pharmacologic actions. It reduces prostaglandin formation via competitive inhibition of the peroxidase moiety of prostaglandin H2 synthase, while its metabolite N-arachidonoyl-phenolamine activates transient vanilloid-subtype 1 receptors and interferes with cannabinoid receptor signaling. The metabolite N-acetyl-p-benzo-quinone-imine, which is pivotal for liver damage after overdosing, exerts oxidative stress and depletes glutathione in the brain already at dosages below the hepatic toxicity threshold. Given the widespread use of paracetamol during pregnancy and the lack of safe alternatives, its impact on the developing brain deserves further investigation.
Granulocyte Colony-Stimulating Factor Restored Impaired Spermatogenesis and Fertility in an AML-Chemotherapy Mice Model
Authors: Michailov Yulia , AbuMadighem Ali , Lunenfeld Eitan , Kapelushnik Joseph , Huleihel Mahmoud
Published: October 2021

Leukemia and treatment of male patients with anticancer therapy (aggressive chemotherapy and/or radiotherapy) may lead to infertility or even permanent male sterility. Their mechanisms of spermatogenesis impairment and the decrease in male fertility are not yet clear. We showed that under acute myeloid leukemia (AML) conditions, alone and in combination with cytarabine (CYT), there was significant damage in the histology of seminiferous tubules, a significant increase in apoptotic cells of the seminiferous tubules, and a reduction in spermatogonial cells (SALL and PLZF) and in meiotic (CREM) and post-meiotic (ACROSIN) cells. In addition, we showed a significant impairment in sperm parameters and fertilization rates and offspring compared to control. Our results showed a significant decrease in the expression of glial cell line-derived neurotrophic factor (GDNF), macrophage colony-stimulating factor (MCSF) and stem cell factor (SCF) under AML conditions, but not under cytarabine treatment compared to control. In addition, our results showed a significant increase in the pro-inflammatory cytokine interleukin-1 (IL-1) alpha in whole testis homogenates in all treatment groups compared to the control. Increase in IL-1 beta level was shown under AML conditions. We identified for the first time the expression of GCSF receptor (GCSFR) in sperm cells. We showed that GCSF injection in combination with AML and cytarabine (AML + CYT + GCSF) extended the survival of mice for a week (from 6.5 weeks to 7.5 weeks) compared to (AML + CYT). Injection of GCSF to all treated groups (post hoc), showed a significant impact on mice testis weight, improved testis histology, decreased apoptosis and increased expression of pre-meiotic, meiotic and post- meiotic markers, improved sperm parameters, fertility capacity and number of offspring compared to the controls (without GCSF). GCSF significantly improved the spermatogonial niche expressed by increased the expression levels of testicular GDNF, SCF and MCSF growth factors in AML-treated mice and (AML + CYT)-treated mice compared to those groups without GCSF. Furthermore, GCSF decreased the expression levels of the pro-inflammatory cytokine IL-12, but increased the expression of IL-10 in the interstitial compartment compared to the relevant groups without GCSF. Our results show for the first time the capacity of post injection of GCSF into AML- and CYT-treated mice to improve the cellular and biomolecular mechanisms that lead to improve/restore spermatogenesis and male fertility. Thus, post injection of GCSF may assist in the development of future therapeutic strategies to preserve/restore male fertility in cancer patients, specifically in AML patients under chemotherapy treatments.
Porphyrin Based 2D-MOF Structures as Dual-Kinetic Sorafenib Nanocarriers for Hepatoma Treatment
Authors: Bieniek Adam , Wiśniewski Marek , Czarnecka Joanna , Wierzbicki Jędrzej , Ziętek Marcin , Nowacki Maciej , Grzanka Dariusz , Kloskowski Tomasz , Roszek Katarzyna
Published: October 2021

The existing clinical protocols of hepatoma treatment require improvement of drug efficacy that can be achieved by harnessing nanomedicine. Porphyrin-based, paddle-wheel framework (PPF) structures were obtained and tested as dual-kinetic Sorafenib (SOR) nanocarriers against hepatoma. We experimentally proved that sloughing of PPF structures combined with gradual dissolving are effective mechanisms for releasing the drug from the nanocarrier. By controlling the PPF degradation and size of adsorbed SOR deposits, we were able to augment SOR anticancer effects, both in vitro and in vivo, due to the dual kinetic behavior of SOR@PPF. Obtained drug delivery systems with slow and fast release of SOR influenced effectively, although in a different way, the cancer cells proliferation (reflected with EC50 and ERK 1/2 phosphorylation level). The in vivo studies proved that fast-released SOR@PPF reduces the tumor size considerably, while the slow-released SOR@PPF much better prevents from lymph nodes involvement and distant metastases.
PPR647 Protein Is Required for Chloroplast RNA Editing, Splicing and Chloroplast Development in Maize
Authors: Zhao Yan , Xu Wei , Zhang Yongzhong , Sun Shilei , Wang Lijing , Zhong Shiyi , Zhao Xiangyu , Liu Baoshen
Published: October 2021

Chloroplasts play an essential role in plant growth and development. Any factors affecting chloroplast development will lead to abnormal plant growth. Here, we characterized a new maize mutant, albino seedling mutant 81647 (as-81647), which exhibits an entirely albino phenotype in leaves and eventually died before the three-leaf stage. Transmission electron microscopy (TEM) demonstrated that the chloroplast thylakoid membrane was impaired and the granum lamellae significantly decreased in as-81647. Map-based cloning and transgenic analysis confirmed that PPR647 encodes a new chloroplast protein consisting of 11 pentratricopeptide repeat domains. Quantitative real-time PCR (qRT-PCR) assays and transcriptome analysis (RNA-seq) showed that the PPR647 mutation significantly disrupted the expression of PEP-dependent plastid genes. In addition, RNA splicing and RNA editing of multiple chloroplast genes showed severe defects in as-81647. These results indicated that PPR647 is crucial for RNA editing, RNA splicing of chloroplast genes, and plays an essential role in chloroplast development.
Encapsulation of Plant Biocontrol Bacteria with Alginate as a Main Polymer Material
Authors: Saberi Riseh Roohallah , Skorik Yury A. , Thakur Vijay Kumar , Moradi Pour Mojde , Tamanadar Elahe , Noghabi Shahnaz Shahidi
Published: October 2021

One of the most favored trends in modern agriculture is biological control. However, many reports show that survival of biocontrol bacteria is poor in host plants. Providing biocontrol agents with protection by encapsulation within external coatings has therefore become a popular idea. Various techniques, including extrusion, spray drying, and emulsion, have been introduced for encapsulation of biocontrol bacteria. One commonly used biopolymer for this type of microencapsulation is alginate, a biopolymer extracted from seaweed. Recent progress has resulted in the production of alginate-based microcapsules that meet key bacterial encapsulation requirements, including biocompatibility, biodegradability, and support of long-term survival and function. However, more studies are needed regarding the effect of encapsulation on protective bacteria and their targeted release in organic crop production systems. Most importantly, the efficacy of alginate use for the encapsulation of biocontrol bacteria in pest and disease management requires further verification. Achieving a new formulation based on biodegradable polymers can have significant effects on increasing the quantity and quality of agricultural products.
Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19
Authors: Theofilis Panagiotis , Sagris Marios , Antonopoulos Alexios S. , Oikonomou Evangelos , Tsioufis Costas , Tousoulis Dimitris
Published: October 2021

Background: Atherosclerotic cardiovascular diseases are characterized by a dysregulated inflammatory and thrombotic state, leading to devastating complications with increased morbidity and mortality rates. Summary: In this review article, we present the available evidence regarding the impact of inflammation on platelet activation in atherosclerosis. Key messages: In the context of a dysfunctional vascular endothelium, structural alterations by means of endothelial glycocalyx thinning or functional modifications through impaired NO bioavailability and increased levels of von Willebrand factor result in platelet activation. Moreover, neutrophil-derived mediators, as well as neutrophil extracellular traps formation, have been implicated in the process of platelet activation and platelet-leukocyte aggregation. The role of pro-inflammatory cytokines is also critical since their receptors are also situated in platelets while TNF-α has also been found to induce inflammatory, metabolic, and bone marrow changes. Additionally, important progress has been made towards novel concepts of the interaction between inflammation and platelet activation, such as the toll-like receptors, myeloperoxidase, and platelet factor-4. The accumulating evidence is especially important in the era of the coronavirus disease-19 pandemic, characterized by an excessive inflammatory burden leading to thrombotic complications, partially mediated by platelet activation. Lastly, recent advances in anti-inflammatory therapies point towards an anti-thrombotic effect secondary to diminished platelet activation.
Supplementation with Lactiplantibacillus plantarum IMC 510 Modifies Microbiota Composition and Prevents Body Weight Gain Induced by Cafeteria Diet in Rats
Authors: Micioni Di Bonaventura Maria Vittoria , Coman Maria Magdalena , Tomassoni Daniele , Micioni Di Bonaventura Emanuela , Botticelli Luca , Gabrielli Maria Gabriella , Rossolini Gian Maria , Di Pilato Vincenzo , Cecchini Cinzia , Amedei Amedeo , Silvi Stefania , Verdenelli Maria Cristina , Cifani Carlo
Published: October 2021

Changes in functionality and composition of gut microbiota (GM) have been associated and may contribute to the development and maintenance of obesity and related diseases. The aim of our study was to investigate for the first time the impact of Lactiplantibacillus (L.) plantarum IMC 510 in a rat model of diet-induced obesity, specifically in the cafeteria (CAF) diet. This diet provides a strong motivation to voluntary overeat, due to the palatability and variety of selected energy-dense foods. The oral administration for 84 days of this probiotic strain, added to the CAF diet, decreased food intake and body weight gain. Accordingly, it ameliorated body mass index, liver and white adipose tissue weight, hepatic lipid accumulation, adipocyte size, serum parameters, including glycemia and low-density lipoprotein levels, in CAF fed rats, potentially through leptin control. In this scenario, L. plantarum IMC 510 showed also beneficial effects on GM, limiting the microbial imbalance established by long exposure to CAF diet and preserving the proportion of different bacterial taxa. Further research is necessary to better elucidate the relationship between GM and overweight and then the mechanism of action by which L. plantarum IMC 510 modifies weight. However, these promising results prompt a clear advantage of probiotic supplementation and identify a new potential probiotic as a novel and safe therapeutic approach in obesity prevention and management.