bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Social Mentality and Health in Promoting Well-Being and Sustainable City
Authors: Liu Zhen , Han Guizhong , Yan Jiajun , Liu Zhichao , Osmani Mohamed
Published: September 2022

In the context of the coronavirus disease 2019 (COVID-19), people’s social mentality and mental health have been severely affected, which has hindered or even reversed the achievement of the United Nations Sustainable Development Goals (SDGs). However, there is a lack of investigation into the potential relationship between social mentality and health, as well as of the comparison between different databases worldwide and in China, in the current context of COVID-19. Hence, the aim of this paper is to explore the research hotspots and development trends of social mentality and health in China and worldwide, while improving people’s health, building a sustainable society, and facilitating the achieving of the SDGs. A bibliometric method is employed in this paper from a macro-quantitative and micro-qualitative perspective to explore the research hotspots and trends of social mentality and health in the world and China from the two databases, namely the English-language Web of Science (WOS) and the Chinese-language China National Knowledge Infrastructure (CNKI). The results indicate that: (1) By using keyword co-occurrence and clustering analysis via the CiteSpace software bibliometric tool, 11 current research hotspots have been identified and studies are increasing in terms of using the Chinese language and the English language. (2) The current studies in the CNKI database mainly focus on the macro social environmental factors affecting social mentality and population research, while the studies in the WOS database pay more attention to social mentality and health in the context of the COVID-19 epidemic situation and a variety of professions. Hence, future research could explore the influencing factors and cultivation methods toward a healthy social mentality from the perspective of methodology and toward achieving SDG 3, providing healthy lives and promote well-being for all at all ages, and SDG 11, building sustainable cities and communities in the post-pandemic COVID-19 era.
Landscape Changes and Optimization in an Ecological Red Line Area: A Case Study in the Upper Reaches of the Ganjiang River
Authors: Liu Guangxu , Xiang Aicun , Huang Yimin , Zha Wen , Chen Yaofang , Mao Benjin
Published: September 2022

The key to optimizing ecological management is to study the spatial configuration of the landscape and the dynamic changes and their driving mechanisms at the landscape scale. The ecological red line area in the hilly area of the upper reaches of the Ganjiang River was chosen as the research area in this study. Based on the theory of landscape ecology and the evolution of biological communities, a multiscale coupling model was adopted and combined with remote sensing (RS) and geographical information system (GIS) technologies to systematically study the evolution of key landscape ecosystems such as forests, patch characteristics, and changes in diversity. The study revealed that: (1) forests represented the largest proportion in the study area, followed by croplands and grasslands; (2) the biological community tended to progress toward climax between 1986 and 1995, but then it moved toward regressive successions between 1995 and 2005 before recovering; (3) the study area was characterized by a high proportion of dominant ecosystems, most of which were at their climax with stable ecological species groups, and which were connected by ecological corridors; and (4) during the period from 1995 to 2010, most landscapes showed a trend of fragmentation. However, during the period from 2010 to 2018, the forest patches were gradually connected. The proportion of dominant landscapes increased, and the landscape uniformity was reduced. Based on the findings, we proposed an ecosystem management strategy that includes strengthening crop management, focusing on the natural restoration of the ecosystems and the cultivation of large patches, exploring disturbances due to mining activities, and applying methods to mitigate damage to and optimize the ecosystem.
Effects of Probiotics Supplementation on Risk and Severity of Infections in Athletes: A Systematic Review
Authors: Di Dio Mirella , Calella Patrizia , Cerullo Giuseppe , Pelullo Concetta Paola , Di Onofrio Valeria , Gallè Francesca , Liguori Giorgio
Published: September 2022

The aim of this review was to appraise the literature on the effects of probiotics supplementation on gastrointestinal (GI) and upper respiratory tract infection (URTI) risk and prognosis in athletes. The search was conducted using the following electronic databases: MEDLINE (PubMed); Web of Science; Scopus; and SPORTDiscus (EBSCO). According to the PRISMA guidelines, randomized controlled studies performed on healthy athletes with a note dose of probiotics supplementation were considered. From the 2304 articles found, after eliminating reviews and studies on animals and unhealthy subjects and after screening of titles and abstracts, 403 studies were considered eligible. From these, in accordance with the inclusion and exclusion criteria, 16 studies were selected, ten of which concerned endurance athletes. The majority of the studies reported beneficial effects of probiotics in reducing the risk of developing the examined infections or the severity of related symptoms. However, due to the differences in formulations used and populations analyzed in the available studies, further research is needed in this field to achieve stronger and more specific evidence.
Special Economic Zone, Carbon Emissions and the Mechanism Role of Green Technology Vertical Spillover: Evidence from Chinese Cities
Authors: Chen Jieping , Long Xianpeng , Lin Shanlang
Published: September 2022

Although the special economic zones (SEZs) are considered the backbone of rapid economic development in China, it is unclear whether they contribute to green economic development. From the perspective of the localized industrial chains formed as a result of the SEZ policy, this paper aims to analyze and explain how the development of SEZs influences carbon emissions in Chinese cities by promoting green technologies’ vertical spillover along the industrial chain. Based on the panel data of 264 prefecture-level cities from 2011 to 2016 and a relatively new and mostly disaggregated city-level MRIO (multi-region input–output) table in China, this paper constructs green technology vertical spillover as a mechanism variable and discusses the influence theoretically and empirically. The results show that the development of SEZs can reduce a city’s carbon emissions. More specifically, for every 10 m2 increase in the size of the SEZ area, the carbon dioxide emission can be reduced by 0.882 g per m2 of the city area. Moreover, mechanism analysis shows that the development of SEZs promotes green technology vertical spillover inside the city, through which the SEZs reduce the city’s carbon emissions. The mediation effect occupies 21.96% of the total effect. Furthermore, the impact of the development of SEZs on carbon emissions has regional heterogeneity due to the city’s industry structure, green technology stocks, and the zones’ administrative hierarchies. The finding of this study could provide several important implications for regional green development, especially in China.
LGBTQ+ Students’ Peer Victimization and Mental Health before and during the COVID-19 Pandemic
Authors: Gill Erin K. , McQuillan Mollie T.
Published: September 2022

Given the well-established health disparities between lesbian, gay, bisexual, transgender, queer, and gender-expansive (LGBTQ+) and cisgender, straight youth, scholars predicted the COVID-19 pandemic would disproportionately impact LGBTQ+ students. Yet, few studies have described changes in LGBTQ+ students’ school experiences and well-being during the pandemic. Using survey data from 40,904 middle and high school students, we examined changes from before (2018) to during (2021) the pandemic in peer victimization, anxiety, and suicide attempts. We conducted bivariate and multivariate regression analyses to assess changes between the two time points among LGBTQ+ and cisgender, straight students. We found LGBTQ+ students experienced more peer victimization, anxiety, and suicide attempts at both points, before and during the pandemic, than cisgender, straight youth. However, LGBTQ+ students reported increased anxiety, decreased peer victimization, and decreased suicide attempts in 2021, during the pandemic, compared to pre-pandemic 2018 reports. These findings suggest pandemic-related school disruptions may have provided LGBTQ+ students some relief from the harmful effects of poor, in-person school climates.
Research on the Impact of Members’ Social Capital within Agricultural Cooperatives on Their Adoption of IPM in China
Authors: Liu Yuying , Liu Ziqi , Liu Jingzheng , Qiu Ling , Wang Yulin , Fu Xinhong
Published: September 2022

Agricultural cooperatives are effective facilitators of green production technology promotion. What is the role of social capital within agricultural cooperatives with the most competitive advantage in technology promotion? Using the survey data of 465 citrus-planting cooperative members in Sichuan Province, this study uses the IV-probit model and mediating effect model to analyze the impact role of social capital within agricultural cooperatives on its members’ adoption of integrated pest management (IPM) technology. The bootstrap method is also used to test the robustness of the parameter estimates. The results show that: (1) the social capital within agricultural cooperatives has a significant positive impact on IPM adoption; (2) cooperative members’ IPM cognition has a partial mediating effect on the impact of the social capital within agricultural cooperatives on its members’ adoption of IPM technology (more than 51.37%). Therefore, among all the optional IPM technology promotion measures of cooperatives, multi-dimensional accumulation of the social capital within agricultural cooperatives and promotion of IPM technology awareness level of members is a viable path.
Modulators of Wnt Signaling Pathway Implied in Dentin Pulp Complex Engineering: A Literature Review
Authors: Florimond Marion , Minic Sandra , Sharpe Paul , Chaussain Catherine , Renard Emmanuelle , Boukpessi Tchilalo
Published: September 2022

The main goal of vital pulp therapy (VPT) is to preserve the vitality of the pulp tissue, even when it is exposed due to bacterial invasion, iatrogenic mechanical preparation, or trauma. The type of new dentin formed as a result of VPT can differ in its cellular origin, its microstructure, and its barrier function. It is generally agreed that the new dentin produced by odontoblasts (reactionary dentin) has a tubular structure, while the dentin produced by pulp cells (reparative dentin) does not or has less. Thus, even VPT aims to maintain the vitality of the pulp. It does not regenerate the dentin pulp complex integrity. Therefore, many studies have sought to identify new therapeutic strategies to successfully regenerate the dentin pulp complex. Among them is a Wnt protein-based strategy based on the fact that Wnt proteins seem to be powerful stem cell factors that allow control of the self-renewal and proliferation of multiple adult stem cell populations, suitable for homeostasis maintenance, tissue healing, and regeneration promotion. Thus, this review outlines the different agents targeting the Wnt signaling that could be applied in a tooth environment, and could be a potential therapy for dentin pulp complex and bone regeneration.
Unveiling the Essential Role of Arkadia’s Non-RING Elements in the Ubiquitination Process
Authors: Birkou Maria , Delegkou Georgia N. , Marousis Konstantinos D. , Fragkaki Nefeli , Toro Tamara , Episkopou Vasso , Spyroulias Georgios A.
Published: September 2022

Arkadia is a positive regulator of the TGFβ-SMAD2/3 pathway, acting through its C-terminal RING-H2 domain and targeting for degradation of its negative regulators. Here we explore the role of regions outside the RING domain (non-RING elements) of Arkadia on the E2-E3 interaction. The contribution of the non-RING elements was addressed using Arkadia RING 68 aa and Arkadia 119 aa polypeptides. The highly conserved NRGA (asparagine-arginine-glycine-alanine) and TIER (threonine-isoleucine-glutamine-arginine) motifs within the 119 aa Arkadia polypeptide, have been shown to be required for pSMAD2/3 substrate recognition and ubiquitination in vivo. However, the role of the NRGA and TIER motifs in the enzymatic activity of Arkadia has not been addressed. Here, nuclear magnetic resonance interaction studies with the E2 enzyme, UBCH5B, C85S UBCH5B-Ub oxyester hydrolysis, and auto-ubiquitination assays were used to address the role of the non-RING elements in E2-E3 interaction and in the enzymatic activity of the RING. The results support that the non-RING elements including the NRGA and TIER motifs are required for E2-E3 recognition and interaction and for efficient auto-ubiquitination. Furthermore, while Arkadia isoform-2 and its close homologue Arkadia 2C are known to interact with free ubiquitin, the results here showed that Arkadia isoform-1 does not interact with free ubiquitin.
Association of Polymorphic Variants in Argonaute Genes with Depression Risk in a Polish Population
Authors: Kowalczyk Mateusz , Kowalczyk Edward , Galita Grzegorz , Majsterek Ireneusz , Talarowska Monika , Popławski Tomasz , Kwiatkowski Paweł , Lichota Anna , Sienkiewicz Monika
Published: September 2022

Argonaute (AGO) proteins, through their key role in the regulation of gene expression, participate in many biological processes, including cell differentiation, proliferation, death and DNA repair. Accurate regulation of gene expression appears to be important for the proper development of complex neural circuits. Loss of AGO proteins is known to lead to early embryonic mortality in mice with various malformations, including anomalies of the central nervous system. Single-nucleotide polymorphisms (SNPs) of AGO genes can lead to deregulation of the processes in which AGO proteins are involved. The contribution of different SNPs in depression has been extensively studied. However, there are hardly any studies on the contribution of AGO genes. The aim of our research was to assess the relationship between the occurrence of depression and the presence of SNPs in genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) in a Polish population. One hundred and one subjects in the study group were diagnosed with recurrent depressive disorder by a psychiatrist. The control group comprised 117 healthy subjects. Study participants performed the HDRS (Hamilton Depression Scale) test to confirm or exclude depression and assess severity. The frequency of polymorphic variants of genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) was determined using TaqMan SNP genotyping assays and the TaqMan universal PCR master mix, no AmpErase UNG. The rs4961280/AGO2 polymorphism was associated with a decrease in depression occurrence in the codominant (OR = 0.51, p = 0.034), dominant (OR = 0.49, p = 0.01), and overdominant (OR = 0.58, p = 0.049) models. Based on the obtained results, we found that the studied patients demonstrated a lower risk of depression with the presence of the polymorphic variant of the rs4961280/AGO2 gene—genotype C/A and C/A-A/A.
The Interplay between Aquaporin-1 and the Hypoxia-Inducible Factor 1α in a Lipopolysaccharide-Induced Lung Injury Model in Human Pulmonary Microvascular Endothelial Cells
Authors: Keskinidou Chrysi , Lotsios Nikolaos S. , Vassiliou Alice G. , Dimopoulou Ioanna , Kotanidou Anastasia , Orfanos Stylianos E.
Published: September 2022

Aquaporin-1 (AQP1), a water channel, and the hypoxia-inducible factor 1α (HIF1A) are implicated in acute lung injury responses, modulating among others pulmonary vascular leakage. We hypothesized that the AQP1 and HIF1A systems interact, affecting mRNA, protein levels and function of AQP1 in human pulmonary microvascular endothelial cells (HPMECs) exposed to lipopolysaccharide (LPS). Moreover, the role of AQP1 in apoptosis and wound healing progression was examined. Both AQP1 mRNA and protein expression levels were higher in HPMECs exposed to LPS compared to untreated HPMECs. However, in the LPS-exposed HIF1A-silenced cells, the mRNA and protein expression levels of AQP1 remained unaltered. In the permeability experiments, a statistically significant volume increase was observed at the 360 s time-point in the LPS-exposed HPMECs, while LPS-exposed HIF1A-silenced HPMECs did not exhibit cell swelling, implying a dysfunctional AQP1. AQP1 did not seem to affect cell apoptosis yet could interfere with endothelial migration and/or proliferation. Based on our results, it seems that HIF1A silencing negatively affects AQP1 mRNA and protein expression, as well as AQP1 function, in the setting of lung injury.
The Association between Clusterin Sialylation Degree and Levels of Oxidative–Antioxidant Balance Markers in Seminal Plasmas and Blood Sera of Male Partners with Abnormal Sperm Parameters
Authors: Janiszewska Ewa , Kokot Izabela , Kmieciak Agnieszka , Stelmasiak Zuzanna , Gilowska Iwona , Faundez Ricardo , Kratz Ewa Maria
Published: September 2022

Nearly 30% of infertility cases are caused by male factor. This study aimed at checking the associations between the sialylation degree of glycoprotein clusterin (CLU) and levels of oxidative–antioxidant balance markers in infertile men. Using lectin-ELISA with biotinylated lectins specific to α2,6-linked (Sambucus nigra agglutinin, SNA) and α2,3-linked (Maackia amurensis agglutinin, MAA) sialic acid (SA), the CLU sialylation in 132 seminal plasmas (SP) and 91 blood sera (BS) were analyzed. Oxidative–antioxidant status was measured by determining Sirtuin-3 (SIRT3), Sirtuin-5 (SIRT5), total antioxidant status (TAS), and ferric reducing antioxidant power (FRAP) levels. We indicate that multiple sperm disorders are associated with decreased expression of MAA-reactive SA in SP. Decreased SP SIRT3 concentrations may be associated with teratozoospermia and oligoasthenoteratozoospermia. ROC curve and cluster analysis revealed that SP relative reactivity of CLU glycans with MAA, the value of MAA/SNA ratio, and SIRT3 and SIRT5 concentrations may constitute an additional set of markers differentiating infertile oligoasthenoteratozoospermic patients (OAT) from normozoospermic (N), asthenoteratozoospermic (AT) and teratozoospermic (T). The multinomial logistic regression analysis confirmed the potential utility of SIRT3 determinations for differentiation between N and OAT groups as well as between N and T groups for SIRT3 and SIRT5. For BS, based on ROC curve and cluster analysis, relative reactivities of CLU glycans with SNA, MAA, SIRT3 and FRAP concentrations may be useful in the differentiation of normozoospermic patients from those with sperm disorders. The multinomial logistic regression analysis showed that the SNA relative reactivity with CLU glycans significantly differentiated the N group from AT, OAT and T groups, and FRAP concentrations significantly differed between N and AT groups, which additionally confirms the potential utility of these biomarkers in the differentiation of infertile patients with abnormal sperm parameters. The knowledge about associations between examined parameters may also influence future research aimed at seeking new male infertility therapies.
Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development
Authors: Chaves-Almagro Carline , Auriau Johanna , Dortignac Alizée , Clerc Pascal , Lulka Hubert , Deleruyelle Simon , Projetti Fabrice , Nakhlé Jessica , Frances Audrey , Berta Judit , Gigoux Véronique , Fourmy Daniel , Dufresne Marlène , Gomez-Brouchet Anne , Guillermet-Guibert Julie , Cordelier Pierre , Knibiehler Bernard , Jockers Ralf , Valet Philippe , Audigier Yves , Masri Bernard
Published: September 2022

Despite decades of effort in understanding pancreatic ductal adenocarcinoma (PDAC), there is still a lack of innovative targeted therapies for this devastating disease. Herein, we report the expression of apelin and its receptor, APJ, in human pancreatic adenocarcinoma and its protumoral function. Apelin and APJ protein expression in tumor tissues from patients with PDAC and their spatiotemporal pattern of expression in engineered mouse models of PDAC were investigated by immunohistochemistry. Apelin signaling function in tumor cells was characterized in pancreatic tumor cell lines by Western blot as well as proliferation, migration assays and in murine orthotopic xenograft experiments. In premalignant lesions, apelin was expressed in epithelial lesions whereas APJ was found in isolated cells tightly attached to premalignant lesions. However, in the invasive stage, apelin and APJ were co-expressed by tumor cells. In human tumor cells, apelin induced a long-lasting activation of PI3K/Akt, upregulated β-catenin and the oncogenes c-myc and cyclin D1 and promoted proliferation, migration and glucose uptake. Apelin receptor blockades reduced cancer cell proliferation along with a reduction in pancreatic tumor burden. These findings identify the apelin signaling pathway as a new actor for PDAC development and a novel therapeutic target for this incurable disease.
High-Content Drug Discovery Targeting Molecular Bladder Cancer Subtypes
Authors: Rinaldetti Sébastien , Zhou Qiong , Abbott Joshua M. , de Jong Florus C. , Esquer Hector , Costello James C. , Theodorescu Dan , LaBarbera Daniel V.
Published: September 2022

Molecular subtypes of muscle-invasive bladder cancer (MIBC) display differential survival and drug sensitivities in clinical trials. To date, they have not been used as a paradigm for phenotypic drug discovery. This study aimed to discover novel subtype-stratified therapy approaches based on high-content screening (HCS) drug discovery. Transcriptome expression data of CCLE and BLA-40 cell lines were used for molecular subtype assignment in basal, luminal, and mesenchymal-like cell lines. Two independent HCSs, using focused compound libraries, were conducted to identify subtype-specific drug leads. We correlated lead drug sensitivity data with functional genomics, regulon analysis, and in-vitro drug response-based enrichment analysis. The basal MIBC subtype displayed sensitivity to HDAC and CHK inhibitors, while the luminal subtype was sensitive to MDM2 inhibitors. The mesenchymal-like cell lines were exclusively sensitive to the ITGAV inhibitor SB273005. The role of integrins within this mesenchymal-like MIBC subtype was confirmed via its regulon activity and gene essentiality based on CRISPR–Cas9 knock-out data. Patients with high ITGAV expression showed a significant decrease in the median overall survival. Phenotypic high-content drug screens based on bladder cancer cell lines provide rationales for novel stratified therapeutic approaches as a framework for further prospective validation in clinical trials.
Case Report: Compound Heterozygous Variants of the MAN1B1 Gene in a Russian Patient with Rafiq Syndrome
Authors: Zhalsanova Irina Zh. , Ravzhaeva Ekatherina G. , Postrigan Anna E. , Seitova Gulnara N. , Zhigalina Daria I. , Udalova Vasilisa Yu. , Danina Maryana M. , Kanivets Ilya V. , Skryabin Nikolay A.
Published: September 2022

Rafiq syndrome (RAFQS) is a congenital disorder of glycosylation (CDG) that is caused by mutations in the MAN1B1 gene and characterized by impaired protein and lipid glycosylation. RAFQS is characterized by a delay in intellectual and motor development, facial and other dysmorphism, truncal obesity, behavior problems, and hypotonia. We describe a Russian patient with delayed intellectual and motor development, a lack of speech, disorientation in space and time, impaired attention and memory, and episodes of aggression. Screening for lysosomal, amino acid, organic acid, and mitochondrial disorders was normal. The patient was referred for the targeted sequencing of the “Hereditary Metabolic Disorders” panel. The genetic testing revealed two heterozygous pathogenic variants in the MAN1B1 gene: the previously reported c.1000C > T (p.Arg334Cys) and the novel c.1065 + 1 G > C. Thus, the patient’s clinical picture and genetic analysis confirmed RAFQS in the patient.
cAMP and the Fibrous Sheath Protein CABYR (Ca2+-Binding Tyrosine-Phosphorylation-Regulated Protein) Is Required for 4D Sperm Movement
Authors: Frintrop Linda , Wiesehöfer Caroline , Stoskus Aura , Hilken Gero , Dubicanac Marko , von Ostau Nicola Edith , Rode Sebastian , Elgeti Jens , Dankert Jaroslaw Thomas , Wennemuth Gunther
Published: September 2022

A new life starts with successful fertilization whereby one sperm from a pool of millions fertilizes the oocyte. Sperm motility is one key factor for this selection process, which depends on a coordinated flagellar movement. The flagellar beat cycle is regulated by Ca2+ entry via CatSper, cAMP, Mg2+, ADP and ATP. This study characterizes the effects of these parameters for 4D sperm motility, especially for flagellar movement and the conserved clockwise (CW) path chirality of murine sperm. Therefore, we use detergent-extracted mouse sperm and digital holographic microscopy (DHM) to show that a balanced ratio of ATP to Mg2+ in addition with 18 µM cAMP and 1 mM ADP is necessary for controlled flagellar movement, induction of rolling along the long axis and CW path chirality. Rolling along the sperm’s long axis, a proposed mechanism for sperm selection, is absent in sea urchin sperm, lacking flagellar fibrous sheath (FS) and outer-dense fibers (ODFs). In sperm lacking CABYR, a Ca2+-binding tyrosine-phosphorylation regulated protein located in the FS, the swim path chirality is preserved. We conclude that specific concentrations of ATP, ADP, cAMP and Mg2+ as well as a functional CABYR play an important role for sperm motility especially for path chirality.
Selected Mediators of Inflammation in Patients with Acute Ischemic Stroke
Authors: Pawluk Hanna , Kołodziejska Renata , Grześk Grzegorz , Kozakiewicz Mariusz , Woźniak Alina , Pawluk Mateusz , Kosinska Agnieszka , Grześk Magdalena , Wojtasik Jakub , Kozera Grzegorz
Published: September 2022

During a stroke, a series of biochemical and metabolic changes occur which eventually lead to the death of cells by necrosis or apoptosis. This is a multi-stage process involving oxidative stress and an inflammatory response from the first signs of occlusion of a blood vessel until the late stages of regeneration and healing of ischemic tissues. The purpose of the research was to assess the concentration of pro-inflammatory cytokines IL-6 and TNF-α in the blood serum of patients with ischemic stroke (AIS) and to investigate their role as new markers in predicting functional prognosis after thrombolytic therapy. The researches have shown that the concentrations of the measured biomarkers were higher compared to the control group. Serum levels of IL-6 and THF-α before the initiation of intravenous thrombolysis were lower in the subgroup of patients with a favourable functional result (mRS: 0–2 pts) compared to the group of patients with an unfavourable functional result (mRS: 3–6 pts). A positive correlation was found between the concentration of IL-6 and TNF-α in patients with AIS during <4.5 h and on one day after the onset of stroke, which means that the concentration of IL-6 increases with the increase in TNF-α concentration. It has also been shown that higher levels of IL-6 in the acute phase of stroke and on the first and seventh days, and TNF-α during onset, were associated with poorer early and late prognosis in patients treated with intravenous thrombolysis. A relationship was found between the level of IL-6 and TNF-α in the subacute AIS and the severity of the neurological deficit. It has been shown that the investigated biomarkers may be a prognostic factor in the treatment of thrombolytic AIS.
Cardio-Oncology: Mechanisms, Drug Combinations, and Reverse Cardio-Oncology
Authors: Liang Zehua , He Yuquan , Hu Xin
Published: September 2022

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy have brought hope to cancer patients. With the prolongation of survival of cancer patients and increased clinical experience, cancer-therapy-induced cardiovascular toxicity has attracted attention. The adverse effects of cancer therapy that can lead to life-threatening or induce long-term morbidity require rational approaches to prevention and treatment, which requires deeper understanding of the molecular biology underpinning the disease. In addition to the drugs used widely for cardio-protection, traditional Chinese medicine (TCM) formulations are also efficacious and can be expected to achieve “personalized treatment” from multiple perspectives. Moreover, the increased prevalence of cancer in patients with cardiovascular disease has spurred the development of “reverse cardio-oncology”, which underscores the urgency of collaboration between cardiologists and oncologists. This review summarizes the mechanisms by which cancer therapy induces cardiovascular toxicity, the combination of antineoplastic and cardioprotective drugs, and recent advances in reverse cardio-oncology.
Polysaccharide from Salviae miltiorrhizae Radix et Rhizoma Attenuates the Progress of Obesity-Induced Non-Alcoholic Fatty Liver Disease through Modulating Intestinal Microbiota-Related Gut–Liver Axis
Authors: Li Lixia , Lan Xinting , Peng Xi , Shi Shuai , Zhao Yanlin , Liu Wentao , Luo Qihui , Jia Lanlan , Feng Bin , Chen Zhengli , Zou Yuanfeng , Huang Chao
Published: September 2022

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, thus treatments for it have attracted lots of interest. In this study, the Salviae miltiorrhizae Radix et Rhizoma (SMRR) polysaccharide was isolated by hot water extraction and ethanol precipitation, and then purified by DEAE anion exchange chromatography and gel filtration. With a high-fat-diet-induced obesity/NAFLD mouse model, we found that consumption of the SMRR polysaccharide could remarkably reverse obesity and its related progress of NAFLD, including attenuated hepatocellular steatosis, hepatic fibrosis and inflammation. In addition, we also reveal the potential mechanism behind these is that the SMRR polysaccharide could regulate the gut–liver axis by modulating the homeostasis of gut microbiota and thereby improving intestinal function.
Formation Mechanism of Inter-Crosslink in DNA by Nitrogen Oxides Pollutants through A Diazonium Intermediate
Authors: Hernandez-Haro Noemi , Solis-Calero Christian , Casasnovas Rodrigo , Morell Christophe , Grand Andre , Frau Juan , Ortega-Castro Joaquín
Published: September 2022

Outdoor air pollution is a mixture of multiple atmospheric pollutants, among which nitrogen oxide (NOx) stands out due to its association with several diseases. NOx reactivity can conduct to DNA damage as severe as interstrand crosslinks (ICL) formation, that in turn is able to block DNA replication and transcription. Experimental studies have suggested that the ICL formation due to NOx is realized through a diazonium intermediate (DI). In this work, we have modeled the DI structure, including a DNA double-strand composed of two base pairs GC/CG, being diazotized as one of the guanine nucleotides. The structural stability of DNA with DI lesion was essayed through 500 ns molecular dynamics simulations. It was found that the DNA structure of the oligonucleotide is stable when the DI is present since the loss of a Guanine–Cytosine hydrogen bond is replaced by the presence of two cation-π interactions. Additionally, we have studied the mechanism of formation of a crosslink between the two guanine nucleobases from the modeled DI by carrying out DFT calculations at the M06-L/DNP+ level of theory. Our results show that the mechanism is thermodynamically favored by a strong stabilization of the ICL product, and the process is kinetically viable since its limiting stage is accessible.
Sympathetic Nerve Activity and Blood Pressure Response to Exercise in Peripheral Artery Disease: From Molecular Mechanisms, Human Studies, to Intervention Strategy Development
Authors: Qin Lu , Cui Jian , Li Jianhua
Published: September 2022

Sympathetic nerve activity (SNA) regulates the contraction of vascular smooth muscle and leads to a change in arterial blood pressure (BP). It was observed that SNA, vascular contractility, and BP are heightened in patients with peripheral artery disease (PAD) during exercise. The exercise pressor reflex (EPR), a neural mechanism responsible for BP response to activation of muscle afferent nerve, is a determinant of the exaggerated exercise-induced BP rise in PAD. Based on recent results obtained from a series of studies in PAD patients and a rat model of PAD, this review will shed light on SNA-driven BP response and the underlying mechanisms by which receptors and molecular mediators in muscle afferent nerves mediate the abnormalities in autonomic activities of PAD. Intervention strategies, particularly non-pharmacological strategies, improving the deleterious exercise-induced SNA and BP in PAD, and enhancing tolerance and performance during exercise will also be discussed.
Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population
Authors: da Silva Mayara Natália Santana , da Veiga Borges Leal Diana Feio , Sena Camille , Pinto Pablo , Gobbo Angélica Rita , da Silva Moises Batista , Salgado Claudio Guedes , dos Santos Ney Pereira Carneiro , dos Santos Sidney Emanuel Batista
Published: September 2022

Leprosy is a chronic neurodermatological disease caused by the bacillus Mycobacterium leprae. Recent studies show that SNPs in genes related to miRNAs have been associated with several diseases in different populations. This study aimed to evaluate the association of twenty-five SNPs in genes encoding miRNAs related to biological processes and immune response with susceptibility to leprosy and its polar forms paucibacillary and multibacillary in the Brazilian Amazon. A total of 114 leprosy patients and 71 household contacts were included in this study. Genotyping was performed using TaqMan Open Array Genotyping. Ancestry-informative markers were used to estimate individual proportions of case and control groups. The SNP rs2505901 (pre-miR938) was associated with protection against the development of paucibacillary leprosy, while the SNPs rs639174 (DROSHA), rs636832 (AGO1), and rs4143815 (miR570) were associated with protection against the development of multibacillary leprosy. In contrast, the SNPs rs10739971 (pri-let-7a1), rs12904 (miR200C), and rs2168518 (miR4513) are associated with the development of the paucibacillary leprosy. The rs10739971 (pri-let-7a1) polymorphism was associated with the development of leprosy, while rs2910164 (miR146A) and rs10035440 (DROSHA) was significantly associated with an increased risk of developing multibacillary leprosy.
Effect of Chronic Treatment with Uridine on Cardiac Mitochondrial Dysfunction in the C57BL/6 Mouse Model of High-Fat Diet–Streptozotocin-Induced Diabetes
Authors: Belosludtseva Natalia V. , Starinets Vlada S. , Mikheeva Irina B. , Belosludtsev Maxim N. , Dubinin Mikhail V. , Mironova Galina D. , Belosludtsev Konstantin N.
Published: September 2022

Long-term hyperglycemia in diabetes mellitus is associated with complex damage to cardiomyocytes and the development of mitochondrial dysfunction in the myocardium. Uridine, a pyrimidine nucleoside, plays an important role in cellular metabolism and is used to improve cardiac function. Herein, the antidiabetic potential of uridine (30 mg/kg/day for 21 days, i.p.) and its effect on mitochondrial homeostasis in the heart tissue were examined in a high-fat diet–streptozotocin-induced model of diabetes in C57BL/6 mice. We found that chronic administration of uridine to diabetic mice normalized plasma glucose and triglyceride levels and the heart weight/body weight ratio and increased the rate of glucose utilization during the intraperitoneal glucose tolerance test. Analysis of TEM revealed that uridine prevented diabetes-induced ultrastructural abnormalities in mitochondria and sarcomeres in ventricular cardiomyocytes. In diabetic heart tissue, the mRNA level of Ppargc1a decreased and Drp1 and Parkin gene expression increased, suggesting the disturbances of mitochondrial biogenesis, fission, and mitophagy, respectively. Uridine treatment of diabetic mice restored the mRNA level of Ppargc1a and enhanced Pink1 gene expression, which may indicate an increase in the intensity of mitochondrial biogenesis and mitophagy, and as a consequence, mitochondrial turnover. Uridine also reduced oxidative phosphorylation dysfunction and suppressed lipid peroxidation, but it had no significant effect on the impaired calcium retention capacity and potassium transport in the heart mitochondria of diabetic mice. Altogether, these findings suggest that, along with its hypoglycemic effect, uridine has a protective action against diabetes-mediated functional and structural damage to cardiac mitochondria and disruption of mitochondrial quality-control systems in the diabetic heart.
Bacillus subtilis: As an Efficient Bacterial Strain for the Reclamation of Water Loaded with Textile Azo Dye, Orange II
Authors: Ikram Muhammad , Naeem Mohammad , Zahoor Muhammad , Hanafiah Marlia Mohd , Oyekanmi Adeleke Abdulrahman , Islam Noor Ul , Ullah Midrar , Mahnashi Mater H. , Ali Amer Al , Jalal Naif A. , Bantun Farkad , Momenah Aiman M. , Sadiq Abdul
Published: September 2022

The azo dye orange II is used extensively in the textile sector for coloring fabrics. High concentrations of it are released into aqueous environments through textile effluents. Therefore, its removal from textile wastewater and effluents is necessary. Herein, initially, we tested 11 bacterial strains for their capabilities in the degradation of orange II dye. It was revealed in the preliminary data that B. subtilis can more potently degrade the selected dye, which was thus used in the subsequent experiments. To achieve maximum decolorization, the experimental conditions were optimized whereby maximum degradation was achieved at: a 25 ppm dye concentration, pH 7, a temperature of 35 °C, a 1000 mg/L concentration of glucose, a 1000 mg/L urea concentration, a 666.66 mg/L NaCl concentration, an incubation period of 3 days, and with hydroquinone as a redox mediator at a concentration of 66.66 mg/L. The effects of the interaction of the operational factors were further confirmed using response surface methodology, which revealed that at optimum conditions of pH 6.45, a dye concentration of 17.07 mg/L, and an incubation time of 9.96 h at 45.38 °C, the maximum degradation of orange II can be obtained at a desirability coefficient of 1, estimated using the central composite design (CCD). To understand the underlying principles of degradation of the metabolites in the aliquot mixture at the optimized condition, the study steps were extracted and analyzed using GC-MS(Gas Chromatography Mass Spectrometry), FTIR(Fourier Transform Infrared Spectroscopy), 1H and carbon 13 NMR(Nuclear Magnetic Resonance Spectroscopy). The GC-MS pattern revealed that the original dye was degraded into o-xylene and naphthalene. Naphthalene was even obtained in a pure state through silica gel column isolation and confirmed using 1H and 13C NMR spectroscopic analysis. Phytotoxicity tests on Vigna radiata were also conducted and the results confirmed that the dye metabolites were less toxic than the parent dye. These results emphasize that B. subtilis should be used as a potential strain for the bioremediation of textile effluents containing orange II and other toxic azo dyes.
Special Issue on the “Regulation and Physiopathology of the Gut Barrier”
Authors: Thenet Sophie , Carrière Véronique
Published: September 2022

The importance of gut barrier integrity in intestinal homeostasis and the consequences of its alteration in the etiology of human pathologies have been subjects of exponentially growing interest during the last decade [...]
Circulating Biomarkers of Endothelial Dysfunction and Inflammation in Predicting Clinical Outcomes in Diabetic Patients with Critical Limb Ischemia
Authors: Vieceli Dalla Sega Francesco , Cimaglia Paolo , Manfrini Marco , Fortini Francesca , Marracino Luisa , Bernucci Davide , Pompei Graziella , Scala Antonella , Trichilo Michele , De Carolis Beatrice , Dalla Paola Luca , Ferrari Roberto , Rizzo Paola , Campo Gianluca
Published: September 2022

Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease characterized by ischemic pain, which is frequently associated with diabetes and non-healing lesions to inferior limbs. The clinical management of diabetic patients with CLI typically includes percutaneous transluminal angioplasty (PTA) to restore limb circulation and surgical treatment of diabetic foot ulcers (DFU). However, even after successful treatment, CLI patients are prone to post-procedure complications, which may lead to unplanned revascularization or foot surgery. Unfortunately, the factors predicting adverse events in treated CLI patients are only partially known. This study aimed to identify potential biomarkers that predict the disease course in diabetic patients with CLI. For this purpose, we measured the circulating levels of a panel of 23 molecules related to inflammation, endothelial dysfunction, platelet activation, and thrombophilia in 92 patients with CLI and DFU requiring PTA and foot surgery. We investigated whether these putative biomarkers were associated with the following clinical endpoints: (1) healing of the treated DFUs; (2) need for new revascularization of the limb; (3) appearance of new lesions or relapses after successful healing. We found that sICAM-1 and endothelin-1 are inversely associated with DFU healing and that PAI-1 and endothelin-1 are associated with the need for new revascularization. Moreover, we found that the levels of thrombomodulin and sCD40L are associated with new lesions or recurrence, and we show that the levels of these biomarkers could be used in a decision tree to assign patients to clusters with different risks of developing new lesions or recurrences.
The Role of the Glutathione System in Stress Adaptation, Morphogenesis and Virulence of Pathogenic Fungi
Authors: Wangsanut Tanaporn , Pongpom Monsicha
Published: September 2022

Morphogenesis and stress adaptation are key attributes that allow fungal pathogens to thrive and infect human hosts. During infection, many fungal pathogens undergo morphological changes, and this ability is highly linked to virulence. Furthermore, pathogenic fungi have developed multiple antioxidant defenses to cope with the host-derived oxidative stress produced by phagocytes. Glutathione is a major antioxidant that can prevent cellular damage caused by various oxidative stressors. While the role of glutathione in stress detoxification is known, studies of the glutathione system in fungal morphological switching and virulence are lacking. This review explores the role of glutathione metabolism in fungal adaptation to stress, morphogenesis, and virulence. Our comprehensive analysis of the fungal glutathione metabolism reveals that the role of glutathione extends beyond stressful conditions. Collectively, glutathione and glutathione-related proteins are necessary for vitality, cellular development and pathogenesis.
In Silico Evaluation of Hexamethylene Amiloride Derivatives as Potential Luminal Inhibitors of SARS-CoV-2 E Protein
Authors: Jalily Pouria H. , Jalily Hasani Horia , Fedida David
Published: September 2022

The coronavirus E proteins are small membrane proteins found in the virus envelope of alpha and beta coronaviruses that have a high degree of overlap in their biochemical and functional properties despite minor sequence variations. The SARS-CoV-2 E is a 75-amino acid transmembrane protein capable of acting as an ion channel when assembled in a pentameric fashion. Various studies have found that hexamethylene amiloride (HMA) can inhibit the ion channel activity of the E protein in bilayers and also inhibit viral replication in cultured cells. Here, we use the available structural data in conjunction with homology modelling to build a comprehensive model of the E protein to assess potential binding sites and molecular interactions of HMA derivatives. Furthermore, we employed an iterative cycle of molecular modelling, extensive docking simulations, molecular dynamics and leveraging steered molecular dynamics to better understand the pore characteristics and quantify the affinity of the bound ligands. Results from this work highlight the potential of acylguanidines as blockers of the E protein and guide the development of subsequent small molecule inhibitors.
Cold Atmospheric Plasma Jet Treatment Improves Human Keratinocyte Migration and Wound Closure Capacity without Causing Cellular Oxidative Stress
Authors: Marches Aurélie , Clement Emily , Albérola Géraldine , Rols Marie-Pierre , Cousty Sarah , Simon Michel , Merbahi Nofel
Published: September 2022

Cold Atmospheric Plasma (CAP) is an emerging technology with great potential for biomedical applications such as sterilizing equipment and antitumor strategies. CAP has also been shown to improve skin wound healing in vivo, but the biological mechanisms involved are not well known. Our study assessed a possible effect of a direct helium jet CAP treatment on keratinocytes, in both the immortalized N/TERT-1 human cell line and primary keratinocytes obtained from human skin samples. The cells were covered with 200 µL of phosphate buffered saline and exposed to the helium plasma jet for 10–120 s. In our experimental conditions, micromolar concentrations of hydrogen peroxide, nitrite and nitrate were produced. We showed that long-time CAP treatments (≥60 s) were cytotoxic, reduced keratinocyte migration, upregulated the expression of heat shock protein 27 (HSP27) and induced oxidative cell stress. In contrast, short-term CAP treatments (<60 s) were not cytotoxic, did not affect keratinocyte proliferation and differentiation, and did not induce any changes in mitochondria, but they did accelerate wound closure in vitro by improving keratinocyte migration. In conclusion, these results suggest that helium-based CAP treatments improve wound healing by stimulating keratinocyte migration. The study confirms that CAP could be a novel therapeutic method to treat recalcitrant wounds.