bluuebunny/crossref_metadata_2025 huggingface dataset:
Regression Models to Study the Total LOS Related to Valvuloplasty
Authors: Scala Arianna , Trunfio Teresa Angela , De Coppi Lucia , Rossi Giovanni , Borrelli Anna , Triassi Maria , Improta Giovanni
Published: March 2022

Background: Valvular heart diseases are diseases that affect the valves by altering the normal circulation of blood within the heart. In recent years, the use of valvuloplasty has become recurrent due to the increase in calcific valve disease, which usually occurs in the elderly, and mitral valve regurgitation. For this reason, it is critical to be able to best manage the patient undergoing this surgery. To accomplish this, the length of stay (LOS) is used as a quality indicator. Methods: A multiple linear regression model and four other regression algorithms were used to study the total LOS function of a set of independent variables related to the clinical and demographic characteristics of patients. The study was conducted at the University Hospital “San Giovanni di Dio e Ruggi d’Aragona” of Salerno (Italy) in the years 2010–2020. Results: Overall, the MLR model proved to be the best, with an R2 value of 0.720. Among the independent variables, age, pre-operative LOS, congestive heart failure, and peripheral vascular disease were those that mainly influenced the output value. Conclusions: LOS proves, once again, to be a strategic indicator for hospital resource management, and simple linear regression models have shown excellent results to analyze it.
Water, Sanitation and Hygiene in Schools in Low- and Middle-Income Countries: A Systematic Review and Implications for the COVID-19 Pandemic
Authors: Poague Kasandra I. H. M. , Blanford Justine I. , Anthonj Carmen
Published: March 2022

The global COVID-19 pandemic has revealed the extent to which schools are struggling with the provision of safe drinking water, sanitation and hygiene (WASH). To describe the WASH conditions in schools and discuss the implications for the safe reopening of schools during the ongoing COVID-19 pandemic, a systematic review of peer-reviewed literature on WASH in schools in low- and middle-income countries was performed. In April 2021, five databases, including MEDLINE (via PubMed), Web of Science, Scopus, AJOL, and LILACS, were used to identify studies. Sixty-five papers met the inclusion criteria. We extracted and analyzed data considering the Joint Monitoring Programme (JMP) definitions and the normative contents of Human Rights to safe drinking water and sanitation. Publications included in this systematic review considered 18,465 schools, across 30 different countries. Results indicate a lack of adequate WASH conditions and menstrual hygiene management requirements in all countries. The largely insufficient and inadequate school infrastructure hampers students to practice healthy hygiene habits and handwashing in particular. In the context of the COVID-19 pandemic, being hindered to implement such a key strategy to contain the spread of SARS-CoV-2 in the school environment is of major concern.
Efficacy of MMP-8 Level in Gingival Crevicular Fluid to Predict the Outcome of Nonsurgical Periodontal Treatment: A Systematic Review
Authors: Gul Sarhang Sarwat , Zardawi Faraedon Mostafa , Abdulkareem Ali Abbas , Shaikh Muhammad Saad , Al-Rawi Natheer Hashim , Zafar Muhammad Sohail
Published: March 2022

Purpose: To explore whether baseline matrix metalloproteinase (MMP)-8 level in gingival crevicular fluid (GCF) (exposure) can predict the outcome (reduction in probing pocket depth (PPD) (outcome)) of nonsurgical periodontal therapy (NSPT) (manual or ultrasonic or both) in patients with periodontitis (population/problem) after 3 months. Methods: Six databases (PubMed, Cochrane library, ProQuest, Ovid, Scopus, EBSCO) were searched for relevant articles published until 30 July 2021. Retrieved articles were passed through a three-phase filtration process on the basis of the eligibility criteria. The primary outcome was the change in PPD after 3 months. Quality of the selected articles was assessed using Cochrane Risk of Bias tool (RoB2) and Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tools. Results: From 1306 articles, five were selected for analysis. The results showed high variations in the level of GCF MMP-8 level at baseline. The average amount of reduction in PPD was 1.20 and 2.30 mm for pockets with initial depth of 4–6 mm and >6 mm, respectively. Conclusion: On the basis of available evidence, it was not possible to reach a consensus on the ability of baseline GCF MMP-8 to forecast the outcome of NSPT. This could have been due to variation in clinical and laboratory techniques used. However, consistency in mean PPD reduction after 3 months was shown.
The Mediating Effects of Work Characteristics on the Relationship between Transformational Leadership and Employee Well-Being: A Meta-Analytic Investigation
Authors: Teetzen Friederike , Bürkner Paul-Christian , Gregersen Sabine , Vincent-Höper Sylvie
Published: March 2022

Evidence points to an indirect relationship between transformational leadership (TFL) and employee well-being, and numerous work characteristics have been identified as mediators. However, the relative mediating effect of different types of job resources and job demands on the TFL–well-being relationship remains unclear, rendering it impossible to determine which ones are the most influential. This study aims to provide a comprehensive analysis of the relative mediation potential of different work characteristics in the TFL–well-being relationship in multiple three-level meta-analytical structural equation models of 243 samples. Based on the JD–R Model, this study extends this theoretical framework by suggesting TFL as a predisposing variable that influences both job resources and job demands, leading to changes in indicators of both positive and negative employee well-being. The results show that, while all the examined job resources and demands mediated the TFL–well-being relationship, organizational resources were identified as the strongest mediators. Furthermore, job demands had a strong mediating effect on the relationship between TFL and negative well-being, while job resources more strongly mediated TFL and positive well-being. We present a differentiated picture of how transformational leaders can influence their employees’ well-being at the workplace, providing valuable knowledge for future research and practice.
Association between Participation in the Short Version of a Workplace Oral Health Promotion Program and Medical and Dental Care Expenditures in Japanese Workers: A Longitudinal Study
Authors: Mochida Yuki , Fuchida Shinya , Yamamoto Tatsuo
Published: March 2022

Studies suggest that intensive oral health promotion programs in the workplace reduce dental and medical care expenditures. The purpose of this longitudinal study was to evaluate the short version of an oral health promotion program in the workplace from the viewpoint of dental and medical care expenditures. Data for annual expenditures and number of days of dental, periodontal, and medical treatment in fiscal year 2018 and participation in the short version of a workplace oral health promotion program of 2545 workers (20–68 years old) in a company in fiscal year 2017 and prior were obtained. Zero-inflated negative binomial regression models or negative binomial regression models were used to evaluate the association between participation in the program and expenditures or number of days of treatment after adjusting for sex and age. Program participants were more likely than non-participants to visit dentists for dental and periodontal treatment. Those who participated twice or more spent less on dental, periodontal, and medical treatment and had fewer visits to dentists than non-participants. These results suggest that the short version of an oral health promotion program in the workplace decreases expenditures for dental, periodontal, and medical treatment.
Nonparametric Regression Analysis of Cyclist Waiting Times across Three Behavioral Typologies
Authors: Walker Jeremy , Poliziani Cristian , Tortora Cristina , Schweizer Joerg , Rupi Federico
Published: March 2022

This paper seeks to predict the average waiting time, defined as the time spent moving at 1 ms−1 or less, of urban bicyclists during rush hours while performing different maneuvers at intersections. Individual predictive models are built for the three cyclist typologies previously identified on a large database of GPS traces recorded in the city of Bologna, Italy. Individual models are built for the three cyclist typologies and bootstrapping has confirmed the validity and robustness of the results. The results allow the integration of waiting times in route choice models for cyclists, thus improving the rational bases by which cyclists makes their decisions. Moreover, the modeling allows transportation engineers to understand how different cyclist typologies perceive different variables that affect their waiting times. Future work should focus on testing the model transferability to other case studies.
Characteristics and Influencing Factors of Spatial Differentiation of Market Service Industries in Rural Areas around Metropolises—A Case Study of Wuhan City’s New Urban Districts
Authors: Chen Jie , Jiang Liang , Luo Jing , Tian Lingling , Tian Ye , Chen Guolei
Published: March 2022

Market services industries are closely related to residents’ lives, and its spatial distribution has an important impact on satisfying residents’ consumption needs and promoting economic development. In recent years, with the rapid development of urban–rural integration and the gradual implementation of a rural revitalization strategy, rural areas around metropolises have become the “frontier” of urban geographic expansion, causing the rural market services industries to specialize, commercialize, and modernize. Taking Wuhan as a case study, the spatial distribution characteristics and influencing factors of the market services industries were measured using the average nearest neighbor index, the kernel density estimate, the spatial correlation analysis, and the Geodetector method. The results are as follows. (1) The market services industries in Wuhan’s new urban districts, as a whole and individually, showed characteristics of agglomeration. The market services industries overall formed two high-density areas and multiple agglomeration areas, and the high-density areas of different types of market services industries showed characteristics of partial spatial overlap. (2) There was a significant positive spatial correlation in market services industries, as a whole and individually. Among them, the life services industry had the strongest spatial correlation, while the accommodation services industry had the weakest. (3) Market demand and traffic conditions were the core factors influencing the distribution of the market services industries in Wuhan’s new urban districts, followed by urbanization and economic levels; and tourism conditions had a lower impact. Each detector had a different impact on the spatial distribution of different market services industries, and the interaction research showed that the spatial distribution of the market services industries was the result of a combination of multiple factors. This research provides a future development direction for market service industries in rural areas.
Street Patrol Routing Optimization in Smart City Management Based on Genetic Algorithm: A Case in Zhengzhou, China
Authors: Jiang Yirui , Li Hongwei , Feng Binbin , Wu Zekang , Zhao Shan , Wang Zhaohui
Published: March 2022

A series of urban law enforcement events involving city inspectors dispatched by the city management department can reflect some problems in smart city management, such as illegal advertising and unlicensed street operation. In this paper, we propose a model for the allocation of city inspectors and the optimization of patrol paths. The objective is to minimize the average response time and the number of inspectors. We also develop a priority-patrol-and-multiobjective genetic algorithm (DP-MOGA) to classify patrol segments according to the frequency of events and develop an improved genetic algorithm to achieve the aforementioned objective. We conduct numerical experiments using patrol data obtained from city inspectors in Zhengzhou, China, to clearly show that the proposed algorithm generates reasonable routes that reduce the average response time of events and the number of patrol inspectors. Furthermore, we test the algorithm for three different time scenarios (roads with different average numbers of events) and demonstrate the efficiency of the algorithm. The experimental results show that our proposed algorithm is more stable and efficient than other existing algorithms.
Musculoskeletal Aging and Sarcopenia in the Elderly
Authors: Marzetti Emanuele
Published: March 2022

The loss of skeletal muscle mass and strength/function, referred to as sarcopenia, is a pervasive feature of aging [...]
Salting-Out of DNA Origami Nanostructures by Ammonium Sulfate
Authors: Hanke Marcel , Hansen Niklas , Chen Ruiping , Grundmeier Guido , Fahmy Karim , Keller Adrian
Published: March 2022

DNA origami technology enables the folding of DNA strands into complex nanoscale shapes whose properties and interactions with molecular species often deviate significantly from that of genomic DNA. Here, we investigate the salting-out of different DNA origami shapes by the kosmotropic salt ammonium sulfate that is routinely employed in protein precipitation. We find that centrifugation in the presence of 3 M ammonium sulfate results in notable precipitation of DNA origami nanostructures but not of double-stranded genomic DNA. The precipitated DNA origami nanostructures can be resuspended in ammonium sulfate-free buffer without apparent formation of aggregates or loss of structural integrity. Even though quasi-1D six-helix bundle DNA origami are slightly less susceptible toward salting-out than more compact DNA origami triangles and 24-helix bundles, precipitation and recovery yields appear to be mostly independent of DNA origami shape and superstructure. Exploiting the specificity of ammonium sulfate salting-out for DNA origami nanostructures, we further apply this method to separate DNA origami triangles from genomic DNA fragments in a complex mixture. Our results thus demonstrate the possibility of concentrating and purifying DNA origami nanostructures by ammonium sulfate-induced salting-out.
Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model
Authors: Wang Xiaohang , Kanda Hirosato , Tsujino Takeshi , Kogure Yoko , Zhu Feng , Yamamoto Satoshi , Sakaguchi Taichi , Noguchi Koichi , Dai Yi
Published: March 2022

Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30–40% patients continue to have angina after a successful PCI, thereby reducing patient satisfaction. The mechanisms underlying persistent angina after revascularisation therapy are still poorly understood; hence, the treatment or guideline for post-PCI angina remains unestablished. Thus, this study aimed to investigate the mechanisms underlying effort angina in animals following myocardial ischaemia-reperfusion (I/R) injury. Phosphorylated extracellular signal-regulated kinase (p-ERK), a marker for painful stimulation-induced neuronal activation, was used for the investigation. After a forced treadmill exercise (FTE), the number of p-ERK-expressing neurons increased in the superficial dorsal horn of the I/R model animals. Moreover, FTE evoked hydrogen peroxide (H2O2) production in the I/R-injured heart, inducing angina through TRPA1 activation on cardiac sensory fibres. Notably, the treatment of a TEMPOL, a reactive oxygen species scavenger, or TRPA1−/− mice successfully alleviated the FTE-induced p-ERK expression in the dorsal horn. The production of H2O2, a reactive oxygen species, through physical exercise contributes to angina development following I/R. Hence, our findings may be useful for understanding and treating angina following revascularisation therapy.
The Tiny Companion Matters: The Important Role of Protons in Active Transports in Plants
Authors: Ku Yee-Shan , Cheng Sau-Shan , Ng Ming-Sin , Chung Gyuhwa , Lam Hon-Ming
Published: March 2022

In plants, the translocation of molecules, such as ions, metabolites, and hormones, between different subcellular compartments or different cells is achieved by transmembrane transporters, which play important roles in growth, development, and adaptation to the environment. To facilitate transport in a specific direction, active transporters that can translocate their substrates against the concentration gradient are needed. Examples of major active transporters in plants include ATP-binding cassette (ABC) transporters, multidrug and toxic compound extrusion (MATE) transporters, monosaccharide transporters (MSTs), sucrose transporters (SUTs), and amino acid transporters. Transport via ABC transporters is driven by ATP. The electrochemical gradient across the membrane energizes these secondary transporters. The pH in each cell and subcellular compartment is tightly regulated and yet highly dynamic, especially when under stress. Here, the effects of cellular and subcellular pH on the activities of ABC transporters, MATE transporters, MSTs, SUTs, and amino acid transporters will be discussed to enhance our understanding of their mechanics. The relation of the altered transporter activities to various biological processes of plants will also be addressed. Although most molecular transport research has focused on the substrate, the role of protons, the tiny counterparts of the substrate, should also not be ignored.
Polymer–Metal Interfacial Friction Characteristics under Ultrasonic Plasticizing Conditions: A United-Atom Molecular Dynamics Study
Authors: Wu Wangqing , He Changsheng , Qiang Yuanbao , Peng Huajian , Zhou Mingyong
Published: March 2022

Understanding the properties of polymer–metal interfacial friction is critical for accurate prototype design and process control in polymer-based advanced manufacturing. The transient polymer–metal interfacial friction characteristics are investigated using united-atom molecular dynamics in this study, which is under the boundary conditions of single sliding friction (SSF) and reciprocating sliding friction (RSF). It reflects the polymer–metal interaction under the conditions of initial compaction and ultrasonic vibration, so that the heat generation mechanism of ultrasonic plasticization microinjection molding (UPMIM) is explored. The contact mechanics, polymer segment rearrangement, and frictional energy transfer features of polymer–metal interface friction are investigated. The results reveal that, in both SSF and RSF modes, the sliding rate has a considerable impact on the dynamic response of the interfacial friction force, where the amplitude has a response time of about 0.6 ns to the friction. The high frequency movement of the polymer segment caused by dynamic interfacial friction may result in the formation of a new coupled interface. Frictional energy transfer is mainly characterized by dihedral and kinetic energy transitions in polymer chains. Our findings also show that the ultrasonic amplitude has a greater impact on polymer–metal interfacial friction heating than the frequency, as much as it does under ultrasonic plasticizing circumstances on the homogeneous polymer–polymer interface. Even if there are differences in thermophysical properties at the heterointerface, transient heating will still cause heat accumulation at the interface with a temperature difference of around 35 K.
Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients
Authors: Oshchepkov Dmitry , Chadaeva Irina , Kozhemyakina Rimma , Zolotareva Karina , Khandaev Bato , Sharypova Ekaterina , Ponomarenko Petr , Bogomolov Anton , Klimova Natalya V. , Shikhevich Svetlana , Redina Olga , Kolosova Nataliya G. , Nazarenko Maria , Kolchanov Nikolay A. , Markel Arcady , Ponomarenko Mikhail
Published: March 2022

Although half of hypertensive patients have hypertensive parents, known hypertension-related human loci identified by genome-wide analysis explain only 3% of hypertension heredity. Therefore, mainstream transcriptome profiling of hypertensive subjects addresses differentially expressed genes (DEGs) specific to gender, age, and comorbidities in accordance with predictive preventive personalized participatory medicine treating patients according to their symptoms, individual lifestyle, and genetic background. Within this mainstream paradigm, here, we determined whether, among the known hypertension-related DEGs that we could find, there is any genome-wide hypertension theranostic molecular marker applicable to everyone, everywhere, anytime. Therefore, we sequenced the hippocampal transcriptome of tame and aggressive rats, corresponding to low and high stress reactivity, an increase of which raises hypertensive risk; we identified stress-reactivity-related rat DEGs and compared them with their known homologous hypertension-related animal DEGs. This yielded significant correlations between stress reactivity-related and hypertension-related fold changes (log2 values) of these DEG homologs. We found principal components, PC1 and PC2, corresponding to a half-difference and half-sum of these log2 values. Using the DEGs of hypertensive versus normotensive patients (as the control), we verified the correlations and principal components. This analysis highlighted downregulation of β-protocadherins and hemoglobin as whole-genome hypertension theranostic molecular markers associated with a wide vascular inner diameter and low blood viscosity, respectively.
The Acute Toxicity of Mineral Fibres: A Systematic In Vitro Study Using Different THP-1 Macrophage Phenotypes
Authors: Mirata Serena , Almonti Vanessa , Di Giuseppe Dario , Fornasini Laura , Raneri Simona , Vernazza Stefania , Bersani Danilo , Gualtieri Alessandro F. , Bassi Anna Maria , Scarfì Sonia
Published: March 2022

Alveolar macrophages are the first line of defence against detrimental inhaled stimuli. To date, no comparative data have been obtained on the inflammatory response induced by different carcinogenic mineral fibres in the three main macrophage phenotypes: M0 (non-activated), M1 (pro-inflammatory) and M2 (alternatively activated). To gain new insights into the different toxicity mechanisms of carcinogenic mineral fibres, the acute effects of fibrous erionite, crocidolite and chrysotile in the three phenotypes obtained by THP-1 monocyte differentiation were investigated. The three mineral fibres apparently act by different toxicity mechanisms. Crocidolite seems to exert its toxic effects mostly as a result of its biodurability, ROS and cytokine production and DNA damage. Chrysotile, due to its low biodurability, displays toxic effects related to the release of toxic metals and the production of ROS and cytokines. Other mechanisms are involved in explaining the toxicity of biodurable fibrous erionite, which induces lower ROS and toxic metal release but exhibits a cation-exchange capacity able to alter the intracellular homeostasis of important cations. Concerning the differences among the three macrophage phenotypes, similar behaviour in the production of pro-inflammatory mediators was observed. The M2 phenotype, although known as a cell type recruited to mitigate the inflammatory state, in the case of asbestos fibres and erionite, serves to support the process by supplying pro-inflammatory mediators.
Chemical Fingerprinting of Heat Stress Responses in the Leaves of Common Wheat by Fourier Transform Infrared Spectroscopy
Authors: Osman Salma O. M. , Saad Abu Sefyan I. , Tadano Shota , Takeda Yoshiki , Konaka Takafumi , Yamasaki Yuji , Tahir Izzat S. A. , Tsujimoto Hisashi , Akashi Kinya
Published: March 2022

Wheat (Triticum aestivum L.) is known to be negatively affected by heat stress, and its production is threatened by global warming, particularly in arid regions. Thus, efforts to better understand the molecular responses of wheat to heat stress are required. In the present study, Fourier transform infrared (FTIR) spectroscopy, coupled with chemometrics, was applied to develop a protocol that monitors chemical changes in common wheat under heat stress. Wheat plants at the three-leaf stage were subjected to heat stress at a 42 °C daily maximum temperature for 3 days, and this led to delayed growth in comparison to that of the control. Measurement of FTIR spectra and their principal component analysis showed partially overlapping features between heat-stressed and control leaves. In contrast, supervised machine learning through linear discriminant analysis (LDA) of the spectra demonstrated clear discrimination of heat-stressed leaves from the controls. Analysis of LDA loading suggested that several wavenumbers in the fingerprinting region (400–1800 cm−1) contributed significantly to their discrimination. Novel spectrum-based biomarkers were developed using these discriminative wavenumbers that enabled the successful diagnosis of heat-stressed leaves. Overall, these observations demonstrate the versatility of FTIR-based chemical fingerprints for use in heat-stress profiling in wheat.
The Anti-Proliferative and Apoptotic Effects of Rutaecarpine on Human Esophageal Squamous Cell Carcinoma Cell Line CE81T/VGH In Vitro and In Vivo
Authors: Wang Li-Yu , Yeh Shu-Lan , Hsu Shih-Tien , Chen Chao-Hsiang , Chen Chien-Chih , Chuang Cheng-Hung
Published: March 2022

The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP’s effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.
Fourier-Transform Infra-Red Microspectroscopy Can Accurately Diagnose Colitis and Assess Severity of Inflammation
Authors: Keung Charlotte , Heraud Philip , Kuk Nathan , Lim Rebecca , Sievert William , Moore Gregory , Wood Bayden
Published: March 2022

The diagnosis and management of inflammatory bowel disease relies on histological assessment, which is costly, subjective, and lacks utility for point-of-care diagnosis. Fourier-transform infra-red spectroscopy provides rapid, non-destructive, reproducible, and automatable label-free biochemical imaging of tissue for diagnostic purposes. This study characterises colitis using spectroscopy, discriminates colitis from healthy tissue, and classifies inflammation severity. Hyperspectral images were obtained from fixed intestinal sections of a murine colitis model treated with cell therapy to improve inflammation. Multivariate analyses and classification modelling were performed using supervised and unsupervised machine-learning algorithms. Quantitative analysis of severe colitis showed increased protein, collagen, and nucleic acids, but reduced glycogen when compared with normal tissue. A partial least squares discriminant analysis model, including spectra from all intestinal layers, classified normal colon and severe colitis with a sensitivity of 91.4% and a specificity of 93.3%. Colitis severity was classified by a stacked ensemble model yielding an average area under the receiver operating characteristic curve of 0.95, 0.88, 0.79, and 0.85 for controls, mild, moderate, and severe colitis, respectively. Infra-red spectroscopy can detect unique biochemical features of intestinal inflammation and accurately classify normal and inflamed tissue and quantify the severity of inflammation. This is a promising alternative to histological assessment.
NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments
Authors: Santos Ariana C. F. , Monteiro Luís P. G. , Gomes Adriana C. C. , Martel Fátima , Santos Teresa M. , Ferreira Bárbara J. M. Leite
Published: March 2022

After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs’ biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs’ properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.
Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management
Authors: Tagde Priti , Najda Agnieszka , Nagpal Kalpana , Kulkarni Giriraj T. , Shah Muddaser , Ullah Obaid , Balant Sebastian , Rahman Md. Habibur
Published: March 2022

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70–80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.
Methylmercury Induces Mitochondria- and Endoplasmic Reticulum Stress-Dependent Pancreatic β-Cell Apoptosis via an Oxidative Stress-Mediated JNK Signaling Pathway
Authors: Yang Ching-Yao , Liu Shing-Hwa , Su Chin-Chuan , Fang Kai-Min , Yang Tsung-Yuan , Liu Jui-Ming , Chen Ya-Wen , Chang Kai-Chih , Chuang Haw-Ling , Wu Cheng-Tien , Lee Kuan-I , Huang Chun-Fa
Published: March 2022

Methylmercury (MeHg), a long-lasting organic pollutant, is known to induce cytotoxic effects in mammalian cells. Epidemiological studies have suggested that environmental exposure to MeHg is linked to the development of diabetes mellitus (DM). The exact molecular mechanism of MeHg-induced pancreatic β-cell cytotoxicity is still unclear. Here, we found that MeHg (1-4 μM) significantly decreased insulin secretion and cell viability in pancreatic β-cell-derived RIN-m5F cells. A concomitant elevation of mitochondrial-dependent apoptotic events was observed, including decreased mitochondrial membrane potential and increased proapoptotic (Bax, Bak, p53)/antiapoptotic (Bcl-2) mRNA ratio, cytochrome c release, annexin V-Cy3 binding, caspase-3 activity, and caspase-3/-7/-9 activation. Exposure of RIN-m5F cells to MeHg (2 μM) also induced protein expression of endoplasmic reticulum (ER) stress-related signaling molecules, including C/EBP homologous protein (CHOP), X-box binding protein (XBP-1), and caspase-12. Pretreatment with 4-phenylbutyric acid (4-PBA; an ER stress inhibitor) and specific siRNAs for CHOP and XBP-1 significantly inhibited their expression and caspase-3/-12 activation in MeHg-exposed RIN-mF cells. MeHg could also evoke c-Jun N-terminal kinase (JNK) activation and reactive oxygen species (ROS) generation. Antioxidant N-acetylcysteine (NAC; 1mM) or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox; 100 μM) markedly prevented MeH-induced ROS generation and decreased cell viability in RIN-m5F cells. Furthermore, pretreatment of cells with SP600125 (JNK inhibitor; 10 μM) or NAC (1 mM) or transfection with JNK-specific siRNA obviously attenuated the MeHg-induced JNK phosphorylation, CHOP and XBP-1 protein expression, apoptotic events, and insulin secretion dysfunction. NAC significantly inhibited MeHg-activated JNK signaling, but SP600125 could not effectively reduce MeHg-induced ROS generation. Collectively, these findings demonstrate that the induction of ROS-activated JNK signaling is a crucial mechanism underlying MeHg-induced mitochondria- and ER stress-dependent apoptosis, ultimately leading to β-cell death.
Early Inactivation of Membrane Estrogen Receptor Alpha (ERα) Recapitulates the Endothelial Dysfunction of Aged Mouse Resistance Arteries
Authors: Favre Julie , Vessieres Emilie , Guihot Anne-Laure , Grimaud Linda , Proux Coralyne , Loufrani Laurent , Lenfant Françoise , Fontaine Coralie , Arnal Jean-François , Henrion Daniel
Published: March 2022

Flow-mediated dilation (FMD) of resistance arteries is essential for tissue perfusion but it decreases with ageing. As estrogen receptor alpha (Erα encoded by Esr1), and more precisely membrane ERα, plays an important role in FMD in young mice in a ligand-independent fashion, we evaluated its influence on this arteriolar function in ageing. We first confirmed that in young (6-month-old) mice, FMD of mesenteric resistance arteries was reduced in Esr1−/− (lacking ERα) and C451A-ERα (lacking membrane ERα). In old (24-month-old) mice, FMD was reduced in WT mice compared to young mice, whereas it was not further decreased in Esr1−/− and C451A-ERα mice. Markers of oxidative stress were similarly increased in old WT and C451A-ERα mice. Reduction in oxidative stress with superoxide dismutase plus catalase or Mito-tempo, which reduces mitochondrial superoxide restored FMD to a normal control level in young C451A-ERα mice as well as in old WT mice and old C451A-ERα mice. Estradiol-mediated dilation was absent in old WT mice. We conclude that oxidative stress is a key event in the decline of FMD, and that an early defect in membrane ERα recapitulates phenotypically and functionally ageing of these resistance arteries. The loss of this function could take part in vascular ageing.
Human Milk Oligosaccharides and Bacterial Profile Modulate Infant Body Composition during Exclusive Breastfeeding
Authors: Cheema Ali S. , Gridneva Zoya , Furst Annalee J. , Roman Ana S. , Trevenen Michelle L. , Turlach Berwin A. , Lai Ching T. , Stinson Lisa F. , Bode Lars , Payne Matthew S. , Geddes Donna T.
Published: March 2022

Human milk is a complex and variable ecosystem fundamental to the development of newborns. This study aimed to investigate relationships between human milk oligosaccharides (HMO) and human milk bacterial profiles and infant body composition. Human milk samples (n = 60) were collected at two months postpartum. Infant and maternal body composition was measured with bioimpedance spectroscopy. Human milk bacterial profiles were assessed using full-length 16S rRNA gene sequencing and 19 HMOs were quantitated using high-performance liquid chromatography. Relative abundance of human milk bacterial taxa were significantly associated with concentrations of several fucosylated and sialylated HMOs. Individual human milk bacteria and HMO intakes and concentrations were also significantly associated with infant anthropometry, fat-free mass, and adiposity. Furthermore, when data were stratified based on maternal secretor status, some of these relationships differed significantly among infants born to secretor vs non-secretor mothers. In conclusion, in this pilot study the human milk bacterial profile and HMO intakes and concentrations were significantly associated with infant body composition, with associations modified by secretor status. Future research designed to increase the understanding of the mechanisms by which HMO and human milk bacteria modulate infant body composition should include intakes in addition to concentrations.
Difference in miRNA Expression in Functioning and Silent Corticotroph Pituitary Adenomas Indicates the Role of miRNA in the Regulation of Corticosteroid Receptors
Authors: Mossakowska Beata J. , Kober Paulina , Rusetska Natalia , Boresowicz Joanna , Maksymowicz Maria , Pękul Monika , Zieliński Grzegorz , Styk Andrzej , Kunicki Jacek , Mandat Tomasz , Bujko Mateusz
Published: March 2022

Corticotroph pituitary adenomas commonly cause Cushing’s disease (CD), but some of them are clinically silent. The reason why they do not cause endocrinological symptoms remains unclear. We used data from small RNA sequencing in adenomas causing CD (n = 28) and silent ones (n = 20) to explore the role of miRNA in hormone secretion and clinical status of the tumors. By comparing miRNA profiles, we identified 19 miRNAs differentially expressed in clinically functioning and silent corticotroph adenomas. The analysis of their putative target genes indicates a role of miRNAs in regulation of the corticosteroid receptors expression. Adenomas causing CD have higher expression of hsa-miR-124-3p and hsa-miR-135-5p and lower expression of their target genes NR3C1 and NR3C2. The role of hsa-miR-124-3p in the regulation of NR3C1 was further validated in vitro using AtT-20/D16v-F2 cells. The cells transfected with miR-124-3p mimics showed lower levels of glucocorticoid receptor expression than control cells while the interaction between miR-124-3p and NR3C1 3′ UTR was confirmed using luciferase reporter assay. The results indicate a relatively small difference in miRNA expression between clinically functioning and silent corticotroph pituitary adenomas. High expression of hsa-miR-124-3p in adenomas causing CD plays a role in the regulation of glucocorticoid receptor level and probably in reducing the effect of negative feedback mediated by corticosteroids.
Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways
Authors: Liu Xuan , Diao Li , Zhang Yudie , Yang Xue , Zhou Junnan , Mao Yuhang , Shi Xiaotian , Zhao Fuli , Liu Mei
Published: March 2022

Wear particle-induced aseptic loosening is the most common complication of total joint arthroplasty (TJA). Excessive osteoclast formation and bone resorptive activation have been considered to be responsible for extensive bone destruction and prosthesis failure. Therefore, identification of anti-osteoclastogenesis agents is a potential therapy strategy for the treatment of aseptic loosening and other osteoclast-related osteolysis diseases. In the present study, we reported, for the first time, that piperlongumine (PL), a key alkaloid compound from Piper longum fruits, could significantly suppress the formation and activation of osteoclasts. Furthermore, PL effectively decreased the mRNA expressions of osteoclastic marker genes such as tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), and cathepsin K (CTSK). In addition, PL suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced activations of MAPKs (ERK, JNK and p38) and NF-κB, which down-regulated the protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Using a titanium (Ti) particle-induced calvarial osteolysis model, we demonstrated that PL could ameliorate Ti particle-induced bone loss in vivo. These data provide strong evidence that PL has the potential to treat osteoclast-related diseases including periprosthetic osteolysis (PPO) and aseptic loosening.
Mutations of Omicron Variant at the Interface of the Receptor Domain Motif and Human Angiotensin-Converting Enzyme-2
Authors: Adhikari Puja , Jawad Bahaa , Podgornik Rudolf , Ching Wai-Yim
Published: March 2022

The most recent Omicron variant of SARS-CoV-2 has caused global concern and anxiety. The only thing certain about this strain, with a large number of mutations in the spike protein, is that it spreads quickly, seems to evade immune defense, and mitigates the benefits of existing vaccines. Based on the ultra-large-scale ab initio computational modeling of the receptor binding motif (RBM) and the human angiotensin-converting enzyme-2 (ACE2) interface, we provide the details of the effect of Omicron mutations at the fundamental atomic scale level. In-depth analysis anchored in the novel concept of amino acid-amino acid bond pair units (AABPU) indicates that mutations in the Omicron variant are connected with (i) significant changes in the shape and structure of AABPU components, together with (ii) significant increase in the positive partial charge, which facilitates the interaction with ACE2. We have identified changes in bonding due to mutations in the RBM. The calculated bond order, based on AABPU, reveals that the Omicron mutations increase the binding strength of RBM to ACE2. Our findings correlate with and are instrumental to explain the current observations and can contribute to the prediction of next potential new variant of concern.
An Overview of Systematic Reviews of the Role of Vitamin D on Inflammation in Patients with Diabetes and the Potentiality of Its Application on Diabetic Patients with COVID-19
Authors: Argano Christiano , Mallaci Bocchio Raffaella , Lo Monaco Marika , Scibetta Salvatore , Natoli Giuseppe , Cavezzi Attilio , Troiani Emidio , Corrao Salvatore
Published: March 2022

Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D’s possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.
CPR Gene Contributes to Integument Function and Ovary Development in a Rice Planthopper
Authors: Wang Zhe-Chao , Tao Shuai , Cheng Xu , Li Dan-Ting , Zhang Chuan-Xi , Bao Yan-Yuan
Published: March 2022

Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is an essential enzyme that transfers electrons from NADPH to cytochrome P450 monooxygenases. CPR is involved in cuticular hydrocarbon (CHC) synthesis in insects and is vital for insect development and survival. Here, we clarify the physiological function of a CPR gene in Nilaparvata lugens, an important rice pest, by using RNA interference. CPR gene knockdown leads to the functional loss of waterproofing and water retention in the integument of female adults, which causes significantly reduced body weight and a lethal phenotype. Scanning electron microscopy shows that the lipid layer on the outermost surface of the abdominal cuticle becomes thin in dsCPR-injected adults. Furthermore, CHC profile analysis reveals that CPR knockdown significantly decreases the contents of CHCs with a carbon chain length ≥ C27 in adult females. Moreover, we find that CPR knockdown generates a deficient phenotype in ovaries with deformed oocytes and a complete failure of egg-laying. These findings suggest that CPR plays multiple functional roles in CHC biosynthesis and embryo development in insects.
Toxicological Impact of Rare Earth Elements (REEs) on the Reproduction and Development of Aquatic Organisms Using Sea Urchins as Biological Models
Authors: Martino Chiara , Chianese Teresa , Chiarelli Roberto , Roccheri Maria Carmela , Scudiero Rosaria
Published: March 2022

The growing presence of lanthanides in the environment has drawn the attention of the scientific community on their safety and toxicity. The sources of lanthanides in the environment include diagnostic medicine, electronic devices, permanent magnets, etc. Their exponential use and the poor management of waste disposal raise serious concerns about the quality and safety of the ecosystems at a global level. This review focused on the impact of lanthanides in marine organisms on reproductive fitness, fertilization and embryonic development, using the sea urchin as a biological model system. Scientific evidence shows that exposure to lanthanides triggers a wide variety of toxic insults, including reproductive performance, fertilization, redox metabolism, embryogenesis, and regulation of embryonic gene expression. This was thoroughly demonstrated for gadolinium, the most widely used lanthanide in diagnostic medicine, whose uptake in sea urchin embryos occurs in a time- and concentration-dependent manner, correlates with decreased calcium absorption and primarily affects skeletal growth, with incorrect regulation of the skeletal gene regulatory network. The results collected on sea urchin embryos demonstrate a variable sensitivity of the early life stages of different species, highlighting the importance of testing the effects of pollution in different species. The accumulation of lanthanides and their emerging negative effects make risk assessment and consequent legislative intervention on their disposal mandatory.