bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Management of Patients with Severe Coronary Artery Disease following Multidisciplinary Heart Team Approach—Insights from Tertiary Cardiovascular Care Center
Authors: Jonik Szymon , Marchel Michał , Pędzich-Placha Ewa , Pietrasik Arkadiusz , Rdzanek Adam , Huczek Zenon , Kochman Janusz , Budnik Monika , Piątkowski Radosław , Scisło Piotr , Czub Paweł , Wilimski Radosław , Maksym Jakub , Grabowski Marcin , Opolski Grzegorz , Mazurek Tomasz
Published: March 2022

Background: The purpose of this retrospective study was to investigate outcomes of patients with severe coronary artery disease (CAD) after implementing various treatment strategies following multidisciplinary Heart Team (MHT) discussion. Methods Primary and secondary endpoints and quality of life during a mean (SD) follow-up of 37 (14) months of patients with severe CAD (three-vessel [3-VD] or/and left main [LM] disease) qualified after MHT discussion to optimal medical treatment (OMT) alone, OMT and coronary artery bypass grafting (CABG), or OMT and percutaneous coronary intervention (PCI) were evaluated. As the primary endpoint, major adverse cardiac or cerebrovascular events (MACCE) (i.e., death from any cause, stroke, myocardial infarction, or repeat/need for revascularization) were considered. Result: From 2016 to 2019, 176 MHT meetings were held, and a total of 1286 participants with severe CAD and completely implemented MHT decisions (OMT, CABG, or PCI for 251, 356, and 679 patients, respectively) were included. The occurrence of the primary endpoint was significantly increased in OMT-group (154 (61.4%) vs. CABG and PCI groups—110 (30.9%) and 302 (44.5%) patients, respectively (p < 0.05). For interventional strategies only—CABG was associated with reduced rates of MACCE and repeat revascularization, while the superiority of PCI for stroke and disabling stroke was observed (p < 0.05). The general health status assessed at the end of the follow-up was significantly better for patients who underwent CABG or PCI than in the OMT group (p < 0.05). Conclusions: In this real-life study, we presented a single-center experience of providing optimal medical care for patients with severe CAD following MHT discussion.
Securing Smokefree Laws Covering Casinos and Bars in Louisiana via Messaging, Continuous Campaigning and Health Coalitions
Authors: Wakefield Tanner D. , Glantz Stanton A.
Published: March 2022

In this paper, we examine efforts by health organizations seeking comprehensive smokefree ordinances over Louisiana casinos and bars between 2010 and 2020 to determine best practices for increasing coverage. Bars and casinos remain less protected from secondhand smoke compared to other workplaces in the United States. Casino behavior is compared to the Policy Dystopia Model (PDM), a tobacco industry strategy framework. We performed a historical case study using snowball searches for news on the Access World News Database and the internet. We performed web searches using the names of key actors, organizations, and locations and interviewed nine participants. Starting in 2010, the Louisiana Campaign for Tobacco-Free Living ran ordinance campaigns supplemented by an ongoing statewide smokefree media initiative. Utilizing consistent strategies, including promoting performers as cultural emblems deserving protection, health organizations coalesced in New Orleans during 2014 and Baton Rouge in 2016 and 2017 to pursue ordinances. The coalitions secured ordinances in Louisiana’s population and tourism centers despite business resistance. Organizations obtained 30 smokefree laws across Louisiana by 2021. Casinos used PDM strategies to resist ordinances, indicating the framework may predict strategies by non-tobacco entities resisting tobacco control. Louisiana shows that ongoing local campaigns, social justice themes and cultural messaging with coalitions in cities can secure smokefree laws covering casinos and bars and that local ordinance campaigns are a viable method for advancing smokefree protections over those venues in states where the state legislatures are resistant to action.
Maternal Time Use Drives Suboptimal Complementary Feeding Practices in the El Niño-Affected Eastern Ethiopia Community
Authors: Irenso Asnake Ararsa , Letta Shiferaw , Chemeda Addisu S. , Asfaw Abiyot , Egata Gudina , Assefa Nega , Campbell Karen J. , Laws Rachel
Published: March 2022

Ethiopia is affected by recurrent drought and food-insecurity crises, including El Niño. El Niño started in mid-2014, worsened in 2015, and continued in 2016, leading to a widespread food-insecurity emergency resulting in a surge in the rate of acute malnutrition in infants due to suboptimal feeding practices. This study explored how El Niño influenced complementary feeding practices in the eastern Ethiopia community from March to September 2016. It was an exploratory qualitative study with a basic interpretative qualitative approach. A general inductive approach was used for the analysis. The study involved 11 focus group discussions (FGD) with a total of 76 people, including three with mothers, three with Health Development Army (HDA) leaders, two with fathers, two with traditional birth attendants, and one with religious leaders. El Niño resulted in failed crops and loss of livestock, resulting in reduced dietary diversity and meal frequency. El Niño resulted in suboptimal complementary feeding practices by reducing food access and altering livelihood and coping strategies, reducing the time mothers allocated to child feeding, keeping them away from home, and stressing community health services. The maternal suboptimal time allocation is central to the poor complementary feeding practices. Thus, the women should be supported with climate-resilient livelihood options in their villages, allowing them to feed their children and attend education sessions with HDA leaders.
Interventions to Improve Treatment Outcomes among Adolescents on Antiretroviral Therapy with Unsuppressed Viral Loads: A Systematic Review
Authors: Munyayi Farai Kevin , van Wyk Brian , Mayman Yolanda
Published: March 2022

Adolescents living with HIV (ALHIV) face unique developmental challenges that increase the risk of unsuppressed viral loads. Current reviews present a need for proven interventions to improve viral suppression among ALHIV on ART, who have a history of unsuppressed viral loads. This systematic review aims to synthesize and appraise evidence of the effectiveness of interventions to improve treatment outcomes among ALHIV with unsuppressed viral loads. Six bibliographic databases were searched for published studies and gray literature from 2010 to 2021. The risk of bias and certainty of evidence was assessed using the ROBINS-I tool, CASP checklists and GRADE. A total of 28 studies were eligible for full-text screening; and only three were included in the qualitative synthesis. In addition, two studies were included from website searches. Four types of interventions to improve viral suppression were identified, namely: intensive adherence counselling; community- and facility-based peer-led differentiated service delivery (DSD); family based economic empowerment; and conditional economic incentives and motivational interviewing. We strongly recommend peer-led community-based DSD interventions, intensive adherence counselling, and family-based economic empowerment as potential interventions to improve viral suppression among ALHIV.
Characteristics and Influencing Factors of Polycyclic Aromatic Hydrocarbons Emitted from Open Burning and Stove Burning of Biomass: A Brief Review
Authors: Zhang Hao , Zhang Xuan , Wang Yan , Bai Pengchu , Hayakawa Kazuichi , Zhang Lulu , Tang Ning
Published: March 2022

To mitigate global warming and achieve carbon neutrality, biomass has become a widely used carbon-neutral energy source due to its low cost and easy availability. However, the incomplete combustion of biomass can produce polycyclic aromatic hydrocarbons (PAHs), which are harmful to human health. Moreover, increasing numbers of wildfires in many regions caused by global warming have greatly increased the emissions of PAHs from biomass burning. To effectively mitigate PAH pollution and health risks associated with biomass usage, the concentrations, compositions and influencing factors of PAH emissions from biomass burning are summarized in this review. High PAH emissions from open burning and stove burning are found, and two- to four-ring PAHs account for a higher proportion than five- and six-ring PAHs. Based on the mechanism of biomass burning, biomass with higher volatile matter, cellulose, lignin, potassium salts and moisture produces more PAHs. Moreover, burning biomass in stoves at a high temperature or with an insufficient oxygen supply can increase PAH emissions. Therefore, the formation and emission of PAHs can be reduced by pelletizing, briquetting or carbonizing biomass to increase its density and burning efficiency. This review contributes to a comprehensive understanding of PAH pollution from biomass burning, providing prospective insight for preventing air pollution and health hazards associated with carbon neutrality.
Placental Related Disorders of Pregnancy
Authors: Lee Eun D. , Mistry Hiten D.
Published: March 2022

We are pleased to present this Special Issue of International Journal of Molecular Sciences, entitled ‘Placental Related Disorders of Pregnancy’ [...]
Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma
Authors: Namakanova Olga A. , Gorshkova Ekaterina A. , Zvartsev Ruslan V. , Nedospasov Sergei A. , Drutskaya Marina S. , Gubernatorova Ekaterina O.
Published: March 2022

Combined anti-cytokine therapy is a promising therapeutic approach for uncontrolled steroid-resistant asthma. In this regard, simultaneous blockade of IL-4 and IL-13 signaling by Dupilumab (anti-IL-4Ra monoclonal antibody) was recently approved for severe eosinophilic asthma. However, no therapeutic options for neutrophilic asthma are currently available. Recent advances in our understanding of asthma pathogenesis suggest that both IL-6 and TNF may represent potential targets for treatment of severe neutrophilic asthma. Nevertheless, the efficacy of simultaneous pharmacological inhibition of TNF and IL-6 in asthma was not yet studied. To evaluate the potency of combined cytokine inhibition, we simultaneously administrated IL-6 and TNF inhibitors to BALB/c mice with HDM-induced asthma. Combined IL-6/TNF inhibition, but not individual blockade of these two cytokines, led to complex anti-inflammatory effects including reduced Th2-induced eosinophilia and less prominent Th17/Th1-mediated neutrophilic infiltrate in the airways. Taken together, our results provide evidence for therapeutic potential of combined IL-6/TNF inhibition in severe steroid-resistant asthma.
Raman Research on Bleomycin-Induced DNA Strand Breaks and Repair Processes in Living Cells
Authors: Czaja Michał , Skirlińska-Nosek Katarzyna , Adamczyk Olga , Sofińska Kamila , Wilkosz Natalia , Rajfur Zenon , Szymoński Marek , Lipiec Ewelina
Published: March 2022

Even several thousands of DNA lesions are induced in one cell within one day. DNA damage may lead to mutations, formation of chromosomal aberrations, or cellular death. A particularly cytotoxic type of DNA damage is single- and double-strand breaks (SSBs and DSBs, respectively). In this work, we followed DNA conformational transitions induced by the disruption of DNA backbone. Conformational changes of chromatin in living cells were induced by a bleomycin (BLM), an anticancer drug, which generates SSBs and DSBs. Raman micro-spectroscopy enabled to observe chemical changes at the level of single cell and to collect hyperspectral images of molecular structure and composition with sub-micrometer resolution. We applied multivariate data analysis methods to extract key information from registered data, particularly to probe DNA conformational changes. Applied methodology enabled to track conformational transition from B-DNA to A-DNA upon cellular response to BLM treatment. Additionally, increased expression of proteins within the cell nucleus resulting from the activation of repair processes was demonstrated. The ongoing DNA repair process under the BLM action was also confirmed with confocal laser scanning fluorescent microscopy.
Identifying QTLs for Grain Size in a Colossal Grain Rice (Oryza sativa L.) Line, and Analysis of Additive Effects of QTLs
Authors: Hou Xuanxuan , Chen Moxian , Chen Yinke , Hou Xin , Jia Zichang , Yang Xue , Zhang Jianhua , Liu Yinggao , Ye Nenghui
Published: March 2022

Grain size is an important component of quality and harvest traits in the field of rice breeding. Although numerous quantitative trait loci (QTLs) of grain size in rice have been reported, the molecular mechanisms of these QTLs remain poorly understood, and further research on QTL observation and candidate gene identification is warranted. In our research, we developed a suite of F2 intercross populations from a cross of 9311 and CG. These primary populations were used to map QTLs conferring grain size, evaluated across three environments, and then subjected to bulked-segregant analysis-seq (BSA-seq). In total, 4, 11, 12 and 14 QTLs for grain length (GL), grain width (GW), 1000-grain weight (TGW), and length/width ratio (LWR), respectively, were detected on the basis of a single-environment analysis. In particular, over 200 splicing-related sites were identified by whole-genome sequencing, including one splicing-site mutation with G>A at the beginning of intron 4 on Os03g0841800 (qGL3.3), producing a smaller open reading frame, without the third and fourth exons. A previous study revealed that the loss-of-function allele caused by this splicing site can negatively regulate rice grain length. Furthermore, qTGW2.1 and qGW2.3 were new QTLs for grain width. We used the near-isogenic lines (NILs) of these GW QTLs to study their genetic effects on individuals and pyramiding, and found that they have additive effects on GW. In summary, these discoveries provide a valuable genetic resource, which will facilitate further study of the genetic polymorphism of new rice varieties in rice breeding.
Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APPswe Alzheimer’s Disease Mouse Model
Authors: Zamarbide Marta , Martinez-Pinilla Eva , Gil-Bea Francisco , Yanagisawa Masashi , Franco Rafael , Perez-Mediavilla Alberto
Published: March 2022

The free fatty acid FFA3 receptor (FFA3R) belongs to the superfamily of G-protein-coupled receptors (GPCRs). In the intestine and adipose tissue, it is involved in the regulation of energy metabolism, but its function in the brain is unknown. We aimed, first, to investigate the expression of the receptor in the hippocampus of Alzheimer disease (AD) patients at different stages of the disease and, second, to assess whether genetic inactivation of the Ffar3 gene could affect the phenotypic features of the APPswe mouse model. The expression of transcripts for FFA receptors in postmortem human hippocampal samples and in the hippocampus of wild-type and transgenic mice was analyzed by RT-qPCR. We generated a double transgenic mouse, FFA3R−/−/APPswe, to perform cognition studies and to assess, by immunoblotting Aβ and tau pathologies and the differential expression of synaptic plasticity-related proteins. For the first time, the occurrence of the FFA3R in the human hippocampus and its overexpression, even in the first stages of AD, was demonstrated. Remarkably, FFA3R−/−/APPswe mice do not have the characteristic memory impairment of 12-month-old APPswe mice. Additionally, this newly generated transgenic line does not develop the most important Alzheimer’s disease (AD)-related features, such as amyloid beta (Aβ) brain accumulations and tau hyperphosphorylation. These findings are accompanied by increased levels of the insulin-degrading enzyme (IDE) and lower activity of the tau kinases GSK3β and Cdk5. We conclude that the brain FFA3R is involved in cognitive processes and that its inactivation prevents AD-like cognitive decline and pathological hallmarks.
The Role of Testosterone in the Elderly: What Do We Know?
Authors: Barone Biagio , Napolitano Luigi , Abate Marco , Cirillo Luigi , Reccia Pasquale , Passaro Francesco , Turco Carmine , Morra Simone , Mastrangelo Francesco , Scarpato Antonio , Amicuzi Ugo , Morgera Vincenzo , Romano Lorenzo , Calace Francesco Paolo , Pandolfo Savio Domenico , De Luca Luigi , Aveta Achille , Sicignano Enrico , Trivellato Massimiliano , Spena Gianluca , D’Alterio Carlo , Fusco Giovanni Maria , Vitale Raffaele , Arcaniolo Davide , Crocetto Felice
Published: March 2022

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.
Roles of Nucleoporin RanBP2/Nup358 in Acute Necrotizing Encephalopathy Type 1 (ANE1) and Viral Infection
Authors: Jiang Jing , Wang Yifan E. , Palazzo Alexander F. , Shen Qingtang
Published: March 2022

Ran Binding Protein 2 (RanBP2 or Nucleoporin358) is one of the main components of the cytoplasmic filaments of the nuclear pore complex. Mutations in the RANBP2 gene are associated with acute necrotizing encephalopathy type 1 (ANE1), a rare condition where patients experience a sharp rise in cytokine production in response to viral infection and undergo hyperinflammation, seizures, coma, and a high rate of mortality. Despite this, it remains unclear howRanBP2 and its ANE1-associated mutations contribute to pathology. Mounting evidence has shown that RanBP2 interacts with distinct viruses to regulate viral infection. In addition, RanBP2 may regulate innate immune response pathways. This review summarizes recent advances in our understanding of how mutations in RANBP2 contribute to ANE1 and discusses how RanBP2 interacts with distinct viruses and affects viral infection. Recent findings indicate that RanBP2 might be an important therapeutic target, not only in the suppression of ANE1-driven cytokine storms, but also to combat hyperinflammation in response to viral infections.
Utilizing Exosomal-EPHs/Ephrins as Biomarkers and as a Potential Platform for Targeted Delivery of Therapeutic Exosomes
Authors: Goutas Dimitrios , Pergaris Alexandros , Goutas Nikolaos , Theocharis Stamatios
Published: March 2022

Exosomes are cell-secreted nanoparticles containing various molecules including small vesicles, microRNAs (miRNAs), messenger RNAs or bioactive proteins which are thought to be of paramount importance for intercellular communication. The unique effects of exosomes in terms of cell penetration capacity, decreased immunogenicity and inherent stability, along with their key role in mediating information exchange among tumor cells and their surrounding tumor microenvironment (TME), render them a promising platform for drug targeted delivery. Compared to synthetic drugs, exosomes boast a plethora of advantages, including higher biocompatibility, lower toxicity and increased ability of tissue infiltration. Nevertheless, the use of artificial exosomes can be limited in practice, partly due to their poor targeting ability and partly due to their limited efficacy. Therefore, efforts have been made to engineer stem cell-derived exosomes in order to increase selectiveness and effectivity, which can then become loaded with various active substances depending on the therapeutic approach followed. Erythropoietin-producing human hepatocellular receptors (EPHs), along with their ligands, the EPH family receptor interacting proteins (ephrins), have been extensively investigated for their key roles in both physiology and cancer pathogenesis. EPHs/ephrins exhibit both tumorigenic and tumor suppressing properties, with their targeting representing a promising, novel therapeutic approach in cancer patients’ management. In our review, the use of ephrin-loaded exosomes as a potential therapeutic targeted delivery system in cancer will be discussed.
Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response
Authors: Kciuk Mateusz , Gielecińska Adrianna , Mujwar Somdutt , Mojzych Mariusz , Kontek Renata
Published: March 2022

Cyclin-dependent kinases (CDKs) are pivotal mediators and effectors of the DNA damage response (DDR) that regulate both the pathway components and proteins involved in repair processes. Synthetic lethality (SL) describes a situation in which two genes are linked in such a way that the lack of functioning of just one maintains cell viability, while depletion of both triggers cell death. Synthetic lethal interactions involving CDKs are now emerging, and this can be used to selectively target tumor cells with DNA repair defects. In this review, SL interactions of CDKs with protooncogene products MYC, poly (ADP-ribose) polymerase (PARP-1), and cellular tumor antigen p53 (TP53) are discussed. The individual roles of each of the SL partners in DDR are described.
Curcumin in Retinal Diseases: A Comprehensive Review from Bench to Bedside
Authors: Allegrini Davide , Raimondi Raffaele , Borgia Alfredo , Sorrentino Tania , Montesano Giovanni , Tsoutsanis Panos , Cancian Giuseppe , Verma Yash , De Rosa Francesco Paolo , Romano Mario R.
Published: March 2022

Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.
The Beneficial Effects of Triterpenic Acid and Acteoside in an In Vitro Model of Nonalcoholic Steatohepatitis (NASH)
Authors: Salvoza Noel , Bedin Chiara , Saccani Andrea , Tiribelli Claudio , Rosso Natalia
Published: March 2022

Triterpenic acid (TA) and acteoside (ACT), the major components of APPLIVER and ACTEOS, respectively, have been reported to exert hepatoprotective effects, but the molecular mechanisms remain elusive, particularly in the NAFLD/NASH context. We assessed their effects in our well-established in vitro model resembling the pathophysiological mechanisms involved in NASH. Human hepatocytes and hepatic stellate cells were exposed to free fatty acids (FFA) alone or in combination with APPLIVER and ACTEOS as a mono- or co-culture. Steatosis, inflammation, generation of reactive oxygen species (ROS), and collagen deposition were determined. ACTEOS reduced both the TNF-α and ROS production, and, most importantly, attenuated collagen deposition elicited by the excess of FFA in the co-culture model. APPLIVER also showed inhibition of both TNF-α production and collagen deposition caused by FFA accumulation. The compounds alone did not induce any cellular effects. The present study showed the efficacy of APPLIVER and ACTEOS on pathophysiological mechanisms related to NASH. These in vitro data suggest that these compounds deserve further investigation for possible use in NASH treatment.
The Involvement of the Endogenous Opioid System in the Gastrointestinal Aging in Mice and Humans
Authors: Szymaszkiewicz Agata , Talar Marcin , Włodarczyk Jakub , Świerczyński Mikołaj , Bartoszek Adrian , Krajewska Julia , Mokrowiecka Anna , Małecka-Wojciesko Ewa , Fichna Jakub , Zielińska Marta
Published: March 2022

Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. In this study, the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly were evaluated. The GI functions were assessed in vitro and in vivo and compared between 6-, 12- and 18-month old mice. Moreover, the effect of opioid receptor (MOP, DOP, KOP) agonists on the mouse GI tract functions and the EOS components expression in mouse tissues and colonic biopsies from patients with functional constipation were determined. In the oldest mice, the GI peristalsis was significantly impaired as compared to the younger groups. The tissue response to MOP and DOP, but not KOP, agonists weakened with age in vitro; for DOP, it was confirmed in vivo. In the mouse upper GI tract, Oprm1, Oprd1, Oprk1 expression decreased with age; in the colon, Oprm1 expression increased. There were no differences in the expression of these genes in the colonic biopsies from patients >50 years old as compared to the younger group. In conclusion, the age-related impairment of the GI peristalsis may result from reduced MOP and DOP response to the activation with opioid agonists or the alterations in the EOS expression.
Non-Invasive Preimplantation Genetic Testing for Aneuploidy and the Mystery of Genetic Material: A Review Article
Authors: Tomic Maja , Vrtacnik Bokal Eda , Stimpfel Martin
Published: March 2022

This review focuses on recent findings in the preimplantation genetic testing (PGT) of embryos. Different preimplantation genetic tests are presented along with different genetic materials and their analysis. Original material concerning preimplantation genetic testing for aneuploidy (PGT-A) was sourced by searching the PubMed and ScienceDirect databases in October and November 2021. The searches comprised keywords such as ‘preimplantation’, ‘cfDNA’; ‘miRNA’, ‘PGT-A’, ‘niPGT-A’, ‘aneuploidy’, ‘mosaicism’, ‘blastocyst biopsy’, ‘blastocentesis’, ‘blastocoel fluid’, ‘NGS’, ‘FISH’, and ‘aCGH’. Non-invasive PGT-A (niPGT-A) is a novel approach to the genetic analysis of embryos. The premise is that the genetic material in the spent embryo culture media (SECM) corresponds to the genetic material in the embryo cells. The limitations of niPGT-A are a lower quantity and lesser quality of the cell-free genetic material, and its unknown origin. The concordance rate varies when compared to invasive PGT-A. Some authors have also hypothesized that mosaicism and aneuploid cells are preferentially excluded from the embryo during early development. Cell-free genetic material is readily available in the spent embryo culture media, which provides an easier, more economic, and safer extraction of genetic material for analysis. The sampling of the SECM and DNA extraction and amplification must be optimized. The origin of the cell-free media, the percentage of apoptotic events, and the levels of DNA contamination are currently unknown; these topics need to be further investigated.
Potential Role of Neutrophil Extracellular Traps in Cardio-Oncology
Authors: Cheng Kai-Hung , Contreras Gregory P. , Yeh Ting-Yu
Published: March 2022

Cardiovascular toxicity has emerged as the leading cause of death in patients undergoing cancer treatment. Thus, cardio-oncology (CO) care must also focus on the prevention and management of related cardiovascular (CV) complications caused by cancer therapy. Neutrophil extracellular traps (NETs)—entities with released DNA, proteases, proinflammatory and prooxidative substances from blasted neutrophils—play an important role in cancer proliferation, propagation metastasis, and incident CV events (acute coronary syndrome, thromboembolic events, and heart failure). Although NETs have been shown to be involved in cancer progression and incident CV events, little is known about their relationship with cardio-oncology, especially on cancer treatment-related cardiovascular toxicity (CTRCT). This review aims to explore the evidence of the impact of NETs on cancer, CV events, and CTRCT, and the possible solutions based on the mechanism of NETs activation and NETs released toxic substances.
Expansion-Based Clearing of Golgi-Cox-Stained Tissue for Multi-Scale Imaging
Authors: Shan Qing-Hong , Qin Xin-Ya , Zhou Jiang-Ning
Published: March 2022

Obtaining fine neuron morphology and connections data is extraordinarily useful in understanding the brain’s functionality. Golgi staining is a widely used method for revealing neuronal morphology. However, Golgi-Cox-stained tissue is difficult to image in three dimensions and lacks cell-type specificity, limiting its use in neuronal circuit studies. Here, we describe an expansion-based method for rapidly clearing Golgi-Cox-stained tissue. The results show that 1 mm thick Golgi-Cox-stained tissue can be cleared within 6 hours with a well preserved Golgi-Cox-stained signal. At the same time, we found for the first time that the cleared Golgi-Cox-stained samples were compatible with three-dimensional (3D) immunostaining and multi-round immunostaining. By combining the Golgi-Cox staining with tissue clearing and immunostaining, Golgi-Cox-stained tissue could be used for large-volume 3D imaging, identification of cell types of Golgi-Cox-stained cells, and reconstruction of the neural circuits at dendritic spines level. More importantly, these methods could also be applied to samples from human brains, providing a tool for analyzing the neuronal circuit of the human brain.
Melatonin Positively Regulates Both Dark- and Age-Induced Leaf Senescence by Reducing ROS Accumulation and Modulating Abscisic Acid and Auxin Biosynthesis in Cucumber Plants
Authors: Jing Tongtong , Liu Kun , Wang Yanan , Ai Xizhen , Bi Huangai
Published: March 2022

Melatonin (MT), as a signaling molecule, plays a vital role in regulating leaf senescence in plants. This study aimed to verify the antioxidant roles of MT in delaying dark- or age-induced leaf senescence of cucumber plants. The results showed that endogenous MT responds to darkness and overexpression of CsASMT, the key gene of MT synthesis, and delays leaf senescence stimulated by darkness, as manifested by significantly lower malonaldehyde (MDA) and reactive oxygen species (ROS) contents as well as higher activities and gene expression of antioxidant enzymes compared to the control. Moreover, MT suppressed both age- or dark-induced leaf senescence of cucumber, as evidenced by a decrease in senescence-related gene SAG20 and cell-death-related gene PDCD expression and ROS content and an increase in antioxidant capacity and chlorophyll biosynthesis compared with the H2O-treated seedlings. Meanwhile, the suppression of age-induced leaf senescence by melatonin was also reflected by the reduction in abscisic acid (ABA) biosynthesis and signaling pathways as well as the promotion of auxin (IAA) biosynthesis and signaling pathways in cucumber plants in the solar greenhouse. Combining the results of the two separate experiments, we demonstrated that MT acts as a powerful antioxidant to alleviate leaf senescence by activating the antioxidant system and IAA synthesis and signaling while inhibiting ABA synthesis and signaling in cucumber plants.
Transcriptomic and Physiological Responses of Chlorella pyrenoidosa during Exposure to 17α-Ethinylestradiol
Authors: Zhang Yurui , Chen Zixu , Tao Yue , Wu Wanyin , Zeng Yuyang , Liao Kejun , Li Xinyue , Chen Lanzhou
Published: March 2022

17α-ethinylestradiol (17α-EE2) is frequently detected in water bodies due to its use being widespread in the treatment of prostate and breast cancer and in the control of alopecia, posing a threat to humans and aquatic organisms. However, studies on its toxicity to Chlorella pyrenoidosa have been limited to date. This study investigated the effects of 17α-EE2 on the growth, photosynthetic activity, and antioxidant system of C. pyrenoidosa and revealed related molecular changes using transcriptomic analysis. The cell density of algae was inhibited in the presence of 17α-EE2, and cell morphology was also altered. Photosynthetics were damaged, while reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) content increased. Further transcriptomic analysis revealed that the pathways of photosynthesis and DNA replication were affected at three concentrations of 17α-EE2, but several specific pathways exhibited various behaviors at different concentrations. Significant changes in differentially expressed genes and their enrichment pathways showed that the low-concentration group was predominantly impaired in photosynthesis, while the higher-concentration groups were biased towards oxidative and DNA damage. This study provides a better understanding of the cellular and molecular variations of microalgae under 17α-EE2 exposure, contributing to the environmental risk assessment of such hazardous pollutants on aquatic organisms.
Melatonin Regulates Iron Homeostasis by Inducing Hepcidin Expression in Hepatocytes
Authors: Park Woo-Ram , Choi Byungyoon , Kim Yu-Ji , Kim Yong-Hoon , Park Min-Jung , Kim Dong-Il , Choi Hueng-Sik , Kim Don-Kyu
Published: March 2022

The pineal hormone, melatonin, plays important roles in circadian rhythms and energy metabolism. The hepatic peptide hormone, hepcidin, regulates iron homeostasis by triggering the degradation of ferroportin (FPN), the protein that transfers cellular iron to the blood. However, the role of melatonin in the transcriptional regulation of hepcidin is largely unknown. Here, we showed that melatonin upregulates hepcidin gene expression by enhancing the melatonin receptor 1 (MT1)-mediated c-Jun N-terminal kinase (JNK) activation in hepatocytes. Interestingly, hepcidin gene expression was increased during the dark cycle in the liver of mice, whereas serum iron levels decreased following hepcidin expression. In addition, melatonin significantly induced hepcidin gene expression and secretion, as well as the subsequent FPN degradation in hepatocytes, which resulted in cellular iron accumulation. Melatonin-induced hepcidin expression was significantly decreased by the melatonin receptor antagonist, luzindole, and by the knockdown of MT1. Moreover, melatonin activated JNK signaling and upregulated hepcidin expression, both of which were significantly decreased by SP600125, a specific JNK inhibitor. Chromatin immunoprecipitation analysis showed that luzindole significantly blocked melatonin-induced c-Jun binding to the hepcidin promoter. Finally, melatonin induced hepcidin expression and secretion by activating the JNK-c-Jun pathway in mice, which were reversed by the luzindole treatment. These findings reveal a previously unrecognized role of melatonin in the circadian regulation of hepcidin expression and iron homeostasis.
The Significance of Selected C-C Motif Chemokine Ligands in Colorectal Cancer Patients
Authors: Zajkowska Monika , Dulewicz Maciej , Kulczyńska-Przybik Agnieszka , Safiejko Kamil , Juchimiuk Marcin , Konopko Marzena , Kozłowski Leszek , Mroczko Barbara
Published: March 2022

Colorectal cancer (CRC) is one of the most frequently diagnosed neoplasms. Despite the advances in diagnostic tools and treatments, the number of CRC cases is increasing. Therefore, it is vital to search for new parameters that could be useful in its diagnosis. Thus, we wanted to assess the usefulness of selected CC chemokines (CCL2, CCL4, and CCL15) in CRC. The study included 115 subjects (75 CRC patients and 40 healthy volunteers). The serum concentrations of all parameters were measured using a multiplexing method (Luminex). The CRP levels were determined by immunoturbidimetry, and the classical tumor markers (CEA and CA 19-9) were measured using CMIA (chemiluminescent microparticle immunoassay). The concentrations of all parameters were higher in the CRC group when compared to the healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of all estimated CC chemokines were higher than those of CA 19-9. Interestingly, the obtained results also suggest CCL2’s significance in the determination of local metastases and CCL4’s significance in the determination of distant metastases. However, further studies concerning the role of selected CC chemokines in the course of colorectal cancer are necessary to confirm and to fully clarify their diagnostic utility and their clinical application as markers of CRC development.
Impact of Myeloid p38α/MAPK on Orthodontic Tooth Movement
Authors: Kirschneck Christian , Nusser Hendrik , Jantsch Jonathan , Proff Peter , Schröder Agnes
Published: March 2022

Objectives: Myeloid p38α/MAPK regulate and coordinate osteoclastogenesis. The present study was conducted to investigate the role of myeloid p38α/MAPK during orthodontic tooth movement. Methods: Orthodontic tooth movement was performed in wildtype and p38αΔmyel mice lacking p38α/MAPK expression in myeloid cells. First, bone parameter as well as osteoblast and osteoclast number were determined in tibiae. RNA was isolated from the untreated and orthodontically treated maxillary jaw side and expression of genes involved in inflammation and bone remodelling were analysed. Finally, periodontal bone loss, alveolar bone density and extent of orthodontic tooth movement were assessed. Results: Bone density was increased in p38αΔmyel mice compared to wildtype mice in tibiae (p = 0.043) and alveolar bone (p = 0.003). This was accompanied by a reduced osteoclast number in tibiae (p = 0.005) and TRAP5b in serum (p = 0.015). Accordingly, expression of osteoclast-specific genes was reduced in p38αΔmyel mice. Extent of tooth movement was reduced in p38αΔmyel mice (p = 0.024). This may be due to the higher bone density of the p38αΔmyel mice. Conclusions: Myeloid p38α/MAPK thus appears to play a regulatory role during orthodontic tooth movement by regulating osteoclastogenesis.
Ablation Index Predicts Successful Ablation of Focal Atrial Tachycardia: Results of a Multicenter Study
Authors: Compagnucci Paolo , Dello Russo Antonio , Bergonti Marco , Anselmino Matteo , Zucchelli Giulio , Gasperetti Alessio , Cipolletta Laura , Volpato Giovanni , Ascione Ciro , Ferraris Federico , Valeri Yari , Bongiorni Maria Grazia , Natale Andrea , Tondo Claudio , De Ferrari Gaetano Maria , Casella Michela
Published: March 2022

A radiofrequency energy lesion transmurality marker incorporating power, contact force, and time (Ablation Index, AI) was shown to be associated with outcomes of catheter ablation (CA) of multiple arrhythmias, but was never systematically assessed in the CA of focal atrial tachycardias (AT). We aimed to evaluate the role of AI as a predictor of outcomes in focal AT CA, and therefore, retrospectively included 45 consecutive patients undergoing CA for focal AT in four referral electrophysiology laboratories. Clinical and procedural information were collected. For each patient, maximum and mean (by averaging maximum AI values for each radiofrequency ablation lesion) AI were measured. The primary outcome was focal AT-free survival, and was systematically assessed with periodical Holter monitors or cardiac implantable electronic devices. CA was acutely effective in each case; however, 20% (n = 9) of the study population experienced a focal AT recurrence over a median follow-up of 288 days. Both maximum and mean AI values were significantly higher among patients without AT recurrences (maximum AI = 568 ± 91, mean AI = 426 ± 105) than in patients with AT relapses (maximum AI = 447 ± 142, mean AI = 352 ± 76, p = 0.036, and p = 0.028, respectively). The optimal cutoffs associated with freedom from recurrences were 461 for maximum AI (sensitivity, 0.89; specificity, 0.56) and 301 for mean AI (sensitivity, 0.97; specificity, 0.44). In a time-to-event analysis, maximum AI was significantly associated with survival free from AT recurrence (p = 0.001), whereas mean AI was not (p = 0.08). In summary, maximum AI is the best procedural parameter associated with the outcomes of CA for focal AT, and may help standardize the procedural approach.
Indirect Volume Estimation for Acute Ischemic Stroke from Diffusion Weighted Image Using Slice Image Segmentation
Authors: Lee Seung-Ah , Jang Jae-Won , Park Sang-Won , Kim Pum-Jun , Yeo Na-Young , Kim Chulho , Kim Yoon , Choi Hyun-Soo , Kim Seongheon
Published: March 2022

The accurate estimation of acute ischemic stroke (AIS) using diffusion-weighted imaging (DWI) is crucial for assessing patients and guiding treatment options. This study aimed to propose a method that estimates AIS volume in DWI objectively, quickly, and accurately. We used a dataset of DWI with AIS, including 2159 participants (1179 for internal validation and 980 for external validation) with various types of AIS. We constructed algorithms using 3D segmentation (direct estimation) and 2D segmentation (indirect estimation) and compared their performances with those annotated by neurologists. The proposed pretrained indirect model demonstrated higher segmentation performance than the direct model, with a sensitivity, specificity, F1-score, and Jaccard index of 75.0%, 77.9%, 76.0, and 62.1%, respectively, for internal validation, and 72.8%, 84.3%, 77.2, and 63.8%, respectively, for external validation. Volume estimation was more reliable for the indirect model, with 93.3% volume similarity (VS), 0.797 mean absolute error (MAE) for internal validation, VS of 89.2% and a MAE of 2.5% for external validation. These results suggest that the indirect model using 2D segmentation developed in this study can provide an accurate estimation of volume from DWI of AIS and may serve as a supporting tool to help physicians make crucial clinical decisions.
The Intestinal Microbiota May Be a Potential Theranostic Tool for Personalized Medicine
Authors: Di Domenico Marina , Ballini Andrea , Boccellino Mariarosaria , Scacco Salvatore , Lovero Roberto , Charitos Ioannis Alexandros , Santacroce Luigi
Published: March 2022

The human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized “mold” for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy.
Effects of Population Declines on Habitat Segregation and Activity Patterns of Rabbits and Hares in Doñana National Park, Spain
Authors: Beltrán Juan F. , Rau Jaime R. , Soriguer Ramón C. , Kufner Maura B. , Delibes Miguel , Carro Francisco
Published: March 2022

Competition, predation, and diseases are key factors shaping animal communities. In recent decades, lagomorphs in Europe have been impacted by virus-borne diseases that have caused substantial declines in their populations and, subsequently, in many of their predators. We examined activity and habitat-use patterns of sympatric European rabbits (Oryctolagus cuniculus L.) and Iberian hares (Lepus granatensis R.) in Doñana National Park, Spain, (DNP) during two periods of disease outbreak. In the first period (1984–1985), fecal pellet counts and roadside counts indicated that lagomorph species were segregated, with rabbits occurring in scrublands and hares in marshlands. Both species also occupied rush and fern belt ecotones. Roadside counts at sunrise, midday, sunset, and midnight revealed that rabbits and hares had the same activity patterns (crepuscular and nocturnal) in the zone of sympatry. During the second period (2005–2016), roadside counts showed that rabbits and hares were mainly nocturnal in scrublands and border marshlands. Hares occupied scrublands; a habitat previously occupied only by rabbits. These results are interpreted in light of the competition theory and predation pressure. The disease-caused decline of rabbits has likely favored hares that moved into scrublands, a vegetation type previously occupied exclusively by rabbits. The decline of rabbits in DNP has also caused the almost disappearance of this area of the Iberian lynx (Lynx pardinus), a rabbit specialist, thus enabling generalist predators to increase. Generalist predators have subsequently increased predation pressure on both rabbits and hares, causing them to switch to nocturnal activity.
Site Wind Right: Identifying Low-Impact Wind Development Areas in the Central United States
Authors: Hise Chris , Obermeyer Brian , Ahlering Marissa , Wilkinson Jessica , Fargione Joseph
Published: March 2022

To help avoid the most catastrophic effects of climate change, society needs to achieve net-zero greenhouse gas emissions by mid-century. Wind energy provides a clean, renewable source of electricity; however, improperly sited wind facilities pose known threats to wildlife populations and contribute to degradation of natural habitats. To support a rapid transition to low-carbon energy while protecting imperiled species, we identified potential low-impact areas for wind development in a 19-state region of the central U.S. by excluding areas with known wildlife sensitivities. By combining maps of sensitive habitats and species with wind speed and land use information, we demonstrate that there is significant potential to develop wind energy in the region while avoiding significant negative impacts to wildlife. These low-impact areas have the potential to yield between 930 and 1550 GW of name-plate wind capacity. This is equivalent to 8–13 times current U.S. installed wind capacity. Our analysis demonstrates that ambitious low-carbon energy goals are achievable while minimizing risks to wildlife.