bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Sleep Duration and Sleep Timing in the General Population from before to during the First COVID-19 Lockdown: A Systematic Review and Meta-Analysis
Authors: Ceolin Chiara , Limongi Federica , Siviero Paola , Trevisan Caterina , Noale Marianna , Catalani Filippo , Conti Silvia , Di Rosa Elisa , Perdixi Elena , Remelli Francesca , Prinelli Federica , Maggi Stefania
Published: May 2024

Background: The COVID-19 lockdown had a profound effect on everyday life, including sleep health. This systematic review and meta-analysis evaluated changes in quantitative sleep parameters during the first lockdown compared with pre-lockdown in the general population. Methods: A search in scientific databases was performed to identify eligible observational studies from inception to 8 February 2023. We performed a random effects meta-analysis of those studies reporting (a) means of sleep duration, time in bed (TIB), and sleep timing (bedtime and wake-up time); (b) the percentages of atypical sleep duration before and during the lockdown; (c) the percentages of change in sleep duration and sleep timing. Results: A total of 154 studies were included. A small increase in sleep duration (0.25 standardized mean difference, 95% CI 0.180–0.315) was found, with 55.0% of the individuals reporting changes, predominantly an increase (35.2%). The pooled relative risk for sleeping more than 8/9 h per night was 3.31 (95% IC 2.60–4.21). There was a moderately significant delay in sleep timing and a surge in napping. Conclusion: An increase in sleep duration and napping, and delayed sleep timing were observed. High-quality studies should evaluate whether these parameters have now become chronic or have returned to pre-lockdown values.
Understanding How Green Space Naturalness Impacts Public Well-Being: Prospects for Designing Healthier Cities
Authors: Bressane Adriano , Silva Mirela Beatriz , Goulart Ana Paula Garcia , Medeiros Líliam César de Castro
Published: May 2024

Statement of problem: Urbanization has brought significant advancements in human well-being; however, it poses challenges to urban green spaces (UGSs), affecting environmental quality and public health. Research gap: Previous studies have established the importance of UGSs for urban well-being but have not sufficiently explored how the naturalness of these spaces—ranging from untouched natural areas to human-designed landscapes—affects mental health outcomes in the context of developing countries, particularly Brazil. Purpose: This study aimed to bridge the research gap by investigating the relationship between the degree of naturalness in UGSs and mental health among residents of Brazilian metropolitan areas. Method: Data were collected through an online survey involving 2136 respondents from various Brazilian urban regions. The study used Welch’s ANOVA and Games–Howell post hoc tests to analyze the impact of UGS naturalness on mental health, considering depression, anxiety, and stress levels. Results and conclusions: The findings revealed that higher degrees of naturalness in UGSs significantly correlate with lower levels of mental distress. These results underscore the necessity of integrating natural elements into urban planning to enhance public health. Practical implications: Urban planners and policymakers are encouraged to prioritize the preservation and creation of naturalistic UGSs in urban environments to improve mental health outcomes. Future directions: Further research should explore the specific attributes of naturalness that most contribute to well-being and examine the scalability of these findings across different cultural and environmental contexts.
Effects on Child Development and Parent–Child Interaction of the FACAM Intervention: A Randomized Controlled Study of an Interdisciplinary Intervention to Support Women in Vulnerable Positions through Pregnancy and Early Motherhood
Authors: Pontoppidan Maiken , Nygaard Lene , Hirani Jonas Cuzulan , Thorsager Mette , Friis-Hansen Mette , Davis Deborah , Nohr Ellen Aagaard
Published: May 2024

Health inequality can have a profound impact on a child’s life. Maternal mental health challenges can hinder bonding, leading to impaired functioning and poorer child outcomes. To provide extra support for vulnerable pregnant women, the FACAM intervention offers the services of a health nurse or family therapist from pregnancy until the child starts school. This study examined the effects of FACAM intervention on pregnant women in vulnerable positions and their children until the child turned two years old. We randomly assigned 331 pregnant women to either FACAM intervention or care as usual and assessed them at baseline and when the infant was 3–6, 12–13.5, and 24 months old. The primary outcome was maternal sensitivity measured by Coding Interactive Behavior (CIB). Secondary outcomes included the parent–child relationship, child social–emotional development, child developmental progress, parent–child interaction, and child development. Our findings indicate that care-as-usual children were significantly more involved than FACAM children when the child was 4–6 months old (b = −0.25, [−0.42; −0.08] d = −0.42). However, we suspect this result is due to a biased dropout. We did not find any significant differences in any other outcomes. Therefore, the study suggests that the FACAM intervention is not superior to care as usual regarding child development and parent–child interaction outcomes.
Medical Interpreting Services for Refugees in Canada: Current State of Practice and Considerations in Promoting this Essential Human Right for All
Authors: Arya Akshaya Neil , Hyman Ilene , Holland Tim , Beukeboom Carolyn , Tong Catherine E. , Talavlikar Rachel , Eagan Grace
Published: May 2024

Language barriers, specifically among refugees, pose significant challenges to delivering quality healthcare in Canada. While the COVID-19 pandemic accelerated the emergence and development of innovative alternatives such as telephone-based and video-conferencing medical interpreting services and AI tools, access remains uneven across Canada. This comprehensive analysis highlights the absence of a cohesive national strategy, reflected in diverse funding models employed across provinces and territories, with gaps and disparities in access to medical interpreting services. Advocating for medical interpreting, both as a moral imperative and a prudent investment, this article draws from human rights principles and ethical considerations, justified in national and international guidelines, charters, codes and regulations. Substantiated by a cost-benefit analysis, it emphasizes that medical interpreting enhances healthcare quality and preserves patient autonomy. Additionally, this article illuminates decision-making processes for utilizing interpreting services; recognizing the pivotal roles of clinicians, interpreters, patients and caregivers within the care circle; appreciating intersectional considerations such as gender, culture and age, underscoring the importance of a collaborative approach. Finally, it provides recommendations at provider, organizational and system levels to ensure equitable access to this right and to promote the health and well-being of refugees and other individuals facing language barriers within Canada’s healthcare system.
Prediction of Parking Space Availability Using Improved MAT-LSTM Network
Authors: Zhang Feizhou , Shang Ke , Yan Lei , Nan Haijing , Miao Zicong
Published: May 2024

The prediction of parking space availability plays a crucial role in information systems providing parking guidance. However, controversy persists regarding the efficiency and accuracy of mainstream time series prediction methods, such as convolutional neural networks (CNNs) and recurrent neural networks (RNNs). In this study, a comparison was made between a temporal convolutional network (TCN) based on CNNs and a long short-term memory (LSTM) network based on RNNs to determine an appropriate baseline for predicting parking space availability. Subsequently, a multi-head attention (MAT) mechanism was incorporated into an LSTM network, attempting to improve its accuracy. Experiments were conducted on three real and two synthetic datasets. The results indicated that the TCN achieved the fastest convergence, whereas the MAT-LSTM method provided the highest average accuracy, namely 0.0330 and 1.102 × 10−6, on the real and synthetic datasets, respectively. Furthermore, the improved MAT-LSTM model accomplished an increase of up to 48% in accuracy compared with the classic LSTM model. Consequently, we concluded that RNN-based networks are better suited for predicting long-time series. In particular, the MAT-LSTM method proposed in this study holds higher application value for predicting parking space availability with a higher accuracy.
A Quantitative and Qualitative Experimental Framework for the Evaluation of Urban Soundscapes: Application to the City of Sidi Bou Saïd
Authors: Hammami Mohamed Amin , Claramunt Christophe
Published: May 2024

This research introduces an experimental framework based on 3D acoustic and psycho-acoustic sensors supplemented with ambisonics and sound morphological analysis, whose objective is to study urban soundscapes. A questionnaire that highlights the differences between what has been measured and what has been perceiveSd by humans complements the quantitative approach with a qualitative evaluation. The comparison of the measurements with the questionnaire provides a global vision of the perception of these soundscapes, as well as differences and similarities. The approach is experimented within the historical center of the Tunisian city of Sidi Bou Saïd, demonstrating that from a range of complementary protocols, a soundscape environment can be qualified. This framework provides an additional dimension to urban planning studies.
Spinning Disk Confocal Microscopy for Optimized and Quantified Live Imaging of 3D Mitochondrial Network
Authors: Ahmadian Somaieh , Lindsey Patrick J. , Smeets Hubert J. M. , van Tienen Florence H. J. , van Zandvoort Marc A. M. J.
Published: May 2024

Mitochondria are the energy factories of a cell, and depending on the metabolic requirements, the mitochondrial morphology, quantity, and membrane potential in a cell change. These changes are frequently assessed using commercially available probes. In this study, we tested the suitability of three commercially available probes—namely 5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolo-carbocyanine iodide (JC-1), MitoTracker Red CMX Rox (CMXRos), and tetramethylrhodamine methyl ester (TMRM)—for assessing the mitochondrial quantity, morphology, and membrane potential in living human mesoangioblasts in 3D with confocal laser scanning microscope (CLSM) and scanning disk confocal microscope (SDCM). Using CLSM, JC-1, and CMXRos—but not TMRM—uncovered considerable background and variation. Using SDCM, the background signal only remained apparent for the JC-1 monomer. Repetitive imaging of CMXRos and JC-1—but not TMRM—demonstrated a 1.5–2-fold variation in signal intensity between cells using CLSM. The use of SDCM drastically reduced this variation. The slope of the relative signal intensity upon repetitive imaging using CLSM was lowest for TMRM (−0.03) and highest for CMXRos (0.16). Upon repetitive imaging using SDCM, the slope varied from 0 (CMXRos) to a maximum of −0.27 (JC-1 C1). Conclusively, our data show that TMRM staining outperformed JC-1 and CMXRos dyes in a (repetitive) 3D analysis of the entire mitochondrial quantity, morphology, and membrane potential in living cells.
Under Stress: Searching for Genes Involved in the Response of Abies pinsapo Boiss to Climate Change
Authors: Blanca-Reyes Irene , Lechuga Víctor , Llebrés María Teresa , Carreira José A. , Ávila Concepción , Cánovas Francisco M. , Castro-Rodríguez Vanessa
Published: May 2024

Currently, Mediterranean forests are experiencing the deleterious effects of global warming, which mainly include increased temperatures and decreased precipitation in the region. Relict Abies pinsapo fir forests, endemic in the southern Iberian Peninsula, are especially sensitive to these recent environmental disturbances, and identifying the genes involved in the response of this endangered tree species to climate-driven stresses is of paramount importance for mitigating their effects. Genomic resources for A. pinsapo allow for the analysis of candidate genes reacting to warming and aridity in their natural habitats. Several members of the complex gene families encoding late embryogenesis abundant proteins (LEAs) and heat shock proteins (HSPs) have been found to exhibit differential expression patterns between wet and dry seasons when samples from distinct geographical locations and dissimilar exposures to the effects of climate change were analyzed. The observed changes were more perceptible in the roots of trees, particularly in declining forests distributed at lower altitudes in the more vulnerable mountains. These findings align with previous studies and lay the groundwork for further research on the molecular level. Molecular and genomic approaches offer valuable insights for mitigating climate stress and safeguarding this endangered conifer.
Galf-Specific Neolectins: Towards Promising Diagnostic Tools
Authors: Seničar Mateja , Roubinet Benoît , Lafite Pierre , Legentil Laurent , Ferrières Vincent , Landemarre Ludovic , Daniellou Richard
Published: May 2024

In the absence of naturally available galactofuranose-specific lectin, we report herein the bioengineering of GalfNeoLect, from the first cloned wild-type galactofuranosidase (Streptomyces sp. strain JHA19), which recognises and binds a single monosaccharide that is only related to nonmammalian species, usually pathogenic microorganisms. We kinetically characterised the GalfNeoLect to confirm attenuation of hydrolytic activity and used competitive inhibition assay, with close structural analogues of Galf, to show that it conserved interaction with its original substrate. We synthetised the bovine serum albumin-based neoglycoprotein (GalfNGP), carrying the multivalent Galf units, as a suitable ligand and high-avidity system for the recognition of GalfNeoLect which we successfully tested directly with the galactomannan spores of Aspergillus brasiliensis (ATCC 16404). Altogether, our results indicate that GalfNeoLect has the necessary versatility and plasticity to be used in both research and diagnostic lectin-based applications.
Impact of Thermo-Responsive N-Acetylcysteine Hydrogel on Dermal Wound Healing and Oral Ulcer Regeneration
Authors: Padalhin Andrew , Abueva Celine , Ryu Hyun Seok , Yoo Seung Hyeon , Seo Hwee Hyon , Park So Young , Chung Phil-Sang , Woo Seung Hoon
Published: May 2024

This study investigates the efficacy of a thermo-responsive N-acetylcysteine (NAC) hydrogel on wound healing and oral ulcer recovery. Formulated by combining NAC with methylcellulose, the hydrogel’s properties were assessed for temperature-induced gelation and cell viability using human fibroblast cells. In vivo experiments on Sprague Dawley rats compared the hydrogel’s effects against saline, NAC solution, and a commercial NAC product. Results show that a 5% NAC and 1% methylcellulose solution exhibited optimal outcomes. While modest improvements in wound healing were observed, significant enhancements were noted in oral ulcer recovery, with histological analyses indicating fully regenerated mucosal tissue. The study concludes that modifying viscosity enhances NAC retention, facilitating tissue regeneration. These findings support previous research on the beneficial effects of antioxidant application on damaged tissues, suggesting the potential of NAC hydrogels in improving wound care and oral ulcer treatment.
Phytochemical Analysis and Antioxidant Effects of Prunella vulgaris in Experimental Acute Inflammation
Authors: Mîrza Camelia-Manuela , Mîrza Tudor-Valentin , Odagiu Antonia Cristina Maria , Uifălean Ana , But Anca Elena , Pârvu Alina Elena , Bulboacă Adriana-Elena
Published: May 2024

Prunella vulgaris (PV) is one of the most commonly used nutraceuticals as it has been proven to have anti-inflammatory and antioxidant properties. The aim of this study was to evaluate the phytochemical composition of PV and its in vivo antioxidant properties. A phytochemical analysis measuring the total phenolic content (TPC), the identification of phenolic compounds by HPLC-DAD-ESI, and the evaluation of the in vitro antioxidant activity by the DPPH assay of the extract were performed. The antioxidant effects on inflammation induced by turpentine oil were experimentally tested in rats. Seven groups with six animals each were used: a control group, the experimental inflammation treatment group, the experimental inflammation and diclofenac sodium (DS) treatment group, and four groups with their inflammation treated using different dilutions of the extract. Serum redox balance was assessed based on total oxidative status (TOS), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), total thiols, and an oxidative stress index (OSI) contents. The TPC was 0.28 mg gallic acid equivalents (GAE)/mL extract, while specific representatives were represented by caffeic acid, p-coumaric acid, dihydroxybenzoic acid, gentisic acid, protocatechuic acid, rosmarinic acid, vanillic acid, apigenin–glucuronide, hesperidin, kaempferol–glucuronide. The highest amount (370.45 μg/mL) was reported for hesperidin, which is a phenolic compound belonging to the flavanone subclass. The antioxidant activity of the extracts, determined using the DPPH assay, was 27.52 mmol Trolox/mL extract. The PV treatment reduced the oxidative stress by lowering the TOS, OSI, NO, and MDA and by increasing the TAC and thiols. In acute inflammation, treatment with the PV extract reduced oxidative stress, with lower concentrations being more efficient and having a better effect than DS.
Special Issue “Molecular and Cellular Advances in Atopic Diseases”
Authors: Cabanillas Beatriz
Published: May 2024

Atopic diseases, which currently affect around one billion people worldwide, are experiencing a rising prevalence [...]
Host RNA Expression Signatures in Young Infants with Urinary Tract Infection: A Prospective Study
Authors: Dungu Kia Hee Schultz , Carlsen Emma Louise Malchau , Glenthøj Jonathan Peter , Schmidt Lisbeth Samsø , Jørgensen Inger Merete , Cortes Dina , Poulsen Anja , Vissing Nadja Hawwa , Bagger Frederik Otzen , Nygaard Ulrikka
Published: May 2024

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.
Antimicrobial Peptides towards Clinical Application—A Long History to Be Concluded
Authors: Cresti Laura , Cappello Giovanni , Pini Alessandro
Published: May 2024

Antimicrobial peptides (AMPs) are molecules with an amphipathic structure that enables them to interact with bacterial membranes. This interaction can lead to membrane crossing and disruption with pore formation, culminating in cell death. They are produced naturally in various organisms, including humans, animals, plants and microorganisms. In higher animals, they are part of the innate immune system, where they counteract infection by bacteria, fungi, viruses and parasites. AMPs can also be designed de novo by bioinformatic approaches or selected from combinatorial libraries, and then produced by chemical or recombinant procedures. Since their discovery, AMPs have aroused interest as potential antibiotics, although few have reached the market due to stability limits or toxicity. Here, we describe the development phase and a number of clinical trials of antimicrobial peptides. We also provide an update on AMPs in the pharmaceutical industry and an overall view of their therapeutic market. Modifications to peptide structures to improve stability in vivo and bioavailability are also described.
Regulatory Role of Meox1 in Muscle Growth of Sebastes schlegelii
Authors: Song Weihao , Liu Xiaotong , Huang Kejia , Qi Jie , He Yan
Published: May 2024

Meox1 is a critical transcription factor that plays a pivotal role in embryogenesis and muscle development. It has been established as a marker gene for growth-specific muscle stem cells in zebrafish. In this study, we identified the SsMeox1 gene in a large teleost fish, Sebastes schlegelii. Through in situ hybridization and histological analysis, we discovered that SsMeox1 can be employed as a specific marker of growth-specific muscle stem cells, which originate from the somite stage and are primarily situated in the external cell layer (ECL) and myosepta, with a minor population distributed among muscle fibers. The knockdown of SsMeox1 resulted in a significant increase in Ccnb1 expression, subsequently promoting cell cycle progression and potentially accelerating the depletion of the stem cell pool, which ultimately led to significant growth retardation. These findings suggest that SsMeox1 arrests the cell cycle of growth-specific muscle stem cells in the G2 phase by suppressing Ccnb1 expression, which is essential for maintaining the stability of the growth-specific muscle stem cell pool. Our study provides significant insights into the molecular mechanisms underlying the indeterminate growth of large teleosts.
Non-Classical Effects of FGF23: Molecular and Clinical Features
Authors: Martínez-Heredia Luis , Canelo-Moreno Juan Manuel , García-Fontana Beatriz , Muñoz-Torres Manuel
Published: May 2024

This article reviews the role of fibroblast growth factor 23 (FGF23) protein in phosphate metabolism, highlighting its regulation of vitamin D, parathyroid hormone, and bone metabolism. Although it was traditionally thought that phosphate–calcium homeostasis was controlled exclusively by parathyroid hormone (PTH) and calcitriol, pathophysiological studies revealed the influence of FGF23. This protein, expressed mainly in bone, inhibits the renal reabsorption of phosphate and calcitriol formation, mediated by the α-klotho co-receptor. In addition to its role in phosphate metabolism, FGF23 exhibits pleiotropic effects in non-renal systems such as the cardiovascular, immune, and metabolic systems, including the regulation of gene expression and cardiac fibrosis. Although it has been proposed as a biomarker and therapeutic target, the inhibition of FGF23 poses challenges due to its potential side effects. However, the approval of drugs such as burosumab represents a milestone in the treatment of FGF23-related diseases.
Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production
Authors: Ramos-Acosta Carlos , Huerta-Pantoja Laura , Salazar-Hidalgo Milton Eduardo , Mayol Elsa , Jiménez-Vega Selene , García-Peña Pablo , Jordi-Cruz Jenifeer , Baquero Cristina , Porras Almudena , Íñigo-Rodríguez Belén , Benavente Celina M. , López-Pastor Andrea R. , Gómez-Delgado Irene , Urcelay Elena , Candel Francisco Javier , Anguita Eduardo
Published: May 2024

Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.
MicroRNA-135b-5p Is a Pathologic Biomarker in the Endothelial Cells of Arteriovenous Malformations
Authors: Lee Joon Seok , Kim Gyeonghwa , Lee Jong Ho , Ryu Jeong Yeop , Oh Eun Jung , Kim Hyun Mi , Kwak Suin , Hur Keun , Chung Ho Yun
Published: May 2024

Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.
Total Synthesis of the Sex Pheromone of Clania variegata Snellen and Its Stereoisomers
Authors: Wang Xueyang , Wu Jianwei , Wang Jianan , Liu Dan , Bian Qinghua , Zhong Jiangchun
Published: May 2024

The paulownia bagworm, Clania variegata Snell, is an economically important pest of agriculture and forests. The sex pheromone of this pest and its stereoisomers were synthesized, and two of the stereoisomers were prepared for the first time. Our strategy was efficient and mainly included the ring-opening reaction of (S)-2-methyloxirane, the coupling of chiral sulfonate, the oxidative cleavage of olefin, and Yamaguchi esterification. Moreover, the overall yields of our synthesis were 23–29%, with eight steps in the longest route.
Peptides Are Cardioprotective Drugs of the Future: The Receptor and Signaling Mechanisms of the Cardioprotective Effect of Glucagon-like Peptide-1 Receptor Agonists
Authors: Boshchenko Alla A. , Maslov Leonid N. , Mukhomedzyanov Alexander V. , Zhuravleva Olga A. , Slidnevskaya Alisa S. , Naryzhnaya Natalia V. , Zinovieva Arina S. , Ilinykh Philipp A.
Published: May 2024

The high mortality rate among patients with acute myocardial infarction (AMI) is one of the main problems of modern cardiology. It is quite obvious that there is an urgent need to create more effective drugs for the treatment of AMI than those currently used in the clinic. Such drugs could be enzyme-resistant peptide analogs of glucagon-like peptide-1 (GLP-1). GLP-1 receptor (GLP1R) agonists can prevent ischemia/reperfusion (I/R) cardiac injury. In addition, chronic administration of GLP1R agonists can alleviate the development of adverse cardiac remodeling in myocardial infarction, hypertension, and diabetes mellitus. GLP1R agonists can protect the heart against oxidative stress and reduce proinflammatory cytokine (IL-1β, TNF-α, IL-6, and MCP-1) expression in the myocardium. GLP1R stimulation inhibits apoptosis, necroptosis, pyroptosis, and ferroptosis of cardiomyocytes. The activation of the GLP1R augments autophagy and mitophagy in the myocardium. GLP1R agonists downregulate reactive species generation through the activation of Epac and the GLP1R/PI3K/Akt/survivin pathway. The GLP1R, kinases (PKCε, PKA, Akt, AMPK, PI3K, ERK1/2, mTOR, GSK-3β, PKG, MEK1/2, and MKK3), enzymes (HO-1 and eNOS), transcription factors (STAT3, CREB, Nrf2, and FoxO3), KATP channel opening, and MPT pore closing are involved in the cardioprotective effect of GLP1R agonists.
Polymer System Based on Polyethylene Glycol and TFE Telomers for Producing Films with Switchable Wettability
Authors: Belov Evgeniy , Nadaraia Konstantine , Imshinetskiy Igor , Mashtalyar Dmitry , Ignatieva Lidia , Marchenko Yurii , Osmushko Ivan , Gerasimenko Maria , Sinebruykhov Sergey , Gnedenkov Sergey
Published: May 2024

Today a lot of attention is paid to the formation of thermosensitive systems for biomedical and industrial applications. The development of new methods for synthesis of such systems is a dynamically developing direction in chemistry and materials science. In this regard, this paper presents results of the studies of a new synthesized supramolecular polymer system based on polyethylene glycol and tetrafluoroethylene telomers. The films formed from the polymer substance have the property of switching wettability depending on temperature after heating activation. It has been established that the wettability changes at 60 °C. The contact angle of activated hydrophobic polymer film reaches 143°. Additionally, the system exhibits its properties regardless of the pH of the environment. Based on data obtained by the methods of infrared and x-ray photoelectron spectroscopy, differential thermal analysis and thermal analysis in conjunction with wettability and morphology, a model of the behavior of molecules in a polymer system was built that ensures switching of the hydrophilic/hydrophobic surface state. The resulting polymer system, as well as films based on it, can be used in targeted drug delivery, implantation surgery, as sensors, etc.
Levels of Small Extracellular Vesicles Containing hERG-1 and Hsp47 as Potential Biomarkers for Cardiovascular Diseases
Authors: Osorio Luis A. , Lozano Mauricio , Soto Paola , Moreno-Hidalgo Viviana , Arévalo-Gil Angely , Ramírez-Balaguera Angie , Hevia Daniel , Cifuentes Jorge , Hidalgo Yessia , Alcayaga-Miranda Francisca , Pasten Consuelo , Morales Danna , Varela Diego , Urquidi Cinthya , Iturriaga Andrés , Rivera-Palma Alejandra , Larrea-Gómez Ricardo , Irarrázabal Carlos E.
Published: May 2024

The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.
Advancements in Synthetic Strategies and Biological Effects of Ciprofloxacin Derivatives: A Review
Authors: Khwaza Vuyolwethu , Mlala Sithenkosi , Aderibigbe Blessing A.
Published: May 2024

Ciprofloxacin is a widely used antibiotic in the fluoroquinolone class. It is widely acknowledged by various researchers worldwide, and it has been documented to have a broad range of other pharmacological activities, such as anticancer, antiviral, antimalarial activities, etc. Researchers have been exploring the synthesis of ciprofloxacin derivatives with enhanced biological activities or tailored capability to target specific pathogens. The various biological activities of some of the most potent and promising ciprofloxacin derivatives, as well as the synthetic strategies used to develop them, are thoroughly reviewed in this paper. Modification of ciprofloxacin via 4-oxo-3-carboxylic acid resulted in derivatives with reduced efficacy against bacterial strains. Hybrid molecules containing ciprofloxacin scaffolds displayed promising biological effects. The current review paper provides reported findings on the development of novel ciprofloxacin-based molecules with enhanced potency and intended therapeutic activities which will be of great interest to medicinal chemists.
Function and Mechanism of Abscisic Acid on Microglia-Induced Neuroinflammation in Parkinson’s Disease
Authors: Han Tingting , Xu Yuxiang , Liu Haixuan , Sun Lin , Cheng Xiangshu , Shen Ying , Wei Jianshe
Published: May 2024

Parkinson’s disease (PD), as a neurologically implemented disease with complex etiological factors, has a complex and variable pathogenesis. Accompanying further research, neuroinflammation has been found to be one of the possible factors in its pathogenesis. Microglia, as intrinsic immune cells in the brain, play an important role in maintaining microenvironmental homeostasis in the brain. However, over-activation of neurotoxic microglia in PD promotes neuroinflammation, which further increases dopaminergic (DA) neuronal damage and exacerbates the disease process. Therefore, targeting and regulating the functional state of microglia is expected to be a potential avenue for PD treatment. In addition, plant extracts have shown great potential in the treatment of neurodegenerative disorders due to their abundant resources, mild effects, and the presence of multiple active ingredients. However, it is worth noting that some natural products have certain toxic side effects, so it is necessary to pay attention to distinguish medicinal ingredients and usage and dosage when using to avoid aggravating the progression of diseases. In this review, the roles of microglia with different functional states in PD and the related pathways inducing microglia to transform into neuroprotective states are described. At the same time, it is discussed that abscisic acid (ABA) may regulate the polarization of microglia by targeting them, promote their transformation into neuroprotective state, reduce the neuroinflammatory response in PD, and provide a new idea for the treatment of PD and the selection of drugs.
A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome—The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1
Authors: Gadd Gustaf , Åberg Daniel , Wall Alexander , Zetterberg Henrik , Blennow Kaj , Jood Katarina , Jern Christina , Isgaard Jörgen , Svensson Johan , Åberg N. David
Published: May 2024

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25–30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled “the obesity paradox”. Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5–25), overweight (25–30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3–6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30–4.14) and obese (OR 2.25, 95% CI 1.08–4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.
Stress-Induced Proteasome Sub-Cellular Translocation in Cardiomyocytes Causes Altered Intracellular Calcium Handling and Arrhythmias
Authors: Neeman-Egozi Shunit , Livneh Ido , Dolgopyat Irit , Nussinovitch Udi , Milman Helena , Cohen Nadav , Eisen Binyamin , Ciechanover Aaron , Binah Ofer
Published: May 2024

The ubiquitin–proteasome system (UPS) is an essential mechanism responsible for the selective degradation of substrate proteins via their conjugation with ubiquitin. Since cardiomyocytes have very limited self-renewal capacity, as they are prone to protein damage due to constant mechanical and metabolic stress, the UPS has a key role in cardiac physiology and pathophysiology. While altered proteasomal activity contributes to a variety of cardiac pathologies, such as heart failure and ischemia/reperfusion injury (IRI), the environmental cues affecting its activity are still unknown, and they are the focus of this work. Following a recent study by Ciechanover’s group showing that amino acid (AA) starvation in cultured cancer cell lines modulates proteasome intracellular localization and activity, we tested two hypotheses in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs, CMs): (i) AA starvation causes proteasome translocation in CMs, similarly to the observation in cultured cancer cell lines; (ii) manipulation of subcellular proteasomal compartmentalization is associated with electrophysiological abnormalities in the form of arrhythmias, mediated via altered intracellular Ca2+ handling. The major findings are: (i) starving CMs to AAs results in proteasome translocation from the nucleus to the cytoplasm, while supplementation with the aromatic amino acids tyrosine (Y), tryptophan (W) and phenylalanine (F) (YWF) inhibits the proteasome recruitment; (ii) AA-deficient treatments cause arrhythmias; (iii) the arrhythmias observed upon nuclear proteasome sequestration(-AA+YWF) are blocked by KB-R7943, an inhibitor of the reverse mode of the sodium–calcium exchanger NCX; (iv) the retrograde perfusion of isolated rat hearts with AA starvation media is associated with arrhythmias. Collectively, our novel findings describe a newly identified mechanism linking the UPS to arrhythmia generation in CMs and whole hearts.
How We Interpret Thrombosis with Thrombocytopenia Syndrome?
Authors: Yamada Shinya , Asakura Hidesaku
Published: May 2024

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.
In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
Authors: Gonzalez María Micaela , Vizoso-Pinto Maria Guadalupe , Erra-Balsells Rosa , Gensch Thomas , Cabrerizo Franco M.
Published: May 2024

Herpes simplex virus (HSV) infections are highly widespread among humans, producing symptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threatening encephalitis. At present, there are no vaccines available, and some existing antiviral treatments can be ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In this report, the in vitro anti-HSV effect of 9,9′-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and did not impede either the attachment or penetration steps of viral particles. The antiviral effect was only exerted under the constant presence of the dimer in the incubation media, and the mechanism of action was found to involve later events of virus infection. Analysis of fluorescence lifetime imaging data showed that the nHo-dimer internalized well into the cells when present in the extracellular incubation medium, with a preferential accumulation into perinuclear organelles including mitochondria. After washing the host cells with fresh medium free of nHo-dimer, the signal decreased, suggesting the partial release of the compound from the cells. This agrees with the observation that the antiviral effect is solely manifested when the alkaloid is consistently present in the incubation media.
Age Prediction Using DNA Methylation Heterogeneity Metrics
Authors: Karetnikov Dmitry I. , Romanov Stanislav E. , Baklaushev Vladimir P. , Laktionov Petr P.
Published: May 2024

Dynamic changes in genomic DNA methylation patterns govern the epigenetic developmental programs and accompany the organism‘s aging. Epigenetic clock (eAge) algorithms utilize DNA methylation to estimate the age and risk factors for diseases as well as analyze the impact of various interventions. High-throughput bisulfite sequencing methods, such as reduced-representation bisulfite sequencing (RRBS) or whole genome bisulfite sequencing (WGBS), provide an opportunity to identify the genomic regions of disordered or heterogeneous DNA methylation, which might be associated with cell-type heterogeneity, DNA methylation erosion, and allele-specific methylation. We systematically evaluated the applicability of five scores assessing the variability of methylation patterns by evaluating within-sample heterogeneity (WSH) to construct human blood epigenetic clock models using RRBS data. The best performance was demonstrated by the model based on a metric designed to assess DNA methylation erosion with an MAE of 3.686 years. We also trained a prediction model that uses the average methylation level over genomic regions. Although this region-based model was relatively more efficient than the WSH-based model, the latter required the analysis of just a few short genomic regions and, therefore, could be a useful tool to design a reduced epigenetic clock that is analyzed by targeted next-generation sequencing.
Micronutrient Status and Breast Cancer: A Narrative Review
Authors: Forma Alicja , Grunwald Arkadiusz , Zembala Patryk , Januszewski Jacek , Brachet Adam , Zembala Roksana , Świątek Kamila , Baj Jacek
Published: May 2024

Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women’s death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of breast cancer and its possible influence on various therapeutic pathways. We researched meta-analyses, systemic and narrative reviews, retrospective studies, as well as original studies on human and animal models. The results of these studies indicate a possible correlation between the different levels of micronutrients and a decreased risk of breast cancer as well as a better survival rate. However, further studies are necessary to establish adequate doses of supplementation of the chosen micronutrients and the exact mechanisms of micronutrient impact on breast cancer therapy.
The Enigma of Tau Protein Aggregation: Mechanistic Insights and Future Challenges
Authors: Zheng Huiting , Sun Huimin , Cai Qixu , Tai Hwan-Ching
Published: May 2024

Tau protein misfolding and aggregation are pathological hallmarks of Alzheimer’s disease and over twenty neurodegenerative disorders. However, the molecular mechanisms of tau aggregation in vivo remain incompletely understood. There are two types of tau aggregates in the brain: soluble aggregates (oligomers and protofibrils) and insoluble filaments (fibrils). Compared to filamentous aggregates, soluble aggregates are more toxic and exhibit prion-like transmission, providing seeds for templated misfolding. Curiously, in its native state, tau is a highly soluble, heat-stable protein that does not form fibrils by itself, not even when hyperphosphorylated. In vitro studies have found that negatively charged molecules such as heparin, RNA, or arachidonic acid are generally required to induce tau aggregation. Two recent breakthroughs have provided new insights into tau aggregation mechanisms. First, as an intrinsically disordered protein, tau is found to undergo liquid-liquid phase separation (LLPS) both in vitro and inside cells. Second, cryo-electron microscopy has revealed diverse fibrillar tau conformations associated with different neurodegenerative disorders. Nonetheless, only the fibrillar core is structurally resolved, and the remainder of the protein appears as a “fuzzy coat”. From this review, it appears that further studies are required (1) to clarify the role of LLPS in tau aggregation; (2) to unveil the structural features of soluble tau aggregates; (3) to understand the involvement of fuzzy coat regions in oligomer and fibril formation.