bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Preterm Birth and Exposure to Endocrine Disrupting Chemicals
Authors: Kolan Anish S. , Hall Julianne M.
Published: January 2023

Several studies in recent years have shown that endocrine disrupting chemicals (EDCs) can exert deleterious effects within several systems of the human body, such as the immune, neurological, and reproductive systems, among others. This review aims to summarize the investigations into the effect of EDC exposure on reproductive systems, namely preterm birth (PTB), and the efforts that international organizations have made to curb the harmful results of EDC exposure. To gather information, PubMed was initially searched for relevant articles containing the following terms: endocrine disrupting chemicals; preterm birth. PubMed was subsequently used to identify articles discussing the association between preterm birth and specific EDC exposures (BPA; phthalates; organochlorine pesticides; organophosphate pesticides; lead; PBDE; preterm birth). Both searches, limited to articles published within the past 20 years, identified several publications that have examined the association between various EDCs and PTB. While the findings of the studies differed, collectively they revealed sufficient evidence of a potential association between EDC exposure and risk of PTB. Thus, international organizations such as the United Nations Environmental Programme (UNEP) and World Health Organization (WHO) should continue to limit EDC exposure across the globe and monitor levels among individuals of reproductive age.
In Silico and In Vitro Inhibition of SARS-CoV-2 PLpro with Gramicidin D
Authors: Protić Sara , Kaličanin Nevena , Sencanski Milan , Prodanović Olivera , Milicevic Jelena , Perovic Vladimir , Paessler Slobodan , Prodanović Radivoje , Glisic Sanja
Published: January 2023

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PLpro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PLpro. After the expression and purification of PLpro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PLpro. The current study’s findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profile.
Endothelial Cell Markers Are Inferior to Vascular Smooth Muscle Cells Markers in Staining Vasa Vasorum and Are Non-Specific for Distinct Endothelial Cell Lineages in Clinical Samples
Authors: Markova Victoria , Bogdanov Leo , Velikanova Elena , Kanonykina Anastasia , Frolov Alexey , Shishkova Daria , Lazebnaya Anastasia , Kutikhin Anton
Published: January 2023

Current techniques for the detection of vasa vasorum (VV) in vascular pathology include staining for endothelial cell (EC) markers such as CD31 or VE-cadherin. However, this approach does not permit an objective assessment of vascular geometry upon vasospasm and the clinical relevance of endothelial specification markers found in developmental biology studies remains unclear. Here, we performed a combined immunostaining of rat abdominal aorta (rAA) and human saphenous vein (hSV) for various EC or vascular smooth muscle cell (VSMC) markers and found that the latter (e.g., alpha smooth muscle actin (α-SMA) or smooth muscle myosin heavy chain (SM-MHC)) ensure a several-fold higher signal-to-noise ratio irrespective of the primary antibody origin, fluorophore, or VV type (arterioles, venules, or capillaries). Further, α-SMA or SM-MHC staining allowed unbiased evaluation of the VV area under vasospasm. Screening of the molecular markers of endothelial heterogeneity (mechanosensitive transcription factors KLF2 and KLF4, arterial transcription factors HES1, HEY1, and ERG, venous transcription factor NR2F2, and venous/lymphatic markers PROX1, LYVE1, VEGFR3, and NRP2) have not revealed specific markers of any lineage in hSV (although KLF2 and PROX1 were restricted to venous endothelium in rAA), suggesting the need in high-throughput searches for the clinically relevant signatures of arterial, venous, lymphatic, or capillary differentiation.
Male Sex Hormones, Metabolic Syndrome, and Aquaporins: A Triad of Players in Male (in)Fertility
Authors: Nunes Diana C. , Ribeiro João C. , Alves Marco G. , Oliveira Pedro F. , Bernardino Raquel L.
Published: January 2023

Infertility is becoming a chronic and emerging problem in the world. There is a resistant stigma that this health condition is mostly due to the female, although the literature supports that the responsibility for the onset of infertility is equally shared between both sexes in more or less equal proportions. Nevertheless, male sex hormones, particularly testosterone (T), are key players in male-related infertility. Indeed, hypogonadism, which is also characterized by changes in T levels, is one of the most common causes of male infertility and its incidence has been interconnected to the increased prevalence of metabolic diseases. Recent data also highlight the role of aquaporin (AQP)-mediated water and solute diffusion and the metabolic homeostasis in testicular cells suggesting a strong correlation between AQPs function, metabolism of testicular cells, and infertility. Indeed, recent studies showed that both metabolic and sexual hormone concentrations can change the expression pattern and function of AQPs. Herein, we review up-to-date information on the involvement of AQP-mediated function and permeability in men with metabolic syndrome and testosterone deficit, highlighting the putative mechanisms that show an interaction between sex hormones, AQPs, and metabolic syndrome that may contribute to male infertility.
Dietary Isothiocyanates: Novel Insights into the Potential for Cancer Prevention and Therapy
Authors: Na Guanqiong , He Canxia , Zhang Shunxi , Tian Sicong , Bao Yongping , Shan Yujuan
Published: January 2023

Diet plays an important role in health. A high intake of plant chemicals such as glucosinolates/isothiocyanates can promote optimal health and decrease the risk of cancer. Recent research has discovered more novel mechanisms of action for the effects of isothiocyanates including the modulation of tumor microenvironment, the inhibition of the self-renewal of stem cells, the rearrangement of multiple pathways of energy metabolism, the modulation of microbiota, and protection against Helicobacter pylori. However, the hormetic/biphasic effects of isothiocyanates may make the recommendations complicated. Isothiocyanates possess potent anti-cancer activities based on up-to-date evidence from in vitro and in vivo studies. The nature of hormesis suggests that the benefits or risks of isothiocyanates largely depend on the dose and endpoint of interest. Isothiocyanates are a promising class of cancer-preventative phytochemicals, but researchers should be aware of the potential adverse (and hormetic) effects. In the authors’ opinion, dietary isothiocyanates are better used as adjunctive treatments in combination with known anti-cancer drugs. The application of nano-formulations and the delivery of isothiocyanates are also discussed in this review.
Does the Blood–Brain Barrier Integrity Change in Regard to the Onset of Fetal Growth Restriction?
Authors: Misan Natalia , Michalak Sławomir , Kapska Katarzyna , Osztynowicz Krystyna , Ropacka-Lesiak Mariola , Kawka-Paciorkowska Katarzyna
Published: January 2023

The aim of the study was to determine whether early-onset and late-onset fetal growth restriction (FGR) differentially affects the blood–brain barrier integrity. Furthermore, the purpose of the study was to investigate the relationship between the blood–brain barrier breakdown and neurological disorders in FGR newborns. To evaluate the serum tight junction (TJ) proteins and the placental TJ proteins expression, an ELISA method was used. A significant difference in serum OCLN concentrations was noticed in pregnancies complicated by the early-onset FGR, in relation to the intraventricular hemorrhage (IVH) occurrence in newborns. No significant differences in concentrations of the NR1 subunit of the N-methyl-d-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), zonula occludens-1 (zo-1), the CLN5/zo-1 ratio, and the placental expression of OCLN, CLN5, claudin-4 (CLN4), zo-1 were noticed between groups. The early-onset FGR was associated with a higher release of NME1 into the maternal circulation in relation to the brain-sparing effect and premature delivery. Additionally, in late-onset FGR, the higher release of the S100B into the maternal serum in regard to fetal distress was observed. Furthermore, there was a higher release of zo-1 into the maternal circulation in relation to newborns’ moderate acidosis in late-onset FGR. Blood–brain barrier disintegration is not dependent on pregnancy advancement at the time of FGR diagnosis. NME1 may serve as a biomarker useful in the prediction of fetal circulatory centralization and extremely low birth weight in pregnancies complicated by the early-onset FGR. Moreover, the serum zo-1 concentration may have prognostic value for moderate neonatal acidosis in late-onset FGR pregnancies.
Effect of CeO2-Reinforcement on Pb Absorption by Coconut Coir-Derived Magnetic Biochar
Authors: Yang Yujia , Shan Rui , Xiao Yaoxin , Zhao Fengxiao , Yuan Haoran , Chen Yong
Published: January 2023

Magnetic separable biochar holds great promise for the treatment of Pb2+-contaminated wastewater. However, the absorption effect of unmodified magnetic biochar is poor. Considering this gap in knowledge, CeO2-doped magnetic coconut coir biochar (Ce-MCB) and magnetic coconut coir biochar (MCB) for Pb2+ absorption were prepared by the impregnation method, and the efficiency of Ce-MCB for Pb2+ absorption was evaluated in comparison with MCB. Conducting the absorption experiments, the study provided theoretical support for the exploration of the absorption mechanism. The quantitative analysis exposed that the enhanced absorption capacity of Ce-MCB was attributed to the increase in oxygen-containing functional groups and mineral precipitation. The Langmuir and Freundlich isotherm model showed that Ce-MCB is a suitable adsorbent for Pb2+. The absorption characteristics of Ce-MCB was fit well with the pseudo-second-order (PSO) and Langmuir models, which revealed that the absorption of Pb2+ in water was monolayer chemisorption with a maximum theoretical adsorption capacity of 140.83 mg·g−1. The adsorption capacity of Ce-MCB for Pb(II) was sustained above 70% after four cycles. In addition, the saturation magnetization intensity of Ce-MCB was 7.15 emu·g−1, which was sufficient to separate out from the solution. Overall, Ce-MCB has wide application prospects in terms of biomass resources recycling and environmental conservation.
circITGB1 Regulates Adipocyte Proliferation and Differentiation via the miR-23a/ARRB1 Pathway
Authors: Yue Xiaoyv , Fan Mengdan , Liang Yv , Qiao Liying , Liu Jianhua , Pan Yangyang , Yang Kaijie , Liu Wenzhong
Published: January 2023

Adipose tissues represent an important energy storage organ in animals and are the largest endocrine organ. It plays an important regulatory role in the pathogenesis of insulin resistance, cardiovascular disease, and metabolic syndrome. Adipose development is a complex biological process involving multiple key genes, signaling pathways, and non-coding RNAs, including microRNAs and circular RNAs. In this study, we characterized circITGB1 and named its host gene ITGB1, which is differentially expressed in sheep of different months based on sequencing data. We collated and analyzed the sequencing data to select miRNA-23a with strong binding to ARRB1. We found that miRNA-23a regulates the development and differentiation of sheep adipocytes by targeting ARRB1. As a competing endogenous RNA, circITGB1 overexpression effectively alleviated the inhibitory effect of miR-23a on ARRB1. Conclusively, we provide evidence that circITGB1 regulates the proliferation and differentiation of sheep adipocytes via the miR-23a/ARRB1 pathway. This study provides a scientific basis for further studies on adipose tissue development at the circRNA level.
Resveratrol Derivative Exhibits Marked Antiproliferative Actions, Affecting Stemness in Pancreatic Cancer Cells
Authors: Florio Rosalba , De Filippis Barbara , Veschi Serena , di Giacomo Viviana , Lanuti Paola , Catitti Giulia , Brocco Davide , di Rienzo Annalisa , Cataldi Amelia , Cacciatore Ivana , Amoroso Rosa , Cama Alessandro , De Lellis Laura
Published: January 2023

Pancreatic cancer (PC) is one of the deadliest malignancies, with an increasing incidence and limited response to current therapeutic options. Therefore, more effective and low-toxic agents are needed to improve PC patients’ outcomes. Resveratrol (RSV) is a natural polyphenol with multiple biological properties, including anticancer effects. In this study, we explored the antiproliferative activities of newly synthetized RSV analogues in a panel of PC cell lines and evaluated the physicochemical properties of the most active compound. This derivative exhibited marked antiproliferative effects in PC cells through mechanisms involving DNA damage, apoptosis induction, and interference in cell cycle progression, as assessed using flow cytometry and immunoblot analysis of cell cycle proteins, PARP cleavage, and H2AX phosphorylation. Notably, the compound induced a consistent reduction in the PC cell subpopulation with a CD133+EpCAM+ stem-like phenotype, paralleled by dramatic effects on cell clonogenicity. Moreover, the RSV derivative had negligible toxicity against normal HFF-1 cells and, thus, good selectivity index values toward PC cell lines. Remarkably, its higher lipophilicity and stability in human plasma, as compared to RSV, might ensure a better permeation along the gastrointestinal tract. Our results provide insights into the mechanisms of action contributing to the antiproliferative activity of a synthetic RSV analogue, supporting its potential value in the search for effective and safe agents in PC treatment.
The Role of Different Types of microRNA in the Pathogenesis of Breast and Prostate Cancer
Authors: Sidorova Ekaterina A. , Zhernov Yury V. , Antsupova Marina A. , Khadzhieva Kamilya R. , Izmailova Angelina A. , Kraskevich Denis A. , Belova Elena V. , Simanovsky Anton A. , Shcherbakov Denis V. , Zabroda Nadezhda N. , Mitrokhin Oleg V.
Published: January 2023

Micro ribonucleic acids (microRNAs or miRNAs) form a distinct subtype of non-coding RNA and are widely recognized as one of the most significant gene expression regulators in mammalian cells. Mechanistically, the regulation occurs through microRNA binding with its response elements in the 3’-untranslated region of target messenger RNAs (mRNAs), resulting in the post-transcriptional silencing of genes, expressing target mRNAs. Compared to small interfering RNAs, microRNAs have more complex regulatory patterns, making them suitable for fine-tuning gene expressions in different tissues. Dysregulation of microRNAs is well known as one of the causative factors in malignant cell growth. Today, there are numerous data points regarding microRNAs in different cancer transcriptomes, the specificity of microRNA expression changes in various tissues, and the predictive value of specific microRNAs as cancer biomarkers. Breast cancer (BCa) is the most common cancer in women worldwide and seriously impairs patients’ physical health. Its incidence has been predicted to rise further. Mounting evidence indicates that microRNAs play key roles in tumorigenesis and development. Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men. Different microRNAs play an important role in PCa. Early diagnosis of BCa and PCa using microRNAs is very useful for improving individual outcomes in the framework of predictive, preventive, and personalized (3P) medicine, thereby reducing the economic burden. This article reviews the roles of different types of microRNA in BCa and PCa progression.
Real-Time Impedance-Based Monitoring of the Growth and Inhibition of Osteomyelitis Biofilm Pathogen Staphylococcus aureus Treated with Novel Bisphosphonate-Fluoroquinolone Antimicrobial Conjugates
Authors: Sedghizadeh Parish P. , Cherian Philip , Roshandel Sahar , Tjokro Natalia , Chen Casey , Junka Adam F. , Hu Eric , Neighbors Jeffrey , Pawlak Jacek , Russell R. Graham G. , McKenna Charles E. , Ebetino Frank H. , Sun Shuting , Sodagar Esmat
Published: January 2023

Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.
The Endocannabinoid System and Physical Exercise
Authors: Matei Daniela , Trofin Dan , Iordan Daniel Andrei , Onu Ilie , Condurache Iustina , Ionite Catalin , Buculei Ioana
Published: January 2023

The endocannabinoid system (ECS) is involved in various processes, including brain plasticity, learning and memory, neuronal development, nociception, inflammation, appetite regulation, digestion, metabolism, energy balance, motility, and regulation of stress and emotions. Physical exercise (PE) is considered a valuable non-pharmacological therapy that is an immediately available and cost-effective method with a lot of health benefits, one of them being the activation of the endogenous cannabinoids. Endocannabinoids (eCBs) are generated as a response to high-intensity activities and can act as short-term circuit breakers, generating antinociceptive responses for a short and variable period of time. A runner’s high is an ephemeral feeling some sport practitioners experience during endurance activities, such as running. The release of eCBs during sustained physical exercise appears to be involved in triggering this phenomenon. The last decades have been characterized by an increased interest in this emotional state induced by exercise, as it is believed to alleviate pain, induce mild sedation, increase euphoric levels, and have anxiolytic effects. This review provides information about the current state of knowledge about endocannabinoids and physical effort and also an overview of the studies published in the specialized literature about this subject.
Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats
Authors: Sitzia Clementina , Vianello Elena , Dozio Elena , Kalousová Marta , Zima Tomáš , Brizzola Stefano , Roccabianca Paola , Tedeschi Gabriella , Lamont John , Tacchini Lorenza , Corsi-Romanelli Massimiliano Marco
Published: January 2023

Obesity is an epidemic condition linked to cardiovascular disease severity and mortality. Fat localization and type represent cardiovascular risk estimators. Importantly, visceral fat secretes adipokines known to promote low-grade inflammation that, in turn, modulate its secretome and cardiac metabolism. In this regard, IL-33 regulates the functions of various immune cells through ST2 binding and—following its role as an immune sensor to infection and stress—is involved in the pro-fibrotic remodeling of the myocardium. Here we further investigated the IL-33/ST2 effects on cardiac remodeling in obesity, focusing on molecular pathways linking adipose-derived IL-33 to the development of fibrosis or hypertrophy. We analyzed the Zucker Fatty rat model, and we developed in vitro models to mimic the adipose and myocardial relationship. We demonstrated a dysregulation of IL-33/ST2 signaling in both adipose and cardiac tissue, where they affected Epac proteins and myocardial gene expression, linked to pro-fibrotic signatures. In Zucker rats, pro-fibrotic effects were counteracted by ghrelin-induced IL-33 secretion, whose release influenced transcription factor expression and ST2 isoforms balance regulation. Finally, the effect of IL-33 signaling is dependent on several factors, such as cell types’ origin and the balancing of ST2 isoforms. Noteworthy, it is reasonable to state that considering IL-33 to have a unique protective role should be considered over-simplistic.
Glycolysis-Related Gene Analyses Indicate That DEPDC1 Promotes the Malignant Progression of Oral Squamous Cell Carcinoma via the WNT/β-Catenin Signaling Pathway
Authors: Huang Guangzhao , Chen Su , Washio Jumpei , Paka Lubamba Grace , Takahashi Nobuhiro , Li Chunjie
Published: January 2023

Increasing evidence suggests that aerobic glycolysis is related to the progression of oral squamous cell carcinoma (OSCC). Hence, we focused on glycolysis-related gene sets to screen for potential therapeutic targets for OSCC. The expression profiles of OSCC samples and normal controls were obtained from The Cancer Genome Atlas (TCGA). Then, the differentially expressed gene sets were selected from the official GSEA website following extraction of the differentially expressed core genes (DECGs). Subsequently, we tried to build a risk model on the basis of DECGs to predict the prognosis of OSCC patients via Cox regression analysis. Furthermore, crucial glycolysis-related genes were selected to explore their biological roles in OSCC. Two active glycolysis-related pathways were acquired and 66 DECGs were identified. Univariate Cox regression analysis showed that six genes, including HMMR, STC2, DDIT4, DEPDC1, SLC16A3, and AURKA, might be potential prognostic factors. Subsequently, a risk formula consisting of DEPDC1, DDIT4, and SLC16A3 was established on basis of the six molecules. Furthermore, DEPDC1 was proven to be related to advanced stage cancer and lymph node metastasis. Moreover, functional experiments suggested that DEPDC1 promoted the aerobic glycolysis, migration, and invasion of OSCC via the WNT/β-catenin pathway. The risk score according to glycolysis-related gene expression might be an independent prognostic factor in OSCC. In addition, DEPDC1 was identified as playing a carcinogenic role in OSCC progression, suggesting that DEPDC1 might be a novel biomarker and therapeutic target for OSCC.
Genome-Wide Identification of Kiwifruit SGR Family Members and Functional Characterization of SGR2 Protein for Chlorophyll Degradation
Authors: Luo Juan , Abid Muhammad , Zhang Yi , Cai Xinxia , Tu Jing , Gao Puxin , Wang Zupeng , Huang Hongwen
Published: January 2023

The STAY-GREEN (SGR) proteins play an important role in chlorophyll (Chl) degradation and are closely related to plant photosynthesis. However, the availability of inadequate studies on SGR motivated us to conduct a comprehensive study on the identification and functional dissection of SGR superfamily members in kiwifruit. Here, we identified five SGR genes for each of the kiwifruit species [Actinidia chinensis (Ac) and Actinidia eriantha (Ae)]. The phylogenetic analysis showed that the kiwifruit SGR superfamily members were divided into two subfamilies the SGR subfamily and the SGRL subfamily. The results of transcriptome data and RT-qPCR showed that the expression of the kiwifruit SGRs was closely related to light and plant developmental stages (regulated by plant growth regulators), which were further supported by the presence of light and the plant hormone-responsive cis-regulatory element in the promoter region. The subcellular localization analysis of the AcSGR2 protein confirmed its localization in the chloroplast. The Fv/Fm, SPAD value, and Chl contents were decreased in overexpressed AcSGR2, but varied in different cultivars of A. chinensis. The sequence analysis showed significant differences within AcSGR2 proteins. Our findings provide valuable insights into the characteristics and evolutionary patterns of SGR genes in kiwifruit, and shall assist kiwifruit breeders to enhance cultivar development.
Cabotegravir Exposure of Zebrafish (Danio rerio) Embryos Impacts on Neurodevelopment and Behavior
Authors: Zizioli Daniela , Zanella Isabella , Mignani Luca , Degli Antoni Melania , Castelli Francesco , Quiros-Roldan Eugenia
Published: January 2023

As most new medications, Cabotegravir (CAB) was recently approved as an antiretroviral treatment of HIV infection without in-depth safety information on in utero exposure. Although no developmental toxicity in rats and rabbits was reported, recent studies demonstrated that CAB decreases pluripotency of human embryonic stem cells. CAB exposure effects during development were assessed in zebrafish embryos by the Fish Embryo Toxicity test after exposure at subtherapeutic concentrations up to 25× the human Cmax. Larvae behavior was assessed by the light–dark locomotion test. The expression of factors involved in neurogenesis was evaluated by whole-mount in situ hybridization. CAB did not cause gross morphological defects at low doses, although pericardial edema, uninflated swim bladder, decreased heartbeats, growth delay, and decreased hatching rate were observed at the highest concentrations. Decreased locomotion was observed even at the subtherapeutic dose, suggesting alterations of nervous system integrity. This hypothesis was supported by the observation of decreased expression of crucial factors involved in early neuronal differentiation in diencephalic and telencephalic dopaminergic areas, midbrain/hindbrain boundary, and craniofacial ganglia. These findings support CAB effects on neurogenesis in zebrafish embryos and suggest long-term follow-up of exposed infants to provide data on drug safety during pregnancy.
Coordinated Loss and Acquisition of NK Cell Surface Markers Accompanied by Generalized Cytokine Dysregulation in COVID-19
Authors: Ustiuzhanina Maria O. , Vavilova Julia D. , Boyko Anna A. , Streltsova Maria A. , Kust Sofya A. , Kanevskiy Leonid M. , Sapozhnikov Alexander M. , Iskhakov Rustam N. , Gubernatorova Ekaterina O. , Drutskaya Marina S. , Bychinin Mikhail V. , Zhukova Oksana A. , Novikova Oksana N. , Sotnikova Anna G. , Yusubalieva Gaukhar M. , Baklaushev Vladimir P. , Kovalenko Elena I.
Published: January 2023

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is accompanied by a dysregulated immune response. In particular, NK cells, involved in the antiviral response, are affected by the infection. This study aimed to investigate circulating NK cells with a focus on their activation, depletion, changes in the surface expression of key receptors, and functional activity during COVID-19, among intensive care unit (ICU) patients, moderately ill patients, and convalescents (CCP). Our data confirmed that NK cell activation in patients with COVID-19 is accompanied by changes in circulating cytokines. The progression of COVID-19 was associated with a coordinated decrease in the proportion of NKG2D+ and CD16+ NK cells, and an increase in PD-1, which indicated their exhaustion. A higher content of NKG2D+ NK cells distinguished surviving patients from non-survivors in the ICU group. NK cell exhaustion in ICU patients was additionally confirmed by a strong negative correlation of PD-1 and natural cytotoxicity levels. In moderately ill patients and convalescents, correlations were found between the levels of CD57, NKG2C, and NKp30, which may indicate the formation of adaptive NK cells. A reduced NKp30 level was observed in patients with a lethal outcome. Altogether, the phenotypic changes in circulating NK cells of COVID-19 patients suggest that the intense activation of NK cells during SARS-CoV-2 infection, most likely induced by cytokines, is accompanied by NK cell exhaustion, the extent of which may be critical for the disease outcome.
Long-Term Cultured Human Glioblastoma Multiforme Cells Demonstrate Increased Radiosensitivity and Senescence-Associated Secretory Phenotype in Response to Irradiation
Authors: Alhaddad Lina , Nofal Zain , Pustovalova Margarita , Osipov Andreyan N. , Leonov Sergey
Published: January 2023

The overall effect of senescence on cancer progression and cancer cell resistance to X-ray radiation (IR) is still not fully understood and remains controversial. How to induce tumor cell senescence and which senescent cell characteristics will ensure the safest therapeutic strategy for cancer treatment are under extensive investigation. While the evidence for passage number-related effects on malignant primary cells or cell lines is compelling, much less is known about how the changes affect safety and Senescence-Associated Secretory Phenotype (SASP), both of which are needed for the senescence cell-based vaccine to be effective against cancer. The present study aimed to investigate the effects of repeated passaging on the biological (self-renewal capacity and radioresistance) and functional (senescence) characteristics of the different populations of short- and long-term passaging glioblastoma multiforme (GBM) cells responding to senescence-inducing DNA-damaging IR stress. For this purpose, we compared radiobiological effects of X-ray exposure on two isogenic human U87 cell lines: U87L, minimally cultured cells (<15 passages after obtaining from the ATCC) and U87H, long-term cultured cells (>3 years of continuous culturing after obtaining from the ATCC). U87L cells displayed IR dose-related changes in the signs of IR stress-induced premature senescence. These included an increase in the proportion of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, and concomitant decrease in the proportion of Ki67-positive cells and metabolically active cells. However, reproductive survival of irradiated short-term cultured U87L cells was higher compared to long-term cultured U87H cells, as the clonogenic activity results demonstrated. In contrast, the irradiated long-term cultured U87H cells possessed dose-related increases in the proportion of multinucleated giant cancer cells (MGCCs), while demonstrating higher radiosensitivity (lower self-renewal) and a significantly reduced fraction of DNA-replicating cells compared to short-term cultured U87L cells. Conditioned culture medium from U87H cells induced a significant rise of SA-β-Gal staining in U87L cells in a paracrine manner suggesting inherent SASP. Our data suggested that low-dose irradiated long-term cultured GBM cells might be a safer candidate for a recently proposed senescence cell-based vaccine against cancer.
Non-Coding RNAs in Pulmonary Diseases: Comparison of Different Airway-Derived Biosamples
Authors: Stachowiak Zuzanna , Narożna Beata , Szczepankiewicz Aleksandra
Published: January 2023

Due to their structural conservation and functional role in critical signalling pathways, non-coding RNA (ncRNA) is a promising biomarker and modulator of pathological conditions. Most research has focussed on the role of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These molecules have been investigated both in a cellular and an extracellular context. Sources of ncRNAs may include organ-specific body fluids. Therefore, studies on ncRNAs in respiratory diseases include those on sputum, bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC). It is worth identifying the limitations of these biosamples in terms of ncRNA abundance, processing and diagnostic potential. This review describes the progress in the literature on the role of ncRNAs in the pathogenesis and progression of severe respiratory diseases, including cystic fibrosis, asthma and interstitial lung disease. We showed that there is a deficit of information on lncRNAs and circRNAs in selected diseases, despite attempts to functionally bind them to miRNAs. miRNAs remain the most well-studied, but only a few investigations have been conducted on the least invasive biosample material, i.e., EBC. To summarise the studies conducted to date, we also performed a preliminary in silico analysis of the reported miRNAs, demonstrating the complexity of their role and interactions in selected respiratory diseases.
Impact of Anti-IL5 Therapies on Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study
Authors: Rojo-Tolosa Susana , González-Gutiérrez María Victoria , Jiménez-Gálvez Gonzalo , Sánchez-Martínez José Antonio , Pineda-Lancheros Laura Elena , Gálvez-Navas José María , Jiménez-Morales Alberto , Pérez-Ramírez Cristina , Morales-García Concepción
Published: January 2023

Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies (p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.
Artificial Neural Networks for Flexible Pavement
Authors: Bayat Ramin , Talatahari Siamak , Gandomi Amir H. , Habibi Mohammadreza , Aminnejad Babak
Published: January 2023

Transportation agencies are primarily responsible for building new roads and maintaining current roads. The main focuses of these agencies are to prioritize maintenance and make significant rehabilitation decisions to handle serious problems facing road authorities. Considerable efforts and an abundance of studies have been performed to determine the nature, mechanisms, test methods, and measurement of pavements for preservation and improvements of roadways. The presented study reports a state-of-the-art review on recent advances in the application of artificial intelligence in various steps of flexible pavement, including pavement construction, performance, cost, and maintenance. Herein, the challenges of gathering large amounts of data, parameter optimization, portability, and low-cost data annotating are discussed. According to the findings, it is suggested that greater attention should be paid to integrating multidisciplinary roadway engineering techniques to address existing challenges and opportunities in the future.
Insect Cell-Based Models: Cell Line Establishment and Application in Insecticide Screening and Toxicology Research
Authors: He Xuan , Lu Lidan , Huang Ping , Yu Bo , Peng Lianxin , Zou Liang , Ren Yuanhang
Published: January 2023

During the past decades, research on insect cell culture has grown tremendously. Thousands of lines have been established from different species of insect orders, originating from several tissue sources. These cell lines have often been employed in insect science research. In particular, they have played important roles in pest management, where they have been used as tools to evaluate the activity and explore the toxic mechanisms of insecticide candidate compounds. This review intends to first briefly summarize the progression of insect cell line establishment. Then, several recent studies based on insect cell lines coupled with advanced technologies are introduced. These investigations revealed that insect cell lines can be exploited as novel models with unique advantages such as increased efficiency and reduced cost compared with traditional insecticide research. Most notably, the insect cell line-based models provide a global and in-depth perspective to study the toxicology mechanisms of insecticides. However, challenges and limitations still exist, especially in the connection between in vitro activity and in vivo effectiveness. Despite all this, recent advances have suggested that insect cell line-based models promote the progress and sensible application of insecticides, which benefits pest management.
Investigation of BaFe12O19 Hexaferrites Manufactured by Various Synthesis Methods Using a Developed Pulsed Magnetometer
Authors: Wagner Dmitry V. , Kareva Katerina V. , Zhuravlev Viktor A. , Dotsenko Olga A. , Minin Roman V.
Published: January 2023

The manufacture and study of the properties of magnetic materials requires the development of new automated devices for measuring their magnetic properties. To obtain nanosized materials with a pure phase, it is necessary to modernize former methods and develop new methods for synthesizing materials. As part of this study, a pulse magnetometer was made to study magnetic hysteresis loops. An exceptional feature of this device is the ability to conduct studies of the full cycle of the hysteresis loop using pulsed magnetic fields. M-type BaFe12O19 hexagonal ferrites were synthesized by standard ceramic, mechanochemical, and sol–gel methods. The structural, phase, and magnetic characteristics of the barium hexaferrites were studied. Methods for the synthesis of BaFe12O19 hexagonal ferrites were estimated and compared. Their structural and magnetic properties essentially depend on the method of synthesis. The mechanochemical technology makes it possible to obtain materials without impurity phases through the use of hydrated reagents in the synthesis. The use of sol–gel technology allows the synthesis to be carried out at much lower temperatures.
The Regulations of Essential WalRK Two-Component System on Enterococcus faecalis
Authors: Zhang Junqi , Fang Rong , Peng Qi , Wu Shizhou , Lei Lei
Published: January 2023

Enterococcus faecalis (E. faecalis) is a Gram-positive, facultative anaerobic bacterium that is highly adaptable to its environment. In humans, it can cause serious infections with biofilm formation. With increasing attention on its health threat, prevention and control of biofilm formation in E. faecalis have been observed. Many factors including polysaccharides as well as autolysis, proteases, and eDNA regulate biofilm formation. Those contributors are regulated by several important regulatory systems involving the two-component signal transduction system (TCS) for its adaptation to the environment. Highly conserved WalRK as one of 17 TCSs is the only essential TCS in E. faecalis. In addition to biofilm formation, various metabolisms, including cell wall construction, drug resistance, as well as interactions among regulatory systems and resistance to the host immune system, can be modulated by the WalRK system. Therefore, WalRK has been identified as a key target for E. faecalis infection control. In the present review, the regulation of WalRK on E. faecalis pathogenesis and associated therapeutic strategies are demonstrated.
Orthodontic Treatment Does Not Affect Frontal Sinus Development in Female Adults: A Clinical Study
Authors: Sawada Masaki , Suetake Saya , Yamada Hiroshi , Higashino Masaaki , Abe Susumu , Tanaka Eiji
Published: January 2023

Frontal sinus growth is gradual and lasts until post-puberty. However, the influence of biomechanical stimuli, such as orthodontic treatment, on frontal sinus development after the growth period has ended remains unclear. This study was designed to elucidate the impact of orthodontic treatment on the frontal sinus morphology of adult females. Sixty women were included and divided into three groups, based on the Frankfort mandibular plane angle. All participants underwent computed tomography and lateral cephalometry before and after treatment. Although two participants exhibited frontal sinus agenesis, most exhibited a bilaterally symmetric frontal sinus without fusion. The frontal sinus width and height were almost similar, irrespective of the vertical skeletal pattern, where the frontal sinus depth was significantly larger in the average mandibular plane angle group than in the low- and high-angle groups. Furthermore, the sinus volume in the low-angle group was likely smaller than that in the average and high-angle groups. On comparing pre-treatment and post-treatment measurements, minimal or no changes to the frontal sinus dimension were detected after treatment. In conclusion, orthodontic treatment did not affect frontal sinus development after the end of growth.
Acknowledgment to the Reviewers of JCM in 2022
Authors:   JCM Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Pregnancy Outcomes in Women after the Fontan Procedure
Authors: Bartczak-Rutkowska Agnieszka , Tomkiewicz-Pająk Lidia , Kawka-Paciorkowska Katarzyna , Bajorek Natalia , Ciepłucha Aleksandra , Ropacka-Lesiak Mariola , Trojnarska Olga
Published: January 2023

Women with single ventricle physiology after the Fontan procedure, despite numerous possible complications, can reach adulthood and give birth. Pregnancy poses a hemodynamic burden for distorted physiology of Fontan circulation, but according to the literature, it is usually well tolerated unless the patient is a “failing” Fontan. Our study aimed to assess maternal and fetal outcomes in patients after the Fontan procedure followed up in two tertiary Polish medical centers. We retrospectively evaluated all pregnancies in women after the Fontan procedure who were followed up between 1995–2022. During the study period, 15 women after the Fontan procedure had 26 pregnancies. Among 26 pregnancies, eleven ended with miscarriages, and 15 pregnancies resulted in 16 live births. Fetal complications were observed in 9 (56.3%) live births, with prematurity being the most common complication (n = 7, 43.8%). We recorded 3 (18.8%) neonatal deaths. Obstetrical complications were present in 6 (40%) out of 15 completed pregnancies—two (13.3%) cases of abruptio placentae, two (13.3%) pregnancies with premature rupture of membranes, and two (13.3%) patients with antepartum hemorrhage. There was neither maternal death nor heart failure decompensation during pregnancy. In two (13.3%) women, atrial arrhythmia developed. One (6.7%) patient in the second trimester developed ventricular arrhythmia. None of the patients suffered from systemic thromboembolism during pregnancy. Pregnancy in women after the Fontan procedure is well tolerated. However, it is burdened by a high risk of miscarriage and multiple obstetrical complications. These women require specialized care provided by both experienced cardiologists and obstetricians.
Building Blocks for Deep Phenotyping in Infancy: A Use Case Comparing Spontaneous Neuromotor Functions in Prader-Willi Syndrome and Cerebral Palsy
Authors: Marschik-Zhang Dajie , Wang Jun , Shen Xiushu , Zhu Xiaoyun , Gao Herong , Yang Hong , Marschik Peter B.
Published: January 2023

With the increasing worldwide application of the Prechtl general movements assessment (GMA) beyond its original field of the early prediction of cerebral palsy (CP), substantial knowledge has been gained on early neuromotor repertoires across a broad spectrum of diagnostic groups. Here, we aimed to profile the neuromotor functions of infants with Prader-Willi syndrome (PWS) and to compare them with two other matched groups. One group included infants with CP; the other included patients who were treated at the same clinic and turned out to have inconspicuous developmental outcomes (IOs). The detailed GMA, i.e., the motor optimality score-revised (MOS-R), was used to prospectively assess the infants’ (N = 54) movements. We underwent cross-condition comparisons to characterise both within-group similarities and variations and between-group distinctions and overlaps in infants’ neuromotor functions. Although infants in both the PWS and the CP groups scored similarly low on MOS-R, their motor patterns were different. Frog-leg and mantis-hand postures were frequently seen in the PWS group. However, a PWS-specific general movements pattern was not observed. We highlight that pursuing in-depth knowledge within and beyond the motor domain in different groups has the potential to better understand different conditions, improve accurate diagnosis and individualised therapy, and contribute to deep phenotyping for precision medicine.