bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherens Junction Integrity Is a Critical Determinant of Sodium Iodide Symporter Residency at the Plasma Membrane of Thyroid Cells
Authors: Faria Márcia , Vareda José , Miranda Micaella , Bugalho Maria João , Silva Ana Luísa , Matos Paulo
Published: November 2022

While most cases of differentiated thyroid carcinoma (DTC) are associated with a good prognosis, a significant number progress to advanced disease exhibiting aggressive clinical characteristics and often becoming refractory to radioactive iodine (RAI) treatment, the current gold-standard therapeutic option for metastatic disease. RAI-refractoriness is caused by defective functional expression of the sodium-iodide symporter (NIS), which is responsible for the active transport of iodide across the plasma membrane (PM) into thyroid follicles. NIS deficiency in these tumors often reflects a transcriptional impairment, but also its defective targeting and retention at the cells’ PM. Using proteomics, we previously characterized an intracellular signaling pathway derived from SRC kinase that acts through the small GTPase RAC1 to recruit and bind the actin-anchoring adaptor EZRIN to NIS, regulating its retention at the PM of both non-transformed and cancer thyroid cells. Here, we describe how by reanalyzing the proteomics data, we identified cell–cell adhesion as the molecular event upstream the pathway involved in the anchoring and retention at the PM. We show that by interacting with NIS at the PM, adherens junction (AJ)-associated P120-catenin recruits and is phosphorylated by SRC, allowing it to recruit RAC1 to the complex. This enables SRC-phosphorylated VAV2 exchange factor to activate RAC1 GTPase, inducing NIS retention at the PM, thus increasing its abundance and function at the surface of thyroid cells. Our findings indicate that the loss of epithelial cell–cell adhesion may contribute to RAI refractoriness, indicating that in addition to stimulating NIS expression, successful resensitization therapies might require the employment of agents that improve cell–cell adhesion and NIS PM retention in refractory TC cells.
Electroporation in Head-and-Neck Cancer: An Innovative Approach with Immunotherapy and Nanotechnology Combination
Authors: Pisani Silvia , Bertino Giulia , Prina-Mello Adriele , Locati Laura Deborah , Mauramati Simone , Genta Ida , Dorati Rossella , Conti Bice , Benazzo Marco
Published: November 2022

Squamous cell carcinoma is the most common malignancy that arises in the head-and-neck district. Traditional treatment could be insufficient in case of recurrent and/or metastatic cancers; for this reason, more selective and enhanced treatments are in evaluation in preclinical and clinical trials to increase in situ concentration of chemotherapy drugs promoting a selectively antineoplastic activity. Among all cancer treatment types (i.e., surgery, chemotherapy, radiotherapy), electroporation (EP) has emerged as a safe, less invasive, and effective approach for cancer treatment. Reversible EP, using an intensive electric stimulus (i.e., 1000 V/cm) applied for a short time (i.e., 100 μs), determines a localized electric field that temporarily permealizes the tumor cell membranes while maintaining high cell viability, promoting cytoplasm cell uptake of antineoplastic agents such as bleomycin and cisplatin (electrochemotherapy), calcium (Ca2+ electroporation), siRNA and plasmid DNA (gene electroporation). The higher intracellular concentration of antineoplastic agents enhances the antineoplastic activity and promotes controlled tumor cell death (apoptosis). As secondary effects, localized EP (i) reduces the capillary blood flow in tumor tissue (“vascular lock”), lowering drug washout, and (ii) stimulates the immune system acting against cancer cells. After years of preclinical development, electrochemotherapy (ECT), in combination with bleomycin or cisplatin, is currently one of the most effective treatments used for cutaneous metastases and primary skin and mucosal cancers that are not amenable to surgery. To reach this clinical evidence, in vitro and in vivo models were preclinically developed for evaluating the efficacy and safety of ECT on different tumor cell lines and animal models to optimize dose and administration routes of drugs, duration, and intensity of the electric field. Improvements in reversible EP efficacy are under evaluation for HNSCC treatment, where the focus is on the development of a combination treatment between EP-enhanced nanotechnology and immunotherapy strategies.
Cell-Free DNA Analysis within the Challenges of Thyroid Cancer Management
Authors: Marotta Vincenzo , Cennamo Michele , La Civita Evelina , Vitale Mario , Terracciano Daniela
Published: November 2022

Thyroid cancer is the most frequent endocrine malignancy with an increasing incidence trend during the past forty years and a concomitant rise in cancer-related mortality. The circulating cell-free DNA (cfDNA) analysis is a patient’s friendly and repeatable procedure allowing to obtain surrogate information about the genetics and epigenetics of the tumor. The aim of the present review was to address the suitability of cfDNA testing in different forms of thyroid cancer, and the potential clinical applications, as referred to the clinical weaknesses. Despite being limited by the absence of standardization and by reproducibility and validity issues, cfDNA assessment has great potential for the improvement of thyroid cancer management. cfDNA may support the pre-surgical definition of thyroid nodules by complementing invasive thyroid fine needle aspiration cytology. In addition, it may empower risk stratification and could be used as a biomarker for monitoring the post-surgical disease status, both during active surveillance and in the case of anti-tumor treatment.
Luteolin, a Potent Anticancer Compound: From Chemistry to Cellular Interactions and Synergetic Perspectives
Authors: Singh Tuli Hardeep , Rath Prangya , Chauhan Abhishek , Sak Katrin , Aggarwal Diwakar , Choudhary Renuka , Sharma Ujjawal , Vashishth Kanupriya , Sharma Sheetu , Kumar Manoj , Yadav Vikas , Singh Tejveer , Yerer Mukerrem Betul , Haque Shafiul
Published: November 2022

Increasing rates of cancer incidence and the toxicity concerns of existing chemotherapeutic agents have intensified the research to explore more alternative routes to combat tumor. Luteolin, a flavone found in numerous fruits, vegetables, and herbs, has exhibited a number of biological activities, such as anticancer and anti-inflammatory. Luteolin inhibits tumor growth by targeting cellular processes such as apoptosis, cell-cycle progression, angiogenesis and migration. Mechanistically, luteolin causes cell death by downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, Bcl-2, and Bcl-xL, while upregulating BAX, caspase-3, and p21. It has also been reported to inhibit STAT3 signaling by the suppression of STAT3 activation and enhanced STAT3 protein degradation in various cancer cells. Therefore, extensive studies on the anticancer properties of luteolin reveal its promising role in chemoprevention. The present review describes all the possible cellular interactions of luteolin in cancer, along with its synergistic mode of action and nanodelivery insight.
Liquid Biopsy in Cancer: Focus on Lymphoproliferative Disorders
Authors: Savino Francesco D. , Rigali Fabio , Giustini Viviana , D’Aliberti Deborah , Spinelli Silvia , Piazza Rocco , Sacco Antonio , Roccaro Aldo M.
Published: November 2022

Within the context of precision medicine, the scientific community is giving particular attention to early diagnosis and intervention, guided by non-invasive methodologies. Liquid biopsy (LBx) is a recent laboratory approach consisting of a non-invasive blood draw, which allows the detection of information about potential prognostic factors, or markers to be used for diagnostic purposes; it might also allow the clinician to establish a treatment regimen and predict a patient’s response. Since the discovery of circulating tumor cells (CTCs) in the nineteenth century, the possibility of integrating LBx into clinical practice has been explored, primarily because of its safeness and easy execution: indeed, compared to solid biopsy, sampling-related risks are less of a concern, and the quickness and repeatability of the process could help confirm a prompt diagnosis or to further corroborate the existence of a metastatic spreading of the disease. LBx’s usefulness has been consolidated in a narrow range of oncological settings, first of all, non-small cell lung carcinoma (NSCLC), and it is now gradually being assessed also in lymphoproliferative diseases, such as acute lymphocytic leukemia (ALL), B-cell lymphomas, and multiple myeloma. The present review aims to summarize LBx’s overall characteristics (such as its advantages and flaws, collection and analysis methodologies, indications, and targets of the test), and to highlight the applications of this technique within the specific field of B-cell malignancies. The perspectives on how such a simple and convenient technique could improve hemato-oncological clinical practice are broadly encouraging, yet far from a complete integration in routine clinical settings.
IGF2BP2 Promotes Epithelial to Mesenchymal Transition and Metastasis through Stabilizing HMGA1 mRNA in Gastric Cancer
Authors: Ouyang Jun , Li Junqing , Li Dongwei , Jiang Jianlong , Hao Tengfei , Xia Yujian , Lu Xiaofang , Zhang Changhua , He Yulong
Published: November 2022

As an RNA-binding protein, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is involved in enhancing the progression of a few malignant tumors by recognizing N6-methyladenosine on targeted RNA. However, the specific effects of IGF2BP2 on gastric cancer (GC) and the underlying mechanisms remain unclear. In this study, the expression level of IGF2BP2 was evaluated by analyzing data from a public database and performing immunohistochemical staining with GC specimens. The effect of IGF2BP2 on GC cell metastasis was investigated by Transwell assays and animal studies. RNA immunoprecipitation (RIP) was performed to identify potential mRNA bound to IGF2BP2. The levels of these identified RNAs were measured by RT-PCR, while corresponding proteins were quantified via Western blot. It was revealed that IGF2BP2 expression in GC tissues was significantly upregulated, and its overexpression was significantly associated with worse survival in GC patients. The aberrant expression of IGF2BP2 was demonstrated to promote the invasion and metastasis of GC cells by both in vivo and in vitro experiments. In subsequent experiments, it was then verified that by directly interacting with HMGA1 mRNA, IGF2BP2 augmented its stability and thus increased its expression. The knocking down of IGF2BP2 could significantly decrease the migration and invasion of GC cells, which could be reversed by increasing HMGA1 expression. Additionally, both in vitro and in vivo epithelial–mesenchymal transition (EMT) of GC cells were enhanced by IGF2BP2/HMGA1 axis. In conclusion, it was proven in our study that the IGF2BP2/HMGA1/EMT axis contributed to GC metastasis, suggesting its potential as a novel predictive and therapeutic biomarker for GC.
Artificial Intelligence-Driven Diagnosis of Pancreatic Cancer
Authors: Hameed Bahrudeen Shahul , Krishnan Uma Maheswari
Published: November 2022

Pancreatic cancer is among the most challenging forms of cancer to treat, owing to its late diagnosis and aggressive nature that reduces the survival rate drastically. Pancreatic cancer diagnosis has been primarily based on imaging, but the current state-of-the-art imaging provides a poor prognosis, thus limiting clinicians’ treatment options. The advancement of a cancer diagnosis has been enhanced through the integration of artificial intelligence and imaging modalities to make better clinical decisions. In this review, we examine how AI models can improve the diagnosis of pancreatic cancer using different imaging modalities along with a discussion on the emerging trends in an AI-driven diagnosis, based on cytopathology and serological markers. Ethical concerns regarding the use of these tools have also been discussed.
Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives
Authors: Svajdova Michaela , Dubinsky Pavol , Kazda Tomas , Jeremic Branislav
Published: November 2022

Over the last two decades, human papillomavirus (HPV) has caused a new pandemic of cancer in many urban areas across the world. The new entity, HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), has been at the center of scientific attention ever since, not only due to its distinct biological behavior, but also because of its significantly better prognosis than observed in its HPV-negative counterpart. The very good treatment outcomes of the disease after primary therapy (minimally-invasive surgery, radiation therapy with or without chemotherapy) resulted in the creation of a separate staging system, reflecting this excellent prognosis. A substantial proportion of newly diagnosed HPV-driven OPSCC is diagnosed in stage I or II, where long-term survival is observed worldwide. Deintensification of the primary therapeutic methods, aiming at a reduction of long-term toxicity in survivors, has emerged, and the quality of life of the patient after treatment has become a key-point in many clinical trials. Current treatment recommendations for the treatment of HPV-driven OPSCC do not differ significantly from HPV-negative OPSCC; however, the results of randomized trials are eagerly awaited and deemed necessary, in order to include deintensification into standard clinical practice.
Catalytic Wood Fractionation into Chemicals in Supercritical Ethanol and n-Heptane: Potential and Limitations
Authors: Eternot Marion , Essayem Nadine
Published: November 2022

Direct selective wood fractionation into chemicals is an approach that has attracted recent attention. The application of sub- and supercritical (SC) alcohols to fractionate wood into solid cellulose and liquefy phenolic monomers is a process now widely known as “lignin first”. It is justified to study the potential of other SC organic solvents of variable polarities. Herein, we compare the abilities of SC ethanol and SC n-heptane to fractionate pine wood near their critical point. While near-critical ethanol has more affinity for lignin fraction, we show that near-critical n-heptane has preference for carbohydrate deconstruction. If SC ethanol favors biooil formation which contains important ethyl/ethoxy groups, the alkane greatly favors solid carbon products. The impact of addition of heterogeneous catalysts (acid, basic and Cu-based catalysts) on wood fractionation and light chemicals formation was investigated deeply in SC ethanol. In SC ethanol, catalysts favor light liquid products such as esters at the expense of biooil with a total oxygenates yield of 33 wt% relative to carbohydrates over β zeolite. However, we show that depending on the catalysts’ nature, wood components fractionation was completely changed, and this is particularly true with solid acid catalysts which promote cellulose deconstruction and the formation of solid carbon products. It is proposed that liquid products’ accumulation in the autoclave, in particular water, is at the origin of the wood fractionation changes which preclude its control by the choice of the SC organic solvent and conditions. Moreover, all the catalysts underwent severe leaching, which also contributed to the wood component fractionation changes.
Construction and Evaluation of a Risk Score Model for Lymph Node Metastasis-Associated Circadian Clock Genes in Esophageal Squamous Carcinoma
Authors: Cheng Jian , Chen Fang , Cheng Yufeng
Published: November 2022

Background: Studies suggested that circadian clock genes (CCGs) in human esophageal squamous carcinoma (ESCC) samples are dysregulated. However, the relevance of CCGs to lymph node metastasis (LNM) and prognosis of ESCC remains unclear. Methods: The differentially expressed genes (DEGs) between normal and ESCC samples in The Cancer Genome Atlas database (TCGA) database were intersected with the genes associated with LNM (LNMGs) in ESCC samples and 300 CCGs to obtain the differentially expressed LNM-associated CCGs (DE-LNM-CCGs). The risk model was constructed by Cox regression analysis in the TCGA-ESCC training set, and the accuracy of the risk model was verified by risk profile and overall survival profile. Furthermore, differences of 23 immune cells, 13 immune functions, and immune checkpoint molecules between the high- and low-risk groups were assessed using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Gene set enrichment analysis (GSEA) was conducted to investigate the functional differences between low- and high-risk groups. Finally, we validated the mRNA expression levels of prognostic model genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of six DE-LNM-CCGs were identified in TCGA-ESCC. TP53 and NAGLU were selected by Cox regression analysis to construct the risk model. Risk profile plots, overall survival plots, and validation results of the risk model in the validation set indicated that the constructed risk model was reliable. The result of ssGSEA showed that the percentages of activated B cells, activated dendritic cells, effector memory CD8 T cells, immune function in neutrophils, plasmacytoid dendritic cells, T cell co-inhibition, and Type 17 T helper cells were different between the high- and low-risk groups. In addition, the expression of CD274, PDCD1, TNFRSF18, and TNFRSF9 was dysregulated between the high- and low-risk groups. GSEA revealed that the high-risk group was associated with cell differentiation, oxidative phosphorylation, and steroid biosynthesis pathways, while the low-risk group was associated with chromosome, ECM–receptor interaction, and other pathways. Finally, qRT-PCR results showed that the mRNA expression levels of two prognostic genes were consistent with TCGA. Conclusion: In conclusion, the risk model constructed based on TP53 and NAGLU could accurately predict the prognosis.
A Novel P53 Nanomedicine Reduces Immunosuppression and Augments Anti-PD-1 Therapy for Non-Small Cell Lung Cancer in Syngeneic Mouse Models
Authors: Kim Sang-Soo , Harford Joe B. , Moghe Manish , Doherty Caroline , Chang Esther H.
Published: November 2022

Lung cancer is among the most common and lethal cancers and warrants novel therapeutic approaches to improving patient outcomes. Although immune checkpoint inhibitors (ICIs) have demonstrated substantial clinical benefits, most patients remain unresponsive to currently approved ICIs or develop resistance after initial response. Many ongoing clinical studies are investigating combination therapies to address the limited efficacy of ICIs. Here, we have assessed whether p53 gene therapy via a tumor-targeting nanomedicine (termed SGT-53) can augment anti-programmed cell death-1 (PD-1) immunotherapy to expand its use in non-responding patients. Using syngeneic mouse models of lung cancers that are resistant to anti-PD-1, we demonstrate that restoration of normal p53 function potentiates anti-PD-1 to inhibit tumor growth and prolong survival of tumor-bearing animals. Our data indicate that SGT-53 can restore effective immune responses against lung cancer cells by reducing immuno-suppressive cells (M2 macrophages and regulatory T cells) and by downregulating immunosuppressive molecules (e.g., galectin-1, a negative regulator of T cell activation and survival) while increasing activity of cytotoxic T cells. These results suggest that combining SGT-53 with anti-PD-1 immunotherapy could increase the fraction of lung cancer patients that responds to anti-PD-1 therapy and support evaluation of this combination particularly in patients with ICI-resistant lung cancers.
Mitochondria-Targeted Antioxidant SkQ1 Prevents the Development of Experimental Colitis in Mice and Impairment of the Barrier Function of the Intestinal Epithelium
Authors: Fedorov Artem V. , Chelombitko Maria A. , Chernyavskij Daniil A. , Galkin Ivan I. , Pletjushkina Olga Yu. , Vasilieva Tamara V. , Zinovkin Roman A. , Chernyak Boris V.
Published: November 2022

Mitochondria-targeted antioxidants have become promising candidates for the therapy of various pathologies. The mitochondria-targeted antioxidant SkQ1, which is a derivative of plastoquinone, has been successfully used in preclinical studies for the treatment of cardiovascular and renal diseases, and has demonstrated anti-inflammatory activity in a number of inflammatory disease models. The present work aimed to investigate the therapeutic potential of SkQ1 and C12TPP, the analog of SkQ1 lacking the antioxidant quinone moiety, in the prevention of sodium dextran sulfate (DSS) experimental colitis and impairment of the barrier function of the intestinal epithelium in mice. DSS-treated animals exhibited weight loss, bloody stool, dysfunction of the intestinal epithelium barrier (which was observed using FITC-dextran permeability), reduced colon length, and histopathological changes in the colon mucosa. SkQ1 prevented the development of clinical and histological changes in DSS-treated mice. SkQ1 also reduced mRNA expression of pro-inflammatory molecules TNF, IL-6, IL-1β, and ICAM-1 in the proximal colon compared with DSS-treated animals. SkQ1 prevented DSS-induced tight junction disassembly in Caco-2 cells. Pretreatment of mice by C12TPP did not protect against DSS-induced colitis. Furthermore, C12TPP did not prevent DSS-induced tight junction disassembly in Caco-2 cells. Our results suggest that SkQ1 may be a promising therapeutic agent for the treatment of inflammatory bowel diseases, in particular ulcerative colitis.
Cellular Senescence in Metabolic-Associated Kidney Disease: An Update
Authors: Gao Pan , Zou Xingjian , Sun Xin , Zhang Chun
Published: November 2022

Cellular senescence is described as the state where the cell cycle is arrested irreversibly, which occurs in response to various forms of stress factors in cells, leading to the senescence-associated secretory phenotype (SASP). We can assess the accumulation of senescent cells in tissues or organs through biomarkers of cellular senescence such as p16INK4a, p53, p21, and SA-β-GAL. In recent decades, a large number of studies have reported the biomarkers of increased cell senescence in pathogenic tissues, demonstrating the possible connection between cell senescence and various diseases. Kidney damage often occurs in the pathophysiological process of certain metabolic diseases, resulting in metabolic-associated kidney diseases. For example, hypertension causes systemic arteriosclerosis, and the kidney can be seriously affected by abundant blood vessels, which may lead to a decreased glomerular filtration rate (GFR) and proteinuria, resulting in hypertension-related kidney diseases. The accumulation of senescent cells may also be observed in some metabolic-associated kidney diseases (such as obesity-related nephropathy, hypertension-related nephropathy, and diabetic nephropathy). In this paper, we review existing knowledge regarding the influence of cellular senescence on metabolic-associated kidney diseases, providing new ideas for future treatment.
The Role of HSP90 Inhibitors in the Treatment of Cardiovascular Diseases
Authors: Qi Shiyu , Yi Guang , Yu Kun , Feng Chong , Deng Shoulong
Published: November 2022

Cardiovascular disease is the result of complicated pathophysiological processes in the tissues that make up the blood vessels and heart. Heat shock protein 90 (HSP90) can interact with 10% of the proteome and is the most widely studied molecular chaperone in recent years. HSP90 is extensively involved in the regulation of protein folding and intracellular protein stability, making HSP90 a hopeful target for the treatment of multiple cardiovascular diseases. Numerous client proteins of HSP90 have been identified in known cardiac disease pathways, including MAPK signaling, PI3K/AKT (PKB)/mTOR, and TNF-α signaling. Therefore, these pathways can be controlled by regulating HSP90. Among them, the activity of HSP90 can be regulated via numerous inhibitors. In this review, first, we will discuss the function of HSP90 and its role in pathological pathways. In addition, HSP90 plays a significant role in most cardiovascular diseases, including hypertension, pulmonary venous hypertension, atherosclerosis, and heart failure; next we will focus on this part. Finally, we will summarize the currently known HSP90 inhibitors and their potential in the treatment of heart disease.
Phenotypical and Functional Alteration of γδ T Lymphocytes in COVID-19 Patients: Reversal by Statins
Authors: Di Simone Marta , Corsale Anna Maria , Lo Presti Elena , Scichilone Nicola , Picone Carmela , Giannitrapani Lydia , Dieli Francesco , Meraviglia Serena
Published: November 2022

(1) Background: statins have been considered an attractive class of drugs in the pharmacological setting of COVID-19 due to their pleiotropic properties and their use correlates with decreased mortality in hospitalized COVID-19 patients. Furthermore, it is well known that statins, which block the mevalonate pathway, affect γδ T lymphocyte activation. As γδ T cells participate in the inflammatory process of COVID-19, we have investigated the therapeutical potential of statins as a tool to inhibit γδ T cell pro-inflammatory activities; (2) Methods: we harvested peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild clinical manifestations, COVID-19 recovered patients, and healthy controls. We performed ex vivo flow cytometry analysis to study γδ T cell frequency, phenotype, and exhaustion status. PBMCs were treated with Atorvastatin followed by non-specific and specific stimulation, to evaluate the expression of pro-inflammatory cytokines; (3) Results: COVID-19 patients had a lower frequency of circulating Vδ2+ T lymphocytes but showed a pronounced pro-inflammatory profile, which was inhibited by in vitro treatment with statins; (4) Conclusions: the in vitro capacity of statins to inhibit Vδ2+ T lymphocytes in COVID-19 patients highlights a new potential biological function of these drugs and supports their therapeutical use in these patients.
Physical Activity and Quality of Life among Patients with Cystic Fibrosis
Authors: Giannakoulakos Stavros , Gioulvanidou Maria , Kouidi Evangelia , Peftoulidou Pauline , Kyrvasili Syrmo Styliani , Savvidou Parthena , Deligiannis Asterios , Tsanakas John , Hatziagorou Elpis
Published: November 2022

Background: Physical activity (PA) improves exercise capacity, slows the decline in lung function, and enhances Quality of Life (QoL) in patients with cystic fibrosis (pwCF). Objectives: The study aimed to evaluate PA and QoL among children with CF compared to healthy controls; the secondary aim was to assess the correlation between PA, QoL, and lung function (FEV1). Methods: Forty-five children and adolescents with CF and 45 age-matched controls completed two self-administered validated questionnaires: The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the DISABKIDS for QoL. Moreover, pwCF performed spirometry and multiple breath washout tests (MBW). In addition, weight, height, and BMI were recorded. The Godin Leisure-Time Exercise Questionnaire was used to evaluate physical activity; QOL was assessed using the DISABKIDS Questionnaire. The correlation of PA with QOL was assessed as well. Results: Mean age of the CF population was 13.22 (±4.6) years, mean BMI 19.58 (±4.1) kg/m2, mean FEV1% 91.15 ± 20.46%, and mean LCI 10.68 ± 4.08. 68% of the CF group were active, 27% were medium active, 5% were sedentary, while 83% of the control group were active and 17% were medium active. PwCF with higher PA scores showed significantly higher emotional health (r2: 0.414, p: 0.006) and total QOL score (r2: 0.372; p: 0.014). The PA score showed no significant correlation with FEV1% or LCI. Conclusions: The children with CF showed satisfactory PA levels, which positively correlated to their QoL. More research is needed on the effect of increased levels of habitual physical activity to establish the decline in pulmonary function among pwCF.
Asymmetric and Symmetric Dimethylarginines as Renal Function Parameters in Paediatric Kidney Diseases: A Literature Review from 2003 to 2022
Authors: Jezierska Michalina , Stefanowicz Joanna
Published: November 2022

Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), inhibitors of nitric oxide synthase, play important roles in many processes in the body. Most data in the literature concern their importance in adult chronic kidney disease (CKD). According to them, SDMA well reflects the glomerular filtration rate (GFR), and higher ADMA concentrations are associated with hypertension and higher mortality. In addition, both substances are recognised cardiovascular risk factors in CKD. The purpose of this review was to summarise the studies on dimethylarginines in renal diseases in children, about which we have much fewer data. The review focuses specifically on dimethylarginine’s relation to routinely used renal function parameters. Finally, we analysed 21 of the 55 articles published between 2003 and 2022 on dimethylarginines in kidney diseases in children (from birth to 18 years of age), obtained by searching PubMed/MEDLINE (search terms: “dimethylarginine” and “kidney”).
Psychopathological Risk Assessment in Children with Hyperphenylalaninemia
Authors: Risoleo Maria Cristina , Siciliano Margherita , Vetri Luigi , Bitetti Ilaria , Di Sessa Anna , Carotenuto Marco , Annunziata Francesca , Concolino Daniela , Marotta Rosa
Published: November 2022

Background: Phenylketonuria (PKU) is a rare congenital disorder caused by decreased metabolism of phenylalanine determining cerebral impairments. If untreated, PKU might lead to intellectual disability, seizures and behavioral disorders. The aim of this study is to provide a characterization of the psychopathological profile of a pediatric population diagnosed with PKU at newborn screening. Methods: an accurate neuropsychological evaluation of 23 patients (aged 8–18 years) with hyperphenylalaninemia (defined as experimental group, EG) and in 23 age-matched healthy controls (defined as control group, CG) was performed using the Child and Adolescent Behavior Inventory (CABI) and Self-Administrated Psychiatric Scales for Children and Adolescents (SAFA) questionnaires. Results: the CABI test showed significant differences for the sub-scales related to “Irritable mood”, “Oppositional-provocative symptoms” and “ADHD” in the EG compared to CG (p = 0.014, p = 0.032, and p = 0.032, respectively). Patients with hyperphenylalaninemia also presented with significant differences both for anxiety disorder scale and depression scale of SAFA test than controls (p = 0.018 and p = 0.009, respectively). Conclusions: children and adolescents with early diagnosis of PKU showed a psychopathological risk profile characterized by an increased risk of experiencing symptoms such as mood deflection, anxiety, attention deficit, oppositional defiant behavior, and obsessive traits than healthy peers. Our findings highlighted the need of the inclusion of a neuropsychiatric evaluation in the management of these patients to improve their overall quality of life.
In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC—Application towards Cancer Therapeutics
Authors: Bennani Fatima Ezzahra , Karrouchi Khalid , Doudach Latifa , Scrima Mario , Rahman Noor , Rastrelli Luca , Tallei Trina Ekawati , Rudd Christopher E. , Faouzi My El Abbes , Ansar M’hammed
Published: November 2022

Despite continual efforts being made with multiple clinical studies and deploying cutting-edge diagnostic tools and technologies, the discovery of new cancer therapies remains of severe worldwide concern. Multiple drug resistance has also emerged in several cancer cell types, leaving them unresponsive to the many cancer treatments. Such a condition always prompts the development of next-generation cancer therapies that have a better chance of inhibiting selective target macromolecules with less toxicity. Therefore, in the present study, extensive computational approaches were implemented combining molecular docking and dynamic simulation studies for identifying potent pyrazole-based inhibitors or modulators for CRMP2, C-RAF, CYP17, c-KIT, VEGFR, and HDAC proteins. All of these proteins are in some way linked to the development of numerous forms of cancer, including breast, liver, prostate, kidney, and stomach cancers. In order to identify potential compounds, 63 in-house synthesized pyrazole-derivative compounds were docked with each selected protein. In addition, single or multiple standard drug compounds of each protein were also considered for docking analyses and their results used for comparison purposes. Afterward, based on the binding affinity and interaction profile of pyrazole compounds of each protein, potentially strong compounds were filtered out and further subjected to 1000 ns MD simulation analyses. Analyzing parameters such as RMSD, RMSF, RoG and protein–ligand contact maps were derived from trajectories of simulated protein–ligand complexes. All these parameters turned out to be satisfactory and within the acceptable range to support the structural integrity and interaction stability of the protein–ligand complexes in dynamic state. Comprehensive computational analyses suggested that a few identified pyrazole compounds, such as M33, M36, M72, and M76, could be potential inhibitors or modulators for HDAC, C-RAF, CYP72 and VEGFR proteins, respectively. Another pyrazole compound, M74, turned out to be a very promising dual inhibitor/modulator for CRMP2 and c-KIT proteins. However, more extensive study may be required for further optimization of the selected chemical framework of pyrazole derivatives to yield improved inhibitory activity against each studied protein receptor.
Comparative Analysis of Natural and Cytochalasin B-Induced Membrane Vesicles from Tumor Cells and Mesenchymal Stem Cells
Authors: Gilazieva Zarema , Chulpanova Daria , Ponomarev Aleksei , Filin Ivan , Garanina Ekaterina , Rizvanov Albert , Solovyeva Valeriya
Published: November 2022

To date, there are numerous protocols for the isolation of extracellular vesicles (EVs). Depending on the isolation method, it is possible to obtain vesicles with different characteristics, enriched with specific groups of proteins, DNA and RNA, which affect similar types of cells in the opposite way. Therefore, it is important to study and compare methods of vesicle isolation. Moreover, the differences between the EVs derived from tumor and mesenchymal stem cells are still poorly understood. This article compares EVs from human glioblastoma cells and mesenchymal stem cells (MSCs) obtained by two different methods, ultracentrifugation and cytochalasin B-mediated induction. The size of the vesicles, the presence of the main EV markers, the presence of nuclear and mitochondrial components, and the molecular composition of the vesicles were determined. It has been shown that EVs obtained by both ultracentrifugation and cytochalasin B treatment have similar features, contain particles of endogenous and membrane origin and can interact with monolayer cultures of tumor cells.
Global Prevalence and Associated Clinical Markers of Thrombocytopenia in People Living with HIV: Evidence from Meta-Analysis
Authors: Alkholifi Faisal K. , Abdi Sayed Aliul Hasan , Qadri Marwa
Published: November 2022

Thrombocytopenia is one of the complications in human immunodeficiency virus (HIV) patients. To improve the health outcomes of patients living with HIV, it is important to understand the prevalence and pattern of associated key clinical markers globally. This meta-analysis, therefore, aimed to estimate the pooled prevalence of and associated clinical marker of thrombocytopenia globally. Methodology: The meta-analysis was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All statistical analyses were conducted using Stata. Twelve full-text papers out of 454 were eligible for meta-analysis. Results: Among 6686 participants, overall pooled prevalence of thrombocytopenia was 10.90% (95% CI: 7.91, 13.88) I2 = 93.62%. In addition, thrombocytopenia was more prevalent by 25.11% (95% CI: 13.33, 36.88) in patients with CD + T < 200 cells/μL, and less prevalent in patients with CD + T < 200 cells/μL 10.10% (95% CI: 7.37, 12.83), respectively. Conclusions and recommendations: This meta-analysis established the prevalence of thrombocytopenia among patients living with HIV, and that it may be more prevalent in patients with CD + T < 200 cells/μL indicating the necessity of routine screening for various haematological markers and a careful treatment plan for HIV patients.
Wall Latex Paint with Graphene Oxide Incorporation
Authors: Araujo Sousa Jean Carlos , de Sousa Rudnei José , de Lima Bruna Pietroski , Cusioli Luís Fernando , Gomes Corrêa Rúbia Carvalho , Bergamasco Rosângela , Ueda Yamaguchi Natália
Published: November 2022

Graphene has stood out in several areas of research. The objective of the present work was an unprecedented study in the production of a commercial wall latex paint with graphene oxide incorporation. The developed paint was assessed by performance tests according to the Brazilian standards, and the characterization was performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR), thermogravimetric analysis (TGA), and contact angle analysis. The results indicated that GO addition led to a better dispersion of the paint compound mixture even at very low concentrations (1% and 2%). For the dry and wet paint coverage performance tests, the results were superior, 2% and 9%, respectively, when compared with the paint without GO addition. All performance tests were in accordance with the requirements of the Brazilian standards. Thus, it was concluded that GO-containing paint could be a promising building material to be used as a paint additive obtaining superior properties.
Magnesium Oxide Production by Plasma Chemical Conversion from Fluorine-Containing Industrial Waste
Authors: Sagdoldina Zhuldyz , Shestakov Konstantin , Yermolenko Michael , Kylyshkanov Manarbek , Podoinikov Mikhail , Rakhadilov Bauyrzhan , Kambarov Yedilzhan
Published: November 2022

This work discusses the possibility of decomposing magnesium fluoride by ionized water vapor to form solid magnesium oxide and hydrogen gas in the reaction: MgF2 + H2O → MgO + 2HF. The technology and individual apparatuses of the plasma-chemical installation are described, and the influence of the fractional composition of magnesium fluoride powder on the productivity of the plasma conversion process is considered. To improve the efficiency of the plasma pyrolysis process, a method for making magnesium fluoride briquettes was developed. The completeness of the conversion process of magnesium fluoride to an oxide was evaluated by energy dispersive X-ray spectroscopy in the study of objects in scanning electron microscopy (SEM) and by X-ray diffractometry. It was found that the conversion process of magnesium fluoride to magnesium oxide has a relatively high degree of decomposition of magnesium fluoride fraction ≤75 µm. The use of the proposed processing method makes it possible to obtain pure magnesium oxide as a commercial product and to utilize fluorine-containing industrial waste.
Characterization of CCP: Can We Use Past Convalescent Plasma from COVID-19 Patients for Treatment of New Emerging Variants?
Authors: Ferrari Alessandro , Cassaniti Irene , Sarasini Antonella , Lilleri Daniele , Sammartino Josè Camilla , Del Fante Claudia , Baldanti Fausto , Percivalle Elena , Perotti Cesare
Published: November 2022

Background and Objectives: New SARS-CoV-2 variants may impact the effectiveness of previously stored convalescent plasma (CCP). We defined levels of anti-delta and anti-omicron SARS-CoV-2 neutralizing antibodies (Nt-Abs) and investigated possible differences of past CCP Nt-Abs responses related to donor location in North and South Italy. Methods: Serum from 153 donors recovered from SARS-COV-2 infection (98 from northern and 55 from southern Italy) were analyzed for Nt-Abs characterization using our in house microneutralization assay. Results were compared to anti-Spike IgG measured by chemiluminescent assay (CLIA) to define a possible agreement with a more affordable test. Results: delta Nt-Abs titer in comparison to the reference strain (PV10734 D614G) showed a reduction of 82% in northern and 77% in southern Italy groups. Omicron Nt-Abs titer showed a reduction of 97%. CCP corresponding to Nt-Abs titer > 1:80 showed a median of 1365 BAU/mL for delta strain and 653 BAU/mL for reference strain. We found no statistical differences between Nt-Abs responses in North and South CCP donors. Conclusions: Not all past CCP could be used to treat patients with SARS-CoV-2 delta and omicron infections due to the lack of specific Nt-Abs. For the moment, the neutralization test remains the gold standard to select potential CCP donors. Interestingly, our study did not find NT-Abs differences between plasma collected from donors living in different areas of Italy.
Effect of Sintering Parameters on Microstructural Evolution of Low Sintered Geopolymer Based on Kaolin and Ground-Granulated Blast-Furnace Slag
Authors: Jamil Noorina , Abdullah Mohd , Ibrahim Wan , Rahim Razna , Sandu Andrei , Vizureanu Petrica , Castro-Gomes João , Gómez-Soberón José
Published: November 2022

The effect of different sintering parameters on the mechanical properties of sintered kaolin-GGBS will influence the variation of mechanical properties of sintered kaolin-GGBS geopolymer. Based on previous research, the samples have major cracking and many large pores due to the sintering temperature and holding time during the sintering process. The first objective is to study the effect of different sintering parameters on the mechanical properties of sintered kaolin-GGBS geopolymer and the second objective is to correlate the strength properties of sintered kaolin-GGBS geopolymer with microstructural analysis. In a solid-to-liquid 2:1 ratio, kaolin and GGBS were combined with an alkali activator. The kaolin-GGBS geopolymer was then cured at room temperature for 24 h. The samples were then cured for 14 days at 60 °C, followed by using double-step sintering at temperatures of 500 °C and 900 °C with varying heating rates and holding durations. The compressive strength and shrinkage of the kaolin-GGBS geopolymer were evaluated, and the morphology was examined using a scanning electron microscope. In comparison to other samples, the sintered kaolin-GGBS geopolymer with a heating rate of 2 °C and a holding duration of 2 h had the optimum compressive strength value: 22.32 MPa. This is due to the contribution of MgO from GGBS that refines the pore and increases the strength. The 13.72% shrinkage with a densified microstructure was also obtained at this parameter due to effective particle rearrangement during sintering.
Local Three-Dimensional Characterization of Nonlinear Grain Boundary Length within Bulk ZnO Using Nanorobot in SEM
Authors: Shen Feiling , Cao Ning , Li Hengyu , Wu Zhizheng , Xie Shaorong , Luo Jun
Published: November 2022

Aiming at the problems of lack of data on the nonlinear morphology to divide uneven grain boundary in bulk ceramics, a unique approach of nanorobot-based characterization of three-dimensional nonlinear structure length can be creatively proposed under scanning electron microscope to quantify the actual morphology of local micro-area grain boundary in bulk ZnO. Contour shapes of the targeted grain boundaries in plane X-Y can be imaged using SEM. Z-directional relative height differences at different positions can be sequentially probed by nanorobot. Experiments demonstrate that it is effective to characterize three-dimensional length structures of nonlinear grain boundaries in bulk materials. By quantifying Z-directional relative height differences, it can be verified to show that irregular characteristics exist in three-dimensional grain boundary length, which can extend the depth effect on nonlinear bulk conductance. Furthermore, this method can also obtain nonlinear quantitative topographies to divide grain boundaries to uneven structure in the analysis of bulk polycrystalline materials.
Olanzapine for the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting: A Review to Identify the Best Way to Administer the Drug
Authors: Zhang Xiao-Ling , Ying Jie-Er
Published: November 2022

Common treatment methods for malignant tumors include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, etc., among which chemotherapy plays an important role. However, chemotherapy brings corresponding side effects while killing tumor cells, and nausea and vomiting are the most common adverse reactions induced by chemotherapy. It not only affects the patient’s appetite, resulting in malnutrition and electrolyte disturbances, but also reduces the patient’s compliance with treatment, which further aggravates the disease. Thus, it is important to quickly prevent and cure nausea and vomiting induced by chemotherapy (CINV). In addition, with the continuous development of medicine, more and more antiemetic drugs have been developed. At present, the most common antiemetic agents for chemotherapy-induced nausea and vomiting are NK-1R antagonists, 5-HT3R antagonists, and dexamethasone. Surprisingly, olanzapine, often used as a psychotropic drug, has been found to be an effective antiemetic and is similar to other regimens on the safety of medicine. However, although there are numerous studies on the antiemetic effects of olanzapine, its comprehensive application remains unclear. Therefore, this review will elaborate the antiemetic effect of olanzapine in terms of the antiemetic mechanism and the safety, economic cost, dose, administration time, and drug delivery aspects.
A New Species of Free-Living Nematodes (Desmodorida, Desmodoridae) in the Romanian Black Sea Waters
Authors: Mureșan Mihaela , Motoc Rozalia , Menabit Selma , Teacă Adrian , Begun Tatiana
Published: November 2022

The paper reports the record of Pseudochromadora gomoi sp.n. in circalittoral habitats (at depths of 47–59 m) of the Romanian Black Sea waters. The species is characterized by a unispiral amphidial fovea, the presence of lateral alae stretching from the posterior end of the cardia to the level of the cloacal opening, but also shows unique features found in other Desmodorida genera (i.e., the presence of a precloacal ventral ala in males similar to several Desmodora or Echinodesmodora species and eight subcephalic setae on the head capsule). The presence of a constrictor cuticle ring and orange elongated ducts in the anterior body part as in Pseudodesmodora lacrima, Leduc and Wharton, 2010, were also noted. The morphometric measurements of our species differ from most of the Pseudochromadora species reported in specialty literature. We extracted and counted all desmodorid individuals from 9 meiobenthic samples collected in June 2020, and performed a detailed morphological analysis of 12 individuals (5 females and 7 males) belonging to our species, also highlighting the dissimilarities with the related desmodorid species.